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345,400 | 16,643,269 | 1,645 | The present invention relates to the surprising discovery that previous hemoglobin-based drug purification methodologies do not remove sufficient endotoxins exposures at the various steps which may complex with the hemoglobin protein. These complexed endotoxins can result in serious health complications (e.g. development of cardiac lesions for one). Additionally, varied endotoxin types and concentration contributes to batch-to-batch variability during hemoglobin-based drug manufacture. Endotoxins are not as much of an issue for peptides as compared to larger protein complexes. Accordingly, the instant disclosure is directed to a purification process using single use systems in many process steps including high performance chromatography systems thereby removing endotoxins while keeping processing costs low. | 1. A method for manufacturing endotoxin-free hemoglobin based drug substance comprising:
collecting bovine blood using a sterile polymeric bag contain CPD anticoagulant; washing the collected blood by diafilitration; lysing said bovine red blood cells producing a hemoglobin solution; stabilizing said hemoglobin solution by removing oxygen producing deoxygenated hemoglobin solution; filtering said deoxygenated hemoglobin solution; purifying said deoxyenated hemoglobin solution thereby reducing non-specific blood cell components, wherein said purification is achieved via chromatography producing a purified hemoglobin solution; stabilizing said purified hemoglobin solution by deoxygenating by filtration through about an 30,000 Da hollow-fiber membrane achieving a desired hemoglobin concentration, wherein the purified hemoglobin is deoxygenated by passage through multiple liquicell membranes; filtering said deoxygenated purified hemoglobin solution by diafiltering against storage buffer by pumping through a 30,000 Da hollow-fiber membrane; polymerizing said purified deoxygenated hemoglobin by cross-linking with glutaraldehyde; stablizing said polymerized purified deoxygnated hemoglobin d reduction with sodium borohydride, wherein said stabilized polymerized purified deoxygenated hemoglobin via diafiltration of said polymerized hemoglobin producing a final polymerized hemoglobin solution; and filtering said final polymerized hemoglobin solution. 2. The method according to claim 1 wherein said final polymerized hemoglobin solution is filtered through a 0.5 μm depth filter, a sterilizing grade 0.2 μm membrane filter, and at least one additional 2nd sterilizing grade 0.2 μm membrane filter. 3. The method according to claim 1, wherein said lysing of bovine red blood cells is by a rapid decrease in osmotic pressure resulting in cell lysis and sequential diafiltration across 100 kDa and 30 kDa membranes. 4. The method according to claim 1 wherein the step of deoxygenating said hemoglobin solution further comprises the step of pumping the hemoglobin solution through two Liquicell Membranes aligned in series at a flow rate of 500 ml-min−1, with a counter-current flow of nitrogen at 75 psi until the dissolved oxygen reading is below 0.02 mg-mL−1. 5. The method according to claim 1 wherein said chromatography system uses a GE Akta Biopilot chromatography system equipped with a GE Healthcare XK borosilicate column (5 cm i.d.×100 cm length) packed with Q Sepharose Fast Flow (GE Healthcare) to a bed height of 70±5 cm. 6. The method according to claim 5 wherein said chromatography system's buffers are prepared using Water for Injection and filtered through a 10 kDa membrane to further reduce pyrogen content said buffers are selected from the group consisting of (1) Buffer A; 2.42 g-L-1 tris base adjusted to pH 9.0±0.1 with acetic acid, (2) Buffer B; 6.05 g-L-1 Tris base adjusted to pH 7.0±0.1 with acetic acid and (3) Buffer C; 2.42 g-L-1 Tris base and 58.38 g-L-1 NaCl adjusted to pH 8.9±0.1 with acetic acid. 7. The method according to claim 1 wherein the hemoglobin solution is polymerized by raising the solution to 42±2° C. and a Glutaraldehyde solution is prepared at a concentration of 6.2 g/L in a temperature controlled Wave bag (T602) and heated to 42±2 C and said Glutaraldehyde solution is pumped into T603 at a rate of 10 mL/min until the ratio of glutaraldehyde to hemoglobin is approximately 0.029:1. 8. The method according to claim 7 wherein the glutaraldehyde is added through a static mixer in a recirculation loop to ensure rapid and homogeneous mixing with the hemoglobin and the temperature of the reaction mixture is cooled to 22±2° C. 9. The method according to claim 8 where the reaction mixture is concentrated by diafiltration through a 30,000 Da hollow-fiber membrane (F601) to a hemoglobin concentration of 80±5 g/L. 10. The method according to claim 1 wherein said sodium borohydride solution is comprised of 9.45 g/L sodium borohydride, 4.58 g/L sodium borate decahydrate and 0.91 g/L sodium hydroxide in Water for Injection and said sodium borohydride solution is filtered through a 10,000 Da membrane to reduce pyrogen content. | The present invention relates to the surprising discovery that previous hemoglobin-based drug purification methodologies do not remove sufficient endotoxins exposures at the various steps which may complex with the hemoglobin protein. These complexed endotoxins can result in serious health complications (e.g. development of cardiac lesions for one). Additionally, varied endotoxin types and concentration contributes to batch-to-batch variability during hemoglobin-based drug manufacture. Endotoxins are not as much of an issue for peptides as compared to larger protein complexes. Accordingly, the instant disclosure is directed to a purification process using single use systems in many process steps including high performance chromatography systems thereby removing endotoxins while keeping processing costs low.1. A method for manufacturing endotoxin-free hemoglobin based drug substance comprising:
collecting bovine blood using a sterile polymeric bag contain CPD anticoagulant; washing the collected blood by diafilitration; lysing said bovine red blood cells producing a hemoglobin solution; stabilizing said hemoglobin solution by removing oxygen producing deoxygenated hemoglobin solution; filtering said deoxygenated hemoglobin solution; purifying said deoxyenated hemoglobin solution thereby reducing non-specific blood cell components, wherein said purification is achieved via chromatography producing a purified hemoglobin solution; stabilizing said purified hemoglobin solution by deoxygenating by filtration through about an 30,000 Da hollow-fiber membrane achieving a desired hemoglobin concentration, wherein the purified hemoglobin is deoxygenated by passage through multiple liquicell membranes; filtering said deoxygenated purified hemoglobin solution by diafiltering against storage buffer by pumping through a 30,000 Da hollow-fiber membrane; polymerizing said purified deoxygenated hemoglobin by cross-linking with glutaraldehyde; stablizing said polymerized purified deoxygnated hemoglobin d reduction with sodium borohydride, wherein said stabilized polymerized purified deoxygenated hemoglobin via diafiltration of said polymerized hemoglobin producing a final polymerized hemoglobin solution; and filtering said final polymerized hemoglobin solution. 2. The method according to claim 1 wherein said final polymerized hemoglobin solution is filtered through a 0.5 μm depth filter, a sterilizing grade 0.2 μm membrane filter, and at least one additional 2nd sterilizing grade 0.2 μm membrane filter. 3. The method according to claim 1, wherein said lysing of bovine red blood cells is by a rapid decrease in osmotic pressure resulting in cell lysis and sequential diafiltration across 100 kDa and 30 kDa membranes. 4. The method according to claim 1 wherein the step of deoxygenating said hemoglobin solution further comprises the step of pumping the hemoglobin solution through two Liquicell Membranes aligned in series at a flow rate of 500 ml-min−1, with a counter-current flow of nitrogen at 75 psi until the dissolved oxygen reading is below 0.02 mg-mL−1. 5. The method according to claim 1 wherein said chromatography system uses a GE Akta Biopilot chromatography system equipped with a GE Healthcare XK borosilicate column (5 cm i.d.×100 cm length) packed with Q Sepharose Fast Flow (GE Healthcare) to a bed height of 70±5 cm. 6. The method according to claim 5 wherein said chromatography system's buffers are prepared using Water for Injection and filtered through a 10 kDa membrane to further reduce pyrogen content said buffers are selected from the group consisting of (1) Buffer A; 2.42 g-L-1 tris base adjusted to pH 9.0±0.1 with acetic acid, (2) Buffer B; 6.05 g-L-1 Tris base adjusted to pH 7.0±0.1 with acetic acid and (3) Buffer C; 2.42 g-L-1 Tris base and 58.38 g-L-1 NaCl adjusted to pH 8.9±0.1 with acetic acid. 7. The method according to claim 1 wherein the hemoglobin solution is polymerized by raising the solution to 42±2° C. and a Glutaraldehyde solution is prepared at a concentration of 6.2 g/L in a temperature controlled Wave bag (T602) and heated to 42±2 C and said Glutaraldehyde solution is pumped into T603 at a rate of 10 mL/min until the ratio of glutaraldehyde to hemoglobin is approximately 0.029:1. 8. The method according to claim 7 wherein the glutaraldehyde is added through a static mixer in a recirculation loop to ensure rapid and homogeneous mixing with the hemoglobin and the temperature of the reaction mixture is cooled to 22±2° C. 9. The method according to claim 8 where the reaction mixture is concentrated by diafiltration through a 30,000 Da hollow-fiber membrane (F601) to a hemoglobin concentration of 80±5 g/L. 10. The method according to claim 1 wherein said sodium borohydride solution is comprised of 9.45 g/L sodium borohydride, 4.58 g/L sodium borate decahydrate and 0.91 g/L sodium hydroxide in Water for Injection and said sodium borohydride solution is filtered through a 10,000 Da membrane to reduce pyrogen content. | 1,600 |
345,401 | 16,643,319 | 1,645 | A data management system is provided with: a storage unit for storing examination information including at least an examination item, an examination location, a consultation location, and a required examination time, the examination item including examination names of a plurality of examinations; an acquisition unit for acquiring patient information relating to severity and an identifier for identifying the patient to be examined; a calculation unit for calculating, in accordance with the patient, the necessary travel time for traveling from the examination location or consultation location at which a completed examination or consultation was performed to the next examination location or consultation location at which the next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and a generating unit for generating a patient examination schedule based on the examination information, the patient information, and the travel time. | 1. A data management system comprising:
a storage unit configured to store examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; an acquisition unit configured to acquire patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; a calculation unit configured to calculate, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and a generating unit configured to generate an examination schedule for the patient based on the examination information, the patient information, and the travel time. 2. The data management system as claimed in claim 1, further comprising a learning unit configured to machine-learn a correlation between the examination information and the patient information,
wherein the generating unit is configured to generate the examination schedule using a learned result of the learning unit. 3. The data management system as claimed in claim 1, wherein, when the acquisition unit acquires the patient information relating to a plurality of patients,
the calculating unit calculates, for each of the plurality of patients, the travel time required for traveling from the examination or consultation location to the next examination or consultation location, and the generating unit generates the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel time for each of the plurality of patients. 4. The data management system as claimed in claim 1, wherein the generating unit is configured to provide a priority order for the examinations of the examination names included in the examination items in accordance with a degree of influence exerted by a state of the patient upon the required examination time and to generate the examination schedule with the priority order taken into account. 5. The data management system as claimed in claim 1, wherein, when the acquisition unit receives information indicative of appearance of an emergency patient, the generating unit automatically renews the examination schedule so that the emergency patient preferentially undergoes the examinations. 6. The data management system as claimed in claim 1, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. 7. A data management method, comprising:
storing examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; acquiring patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; calculating, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and generating an examination schedule for the patient based on the examination information, the patient information, and the travel time. 8. The data management method as claimed in claim 7, comprising:
machine-learning a correlation between the examination information and the patient information; and generating the examination schedule using a learned result of the machine learning. 9. The data management method as claimed in claim 7, comprising, when the patient information relating to a plurality of patients are acquired:
calculating the travel time required for traveling from the examination or consultation location to the next examination or consultation location for each of the plurality of patients, and generating the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel times for each of the plurality of patients. 10. The data management method as claimed in claim 7, wherein, a priority order for the examinations of the examination names included in the examination items is provided in accordance with a degree of influence exerted by a state of the patient upon the required examination time and the examination schedule is generated with the priority order taken into account. 11. The data management method as claimed in claim 7, wherein, when information indicative of appearance of an emergency patient is received, the examination schedule is automatically renewed so that the emergency patient preferentially undergoes the examinations. 12. The data management method as claimed in claim 7, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. 13. A non-transitory computer readable recording medium recording a data management program which causes a computer to execute the procedures of:
storing examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; acquiring patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; calculating, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and generating an examination schedule for the patient based on the examination information, the patient information, and the travel time. 14. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute the procedures of:
machine-learning a correlation between the examination information and the patient information; and generating the examination schedule using a learned result of the machine learning. 15. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute, when the patient information relating to a plurality of patients are acquired, the procedures of:
calculating, for each of the plurality of patients, the travel time required for traveling from the examination or consultation location to the next examination or consultation location, and generating the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel time for each of the plurality of patients. 16. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute the procedure of:
providing a priority order for the examinations of the examination names included in the examination items in accordance with a degree of influence exerted by a state of the patient upon the required examination time and generating the examination schedule with the priority order taken into account. 17. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute, when information indicative of appearance of an emergency patient is received, the procedure of:
automatically renewing the examination schedule so that the emergency patient preferentially undergoes the examinations. 18. The non-transitory computer readable recording medium as claimed in claim 13, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. | A data management system is provided with: a storage unit for storing examination information including at least an examination item, an examination location, a consultation location, and a required examination time, the examination item including examination names of a plurality of examinations; an acquisition unit for acquiring patient information relating to severity and an identifier for identifying the patient to be examined; a calculation unit for calculating, in accordance with the patient, the necessary travel time for traveling from the examination location or consultation location at which a completed examination or consultation was performed to the next examination location or consultation location at which the next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and a generating unit for generating a patient examination schedule based on the examination information, the patient information, and the travel time.1. A data management system comprising:
a storage unit configured to store examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; an acquisition unit configured to acquire patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; a calculation unit configured to calculate, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and a generating unit configured to generate an examination schedule for the patient based on the examination information, the patient information, and the travel time. 2. The data management system as claimed in claim 1, further comprising a learning unit configured to machine-learn a correlation between the examination information and the patient information,
wherein the generating unit is configured to generate the examination schedule using a learned result of the learning unit. 3. The data management system as claimed in claim 1, wherein, when the acquisition unit acquires the patient information relating to a plurality of patients,
the calculating unit calculates, for each of the plurality of patients, the travel time required for traveling from the examination or consultation location to the next examination or consultation location, and the generating unit generates the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel time for each of the plurality of patients. 4. The data management system as claimed in claim 1, wherein the generating unit is configured to provide a priority order for the examinations of the examination names included in the examination items in accordance with a degree of influence exerted by a state of the patient upon the required examination time and to generate the examination schedule with the priority order taken into account. 5. The data management system as claimed in claim 1, wherein, when the acquisition unit receives information indicative of appearance of an emergency patient, the generating unit automatically renews the examination schedule so that the emergency patient preferentially undergoes the examinations. 6. The data management system as claimed in claim 1, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. 7. A data management method, comprising:
storing examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; acquiring patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; calculating, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and generating an examination schedule for the patient based on the examination information, the patient information, and the travel time. 8. The data management method as claimed in claim 7, comprising:
machine-learning a correlation between the examination information and the patient information; and generating the examination schedule using a learned result of the machine learning. 9. The data management method as claimed in claim 7, comprising, when the patient information relating to a plurality of patients are acquired:
calculating the travel time required for traveling from the examination or consultation location to the next examination or consultation location for each of the plurality of patients, and generating the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel times for each of the plurality of patients. 10. The data management method as claimed in claim 7, wherein, a priority order for the examinations of the examination names included in the examination items is provided in accordance with a degree of influence exerted by a state of the patient upon the required examination time and the examination schedule is generated with the priority order taken into account. 11. The data management method as claimed in claim 7, wherein, when information indicative of appearance of an emergency patient is received, the examination schedule is automatically renewed so that the emergency patient preferentially undergoes the examinations. 12. The data management method as claimed in claim 7, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. 13. A non-transitory computer readable recording medium recording a data management program which causes a computer to execute the procedures of:
storing examination information including at least examination items which include examination names of a plurality of examinations, examination locations at which the examinations are performed, consultation locations at which consultations are performed, and required examination times which are required for the respective examinations; acquiring patient information relating to an identifier for identifying a patient to be examined and degree of severity thereof; calculating, in accordance with the patient, a travel time required for traveling from an examination or consultation location at which an examination or consultation already completed has been performed to a next examination or consultation location at which a next examination or consultation subsequent to the examination or consultation is to be performed, based on the patient information and the examination information; and generating an examination schedule for the patient based on the examination information, the patient information, and the travel time. 14. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute the procedures of:
machine-learning a correlation between the examination information and the patient information; and generating the examination schedule using a learned result of the machine learning. 15. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute, when the patient information relating to a plurality of patients are acquired, the procedures of:
calculating, for each of the plurality of patients, the travel time required for traveling from the examination or consultation location to the next examination or consultation location, and generating the examination schedule for each of the plurality of patients based on the examination information, the patient information, and the travel time for each of the plurality of patients. 16. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute the procedure of:
providing a priority order for the examinations of the examination names included in the examination items in accordance with a degree of influence exerted by a state of the patient upon the required examination time and generating the examination schedule with the priority order taken into account. 17. The non-transitory computer readable recording medium as claimed in claim 13, wherein the data management program causes the computer to execute, when information indicative of appearance of an emergency patient is received, the procedure of:
automatically renewing the examination schedule so that the emergency patient preferentially undergoes the examinations. 18. The non-transitory computer readable recording medium as claimed in claim 13, wherein the patient information includes at least one of a paralysis state, an age, a level of consciousness, a cognitive level, a motor function of the patient. | 1,600 |
345,402 | 16,643,315 | 1,645 | Liquid crystal display panel, display device, operating method are provided. Liquid crystal display panel includes: first substrate and opposite second substrate, where second substrate is on light exiting side of liquid crystal display panel; first electrode, second electrode, liquid crystal layer, between first substrate and second substrate; light extracting component on first substrate, for extracting polarized light propagated in totally reflected manner in first substrate; and filter layer on second substrate, including color filter unit corresponding to a color, where color filter unit is configured to transmit polarized light with the color and prevent transmission of polarized light with a color different from the color; first electrode and second electrode are for controlling deflection direction of liquid crystal molecules in liquid crystal layer in response to electrical signals applied to first and second electrodes, to control propagation direction of polarized light extracted by light extracting component. | 1. A liquid crystal display panel, comprising:
a first substrate and a second substrate opposite to each other, wherein the second substrate is on a light exiting side of the liquid crystal display panel; a first electrode, a second electrode, and a liquid crystal layer which are between the first substrate and the second substrate; a light extracting component on the first substrate, configured to extract polarized light that is propagated in a totally reflected manner in the first substrate; and a filter layer on the second substrate, comprising a color filter unit corresponding to a color, wherein the color filter unit is configured to transmit polarized light with the color and prevent transmission of polarized light with a color which is different from the color; wherein the first electrode and the second electrode are configured to control a deflection direction of liquid crystal molecules in the liquid crystal layer in response to electrical signals applied to the first electrode and the second electrode, to control a propagation direction of the polarized light extracted by the light extracting component. 2. The liquid crystal display panel according to claim 1, wherein the first electrode and the second electrode are configured to control the deflection direction of the liquid crystal molecules in the liquid crystal layer in response to voltage signals applied to the first electrode and the second electrode, so as to control the polarized light to propagate to the color filter unit with the corresponding color for realizing bright state display or to control the polarized light to propagate to the color filter unit with another color for realizing dark state display. 3. The liquid crystal display panel according to claim 1, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; and a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, and the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light. 4. The liquid crystal display panel according to claim 3, wherein the filter layer comprises a first color sub-pixel configured to transmit the first monochromatic light, a second color sub-pixel configured to transmit the second monochromatic light, and a third color sub-pixel configured to transmit the third monochromatic light, the first light extracting grating corresponds to at least one first color sub-pixel, the second light extracting grating corresponds to at least one second color sub-pixel, and the third light extracting grating corresponds to at least one third color sub-pixel. 5. The liquid crystal display panel according to claim 1, wherein the light extracting component comprises:
a fourth light extracting grating, configured to extract first monochromatic light, second monochromatic light, and third monochromatic light that are propagated in a totally reflected manner in the first substrate, wherein the first monochromatic light, the second first monochromatic light and the third monochromatic light are capable of being mixed into white light. 6. The liquid crystal display panel according to claim 1, further comprising:
a first alignment layer on a side of the first substrate facing the second substrate; and a second alignment layer on a side of the second substrate facing the first substrate. 7. The liquid crystal display panel according to claim 1, wherein an orthographic projection of a long axis of liquid crystal molecules in the liquid crystal layer onto the first substrate is parallel to a vibration direction of the polarized light propagating in the liquid crystal layer. 8. The liquid crystal display panel according to claim 1, wherein the light extracting component is on a surface on a side of the first substrate close to the second substrate. 9. The liquid crystal display panel according to claim 1, wherein the light extracting component is on a surface on a side of the first substrate away from the second substrate. 10. The liquid crystal display panel according to claim 4, wherein the first color sub-pixel is configured to absorb the second monochromatic light and the third monochromatic light to prevent transmission of the second monochromatic light and the third monochromatic light;
wherein the second color sub-pixel is configured to absorb the first monochromatic light and the third monochromatic light to prevent transmission of the first monochromatic light and the third monochromatic light; and wherein the third color sub-pixel is configured to absorb the first monochromatic light and the second monochromatic light to prevent transmission of the first monochromatic light and the second monochromatic light. 11. A display device, comprising:
the liquid crystal display panel according to claim 1; a light source on a light incident side of the first substrate of the liquid crystal display panel; and an optical coupling component, configured to convert light emitted by the light source into collimated polarized light, and enable the collimated polarized light to enter the first substrate at a preset angle, so that the polarized light propagates in the first substrate in a totally reflected manner. 12. The display device according to claim 11, wherein the optical coupling component comprises:
a coupling lampshade, configured to change a propagation direction of the light emitted by the light source, so that the light enters the first substrate at the preset angle to propagate in a totally reflected manner in the first substrate; and a polarizer on a light exiting side of the coupling lampshade or the light incident side of the first substrate, configured to convert the light into the polarized light. 13. The display device according to claim 11, wherein the light source is a white light source. 14. The display device according to claim 11, wherein the light source comprises a first monochromatic light source, a second monochromatic light source, and a third monochromatic light source, the first monochromatic light source is configured to emit first monochromatic light, the second monochromatic light source is configured to emit second monochromatic light, the third monochromatic light source is configured to emit third monochromatic light, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, and the light source is configured to sequentially emit the first monochromatic light, the second monochromatic light, and the third monochromatic light in three display time periods of a frame. 15. An operating method for a display device, applied to the display device according to claim 11, comprising:
applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the polarized light extracted by the light extracting component is changed. 16. The operating method for the display device according to claim 15, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; and wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, the light source is a white light source, and the operating method comprises: applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the first monochromatic light extracted by the first light extracting grating; applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the second monochromatic light extracted by the second light extracting grating; and applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the third monochromatic light extracted by the third light extracting grating. 17. The operating method for the display device according to claim 15, wherein the light extracting component comprises: a fourth light extracting grating, configured to extract first monochromatic light, second monochromatic and third monochromatic light which are propagated in a totally reflected manner in the first substrate, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, the light source is configured to sequentially emit the first monochromatic light, the second monochromatic light, and the third monochromatic light, and the operating method comprises:
in a first stage of each display time period, controlling the light source to emit the first monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the first monochromatic light extracted by the fourth light extracting grating is changed; in a second stage of each display time period, controlling the light source to emit the second monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the second monochromatic light extracted by the fourth light extracting grating is changed; and in a third stage of each display time period, controlling the light source to emit the third monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the third monochromatic light extracted by the fourth light extracting grating is changed. 18. The display device according to claim 11, wherein the first electrode and the second electrode are configured to control the deflection direction of the liquid crystal molecules in the liquid crystal layer in response to voltage signals applied to the first electrode and the second electrode, so as to control the polarized light to propagate to the color filter unit with the corresponding color for realizing bright state display or to control the polarized light to propagate to the color filter unit with another color for realizing dark state display. 19. The display device according to claim 11, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; and a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, and the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light. 20. The display device according to claim 19, wherein the filter layer comprises a first color sub-pixel configured to transmit the first monochromatic light, a second color sub-pixel configured to transmit the second monochromatic light, and a third color sub-pixel configured to transmit the third monochromatic light, the first light extracting grating corresponds to at least one first color sub-pixel, the second light extracting grating corresponds to at least one second color sub-pixel, and the third light extracting grating corresponds to at least one third color sub-pixel. | Liquid crystal display panel, display device, operating method are provided. Liquid crystal display panel includes: first substrate and opposite second substrate, where second substrate is on light exiting side of liquid crystal display panel; first electrode, second electrode, liquid crystal layer, between first substrate and second substrate; light extracting component on first substrate, for extracting polarized light propagated in totally reflected manner in first substrate; and filter layer on second substrate, including color filter unit corresponding to a color, where color filter unit is configured to transmit polarized light with the color and prevent transmission of polarized light with a color different from the color; first electrode and second electrode are for controlling deflection direction of liquid crystal molecules in liquid crystal layer in response to electrical signals applied to first and second electrodes, to control propagation direction of polarized light extracted by light extracting component.1. A liquid crystal display panel, comprising:
a first substrate and a second substrate opposite to each other, wherein the second substrate is on a light exiting side of the liquid crystal display panel; a first electrode, a second electrode, and a liquid crystal layer which are between the first substrate and the second substrate; a light extracting component on the first substrate, configured to extract polarized light that is propagated in a totally reflected manner in the first substrate; and a filter layer on the second substrate, comprising a color filter unit corresponding to a color, wherein the color filter unit is configured to transmit polarized light with the color and prevent transmission of polarized light with a color which is different from the color; wherein the first electrode and the second electrode are configured to control a deflection direction of liquid crystal molecules in the liquid crystal layer in response to electrical signals applied to the first electrode and the second electrode, to control a propagation direction of the polarized light extracted by the light extracting component. 2. The liquid crystal display panel according to claim 1, wherein the first electrode and the second electrode are configured to control the deflection direction of the liquid crystal molecules in the liquid crystal layer in response to voltage signals applied to the first electrode and the second electrode, so as to control the polarized light to propagate to the color filter unit with the corresponding color for realizing bright state display or to control the polarized light to propagate to the color filter unit with another color for realizing dark state display. 3. The liquid crystal display panel according to claim 1, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; and a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, and the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light. 4. The liquid crystal display panel according to claim 3, wherein the filter layer comprises a first color sub-pixel configured to transmit the first monochromatic light, a second color sub-pixel configured to transmit the second monochromatic light, and a third color sub-pixel configured to transmit the third monochromatic light, the first light extracting grating corresponds to at least one first color sub-pixel, the second light extracting grating corresponds to at least one second color sub-pixel, and the third light extracting grating corresponds to at least one third color sub-pixel. 5. The liquid crystal display panel according to claim 1, wherein the light extracting component comprises:
a fourth light extracting grating, configured to extract first monochromatic light, second monochromatic light, and third monochromatic light that are propagated in a totally reflected manner in the first substrate, wherein the first monochromatic light, the second first monochromatic light and the third monochromatic light are capable of being mixed into white light. 6. The liquid crystal display panel according to claim 1, further comprising:
a first alignment layer on a side of the first substrate facing the second substrate; and a second alignment layer on a side of the second substrate facing the first substrate. 7. The liquid crystal display panel according to claim 1, wherein an orthographic projection of a long axis of liquid crystal molecules in the liquid crystal layer onto the first substrate is parallel to a vibration direction of the polarized light propagating in the liquid crystal layer. 8. The liquid crystal display panel according to claim 1, wherein the light extracting component is on a surface on a side of the first substrate close to the second substrate. 9. The liquid crystal display panel according to claim 1, wherein the light extracting component is on a surface on a side of the first substrate away from the second substrate. 10. The liquid crystal display panel according to claim 4, wherein the first color sub-pixel is configured to absorb the second monochromatic light and the third monochromatic light to prevent transmission of the second monochromatic light and the third monochromatic light;
wherein the second color sub-pixel is configured to absorb the first monochromatic light and the third monochromatic light to prevent transmission of the first monochromatic light and the third monochromatic light; and wherein the third color sub-pixel is configured to absorb the first monochromatic light and the second monochromatic light to prevent transmission of the first monochromatic light and the second monochromatic light. 11. A display device, comprising:
the liquid crystal display panel according to claim 1; a light source on a light incident side of the first substrate of the liquid crystal display panel; and an optical coupling component, configured to convert light emitted by the light source into collimated polarized light, and enable the collimated polarized light to enter the first substrate at a preset angle, so that the polarized light propagates in the first substrate in a totally reflected manner. 12. The display device according to claim 11, wherein the optical coupling component comprises:
a coupling lampshade, configured to change a propagation direction of the light emitted by the light source, so that the light enters the first substrate at the preset angle to propagate in a totally reflected manner in the first substrate; and a polarizer on a light exiting side of the coupling lampshade or the light incident side of the first substrate, configured to convert the light into the polarized light. 13. The display device according to claim 11, wherein the light source is a white light source. 14. The display device according to claim 11, wherein the light source comprises a first monochromatic light source, a second monochromatic light source, and a third monochromatic light source, the first monochromatic light source is configured to emit first monochromatic light, the second monochromatic light source is configured to emit second monochromatic light, the third monochromatic light source is configured to emit third monochromatic light, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, and the light source is configured to sequentially emit the first monochromatic light, the second monochromatic light, and the third monochromatic light in three display time periods of a frame. 15. An operating method for a display device, applied to the display device according to claim 11, comprising:
applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the polarized light extracted by the light extracting component is changed. 16. The operating method for the display device according to claim 15, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; and wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, the light source is a white light source, and the operating method comprises: applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the first monochromatic light extracted by the first light extracting grating; applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the second monochromatic light extracted by the second light extracting grating; and applying the electrical signals to the first electrode and the second electrode to deflect the liquid crystal molecules so as to change a propagation direction of the third monochromatic light extracted by the third light extracting grating. 17. The operating method for the display device according to claim 15, wherein the light extracting component comprises: a fourth light extracting grating, configured to extract first monochromatic light, second monochromatic and third monochromatic light which are propagated in a totally reflected manner in the first substrate, the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light, the light source is configured to sequentially emit the first monochromatic light, the second monochromatic light, and the third monochromatic light, and the operating method comprises:
in a first stage of each display time period, controlling the light source to emit the first monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the first monochromatic light extracted by the fourth light extracting grating is changed; in a second stage of each display time period, controlling the light source to emit the second monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the second monochromatic light extracted by the fourth light extracting grating is changed; and in a third stage of each display time period, controlling the light source to emit the third monochromatic light, and applying electrical signals to the first electrode and the second electrode, so that the liquid crystal molecules are deflected, and a propagation direction of the third monochromatic light extracted by the fourth light extracting grating is changed. 18. The display device according to claim 11, wherein the first electrode and the second electrode are configured to control the deflection direction of the liquid crystal molecules in the liquid crystal layer in response to voltage signals applied to the first electrode and the second electrode, so as to control the polarized light to propagate to the color filter unit with the corresponding color for realizing bright state display or to control the polarized light to propagate to the color filter unit with another color for realizing dark state display. 19. The display device according to claim 11, wherein the light extracting component comprises:
a first light extracting grating configured to extract first monochromatic light that is propagated in a totally reflected manner in the first substrate; a second light extracting grating configured to extract second monochromatic light that is propagated in a totally reflected manner in the first substrate; and a third light extracting grating configured to extract third monochromatic light that is propagated in a totally reflected manner in the first substrate; wherein the first light extracting grating, the second light extracting grating, and the third light extracting grating have different periods, and the first monochromatic light, the second monochromatic light, and the third monochromatic light are capable of being mixed into white light. 20. The display device according to claim 19, wherein the filter layer comprises a first color sub-pixel configured to transmit the first monochromatic light, a second color sub-pixel configured to transmit the second monochromatic light, and a third color sub-pixel configured to transmit the third monochromatic light, the first light extracting grating corresponds to at least one first color sub-pixel, the second light extracting grating corresponds to at least one second color sub-pixel, and the third light extracting grating corresponds to at least one third color sub-pixel. | 1,600 |
345,403 | 16,643,316 | 1,645 | An absorbent member (10) according to the present invention includes: a plurality of fiber clusters (11) containing synthetic fibers (11F); and a plurality of absorbent fibers (12F). The fiber clusters (11) are entangled with each other, or the fiber clusters (11) and the absorbent fibers (12F) are entangled. Each of the fiber clusters (11) includes two opposing base surfaces (111) and a body surface (112) that connects the two base surfaces (111). The number of fiber end portions per unit area in the body surface (112) is greater than the number of fiber end portions per unit area in each of the base surfaces (111). | 1. An absorbent member comprising:
a plurality of fiber clusters containing synthetic fibers; and a plurality of absorbent fibers, wherein the fiber clusters are entangled with each other, or the fiber clusters and the absorbent fibers are entangled, each of the fiber clusters includes two opposing base surfaces and a body surface that connects the two base surfaces, and the number of fiber end portions per unit area in the body surface is greater than the number of fiber end portions per unit area in each of the base surfaces. 2. The absorbent member according to claim 1,
wherein a total area of the two base surfaces is larger than a total area of the body surface. 3. The absorbent member according to claim 1,
wherein each of the fiber clusters includes an extended fiber bundle portion extending outward from the body surface and containing a plurality of fibers. 4. The absorbent member according to claim 3,
wherein the extended fiber bundle portion includes a thermally fused portion in which a plurality of fibers are thermally fused to each other. 5. The absorbent member according to claim 1,
wherein an outer shape of each of the fiber clusters is a rectangular parallelepiped shape or a disc shape. 6. The absorbent member according to claim 1,
wherein each of the base surfaces has a rectangular shape in a plan view, and a short side of the rectangular shape is smaller than or equal to a thickness of the absorbent member. 7. The absorbent member according to claim 1,
wherein, in projected views in two directions of the absorbent member that are orthogonal to each other, there are overlapping portions of the plurality of fiber clusters in an arbitral unit region of 10 mm square. 8. The absorbent member according to claim 1,
wherein each of the fiber clusters contains a plurality of thermoplastic fibers as the synthetic fibers, and has a three-dimensional structure in which the plurality of thermoplastic fibers are thermally fused to each other. 9. The absorbent member according to claim 1,
wherein a mass ratio of the fiber clusters and the absorbent fibers included, former/latter, is 20/80 to 80/20. 10. The absorbent member according to claim 1,
wherein, in the absorbent member, some fiber clusters are bonded to other fiber clusters or the absorbent fibers by means of entanglement, and some fiber clusters are capable of being entangled with other fiber clusters or the absorbent fibers. 11. The absorbent member according to claim 1,
wherein the fiber clusters are derived from a nonwoven fabric. 12. The absorbent member according to claim 1,
wherein a ratio of the number N1 of the fiber end portions per unit area in the base surfaces to the number N2 of the fiber end portions per unit area in the body surface, N1/N2, is 0 or more and 0.90 or less. 13. The absorbent member according to claim 1,
wherein the number of fiber end portions per unit area in the base surfaces is 0 fiber end portions/mm2 or more and 8 fiber end portions/mm2 or less. 14. An absorbent member comprising:
a plurality of fiber clusters containing synthetic fibers; and a plurality of absorbent fibers, wherein the fiber clusters are entangled with each other, or the fiber clusters and the absorbent fibers are entangled, each of the fiber clusters includes two opposing base surfaces and a body surface that connects the two base surfaces, and each of the fiber clusters includes an extended fiber bundle portion extending outward from the body surface and containing a plurality of fibers. 15. An absorbent article comprising the absorbent member according to claim 1. 16-25. (canceled) | An absorbent member (10) according to the present invention includes: a plurality of fiber clusters (11) containing synthetic fibers (11F); and a plurality of absorbent fibers (12F). The fiber clusters (11) are entangled with each other, or the fiber clusters (11) and the absorbent fibers (12F) are entangled. Each of the fiber clusters (11) includes two opposing base surfaces (111) and a body surface (112) that connects the two base surfaces (111). The number of fiber end portions per unit area in the body surface (112) is greater than the number of fiber end portions per unit area in each of the base surfaces (111).1. An absorbent member comprising:
a plurality of fiber clusters containing synthetic fibers; and a plurality of absorbent fibers, wherein the fiber clusters are entangled with each other, or the fiber clusters and the absorbent fibers are entangled, each of the fiber clusters includes two opposing base surfaces and a body surface that connects the two base surfaces, and the number of fiber end portions per unit area in the body surface is greater than the number of fiber end portions per unit area in each of the base surfaces. 2. The absorbent member according to claim 1,
wherein a total area of the two base surfaces is larger than a total area of the body surface. 3. The absorbent member according to claim 1,
wherein each of the fiber clusters includes an extended fiber bundle portion extending outward from the body surface and containing a plurality of fibers. 4. The absorbent member according to claim 3,
wherein the extended fiber bundle portion includes a thermally fused portion in which a plurality of fibers are thermally fused to each other. 5. The absorbent member according to claim 1,
wherein an outer shape of each of the fiber clusters is a rectangular parallelepiped shape or a disc shape. 6. The absorbent member according to claim 1,
wherein each of the base surfaces has a rectangular shape in a plan view, and a short side of the rectangular shape is smaller than or equal to a thickness of the absorbent member. 7. The absorbent member according to claim 1,
wherein, in projected views in two directions of the absorbent member that are orthogonal to each other, there are overlapping portions of the plurality of fiber clusters in an arbitral unit region of 10 mm square. 8. The absorbent member according to claim 1,
wherein each of the fiber clusters contains a plurality of thermoplastic fibers as the synthetic fibers, and has a three-dimensional structure in which the plurality of thermoplastic fibers are thermally fused to each other. 9. The absorbent member according to claim 1,
wherein a mass ratio of the fiber clusters and the absorbent fibers included, former/latter, is 20/80 to 80/20. 10. The absorbent member according to claim 1,
wherein, in the absorbent member, some fiber clusters are bonded to other fiber clusters or the absorbent fibers by means of entanglement, and some fiber clusters are capable of being entangled with other fiber clusters or the absorbent fibers. 11. The absorbent member according to claim 1,
wherein the fiber clusters are derived from a nonwoven fabric. 12. The absorbent member according to claim 1,
wherein a ratio of the number N1 of the fiber end portions per unit area in the base surfaces to the number N2 of the fiber end portions per unit area in the body surface, N1/N2, is 0 or more and 0.90 or less. 13. The absorbent member according to claim 1,
wherein the number of fiber end portions per unit area in the base surfaces is 0 fiber end portions/mm2 or more and 8 fiber end portions/mm2 or less. 14. An absorbent member comprising:
a plurality of fiber clusters containing synthetic fibers; and a plurality of absorbent fibers, wherein the fiber clusters are entangled with each other, or the fiber clusters and the absorbent fibers are entangled, each of the fiber clusters includes two opposing base surfaces and a body surface that connects the two base surfaces, and each of the fiber clusters includes an extended fiber bundle portion extending outward from the body surface and containing a plurality of fibers. 15. An absorbent article comprising the absorbent member according to claim 1. 16-25. (canceled) | 1,600 |
345,404 | 16,643,295 | 1,645 | Embodiments of the present disclosure provide a display substrate, a display panel, a display device and a manufacturing method thereof. The display substrate includes a base substrate and a metal wire grating layer on the base substrate. The metal wire grating layer includes a plurality of metal wire grating units, and polarization directions of the plurality of metal wire grating units are different. | 1. A display substrate, comprising a base substrate and a metal wire grating layer on the base substrate, wherein the metal wire grating layer comprises a plurality of metal wire grating units, and polarization directions of the plurality of metal wire grating units are different. 2. The display substrate according to claim 1, wherein the plurality of metal wire grating units are arranged in an array, and the polarization direction of each metal wire grating unit is different from the polarization direction of an adjacent metal wire grating unit that each metal wire grating unit is adjacent to. 3. The display substrate according to claim 2, wherein the polarization direction of each metal wire grating unit is perpendicular to the polarization direction of the adjacent metal wire grating unit that each metal wire grating unit is adjacent to. 4. The display substrate according to claim 1, wherein the plurality of metal wire grating units are arranged in an array, the metal wire grating units in a first direction have a same polarization direction, adjacent metal wire grating units among the metal wire grating units in a second direction have different polarization directions, and the first direction and the second direction are perpendicular to each other. 5. The display substrate according to claim 4, wherein the polarization directions of the adjacent metal wire grating units among the metal wire grating units in the second direction are perpendicular to each other. 6. The display substrate according to claim 1, wherein the polarization direction of each metal wire grating unit is parallel or perpendicular to a horizontal direction. 7. The display substrate according to claim 1, wherein the polarization direction of each metal wire grating unit is at a position of constituting an acute angle with respect to a horizontal direction. 8. A display panel, comprising a first display substrate and a second display substrate which are opposite to each other and are bonded to each other, wherein
each of the first display substrate and the second display substrate is the display substrate according to claim 1; and orthographic projections of the plurality of metal wire grating units of the first display substrate on the second display substrate respectively overlap the plurality of metal wire grating units of the second display substrate in a one-to-one manner, and the polarization directions of the metal wire grating unit of the first display substrate and the metal wire grating unit of the second display substrate which directly face each other are perpendicular to each other. 9. The display panel according to claim 8, wherein
the first display substrate is a color filter substrate, the color filter substrate further comprises a black matrix and a color filter layer, the color filter layer comprises a plurality of color filter units arranged in an array, and each color filter unit of the color filter layer is in a color filter region surrounded by the black matrix; and orthographic projections of the plurality of color filter units on the metal wire grating layer respectively overlap the plurality of metal wire grating units in a one-to-one manner. 10. The display panel according to claim 9, wherein the black matrix, the color filter layer and the metal wire grating layer are on a same side of the color filter substrate, and the plurality of color filter units of the color filter layer respectively cover the plurality of metal wire grating units of the metal wire grating layer. 11. The display panel according to claim 9, wherein the black matrix and the color filter layer are on a first side of the color filter substrate facing the second display substrate, the metal wire grating layer is on a second side of the color filter substrate, and the first side and the second side are opposite sides. 12. The display panel according to claim 8, wherein
the second display substrate is an array substrate, the array substrate further comprises a pixel layer, the pixel layer comprises a plurality of pixel units arranged in an array, and orthographic projections of the plurality of pixel units on the metal wire grating layer respectively overlap the plurality of metal wire grating units in a one-to-one manner. 13. The display panel according to claim 12, wherein the pixel layer and the metal wire grating layer are on a same side of the array substrate, and the plurality of pixel units of the pixel layer respectively cover the plurality of metal wire grating units of the metal wire grating layer. 14. The display panel according to claim 12, wherein the pixel layer is on a first side of the array substrate facing the first display substrate, the metal wire grating layer is on a second side of the array substrate, and the first side and the second side are opposite sides. 15. The display panel according to claim 13, wherein
the array substrate further comprises a plurality of gate wires and a plurality of data wires, the plurality of gate wires and the plurality of data wires cross each other to define the plurality of pixel units, and the metal wire grating layer is in a layer where the plurality of gate wires or the plurality of data wires are located. 16. The display panel according to claim 15, wherein among the plurality of metal wire grating units of the array substrate, an extension direction of metal wires in a part of the plurality of the metal wire grating units is parallel to the plurality of gate wires, and an extension direction of metal wires in another part of the plurality of the metal wire grating units is parallel to the plurality of data wires. 17. A display device, comprising the display panel according to claim 8. 18. A manufacturing method of the display substrate according to claim 1, comprising:
providing the base substrate; and forming the metal wire grating layer on the base substrate through a patterning process. 19. The display substrate according to claim 2, wherein the polarization direction of each metal wire grating unit is parallel or perpendicular to a horizontal direction. 20. The display substrate according to claim 4, wherein the polarization direction of each metal wire grating unit is at a position of constituting an acute angle with respect to a horizontal direction. | Embodiments of the present disclosure provide a display substrate, a display panel, a display device and a manufacturing method thereof. The display substrate includes a base substrate and a metal wire grating layer on the base substrate. The metal wire grating layer includes a plurality of metal wire grating units, and polarization directions of the plurality of metal wire grating units are different.1. A display substrate, comprising a base substrate and a metal wire grating layer on the base substrate, wherein the metal wire grating layer comprises a plurality of metal wire grating units, and polarization directions of the plurality of metal wire grating units are different. 2. The display substrate according to claim 1, wherein the plurality of metal wire grating units are arranged in an array, and the polarization direction of each metal wire grating unit is different from the polarization direction of an adjacent metal wire grating unit that each metal wire grating unit is adjacent to. 3. The display substrate according to claim 2, wherein the polarization direction of each metal wire grating unit is perpendicular to the polarization direction of the adjacent metal wire grating unit that each metal wire grating unit is adjacent to. 4. The display substrate according to claim 1, wherein the plurality of metal wire grating units are arranged in an array, the metal wire grating units in a first direction have a same polarization direction, adjacent metal wire grating units among the metal wire grating units in a second direction have different polarization directions, and the first direction and the second direction are perpendicular to each other. 5. The display substrate according to claim 4, wherein the polarization directions of the adjacent metal wire grating units among the metal wire grating units in the second direction are perpendicular to each other. 6. The display substrate according to claim 1, wherein the polarization direction of each metal wire grating unit is parallel or perpendicular to a horizontal direction. 7. The display substrate according to claim 1, wherein the polarization direction of each metal wire grating unit is at a position of constituting an acute angle with respect to a horizontal direction. 8. A display panel, comprising a first display substrate and a second display substrate which are opposite to each other and are bonded to each other, wherein
each of the first display substrate and the second display substrate is the display substrate according to claim 1; and orthographic projections of the plurality of metal wire grating units of the first display substrate on the second display substrate respectively overlap the plurality of metal wire grating units of the second display substrate in a one-to-one manner, and the polarization directions of the metal wire grating unit of the first display substrate and the metal wire grating unit of the second display substrate which directly face each other are perpendicular to each other. 9. The display panel according to claim 8, wherein
the first display substrate is a color filter substrate, the color filter substrate further comprises a black matrix and a color filter layer, the color filter layer comprises a plurality of color filter units arranged in an array, and each color filter unit of the color filter layer is in a color filter region surrounded by the black matrix; and orthographic projections of the plurality of color filter units on the metal wire grating layer respectively overlap the plurality of metal wire grating units in a one-to-one manner. 10. The display panel according to claim 9, wherein the black matrix, the color filter layer and the metal wire grating layer are on a same side of the color filter substrate, and the plurality of color filter units of the color filter layer respectively cover the plurality of metal wire grating units of the metal wire grating layer. 11. The display panel according to claim 9, wherein the black matrix and the color filter layer are on a first side of the color filter substrate facing the second display substrate, the metal wire grating layer is on a second side of the color filter substrate, and the first side and the second side are opposite sides. 12. The display panel according to claim 8, wherein
the second display substrate is an array substrate, the array substrate further comprises a pixel layer, the pixel layer comprises a plurality of pixel units arranged in an array, and orthographic projections of the plurality of pixel units on the metal wire grating layer respectively overlap the plurality of metal wire grating units in a one-to-one manner. 13. The display panel according to claim 12, wherein the pixel layer and the metal wire grating layer are on a same side of the array substrate, and the plurality of pixel units of the pixel layer respectively cover the plurality of metal wire grating units of the metal wire grating layer. 14. The display panel according to claim 12, wherein the pixel layer is on a first side of the array substrate facing the first display substrate, the metal wire grating layer is on a second side of the array substrate, and the first side and the second side are opposite sides. 15. The display panel according to claim 13, wherein
the array substrate further comprises a plurality of gate wires and a plurality of data wires, the plurality of gate wires and the plurality of data wires cross each other to define the plurality of pixel units, and the metal wire grating layer is in a layer where the plurality of gate wires or the plurality of data wires are located. 16. The display panel according to claim 15, wherein among the plurality of metal wire grating units of the array substrate, an extension direction of metal wires in a part of the plurality of the metal wire grating units is parallel to the plurality of gate wires, and an extension direction of metal wires in another part of the plurality of the metal wire grating units is parallel to the plurality of data wires. 17. A display device, comprising the display panel according to claim 8. 18. A manufacturing method of the display substrate according to claim 1, comprising:
providing the base substrate; and forming the metal wire grating layer on the base substrate through a patterning process. 19. The display substrate according to claim 2, wherein the polarization direction of each metal wire grating unit is parallel or perpendicular to a horizontal direction. 20. The display substrate according to claim 4, wherein the polarization direction of each metal wire grating unit is at a position of constituting an acute angle with respect to a horizontal direction. | 1,600 |
345,405 | 16,643,282 | 1,645 | A medication for preventing or treating influenza, said medication including an inactivated influenza virus or a recombinant vaccinia virus that includes, within the genome of the vaccinia virus DIs strain, an expression promoter and all or a portion of DNA coding for an influenza virus-derived protein. | 1. A method for prophylaxis or treatment of influenza, comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 2. The method according to claim 1, wherein prophylaxis or treatment of influenza is by the action of an activated CD4-positive cell and/or an activated CD8-positive cell. 3. The method according to claim 1, further comprising administering an antibody against an influenza virus-derived protein. 4. The method according to claim 3, wherein the antibody is a binding antibody. 5. The method of claim 1, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 6. A method for prophylaxis or treatment of influenza, comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of any one of components (a)-(c) below:
(a) at least one component selected from the group consisting of an activated CD4-positive cell, an activator of a CD4-positive cell and a combination of a CD4-positive cell and an activator of a CD4-positive cell; (b) at least one component selected from the group consisting of an activated CD8-positive cell, an activator of a CD8-positive cell and a combination of a CD8-positive cell and an activator of a CD8-positive cell; and (c) a component consisting of a combination of the components (a) and (b). 7. The method according to claim 6, further comprising administering a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 8. The method according to claim 6, further comprising administering an antibody against an influenza virus-derived protein. 9. The method according to claim 8, wherein the antibody is a binding antibody. 10. The medication method according to claim 7, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 11. A kit for prophylaxis or treatment of influenza, comprising a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 12. The kit according to claim 11, wherein prophylaxis or treatment of influenza is by the action of an activated CD4-positive cell and/or an activated CD8-positive cell. 13. The kit according to claim 11, further comprising an antibody against an influenza virus-derived protein. 14. The kit according to claim 13, wherein the antibody is a binding antibody. 15. The kit according to claim 11, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 16. A kit for prophylaxis or treatment of influenza, comprising any one of components (a)-(c) below:
(a) at least one component selected from the group consisting of an activated CD4-positive cell, an activator of a CD4-positive cell and a combination of a CD4-positive cell and an activator of a CD4-positive cell; (b) at least one component selected from the group consisting of an activated CD8-positive cell, an activator of a CD8-positive cell and a combination of a CD8-positive cell and an activator of a CD8-positive cell; and (c) a component consisting of a combination of the components (a) and (b). 17. The kit according to claim 16, further comprising a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 18. The kit according to claim 16, further comprising an antibody against an influenza virus-derived protein. 19. The kit according to claim 18, wherein the antibody is a binding antibody. 20. The kit according to claim 17, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. | A medication for preventing or treating influenza, said medication including an inactivated influenza virus or a recombinant vaccinia virus that includes, within the genome of the vaccinia virus DIs strain, an expression promoter and all or a portion of DNA coding for an influenza virus-derived protein.1. A method for prophylaxis or treatment of influenza, comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 2. The method according to claim 1, wherein prophylaxis or treatment of influenza is by the action of an activated CD4-positive cell and/or an activated CD8-positive cell. 3. The method according to claim 1, further comprising administering an antibody against an influenza virus-derived protein. 4. The method according to claim 3, wherein the antibody is a binding antibody. 5. The method of claim 1, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 6. A method for prophylaxis or treatment of influenza, comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of any one of components (a)-(c) below:
(a) at least one component selected from the group consisting of an activated CD4-positive cell, an activator of a CD4-positive cell and a combination of a CD4-positive cell and an activator of a CD4-positive cell; (b) at least one component selected from the group consisting of an activated CD8-positive cell, an activator of a CD8-positive cell and a combination of a CD8-positive cell and an activator of a CD8-positive cell; and (c) a component consisting of a combination of the components (a) and (b). 7. The method according to claim 6, further comprising administering a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 8. The method according to claim 6, further comprising administering an antibody against an influenza virus-derived protein. 9. The method according to claim 8, wherein the antibody is a binding antibody. 10. The medication method according to claim 7, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 11. A kit for prophylaxis or treatment of influenza, comprising a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 12. The kit according to claim 11, wherein prophylaxis or treatment of influenza is by the action of an activated CD4-positive cell and/or an activated CD8-positive cell. 13. The kit according to claim 11, further comprising an antibody against an influenza virus-derived protein. 14. The kit according to claim 13, wherein the antibody is a binding antibody. 15. The kit according to claim 11, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. 16. A kit for prophylaxis or treatment of influenza, comprising any one of components (a)-(c) below:
(a) at least one component selected from the group consisting of an activated CD4-positive cell, an activator of a CD4-positive cell and a combination of a CD4-positive cell and an activator of a CD4-positive cell; (b) at least one component selected from the group consisting of an activated CD8-positive cell, an activator of a CD8-positive cell and a combination of a CD8-positive cell and an activator of a CD8-positive cell; and (c) a component consisting of a combination of the components (a) and (b). 17. The kit according to claim 16, further comprising a recombinant vaccinia virus that contains an expression promoter and the entire or a part of DNA coding for an influenza virus-derived protein within a genome of a vaccinia virus DIs strain, or an inactivated influenza virus. 18. The kit according to claim 16, further comprising an antibody against an influenza virus-derived protein. 19. The kit according to claim 18, wherein the antibody is a binding antibody. 20. The kit according to claim 17, wherein the influenza virus-derived protein is a hemagglutinin protein derived from highly pathogenic H5N1 avian influenza virus. | 1,600 |
345,406 | 16,643,305 | 1,645 | In one embodiment of the present invention, a production device which produces a medical product and analyzes a starting material and a central management device which determines processing conditions in the production device are provided separately. In addition, by transmitting and receiving data and the like pertaining to the starting material between the production device and central management device data, the medical product is produced while production conditions therefor are continuously optimized. Thus, it is easy to produce a medical product while reducing or eliminating effects from changes in cells and tissues over time, from oscillation during transport, and from changes in surrounding environment such as changes in temperature, and to produce the desired medical product even when there are individual differences in the starting material. | 1. A production device, comprising:
an analysis unit that generates initial analysis data of human or animal cell or tissue that is a starting material of a medical product; a communication unit that transmits the initial analysis data to a central management device and receives initial processing data indicating a processing condition of the starting material optimized by the central management device based on the initial analysis data within a range of a predetermined design space as the processing condition of the starting material; and a processing unit that processes the starting material according to the initial processing data. 2. A production device, comprising:
an analysis unit that generates initial analysis data of human or animal cell or tissue that is a starting material of a medical product and a clinical data of the human or animal; a communication unit that transmits the initial analysis data and the clinical data to a central management device and receives initial processing data indicating a processing condition of the starting material optimized by the central management device based on the initial analysis data and the clinical data within a range of a predetermined design space as the processing condition of the starting material; and a processing unit that processes the starting material according to the initial processing data. 3. The production device according to claim 1, wherein the analysis unit generates intermediate analysis data of the intermediate product obtained by processing the starting material,
the communication unit transmits the intermediate analysis data to the central management device and receives intermediate processing data indicating the processing condition of the intermediate product optimized by the central management device based on the intermediate analysis data within a range of a predetermined design space as the processing condition of the intermediate product, and the processing unit processes the intermediate product according to the intermediate processing data. 4. The production device according to claim 1, wherein the analysis unit measures at least one of the number of viable cells and a viable cell rate of the starting material. 5. The production device according to claim 1, wherein the processing unit cultivates the cell or tissue. 6. The production device according to claim 1, further comprising: a transfer unit that transfers the starting material from at least one of the analysis unit and the processing unit to the other of the analysis unit and the processing unit. 7. The production device according to claim 1, wherein the medical product is an autologous product. 8. The production device according to claim 1, wherein the analysis unit generates final analysis data of the medical product produced from the starting material, and
the communication unit transmits the final analysis data to the central management device to record the final analysis data by associating the final analysis data with the initial analysis data and the initial processing data in the central management device. 9. A system, comprising:
the plurality of production devices according to claim 8, wherein the central management device includes: a central storage unit that records the initial analysis data, the initial processing data, and the final analysis data transmitted from each of the plurality of production devices in association with each other, a central analysis unit that when a target production device transmits latest initial analysis data newly generated in the target production device which is any one of the plurality of production devices, generates latest initial processing data optimal for the latest initial analysis data by referring to the initial analysis data, the initial processing data, and the final analysis data recorded in association with each other in the central storage unit; and a central communication unit that transmits the latest initial processing data to the target production device. 10. A method for producing a medical product in a production device controlled by a central management device, the method comprising:
generating, by the production device, initial analysis data of human or animal cell or tissue that is a starting material of the medical product; transmitting, by the production device, the initial analysis data to the central management device; generating, by the central management device, initial processing data indicating a processing condition of the starting material optimized based on the initial analysis data within a range of a predetermined design space as a processing condition of the starting material; transmitting, by the central management device, the initial processing data to the production device; and processing, by the production device, the starting material according to the initial processing data. | In one embodiment of the present invention, a production device which produces a medical product and analyzes a starting material and a central management device which determines processing conditions in the production device are provided separately. In addition, by transmitting and receiving data and the like pertaining to the starting material between the production device and central management device data, the medical product is produced while production conditions therefor are continuously optimized. Thus, it is easy to produce a medical product while reducing or eliminating effects from changes in cells and tissues over time, from oscillation during transport, and from changes in surrounding environment such as changes in temperature, and to produce the desired medical product even when there are individual differences in the starting material.1. A production device, comprising:
an analysis unit that generates initial analysis data of human or animal cell or tissue that is a starting material of a medical product; a communication unit that transmits the initial analysis data to a central management device and receives initial processing data indicating a processing condition of the starting material optimized by the central management device based on the initial analysis data within a range of a predetermined design space as the processing condition of the starting material; and a processing unit that processes the starting material according to the initial processing data. 2. A production device, comprising:
an analysis unit that generates initial analysis data of human or animal cell or tissue that is a starting material of a medical product and a clinical data of the human or animal; a communication unit that transmits the initial analysis data and the clinical data to a central management device and receives initial processing data indicating a processing condition of the starting material optimized by the central management device based on the initial analysis data and the clinical data within a range of a predetermined design space as the processing condition of the starting material; and a processing unit that processes the starting material according to the initial processing data. 3. The production device according to claim 1, wherein the analysis unit generates intermediate analysis data of the intermediate product obtained by processing the starting material,
the communication unit transmits the intermediate analysis data to the central management device and receives intermediate processing data indicating the processing condition of the intermediate product optimized by the central management device based on the intermediate analysis data within a range of a predetermined design space as the processing condition of the intermediate product, and the processing unit processes the intermediate product according to the intermediate processing data. 4. The production device according to claim 1, wherein the analysis unit measures at least one of the number of viable cells and a viable cell rate of the starting material. 5. The production device according to claim 1, wherein the processing unit cultivates the cell or tissue. 6. The production device according to claim 1, further comprising: a transfer unit that transfers the starting material from at least one of the analysis unit and the processing unit to the other of the analysis unit and the processing unit. 7. The production device according to claim 1, wherein the medical product is an autologous product. 8. The production device according to claim 1, wherein the analysis unit generates final analysis data of the medical product produced from the starting material, and
the communication unit transmits the final analysis data to the central management device to record the final analysis data by associating the final analysis data with the initial analysis data and the initial processing data in the central management device. 9. A system, comprising:
the plurality of production devices according to claim 8, wherein the central management device includes: a central storage unit that records the initial analysis data, the initial processing data, and the final analysis data transmitted from each of the plurality of production devices in association with each other, a central analysis unit that when a target production device transmits latest initial analysis data newly generated in the target production device which is any one of the plurality of production devices, generates latest initial processing data optimal for the latest initial analysis data by referring to the initial analysis data, the initial processing data, and the final analysis data recorded in association with each other in the central storage unit; and a central communication unit that transmits the latest initial processing data to the target production device. 10. A method for producing a medical product in a production device controlled by a central management device, the method comprising:
generating, by the production device, initial analysis data of human or animal cell or tissue that is a starting material of the medical product; transmitting, by the production device, the initial analysis data to the central management device; generating, by the central management device, initial processing data indicating a processing condition of the starting material optimized based on the initial analysis data within a range of a predetermined design space as a processing condition of the starting material; transmitting, by the central management device, the initial processing data to the production device; and processing, by the production device, the starting material according to the initial processing data. | 1,600 |
345,407 | 16,643,311 | 1,645 | A method for managing network congestion is provided. The method comprises: receiving, at a receiver, a packet comprising a timestamp provided by a first clock of a sender; deriving, by the receiver, a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of the receiver; determining a latency change by comparing the latency value with a previous latency value; and determining a state of network congestion based at least in part on the latency change. | 1. A method for managing network congestion, comprising:
a) receiving, at a receiver, a packet comprising a timestamp provided by a first clock of a sender; b) deriving, by the receiver, a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of the receiver; c) determining a latency change by comparing the latency value with a previous latency value; and d) determining a state of network congestion based at least in part on the latency change. 2. The method of claim 1, wherein the packet is a regular packet. 3. The method of claim 1, wherein the packet is a notification packet. 4. The method of claim 3, wherein the packet is a congestion notification packet. 5. The method of claim 1, wherein the first clock and the second clock are not synchronized. 6. The method of claim 1, wherein the first clock and the second clock operate at a pre-determined frequency. 7. The method of claim 6, wherein the pre-determined frequency is set up prior to transmission of the packet. 8. The method of claim 6, wherein the pre-determined frequency is set up by a connection protocol. 9. The method of claim 1, wherein the first clock and the second clock operate at different frequencies. 10. The method of claim 9, wherein the frequency of the first clock is known by the receiver during a connection setup between the sender and receiver. 11. The method of claim 6, wherein a frequency drift is prevented by resetting one or more previously obtained latency values stored in a memory accessible by the receiver. 12. The method of claim 6, wherein a frequency drift is detected based on a minimum latency value tracked by the sender. 13. The method of claim 1, wherein the latency value is associated with a forward path latency. 14. The method of claim 1, wherein the latency value is derived by calculating the time difference between the timestamp and the receipt time provided by the second clock. 15. The method of claim 1, wherein the previous latency value is a minimum latency value or a latency value of a first packet among one or more previously obtained latency values. 16. The method of claim 15, wherein the one or more previously obtained latency values are calculated by the receiver and stored in a memory accessible by the receiver. 17. The method of claim 15, wherein the minimum latency value is updated when the latency change is a decrease. 18. The method of claim 1, wherein the state of network congestion is determined by comparing the latency change against a threshold. 19. The method of claim 18, wherein the threshold is configurable. 20. The method of claim 18, wherein the state of network congestion is determined when the latency change is above the threshold. 21. The method of claim 1, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with the previous latency value. 22. The method of claim 1, wherein the latency change is determined by the receiver. 23. The method of claim 1, wherein the latency change is determined by the sender. 24. The method of claim 1, wherein the state of network congestion is determined by the receiver. 25. The method of claim 1, wherein the state of network congestion is determined by the sender. 26. The method of claim 1, further comprising generating a report message comprising the latency change. 27. The method of claim 26, wherein the report message is a congestion notification packet. 28. The method of claim 26, wherein the report message is contained in a regular data packet transmitted from the receiver to the sender. 29. The method of claim 26, wherein the report message is transmitted from the receiver to the sender. 30. The method of claim 26, wherein the report message is generated upon determination of the state of network congestion. 31. The method of claim 26, wherein the report message is generated at receipt of the packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold. 32. The method of claim 26, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 33. The method of claim 26, further comprising adjusting a packet flow rate when a lapse of time since last received report message exceeds a pre-determined lapse threshold. 34. The method of claim 1, further comprising adjusting a packet flow rate based at least in part on the latency change. 35. The method of claim 34, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 36. The method of claim 35, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate, or a combination of the above. 37. The method of claim 35, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 38. A system for managing network congestion, comprising:
a) a memory for storing one or more previously obtained latency values and a set of instructions; and b) one or more processors configured to execute the set of instructions to:
i) receive a packet comprising a timestamp provided by a first clock of a sender;
ii) derive a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of a receiver;
iii) determine a latency change by comparing the latency value with a previous latency value from the one or more previously obtained latency values; and
iv) determine a state of network congestion based at least in part on the latency change. 39. The system of claim 38, wherein the first clock and the second clock are not synchronized. 40. The system of claim 38, wherein the first clock and the second clock operate at a pre-determined frequency. 41. The system of claim 38, wherein the first clock and the second clock operate at different frequencies. 42. The system of claim 38, wherein the latency value is associated with a forward path latency. 43. The system of claim 38, wherein the previous latency value is a minimum latency value or a latency value of a first packet among one or more previously obtained latency values. 44. The system of claim 38, wherein the state of network congestion is determined by comparing the latency change against a threshold. 45. The system of claim 44, wherein the state of network congestion is determined when the latency change is above the threshold. 46. The system of claim 38, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with the previous latency value. 47. The system of claim 38, wherein the one or more processors are local to the receiver. 48. A method for managing network congestion, comprising:
a) receiving, at a sender, a report message comprising a latency change, wherein the latency change is associated with a one-way path from the sender to a receiver; and b) adjusting a packet flow rate based at least in part on the latency change. 49. The method of claim 48, wherein the latency change is obtained by comparing a latency value with a previous latency value. 50. The method of claim 49, wherein the latency value is obtained based at least in part on a timestamp provided by a first clock of the sender and a receipt time provided by a second clock of the receiver. 51. The method of claim 50, wherein the first clock and the second clock are not synchronized. 52. The method of claim 50, wherein the previous latency value is a minimum latency value among one or more previously obtained latency values. 53. The method of claim 52, wherein the one or more previously obtained latency values are calculated by the receiver and stored in a memory accessible by the receiver. 54. The method of claim 52, wherein the minimum value is updated when the latency change is a decrease. 55. The method of claim 48, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with a previous latency value. 56. The method of claim 48, wherein the report message is a congestion notification packet generated by the receiver. 57. The method of claim 56, wherein the congestion notification packet is generated upon determination of a state of network congestion. 58. The method of claim 57, wherein the state of network congestion is determined by comparing the latency change against a threshold. 59. The method of claim 58, wherein the threshold is pre-determined or configurable. 60. The method of claim 58, wherein the state of network congestion is determined when the latency change is above the threshold. 61. The method of claim 56, wherein the congestion notification packet is generated at receipt of a packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold, and wherein the packet is generated by the sender. 62. The method of claim 48, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 63. The method of claim 62, wherein the minimum latency value is used for deriving the latency change. 64. The method of claim 62, further comprising adjusting a packet flow rate when a lapse of time since last received report message by the sender exceeds a pre-determined lapse threshold. 65. The method of claim 48, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 66. The method of claim 65, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate or a combination of the above. 67. The method of claim 65, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 68. A system for managing network congestion, comprising:
a) a memory for storing a set of instructions; and b) one or more processors configured to execute the set of instructions to:
i) receive, a report message comprising a latency change, wherein the latency change is associated with a one-way path from a sender to a receiver; and
ii) adjust a packet flow rate based at least in part on the latency change. 69. The system of claim 68, wherein the latency change is obtained by comparing a latency value with a previous latency value. 70. The system of claim 69, wherein the latency value is obtained based at least in part on a timestamp provided by a first clock of the sender and a receipt time provided by a second clock of the receiver. 71. The system of claim 70, wherein the first clock and the second clock are not synchronized. 72. The system of claim 70, wherein the previous latency value is a minimum latency value among one or more previously obtained latency values. 73. The system of claim 68, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with a previous latency value. 74. The system of claim 68, wherein the report message is a congestion notification packet generated by the receiver. 75. The system of claim 74, wherein the congestion notification packet is generated upon determination of a state of network congestion. 76. The system of claim 75, wherein the state of network congestion is determined by comparing the latency change against a threshold. 77. The system of claim 76, wherein the threshold is pre-determined or configurable. 78. The system of claim 76, wherein the state of network congestion is determined when the latency change is above the threshold. 79. The system of claim 74, wherein the congestion notification packet is generated at receipt of a packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold, and wherein the packet is generated by the sender. 80. The system of claim 68, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 81. The system of claim 80, further comprising adjusting the packet flow rate when a lapse of time since last received report message by the sender exceeds a pre-determined lapse threshold. 82. The system of claim 80, wherein the minimum latency value is used for deriving a queueing delay. 83. The system of claim 68, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 84. The system of claim 83, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate or a combination of the above. 85. The system of claim 84, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 86. The system of claim 68, wherein the one or more processors are local to the sender. | A method for managing network congestion is provided. The method comprises: receiving, at a receiver, a packet comprising a timestamp provided by a first clock of a sender; deriving, by the receiver, a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of the receiver; determining a latency change by comparing the latency value with a previous latency value; and determining a state of network congestion based at least in part on the latency change.1. A method for managing network congestion, comprising:
a) receiving, at a receiver, a packet comprising a timestamp provided by a first clock of a sender; b) deriving, by the receiver, a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of the receiver; c) determining a latency change by comparing the latency value with a previous latency value; and d) determining a state of network congestion based at least in part on the latency change. 2. The method of claim 1, wherein the packet is a regular packet. 3. The method of claim 1, wherein the packet is a notification packet. 4. The method of claim 3, wherein the packet is a congestion notification packet. 5. The method of claim 1, wherein the first clock and the second clock are not synchronized. 6. The method of claim 1, wherein the first clock and the second clock operate at a pre-determined frequency. 7. The method of claim 6, wherein the pre-determined frequency is set up prior to transmission of the packet. 8. The method of claim 6, wherein the pre-determined frequency is set up by a connection protocol. 9. The method of claim 1, wherein the first clock and the second clock operate at different frequencies. 10. The method of claim 9, wherein the frequency of the first clock is known by the receiver during a connection setup between the sender and receiver. 11. The method of claim 6, wherein a frequency drift is prevented by resetting one or more previously obtained latency values stored in a memory accessible by the receiver. 12. The method of claim 6, wherein a frequency drift is detected based on a minimum latency value tracked by the sender. 13. The method of claim 1, wherein the latency value is associated with a forward path latency. 14. The method of claim 1, wherein the latency value is derived by calculating the time difference between the timestamp and the receipt time provided by the second clock. 15. The method of claim 1, wherein the previous latency value is a minimum latency value or a latency value of a first packet among one or more previously obtained latency values. 16. The method of claim 15, wherein the one or more previously obtained latency values are calculated by the receiver and stored in a memory accessible by the receiver. 17. The method of claim 15, wherein the minimum latency value is updated when the latency change is a decrease. 18. The method of claim 1, wherein the state of network congestion is determined by comparing the latency change against a threshold. 19. The method of claim 18, wherein the threshold is configurable. 20. The method of claim 18, wherein the state of network congestion is determined when the latency change is above the threshold. 21. The method of claim 1, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with the previous latency value. 22. The method of claim 1, wherein the latency change is determined by the receiver. 23. The method of claim 1, wherein the latency change is determined by the sender. 24. The method of claim 1, wherein the state of network congestion is determined by the receiver. 25. The method of claim 1, wherein the state of network congestion is determined by the sender. 26. The method of claim 1, further comprising generating a report message comprising the latency change. 27. The method of claim 26, wherein the report message is a congestion notification packet. 28. The method of claim 26, wherein the report message is contained in a regular data packet transmitted from the receiver to the sender. 29. The method of claim 26, wherein the report message is transmitted from the receiver to the sender. 30. The method of claim 26, wherein the report message is generated upon determination of the state of network congestion. 31. The method of claim 26, wherein the report message is generated at receipt of the packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold. 32. The method of claim 26, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 33. The method of claim 26, further comprising adjusting a packet flow rate when a lapse of time since last received report message exceeds a pre-determined lapse threshold. 34. The method of claim 1, further comprising adjusting a packet flow rate based at least in part on the latency change. 35. The method of claim 34, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 36. The method of claim 35, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate, or a combination of the above. 37. The method of claim 35, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 38. A system for managing network congestion, comprising:
a) a memory for storing one or more previously obtained latency values and a set of instructions; and b) one or more processors configured to execute the set of instructions to:
i) receive a packet comprising a timestamp provided by a first clock of a sender;
ii) derive a latency value based at least in part on the timestamp provided by the first clock and a receipt time provided by a second clock of a receiver;
iii) determine a latency change by comparing the latency value with a previous latency value from the one or more previously obtained latency values; and
iv) determine a state of network congestion based at least in part on the latency change. 39. The system of claim 38, wherein the first clock and the second clock are not synchronized. 40. The system of claim 38, wherein the first clock and the second clock operate at a pre-determined frequency. 41. The system of claim 38, wherein the first clock and the second clock operate at different frequencies. 42. The system of claim 38, wherein the latency value is associated with a forward path latency. 43. The system of claim 38, wherein the previous latency value is a minimum latency value or a latency value of a first packet among one or more previously obtained latency values. 44. The system of claim 38, wherein the state of network congestion is determined by comparing the latency change against a threshold. 45. The system of claim 44, wherein the state of network congestion is determined when the latency change is above the threshold. 46. The system of claim 38, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with the previous latency value. 47. The system of claim 38, wherein the one or more processors are local to the receiver. 48. A method for managing network congestion, comprising:
a) receiving, at a sender, a report message comprising a latency change, wherein the latency change is associated with a one-way path from the sender to a receiver; and b) adjusting a packet flow rate based at least in part on the latency change. 49. The method of claim 48, wherein the latency change is obtained by comparing a latency value with a previous latency value. 50. The method of claim 49, wherein the latency value is obtained based at least in part on a timestamp provided by a first clock of the sender and a receipt time provided by a second clock of the receiver. 51. The method of claim 50, wherein the first clock and the second clock are not synchronized. 52. The method of claim 50, wherein the previous latency value is a minimum latency value among one or more previously obtained latency values. 53. The method of claim 52, wherein the one or more previously obtained latency values are calculated by the receiver and stored in a memory accessible by the receiver. 54. The method of claim 52, wherein the minimum value is updated when the latency change is a decrease. 55. The method of claim 48, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with a previous latency value. 56. The method of claim 48, wherein the report message is a congestion notification packet generated by the receiver. 57. The method of claim 56, wherein the congestion notification packet is generated upon determination of a state of network congestion. 58. The method of claim 57, wherein the state of network congestion is determined by comparing the latency change against a threshold. 59. The method of claim 58, wherein the threshold is pre-determined or configurable. 60. The method of claim 58, wherein the state of network congestion is determined when the latency change is above the threshold. 61. The method of claim 56, wherein the congestion notification packet is generated at receipt of a packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold, and wherein the packet is generated by the sender. 62. The method of claim 48, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 63. The method of claim 62, wherein the minimum latency value is used for deriving the latency change. 64. The method of claim 62, further comprising adjusting a packet flow rate when a lapse of time since last received report message by the sender exceeds a pre-determined lapse threshold. 65. The method of claim 48, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 66. The method of claim 65, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate or a combination of the above. 67. The method of claim 65, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 68. A system for managing network congestion, comprising:
a) a memory for storing a set of instructions; and b) one or more processors configured to execute the set of instructions to:
i) receive, a report message comprising a latency change, wherein the latency change is associated with a one-way path from a sender to a receiver; and
ii) adjust a packet flow rate based at least in part on the latency change. 69. The system of claim 68, wherein the latency change is obtained by comparing a latency value with a previous latency value. 70. The system of claim 69, wherein the latency value is obtained based at least in part on a timestamp provided by a first clock of the sender and a receipt time provided by a second clock of the receiver. 71. The system of claim 70, wherein the first clock and the second clock are not synchronized. 72. The system of claim 70, wherein the previous latency value is a minimum latency value among one or more previously obtained latency values. 73. The system of claim 68, wherein the latency change is obtained by comparing an average of a sequence of latency values within a window with a previous latency value. 74. The system of claim 68, wherein the report message is a congestion notification packet generated by the receiver. 75. The system of claim 74, wherein the congestion notification packet is generated upon determination of a state of network congestion. 76. The system of claim 75, wherein the state of network congestion is determined by comparing the latency change against a threshold. 77. The system of claim 76, wherein the threshold is pre-determined or configurable. 78. The system of claim 76, wherein the state of network congestion is determined when the latency change is above the threshold. 79. The system of claim 74, wherein the congestion notification packet is generated at receipt of a packet by the receiver or when a lapse of time since last received packet exceeds a pre-determined lapse threshold, and wherein the packet is generated by the sender. 80. The system of claim 68, wherein the report message further comprises a minimum latency value among one or more previously obtained latency values and/or a delivery rate. 81. The system of claim 80, further comprising adjusting the packet flow rate when a lapse of time since last received report message by the sender exceeds a pre-determined lapse threshold. 82. The system of claim 80, wherein the minimum latency value is used for deriving a queueing delay. 83. The system of claim 68, wherein the packet flow rate is adjusted in response to the latency change according to a pre-determined reaction scheme. 84. The system of claim 83, wherein the reaction scheme comprises adjusting the packet flow rate based on the latency change, the first order derivative of latency change, the second order derivative of latency change, a delivery rate or a combination of the above. 85. The system of claim 84, wherein the reaction scheme comprises one or more coefficients for adjusting the packet flow rate. 86. The system of claim 68, wherein the one or more processors are local to the sender. | 1,600 |
345,408 | 16,643,321 | 2,667 | This disclosure provides a system and method for producing ultrasound images based on Full Waveform Inversion (FWI). The system captures acoustic/(an)elastic waves transmitted through and reflected and/or diffracted from a medium. The system performs an FWI process in a time domain in conjunction with an accurate wave propagation solver. The system produces 3D maps of physical parameters that control wave propagation, such as shear and compressional wavespeeds, mass density, attenuation, Poisson's ratio, bulk and shear moduli, impedance, and even the fourth-order elastic tensor containing up to 21 independent parameters, which are of significant diagnostic value, e.g., for medical imaging and non-destructive testing. | 1. A system for producing ultrasound images, comprising:
a transmitting element, configured to emit a signal having a special band of frequencies specified by a priori knowledge of a medium and an image reconstruction algorithm, wherein the transmitting element has a precisely known and controlled location within the system; a receiving element, configured to capture acoustic/(an)elastic waves that are emitted by the transmitting element and that are transmitted through and reflected from the medium, wherein the receiving element has a small lateral extent and a precisely known and controlled location within the system; a processor; and a non-transitory computer readable medium containing programming instructions that, when executed, cause the processor to: convert the captured acoustic/(an)elastic waves into observed imaging data; perform a Full Waveform Inversion process in a time domain on the observed imaging data against synthesized data derived from a simulated model of the observed imaging data using an accurate wave propagation solver; use the synthesized data to generate image representations of the medium; and store or display the image representations of the medium. 2. The system of claim 1, further comprising one or more additional receiving elements located at a different position from the transmitting element, configured to capture the acoustic/(an)elastic waves that are transmitted through the medium. 3. The system of claim 1 or 2, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to perform three-dimensional acoustic or viscoacoustic simulations. 4. The system of claim 1 or 2, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to perform three-dimensional elastic or anelastic simulations. 5. The system of any one of the preceding claims, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to invert low-frequency content of the observed imaging data followed by progressively adding higher frequency content of the observed imaging data. 6. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to smooth the simulated model. 7. The system of claim 6, wherein the programming instructions for smoothing the simulated model further comprise programming instructions that, when executed, cause the processor to smooth the simulated model by a Gaussian smoothing process. 8. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is a physical three-dimensional model. 9. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of a human tissue or of a non-human object. 10. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is immersed in a liquid. 11. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is immersed in water. 12. The system of any one of the preceding claims, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to:
(i) provide an initial physical model; (ii) determine the synthesized data, by a computer, by simulating wave propagation through the physical model; (iii) back-propagate adjoint source terms determined by a cost function based on a comparison of the synthesized data and the converted acoustic/(an)elastic wave data to update the physical model; and (iv) repeat (ii) and (iii) until the residual between the synthesized data and the converted acoustic/(an)elastic wave data is less than a predetermined threshold. 13. A method of producing a set of ultrasound images, the method comprising:
emitting, by a transmitting element, a signal having a special band of frequencies specified by a priori knowledge of a medium and the image reconstruction algorithm, wherein the transmitting element has a precisely known and controlled location within a system; capturing, by a receiving element, acoustic/(an)elastic waves that are emitted by the transmitting element and that are transmitted through and reflected from the medium, wherein the receiving element has a small lateral extent and a precisely known and controlled location within the system; converting the captured acoustic/(an)elastic waves into observed imaging data; performing a Full Waveform Inversion process in a time domain on the observed imaging data against synthesized data derived from a simulated model of the observed imaging data using an accurate wave propagation solver; using the synthesized data to generate image representations of the medium; and storing or displaying image representations of the medium. 14. The method of claim 13, further comprising:
capturing, by one or more additional receiving elements located at a different location from the transmitting element, the acoustic/(an)elastic waves that are transmitted through the medium. 15. The method of claim 13 or 14, wherein performing the Full Waveform Inversion process further comprises performing three-dimensional acoustic or viscoacoustic simulations. 16. The method of claim 13 or 14, wherein performing the Full Waveform Inversion process further comprises performing three-dimensional elastic or anelastic simulations. 17. The method of any one of claims 13 to 16, wherein performing the Full Waveform Inversion process comprises inverting low-frequency content of the observed imaging data followed by progressively adding higher frequency content of the observed imaging data. 18. The method of claim any one of claims 13 to 17, further comprising smoothing the simulated model. 19. The method of claim 18, wherein smoothing the simulated model comprises applying a Gaussian smoothing process to the simulation model. 20. The method of any one of claims 13 to 19, wherein the image representations of the medium is a physical three-dimensional model. 21. The method of any one of claims 13 to 20, wherein the medium is a human tissue or a non-human object. 22. The method of any one of claims 13 to 21, wherein the medium is an object being non-destructively tested (NDT) for quality assurance/quality control (QA/QC) or for measurement purposes. 23. The method of any one of claims 13 to 21, wherein capturing the acoustic waves further comprises immersing the medium in a liquid. 24. The method of claim 23, wherein the liquid is water. 25. The method of any one of claims 13 to 24, wherein performing the Full Waveform Inversion process comprises:
(i) providing an initial physical model;
(ii) determining the synthesized data, by a computer, by simulating wave propagation through the physical model;
(iii) back-propagating adjoint source terms determined by a cost function based on a comparison of the synthesized data and the converted acoustic/(an)elastic wave data to update the physical model; and
(iv) repeating (ii) and (iii) until the residual is less than a predetermined threshold. 26. The method of claim 25, wherein the cost function is a waveform cost function, an expression of the waveform cost function comprising:
F W(m)=½Σr=1 N rec ∫0 T |p obs(x r ,t)−p syn(x r ,t,m)|2 dt,
wherein FW(m) is a sum of the residuals between the synthesized data, psyn(xr, t, m), and the converted acoustic/(an)elastic wave data, pobs(xr, t), over Nrec number of the receiving transducers r at xr, over a time window T, wherein m are the maps of selected parameters. 27. The method of claim 25, wherein the cost function is a traveltime cost function, an expression of the traveltime cost function comprising:
F T(m)=½Σr=1 N rec |T obs(x r)−T syn(x r ,m)|2,
wherein FT (m) is a sum of the residuals between the synthetic time of flight, Tsyn (xr, m), and the time of flight of converted acoustic/(an)elastic wave data, Tobs(xr), over Nrec number of the receiving transducers r at xr, wherein m are the maps of selected parameters. 28. The method of claim 25, wherein the cost function is an instantaneous phase (IP) cost function, an expression of the instantaneous phase cost function comprising:
F IP(m)=½Σr=1 N rec ∫0 T|ψobs(x r ,t)−ψsyn(x r ,t,m)|2 dt,
wherein FIP(m) is a sum of the residuals between the IP of synthesized data, ψsyn(xr, t, m), and the IP of converted acoustic/(an)elastic wave data, ψobs(xr, t), over Nrec number of the receiving transducers r at xr, over a time window T, wherein m are the maps of selected parameters. 29. The method of claim 25, wherein the cost function is a double difference cost function, an expression of the double difference cost function comprising:
F DD(m)=½Σi=1 N rec Σj>i N rec |Δt ij(p obs)−Δt ij(p syn(m))|2,
wherein FDD (m) is a sum of the residuals between the synthetic time of flight difference Δtij(psyn(m)), and the converted acoustic/(an)elastic wave data time of flight difference Δtij (pobs), between each pair from the Nrec receiving transducers, wherein m are the maps of selected parameters. 30. The method of claim 25, wherein the cost function is a hybrid cost function, an expression of the hybrid cost function comprising:
F H(m)=αF T(m)+βF DD(m)+γF IP(m)+δF W(m),
Wherein FT(m) is the traveltime cost function, FDD(m) is the double difference cost function, FIP (m) is the instantaneous phase cost function and FW(m) is the waveform cost function, wherein α, β, γ and δ are weights of FT(m), FDD(m), FIP(m) and FW(m), respectively. | This disclosure provides a system and method for producing ultrasound images based on Full Waveform Inversion (FWI). The system captures acoustic/(an)elastic waves transmitted through and reflected and/or diffracted from a medium. The system performs an FWI process in a time domain in conjunction with an accurate wave propagation solver. The system produces 3D maps of physical parameters that control wave propagation, such as shear and compressional wavespeeds, mass density, attenuation, Poisson's ratio, bulk and shear moduli, impedance, and even the fourth-order elastic tensor containing up to 21 independent parameters, which are of significant diagnostic value, e.g., for medical imaging and non-destructive testing.1. A system for producing ultrasound images, comprising:
a transmitting element, configured to emit a signal having a special band of frequencies specified by a priori knowledge of a medium and an image reconstruction algorithm, wherein the transmitting element has a precisely known and controlled location within the system; a receiving element, configured to capture acoustic/(an)elastic waves that are emitted by the transmitting element and that are transmitted through and reflected from the medium, wherein the receiving element has a small lateral extent and a precisely known and controlled location within the system; a processor; and a non-transitory computer readable medium containing programming instructions that, when executed, cause the processor to: convert the captured acoustic/(an)elastic waves into observed imaging data; perform a Full Waveform Inversion process in a time domain on the observed imaging data against synthesized data derived from a simulated model of the observed imaging data using an accurate wave propagation solver; use the synthesized data to generate image representations of the medium; and store or display the image representations of the medium. 2. The system of claim 1, further comprising one or more additional receiving elements located at a different position from the transmitting element, configured to capture the acoustic/(an)elastic waves that are transmitted through the medium. 3. The system of claim 1 or 2, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to perform three-dimensional acoustic or viscoacoustic simulations. 4. The system of claim 1 or 2, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to perform three-dimensional elastic or anelastic simulations. 5. The system of any one of the preceding claims, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to invert low-frequency content of the observed imaging data followed by progressively adding higher frequency content of the observed imaging data. 6. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to smooth the simulated model. 7. The system of claim 6, wherein the programming instructions for smoothing the simulated model further comprise programming instructions that, when executed, cause the processor to smooth the simulated model by a Gaussian smoothing process. 8. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is a physical three-dimensional model. 9. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of a human tissue or of a non-human object. 10. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is immersed in a liquid. 11. The system of any one of the preceding claims, wherein the programming instructions further comprise programming instructions that, when executed, cause the processor to generate the image representation of the medium that is immersed in water. 12. The system of any one of the preceding claims, wherein the programming instructions for performing the Full Waveform Inversion process further comprises programming instructions that, when executed, cause the processor to:
(i) provide an initial physical model; (ii) determine the synthesized data, by a computer, by simulating wave propagation through the physical model; (iii) back-propagate adjoint source terms determined by a cost function based on a comparison of the synthesized data and the converted acoustic/(an)elastic wave data to update the physical model; and (iv) repeat (ii) and (iii) until the residual between the synthesized data and the converted acoustic/(an)elastic wave data is less than a predetermined threshold. 13. A method of producing a set of ultrasound images, the method comprising:
emitting, by a transmitting element, a signal having a special band of frequencies specified by a priori knowledge of a medium and the image reconstruction algorithm, wherein the transmitting element has a precisely known and controlled location within a system; capturing, by a receiving element, acoustic/(an)elastic waves that are emitted by the transmitting element and that are transmitted through and reflected from the medium, wherein the receiving element has a small lateral extent and a precisely known and controlled location within the system; converting the captured acoustic/(an)elastic waves into observed imaging data; performing a Full Waveform Inversion process in a time domain on the observed imaging data against synthesized data derived from a simulated model of the observed imaging data using an accurate wave propagation solver; using the synthesized data to generate image representations of the medium; and storing or displaying image representations of the medium. 14. The method of claim 13, further comprising:
capturing, by one or more additional receiving elements located at a different location from the transmitting element, the acoustic/(an)elastic waves that are transmitted through the medium. 15. The method of claim 13 or 14, wherein performing the Full Waveform Inversion process further comprises performing three-dimensional acoustic or viscoacoustic simulations. 16. The method of claim 13 or 14, wherein performing the Full Waveform Inversion process further comprises performing three-dimensional elastic or anelastic simulations. 17. The method of any one of claims 13 to 16, wherein performing the Full Waveform Inversion process comprises inverting low-frequency content of the observed imaging data followed by progressively adding higher frequency content of the observed imaging data. 18. The method of claim any one of claims 13 to 17, further comprising smoothing the simulated model. 19. The method of claim 18, wherein smoothing the simulated model comprises applying a Gaussian smoothing process to the simulation model. 20. The method of any one of claims 13 to 19, wherein the image representations of the medium is a physical three-dimensional model. 21. The method of any one of claims 13 to 20, wherein the medium is a human tissue or a non-human object. 22. The method of any one of claims 13 to 21, wherein the medium is an object being non-destructively tested (NDT) for quality assurance/quality control (QA/QC) or for measurement purposes. 23. The method of any one of claims 13 to 21, wherein capturing the acoustic waves further comprises immersing the medium in a liquid. 24. The method of claim 23, wherein the liquid is water. 25. The method of any one of claims 13 to 24, wherein performing the Full Waveform Inversion process comprises:
(i) providing an initial physical model;
(ii) determining the synthesized data, by a computer, by simulating wave propagation through the physical model;
(iii) back-propagating adjoint source terms determined by a cost function based on a comparison of the synthesized data and the converted acoustic/(an)elastic wave data to update the physical model; and
(iv) repeating (ii) and (iii) until the residual is less than a predetermined threshold. 26. The method of claim 25, wherein the cost function is a waveform cost function, an expression of the waveform cost function comprising:
F W(m)=½Σr=1 N rec ∫0 T |p obs(x r ,t)−p syn(x r ,t,m)|2 dt,
wherein FW(m) is a sum of the residuals between the synthesized data, psyn(xr, t, m), and the converted acoustic/(an)elastic wave data, pobs(xr, t), over Nrec number of the receiving transducers r at xr, over a time window T, wherein m are the maps of selected parameters. 27. The method of claim 25, wherein the cost function is a traveltime cost function, an expression of the traveltime cost function comprising:
F T(m)=½Σr=1 N rec |T obs(x r)−T syn(x r ,m)|2,
wherein FT (m) is a sum of the residuals between the synthetic time of flight, Tsyn (xr, m), and the time of flight of converted acoustic/(an)elastic wave data, Tobs(xr), over Nrec number of the receiving transducers r at xr, wherein m are the maps of selected parameters. 28. The method of claim 25, wherein the cost function is an instantaneous phase (IP) cost function, an expression of the instantaneous phase cost function comprising:
F IP(m)=½Σr=1 N rec ∫0 T|ψobs(x r ,t)−ψsyn(x r ,t,m)|2 dt,
wherein FIP(m) is a sum of the residuals between the IP of synthesized data, ψsyn(xr, t, m), and the IP of converted acoustic/(an)elastic wave data, ψobs(xr, t), over Nrec number of the receiving transducers r at xr, over a time window T, wherein m are the maps of selected parameters. 29. The method of claim 25, wherein the cost function is a double difference cost function, an expression of the double difference cost function comprising:
F DD(m)=½Σi=1 N rec Σj>i N rec |Δt ij(p obs)−Δt ij(p syn(m))|2,
wherein FDD (m) is a sum of the residuals between the synthetic time of flight difference Δtij(psyn(m)), and the converted acoustic/(an)elastic wave data time of flight difference Δtij (pobs), between each pair from the Nrec receiving transducers, wherein m are the maps of selected parameters. 30. The method of claim 25, wherein the cost function is a hybrid cost function, an expression of the hybrid cost function comprising:
F H(m)=αF T(m)+βF DD(m)+γF IP(m)+δF W(m),
Wherein FT(m) is the traveltime cost function, FDD(m) is the double difference cost function, FIP (m) is the instantaneous phase cost function and FW(m) is the waveform cost function, wherein α, β, γ and δ are weights of FT(m), FDD(m), FIP(m) and FW(m), respectively. | 2,600 |
345,409 | 16,643,334 | 2,667 | Disclosed is a selenium-doped black phosphorus prodrug comprising selenium-doped black phosphorus nanosheets and polyethylene glycol amine coating the surface of the selenium-doped black phosphorus nanosheets. The selenium-doped black phosphorus nanosheets comprise black phosphorus nanosheets and selenium elements doped in the black phosphorus nanosheets, with the selenium elements replacing positions of a portion of the phosphorus atoms in the black phosphorus crystal lattice. The selenium-doped black phosphorus prodrug is a controlled-release prodrug of selenium elements, which can realize the near-infrared light controlled-release of selenium elements, thereby controllably regulating selenium content in the human body, regulating human immunity, and preventing and treating cancers. Also provided is a method for preparing the selenium-doped black phosphorus prodrug. | 1. A selenium-doped black phosphorus prodrug comprising:
selenium-doped black phosphorus nanosheets, and polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets, wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice. 2. The selenium-doped black phosphorus prodrug of claim 1, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 0.1-5%. 3. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 2-5%. 4. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 1-4%. 5. The selenium-doped black phosphorus prodrug of claim 1, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 50 nm-200 nm. 6. The selenium-doped black phosphorus prodrug of claim 5, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 100 nm-200 nm. 7. The selenium-doped black phosphorus prodrug of claim 1, wherein thickness of the selenium-doped black phosphorus nanosheets is in a range of 1 nm-5 nm. 8. The selenium-doped black phosphorus prodrug of claim 1, wherein mass ratio of the selenium-doped black phosphorus nanosheets to the polyethylene glycol amine is in a range of 1:(0.2-10). 9. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine is adsorbed on the surface of the selenium-doped black phosphorus nanosheets due to electrostatic force, and wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000. 10. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine. 11. A method for preparing a selenium-doped black phosphorus prodrug, comprising:
sealing red phosphorus, tin, tin tetraiodide and selenium in a silicon glass vacuum tube at a mass ratio of (200-500):(10-20):(5-10):(0.5-10); placing the silicon glass vacuum tube horizontally in a heating furnace, followed by heating the silicon glass vacuum to 700-800° C. and maintaining for 1-5 hours, and then cooling to 450-550° C. and maintaining for 5-9 hours, and then further cooling to 100-200° C. and maintaining for 6-10 hours, followed by cooling to room temperature to obtain selenium-doped black phosphorus crystals in the silicon glass vacuum tube; dispersing the selenium-doped black phosphorus crystals into an aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets; coating the selenium-doped black phosphorus nanosheets with polyethylene glycol amine while ultrasonicating and stirring to obtain a selenium-doped black phosphorus prodrug, which comprises:
selenium-doped black phosphorus nanosheets, and
polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets,
wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and
wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice. 12. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of heating is performed at a heating rate of 1-5° C./min. 13. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 450-550° C. is performed at a cooling rate of 1-3° C./min. 14. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 100-200° C. is performed at a cooling rate of 1-3° C./min. 15. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass ratio of the selenium-doped black phosphorus nanosheets to polyethylene glycol amine is in a range of 1:(0.2-10). 16. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000. 17. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine. 18. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the selenium is 0.1-5% of mass of the red phosphorus. 19. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the tin is 2-10% of mass of the red phosphorus. 20. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the ultrasonic treatment uses an ultrasonic frequency of 3000-4500 HZ and lasts for 0.5-2 hours, and the step of stirring is performed at a speed of 800 rpm-1200 rpm for 2-4 hours. | Disclosed is a selenium-doped black phosphorus prodrug comprising selenium-doped black phosphorus nanosheets and polyethylene glycol amine coating the surface of the selenium-doped black phosphorus nanosheets. The selenium-doped black phosphorus nanosheets comprise black phosphorus nanosheets and selenium elements doped in the black phosphorus nanosheets, with the selenium elements replacing positions of a portion of the phosphorus atoms in the black phosphorus crystal lattice. The selenium-doped black phosphorus prodrug is a controlled-release prodrug of selenium elements, which can realize the near-infrared light controlled-release of selenium elements, thereby controllably regulating selenium content in the human body, regulating human immunity, and preventing and treating cancers. Also provided is a method for preparing the selenium-doped black phosphorus prodrug.1. A selenium-doped black phosphorus prodrug comprising:
selenium-doped black phosphorus nanosheets, and polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets, wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice. 2. The selenium-doped black phosphorus prodrug of claim 1, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 0.1-5%. 3. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 2-5%. 4. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 1-4%. 5. The selenium-doped black phosphorus prodrug of claim 1, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 50 nm-200 nm. 6. The selenium-doped black phosphorus prodrug of claim 5, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 100 nm-200 nm. 7. The selenium-doped black phosphorus prodrug of claim 1, wherein thickness of the selenium-doped black phosphorus nanosheets is in a range of 1 nm-5 nm. 8. The selenium-doped black phosphorus prodrug of claim 1, wherein mass ratio of the selenium-doped black phosphorus nanosheets to the polyethylene glycol amine is in a range of 1:(0.2-10). 9. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine is adsorbed on the surface of the selenium-doped black phosphorus nanosheets due to electrostatic force, and wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000. 10. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine. 11. A method for preparing a selenium-doped black phosphorus prodrug, comprising:
sealing red phosphorus, tin, tin tetraiodide and selenium in a silicon glass vacuum tube at a mass ratio of (200-500):(10-20):(5-10):(0.5-10); placing the silicon glass vacuum tube horizontally in a heating furnace, followed by heating the silicon glass vacuum to 700-800° C. and maintaining for 1-5 hours, and then cooling to 450-550° C. and maintaining for 5-9 hours, and then further cooling to 100-200° C. and maintaining for 6-10 hours, followed by cooling to room temperature to obtain selenium-doped black phosphorus crystals in the silicon glass vacuum tube; dispersing the selenium-doped black phosphorus crystals into an aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets; coating the selenium-doped black phosphorus nanosheets with polyethylene glycol amine while ultrasonicating and stirring to obtain a selenium-doped black phosphorus prodrug, which comprises:
selenium-doped black phosphorus nanosheets, and
polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets,
wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and
wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice. 12. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of heating is performed at a heating rate of 1-5° C./min. 13. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 450-550° C. is performed at a cooling rate of 1-3° C./min. 14. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 100-200° C. is performed at a cooling rate of 1-3° C./min. 15. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass ratio of the selenium-doped black phosphorus nanosheets to polyethylene glycol amine is in a range of 1:(0.2-10). 16. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000. 17. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine. 18. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the selenium is 0.1-5% of mass of the red phosphorus. 19. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the tin is 2-10% of mass of the red phosphorus. 20. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the ultrasonic treatment uses an ultrasonic frequency of 3000-4500 HZ and lasts for 0.5-2 hours, and the step of stirring is performed at a speed of 800 rpm-1200 rpm for 2-4 hours. | 2,600 |
345,410 | 16,643,337 | 3,621 | Methods, apparatus, systems, and articles of manufacture for facilitating task execution using a drone are disclosed. An example method includes accessing a result of a task performed by a task executor. The result includes one or more images of a task objective captured by the task executor. The result is validated based on a task definition provided by a task issuer. In response to the validation of the result indicating that the result complies with the task definition, the result is provided to the task issuer, and a reward is issued to the task executor. | 1-25. (canceled) 26. An apparatus for facilitating execution of a task using a drone, the apparatus comprising:
a result receiver to access a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; a result validator to validate the result based on a task definition provided by a task issuer; a result provider to, in response to the validation of the result indicating that the result complies with the task definition, provide the result to the task issuer; and a reward issuer to, in response to the validation of the result indicating that the result complies with the task definition, issue a reward to the task executor. 27. The apparatus of claim 26, further including a task allocator to allocate the task to the task executor. 28. The apparatus of claim 27, wherein the task allocator is further to determine a number of task executors to whom the task has been allocated, and disable allocation of the task to the task allocator when a threshold maximum number of task executors have been allocated the task. 29. The apparatus of claim 26, wherein the result validator is further to determine a similarity score between the one or more images and known images of the task objective, and identify the result as invalid when the similarity score exceeds a first threshold similarity. 30. The apparatus of claim 29, wherein the first threshold similarity is at least a ninety percent similarity. 31. The apparatus of claim 29, wherein the result validator is further to identify the result as invalid when the similarity score does not meet a second threshold similarity lesser than the first threshold similarity. 32. The apparatus of claim 31, wherein the second threshold similarity is no more than a ten percent similarity. 33. The apparatus of claim 26, wherein the reward is a financial compensation. 34. The apparatus of claim 26, wherein the result provider is further to provide the result to a third party. 35. The apparatus of claim 34, wherein a portion of the reward issued to the task executor is provided by the third party. 36. At least one non-transitory computer readable medium comprising instructions which, when executed, cause a machine to at least:
access a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; validate the result based on a task definition provided by a task issuer; and in response to the validation of the result indicating that the result complies with the task definition: provide the result to the task issuer; and issue a reward to the task executor. 37. The at least one non-transitory computer readable medium of claim 36, wherein the instructions, when executed, cause the machine to allocate the task to the task executor. 38. The at least one non-transitory computer readable medium of claim 37, wherein the instructions, when executed, cause the machine to at least:
determine a number of task executors to whom the task has been allocated; and not allocate the task to the task executor when a threshold maximum number of task executors have been allocated the task. 39. The at least one non-transitory computer readable medium of claim 36, wherein the instructions, when executed, cause the machine to validate the result by:
determining a similarity score between the one or more images and known images of the task objective; and identifying the result as invalid when the similarity score exceeds a first threshold similarity. 40. The at least one non-transitory computer readable medium of claim 39, wherein the first threshold similarity is at least a ninety percent similarity. 41. The at least one non-transitory computer readable medium of claim 39, wherein the instructions, when executed, cause the machine to identify the result as invalid when the similarity score does not meet a second threshold similarity lesser than the first threshold similarity. 42. The at least one non-transitory computer readable medium of claim 41, wherein the second threshold similarity is no more than a ten percent similarity. 43. A method of for facilitating execution of a task using a drone, the method comprising:
accessing a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; validating, by executing an instruction with a processor, the result based on a task definition provided by a task issuer; in response to the validation of the result indicating that the result complies with the task definition: providing the result to the task issuer; and issuing a reward to the task executor. 44. The method of claim 43, further including:
allocating the task to the task executor; determining a number of task executors to whom the task has been allocated; and not allocating the task to the task executor when a threshold maximum number of task executors have been allocated the task. 45. The method of claim 43, wherein the validating of the result includes:
determining a similarity score between the one or more images and known images of the task objective; and identifying the result as invalid when the similarity score exceeds a first threshold similarity. | Methods, apparatus, systems, and articles of manufacture for facilitating task execution using a drone are disclosed. An example method includes accessing a result of a task performed by a task executor. The result includes one or more images of a task objective captured by the task executor. The result is validated based on a task definition provided by a task issuer. In response to the validation of the result indicating that the result complies with the task definition, the result is provided to the task issuer, and a reward is issued to the task executor.1-25. (canceled) 26. An apparatus for facilitating execution of a task using a drone, the apparatus comprising:
a result receiver to access a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; a result validator to validate the result based on a task definition provided by a task issuer; a result provider to, in response to the validation of the result indicating that the result complies with the task definition, provide the result to the task issuer; and a reward issuer to, in response to the validation of the result indicating that the result complies with the task definition, issue a reward to the task executor. 27. The apparatus of claim 26, further including a task allocator to allocate the task to the task executor. 28. The apparatus of claim 27, wherein the task allocator is further to determine a number of task executors to whom the task has been allocated, and disable allocation of the task to the task allocator when a threshold maximum number of task executors have been allocated the task. 29. The apparatus of claim 26, wherein the result validator is further to determine a similarity score between the one or more images and known images of the task objective, and identify the result as invalid when the similarity score exceeds a first threshold similarity. 30. The apparatus of claim 29, wherein the first threshold similarity is at least a ninety percent similarity. 31. The apparatus of claim 29, wherein the result validator is further to identify the result as invalid when the similarity score does not meet a second threshold similarity lesser than the first threshold similarity. 32. The apparatus of claim 31, wherein the second threshold similarity is no more than a ten percent similarity. 33. The apparatus of claim 26, wherein the reward is a financial compensation. 34. The apparatus of claim 26, wherein the result provider is further to provide the result to a third party. 35. The apparatus of claim 34, wherein a portion of the reward issued to the task executor is provided by the third party. 36. At least one non-transitory computer readable medium comprising instructions which, when executed, cause a machine to at least:
access a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; validate the result based on a task definition provided by a task issuer; and in response to the validation of the result indicating that the result complies with the task definition: provide the result to the task issuer; and issue a reward to the task executor. 37. The at least one non-transitory computer readable medium of claim 36, wherein the instructions, when executed, cause the machine to allocate the task to the task executor. 38. The at least one non-transitory computer readable medium of claim 37, wherein the instructions, when executed, cause the machine to at least:
determine a number of task executors to whom the task has been allocated; and not allocate the task to the task executor when a threshold maximum number of task executors have been allocated the task. 39. The at least one non-transitory computer readable medium of claim 36, wherein the instructions, when executed, cause the machine to validate the result by:
determining a similarity score between the one or more images and known images of the task objective; and identifying the result as invalid when the similarity score exceeds a first threshold similarity. 40. The at least one non-transitory computer readable medium of claim 39, wherein the first threshold similarity is at least a ninety percent similarity. 41. The at least one non-transitory computer readable medium of claim 39, wherein the instructions, when executed, cause the machine to identify the result as invalid when the similarity score does not meet a second threshold similarity lesser than the first threshold similarity. 42. The at least one non-transitory computer readable medium of claim 41, wherein the second threshold similarity is no more than a ten percent similarity. 43. A method of for facilitating execution of a task using a drone, the method comprising:
accessing a result of a task performed by a task executor, the result including one or more images of a task objective captured by the task executor; validating, by executing an instruction with a processor, the result based on a task definition provided by a task issuer; in response to the validation of the result indicating that the result complies with the task definition: providing the result to the task issuer; and issuing a reward to the task executor. 44. The method of claim 43, further including:
allocating the task to the task executor; determining a number of task executors to whom the task has been allocated; and not allocating the task to the task executor when a threshold maximum number of task executors have been allocated the task. 45. The method of claim 43, wherein the validating of the result includes:
determining a similarity score between the one or more images and known images of the task objective; and identifying the result as invalid when the similarity score exceeds a first threshold similarity. | 3,600 |
345,411 | 16,643,336 | 3,621 | Provided is a headup display device that suppresses luminance variance of diffusion light with respect to an obliquely disposed screen. A screen is tilted with respect to an orthogonal plane that is orthogonal to an optical axis of projection light. In the cases where the screen and the optical axis of the projection light are orthogonal to each other, a center line of a distribution angle (β) of diffusion light is set such that the center line tilts in a direction with respect to an output surface of the screen, said direction being identical to a tilt direction of the screen. | 1. A headup display device comprising:
a projector for projecting projection light; and a screen on which the projection light forms an image for diffusing the projection light, the screen being tilted with respect to an orthogonal plane orthogonal to an optical axis of the projection light, and including a diffusion unit for converting the projection light into diffusion light, wherein a center line of a distribution angle of the diffusion light in a case where the screen and the optical axis of the projection light are orthogonal to each other is set to tilt in a direction identical to a tilt direction of the screen with respect to an orthogonal line orthogonal to an output surface of the screen. 2. The headup display device according to claim 1, wherein the diffusion unit is a microlens array, and
the microlens array has a curvature increasing in a direction identical to the tilt direction of the screen. | Provided is a headup display device that suppresses luminance variance of diffusion light with respect to an obliquely disposed screen. A screen is tilted with respect to an orthogonal plane that is orthogonal to an optical axis of projection light. In the cases where the screen and the optical axis of the projection light are orthogonal to each other, a center line of a distribution angle (β) of diffusion light is set such that the center line tilts in a direction with respect to an output surface of the screen, said direction being identical to a tilt direction of the screen.1. A headup display device comprising:
a projector for projecting projection light; and a screen on which the projection light forms an image for diffusing the projection light, the screen being tilted with respect to an orthogonal plane orthogonal to an optical axis of the projection light, and including a diffusion unit for converting the projection light into diffusion light, wherein a center line of a distribution angle of the diffusion light in a case where the screen and the optical axis of the projection light are orthogonal to each other is set to tilt in a direction identical to a tilt direction of the screen with respect to an orthogonal line orthogonal to an output surface of the screen. 2. The headup display device according to claim 1, wherein the diffusion unit is a microlens array, and
the microlens array has a curvature increasing in a direction identical to the tilt direction of the screen. | 3,600 |
345,412 | 16,643,352 | 2,855 | A brake actuator for a rail vehicle has a sensor for detecting a braking force generated in the brake actuator, a sensor for detecting vibrations generated by the braking force in the brake actuator, and a control unit. The control unit is configured so as to generate a relationship between the speed of the rail vehicle with a generated braking force and a frequency of the vibrations generated by the braking force. | 1. A brake actuator for a rail vehicle, the brake actuator comprising:
a sensor for detecting a brake force produced in the brake actuator, a sensor for detecting oscillations produced by the brake force in the brake actuator; and a control unit configured to produce a relationship of a speed of the rail vehicle with the brake force produced and a frequency of the oscillations produced by the brake force. 2. The brake actuator of claim 1, wherein the brake actuator has a pressing component which is configured to be pressed against a brake disk. 3. The brake actuator of claim 1, wherein the sensor for detecting the brake force produced in the brake actuator and the sensor for detecting oscillations produced by the brake force in the brake actuator are constructed as a single sensor. 4. The brake actuator of claim 1, wherein the control unit is connected during normal operation to a superordinate control system which is configured to provide a speed signal of the rail vehicle. 5. The brake actuator of claim 1, wherein the control unit is configured to produce a stop signal in the event of a stoppage of the rail vehicle (2). 6. The brake actuator of claim 1, wherein the control unit is configured to establish portions of the frequency via a calculation of correlation factors via a calculation of the standard deviation, a fast Fourier transformation or a discrete Fourier transformation. 7. A method for determining a speed of a rail vehicle with a brake actuator, the method comprising:
detecting a brake force produced in the brake actuator; detecting oscillations produced by the brake force in the brake actuator; and producing a relationship of the speed of the rail vehicle with the brake force produced and a frequency of the oscillations produced by the brake force. 8. The method of claim 7, wherein the speed is provided by a superordinate control system. 9. The method of claim 7, wherein the speed of the rail vehicle is converted into a rotation speed of a brake disk. 10. The method of claim 7, wherein the method is carried out during service braking operations. 11. The method of claim 7, wherein a stop signal is transmitted in the event of a stoppage of the rail vehicle. 12. The method of claim 7, wherein portions of the frequency are established via a calculation of the correlation factors via the calculation of the standard deviation, the fast Fourier transformation or the discrete Fourier transformation. 13. The method of claim 12, further comprising:
determining coefficients from the correlation factors; and storing the coefficients in a characteristic diagram. 14. The method of claim 13, wherein the characteristic diagram is continuously adapted. 15. The method of claim 13, wherein the control unit, in response to the event of an interruption of a communication, establishes the speed from the detected brake force produced, the oscillations produced by the brake force and the coefficients stored in the characteristic diagram. | A brake actuator for a rail vehicle has a sensor for detecting a braking force generated in the brake actuator, a sensor for detecting vibrations generated by the braking force in the brake actuator, and a control unit. The control unit is configured so as to generate a relationship between the speed of the rail vehicle with a generated braking force and a frequency of the vibrations generated by the braking force.1. A brake actuator for a rail vehicle, the brake actuator comprising:
a sensor for detecting a brake force produced in the brake actuator, a sensor for detecting oscillations produced by the brake force in the brake actuator; and a control unit configured to produce a relationship of a speed of the rail vehicle with the brake force produced and a frequency of the oscillations produced by the brake force. 2. The brake actuator of claim 1, wherein the brake actuator has a pressing component which is configured to be pressed against a brake disk. 3. The brake actuator of claim 1, wherein the sensor for detecting the brake force produced in the brake actuator and the sensor for detecting oscillations produced by the brake force in the brake actuator are constructed as a single sensor. 4. The brake actuator of claim 1, wherein the control unit is connected during normal operation to a superordinate control system which is configured to provide a speed signal of the rail vehicle. 5. The brake actuator of claim 1, wherein the control unit is configured to produce a stop signal in the event of a stoppage of the rail vehicle (2). 6. The brake actuator of claim 1, wherein the control unit is configured to establish portions of the frequency via a calculation of correlation factors via a calculation of the standard deviation, a fast Fourier transformation or a discrete Fourier transformation. 7. A method for determining a speed of a rail vehicle with a brake actuator, the method comprising:
detecting a brake force produced in the brake actuator; detecting oscillations produced by the brake force in the brake actuator; and producing a relationship of the speed of the rail vehicle with the brake force produced and a frequency of the oscillations produced by the brake force. 8. The method of claim 7, wherein the speed is provided by a superordinate control system. 9. The method of claim 7, wherein the speed of the rail vehicle is converted into a rotation speed of a brake disk. 10. The method of claim 7, wherein the method is carried out during service braking operations. 11. The method of claim 7, wherein a stop signal is transmitted in the event of a stoppage of the rail vehicle. 12. The method of claim 7, wherein portions of the frequency are established via a calculation of the correlation factors via the calculation of the standard deviation, the fast Fourier transformation or the discrete Fourier transformation. 13. The method of claim 12, further comprising:
determining coefficients from the correlation factors; and storing the coefficients in a characteristic diagram. 14. The method of claim 13, wherein the characteristic diagram is continuously adapted. 15. The method of claim 13, wherein the control unit, in response to the event of an interruption of a communication, establishes the speed from the detected brake force produced, the oscillations produced by the brake force and the coefficients stored in the characteristic diagram. | 2,800 |
345,413 | 16,643,329 | 3,774 | The present invention discloses an exoskeleton which comprises a force balance back-carrying unit composed of a back-carrying assisting unit and a front-carrying assisting unit, a hip unit and a lower limb supporting unit, wherein the force balance back-carrying unit transfer the weight of a back-carrying load and/or a front-carrying load to the lower limb supporting unit through the hip unit to achieve the effort of assisting for the back-carrying load and/or the front-carrying load, wherein the length of the hip unit can be adjusted on the left-right plane and the upper-lower plane to adapt to wearers with different body types. On the other hand, the exoskeleton of the present invention is also provided with a buffer device to reduce the impact of the loads on the exoskeleton. The exoskeleton of the present invention also adopts quick-release joints, so as to modularize each part and standardize a docking interface of each module. The present invention can adapt to wearers with different hip shapes, and can transfer the weight of the back-carrying load and the front-carrying load to the lower limb supporting unit separately and simultaneously, so as to increase the weight-bearing efficiency and reduce the injuries to the back, the hands and the ankle joint. | 1. An exoskeleton, comprising a back-carrying assisting unit, wherein the back-carrying assisting unit comprises a spinal locomotion adaptation unit arranged to be adapted to locomotion of back of human body when the back-carrying assisting unit carries a load or spine of the human body bends forwards, backwards, leftwards or rightwards;
wherein the spinal locomotion adaptation unit is a flexible body; and a plurality of groups of spinal locomotion adaptation structures are arranged on the flexible body evenly along a lengthwise direction from top to bottom, and are used to provide a deformation space in a corresponding direction for the flexible body when the human body bends forwards, backwards, leftwards or rightwards. 2. (canceled) 3. The exoskeleton according to claim 1, wherein the spinal locomotion adaptation unit is an elastic backplane; a plurality of bulges are arranged at even intervals at one side of the elastic backplane away from the human body; or the spinal locomotion adaptation unit is formed by laminating a plurality of elastic bar-shaped bodies; or the spinal locomotion adaptation unit is a bionic spine. 4. The exoskeleton according to claim 1, wherein each group of spinal locomotion adaptation structure comprises a left-tilting slot, a rear-tilting slot, a right-tilting slot, and a front-tilting slot that are staggered in sequence from top to bottom. 5. The exoskeleton according to claim 1, wherein the bottom of the flexible body is provided with a rotating adaptation structure so that the flexible body can rotate and deform in a horizontal plane. 6. The exoskeleton according to claim 1, wherein the flexible body is further provided with a rigidity regulating unit used for regulating the rigidity of the flexible body. 7. The exoskeleton according to claim 6, wherein the rigidity regulating unit comprises two pull lines; left and right sides of the flexible body are provided with a first pull line passage and a second pull line passage side by side along the lengthwise direction, wherein fixed ends of the pull lines are fixed to the bottom of the first pull line passage, and free ends of the pull lines penetrate through the first pull line passage and the second pull line passage in sequence and penetrate out of the bottom of the second pull line passage;
when the free ends of the two pull lines are simultaneously pulled downwards, pulling force generated by the pull lines compresses the each group of spinal locomotion adaptation structure, so as to enhance the rigidity of the flexible body. 8. The exoskeleton according to claim 7, wherein elastic components are connected at the fixed ends of the pull lines and are used to bear the pulling force of the pull lines, finally achieving force balance with the pulling force of the pull lines and simultaneously compressing the spinal locomotion adaptation structure. 9. The exoskeleton according to claim 7, the back-carrying assisting unit further comprises a back-carrying weight-bearing unit, wherein the back-carrying weight-bearing unit is associated with the rigidity regulating unit, so that the gravity of the back-carrying load is transmitted to the rigidity regulating unit when the back-carrying weight-bearing unit carries the load, to compress the spinal locomotion adaptation structure. 10. The exoskeleton according to claim 9, wherein the back-carrying weight-bearing unit comprises a fixed seat and a weight-bearing platform hinged on a fixed platform, wherein the fixed seat is arranged at the bottom of the flexible body by sliding up and down relative to the flexible body, and is connected with the free ends of the two pull lines;
in an initial state, the weight-bearing platform is attached to the fixed seat; when the weight-bearing platform rotates to form an angle of 45° to 90° with one side of the fixed seat away from the back/hip, the weight-bearing platform and the fixed seat form a weight-bearing space for accommodating loads; and when the loads are put into the weight-bearing space, the fixed seat drives the free ends of the two pull lines to slide downwards, to compress the spinal locomotion adaptation structure. 11-16. (canceled) 17. An exoskeleton, characterized by comprising a force balance back-carrying unit used for a back-carrying load and a front-carrying load; the force balance back-carrying unit comprises a back-carrying assisting unit and a front-carrying assisting unit which are connected through a force transmission unit, wherein the front-carrying assisting unit transmits weight of the front-carrying load to the back-carrying assisting unit through the force transmission unit; wherein the force transmission unit comprises a left and a right force transmission components and a left and a right contraction devices having self-locking units, wherein one end of each of the left and the right force transmission components is respectively twined into the left and the right contraction devices; and when the self-locking units in the contraction devices are unlocked, the contraction devices release the force transmission components twined into the contraction devices; and
when the other end of each of the left and the right force transmission components is respectively fixedly connected with the left side and the right side of the front-carrying assisting unit, the left and the right contraction devices are respectively fixed to the left side and the right side of the back-carrying assisting unit or when the other end of each of the left and the right force transmission components is respectively fixedly connected with the left side and the right side of the back-carrying assisting unit, the left and the right contraction devices are respectively fixed to the left side and the right side of the front-carrying assisting unit. 18. (canceled) 19. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion, a finger supporting cushion and a wearable component, wherein one end of the palm supporting cushion is connected with fixed end of the force transmission component, and the other end is hinged with the finger supporting cushion; and the wearable component is arranged on the palm supporting cushion;
wherein the back surface of the finger supporting cushion is also provided with a clamping part used for clamping between two fingers. 20. (canceled) 21. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion, a finger supporting cushion and a finger connecting piece, wherein the palm supporting cushion and the finger supporting cushion are respectively hinged with the finger connecting piece, and the palm supporting cushion is also connected with the fixed end of the force transmission component;
wherein each of the contactors further comprises a fingertip protecting jacket arranged at the end of the finger supporting cushion. 22. (canceled) 23. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion and a hooked weight-bearing part; one end of the hooked weight-bearing part is rotatably connected with the palm supporting cushion; the palm supporting cushion is provided with an accommodating groove with an L-shaped cross section; and
in an initial state, the hooked weight-bearing part is located on the accommodating groove to form, with a load base, a surface contactor that can be attached to the side surface of the front-carrying load; when the hooked weight-bearing part rotates to be perpendicular to the vertical plane, the hooked weight-bearing part and the palm supporting cushion form a weight-bearing unit with an L-shaped cross section used for front lifting of a load; or when the hooked weight-bearing part rotates to be parallel to the vertical plane, the hooked weight-bearing part is used to lift the load. 24. The exoskeleton according to claim 17, wherein the back-carrying assisting unit comprises a shoulder supporting piece, a spinal locomotion adaptation unit and a back-carrying weight-bearing unit which are connected in sequence, wherein the shoulder supporting piece is connected with the force transmission unit. 25. The exoskeleton according to claim 24, wherein the spinal locomotion adaptation unit is an elastic backplane; and a plurality of bulges are arranged at even intervals at one side of the elastic backplane away from the human body. 26. The exoskeleton according to claim 24, wherein the spinal locomotion adaptation unit is a flexible body; and a plurality of groups of spinal locomotion adaptation structures are arranged on the flexible body evenly along a lengthwise direction from top to bottom, and are used to provide a deformation space in a corresponding direction for the flexible body when the human body bends forwards, backwards, leftwards or rightwards;
wherein each group of spinal locomotion adaptation structure comprises a left-tilting slot, a rear-tilting slot, a right-tilting slot, and a front-tilting slot that are staggered from top to bottom. 27. (canceled) 28. The exoskeleton according to claim 26, wherein the bottom of the flexible body is provided with a rotating slot so that the flexible body can rotate and deform in the horizontal plane. 29. The exoskeleton according to claim 26, wherein the flexible body is also provided with a rigidity regulating unit used for regulating the rigidity of the flexible body when the back-carrying assisting unit carries the load;
wherein the rigidity regulating unit comprises two force transmission lines used to transmit front load, and at least two third and fourth pull line passages are arranged in the flexible body side by side along the lengthwise direction; fixed ends of the force transmission lines are fixed to the top of the third pull line passage, and movable ends penetrate through the third pull line passage and the fourth pull line passage in sequence and penetrate out of the top of the fourth pull line passage to connect with the shoulder supporting piece; when a front-carrying weight-bearing unit carries the load, the force transmission unit transmits the weight of the load to the shoulder supporting piece and the shoulder supporting piece drives the force transmission lines to compress the plurality of groups of spinal locomotion adaptation structures. 30. (canceled) 31. The exoskeleton according to claim 29, wherein the rigidity regulating unit further comprises two pull lines located on the left side and the right side of the flexible body, and a first and a second pull line passages are arranged on the left side and the right side of the flexible body side by side along the lengthwise direction, wherein
fixed ends of the pull lines are fixed to the bottom of the first pull line passage, and free ends of the pull lines penetrate through the first pull line passage and the second pull line passage in sequence and penetrate out of the bottom of the second pull line passage; when the free ends of the two pull lines are simultaneously pulled downwards, pulling force generated by the pull lines compresses the spinal locomotion adaptation structures, so as to enhance the rigidity of the flexible spine. 32. The exoskeleton according to claim 29, wherein elastic components are connected at the fixed ends of the force transmission lines; and/or elastic components are connected at the fixed ends of the force transmission lines. 33-49. (canceled) | The present invention discloses an exoskeleton which comprises a force balance back-carrying unit composed of a back-carrying assisting unit and a front-carrying assisting unit, a hip unit and a lower limb supporting unit, wherein the force balance back-carrying unit transfer the weight of a back-carrying load and/or a front-carrying load to the lower limb supporting unit through the hip unit to achieve the effort of assisting for the back-carrying load and/or the front-carrying load, wherein the length of the hip unit can be adjusted on the left-right plane and the upper-lower plane to adapt to wearers with different body types. On the other hand, the exoskeleton of the present invention is also provided with a buffer device to reduce the impact of the loads on the exoskeleton. The exoskeleton of the present invention also adopts quick-release joints, so as to modularize each part and standardize a docking interface of each module. The present invention can adapt to wearers with different hip shapes, and can transfer the weight of the back-carrying load and the front-carrying load to the lower limb supporting unit separately and simultaneously, so as to increase the weight-bearing efficiency and reduce the injuries to the back, the hands and the ankle joint.1. An exoskeleton, comprising a back-carrying assisting unit, wherein the back-carrying assisting unit comprises a spinal locomotion adaptation unit arranged to be adapted to locomotion of back of human body when the back-carrying assisting unit carries a load or spine of the human body bends forwards, backwards, leftwards or rightwards;
wherein the spinal locomotion adaptation unit is a flexible body; and a plurality of groups of spinal locomotion adaptation structures are arranged on the flexible body evenly along a lengthwise direction from top to bottom, and are used to provide a deformation space in a corresponding direction for the flexible body when the human body bends forwards, backwards, leftwards or rightwards. 2. (canceled) 3. The exoskeleton according to claim 1, wherein the spinal locomotion adaptation unit is an elastic backplane; a plurality of bulges are arranged at even intervals at one side of the elastic backplane away from the human body; or the spinal locomotion adaptation unit is formed by laminating a plurality of elastic bar-shaped bodies; or the spinal locomotion adaptation unit is a bionic spine. 4. The exoskeleton according to claim 1, wherein each group of spinal locomotion adaptation structure comprises a left-tilting slot, a rear-tilting slot, a right-tilting slot, and a front-tilting slot that are staggered in sequence from top to bottom. 5. The exoskeleton according to claim 1, wherein the bottom of the flexible body is provided with a rotating adaptation structure so that the flexible body can rotate and deform in a horizontal plane. 6. The exoskeleton according to claim 1, wherein the flexible body is further provided with a rigidity regulating unit used for regulating the rigidity of the flexible body. 7. The exoskeleton according to claim 6, wherein the rigidity regulating unit comprises two pull lines; left and right sides of the flexible body are provided with a first pull line passage and a second pull line passage side by side along the lengthwise direction, wherein fixed ends of the pull lines are fixed to the bottom of the first pull line passage, and free ends of the pull lines penetrate through the first pull line passage and the second pull line passage in sequence and penetrate out of the bottom of the second pull line passage;
when the free ends of the two pull lines are simultaneously pulled downwards, pulling force generated by the pull lines compresses the each group of spinal locomotion adaptation structure, so as to enhance the rigidity of the flexible body. 8. The exoskeleton according to claim 7, wherein elastic components are connected at the fixed ends of the pull lines and are used to bear the pulling force of the pull lines, finally achieving force balance with the pulling force of the pull lines and simultaneously compressing the spinal locomotion adaptation structure. 9. The exoskeleton according to claim 7, the back-carrying assisting unit further comprises a back-carrying weight-bearing unit, wherein the back-carrying weight-bearing unit is associated with the rigidity regulating unit, so that the gravity of the back-carrying load is transmitted to the rigidity regulating unit when the back-carrying weight-bearing unit carries the load, to compress the spinal locomotion adaptation structure. 10. The exoskeleton according to claim 9, wherein the back-carrying weight-bearing unit comprises a fixed seat and a weight-bearing platform hinged on a fixed platform, wherein the fixed seat is arranged at the bottom of the flexible body by sliding up and down relative to the flexible body, and is connected with the free ends of the two pull lines;
in an initial state, the weight-bearing platform is attached to the fixed seat; when the weight-bearing platform rotates to form an angle of 45° to 90° with one side of the fixed seat away from the back/hip, the weight-bearing platform and the fixed seat form a weight-bearing space for accommodating loads; and when the loads are put into the weight-bearing space, the fixed seat drives the free ends of the two pull lines to slide downwards, to compress the spinal locomotion adaptation structure. 11-16. (canceled) 17. An exoskeleton, characterized by comprising a force balance back-carrying unit used for a back-carrying load and a front-carrying load; the force balance back-carrying unit comprises a back-carrying assisting unit and a front-carrying assisting unit which are connected through a force transmission unit, wherein the front-carrying assisting unit transmits weight of the front-carrying load to the back-carrying assisting unit through the force transmission unit; wherein the force transmission unit comprises a left and a right force transmission components and a left and a right contraction devices having self-locking units, wherein one end of each of the left and the right force transmission components is respectively twined into the left and the right contraction devices; and when the self-locking units in the contraction devices are unlocked, the contraction devices release the force transmission components twined into the contraction devices; and
when the other end of each of the left and the right force transmission components is respectively fixedly connected with the left side and the right side of the front-carrying assisting unit, the left and the right contraction devices are respectively fixed to the left side and the right side of the back-carrying assisting unit or when the other end of each of the left and the right force transmission components is respectively fixedly connected with the left side and the right side of the back-carrying assisting unit, the left and the right contraction devices are respectively fixed to the left side and the right side of the front-carrying assisting unit. 18. (canceled) 19. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion, a finger supporting cushion and a wearable component, wherein one end of the palm supporting cushion is connected with fixed end of the force transmission component, and the other end is hinged with the finger supporting cushion; and the wearable component is arranged on the palm supporting cushion;
wherein the back surface of the finger supporting cushion is also provided with a clamping part used for clamping between two fingers. 20. (canceled) 21. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion, a finger supporting cushion and a finger connecting piece, wherein the palm supporting cushion and the finger supporting cushion are respectively hinged with the finger connecting piece, and the palm supporting cushion is also connected with the fixed end of the force transmission component;
wherein each of the contactors further comprises a fingertip protecting jacket arranged at the end of the finger supporting cushion. 22. (canceled) 23. The exoskeleton according to claim 17, wherein the front-carrying assisting unit comprises a left contactor and a right contactor; each contactor comprises a palm supporting cushion and a hooked weight-bearing part; one end of the hooked weight-bearing part is rotatably connected with the palm supporting cushion; the palm supporting cushion is provided with an accommodating groove with an L-shaped cross section; and
in an initial state, the hooked weight-bearing part is located on the accommodating groove to form, with a load base, a surface contactor that can be attached to the side surface of the front-carrying load; when the hooked weight-bearing part rotates to be perpendicular to the vertical plane, the hooked weight-bearing part and the palm supporting cushion form a weight-bearing unit with an L-shaped cross section used for front lifting of a load; or when the hooked weight-bearing part rotates to be parallel to the vertical plane, the hooked weight-bearing part is used to lift the load. 24. The exoskeleton according to claim 17, wherein the back-carrying assisting unit comprises a shoulder supporting piece, a spinal locomotion adaptation unit and a back-carrying weight-bearing unit which are connected in sequence, wherein the shoulder supporting piece is connected with the force transmission unit. 25. The exoskeleton according to claim 24, wherein the spinal locomotion adaptation unit is an elastic backplane; and a plurality of bulges are arranged at even intervals at one side of the elastic backplane away from the human body. 26. The exoskeleton according to claim 24, wherein the spinal locomotion adaptation unit is a flexible body; and a plurality of groups of spinal locomotion adaptation structures are arranged on the flexible body evenly along a lengthwise direction from top to bottom, and are used to provide a deformation space in a corresponding direction for the flexible body when the human body bends forwards, backwards, leftwards or rightwards;
wherein each group of spinal locomotion adaptation structure comprises a left-tilting slot, a rear-tilting slot, a right-tilting slot, and a front-tilting slot that are staggered from top to bottom. 27. (canceled) 28. The exoskeleton according to claim 26, wherein the bottom of the flexible body is provided with a rotating slot so that the flexible body can rotate and deform in the horizontal plane. 29. The exoskeleton according to claim 26, wherein the flexible body is also provided with a rigidity regulating unit used for regulating the rigidity of the flexible body when the back-carrying assisting unit carries the load;
wherein the rigidity regulating unit comprises two force transmission lines used to transmit front load, and at least two third and fourth pull line passages are arranged in the flexible body side by side along the lengthwise direction; fixed ends of the force transmission lines are fixed to the top of the third pull line passage, and movable ends penetrate through the third pull line passage and the fourth pull line passage in sequence and penetrate out of the top of the fourth pull line passage to connect with the shoulder supporting piece; when a front-carrying weight-bearing unit carries the load, the force transmission unit transmits the weight of the load to the shoulder supporting piece and the shoulder supporting piece drives the force transmission lines to compress the plurality of groups of spinal locomotion adaptation structures. 30. (canceled) 31. The exoskeleton according to claim 29, wherein the rigidity regulating unit further comprises two pull lines located on the left side and the right side of the flexible body, and a first and a second pull line passages are arranged on the left side and the right side of the flexible body side by side along the lengthwise direction, wherein
fixed ends of the pull lines are fixed to the bottom of the first pull line passage, and free ends of the pull lines penetrate through the first pull line passage and the second pull line passage in sequence and penetrate out of the bottom of the second pull line passage; when the free ends of the two pull lines are simultaneously pulled downwards, pulling force generated by the pull lines compresses the spinal locomotion adaptation structures, so as to enhance the rigidity of the flexible spine. 32. The exoskeleton according to claim 29, wherein elastic components are connected at the fixed ends of the force transmission lines; and/or elastic components are connected at the fixed ends of the force transmission lines. 33-49. (canceled) | 3,700 |
345,414 | 16,643,348 | 1,798 | The invention relates to a tube assembly comprising at least two tubes arranged in at least one plane at predefined distances and to a casing covering the tubes in the longitudinal direction. | 1.-10. (canceled) 11. A tubing arrangement comprising
at least two tubings arranged at predefined spacings in at least one plane; and a jacket surrounding the tubings in the longitudinal direction. 12. The tubing arrangement in accordance with claim 11,
wherein the tubings are manufactured from plastic such as polyether ether ketone or silicone or fluoropolymers, e.g. tetrafluoroethylene-perfluoropropylene copolymers; and wherein the jacket is manufactured from plastic such as polyurethane or polyvinyl chloride or silicone. 13. The tubing arrangement in accordance with claim 12,
wherein the plastic of the tubing comprises one of polyether ether ketone, silicone, fluoropolymers, and tetrafluoroethylene-perfluoropropylene copolymers. 14. The tubing arrangement in accordance with claim 12,
wherein the plastic of the jacket comprises one of polyurethane, polyvinyl chloride and silicone. 15. The tubing arrangement in accordance with claim 11,
wherein the jacket is manufactured by extrusion around the tubings by means of an extrusion tool or by molding the tubings by means of injection molding or by connecting two jacket halves while interposing the tubings by means of adhesive bonding, ultrasound welding, or the like. 16. The tubing arrangement in accordance with claim 11,
wherein end sections of the tubings can be exposed by making an incision in the jacket up to the outer diameter of the tubings and pulling off the end sections of the jacket thereby cut off from the end sections of the tubings. 17. The tubing arrangement in accordance with claim 16,
wherein fittings can be attached to the end sections of the tubings. 18. The tubing arrangement in accordance with claim 11,
wherein the individual tubings of the tubing arrangement have one of an individual color and a code. 19. The tubing arrangement in accordance with claim 11,
wherein the outer contour of the jacket having the tubings located therein is adapted such that it complements the outer contour of a drag chain that is used in connection with the tubing arrangement at a liquid handling device for use in analysis or in medical diagnosis, for instance in liquid chromatography. 20. The tubing arrangement in accordance with claim 11,
wherein the tubing arrangement replaces a drag chain that is used at a liquid handling device for use in analysis or medical diagnosis. 21. A liquid handling device for use in analysis or medical diagnosis, the liquid handling device having a tubing arrangement, the tubing arrangement comprising
at least two tubings arranged at predefined spacings in at least one plane; and a jacket surrounding the tubings in the longitudinal direction. 22. A method of manufacturing a tubing arrangement that comprises the following steps:
providing at least two tubings of plastic in at least one plane, starting from a tubing roll or tubing precuts; and sheathing the provided tubings with a jacket of plastic by one of extrusion in an extrusion tool, injection molding in an injection molding mold, and embedding the tubings into two jacket halves and by subsequent adhesive bonding or welding of the jacket halves. 23. The method of claim 22,
wherein the plastic of the tubing comprises one of polyether ether ketone, silicone, fluoropolymers and tetrafluoroethylene-perfluoropropylene copolymers. 24. The method of claim 22,
wherein the plastic of the jacket comprises on of polyurethane, polyvinyl chloride, and silicone. | The invention relates to a tube assembly comprising at least two tubes arranged in at least one plane at predefined distances and to a casing covering the tubes in the longitudinal direction.1.-10. (canceled) 11. A tubing arrangement comprising
at least two tubings arranged at predefined spacings in at least one plane; and a jacket surrounding the tubings in the longitudinal direction. 12. The tubing arrangement in accordance with claim 11,
wherein the tubings are manufactured from plastic such as polyether ether ketone or silicone or fluoropolymers, e.g. tetrafluoroethylene-perfluoropropylene copolymers; and wherein the jacket is manufactured from plastic such as polyurethane or polyvinyl chloride or silicone. 13. The tubing arrangement in accordance with claim 12,
wherein the plastic of the tubing comprises one of polyether ether ketone, silicone, fluoropolymers, and tetrafluoroethylene-perfluoropropylene copolymers. 14. The tubing arrangement in accordance with claim 12,
wherein the plastic of the jacket comprises one of polyurethane, polyvinyl chloride and silicone. 15. The tubing arrangement in accordance with claim 11,
wherein the jacket is manufactured by extrusion around the tubings by means of an extrusion tool or by molding the tubings by means of injection molding or by connecting two jacket halves while interposing the tubings by means of adhesive bonding, ultrasound welding, or the like. 16. The tubing arrangement in accordance with claim 11,
wherein end sections of the tubings can be exposed by making an incision in the jacket up to the outer diameter of the tubings and pulling off the end sections of the jacket thereby cut off from the end sections of the tubings. 17. The tubing arrangement in accordance with claim 16,
wherein fittings can be attached to the end sections of the tubings. 18. The tubing arrangement in accordance with claim 11,
wherein the individual tubings of the tubing arrangement have one of an individual color and a code. 19. The tubing arrangement in accordance with claim 11,
wherein the outer contour of the jacket having the tubings located therein is adapted such that it complements the outer contour of a drag chain that is used in connection with the tubing arrangement at a liquid handling device for use in analysis or in medical diagnosis, for instance in liquid chromatography. 20. The tubing arrangement in accordance with claim 11,
wherein the tubing arrangement replaces a drag chain that is used at a liquid handling device for use in analysis or medical diagnosis. 21. A liquid handling device for use in analysis or medical diagnosis, the liquid handling device having a tubing arrangement, the tubing arrangement comprising
at least two tubings arranged at predefined spacings in at least one plane; and a jacket surrounding the tubings in the longitudinal direction. 22. A method of manufacturing a tubing arrangement that comprises the following steps:
providing at least two tubings of plastic in at least one plane, starting from a tubing roll or tubing precuts; and sheathing the provided tubings with a jacket of plastic by one of extrusion in an extrusion tool, injection molding in an injection molding mold, and embedding the tubings into two jacket halves and by subsequent adhesive bonding or welding of the jacket halves. 23. The method of claim 22,
wherein the plastic of the tubing comprises one of polyether ether ketone, silicone, fluoropolymers and tetrafluoroethylene-perfluoropropylene copolymers. 24. The method of claim 22,
wherein the plastic of the jacket comprises on of polyurethane, polyvinyl chloride, and silicone. | 1,700 |
345,415 | 16,643,331 | 1,798 | A solid-state imaging element includes a pixel including a first imaging element, a second imaging element, a third imaging element, and an on-chip micro lens 90. The first imaging element includes a first electrode 11, a third electrode 12, and a second electrode 16. The pixel further includes a third electrode control line VOA connected to the third electrode 12 and a plurality of control lines 62B connected to various transistors included in the second and third imaging elements and different from the third electrode control line VOA. In the pixel, a distance between the center of the on-chip micro lens 90 included in the pixel and any one of the plurality of control lines 62B included in the pixel is shorter than a distance between the center of the on-chip micro lens 90 included in the pixel and the third electrode control line VOA included in the pixel. | 1. A solid-state imaging element comprising a pixel including:
a first imaging element; a second imaging element; a first transfer transistor, a first reset transistor, and a first selection transistor electrically connected to the second imaging element; a third imaging element; a second transfer transistor, a second reset transistor, and a second selection transistor electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, the pixel further includes: a third electrode control line connected to the third electrode; and a plurality of control lines connected to the first transfer transistor, the first reset transistor, the first selection transistor, the second transfer transistor, the second reset transistor, and the second selection transistor, and different from the third electrode control line, and in the pixel, a distance between a center of the on-chip micro lens included in the pixel and any one of the plurality of control lines included in the pixel is shorter than a distance between the center of the on-chip micro lens included in the pixel and the third electrode control line included in the pixel. 2. A solid-state imaging device comprising a pixel including:
a first imaging element; a second imaging element; a third imaging element; and an on-chip micro lens, wherein each of a distance d1 between a center of an inscribed circle of a charge accumulation electrode and a center of the on-chip micro lens, a distance d2 between a center of an inscribed circle of the second imaging element and the center of the on-chip micro lens, and a distance d3 between a center of an inscribed circle of the third imaging element and the center of the on-chip micro lens is shorter than a distance d4 between a center of an inscribed circle of a first electrode and the center of the on-chip micro lens or a distance d5 between a center of an inscribed circle of a floating diffusion region and the center of the on-chip micro lens. 3. A solid-state imaging element comprising a pixel including:
a first imaging element; a first floating diffusion region electrically connected to the first imaging element; a second imaging element; a second floating diffusion region electrically connected to the second imaging element; a third imaging element; a third floating diffusion region electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and each of centers of the first to third floating diffusion layers is disposed outside an inscribed circle of the third electrode, outside an outline of the third electrode, or outside a circumscribed circle of the third electrode. 4. A solid-state imaging element comprising a pixel including:
a first imaging element; a second imaging element; a first transfer transistor, a first reset transistor, and a first selection transistor electrically connected to the second imaging element; a third imaging element; a second transfer transistor, a second reset transistor, and a second selection transistor electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and a minimum channel length in the first and second transfer transistors, the first and second reset transistors, and the first and second selection transistors is shorter than a minimum distance between the third electrode and the first electrode. 5. A solid-state imaging device comprising a pixel including:
a first imaging element; a second imaging element; a third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and the third electrode has an area larger than the third imaging element. 6. The solid-state imaging device according to claim 5, wherein the third electrode has an area smaller than the second imaging element. | A solid-state imaging element includes a pixel including a first imaging element, a second imaging element, a third imaging element, and an on-chip micro lens 90. The first imaging element includes a first electrode 11, a third electrode 12, and a second electrode 16. The pixel further includes a third electrode control line VOA connected to the third electrode 12 and a plurality of control lines 62B connected to various transistors included in the second and third imaging elements and different from the third electrode control line VOA. In the pixel, a distance between the center of the on-chip micro lens 90 included in the pixel and any one of the plurality of control lines 62B included in the pixel is shorter than a distance between the center of the on-chip micro lens 90 included in the pixel and the third electrode control line VOA included in the pixel.1. A solid-state imaging element comprising a pixel including:
a first imaging element; a second imaging element; a first transfer transistor, a first reset transistor, and a first selection transistor electrically connected to the second imaging element; a third imaging element; a second transfer transistor, a second reset transistor, and a second selection transistor electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, the pixel further includes: a third electrode control line connected to the third electrode; and a plurality of control lines connected to the first transfer transistor, the first reset transistor, the first selection transistor, the second transfer transistor, the second reset transistor, and the second selection transistor, and different from the third electrode control line, and in the pixel, a distance between a center of the on-chip micro lens included in the pixel and any one of the plurality of control lines included in the pixel is shorter than a distance between the center of the on-chip micro lens included in the pixel and the third electrode control line included in the pixel. 2. A solid-state imaging device comprising a pixel including:
a first imaging element; a second imaging element; a third imaging element; and an on-chip micro lens, wherein each of a distance d1 between a center of an inscribed circle of a charge accumulation electrode and a center of the on-chip micro lens, a distance d2 between a center of an inscribed circle of the second imaging element and the center of the on-chip micro lens, and a distance d3 between a center of an inscribed circle of the third imaging element and the center of the on-chip micro lens is shorter than a distance d4 between a center of an inscribed circle of a first electrode and the center of the on-chip micro lens or a distance d5 between a center of an inscribed circle of a floating diffusion region and the center of the on-chip micro lens. 3. A solid-state imaging element comprising a pixel including:
a first imaging element; a first floating diffusion region electrically connected to the first imaging element; a second imaging element; a second floating diffusion region electrically connected to the second imaging element; a third imaging element; a third floating diffusion region electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and each of centers of the first to third floating diffusion layers is disposed outside an inscribed circle of the third electrode, outside an outline of the third electrode, or outside a circumscribed circle of the third electrode. 4. A solid-state imaging element comprising a pixel including:
a first imaging element; a second imaging element; a first transfer transistor, a first reset transistor, and a first selection transistor electrically connected to the second imaging element; a third imaging element; a second transfer transistor, a second reset transistor, and a second selection transistor electrically connected to the third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and a minimum channel length in the first and second transfer transistors, the first and second reset transistors, and the first and second selection transistors is shorter than a minimum distance between the third electrode and the first electrode. 5. A solid-state imaging device comprising a pixel including:
a first imaging element; a second imaging element; a third imaging element; and an on-chip micro lens, wherein the first imaging element includes a first electrode, a third electrode, and a second electrode facing the first and third electrodes, and the third electrode has an area larger than the third imaging element. 6. The solid-state imaging device according to claim 5, wherein the third electrode has an area smaller than the second imaging element. | 1,700 |
345,416 | 16,643,324 | 3,679 | An auxiliary control system, having a method for controlling same, controls subsea equipment such as a tree or manifold, for example, in the event of failure of a control umbilical. A power unit is installed subsea, and then a control tool is coupled to the subsea equipment. Control signals from topside source are transmitted to the power unit, which powers and controls the control tool in response to the control signals to operate a control element of the subsea equipment, such as a valve. | 1-27. (canceled) 28. An auxiliary control system for controlling subsea equipment, the system comprising:
a subsea-installed power unit having an on-board battery and a power supply; a data capture device connected to the power unit by a subsea communications link, the data capture device being arranged to capture control signals issued from a remote topside source and to transmit those signals to the power unit along the communications link; at least one control tool that is connected to the power supply by a first flying lead or flexible hose to receive power from the power unit and that is movable relative to the power unit to be coupled to the subsea equipment, enabling the coupled control tool to operate at least one control element of the subsea equipment in response to the control signals; and at least one power connector that is movable relative to the power unit to be coupled to the subsea equipment and that is connected to the power supply by a second flying lead or flexible hose to receive power for energising the subsea equipment. 29. The system of claim 28, wherein the data capture device is supported by a surface buoy to receive control signals transmitted from the remote topside source through air. 30. The system of claim 29, wherein the buoy is anchored by the power unit via a tether extending from the power unit to the buoy. 31. The system of claim 30, wherein the tether incorporates the communications link. 32. The system of claim 29, wherein the buoy supports at least one electricity-generation device and a power line connects that device to the battery of the power unit. 33. The system of claim 28, wherein the data capture device is coupled to a subsea data carrier to receive control signals transmitted from the remote topside source along the data carrier. 34. The system of claim 28, wherein the power supply comprises an electrical power supply and a hydraulic power supply. 35. The system of claim 34, wherein the hydraulic power supply is pressurised by a pump that is driven by a motor powered by the electric power supply. 36. The system of claim 28, further comprising a power connection between the power unit and a power supply of another item of subsea equipment to charge the battery. 37. The system of claim 28, further comprising a subsea-installed robotised positioning system for moving the or each control tool between different locations on the subsea equipment to operate different control elements of the subsea equipment in succession. 38. A method for controlling subsea equipment, the method comprising:
installing a power unit subsea; moving at least one control tool relative to the power unit to couple the control tool to the subsea equipment, where the at least one control tool is connected to the power unit by a first flying lead or flexible hose; capturing control signals issued from a remote topside source and transmitting those signals to the power unit; providing power to the control tool from the power unit; using the coupled control tool to operate at least one control element of the subsea equipment in response to the control signals; moving at last one power connector relative to the power unit to couple the connector to the subsea equipment, wherein the at least one power connector is connected to the power unit by a second flying lead or flexible hose; and providing power to the connector from the power unit to energise the subsea equipment. 39. The method of claim 38, comprising capturing the control signals at a surface location. 40. The method of claim 39, comprising generating electrical power at the surface location and transmitting that power from the surface location to charge a battery of the power unit. 41. The method of claim 38, comprising capturing the control signals from a subsea data carrier. 42. The method of claim 38, comprising providing electrical and hydraulic power from the power unit. 43. The method of claim 42, comprising producing hydraulic power from electric power onboard the power unit. 44. The method of claim 38, comprising charging the battery from a power supply of another item of subsea equipment. 45. The method of claim 38, comprising moving the or each control tool between different locations on the subsea equipment to operate different control elements of the subsea equipment in succession. 46. The method of claim 45, comprising moving the or each control tool by a positioning system distinct from the power unit. 47. The method of claim 38, wherein the remote topside source of control signals is a topside installation connected to the subsea equipment by an umbilical. | An auxiliary control system, having a method for controlling same, controls subsea equipment such as a tree or manifold, for example, in the event of failure of a control umbilical. A power unit is installed subsea, and then a control tool is coupled to the subsea equipment. Control signals from topside source are transmitted to the power unit, which powers and controls the control tool in response to the control signals to operate a control element of the subsea equipment, such as a valve.1-27. (canceled) 28. An auxiliary control system for controlling subsea equipment, the system comprising:
a subsea-installed power unit having an on-board battery and a power supply; a data capture device connected to the power unit by a subsea communications link, the data capture device being arranged to capture control signals issued from a remote topside source and to transmit those signals to the power unit along the communications link; at least one control tool that is connected to the power supply by a first flying lead or flexible hose to receive power from the power unit and that is movable relative to the power unit to be coupled to the subsea equipment, enabling the coupled control tool to operate at least one control element of the subsea equipment in response to the control signals; and at least one power connector that is movable relative to the power unit to be coupled to the subsea equipment and that is connected to the power supply by a second flying lead or flexible hose to receive power for energising the subsea equipment. 29. The system of claim 28, wherein the data capture device is supported by a surface buoy to receive control signals transmitted from the remote topside source through air. 30. The system of claim 29, wherein the buoy is anchored by the power unit via a tether extending from the power unit to the buoy. 31. The system of claim 30, wherein the tether incorporates the communications link. 32. The system of claim 29, wherein the buoy supports at least one electricity-generation device and a power line connects that device to the battery of the power unit. 33. The system of claim 28, wherein the data capture device is coupled to a subsea data carrier to receive control signals transmitted from the remote topside source along the data carrier. 34. The system of claim 28, wherein the power supply comprises an electrical power supply and a hydraulic power supply. 35. The system of claim 34, wherein the hydraulic power supply is pressurised by a pump that is driven by a motor powered by the electric power supply. 36. The system of claim 28, further comprising a power connection between the power unit and a power supply of another item of subsea equipment to charge the battery. 37. The system of claim 28, further comprising a subsea-installed robotised positioning system for moving the or each control tool between different locations on the subsea equipment to operate different control elements of the subsea equipment in succession. 38. A method for controlling subsea equipment, the method comprising:
installing a power unit subsea; moving at least one control tool relative to the power unit to couple the control tool to the subsea equipment, where the at least one control tool is connected to the power unit by a first flying lead or flexible hose; capturing control signals issued from a remote topside source and transmitting those signals to the power unit; providing power to the control tool from the power unit; using the coupled control tool to operate at least one control element of the subsea equipment in response to the control signals; moving at last one power connector relative to the power unit to couple the connector to the subsea equipment, wherein the at least one power connector is connected to the power unit by a second flying lead or flexible hose; and providing power to the connector from the power unit to energise the subsea equipment. 39. The method of claim 38, comprising capturing the control signals at a surface location. 40. The method of claim 39, comprising generating electrical power at the surface location and transmitting that power from the surface location to charge a battery of the power unit. 41. The method of claim 38, comprising capturing the control signals from a subsea data carrier. 42. The method of claim 38, comprising providing electrical and hydraulic power from the power unit. 43. The method of claim 42, comprising producing hydraulic power from electric power onboard the power unit. 44. The method of claim 38, comprising charging the battery from a power supply of another item of subsea equipment. 45. The method of claim 38, comprising moving the or each control tool between different locations on the subsea equipment to operate different control elements of the subsea equipment in succession. 46. The method of claim 45, comprising moving the or each control tool by a positioning system distinct from the power unit. 47. The method of claim 38, wherein the remote topside source of control signals is a topside installation connected to the subsea equipment by an umbilical. | 3,600 |
345,417 | 16,643,327 | 3,679 | The present invention provides an industrially-advantageous process for preparing a benzoyl formic acid compound, and an efficient process for preparing a pyridazine compound using the same process. Specifically, the present invention provides a process for preparing a compound represented by formula (2), which comprises a step (B): a step of reacting a compound represented by formula (1) with a nitrosyl sulfuric acid in water to produce the compound represented by formula (2). | 1. A process for preparing a below-mentioned compound represented by formula (2), which comprises a step (B): a step of reacting a compound represented by formula (1): 2. The process according to claim 1 wherein the step (B) is conducted in the presence of a silicon dioxide-containing inorganic material. 3. A process for preparing a below-mentioned compound represented by formula (2): 4. A process for preparing a compound represented by formula (5): 5. The process according to claim 4 wherein the step (C) is conducted in the presence of an alkaline earth metal salt. 6. A process for preparing a compound represented by formula (7): 7. The process according to claim 6 wherein the step (D) is conducted in the presence of an alkaline earth metal salt. 8. A process for preparing a compound represented by formula (8): 9. The process according to claim 8 wherein the step (E) is conducted in the presence of an alkaline earth metal salt. 10. The process according to claim 1 wherein R1 and R5 each independently represents a fluorine atom, and R2, R3 and R4 each independently represents a hydrogen atom. 11. The process according to claim 6 wherein R1 and R5 each independently represents a fluorine atom, and R2, R3 and R4 each independently represents a hydrogen atom, and R6 represents a hydrogen atom, a fluorine atom, a chlorine atom, or a bromine atom. | The present invention provides an industrially-advantageous process for preparing a benzoyl formic acid compound, and an efficient process for preparing a pyridazine compound using the same process. Specifically, the present invention provides a process for preparing a compound represented by formula (2), which comprises a step (B): a step of reacting a compound represented by formula (1) with a nitrosyl sulfuric acid in water to produce the compound represented by formula (2).1. A process for preparing a below-mentioned compound represented by formula (2), which comprises a step (B): a step of reacting a compound represented by formula (1): 2. The process according to claim 1 wherein the step (B) is conducted in the presence of a silicon dioxide-containing inorganic material. 3. A process for preparing a below-mentioned compound represented by formula (2): 4. A process for preparing a compound represented by formula (5): 5. The process according to claim 4 wherein the step (C) is conducted in the presence of an alkaline earth metal salt. 6. A process for preparing a compound represented by formula (7): 7. The process according to claim 6 wherein the step (D) is conducted in the presence of an alkaline earth metal salt. 8. A process for preparing a compound represented by formula (8): 9. The process according to claim 8 wherein the step (E) is conducted in the presence of an alkaline earth metal salt. 10. The process according to claim 1 wherein R1 and R5 each independently represents a fluorine atom, and R2, R3 and R4 each independently represents a hydrogen atom. 11. The process according to claim 6 wherein R1 and R5 each independently represents a fluorine atom, and R2, R3 and R4 each independently represents a hydrogen atom, and R6 represents a hydrogen atom, a fluorine atom, a chlorine atom, or a bromine atom. | 3,600 |
345,418 | 16,643,332 | 3,679 | An air-conditioning apparatus includes a refrigerant circuit in which an outdoor unit, at least one load-side expansion device, and at least one load-side heat exchanger are connected by pipes to allow refrigerant to circulate. The outdoor unit includes a compressor including an injection port allowing the refrigerant to flow into a suction chamber, a heat-source-side heat exchanger for heat exchange for the refrigerant, and an accumulator. The load-side heat exchanger transfers heat between a load and the refrigerant. The outdoor unit includes: an injection pipe having one end connected between the heat-source-side heat exchanger and the load-side expansion device, and the other end connected to the injection port, in the refrigerant circuit; an outdoor-side expansion device located downstream from the one end of the injection pipe in the flow of the refrigerant from the load-side expansion device to the heat-source-side heat exchanger; and an injection expansion device that adjusts the amount of the refrigerant flowing through the injection pipe. Also, a controller is provided to control the opening degrees of the outdoor-side expansion device and the injection expansion device. | 1. An air-conditioning apparatus comprising:
an outdoor unit including a compressor, a heat-source-side heat exchanger, and an accumulator, the compressor including a suction chamber having an injection port that allows refrigerant to flow into the suction chamber, the compressor being configured to compress and discharge the refrigerant, the heat-source-side heat exchanger being configured to cause heat exchange for the refrigerant to be performed, the accumulator being configured to accumulate the refrigerant; at least one load-side expansion device configured to reduce a pressure of the refrigerant; and at least one load-side heat exchanger configured to cause heat exchange to be performed between a load and the refrigerant, the outdoor unit, the at least one load-side expansion device, and the at least one load-side heat exchanger being connected by pipes, whereby a refrigerant circuit is formed to circulate the refrigerant, the outdoor unit including:
an injection pipe having one end connected between the heat-source-side heat exchanger and the load-side expansion device and an other end connected to the injection port, the injection pipe being configured to allow part of the refrigerant in the refrigerant circuit to flow toward the injection port;
an outdoor-side expansion device located downstream of the one end of the injection pipe in a flow of the refrigerant in a case where the refrigerant flows from the load-side expansion device to the heat-source-side heat exchanger in the refrigerant circuit, the outdoor-side expansion device being configured to reduce the pressure of the refrigerant to adjust a flow rate thereof; and
an injection expansion device configured to adjust an amount of the refrigerant that flows in the injection pipe,
the air-conditioning apparatus further comprising a controller configured to control an opening degree of the outdoor-side expansion device and an opening degree of the injection expansion device. 2. The air-conditioning apparatus of claim 1, wherein
a plurality of the outdoor units are connected in parallel by pipes, whereby the refrigerant circuit is formed. 3. The air-conditioning apparatus of claim 1, wherein when determining that a discharge temperature of the refrigerant that is discharged from the compressor is higher than or equal to a predetermined discharge temperature threshold, the controller controls the opening degree of the injection expansion device such that the discharge temperature becomes lower than the discharge temperature threshold. 4. The air-conditioning apparatus of claim 1, wherein the controller controls the opening degree of the injection expansion device such that a discharge temperature of the refrigerant that is discharged from the compressor approaches a predetermined discharge temperature threshold. 5. The air-conditioning apparatus of claim 1, wherein when determining a discharge temperature of the compressor that is reduced because of a return liquid from the accumulator is lower than or equal to a predetermined liquid-level adjustment threshold, the controller controls the opening degree of the outdoor-side expansion device such that the discharge temperature of the compressor becomes higher than the liquid-level adjustment threshold. 6. The air-conditioning apparatus of claim 5, wherein the liquid-level adjustment threshold is a value obtained by adding a temperature value by which the discharge temperature is reduced in accordance with the opening degree of the injection expansion device, to the discharge temperature that is reduced because of the return liquid from the accumulator, when the injection expansion device is in an opened state. 7. The air-conditioning apparatus of claim 3, wherein the controller calculates a degree of discharge superheat of the refrigerant that is discharged from the compressor, and performs processing based on the degree of discharge superheat instead of the discharge temperature. 8. The air-conditioning apparatus of claim 1, wherein
the outdoor unit further includes a refrigerant flow switching device configured to switch a flow passage for the refrigerant between a flow passage for a cooling operation mode and a flow passage for a heating operation mode, and the controller controls the opening degree of the injection expansion device in the heating operation mode. 9. The air-conditioning apparatus of claim 8, wherein the heating operation mode includes a heating only operation mode in which ones of the load-side heat exchangers that are not in a stopped state all operate as condensers, and a heating main operation mode in which one or ones of the load-side heat exchangers not being in the stopped state operate as condensers, and a remaining one or ones of the load-side heat exchangers not being in the stopped state operate as evaporators. 10. The air-conditioning apparatus of claim 1, further comprising:
a plurality of indoor units each including the load-side expansion device and the load-side heat exchanger; and a relay unit configured to operate as a relay between the outdoor unit and the plurality of indoor units, wherein the outdoor unit, the plurality of indoor units, and the relay unit are connected by pipes such that the refrigerant circulates between components included in the outdoor unit and components included in the plurality of indoor units, through the relay unit, whereby the refrigerant circuit is formed. 11. The air-conditioning apparatus of claim 1, comprising:
the refrigerant circuit including the load-side heat exchanger, the load-side heat exchanger being configured to cause heat exchange to be performed between the refrigerant and a heat medium that is applied as the load and different from the refrigerant; and a heat-medium circulation circuit in which a pump, the load-side heat exchanger, a use-side heat exchanger, and a heat-medium flow adjusting device are connected by pipes to circulate the heat medium, the pump being configured to pressurize the heat medium, the use-side heat exchanger being configured to cause heat exchange for air to be conditioned to be performed, the heat-medium flow adjusting device being configured to adjust a flow rate of the heat medium that flows into and out of the use-side heat exchanger. 12. The air-conditioning apparatus of claim 1, wherein the heat-source-side heat exchanger is a water-refrigerant heat exchanger configured to cause heat exchange to be performed between water and the refrigerant. | An air-conditioning apparatus includes a refrigerant circuit in which an outdoor unit, at least one load-side expansion device, and at least one load-side heat exchanger are connected by pipes to allow refrigerant to circulate. The outdoor unit includes a compressor including an injection port allowing the refrigerant to flow into a suction chamber, a heat-source-side heat exchanger for heat exchange for the refrigerant, and an accumulator. The load-side heat exchanger transfers heat between a load and the refrigerant. The outdoor unit includes: an injection pipe having one end connected between the heat-source-side heat exchanger and the load-side expansion device, and the other end connected to the injection port, in the refrigerant circuit; an outdoor-side expansion device located downstream from the one end of the injection pipe in the flow of the refrigerant from the load-side expansion device to the heat-source-side heat exchanger; and an injection expansion device that adjusts the amount of the refrigerant flowing through the injection pipe. Also, a controller is provided to control the opening degrees of the outdoor-side expansion device and the injection expansion device.1. An air-conditioning apparatus comprising:
an outdoor unit including a compressor, a heat-source-side heat exchanger, and an accumulator, the compressor including a suction chamber having an injection port that allows refrigerant to flow into the suction chamber, the compressor being configured to compress and discharge the refrigerant, the heat-source-side heat exchanger being configured to cause heat exchange for the refrigerant to be performed, the accumulator being configured to accumulate the refrigerant; at least one load-side expansion device configured to reduce a pressure of the refrigerant; and at least one load-side heat exchanger configured to cause heat exchange to be performed between a load and the refrigerant, the outdoor unit, the at least one load-side expansion device, and the at least one load-side heat exchanger being connected by pipes, whereby a refrigerant circuit is formed to circulate the refrigerant, the outdoor unit including:
an injection pipe having one end connected between the heat-source-side heat exchanger and the load-side expansion device and an other end connected to the injection port, the injection pipe being configured to allow part of the refrigerant in the refrigerant circuit to flow toward the injection port;
an outdoor-side expansion device located downstream of the one end of the injection pipe in a flow of the refrigerant in a case where the refrigerant flows from the load-side expansion device to the heat-source-side heat exchanger in the refrigerant circuit, the outdoor-side expansion device being configured to reduce the pressure of the refrigerant to adjust a flow rate thereof; and
an injection expansion device configured to adjust an amount of the refrigerant that flows in the injection pipe,
the air-conditioning apparatus further comprising a controller configured to control an opening degree of the outdoor-side expansion device and an opening degree of the injection expansion device. 2. The air-conditioning apparatus of claim 1, wherein
a plurality of the outdoor units are connected in parallel by pipes, whereby the refrigerant circuit is formed. 3. The air-conditioning apparatus of claim 1, wherein when determining that a discharge temperature of the refrigerant that is discharged from the compressor is higher than or equal to a predetermined discharge temperature threshold, the controller controls the opening degree of the injection expansion device such that the discharge temperature becomes lower than the discharge temperature threshold. 4. The air-conditioning apparatus of claim 1, wherein the controller controls the opening degree of the injection expansion device such that a discharge temperature of the refrigerant that is discharged from the compressor approaches a predetermined discharge temperature threshold. 5. The air-conditioning apparatus of claim 1, wherein when determining a discharge temperature of the compressor that is reduced because of a return liquid from the accumulator is lower than or equal to a predetermined liquid-level adjustment threshold, the controller controls the opening degree of the outdoor-side expansion device such that the discharge temperature of the compressor becomes higher than the liquid-level adjustment threshold. 6. The air-conditioning apparatus of claim 5, wherein the liquid-level adjustment threshold is a value obtained by adding a temperature value by which the discharge temperature is reduced in accordance with the opening degree of the injection expansion device, to the discharge temperature that is reduced because of the return liquid from the accumulator, when the injection expansion device is in an opened state. 7. The air-conditioning apparatus of claim 3, wherein the controller calculates a degree of discharge superheat of the refrigerant that is discharged from the compressor, and performs processing based on the degree of discharge superheat instead of the discharge temperature. 8. The air-conditioning apparatus of claim 1, wherein
the outdoor unit further includes a refrigerant flow switching device configured to switch a flow passage for the refrigerant between a flow passage for a cooling operation mode and a flow passage for a heating operation mode, and the controller controls the opening degree of the injection expansion device in the heating operation mode. 9. The air-conditioning apparatus of claim 8, wherein the heating operation mode includes a heating only operation mode in which ones of the load-side heat exchangers that are not in a stopped state all operate as condensers, and a heating main operation mode in which one or ones of the load-side heat exchangers not being in the stopped state operate as condensers, and a remaining one or ones of the load-side heat exchangers not being in the stopped state operate as evaporators. 10. The air-conditioning apparatus of claim 1, further comprising:
a plurality of indoor units each including the load-side expansion device and the load-side heat exchanger; and a relay unit configured to operate as a relay between the outdoor unit and the plurality of indoor units, wherein the outdoor unit, the plurality of indoor units, and the relay unit are connected by pipes such that the refrigerant circulates between components included in the outdoor unit and components included in the plurality of indoor units, through the relay unit, whereby the refrigerant circuit is formed. 11. The air-conditioning apparatus of claim 1, comprising:
the refrigerant circuit including the load-side heat exchanger, the load-side heat exchanger being configured to cause heat exchange to be performed between the refrigerant and a heat medium that is applied as the load and different from the refrigerant; and a heat-medium circulation circuit in which a pump, the load-side heat exchanger, a use-side heat exchanger, and a heat-medium flow adjusting device are connected by pipes to circulate the heat medium, the pump being configured to pressurize the heat medium, the use-side heat exchanger being configured to cause heat exchange for air to be conditioned to be performed, the heat-medium flow adjusting device being configured to adjust a flow rate of the heat medium that flows into and out of the use-side heat exchanger. 12. The air-conditioning apparatus of claim 1, wherein the heat-source-side heat exchanger is a water-refrigerant heat exchanger configured to cause heat exchange to be performed between water and the refrigerant. | 3,600 |
345,419 | 16,643,326 | 3,679 | A method for treating converter slag for the purpose of recirculating iron, wherein a converter slag is brought into contact with oxygen in such a way that by means of turbulence, the slag is mixed, the iron and iron oxide components that are present are oxidized, and the slag is then allowed to stand in the vessel or a vessel until a segregation into a solidifying, silicate and phosphorus-rich first fraction and an underlying liquid iron oxide-rich second fraction has taken place, with the converter slag that is used being mixed with a partial flow from the iron oxide-rich second fraction in such a way that the total FeO content of the slag that is to be treated with oxygen is over 35% by weight, thus enabling the segregation into two fractions. | 1. A method for treating converter slag for the purpose of recirculating iron, the method comprising the steps of: contacting a converter slag with oxygen in such a way that by means of turbulence, the slag is mixed, and iron and iron oxide components that are present are oxidized; and resting the slag such that is allowed to stand until a segregation into a solidifying, silicate and phosphorus-rich first fraction and an underlying liquid iron oxide-rich second fraction has taken place. 2. The method according to claim 1, wherein after the contacting step the slag rests for 24 hours. 3. The method according to claim 1, wherein during the contacting step oxygen, air, or mixtures of oxygen and air or oxygen and gas are blown onto or into the slag in order to bring it into contact with oxygen. 4. The method according to claim 1, further comprising measuring the FeO and iron content of a first liquid melt of a pre-contacting step portion of converter slag and measuring the iron content of the second fraction as a second liquid melt generated after the contacting and resting steps; and, then, calculating and mixing a ratio of the two liquid melts so that after the mixing, a FeO content of over 35% by weight of the mixed liquid melts is achieved. 5. The method according to claim 4, further comprising, prior to the contacting step, feeding the converter slag into a receptacle and supplying iron-rich second fraction residual melt to the receptacle, in accordance with the calculating, and then the contacting with oxygen in the vessel and the resting take place until the solidification of the first fraction has taken place and the second liquid fraction is present underneath it. 6. The method according to claim 1, characterized in that a vessel with two chambers is used; first and second chambers of the vessel are separated from each other by a partition having at least one opening above a bottom of the wall; the first chamber is filled with liquid converter slag and after each filling of the first chamber with a slag charge, oxygen is introduced above the slag charge in the first chamber in that oxygen or an oxygen-containing gas is blown onto or through it; through an opening near the bottom of the partition wall, slag flows into the second chamber, which is embodied as a quieting and sedimentation tank; the second chamber comprising a scouring apparatus; solidified slags composed predominately of silicates are removed; the supply with fresh slag takes place in such a way that a relatively constant bath level is present in the chambers; and liquid FeO-rich residual melt that collects at a bottom of the second chamber is removed and is supplied to the first chamber in order to adjust the FeO content. 7. The method according to claim 6, characterized in that the iron content of the freshly supplied slag is continuously measured and the FeO content of the residual melt is measured in order to adjust to a FeO content that is always above 35% in the continuous process. | A method for treating converter slag for the purpose of recirculating iron, wherein a converter slag is brought into contact with oxygen in such a way that by means of turbulence, the slag is mixed, the iron and iron oxide components that are present are oxidized, and the slag is then allowed to stand in the vessel or a vessel until a segregation into a solidifying, silicate and phosphorus-rich first fraction and an underlying liquid iron oxide-rich second fraction has taken place, with the converter slag that is used being mixed with a partial flow from the iron oxide-rich second fraction in such a way that the total FeO content of the slag that is to be treated with oxygen is over 35% by weight, thus enabling the segregation into two fractions.1. A method for treating converter slag for the purpose of recirculating iron, the method comprising the steps of: contacting a converter slag with oxygen in such a way that by means of turbulence, the slag is mixed, and iron and iron oxide components that are present are oxidized; and resting the slag such that is allowed to stand until a segregation into a solidifying, silicate and phosphorus-rich first fraction and an underlying liquid iron oxide-rich second fraction has taken place. 2. The method according to claim 1, wherein after the contacting step the slag rests for 24 hours. 3. The method according to claim 1, wherein during the contacting step oxygen, air, or mixtures of oxygen and air or oxygen and gas are blown onto or into the slag in order to bring it into contact with oxygen. 4. The method according to claim 1, further comprising measuring the FeO and iron content of a first liquid melt of a pre-contacting step portion of converter slag and measuring the iron content of the second fraction as a second liquid melt generated after the contacting and resting steps; and, then, calculating and mixing a ratio of the two liquid melts so that after the mixing, a FeO content of over 35% by weight of the mixed liquid melts is achieved. 5. The method according to claim 4, further comprising, prior to the contacting step, feeding the converter slag into a receptacle and supplying iron-rich second fraction residual melt to the receptacle, in accordance with the calculating, and then the contacting with oxygen in the vessel and the resting take place until the solidification of the first fraction has taken place and the second liquid fraction is present underneath it. 6. The method according to claim 1, characterized in that a vessel with two chambers is used; first and second chambers of the vessel are separated from each other by a partition having at least one opening above a bottom of the wall; the first chamber is filled with liquid converter slag and after each filling of the first chamber with a slag charge, oxygen is introduced above the slag charge in the first chamber in that oxygen or an oxygen-containing gas is blown onto or through it; through an opening near the bottom of the partition wall, slag flows into the second chamber, which is embodied as a quieting and sedimentation tank; the second chamber comprising a scouring apparatus; solidified slags composed predominately of silicates are removed; the supply with fresh slag takes place in such a way that a relatively constant bath level is present in the chambers; and liquid FeO-rich residual melt that collects at a bottom of the second chamber is removed and is supplied to the first chamber in order to adjust the FeO content. 7. The method according to claim 6, characterized in that the iron content of the freshly supplied slag is continuously measured and the FeO content of the residual melt is measured in order to adjust to a FeO content that is always above 35% in the continuous process. | 3,600 |
345,420 | 16,643,325 | 3,679 | A method and a corresponding device are described for creating a first map. The method includes receiving surroundings data values representing surroundings of a vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected using a first surroundings sensor system of the vehicle. The method also includes determining an object class of the surroundings feature, as a function of the first surroundings sensor system of the vehicle, and creating an assignment of the object class to at least one further object class. The further object class is determined proceeding from at least one further surroundings feature, the further surroundings feature being detectable with using a second surroundings sensor system. The second surroundings sensor system is not identical in design to the first surroundings sensor system. The method also includes creating the first map, as a function of the surroundings data values, based on the assignment. | 1-8. (canceled) 9. A method for creating a first map, comprising the following steps:
receiving surroundings data values, the surroundings data values representing surroundings of at least one vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected with using a first surroundings sensor system of the at least one vehicle; determining an object class of the at least one surroundings feature as a function of the first surroundings sensor system of the at least one vehicle; creating an assignment of the object class to at least one further object class, the at least one further object class being determined proceeding from at least one further surroundings feature, the at least one further surroundings feature being detectable using a second surroundings sensor system, and the second surroundings sensor system not being identical in design to the first surroundings sensor system; and creating the first map as a function of the surroundings data values, based on the assignment. 10. The method as recited in claim 9, wherein:
(i) the at least one further surroundings feature is encompassed by a second map, and/or (ii) a step of providing the first map takes place in such a way that: (a) an automated vehicle is operated as a function of the first map and/or as a function of the second map and/or as a function of the assignment, and/or (b) a mobile terminal is operated as a function of the first map and/or as a function of the second map and/or as a function of the assignment. 11. The method as recited in claim 9, wherein the object class is determined: (i) as a function of a geometrical structure of the at least one surroundings feature, and/or (ii) as a function of a material property of the at least one surroundings feature. 12. The method as recited in claim 11, wherein the assignment of the object class to the at least one further object class is created: (i) as a function of the geometrical structure of the at least one surroundings feature, and/or (ii) as a function of a geometrical structure of the at least one further surroundings feature. 13. The method as recited in claim 9, wherein:
(i) the first surroundings sensor system includes a radar sensor, the surroundings data values are detected using the radar sensor, the at least one surroundings feature includes a characteristic radar signature, and the object class is determined as a function of the characteristic radar signature, and/or (ii) the second surroundings sensor system includes a video sensor and/or a LIDAR sensor. 14. The method as recited in claim 9, wherein the assignment is created, proceeding from the surroundings data values, using: a SLAM method, and/or a correlation method. 15. A device for creating a first map, the device comprising:
a first device configured to receive surroundings data values, the surroundings data values representing surroundings of at least one vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected using a first surroundings sensor system of the at least one vehicle; a second device configured to determine an object class of the at least one surroundings feature, as a function of the first surroundings sensor system of the at least one vehicle; a third device configured to create an assignment of the object class to at least one further object class, the at least one further object class being determined proceeding from at least one further surroundings feature, the at least one further surroundings feature being detectable using a second surroundings sensor system, and the second surroundings sensor system not being identical in design to the first surroundings sensor system; and a fourth device configured to create the first map, as a function of the surroundings data values, based on the assignment. 16. The device as recited in claim 15, wherein the first device includes a transceiver, and the second device, the third device, and the fourth device includes an electronic processor including a working memory. | A method and a corresponding device are described for creating a first map. The method includes receiving surroundings data values representing surroundings of a vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected using a first surroundings sensor system of the vehicle. The method also includes determining an object class of the surroundings feature, as a function of the first surroundings sensor system of the vehicle, and creating an assignment of the object class to at least one further object class. The further object class is determined proceeding from at least one further surroundings feature, the further surroundings feature being detectable with using a second surroundings sensor system. The second surroundings sensor system is not identical in design to the first surroundings sensor system. The method also includes creating the first map, as a function of the surroundings data values, based on the assignment.1-8. (canceled) 9. A method for creating a first map, comprising the following steps:
receiving surroundings data values, the surroundings data values representing surroundings of at least one vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected with using a first surroundings sensor system of the at least one vehicle; determining an object class of the at least one surroundings feature as a function of the first surroundings sensor system of the at least one vehicle; creating an assignment of the object class to at least one further object class, the at least one further object class being determined proceeding from at least one further surroundings feature, the at least one further surroundings feature being detectable using a second surroundings sensor system, and the second surroundings sensor system not being identical in design to the first surroundings sensor system; and creating the first map as a function of the surroundings data values, based on the assignment. 10. The method as recited in claim 9, wherein:
(i) the at least one further surroundings feature is encompassed by a second map, and/or (ii) a step of providing the first map takes place in such a way that: (a) an automated vehicle is operated as a function of the first map and/or as a function of the second map and/or as a function of the assignment, and/or (b) a mobile terminal is operated as a function of the first map and/or as a function of the second map and/or as a function of the assignment. 11. The method as recited in claim 9, wherein the object class is determined: (i) as a function of a geometrical structure of the at least one surroundings feature, and/or (ii) as a function of a material property of the at least one surroundings feature. 12. The method as recited in claim 11, wherein the assignment of the object class to the at least one further object class is created: (i) as a function of the geometrical structure of the at least one surroundings feature, and/or (ii) as a function of a geometrical structure of the at least one further surroundings feature. 13. The method as recited in claim 9, wherein:
(i) the first surroundings sensor system includes a radar sensor, the surroundings data values are detected using the radar sensor, the at least one surroundings feature includes a characteristic radar signature, and the object class is determined as a function of the characteristic radar signature, and/or (ii) the second surroundings sensor system includes a video sensor and/or a LIDAR sensor. 14. The method as recited in claim 9, wherein the assignment is created, proceeding from the surroundings data values, using: a SLAM method, and/or a correlation method. 15. A device for creating a first map, the device comprising:
a first device configured to receive surroundings data values, the surroundings data values representing surroundings of at least one vehicle, the surroundings encompassing at least one surroundings feature, the surroundings data values being detected using a first surroundings sensor system of the at least one vehicle; a second device configured to determine an object class of the at least one surroundings feature, as a function of the first surroundings sensor system of the at least one vehicle; a third device configured to create an assignment of the object class to at least one further object class, the at least one further object class being determined proceeding from at least one further surroundings feature, the at least one further surroundings feature being detectable using a second surroundings sensor system, and the second surroundings sensor system not being identical in design to the first surroundings sensor system; and a fourth device configured to create the first map, as a function of the surroundings data values, based on the assignment. 16. The device as recited in claim 15, wherein the first device includes a transceiver, and the second device, the third device, and the fourth device includes an electronic processor including a working memory. | 3,600 |
345,421 | 16,643,330 | 3,679 | The invention relates to an apparatus for manufacturing mineral wool. The apparatus includes means (1) for producing molten mineral material, at least one fiberizing device (3) for forming fibres, into which fiberizing device the molten mineral material is fed (2) and by which fibres (12) are formed. The fiberizing device (3) comprises, rotationally arranged around a vertical axis (15), at least one fiberizing plate (13) having a vertical peripheral edge, into which are formed numerous small-sized holes (14), through which the molten material is led by centrifugal force to form fibres (12). Into the fiberizing device (3) are arranged elements to produce a vertical flow of blowing medium (16) to be led around the fiberizing plate (13), the flow causing the fibres (12) to turn downwards and, at the same time, to thin. Downstream the fiberizing device (3) is arranged a collection device (6), into which the formed fibres (12) are led and collected into a mat-like material. In connection with said at least one fiberizing plate (13) is arranged a substantially horizontal, relatively narrow channel (5), through which the fibres (12) are brought into the chamber space (7) of the collection device (6). The invention further relates to a method for manufacturing mineral wool and a mineral wool product manufactured by the method | 1. An apparatus for manufacturing mineral wool, the apparatus comprising:
means for producing molten mineral material; at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes through which the molten material is led by centrifugal force to form fibres, wherein to the fiberizing device are arranged elements to produce a vertical flow of blowing medium to be led around the fiberizing plate, the flow causing the fibres to turn downwards and, at the same time, to thin; a collection device arranged downstream of the fiberizing device, into which the formed fibres are led and collected into a mat-like material; wherein the apparatus includes at least two fiberizing devices placed at different height levels with each other and at different horizontal distances from the collection device, and that in connection with said at least one fiberizing plate of each fiberizing device is arranged a conveying device, where the fibres are brought before reaching the collection device. 2. The apparatus according to claim 1, wherein the conveying device comprises a horizontal or inclined channel located between the fiberizing plate and collection device. 3. The apparatus according to claim 2, wherein the channel is straight or curved. 4. The apparatus according to claim 1, wherein the conveying device comprises a belt. 5. The apparatus according to claim 1, wherein the conveying device comprises air producing means and/or suction means for transporting fibres to the collection device. 6. The apparatus according to claim 1, wherein the collection device has a collection chamber and collector elements, which comprise a collection drum equipped with a perforated peripheral surface, inside which is a suction box, onto which drum the fibres are collected into a primary mat or web. 7. The apparatus according to claim 2, wherein a length of the channel is in the range of 1-10 m. 8. The apparatus according to claim 1, wherein a diameter of the holes on the periphery of the fiberizing plate is in the range of about 0.3 mm to about 2 mm. 9. The apparatus according to claim 1, wherein at least one fiberizing plate has holes of different size in relation to the holes of at least one other fiberizing plate for forming fibres of different thicknesses by different fiberizing plates. 10. The apparatus according to claim 1, wherein the fiberizing plates are similar to each other. 11. The apparatus according to claim 1, wherein the fiberizing plates are different from each other. 12. A method for manufacturing mineral wool, the method using an apparatus, which includes means for producing molten mineral material, at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes, through which the molten material is led by centrifugal force to form fibres, wherein into the fiberizing device are arranged elements to produce an annular flow of blowing medium directed vertically downwards around the fiberizing plate, the flow causing the fibres to turn downwards and to thin, as well as a collection device arranged downstream the fiberizing device, into which the formed fibres are led and collected into a mat-like material, wherein at least two fiberizing devices are arranged to feed fibres into a common collection device, the fiberizing devices being placed at different height levels with each other and/or at different horizontal distance from the collection device, and that in connection with the fiberizing plate of each fiberizing device is arranged a conveying device where the fibres are brought and by means of which the fibres are conveyed into the collection device to form a primary fibre mat or web. 13. The method according to claim 12, wherein with different fiberizing plates (13) are used different fiberizing parameters and/or holes of different size (14) to vary in a desired manner the characteristics of the intermediate product and/or final product to be manufactured by the apparatus. 14. The method according to claim 12, wherein blowing medium is used to transport the fibres with the conveying means into the collection device (6). 15. The method according to claim 12, wherein the fiberizing devices (3) are installed in place of an existing fiberizing apparatus in an existing manufacturing line. 16. An apparatus for manufacturing mineral wool, the apparatus comprising:
means for producing molten mineral material; at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes through which the molten material is led by centrifugal force to form fibres, wherein to the fiberizing device are arranged elements to produce a vertical flow of blowing medium to be led around the fiberizing plate, the flow causing the fibres to turn downwards and, at the same time, to thin; a collection device arranged downstream of the fiberizing device, into which the formed fibres are led and collected into a mat-like material; wherein the apparatus includes at least two fiberizing devices, and that in connection with said at least one fiberizing plate of each fiberizing device is arranged a conveying device, where the fibres are brought before reaching the collection device. | The invention relates to an apparatus for manufacturing mineral wool. The apparatus includes means (1) for producing molten mineral material, at least one fiberizing device (3) for forming fibres, into which fiberizing device the molten mineral material is fed (2) and by which fibres (12) are formed. The fiberizing device (3) comprises, rotationally arranged around a vertical axis (15), at least one fiberizing plate (13) having a vertical peripheral edge, into which are formed numerous small-sized holes (14), through which the molten material is led by centrifugal force to form fibres (12). Into the fiberizing device (3) are arranged elements to produce a vertical flow of blowing medium (16) to be led around the fiberizing plate (13), the flow causing the fibres (12) to turn downwards and, at the same time, to thin. Downstream the fiberizing device (3) is arranged a collection device (6), into which the formed fibres (12) are led and collected into a mat-like material. In connection with said at least one fiberizing plate (13) is arranged a substantially horizontal, relatively narrow channel (5), through which the fibres (12) are brought into the chamber space (7) of the collection device (6). The invention further relates to a method for manufacturing mineral wool and a mineral wool product manufactured by the method1. An apparatus for manufacturing mineral wool, the apparatus comprising:
means for producing molten mineral material; at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes through which the molten material is led by centrifugal force to form fibres, wherein to the fiberizing device are arranged elements to produce a vertical flow of blowing medium to be led around the fiberizing plate, the flow causing the fibres to turn downwards and, at the same time, to thin; a collection device arranged downstream of the fiberizing device, into which the formed fibres are led and collected into a mat-like material; wherein the apparatus includes at least two fiberizing devices placed at different height levels with each other and at different horizontal distances from the collection device, and that in connection with said at least one fiberizing plate of each fiberizing device is arranged a conveying device, where the fibres are brought before reaching the collection device. 2. The apparatus according to claim 1, wherein the conveying device comprises a horizontal or inclined channel located between the fiberizing plate and collection device. 3. The apparatus according to claim 2, wherein the channel is straight or curved. 4. The apparatus according to claim 1, wherein the conveying device comprises a belt. 5. The apparatus according to claim 1, wherein the conveying device comprises air producing means and/or suction means for transporting fibres to the collection device. 6. The apparatus according to claim 1, wherein the collection device has a collection chamber and collector elements, which comprise a collection drum equipped with a perforated peripheral surface, inside which is a suction box, onto which drum the fibres are collected into a primary mat or web. 7. The apparatus according to claim 2, wherein a length of the channel is in the range of 1-10 m. 8. The apparatus according to claim 1, wherein a diameter of the holes on the periphery of the fiberizing plate is in the range of about 0.3 mm to about 2 mm. 9. The apparatus according to claim 1, wherein at least one fiberizing plate has holes of different size in relation to the holes of at least one other fiberizing plate for forming fibres of different thicknesses by different fiberizing plates. 10. The apparatus according to claim 1, wherein the fiberizing plates are similar to each other. 11. The apparatus according to claim 1, wherein the fiberizing plates are different from each other. 12. A method for manufacturing mineral wool, the method using an apparatus, which includes means for producing molten mineral material, at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes, through which the molten material is led by centrifugal force to form fibres, wherein into the fiberizing device are arranged elements to produce an annular flow of blowing medium directed vertically downwards around the fiberizing plate, the flow causing the fibres to turn downwards and to thin, as well as a collection device arranged downstream the fiberizing device, into which the formed fibres are led and collected into a mat-like material, wherein at least two fiberizing devices are arranged to feed fibres into a common collection device, the fiberizing devices being placed at different height levels with each other and/or at different horizontal distance from the collection device, and that in connection with the fiberizing plate of each fiberizing device is arranged a conveying device where the fibres are brought and by means of which the fibres are conveyed into the collection device to form a primary fibre mat or web. 13. The method according to claim 12, wherein with different fiberizing plates (13) are used different fiberizing parameters and/or holes of different size (14) to vary in a desired manner the characteristics of the intermediate product and/or final product to be manufactured by the apparatus. 14. The method according to claim 12, wherein blowing medium is used to transport the fibres with the conveying means into the collection device (6). 15. The method according to claim 12, wherein the fiberizing devices (3) are installed in place of an existing fiberizing apparatus in an existing manufacturing line. 16. An apparatus for manufacturing mineral wool, the apparatus comprising:
means for producing molten mineral material; at least one fiberizing device for forming fibres, into which fiberizing device the molten mineral material is fed and by which fibres are formed, the fiberizing device comprising, rotationally arranged around a vertical axis, at least one fiberizing plate having a vertical peripheral edge, into which are formed a plurality of holes through which the molten material is led by centrifugal force to form fibres, wherein to the fiberizing device are arranged elements to produce a vertical flow of blowing medium to be led around the fiberizing plate, the flow causing the fibres to turn downwards and, at the same time, to thin; a collection device arranged downstream of the fiberizing device, into which the formed fibres are led and collected into a mat-like material; wherein the apparatus includes at least two fiberizing devices, and that in connection with said at least one fiberizing plate of each fiberizing device is arranged a conveying device, where the fibres are brought before reaching the collection device. | 3,600 |
345,422 | 16,643,351 | 3,679 | Disclosed is an electrode for an energy storage rechargeable device, including a plurality of electrode material layers and a plurality of porous current collector layers, the electrode material layers and current collector layers being arranged in a specific manner, an energy storage rechargeable device including the electrode, and the uses of the electrode. | 1. An electrode for a rechargeable energy storage device, wherein said electrode comprises two external layers and several internal layers interposed between the two external layers, said internal and external layers comprising several electrode material layers ME and several porous current collector layers CC, said electrode material ME and current collector CC layers being alternated according to the repetition pattern —[CC—ME]— and at least one of the two external layers of the electrode is an electrode material layer ME. 2. The electrode according to claim 1, wherein the electrode has a thickness varying from 50 μm to 4 mm. 3. The electrode according to claim 1, wherein at least a part or each of the porous current collector layers CC is in the form of a grid, a perforated sheet, a felt, a meshing, a fabric or a foam. 4. The electrode according to claim 1, wherein the porous current collector layers CC, identical or different, are conductive material layers. 5. The electrode according to claim 1, wherein said electrode comprises an external layer that is an electrode material layer ME and an external layer that is a porous current collector layer CC and wherein said electrode is in the form of an assembly of successive layers having the following structure:
[CC—ME]n
wherein ME is an electrode material layer, CC is a porous current collector layer, and 2≤n≤8. 6. The electrode according to claim 1, wherein the other external layer of the electrode is an electrode material layer ME and said electrode is in the form of an assembly of successive layers having the following structure:
ME—[CC—ME]p-1
wherein ME is an electrode material layer, CC is a porous current collector layer, and 2≤p≤8. 7. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material. 8. The electrode according to claim 1, wherein said electrode is a zinc-based negative electrode. 9. The electrode according to claim 1, wherein said electrode is intended to be arranged into a rechargeable energy storage device comprising the electrode, a counter-electrode and an electrolyte, the external electrode material layer ME being intended to face an external layer of the counter-layer and intended to be in direct contact with the electrolyte. 10. A rechargeable energy storage device comprising:
at least one positive electrode, at least one negative electrode, an electrolyte, wherein in said device, at least one of the positive or negative electrodes is an electrode as defined in claim 1. 11. The device according to claim 10, wherein the electrolyte is in direct contact with the electrode as defined in claim 1, through the external layer that is an electrode material layer ME of said electrode. 12. The device according to claim 10, wherein said device is chosen among an alkaline accumulator, a lithium-ion battery, a lead battery, a nickel-metal hydride battery and a supercapacitor. 13. The device according to claim 10, wherein said device is an alkaline accumulator chosen among a zinc/air battery and a zinc/nickel battery. 14. Method for improving the energy density of a rechargeable energy storage device, comprising providing the electrode as defined in claim 1, and applying the electrode to the energy storage device. 15. The method according to claim 14, wherein the electrode is in an alkaline accumulator. 16. The electrode according to claim 2, wherein at least a part or each of the porous current collector layers CC is in the form of a grid, a perforated sheet, a felt, a meshing, a fabric or a foam. 17. The electrode according to claim 2, wherein the porous current collector layers CC, identical or different, are conductive material layers. 18. The electrode according to claim 3, wherein the porous current collector layers CC, identical or different, are conductive material layers. 19. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material comprising a polymer binder. 20. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material comprises an electronic conductivity agent. | Disclosed is an electrode for an energy storage rechargeable device, including a plurality of electrode material layers and a plurality of porous current collector layers, the electrode material layers and current collector layers being arranged in a specific manner, an energy storage rechargeable device including the electrode, and the uses of the electrode.1. An electrode for a rechargeable energy storage device, wherein said electrode comprises two external layers and several internal layers interposed between the two external layers, said internal and external layers comprising several electrode material layers ME and several porous current collector layers CC, said electrode material ME and current collector CC layers being alternated according to the repetition pattern —[CC—ME]— and at least one of the two external layers of the electrode is an electrode material layer ME. 2. The electrode according to claim 1, wherein the electrode has a thickness varying from 50 μm to 4 mm. 3. The electrode according to claim 1, wherein at least a part or each of the porous current collector layers CC is in the form of a grid, a perforated sheet, a felt, a meshing, a fabric or a foam. 4. The electrode according to claim 1, wherein the porous current collector layers CC, identical or different, are conductive material layers. 5. The electrode according to claim 1, wherein said electrode comprises an external layer that is an electrode material layer ME and an external layer that is a porous current collector layer CC and wherein said electrode is in the form of an assembly of successive layers having the following structure:
[CC—ME]n
wherein ME is an electrode material layer, CC is a porous current collector layer, and 2≤n≤8. 6. The electrode according to claim 1, wherein the other external layer of the electrode is an electrode material layer ME and said electrode is in the form of an assembly of successive layers having the following structure:
ME—[CC—ME]p-1
wherein ME is an electrode material layer, CC is a porous current collector layer, and 2≤p≤8. 7. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material. 8. The electrode according to claim 1, wherein said electrode is a zinc-based negative electrode. 9. The electrode according to claim 1, wherein said electrode is intended to be arranged into a rechargeable energy storage device comprising the electrode, a counter-electrode and an electrolyte, the external electrode material layer ME being intended to face an external layer of the counter-layer and intended to be in direct contact with the electrolyte. 10. A rechargeable energy storage device comprising:
at least one positive electrode, at least one negative electrode, an electrolyte, wherein in said device, at least one of the positive or negative electrodes is an electrode as defined in claim 1. 11. The device according to claim 10, wherein the electrolyte is in direct contact with the electrode as defined in claim 1, through the external layer that is an electrode material layer ME of said electrode. 12. The device according to claim 10, wherein said device is chosen among an alkaline accumulator, a lithium-ion battery, a lead battery, a nickel-metal hydride battery and a supercapacitor. 13. The device according to claim 10, wherein said device is an alkaline accumulator chosen among a zinc/air battery and a zinc/nickel battery. 14. Method for improving the energy density of a rechargeable energy storage device, comprising providing the electrode as defined in claim 1, and applying the electrode to the energy storage device. 15. The method according to claim 14, wherein the electrode is in an alkaline accumulator. 16. The electrode according to claim 2, wherein at least a part or each of the porous current collector layers CC is in the form of a grid, a perforated sheet, a felt, a meshing, a fabric or a foam. 17. The electrode according to claim 2, wherein the porous current collector layers CC, identical or different, are conductive material layers. 18. The electrode according to claim 3, wherein the porous current collector layers CC, identical or different, are conductive material layers. 19. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material comprising a polymer binder. 20. The electrode according to claim 1, wherein each of the electrode material layers ME comprises at least one electrode active material comprises an electronic conductivity agent. | 3,600 |
345,423 | 16,643,328 | 3,679 | The present disclosure provides a collimation backlight source, a display device and a driving method thereof. The collimation backlight source includes a light guide plate, a plurality of light sources of different colors, and a light-extraction grating assembly in each light-extraction region on the surface of the light guide plate. | 1. A collimation backlight source comprising:
a light guide plate with a surface and a lateral side adjacent to the surface; a plurality of light sources of different colors at the lateral side; a light-extraction grating assembly in each of a plurality of light-extraction regions on the surface of the light guide plate. 2. The collimation backlight source according to claim 1, wherein each light-extraction region includes a plurality of spaced light-extraction sub-regions;
the light-extraction grating assembly includes a first light-extraction grating set in each light-extraction sub-region; the collimation backlight source further includes a first buffer layer covering the first light-extraction grating set; a refractive index of the first buffer layer is less than a refractive index of the light guide plate; the first light-extraction grating set in each light-extraction sub-region includes: a first electrode and a second electrode on the light guide plate; wherein the first electrodes of adjacent two light-extraction sub-regions are insulated from each other; a first light-extraction grating on the first electrode or the second electrode; wherein the first light-extraction grating is between the first electrode and the second electrode, and the first light-extraction grating is a step grating; first liquid crystal filled between the first electrode and the second electrode; when the refractive index of the first light-extraction grating is the same as the refractive index of the first liquid crystal, the first light-extraction grating is in a direct light transmission state; for one light-extraction sub-region, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, for any two light-extraction sub-regions in the same light-extraction region, the first light-extraction gratings in the two light-extraction sub-regions project light rays of different colors transmitted in the light guide plate by diffraction. 3. The collimation backlight source according to claim 2, wherein for each light-extraction region, periods of the first light-extraction gratings in all the light-extraction sub-regions are different;
for each light-extraction sub-region, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating directly projects the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction. 4. The collimation backlight source according to claim 2, wherein for each light-extraction region, periods of the first light-extraction gratings in all the light-extraction sub-regions are the same;
for one of the light-extraction sub-regions, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating directly projects the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction; for other ones of the light-extraction sub-regions, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating projects the light rays of other color transmitted in the light guide plate at a diffraction angle greater than 0° by diffraction. 5. The collimation backlight source according to claim 4, wherein the light-extraction grating assembly further includes a second light-extraction grating set in each light-extraction region; the second light-extraction grating set is on the first buffer layer and is at a light-emitting side of the first light-extraction grating set;
the second light-extraction grating set in each light-extraction region includes a plurality of second light-extraction gratings; periods of the second light-extraction gratings are different; the second light-extraction gratings are in other ones of the light-extraction sub-regions in a one-to-one manner; the light rays projected at a diffraction angle greater than 0° by the first light-extraction grating in corresponding light-extraction sub-region, are further diffracted by the second light-extraction grating by diffraction and are projected at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface; the second light-extraction grating is a step grating. 6. The collimation backlight source according to claim 1, wherein the light-extraction grating assembly includes a third light-extraction grating in each light-extraction region; periods of the third light-extraction gratings in all the light-extraction regions are the same;
the collimation backlight source further includes a second buffer layer covering the third light-extraction grating; a refractive index of the second buffer layer is less than a refractive index of the light guide plate; for each light-extraction region, the third light-extraction grating directly projects by diffraction, the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction, and projects the light rays of other color transmitted in the light guide plate at a diffraction angle greater than 0°; the light-extraction grating assembly further includes a plurality of fourth light-extraction gratings in each light-extraction region; the fourth light-extraction gratings are on the second buffer layer and at a light-emitting side of the third light-extraction grating; periods of the fourth light-extraction gratings in each light-extraction region are different; the third light-extraction grating is a step grating, and the fourth light-extraction grating is a step grating; the fourth light-extraction gratings in each light-extraction region sequentially diffract by diffraction, the light rays of other colors projected at a diffraction angle greater than 0° by the third light-extraction grating, and project the light rays of other colors onto preset irradiation areas. 7. The collimation backlight source according to claim 2, wherein the first light-extraction grating is composed of a plurality of light-transmission stripes arranged at equal intervals, and space between two adjacent light-transmission stripes is transparent. 8. The collimation backlight source according to claim 2, wherein in the first light-extraction grating set in each light-extraction sub-region, the first light-extraction grating is in the first liquid crystal. 9. The collimation backlight source according to claim 1, wherein the light-extraction grating assembly in each light-extraction region is on a light emitting surface of the light guide plate. 10. A display device comprising: a display panel and a backlight source;
wherein the display panel includes a plurality of pixel regions; the display panel includes a cell defined by an array substrate and a color filter substrate, and second liquid crystal filled between the array substrate and the color filter substrate; each pixel region of the color filter substrate includes a light-shielding pattern and a light transmission region around the light-shielding pattern; where the backlight source adopts the collimation backlight source according to claim 1; light-extraction regions of the backlight source are corresponding to positions of the pixel regions in a one-to-one manner; the display device further includes: a controller configured to control the light sources of different colors in the backlight source to emit light rays, and control the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction; when the second liquid crystal corresponding to one light-extraction region is not deflected, control the light-extraction grating assembly in the one light-extraction region to project the light rays to a region where the light-shielding pattern of the corresponding pixel region on the color film substrate is located; when the second liquid crystal corresponding to one light-extraction region is deflected, the light rays projected by the light-extraction grating assembly in the one light-extraction region, are adjusted by the second liquid crystal and projected onto the light-transmission region of the corresponding pixel region on the color filter substrate, and then are emitted to a display side. 11. The display device according to claim 10, wherein the light-extraction region includes a plurality of spaced light-extraction sub-regions; the pixel region includes a plurality of sub-pixel regions;
the light-extraction grating assembly includes a first light-extraction grating set in each light-extraction sub-region; the controller is configured to, by applying a voltage to a first electrode and a second electrode, control a refractive index of the first liquid crystal in one light-extraction sub-region to be different from a refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the one light-extraction sub-region to project light rays of a certain color transmitted in the light guide plate by diffraction; for any two light-extraction sub-regions in the same light-extraction region, control the first light-extraction gratings in the two light-extraction sub-regions to project light rays of different colors transmitted in the light guide plate by diffraction. 12. A driving method of the display device according to claim 10, comprising:
controlling the light sources of different colors in the backlight source to sequentially emit light rays, and controlling the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction; when the second liquid crystal corresponding to one light-extraction region is not deflected, controlling the light-extraction grating assembly in the one light-extraction region to project the light rays to a region where the light-shielding pattern of the corresponding pixel region on the color film substrate is located; when the second liquid crystal corresponding to one light-extraction region is deflected, adjusting by the second liquid crystal, the light rays projected by the light-extraction grating assembly in the one light-extraction region, and projecting the adjusted light rays onto the light-transmission region of the corresponding pixel region on the color filter substrate for emitting adjusted light rays to a display side. 13. The driving method according to claim 12, wherein controlling the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction, includes:
by applying a voltage to a first electrode and a second electrode, controlling a refractive index of the first liquid crystal in one light-extraction sub-region to be different from a refractive index of the first light-extraction grating, thereby controlling the first light-extraction grating in the one light-extraction sub-region to project light rays of a certain color transmitted in the light guide plate by diffraction; for any two light-extraction sub-regions in the same light-extraction region, controlling the first light-extraction gratings in the two light-extraction sub-regions to project light rays of different colors transmitted in the light guide plate by diffraction. 14. The driving method according to claim 13, wherein the backlight sources include a red light source, a green light source and a blue light source; each light-extraction region includes a red-light-extraction sub-region, a green-light-extraction sub-region and a blue-light-extraction sub-region; each pixel region includes a red sub-pixel region, a green sub-pixel region and a blue sub-pixel region;
a duration for displaying one frame picture includes a red-image display period, a green-image display period and a blue-image display period; the driving method specifically includes: during the red-image display period in the duration for displaying one frame picture, controlling the red light source to emit light rays, controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region to be different from a refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the green-light-extraction sub-region and the blue-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the red-light-extraction sub-region to project red light rays transmitted in the light guide plate by diffraction; meanwhile, controlling the second liquid crystal in the red sub-pixel region to deflect, thereby achieving corresponding grayscale display; during the green-image display period in the duration for displaying one frame picture, controlling the green light source to emit light rays, controlling a refractive index of the first liquid crystal in the green-light-extraction sub-region to be different from the refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region and the blue-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the green-light-extraction sub-region to project green light rays transmitted in the light guide plate by diffraction; during the blue-image display period in the duration for displaying one frame picture, controlling the blue light source to emit light rays, controlling a refractive index of the first liquid crystal in the blue-light-extraction sub-region to be different from the refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region and the green-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the blue-light-extraction sub-region to project blue light rays transmitted in the light guide plate by diffraction. | The present disclosure provides a collimation backlight source, a display device and a driving method thereof. The collimation backlight source includes a light guide plate, a plurality of light sources of different colors, and a light-extraction grating assembly in each light-extraction region on the surface of the light guide plate.1. A collimation backlight source comprising:
a light guide plate with a surface and a lateral side adjacent to the surface; a plurality of light sources of different colors at the lateral side; a light-extraction grating assembly in each of a plurality of light-extraction regions on the surface of the light guide plate. 2. The collimation backlight source according to claim 1, wherein each light-extraction region includes a plurality of spaced light-extraction sub-regions;
the light-extraction grating assembly includes a first light-extraction grating set in each light-extraction sub-region; the collimation backlight source further includes a first buffer layer covering the first light-extraction grating set; a refractive index of the first buffer layer is less than a refractive index of the light guide plate; the first light-extraction grating set in each light-extraction sub-region includes: a first electrode and a second electrode on the light guide plate; wherein the first electrodes of adjacent two light-extraction sub-regions are insulated from each other; a first light-extraction grating on the first electrode or the second electrode; wherein the first light-extraction grating is between the first electrode and the second electrode, and the first light-extraction grating is a step grating; first liquid crystal filled between the first electrode and the second electrode; when the refractive index of the first light-extraction grating is the same as the refractive index of the first liquid crystal, the first light-extraction grating is in a direct light transmission state; for one light-extraction sub-region, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, for any two light-extraction sub-regions in the same light-extraction region, the first light-extraction gratings in the two light-extraction sub-regions project light rays of different colors transmitted in the light guide plate by diffraction. 3. The collimation backlight source according to claim 2, wherein for each light-extraction region, periods of the first light-extraction gratings in all the light-extraction sub-regions are different;
for each light-extraction sub-region, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating directly projects the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction. 4. The collimation backlight source according to claim 2, wherein for each light-extraction region, periods of the first light-extraction gratings in all the light-extraction sub-regions are the same;
for one of the light-extraction sub-regions, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating directly projects the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction; for other ones of the light-extraction sub-regions, when the refractive index of the first light-extraction grating is different from the refractive index of the first liquid crystal, the first light-extraction grating projects the light rays of other color transmitted in the light guide plate at a diffraction angle greater than 0° by diffraction. 5. The collimation backlight source according to claim 4, wherein the light-extraction grating assembly further includes a second light-extraction grating set in each light-extraction region; the second light-extraction grating set is on the first buffer layer and is at a light-emitting side of the first light-extraction grating set;
the second light-extraction grating set in each light-extraction region includes a plurality of second light-extraction gratings; periods of the second light-extraction gratings are different; the second light-extraction gratings are in other ones of the light-extraction sub-regions in a one-to-one manner; the light rays projected at a diffraction angle greater than 0° by the first light-extraction grating in corresponding light-extraction sub-region, are further diffracted by the second light-extraction grating by diffraction and are projected at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface; the second light-extraction grating is a step grating. 6. The collimation backlight source according to claim 1, wherein the light-extraction grating assembly includes a third light-extraction grating in each light-extraction region; periods of the third light-extraction gratings in all the light-extraction regions are the same;
the collimation backlight source further includes a second buffer layer covering the third light-extraction grating; a refractive index of the second buffer layer is less than a refractive index of the light guide plate; for each light-extraction region, the third light-extraction grating directly projects by diffraction, the light rays of a certain color transmitted in the light guide plate at a diffraction angle of 0° to a corresponding irradiation area of the light receiving surface by diffraction, and projects the light rays of other color transmitted in the light guide plate at a diffraction angle greater than 0°; the light-extraction grating assembly further includes a plurality of fourth light-extraction gratings in each light-extraction region; the fourth light-extraction gratings are on the second buffer layer and at a light-emitting side of the third light-extraction grating; periods of the fourth light-extraction gratings in each light-extraction region are different; the third light-extraction grating is a step grating, and the fourth light-extraction grating is a step grating; the fourth light-extraction gratings in each light-extraction region sequentially diffract by diffraction, the light rays of other colors projected at a diffraction angle greater than 0° by the third light-extraction grating, and project the light rays of other colors onto preset irradiation areas. 7. The collimation backlight source according to claim 2, wherein the first light-extraction grating is composed of a plurality of light-transmission stripes arranged at equal intervals, and space between two adjacent light-transmission stripes is transparent. 8. The collimation backlight source according to claim 2, wherein in the first light-extraction grating set in each light-extraction sub-region, the first light-extraction grating is in the first liquid crystal. 9. The collimation backlight source according to claim 1, wherein the light-extraction grating assembly in each light-extraction region is on a light emitting surface of the light guide plate. 10. A display device comprising: a display panel and a backlight source;
wherein the display panel includes a plurality of pixel regions; the display panel includes a cell defined by an array substrate and a color filter substrate, and second liquid crystal filled between the array substrate and the color filter substrate; each pixel region of the color filter substrate includes a light-shielding pattern and a light transmission region around the light-shielding pattern; where the backlight source adopts the collimation backlight source according to claim 1; light-extraction regions of the backlight source are corresponding to positions of the pixel regions in a one-to-one manner; the display device further includes: a controller configured to control the light sources of different colors in the backlight source to emit light rays, and control the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction; when the second liquid crystal corresponding to one light-extraction region is not deflected, control the light-extraction grating assembly in the one light-extraction region to project the light rays to a region where the light-shielding pattern of the corresponding pixel region on the color film substrate is located; when the second liquid crystal corresponding to one light-extraction region is deflected, the light rays projected by the light-extraction grating assembly in the one light-extraction region, are adjusted by the second liquid crystal and projected onto the light-transmission region of the corresponding pixel region on the color filter substrate, and then are emitted to a display side. 11. The display device according to claim 10, wherein the light-extraction region includes a plurality of spaced light-extraction sub-regions; the pixel region includes a plurality of sub-pixel regions;
the light-extraction grating assembly includes a first light-extraction grating set in each light-extraction sub-region; the controller is configured to, by applying a voltage to a first electrode and a second electrode, control a refractive index of the first liquid crystal in one light-extraction sub-region to be different from a refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the one light-extraction sub-region to project light rays of a certain color transmitted in the light guide plate by diffraction; for any two light-extraction sub-regions in the same light-extraction region, control the first light-extraction gratings in the two light-extraction sub-regions to project light rays of different colors transmitted in the light guide plate by diffraction. 12. A driving method of the display device according to claim 10, comprising:
controlling the light sources of different colors in the backlight source to sequentially emit light rays, and controlling the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction; when the second liquid crystal corresponding to one light-extraction region is not deflected, controlling the light-extraction grating assembly in the one light-extraction region to project the light rays to a region where the light-shielding pattern of the corresponding pixel region on the color film substrate is located; when the second liquid crystal corresponding to one light-extraction region is deflected, adjusting by the second liquid crystal, the light rays projected by the light-extraction grating assembly in the one light-extraction region, and projecting the adjusted light rays onto the light-transmission region of the corresponding pixel region on the color filter substrate for emitting adjusted light rays to a display side. 13. The driving method according to claim 12, wherein controlling the light-extraction grating assembly in each light-extraction region to project light rays of all colors transmitted in the light guide plate by diffraction, includes:
by applying a voltage to a first electrode and a second electrode, controlling a refractive index of the first liquid crystal in one light-extraction sub-region to be different from a refractive index of the first light-extraction grating, thereby controlling the first light-extraction grating in the one light-extraction sub-region to project light rays of a certain color transmitted in the light guide plate by diffraction; for any two light-extraction sub-regions in the same light-extraction region, controlling the first light-extraction gratings in the two light-extraction sub-regions to project light rays of different colors transmitted in the light guide plate by diffraction. 14. The driving method according to claim 13, wherein the backlight sources include a red light source, a green light source and a blue light source; each light-extraction region includes a red-light-extraction sub-region, a green-light-extraction sub-region and a blue-light-extraction sub-region; each pixel region includes a red sub-pixel region, a green sub-pixel region and a blue sub-pixel region;
a duration for displaying one frame picture includes a red-image display period, a green-image display period and a blue-image display period; the driving method specifically includes: during the red-image display period in the duration for displaying one frame picture, controlling the red light source to emit light rays, controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region to be different from a refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the green-light-extraction sub-region and the blue-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the red-light-extraction sub-region to project red light rays transmitted in the light guide plate by diffraction; meanwhile, controlling the second liquid crystal in the red sub-pixel region to deflect, thereby achieving corresponding grayscale display; during the green-image display period in the duration for displaying one frame picture, controlling the green light source to emit light rays, controlling a refractive index of the first liquid crystal in the green-light-extraction sub-region to be different from the refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region and the blue-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the green-light-extraction sub-region to project green light rays transmitted in the light guide plate by diffraction; during the blue-image display period in the duration for displaying one frame picture, controlling the blue light source to emit light rays, controlling a refractive index of the first liquid crystal in the blue-light-extraction sub-region to be different from the refractive index of light-transmission stripes of the first light-extraction grating while controlling a refractive index of the first liquid crystal in the red-light-extraction sub-region and the green-light-extraction sub-region to be the same as the refractive index of light-transmission stripes of the first light-extraction grating, thereby controlling the first light-extraction grating in the blue-light-extraction sub-region to project blue light rays transmitted in the light guide plate by diffraction. | 3,600 |
345,424 | 16,643,338 | 3,679 | Disclosed is an electronic device. The electronic device comprises: a display and a processor, wherein, when at least one condition among the time required to treat an object and an object treatment completion time is input, the processor identifies a plurality of object treatment courses that comply with the condition, identifies the order of priority of the plurality of object treatment courses according to predetermined criteria, and controls the display to provide a list listing information about the plurality of object treatment courses on the basis of the identified order of priority, wherein the object treatment is a process in which an object is cleaned or dried by means of at least one among a cleaning operation and a drying operation. | 1. An electronic device comprising:
a display; and a processor configured to identify a plurality of object treating courses meeting an input condition when at least one of a condition for an object treatment required time or a condition for an object treatment completion time is input, identify priorities of the plurality of object treating courses according to a predetermined criterion, and control the display to provide a list in which information on the plurality of object treating courses is listed on the basis of the identified priorities, wherein object treatment is a process of washing or drying an object by at least one of a washing operation or a drying operation. 2. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by removing at least some object treating courses from the list on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of a kind of object, a color of the object, or a soil of the object. 3. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by reordering an order of the plurality of object treating courses on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of a kind of object, a color of the object, or a soil of the object. 4. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by removing at least some object treating courses from the list or reordering an order of the plurality of object treating courses on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of information related to consumed energy or information related to a damage degree of the object. 5. The electronic device as claimed in claim 1, wherein the processor is configured to identify the priorities of the plurality of object treating courses on the basis of object treatment required times of each of the plurality of object treating courses. 6. The electronic device as claimed in claim 1, wherein the processor is configured to provide an animation image representing an object treatment status on the basis of information on the object treatment status when an object treating course is chosen on the list and object treatment according to the chosen object treating course is started. 7. The electronic device as claimed in claim 6, wherein the processor is configured to provide the animation image that includes a progress bar guiding a remaining object treatment required time on the basis of an object treatment required time of the object treating course and an object treating progress time at a current point in time and color information. 8. The electronic device as claimed in claim 1, wherein the processor is configured to provide a summed time of the washing operation and the drying operation according to each object course on the display when the plurality of object treating courses meeting the condition are identified. 9. The electronic device as claimed in claim 1, wherein the processor is configured to identify object treating courses regarding the drying operation on the basis of a chosen object treating course when one of the plurality of object treating courses regarding the washing operation is chosen, and provide a list in which information on the identified object treating courses regarding the drying operation is listed, on the display. 10. The electronic device as claimed in claim 1, wherein the processor is configured to provide a user interface (UI) including items representing kinds of different objects, and provide a guide for adding a kind of object on the basis of a kind of specific object when an item representing the kind of specific object is chosen on the UI. 11. The electronic device as claimed in claim 1, wherein the electronic device is implemented by a user terminal device communicating with at least one of a washing machine or a drying machine performing the object treatment. 12. A method for controlling an electronic device, comprising:
identifying a plurality of object treating courses meeting an input condition when at least one of a condition for an object treatment required time or a condition for an object treatment completion time is input; identifying priorities of the plurality of object treating courses according to a predetermined criterion; and providing a list in which information on the plurality of object treating courses is listed on the basis of the identified priorities, wherein object treatment is a process of washing or drying the object by at least one of a washing operation or a drying operation. 13. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of a kind of object, a color of the object, or a soil of the object; and updating the list by removing at least some object treating courses from the list on the basis of the additional condition. 14. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of a kind of object, a color of the object, or a soil of the object; and updating the list by reordering an order of the plurality of object treating courses on the basis of the additional condition. 15. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of information related to consumed energy or information related to a damage degree of the object; and updating the list by removing at least some object treating courses from the list or reordering an order of the plurality of object treating courses on the basis of the additional condition. | Disclosed is an electronic device. The electronic device comprises: a display and a processor, wherein, when at least one condition among the time required to treat an object and an object treatment completion time is input, the processor identifies a plurality of object treatment courses that comply with the condition, identifies the order of priority of the plurality of object treatment courses according to predetermined criteria, and controls the display to provide a list listing information about the plurality of object treatment courses on the basis of the identified order of priority, wherein the object treatment is a process in which an object is cleaned or dried by means of at least one among a cleaning operation and a drying operation.1. An electronic device comprising:
a display; and a processor configured to identify a plurality of object treating courses meeting an input condition when at least one of a condition for an object treatment required time or a condition for an object treatment completion time is input, identify priorities of the plurality of object treating courses according to a predetermined criterion, and control the display to provide a list in which information on the plurality of object treating courses is listed on the basis of the identified priorities, wherein object treatment is a process of washing or drying an object by at least one of a washing operation or a drying operation. 2. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by removing at least some object treating courses from the list on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of a kind of object, a color of the object, or a soil of the object. 3. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by reordering an order of the plurality of object treating courses on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of a kind of object, a color of the object, or a soil of the object. 4. The electronic device as claimed in claim 1, wherein the processor is configured to update the list by removing at least some object treating courses from the list or reordering an order of the plurality of object treating courses on the basis of an additional condition when the additional condition is input, the additional condition being an additional condition for at least one of information related to consumed energy or information related to a damage degree of the object. 5. The electronic device as claimed in claim 1, wherein the processor is configured to identify the priorities of the plurality of object treating courses on the basis of object treatment required times of each of the plurality of object treating courses. 6. The electronic device as claimed in claim 1, wherein the processor is configured to provide an animation image representing an object treatment status on the basis of information on the object treatment status when an object treating course is chosen on the list and object treatment according to the chosen object treating course is started. 7. The electronic device as claimed in claim 6, wherein the processor is configured to provide the animation image that includes a progress bar guiding a remaining object treatment required time on the basis of an object treatment required time of the object treating course and an object treating progress time at a current point in time and color information. 8. The electronic device as claimed in claim 1, wherein the processor is configured to provide a summed time of the washing operation and the drying operation according to each object course on the display when the plurality of object treating courses meeting the condition are identified. 9. The electronic device as claimed in claim 1, wherein the processor is configured to identify object treating courses regarding the drying operation on the basis of a chosen object treating course when one of the plurality of object treating courses regarding the washing operation is chosen, and provide a list in which information on the identified object treating courses regarding the drying operation is listed, on the display. 10. The electronic device as claimed in claim 1, wherein the processor is configured to provide a user interface (UI) including items representing kinds of different objects, and provide a guide for adding a kind of object on the basis of a kind of specific object when an item representing the kind of specific object is chosen on the UI. 11. The electronic device as claimed in claim 1, wherein the electronic device is implemented by a user terminal device communicating with at least one of a washing machine or a drying machine performing the object treatment. 12. A method for controlling an electronic device, comprising:
identifying a plurality of object treating courses meeting an input condition when at least one of a condition for an object treatment required time or a condition for an object treatment completion time is input; identifying priorities of the plurality of object treating courses according to a predetermined criterion; and providing a list in which information on the plurality of object treating courses is listed on the basis of the identified priorities, wherein object treatment is a process of washing or drying the object by at least one of a washing operation or a drying operation. 13. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of a kind of object, a color of the object, or a soil of the object; and updating the list by removing at least some object treating courses from the list on the basis of the additional condition. 14. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of a kind of object, a color of the object, or a soil of the object; and updating the list by reordering an order of the plurality of object treating courses on the basis of the additional condition. 15. The method as claimed in claim 12, further comprising:
receiving an input of an additional condition for at least one of information related to consumed energy or information related to a damage degree of the object; and updating the list by removing at least some object treating courses from the list or reordering an order of the plurality of object treating courses on the basis of the additional condition. | 3,600 |
345,425 | 16,643,333 | 3,679 | The present invention provides 1-(N,N-disubstituted carbamoyl) 4-(substituted sulfonyl)triazolin-5-one derivatives represented general formula 1, and 4-(N,N-disubstituted carbamoyl) 1-(substituted sulfonyl)triazolin-5-one derivatives represented by general formula (11), which show excellent herbicidal activity, and herbicides characterized by containing the derivatives as an active ingredient. In general formula (1), R1-R4 represent predetermined substituents. In general formula (11), R11-R14 represent predetermined substituents. | 1. A 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative represented by formula (1): 2. The 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1, wherein in formula (1),
R1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a C1-C6 alkylamino group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, a tetrahydropyranyl group, a tetrahydrofuryl group, a tetrahydropyranylmethyl group, or a tetrahydrofurfuryl group; R2 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, or a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; R3 represents a C1-C6 alkyl group, a C3-C6 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, a thiazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or a pyrazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R2 and R3 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R4 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group. 3. The 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1, wherein in formula (1),
R1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group), a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, a tetrahydropyranyl group, or a tetrahydrofuryl group; R2 represents a C1-C6 alkyl group; R3 represents a C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; and R4 represents a hydrogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group. 4. A 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative represented by formula (11): 5. The 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4, wherein in formula (11),
R11 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a C1-C6 alkylamino group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring), a tetrahydropyranyl group, a tetrahydrofuryl group, a tetrahydropyranylmethyl group, or a tetrahydrofurfuryl group; R12 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, or a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; R3 represents a C1-C6 alkyl group, a C3-C6 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, a thiazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or a pyrazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R12 and R13 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R14 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group. 6. The 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4, wherein in formula (11),
R11 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, or a tetrahydropyranyl group; R12 represents a C1-C6 alkyl group or a C1-C6 haloalkyl group; R13 represents a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R12 and R13 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R14 represents a hydrogen atom or a C1-C6 alkyl group. 7. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1. 8. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4. 9. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 2. 10. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 3. 11. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 5. 12. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 6. | The present invention provides 1-(N,N-disubstituted carbamoyl) 4-(substituted sulfonyl)triazolin-5-one derivatives represented general formula 1, and 4-(N,N-disubstituted carbamoyl) 1-(substituted sulfonyl)triazolin-5-one derivatives represented by general formula (11), which show excellent herbicidal activity, and herbicides characterized by containing the derivatives as an active ingredient. In general formula (1), R1-R4 represent predetermined substituents. In general formula (11), R11-R14 represent predetermined substituents.1. A 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative represented by formula (1): 2. The 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1, wherein in formula (1),
R1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a C1-C6 alkylamino group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, a tetrahydropyranyl group, a tetrahydrofuryl group, a tetrahydropyranylmethyl group, or a tetrahydrofurfuryl group; R2 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, or a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; R3 represents a C1-C6 alkyl group, a C3-C6 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, a thiazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or a pyrazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R2 and R3 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R4 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group. 3. The 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1, wherein in formula (1),
R1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group), a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, a tetrahydropyranyl group, or a tetrahydrofuryl group; R2 represents a C1-C6 alkyl group; R3 represents a C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; and R4 represents a hydrogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group. 4. A 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative represented by formula (11): 5. The 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4, wherein in formula (11),
R11 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a C1-C6 alkylamino group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring), a tetrahydropyranyl group, a tetrahydrofuryl group, a tetrahydropyranylmethyl group, or a tetrahydrofurfuryl group; R12 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a C1-C6 alkoxy C1-C6 alkyl group, a C1-C6 haloalkoxy C1-C6 alkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, or a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group; R3 represents a C1-C6 alkyl group, a C3-C6 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, a thiazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or a pyrazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R12 and R13 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R14 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group. 6. The 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4, wherein in formula (11),
R11 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C6 cycloalkyl C1-C6 alkyl group, a phenyl group, or a C7-C11 aralkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a thiophene ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a di C1-C6 alkylamino group in which alkyl groups may be the same or different and the alkyl groups may also combine with each other via an alkylene group to form a 3-membered ring, a 4-membered ring, a 5-membered ring and a 6-membered ring, or a tetrahydropyranyl group; R12 represents a C1-C6 alkyl group or a C1-C6 haloalkyl group; R13 represents a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a phenyl group which may be monosubstituted or polysubstituted by a halogen atom, cyano, nitro, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylthio group, or a C1-C6 haloalkylthio group, a C7-C11 aralkyl group which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group, a pyridine ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, or an isoxazole ring which may be monosubstituted or polysubstituted by a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, or a C1-C6 alkoxy group, and when R12 and R13 are C1-C6 alkyl groups, these may also combine with each other to form a 3-membered ring, a 4-membered ring, a 5-membered ring, and a 6-membered ring with an alkylene group having from 2 to 5 carbon atoms as ring members; and R14 represents a hydrogen atom or a C1-C6 alkyl group. 7. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 1. 8. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 4. 9. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 2. 10. A herbicide comprising as an active ingredient the 1-(N,N-disubstituted carbamoyl)4-(substituted sulfonyl)triazolin-5-one derivative according to claim 3. 11. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 5. 12. A herbicide comprising as an active ingredient the 4-(N,N-disubstituted carbamoyl)1-(substituted sulfonyl)triazolin-5-one derivative according to claim 6. | 3,600 |
345,426 | 16,643,359 | 3,679 | The present invention relates to novel (per)fluoropolyether (PFPE) polymers, to a process for their manufacture and to their use as additives in coating compositions. | 1. A (per)fluoropolyether polymer (P) comprising at least one (per)fluoropolyoxyalkylene chain (Rpf) having two chain ends, wherein at least one of said chain ends bears at least one group of formula -B-(E)t, wherein:
t is an integer equal to or higher than 2; B is a group complying with the following formula (B-I): 2. The polymer (P) according to claim 1, wherein said chain (Rpf) is a chain of formula
—(CFX)z1O(Rf)(CFX′)z2-D—O— 3. The polymer (P) according to claim 1, wherein said moiety (RU) is selected from the group consisting of:
—O—C(═O)—CRH═CH2 (RU-I)
—O—C(═O)—NH—CO—CRH═CH2 (RU-II) 4. The polymer (P) according to claim 1, wherein said group (B) complies with one of the following formulae (B-I-i) to (B-I-v): 5. The polymer (P) according to claim 1, wherein said polymer (P) complies with the following formula (P-I):
T-(Rpf)-B-[(E-I)]t (P-I) 6. A process for the synthesis of polymer (P) as defined in claim 1, said process comprising:
(I) contacting at least one polyisocyanate compound (NCO) with at least one compound (U) of formula
H—[OCH(CH3)CH2]z—RU (U)
wherein RU is an unsaturated moiety and z is an integer from 1 to 15, wherein the ratio between the equivalents of said compound (NCO) and of said compound (U) is higher than 1; (II) contacting the compound obtained in step (I) with at least one polymer (PFPE-OH), wherein polymer (PFPE-OH) is at least one (per)fluoropolyether polymer comprising a (per)fluoropolyoxyalkylene chain having two chain ends, wherein at least one of said chain ends comprises a hydroxy group, thus obtaining said polymer (P). 7. The process according to claim 6, wherein said compound (NCO) is obtained from the reaction of at least three molecules of the same diisocyanate compound, which react together to form a linear or cyclic molecule comprising at least three isocyanate groups. 8. The process according to claim 7, wherein said compound (NCO) comprises at least four isocyanate groups. 9. The process according to claim 6, wherein said compound (NCO) comprises three isocyanate groups and is represented by at least one of the following formulae (I) to (IV): 10. The process according to claim 6, wherein the equivalent ratio between said compound (NCO) and said compound (U) is from 1.1 to 2. 11. The process according to claim 6, wherein said step (II) is performed in the presence of a fluorinated solvent. 12. A composition (C) comprising at least one polymer (P) as defined in claim 1 and at least one solvent selected from: ketones; esters; organic solvents containing in the molecule an ester-ether group; and mixtures thereof. 13. The composition (C) according to claim 12, said composition (C) further comprising at least one UV-curable component, such that the amount of said polymer (P) in said composition (C) is from 0.01 to 8 wt. %, based on the total weight of said composition (C). 14. A method for providing a transparent coating onto at least one surface of a plastic substrate, said method comprising:
contacting at least one surface of at least one plastic substrate with polymer (P) as defined in claim 1; and curing said polymer (P) onto said at least one surface. 15. The method according to claim 14, wherein the plastic substrate is selected from the group consisting of: polyethylene terephthalate (PET), polycarbonate (PC), polyvinyl chloride (PVC), thermoplastic olefin (TPO), thermoplastic polyurethane (TPU), polypropylene (PP), acrylonitrile butadiene styrene (ABS) and polyamides (PA). 16. The polymer (P) according to claim 1, wherein:
t is an integer from 2 to 3; n is an integer from 1 to 2. 17. The polymer (P) according to claim 2, wherein z1 and z2, equal or different from each other, are from 1 to 3. 18. The polymer (P) according to claim 3, wherein RH is H or a linear or branched C1-C3 alkyl group. 19. The process according to claim 7, wherein said diisocyanate compound is selected from the group consisting of: hexamethylene diisocyanate; isophorone diisocyanate; xylylene diisocyanate; hydrogenated xylylene diisocyanate; isomers of methylene-bis(cyclohexyl isocyanate) and mixtures thereof; isomers of toluene diisocyanate and mixtures thereof; isomers of methylene diphenyl diisocyanate and mixtures thereof; toluidine diisocyanate; and naphthalene diisocyanate. 20. The process according to claim 10, wherein the equivalent ratio between said compound (NCO) and said compound (U) is from 1.2 to 1.8. | The present invention relates to novel (per)fluoropolyether (PFPE) polymers, to a process for their manufacture and to their use as additives in coating compositions.1. A (per)fluoropolyether polymer (P) comprising at least one (per)fluoropolyoxyalkylene chain (Rpf) having two chain ends, wherein at least one of said chain ends bears at least one group of formula -B-(E)t, wherein:
t is an integer equal to or higher than 2; B is a group complying with the following formula (B-I): 2. The polymer (P) according to claim 1, wherein said chain (Rpf) is a chain of formula
—(CFX)z1O(Rf)(CFX′)z2-D—O— 3. The polymer (P) according to claim 1, wherein said moiety (RU) is selected from the group consisting of:
—O—C(═O)—CRH═CH2 (RU-I)
—O—C(═O)—NH—CO—CRH═CH2 (RU-II) 4. The polymer (P) according to claim 1, wherein said group (B) complies with one of the following formulae (B-I-i) to (B-I-v): 5. The polymer (P) according to claim 1, wherein said polymer (P) complies with the following formula (P-I):
T-(Rpf)-B-[(E-I)]t (P-I) 6. A process for the synthesis of polymer (P) as defined in claim 1, said process comprising:
(I) contacting at least one polyisocyanate compound (NCO) with at least one compound (U) of formula
H—[OCH(CH3)CH2]z—RU (U)
wherein RU is an unsaturated moiety and z is an integer from 1 to 15, wherein the ratio between the equivalents of said compound (NCO) and of said compound (U) is higher than 1; (II) contacting the compound obtained in step (I) with at least one polymer (PFPE-OH), wherein polymer (PFPE-OH) is at least one (per)fluoropolyether polymer comprising a (per)fluoropolyoxyalkylene chain having two chain ends, wherein at least one of said chain ends comprises a hydroxy group, thus obtaining said polymer (P). 7. The process according to claim 6, wherein said compound (NCO) is obtained from the reaction of at least three molecules of the same diisocyanate compound, which react together to form a linear or cyclic molecule comprising at least three isocyanate groups. 8. The process according to claim 7, wherein said compound (NCO) comprises at least four isocyanate groups. 9. The process according to claim 6, wherein said compound (NCO) comprises three isocyanate groups and is represented by at least one of the following formulae (I) to (IV): 10. The process according to claim 6, wherein the equivalent ratio between said compound (NCO) and said compound (U) is from 1.1 to 2. 11. The process according to claim 6, wherein said step (II) is performed in the presence of a fluorinated solvent. 12. A composition (C) comprising at least one polymer (P) as defined in claim 1 and at least one solvent selected from: ketones; esters; organic solvents containing in the molecule an ester-ether group; and mixtures thereof. 13. The composition (C) according to claim 12, said composition (C) further comprising at least one UV-curable component, such that the amount of said polymer (P) in said composition (C) is from 0.01 to 8 wt. %, based on the total weight of said composition (C). 14. A method for providing a transparent coating onto at least one surface of a plastic substrate, said method comprising:
contacting at least one surface of at least one plastic substrate with polymer (P) as defined in claim 1; and curing said polymer (P) onto said at least one surface. 15. The method according to claim 14, wherein the plastic substrate is selected from the group consisting of: polyethylene terephthalate (PET), polycarbonate (PC), polyvinyl chloride (PVC), thermoplastic olefin (TPO), thermoplastic polyurethane (TPU), polypropylene (PP), acrylonitrile butadiene styrene (ABS) and polyamides (PA). 16. The polymer (P) according to claim 1, wherein:
t is an integer from 2 to 3; n is an integer from 1 to 2. 17. The polymer (P) according to claim 2, wherein z1 and z2, equal or different from each other, are from 1 to 3. 18. The polymer (P) according to claim 3, wherein RH is H or a linear or branched C1-C3 alkyl group. 19. The process according to claim 7, wherein said diisocyanate compound is selected from the group consisting of: hexamethylene diisocyanate; isophorone diisocyanate; xylylene diisocyanate; hydrogenated xylylene diisocyanate; isomers of methylene-bis(cyclohexyl isocyanate) and mixtures thereof; isomers of toluene diisocyanate and mixtures thereof; isomers of methylene diphenyl diisocyanate and mixtures thereof; toluidine diisocyanate; and naphthalene diisocyanate. 20. The process according to claim 10, wherein the equivalent ratio between said compound (NCO) and said compound (U) is from 1.2 to 1.8. | 3,600 |
345,427 | 16,643,354 | 3,679 | The present disclosure provides a light-emitting device, a pixel unit, a method for manufacturing the pixel unit, and a display device. The light-emitting device comprises a first electrode, an organic light-emitting layer and a second electrode which are sequentially disposed on a substrate; the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer which are sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode, so that a cavity is formed between the second electrode and the reflecting layer. | 1. A light-emitting device, comprising a first electrode, an organic light-emitting layer, and a second electrode sequentially disposed on a substrate, wherein,
the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode, such that a cavity is formed between the second electrode and the reflecting layer. 2. The light-emitting device according to claim 1, wherein the insulating layer is provided with a via hole therein, the via hole is filled with a conductive material to form a connecting pillar, and the reflecting layer and the contact layer are electrically coupled to each other through the connecting pillar. 3. The light-emitting device according to claim 2, wherein the organic light-emitting layer comprises at least one hole layer of a hole injection layer and a hole transport layer, at least one electron layer of an electron injection layer and an electron transport layer, and at least one of a red light-emitting body layer, a green light-emitting body layer and a blue light-emitting body layer disposed between the at least one hole layer and the at least one electron layer. 4. The light-emitting device according to claim 3, wherein the first electrode is an anode, the second electrode is a cathode, and the organic light-emitting layer comprises a hole injection layer, a hole transport layer, a red light-emitting body layer, a green light-emitting body layer, an electron transport layer, a charge generation layer, a hole injection layer, a hole transport layer, a blue light-emitting body layer, an electron transport layer, and an electron injection layer sequentially disposed on the first electrode. 5. A pixel unit, comprising at least a first light-emitting device emitting light of a first color and a second light-emitting device emitting light of a second color, the first color being different from the second color, wherein,
the first light-emitting device and the second light-emitting device each comprise a first electrode, an organic light-emitting layer and a second electrode sequentially disposed on a substrate, wherein the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially arranged on the substrate; and the second electrode is a semi-transparent electrode; a first cavity is formed between the second electrode of the first light-emitting device and the reflecting layer of the first light-emitting device, and a second cavity is formed between the second electrode of the second light-emitting device and the reflecting layer of the second light-emitting device; and the first cavity of the first light-emitting device has a first cavity length corresponding to a wavelength of light of the first color, the second cavity of the second light-emitting device has a second cavity length corresponding to a wavelength of light of the second color, and the first cavity length is different from the second cavity length. 6. The pixel unit according to claim 5, further comprising a third light-emitting device emitting light of a third color different from both the first color and the second color, wherein
the third light-emitting device comprises a first electrode, an organic light-emitting layer and a second electrode sequentially disposed on a substrate, the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode; a third cavity is formed between the second electrode of the third light-emitting device and the reflecting layer of the third light-emitting device, and the third cavity of the third light-emitting device has a third cavity length corresponding to a wavelength of light of the third color, and the third cavity length is different from at least one of the first cavity length and the second cavity length. 7. The pixel unit according to claim 6, wherein a via hole is formed in the insulating layer of each of the first to third light-emitting devices, wherein the via hole is filled with a conductive material to form a connecting pillar, and the reflecting layer of the light-emitting device and the contact layer of the light-emitting device are electrically coupled to each other through the connecting pillar. 8. The pixel unit according to claim 7, wherein the first to third light-emitting devices have the reflecting layers of a same thickness, have the contact layers of a same thickness, and have the insulating layers of thicknesses corresponding to the wavelength of respective emitted light. 9. The pixel unit according to claim 8, wherein every two adjacent light-emitting devices emitting light of different colors are provided with a gap region therebetween, the insulating layers of the two adjacent light-emitting devices extended to the gap region and connected at the gap region to form a step structure; a support film is provided in the thicker insulating layer of the two insulating layers at the gap region, and the support film has a density greater than that of the other region of the insulating layer. 10. The pixel unit according to claim 9, wherein the light-emitting devices emitting light of different colors have the same organic light-emitting layer and/or the same first electrode. 11. The pixel unit according to claim 10, wherein the organic light-emitting layer comprises at least one hole layer of a hole injection layer and a hole transport layer, at least one electron layer of an electron injection layer and an electron transport layer, and at least one of a red light-emitting body layer, a green light-emitting body layer, and a blue light-emitting body layer disposed between the at least one hole layer and the at least one electron layer. 12. The pixel unit according to claim 11, wherein the first electrode is an anode and the second electrode is a cathode, and the organic light-emitting layer comprises a hole injection layer, a hole transport layer, a red light-emitting body layer, a green light-emitting body layer, an electron transport layer, a charge generation layer, a hole injection layer, a hole transport layer, a blue light-emitting body layer, an electron transport layer, and an electron injection layer sequentially disposed on the first electrode. 13. The pixel unit according to claim 12, further comprising a pixel define layer disposed on the step structure. 14. The pixel unit according to claim 13, wherein in each of the light-emitting devices, a color filter layer is further disposed on a side distal to the first electrode, the color filter layers disposed on the light-emitting devices emitting light of different colors are different in color, and the color filter layers enable the light-emitting devices to emit light of a single color, respectively. 15. The pixel unit according to claim 13, wherein the first light-emitting device, the second light-emitting device and the third light-emitting devices emit red, green and blue light, respectively, and the thicknesses of the insulating layers of the first light-emitting device, the second light-emitting device and the third light-emitting devices increase sequentially. 16. A method for manufacturing a pixel unit comprising at least a first light-emitting device emitting light of a first color and a second light-emitting device emitting light of a second color, the first color being different from the second color, the method comprising:
forming a first reflecting layer of the first light-emitting device and a second reflecting layer of the second light-emitting device on a substrate; forming a transparent first insulating layer of the first light-emitting device and a transparent second insulating layer of the second light-emitting device on the first reflecting layer and the second reflecting layer, respectively; forming a transparent first contact layer of the first light-emitting device and a transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer, respectively; forming a first organic light-emitting layer of the first light-emitting device and a second organic light-emitting layer of the second light-emitting device on the first contact layer and the second contact layer, respectively; and forming a second electrode of the first light-emitting device and a second electrode of the second light-emitting device on the first organic light-emitting layer and the second organic light-emitting layer, respectively, such that the first cavity is formed between the second electrode and the first reflecting layer of the first light-emitting device, the second cavity is formed between the second electrode and the second reflecting layer of the second light-emitting device, and a first cavity length of the first cavity corresponding to a wavelength of light of the first color is different from a second cavity length of the second cavity corresponding to a wavelength of light of the second color. 17. The method according to claim 16, wherein,
forming the first reflecting layer of the first light-emitting device and the second reflecting layer of the second light-emitting device on the substrate by a single patterning process, such that the first reflecting layer and the second reflecting layer are spaced apart from each other to form a gap region between the first light-emitting device and the second light-emitting device; forming the transparent first contact layer of the first light-emitting device and the transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer respectively by a single patterning process, such that the first contact layer and the second contact layer are spaced apart each other and disposed on the first reflecting layer and the second reflecting layer respectively; forming the first organic light-emitting layer of the first light-emitting device and the second organic light-emitting layer of the second light-emitting device on the first contact layer and the second contact layer respectively by a single patterning process; and forming the second electrode of the first light-emitting device and the second electrode of the second light-emitting device on the first organic light-emitting layer and the second organic light-emitting layer respectively by a single patterning process. 18. The method according to claim 17, wherein the forming the transparent first insulating layer of the first light-emitting device and the transparent second insulating layer of the second light-emitting device on the first reflecting layer and the second reflecting layer respectively comprises:
forming a first insulating film on the first reflecting layer, the second reflecting layer and the gap region such that the first insulating film is provided with a groove at the gap region; forming a support film in the groove by a plasma enhanced chemical vapor deposition process; and forming a second insulating film on the first insulating film of the second light-emitting device and the support film by a patterning process, wherein an orthogonal projection of the second insulating film on the substrate does not overlap an orthogonal projection of the first reflecting layer on the substrate. 19. The method according to claim 18, further comprising:
forming a first via hole in the first insulating film of the first light-emitting device and filling a conductive material in the first via hole to form a first connecting pillar; and forming a second via hole in the first insulating film and the second insulating film of the second light-emitting device and filling a conductive material in the second via hole to form a second connecting pillar. 20. The method according to claim 19, wherein the forming the transparent first contact layer of the first light-emitting device and the transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer respectively by a single patterning process, such that the first contact layer and the second contact layer are spaced apart each other and disposed on the first reflecting layer and the second reflecting layer respectively comprises:
coating a photoresist on a part of the first insulating layer at the gap region and a part of the second insulating layer at the gap region; forming a contact film layer on a residual part of the first insulating layer, a residual part of the second insulating layer and the photoresist; and forming a first contact layer and a second contact layer by removing the photoresist. 21-23. (canceled) | The present disclosure provides a light-emitting device, a pixel unit, a method for manufacturing the pixel unit, and a display device. The light-emitting device comprises a first electrode, an organic light-emitting layer and a second electrode which are sequentially disposed on a substrate; the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer which are sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode, so that a cavity is formed between the second electrode and the reflecting layer.1. A light-emitting device, comprising a first electrode, an organic light-emitting layer, and a second electrode sequentially disposed on a substrate, wherein,
the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode, such that a cavity is formed between the second electrode and the reflecting layer. 2. The light-emitting device according to claim 1, wherein the insulating layer is provided with a via hole therein, the via hole is filled with a conductive material to form a connecting pillar, and the reflecting layer and the contact layer are electrically coupled to each other through the connecting pillar. 3. The light-emitting device according to claim 2, wherein the organic light-emitting layer comprises at least one hole layer of a hole injection layer and a hole transport layer, at least one electron layer of an electron injection layer and an electron transport layer, and at least one of a red light-emitting body layer, a green light-emitting body layer and a blue light-emitting body layer disposed between the at least one hole layer and the at least one electron layer. 4. The light-emitting device according to claim 3, wherein the first electrode is an anode, the second electrode is a cathode, and the organic light-emitting layer comprises a hole injection layer, a hole transport layer, a red light-emitting body layer, a green light-emitting body layer, an electron transport layer, a charge generation layer, a hole injection layer, a hole transport layer, a blue light-emitting body layer, an electron transport layer, and an electron injection layer sequentially disposed on the first electrode. 5. A pixel unit, comprising at least a first light-emitting device emitting light of a first color and a second light-emitting device emitting light of a second color, the first color being different from the second color, wherein,
the first light-emitting device and the second light-emitting device each comprise a first electrode, an organic light-emitting layer and a second electrode sequentially disposed on a substrate, wherein the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially arranged on the substrate; and the second electrode is a semi-transparent electrode; a first cavity is formed between the second electrode of the first light-emitting device and the reflecting layer of the first light-emitting device, and a second cavity is formed between the second electrode of the second light-emitting device and the reflecting layer of the second light-emitting device; and the first cavity of the first light-emitting device has a first cavity length corresponding to a wavelength of light of the first color, the second cavity of the second light-emitting device has a second cavity length corresponding to a wavelength of light of the second color, and the first cavity length is different from the second cavity length. 6. The pixel unit according to claim 5, further comprising a third light-emitting device emitting light of a third color different from both the first color and the second color, wherein
the third light-emitting device comprises a first electrode, an organic light-emitting layer and a second electrode sequentially disposed on a substrate, the first electrode comprises a reflecting layer, a transparent insulating layer and a transparent contact layer sequentially disposed on the substrate; and the second electrode is a semi-transparent electrode; a third cavity is formed between the second electrode of the third light-emitting device and the reflecting layer of the third light-emitting device, and the third cavity of the third light-emitting device has a third cavity length corresponding to a wavelength of light of the third color, and the third cavity length is different from at least one of the first cavity length and the second cavity length. 7. The pixel unit according to claim 6, wherein a via hole is formed in the insulating layer of each of the first to third light-emitting devices, wherein the via hole is filled with a conductive material to form a connecting pillar, and the reflecting layer of the light-emitting device and the contact layer of the light-emitting device are electrically coupled to each other through the connecting pillar. 8. The pixel unit according to claim 7, wherein the first to third light-emitting devices have the reflecting layers of a same thickness, have the contact layers of a same thickness, and have the insulating layers of thicknesses corresponding to the wavelength of respective emitted light. 9. The pixel unit according to claim 8, wherein every two adjacent light-emitting devices emitting light of different colors are provided with a gap region therebetween, the insulating layers of the two adjacent light-emitting devices extended to the gap region and connected at the gap region to form a step structure; a support film is provided in the thicker insulating layer of the two insulating layers at the gap region, and the support film has a density greater than that of the other region of the insulating layer. 10. The pixel unit according to claim 9, wherein the light-emitting devices emitting light of different colors have the same organic light-emitting layer and/or the same first electrode. 11. The pixel unit according to claim 10, wherein the organic light-emitting layer comprises at least one hole layer of a hole injection layer and a hole transport layer, at least one electron layer of an electron injection layer and an electron transport layer, and at least one of a red light-emitting body layer, a green light-emitting body layer, and a blue light-emitting body layer disposed between the at least one hole layer and the at least one electron layer. 12. The pixel unit according to claim 11, wherein the first electrode is an anode and the second electrode is a cathode, and the organic light-emitting layer comprises a hole injection layer, a hole transport layer, a red light-emitting body layer, a green light-emitting body layer, an electron transport layer, a charge generation layer, a hole injection layer, a hole transport layer, a blue light-emitting body layer, an electron transport layer, and an electron injection layer sequentially disposed on the first electrode. 13. The pixel unit according to claim 12, further comprising a pixel define layer disposed on the step structure. 14. The pixel unit according to claim 13, wherein in each of the light-emitting devices, a color filter layer is further disposed on a side distal to the first electrode, the color filter layers disposed on the light-emitting devices emitting light of different colors are different in color, and the color filter layers enable the light-emitting devices to emit light of a single color, respectively. 15. The pixel unit according to claim 13, wherein the first light-emitting device, the second light-emitting device and the third light-emitting devices emit red, green and blue light, respectively, and the thicknesses of the insulating layers of the first light-emitting device, the second light-emitting device and the third light-emitting devices increase sequentially. 16. A method for manufacturing a pixel unit comprising at least a first light-emitting device emitting light of a first color and a second light-emitting device emitting light of a second color, the first color being different from the second color, the method comprising:
forming a first reflecting layer of the first light-emitting device and a second reflecting layer of the second light-emitting device on a substrate; forming a transparent first insulating layer of the first light-emitting device and a transparent second insulating layer of the second light-emitting device on the first reflecting layer and the second reflecting layer, respectively; forming a transparent first contact layer of the first light-emitting device and a transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer, respectively; forming a first organic light-emitting layer of the first light-emitting device and a second organic light-emitting layer of the second light-emitting device on the first contact layer and the second contact layer, respectively; and forming a second electrode of the first light-emitting device and a second electrode of the second light-emitting device on the first organic light-emitting layer and the second organic light-emitting layer, respectively, such that the first cavity is formed between the second electrode and the first reflecting layer of the first light-emitting device, the second cavity is formed between the second electrode and the second reflecting layer of the second light-emitting device, and a first cavity length of the first cavity corresponding to a wavelength of light of the first color is different from a second cavity length of the second cavity corresponding to a wavelength of light of the second color. 17. The method according to claim 16, wherein,
forming the first reflecting layer of the first light-emitting device and the second reflecting layer of the second light-emitting device on the substrate by a single patterning process, such that the first reflecting layer and the second reflecting layer are spaced apart from each other to form a gap region between the first light-emitting device and the second light-emitting device; forming the transparent first contact layer of the first light-emitting device and the transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer respectively by a single patterning process, such that the first contact layer and the second contact layer are spaced apart each other and disposed on the first reflecting layer and the second reflecting layer respectively; forming the first organic light-emitting layer of the first light-emitting device and the second organic light-emitting layer of the second light-emitting device on the first contact layer and the second contact layer respectively by a single patterning process; and forming the second electrode of the first light-emitting device and the second electrode of the second light-emitting device on the first organic light-emitting layer and the second organic light-emitting layer respectively by a single patterning process. 18. The method according to claim 17, wherein the forming the transparent first insulating layer of the first light-emitting device and the transparent second insulating layer of the second light-emitting device on the first reflecting layer and the second reflecting layer respectively comprises:
forming a first insulating film on the first reflecting layer, the second reflecting layer and the gap region such that the first insulating film is provided with a groove at the gap region; forming a support film in the groove by a plasma enhanced chemical vapor deposition process; and forming a second insulating film on the first insulating film of the second light-emitting device and the support film by a patterning process, wherein an orthogonal projection of the second insulating film on the substrate does not overlap an orthogonal projection of the first reflecting layer on the substrate. 19. The method according to claim 18, further comprising:
forming a first via hole in the first insulating film of the first light-emitting device and filling a conductive material in the first via hole to form a first connecting pillar; and forming a second via hole in the first insulating film and the second insulating film of the second light-emitting device and filling a conductive material in the second via hole to form a second connecting pillar. 20. The method according to claim 19, wherein the forming the transparent first contact layer of the first light-emitting device and the transparent second contact layer of the second light-emitting device on the first insulating layer and the second insulating layer respectively by a single patterning process, such that the first contact layer and the second contact layer are spaced apart each other and disposed on the first reflecting layer and the second reflecting layer respectively comprises:
coating a photoresist on a part of the first insulating layer at the gap region and a part of the second insulating layer at the gap region; forming a contact film layer on a residual part of the first insulating layer, a residual part of the second insulating layer and the photoresist; and forming a first contact layer and a second contact layer by removing the photoresist. 21-23. (canceled) | 3,600 |
345,428 | 16,643,335 | 3,679 | The present invention relates to a sound emitter device (1) that is immersible or semi-immersible in a liquid, the device comprising both a rigid hollow body (3) having at least one opening one of its ends (31, 32) and arranged to be immersed at least in part in the liquid, in such a manner that the main axis (4) passing through the opening of the hollow body (3) is substantially vertical, and also at least one electrodynamic loudspeaker (5, 51, 52) comprising at least one diaphragm (6, 61, 62), at least one magnet, at least one moving coil (7, 71, 72). The at least one loudspeaker (5, 51, 52) is fastened inside the hollow body (3) in the proximity of at least one immersed opening of the hollow body (3), the device (1) and its hollow body (3) being arranged so that, when the device (1) is at least semi-immersed, the diaphragm (6, 61, 62) of the at least one loudspeaker (5, 51, 52) is in contact with the liquid on at least one of its sides and closes the immersed opening (32) of the hollow body (3). | 1. A sound emitter device that is immersible or semi-immersible in an ambient liquid, the device being characterized in that it comprises:
a rigid hollow body having a first opening and a second opening, the hollow body being arranged to be immersed at least in part in the ambient liquid and having a main axis passing through the first opening of the hollow body; an electrodynamic loudspeaker comprising a diaphragm closing the first opening , a magnet that is mounted stationary relative to the hollow body, and a coil that is mounted to be movable relative to the hollow body along a travel direction parallel to the main axis of the hollow body; and a pressure balancing pouch comprising a flexible membrane and suitable for containing a pressure compensation fluid, the flexible membrane being suitable for deforming under the effect of a variation in the pressure of the ambient liquid, the deformation of the flexible membrane giving rise to a flow of pressure compensation fluid through the second opening in such a manner as to balance the pressures exerted on either side of the diaphragm of the loudspeaker; wherein the device and its hollow body are arranged in such a manner that, when the device is at least semi-immersed in the ambient liquid, the device spontaneously takes up orientation with the main axis of the hollow body extending vertically and with a face) of the diaphragm of the loudspeaker being in contact with the ambient liquid. 2. A device according to claim 1, wherein the hollow body defines an internal cavity, and the pressure balancing pouch extends inside the internal cavity. 3. A device according to claim 2, wherein the inside of the pressure balancing pouch is in communication with the ambient liquid via the second opening in such a manner that the ambient liquid forms the compensation fluid. 4. A device according to claim 1, wherein the hollow body defines an internal cavity, and the pressure balancing pouch extends outside the internal cavity. 5. A device according to claim 4, including a fluid flow duct connecting the pressure balancing pouch to the second opening. 6. A device according to claim 4, wherein the pressure balancing pouch is arranged relative to the hollow body in such a manner that, when the device is at least semi-immersed in the ambient liquid with the main axis vertical, the balancing pouch is positioned at a depth substantially identical to the depth of the diaphragm of the loudspeaker. 7. A device according to claim 1, wherein the device spontaneously takes up an orientation such that the hollow body is semi-immersed in the ambient liquid. 8. A device according to claim 1, further comprising a floating part arranged outside the hollow body and fastened to the hollow body. 9. A device according to claim 1, wherein the device and its hollow body are arranged in such a manner that, when the device is at least semi-immersed in the ambient liquid, the device spontaneously takes up an orientation with the main axis of the hollow body extending vertically and with the first opening being situated above the second opening. 10. A device according to claim 1, wherein the coil of the loudspeaker is arranged in a protection chamber , the protection chamber being formed by the diaphragm of the loudspeaker, by a flexible membrane, and by a wall of the hollow body. 11. A device according to claim 1, having two loudspeakers arranged on the main axis of the hollow body and defining a chamber with their diaphragms and with a wall of the hollow body, the chamber being filled with the pressure compensation fluid. 12. A device according to claim 1, having two loudspeakers and wherein one of the loudspeakers is an active loudspeaker comprising a diaphragm and a coil, and the other loudspeaker comprises a passive diaphragm. 13. A device according to claim 1, wherein the or one of the loudspeakers is capable of delivering an acoustic pressure level of at least 160 dB at a distance of 1 m from the loudspeaker in a frequency band lying in the range 1 Hz and 500 Hz. 14. A device according to claim 1, wherein the loudspeaker or one of the loudspeakers has a respective motor on each side of the diaphragm. | The present invention relates to a sound emitter device (1) that is immersible or semi-immersible in a liquid, the device comprising both a rigid hollow body (3) having at least one opening one of its ends (31, 32) and arranged to be immersed at least in part in the liquid, in such a manner that the main axis (4) passing through the opening of the hollow body (3) is substantially vertical, and also at least one electrodynamic loudspeaker (5, 51, 52) comprising at least one diaphragm (6, 61, 62), at least one magnet, at least one moving coil (7, 71, 72). The at least one loudspeaker (5, 51, 52) is fastened inside the hollow body (3) in the proximity of at least one immersed opening of the hollow body (3), the device (1) and its hollow body (3) being arranged so that, when the device (1) is at least semi-immersed, the diaphragm (6, 61, 62) of the at least one loudspeaker (5, 51, 52) is in contact with the liquid on at least one of its sides and closes the immersed opening (32) of the hollow body (3).1. A sound emitter device that is immersible or semi-immersible in an ambient liquid, the device being characterized in that it comprises:
a rigid hollow body having a first opening and a second opening, the hollow body being arranged to be immersed at least in part in the ambient liquid and having a main axis passing through the first opening of the hollow body; an electrodynamic loudspeaker comprising a diaphragm closing the first opening , a magnet that is mounted stationary relative to the hollow body, and a coil that is mounted to be movable relative to the hollow body along a travel direction parallel to the main axis of the hollow body; and a pressure balancing pouch comprising a flexible membrane and suitable for containing a pressure compensation fluid, the flexible membrane being suitable for deforming under the effect of a variation in the pressure of the ambient liquid, the deformation of the flexible membrane giving rise to a flow of pressure compensation fluid through the second opening in such a manner as to balance the pressures exerted on either side of the diaphragm of the loudspeaker; wherein the device and its hollow body are arranged in such a manner that, when the device is at least semi-immersed in the ambient liquid, the device spontaneously takes up orientation with the main axis of the hollow body extending vertically and with a face) of the diaphragm of the loudspeaker being in contact with the ambient liquid. 2. A device according to claim 1, wherein the hollow body defines an internal cavity, and the pressure balancing pouch extends inside the internal cavity. 3. A device according to claim 2, wherein the inside of the pressure balancing pouch is in communication with the ambient liquid via the second opening in such a manner that the ambient liquid forms the compensation fluid. 4. A device according to claim 1, wherein the hollow body defines an internal cavity, and the pressure balancing pouch extends outside the internal cavity. 5. A device according to claim 4, including a fluid flow duct connecting the pressure balancing pouch to the second opening. 6. A device according to claim 4, wherein the pressure balancing pouch is arranged relative to the hollow body in such a manner that, when the device is at least semi-immersed in the ambient liquid with the main axis vertical, the balancing pouch is positioned at a depth substantially identical to the depth of the diaphragm of the loudspeaker. 7. A device according to claim 1, wherein the device spontaneously takes up an orientation such that the hollow body is semi-immersed in the ambient liquid. 8. A device according to claim 1, further comprising a floating part arranged outside the hollow body and fastened to the hollow body. 9. A device according to claim 1, wherein the device and its hollow body are arranged in such a manner that, when the device is at least semi-immersed in the ambient liquid, the device spontaneously takes up an orientation with the main axis of the hollow body extending vertically and with the first opening being situated above the second opening. 10. A device according to claim 1, wherein the coil of the loudspeaker is arranged in a protection chamber , the protection chamber being formed by the diaphragm of the loudspeaker, by a flexible membrane, and by a wall of the hollow body. 11. A device according to claim 1, having two loudspeakers arranged on the main axis of the hollow body and defining a chamber with their diaphragms and with a wall of the hollow body, the chamber being filled with the pressure compensation fluid. 12. A device according to claim 1, having two loudspeakers and wherein one of the loudspeakers is an active loudspeaker comprising a diaphragm and a coil, and the other loudspeaker comprises a passive diaphragm. 13. A device according to claim 1, wherein the or one of the loudspeakers is capable of delivering an acoustic pressure level of at least 160 dB at a distance of 1 m from the loudspeaker in a frequency band lying in the range 1 Hz and 500 Hz. 14. A device according to claim 1, wherein the loudspeaker or one of the loudspeakers has a respective motor on each side of the diaphragm. | 3,600 |
345,429 | 16,643,356 | 3,679 | An inorganic structure body has a free-standing structure including a fibrous member and/or a shell. The fibrous member and/or the shell include a metal and/or an inorganic material and have a three-dimensionally continuous configuration. The free-standing structure may have a structure that is based on a nonwoven fabric or a porous membrane used as a substrate. | 1. An inorganic structure body comprising a free-standing structure including at least one of a fibrous member and a shell, the at least one of the fibrous member and the shell including at least one of a metal and an inorganic material and having a three-dimensionally continuous configuration. 2. The inorganic structure body according to claim 1, wherein the free-standing structure includes at least one of the following (a) to (d):
(a) metal nanoparticles containing one of a noble metal, a main group metal, and a transition metal; (b) metal nanoparticles made of an alloy containing at least one of a noble metal, a main group metal, and a transition metal; (c) metal compound nanoparticles made of a metal oxide, a metal sulfide, a metal nitride, a metal carbide, a metal phosphide, or a metal iodide; and (d) carbon nanoparticles. 3. The inorganic structure body according to claim 1,
wherein the free-standing structure includes, on a surface of the free-standing structure, protruding structures that include the at least one of the metal and the inorganic material and which have a diameter of 3 nm or greater and 10 nm or less. 4. The inorganic structure body according to claim 1, wherein the free-standing structure is a nonwoven fabric structure having flexibility, the nonwoven fabric structure including a semi-tubular nanowire that has a three-dimensionally continuous configuration. 5. The inorganic structure body according to claim 1, wherein the free-standing structure is a porous membrane structure having flexibility, the porous membrane structure having pores that have a radius of curvature of 20 nm or greater and 200 nm or less. 6. The inorganic structure body according to claim 1, further comprising a support portion made of a polymer, the support portion supporting at least a portion of the free-standing structure. 7. The inorganic structure body according to claim 1, wherein the free-standing structure contains at least one of Pt, Au, Ag, Ru, Ir, Cu, Sn, Ni, Cr, and Zn. 8. A device in which the inorganic structure body according to claim 1 is used as at least one of a catalyst layer, a filter, and an electrically conductive member. 9. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a recovery member that selectively recovers a protein. 10. The device according to claim 9, wherein the inorganic structure body contains at least one of Cu, Ni, Zn, and Co and selectively recovers a His-tagged protein. 11. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a catalyst member for electrolysis of water. 12. The device according to claim 11, wherein the inorganic structure body contains at least one of Pt, Au, Ag, Ru, and Ir and has an average diameter of 200 nm or greater and 800 nm or less. 13. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a photothermal conversion member that absorbs light and converts the light to heat. 14. The device according to claim 13, wherein the inorganic structure body contains at least one of Ag and Cu. 15. The device according to claim 13, further comprising a support body that has a water absorbing property and a thermal insulation property, a first surface of the support body being in contact with the inorganic structure body, a second surface of the support body being in contact with a liquid, the device being configured to evaporate the liquid by using the heat converted by the inorganic structure body. 16. A method for manufacturing an inorganic structure body, the method comprising:
a forming step of forming at least one of a metal and an inorganic material on a surface of a substrate including a polymer, thereby forming, on the surface of the substrate, a free-standing structure that includes at least one of a fibrous member and a shell, the at least one of the fibrous member and the shell including the at least one of the metal and the inorganic material and having a three-dimensionally continuous configuration; and a removing step of removing all or a portion of the substrate. 17. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, a nonwoven fabric is used as the substrate, the nonwoven fabric including the polymer. 18. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, a porous membrane is used as the substrate, the porous membrane including the polymer and having pores that have a radius of curvature of 20 nm or greater and 200 nm or less. 19. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, the at least one of the metal and the inorganic material is physically vapor deposited onto one side of the substrate. 20. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, at least one of Pt, Au, Ag, Ru, Ir, Cu, Sn, Ni, Cr, and Zn is used as the metal. 21. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the removing step, a support portion is formed by removing a portion of the substrate, the support portion being to support at least a portion of the free-standing structure that includes the at least one of the fibrous member and the shell, the at least one of the fibrous member and the shell including the at least one of the metal and the inorganic material and having the three-dimensionally continuous configuration. 22. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, at least one of Cu, Ni, Zn, and Co is used as the metal to produce the inorganic structure body, the inorganic structure body being to selectively recover a His-tagged protein. 23. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step and the removing step, the inorganic structure body is produced, the inorganic structure body containing at least one of Pt, Au, Ag, Ru, and Ir and having an average diameter of 200 nm or greater and 800 nm or less, the inorganic structure body being to serve as a catalyst member for electrolysis of water. 24. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step and the removing step, the inorganic structure body is produced, the inorganic structure body containing at least one of Ag and Cu, the inorganic structure body being to serve as a photothermal conversion member that absorbs light and converts the light to heat. | An inorganic structure body has a free-standing structure including a fibrous member and/or a shell. The fibrous member and/or the shell include a metal and/or an inorganic material and have a three-dimensionally continuous configuration. The free-standing structure may have a structure that is based on a nonwoven fabric or a porous membrane used as a substrate.1. An inorganic structure body comprising a free-standing structure including at least one of a fibrous member and a shell, the at least one of the fibrous member and the shell including at least one of a metal and an inorganic material and having a three-dimensionally continuous configuration. 2. The inorganic structure body according to claim 1, wherein the free-standing structure includes at least one of the following (a) to (d):
(a) metal nanoparticles containing one of a noble metal, a main group metal, and a transition metal; (b) metal nanoparticles made of an alloy containing at least one of a noble metal, a main group metal, and a transition metal; (c) metal compound nanoparticles made of a metal oxide, a metal sulfide, a metal nitride, a metal carbide, a metal phosphide, or a metal iodide; and (d) carbon nanoparticles. 3. The inorganic structure body according to claim 1,
wherein the free-standing structure includes, on a surface of the free-standing structure, protruding structures that include the at least one of the metal and the inorganic material and which have a diameter of 3 nm or greater and 10 nm or less. 4. The inorganic structure body according to claim 1, wherein the free-standing structure is a nonwoven fabric structure having flexibility, the nonwoven fabric structure including a semi-tubular nanowire that has a three-dimensionally continuous configuration. 5. The inorganic structure body according to claim 1, wherein the free-standing structure is a porous membrane structure having flexibility, the porous membrane structure having pores that have a radius of curvature of 20 nm or greater and 200 nm or less. 6. The inorganic structure body according to claim 1, further comprising a support portion made of a polymer, the support portion supporting at least a portion of the free-standing structure. 7. The inorganic structure body according to claim 1, wherein the free-standing structure contains at least one of Pt, Au, Ag, Ru, Ir, Cu, Sn, Ni, Cr, and Zn. 8. A device in which the inorganic structure body according to claim 1 is used as at least one of a catalyst layer, a filter, and an electrically conductive member. 9. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a recovery member that selectively recovers a protein. 10. The device according to claim 9, wherein the inorganic structure body contains at least one of Cu, Ni, Zn, and Co and selectively recovers a His-tagged protein. 11. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a catalyst member for electrolysis of water. 12. The device according to claim 11, wherein the inorganic structure body contains at least one of Pt, Au, Ag, Ru, and Ir and has an average diameter of 200 nm or greater and 800 nm or less. 13. A device comprising the inorganic structure body according to claim 1, the inorganic structure body serving as a photothermal conversion member that absorbs light and converts the light to heat. 14. The device according to claim 13, wherein the inorganic structure body contains at least one of Ag and Cu. 15. The device according to claim 13, further comprising a support body that has a water absorbing property and a thermal insulation property, a first surface of the support body being in contact with the inorganic structure body, a second surface of the support body being in contact with a liquid, the device being configured to evaporate the liquid by using the heat converted by the inorganic structure body. 16. A method for manufacturing an inorganic structure body, the method comprising:
a forming step of forming at least one of a metal and an inorganic material on a surface of a substrate including a polymer, thereby forming, on the surface of the substrate, a free-standing structure that includes at least one of a fibrous member and a shell, the at least one of the fibrous member and the shell including the at least one of the metal and the inorganic material and having a three-dimensionally continuous configuration; and a removing step of removing all or a portion of the substrate. 17. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, a nonwoven fabric is used as the substrate, the nonwoven fabric including the polymer. 18. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, a porous membrane is used as the substrate, the porous membrane including the polymer and having pores that have a radius of curvature of 20 nm or greater and 200 nm or less. 19. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, the at least one of the metal and the inorganic material is physically vapor deposited onto one side of the substrate. 20. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, at least one of Pt, Au, Ag, Ru, Ir, Cu, Sn, Ni, Cr, and Zn is used as the metal. 21. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the removing step, a support portion is formed by removing a portion of the substrate, the support portion being to support at least a portion of the free-standing structure that includes the at least one of the fibrous member and the shell, the at least one of the fibrous member and the shell including the at least one of the metal and the inorganic material and having the three-dimensionally continuous configuration. 22. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step, at least one of Cu, Ni, Zn, and Co is used as the metal to produce the inorganic structure body, the inorganic structure body being to selectively recover a His-tagged protein. 23. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step and the removing step, the inorganic structure body is produced, the inorganic structure body containing at least one of Pt, Au, Ag, Ru, and Ir and having an average diameter of 200 nm or greater and 800 nm or less, the inorganic structure body being to serve as a catalyst member for electrolysis of water. 24. The method for manufacturing an inorganic structure body according to claim 16, wherein, in the forming step and the removing step, the inorganic structure body is produced, the inorganic structure body containing at least one of Ag and Cu, the inorganic structure body being to serve as a photothermal conversion member that absorbs light and converts the light to heat. | 3,600 |
345,430 | 16,643,344 | 3,679 | A compact subsea pig launcher comprises a tubular magazine for holding a plurality of pipeline pigs in longitudinal succession ready for launching successively into a subsea pipeline. The magazine is shaped to define at least one turn such as a coil around an upright axis. Thus, a series of pigs are stored in longitudinal succession along a path that is curved in plan view around the upright axis. During launching, at least one of the series of pigs is advanced along the path with angular movement around the upright axis. | 1-33. (canceled) 34. A subsea pig launcher comprises a tubular magazine for holding a plurality of pipeline pigs in longitudinal succession ready for launching successively into a subsea pipeline, wherein the magazine is shaped to define at least one turn around an upright axis, the or each turn of the magazine completing a full or partial loop, so that the magazine comprises a succession of full, intercommunicating loops stacked or layered along the upright axis. 35. The pig launcher of claim 34, wherein the successive loops have substantially the same size or shape as each other. 36. The pig launcher of claim 35, wherein the successive loops of the magazine define a generally helical arrangement of successive coils. 37. The pig launcher of claim 34, wherein a substantially cylindrical lumen extends along the upright axis within the succession of loops. 38. The pig launcher of claim 34, wherein a launch system is housed within the succession of loops, the launch system communicating with the magazine to launch the pigs. 39. The pig launcher of claim 38, wherein the launch system comprises a plurality of kick lines each communicating with a respective loop. 40. The pig launcher of claim 39, wherein the kick lines are pressurised by a common line extending within and along the succession of loops. 41. The pig launcher of claim 34, wherein the magazine is shaped to define an inner turn within an outer turn. 42. The pig launcher of claim 41, wherein the inner and outer turns are, respectively, part of inner and outer intercommunicating loops. 43. The pig launcher of claim 34, wherein successive turns are in mutually-opposed directions. 44. The pig launcher of claim 43, wherein the directions are clockwise and anticlockwise with respect to the upright axis. 45. The pig launcher of claim 43, wherein the magazine is shaped to define intercommunicating loops that lie beside each other in a plane intersecting the upright axis. 46. The pig launcher of claim 34, comprising an exit tube that extends downwardly from a lower end of the magazine. 47. The pig launcher of claim 34, wherein at least one twins curved along its length continuously with a substantially constant radius of curvature. 48. The pig launcher of claim 34, wherein at least one turn is curved along its length with a variable radius of curvature. 49. The pig launcher of claim 34, wherein at least one tiara has discontinuous curvature. 50. The pig launcher of claim 49, wherein the at least one turn has at least one substantially straight section and. at least one bend. 51. The pig launcher of claim 50, wherein, in top plan view, the magazine has substantially polygonal shape. 52. The pig launcher of claim 51, wherein the polygonal shape is rectangular, hexagonal, or octagonal. 53. The pig launcher of claim 34, wherein the radius of curvature of any section of a turn is greater than three times the diameter of a tube defining the magazine. 54. The pig launcher of claim 34, supported in a frame as a subsea-connectable module. 55. The pig launcher of claim 54, wherein the frame is substantially cuboidal. 56. The pig launcher of claim 55, wherein a substantially straight section of the magazine lies substantially parallel to a face of the cuboidal frame. 57. The pig launcher of claim 54. wherein the magazine has a substantially polygonal or part-polygonal shape in plan view and at least one side of that shape lies substantially parallel to a face of the cuboidal frame. 58. The pig launcher of claim 54, wherein the frame has a height greater than its width. 59. The pig launcher of claim 54. wherein the frame comprises at least one upright guide formation. 60. The pig launcher of claim 59, wherein the or each guide formation extends in a direction substantially parallel to the upright axis. 61. A method of launching pipeline pigs subsea, tine method comprising:
providing a series of pigs stored in longitudinal succession along a path that is curved in plan view around an upright axis; and advancing at least one of the series of pigs along the path with angular movement at least 720° around the upright axis. 62. The method of claim 61, comprising conveying launch pressure to the pigs from an inner side of the curve of the path. 63. The method of claim 61, comprising moving a modular structure that supports the pigs in a direction of movement substantially parallel to the upright axis during installation and removal operations. | A compact subsea pig launcher comprises a tubular magazine for holding a plurality of pipeline pigs in longitudinal succession ready for launching successively into a subsea pipeline. The magazine is shaped to define at least one turn such as a coil around an upright axis. Thus, a series of pigs are stored in longitudinal succession along a path that is curved in plan view around the upright axis. During launching, at least one of the series of pigs is advanced along the path with angular movement around the upright axis.1-33. (canceled) 34. A subsea pig launcher comprises a tubular magazine for holding a plurality of pipeline pigs in longitudinal succession ready for launching successively into a subsea pipeline, wherein the magazine is shaped to define at least one turn around an upright axis, the or each turn of the magazine completing a full or partial loop, so that the magazine comprises a succession of full, intercommunicating loops stacked or layered along the upright axis. 35. The pig launcher of claim 34, wherein the successive loops have substantially the same size or shape as each other. 36. The pig launcher of claim 35, wherein the successive loops of the magazine define a generally helical arrangement of successive coils. 37. The pig launcher of claim 34, wherein a substantially cylindrical lumen extends along the upright axis within the succession of loops. 38. The pig launcher of claim 34, wherein a launch system is housed within the succession of loops, the launch system communicating with the magazine to launch the pigs. 39. The pig launcher of claim 38, wherein the launch system comprises a plurality of kick lines each communicating with a respective loop. 40. The pig launcher of claim 39, wherein the kick lines are pressurised by a common line extending within and along the succession of loops. 41. The pig launcher of claim 34, wherein the magazine is shaped to define an inner turn within an outer turn. 42. The pig launcher of claim 41, wherein the inner and outer turns are, respectively, part of inner and outer intercommunicating loops. 43. The pig launcher of claim 34, wherein successive turns are in mutually-opposed directions. 44. The pig launcher of claim 43, wherein the directions are clockwise and anticlockwise with respect to the upright axis. 45. The pig launcher of claim 43, wherein the magazine is shaped to define intercommunicating loops that lie beside each other in a plane intersecting the upright axis. 46. The pig launcher of claim 34, comprising an exit tube that extends downwardly from a lower end of the magazine. 47. The pig launcher of claim 34, wherein at least one twins curved along its length continuously with a substantially constant radius of curvature. 48. The pig launcher of claim 34, wherein at least one turn is curved along its length with a variable radius of curvature. 49. The pig launcher of claim 34, wherein at least one tiara has discontinuous curvature. 50. The pig launcher of claim 49, wherein the at least one turn has at least one substantially straight section and. at least one bend. 51. The pig launcher of claim 50, wherein, in top plan view, the magazine has substantially polygonal shape. 52. The pig launcher of claim 51, wherein the polygonal shape is rectangular, hexagonal, or octagonal. 53. The pig launcher of claim 34, wherein the radius of curvature of any section of a turn is greater than three times the diameter of a tube defining the magazine. 54. The pig launcher of claim 34, supported in a frame as a subsea-connectable module. 55. The pig launcher of claim 54, wherein the frame is substantially cuboidal. 56. The pig launcher of claim 55, wherein a substantially straight section of the magazine lies substantially parallel to a face of the cuboidal frame. 57. The pig launcher of claim 54. wherein the magazine has a substantially polygonal or part-polygonal shape in plan view and at least one side of that shape lies substantially parallel to a face of the cuboidal frame. 58. The pig launcher of claim 54, wherein the frame has a height greater than its width. 59. The pig launcher of claim 54. wherein the frame comprises at least one upright guide formation. 60. The pig launcher of claim 59, wherein the or each guide formation extends in a direction substantially parallel to the upright axis. 61. A method of launching pipeline pigs subsea, tine method comprising:
providing a series of pigs stored in longitudinal succession along a path that is curved in plan view around an upright axis; and advancing at least one of the series of pigs along the path with angular movement at least 720° around the upright axis. 62. The method of claim 61, comprising conveying launch pressure to the pigs from an inner side of the curve of the path. 63. The method of claim 61, comprising moving a modular structure that supports the pigs in a direction of movement substantially parallel to the upright axis during installation and removal operations. | 3,600 |
345,431 | 16,643,322 | 3,679 | Disclosed herein are quantum dot devices and techniques. In some embodiments, a quantum computing processing device may include a quantum well stack, an array of quantum dot gate electrodes above the quantum well stack, and an associated array of selectors above the array of quantum dot gate electrodes. The array of quantum dot gate electrodes and the array of selectors may each be arranged in a grid. | 1. A quantum dot device, comprising:
a quantum well stack; a quantum dot gate electrode above the quantum well stack; and a selector above the quantum dot gate electrode, wherein the selector includes a first contact, a second contact, and a selector material between the first contact and the second contact, and wherein the first contact is electrically coupled to the quantum dot gate electrode. 2. The quantum dot device of claim 1, wherein the quantum dot gate electrode is a first quantum dot gate electrode, the selector is a first selector, and the quantum dot device further includes:
a second quantum dot gate electrode above the quantum well stack; and a second selector above the second quantum dot gate electrode, wherein the second selector includes a first contact, a second contact, and a selector material between the first contact and the second contact of the second selector, and wherein the first contact of the second selector is electrically coupled to the second quantum dot gate electrode. 3. The quantum dot device of claim 2, wherein the second contact of the first selector is electrically coupled to the second contact of the second selector. 4. The quantum dot device of claim 3, wherein the quantum dot device further includes:
a third quantum dot gate electrode above the quantum well stack; and a third selector above the third quantum dot gate electrode, wherein the third selector includes a first contact, a second contact, and a selector material between the first contact and the second contact of the third selector, wherein the first contact of the third selector is electrically coupled to the third quantum dot gate electrode, and wherein the second contact of the third selector is electrically coupled to the second contact of the second selector. 5. The quantum dot device of claim 2, further comprising:
an accumulation region; a first pair of conductive pathways in contact with the accumulation region, wherein the first quantum dot gate electrode is at least partially between the conductive pathways in the first pair of conductive pathways; and a second pair of conductive pathways in contact with the accumulation region, wherein the second quantum dot gate electrode is at least partially between the conductive pathways in the second pair of conductive pathways. 6. The quantum dot device of claim 1, further comprising:
a selector gate electrode; and a selector gate dielectric between the selector material and the selector gate electrode. 7. The quantum dot device of claim 6, wherein the selector gate dielectric wraps around the selector material, and the selector gate electrode wraps around the selector gate dielectric. 8. The quantum dot device of claim 6, wherein the quantum dot gate electrode is a first quantum dot gate electrode, the selector is a first selector, the selector gate electrode is a first selector gate electrode, the selector gate dielectric is a first selector gate dielectric, and the quantum dot device further includes:
a second quantum dot gate electrode above the quantum well stack; a second selector above the second quantum dot gate electrode, wherein the second selector includes a selector material; a second selector gate electrode; and a second selector gate dielectric between the selector material of the second selector and the second selector gate electrode; wherein the second selector gate electrode is materially continuous with the first selector gate electrode. 9. The quantum dot device of claim 8, wherein the quantum dot device further includes:
a third quantum dot gate electrode above the quantum well stack; a third selector above the third quantum dot gate electrode, wherein the third selector includes a selector material; a third selector gate electrode; and a third selector gate dielectric between the selector material of the third selector and the third selector gate electrode; wherein the third selector gate electrode of the second selector is not materially continuous with the first selector gate electrode. 10. The quantum dot device of claim 1, wherein the selector material includes an oxide material, a chalcogenide material, a group IV element, a group VI element, or an ovonic material. 11. The quantum dot device of claim 1, wherein a bit line is coupled to the second contact. 12. The quantum dot device of claim 11, wherein a word line is coupled to an accumulation region. 13. A method of manufacturing a quantum dot device, comprising:
forming a quantum well stack; forming an array of quantum dot gate electrodes above the quantum well stack; and forming an array of selectors above the array of quantum dot gate electrodes. 14. The method of claim 13, wherein forming the array of quantum dot gate electrodes and forming the array of selectors includes:
depositing a quantum dot gate electrode material above the quantum well stack; depositing a selector material above the quantum dot gate electrode material; and simultaneously patterning the quantum dot gate electrode material and the selector material to form the array of quantum dot gate electrodes and the array of selectors. 15-19. (canceled) 20. A quantum computing device, comprising:
a quantum processing device, wherein the quantum processing device includes: a quantum well stack, an array of quantum dot gate electrodes above the quantum well stack, and an associated array of selectors above the array of quantum dot gate electrodes, wherein the array of quantum dot gate electrodes and the array of selectors are each arranged in a grid, and the grids have a same pitch. 21. The quantum computing device of claim 20, further comprising:
a non-quantum processing device, coupled to the quantum processing device, to control electrical signals applied to the quantum dot gate electrodes; and a memory device to store data generated by the quantum processing device. 22. The quantum computing device of claim 20, further comprising:
a plurality of word/bit lines, wherein different individual word/bit lines electrically connect contacts in different individual rows of selectors in the array of selectors. 23. The quantum computing device of claim 22, wherein the plurality of word/bit lines is a plurality of first word/bit lines, and the quantum computing device further includes:
a plurality of second word/bit lines, wherein different individual second word/bit lines electrically connect portions of the quantum well stack under quantum dot gate electrodes in different individual columns of quantum dot gate electrodes in the array of quantum dot gate electrodes. 24. The quantum computing device of claim 23, further comprising:
a plurality of gate lines, wherein different individual gate lines electrically connect selector material in different individual rows of selectors in the array of selectors. 25. The quantum computing device of claim 23, further comprising:
a plurality of gate lines, wherein different individual gate lines electrically connect selector material in different individual columns of selectors in the array of selectors. | Disclosed herein are quantum dot devices and techniques. In some embodiments, a quantum computing processing device may include a quantum well stack, an array of quantum dot gate electrodes above the quantum well stack, and an associated array of selectors above the array of quantum dot gate electrodes. The array of quantum dot gate electrodes and the array of selectors may each be arranged in a grid.1. A quantum dot device, comprising:
a quantum well stack; a quantum dot gate electrode above the quantum well stack; and a selector above the quantum dot gate electrode, wherein the selector includes a first contact, a second contact, and a selector material between the first contact and the second contact, and wherein the first contact is electrically coupled to the quantum dot gate electrode. 2. The quantum dot device of claim 1, wherein the quantum dot gate electrode is a first quantum dot gate electrode, the selector is a first selector, and the quantum dot device further includes:
a second quantum dot gate electrode above the quantum well stack; and a second selector above the second quantum dot gate electrode, wherein the second selector includes a first contact, a second contact, and a selector material between the first contact and the second contact of the second selector, and wherein the first contact of the second selector is electrically coupled to the second quantum dot gate electrode. 3. The quantum dot device of claim 2, wherein the second contact of the first selector is electrically coupled to the second contact of the second selector. 4. The quantum dot device of claim 3, wherein the quantum dot device further includes:
a third quantum dot gate electrode above the quantum well stack; and a third selector above the third quantum dot gate electrode, wherein the third selector includes a first contact, a second contact, and a selector material between the first contact and the second contact of the third selector, wherein the first contact of the third selector is electrically coupled to the third quantum dot gate electrode, and wherein the second contact of the third selector is electrically coupled to the second contact of the second selector. 5. The quantum dot device of claim 2, further comprising:
an accumulation region; a first pair of conductive pathways in contact with the accumulation region, wherein the first quantum dot gate electrode is at least partially between the conductive pathways in the first pair of conductive pathways; and a second pair of conductive pathways in contact with the accumulation region, wherein the second quantum dot gate electrode is at least partially between the conductive pathways in the second pair of conductive pathways. 6. The quantum dot device of claim 1, further comprising:
a selector gate electrode; and a selector gate dielectric between the selector material and the selector gate electrode. 7. The quantum dot device of claim 6, wherein the selector gate dielectric wraps around the selector material, and the selector gate electrode wraps around the selector gate dielectric. 8. The quantum dot device of claim 6, wherein the quantum dot gate electrode is a first quantum dot gate electrode, the selector is a first selector, the selector gate electrode is a first selector gate electrode, the selector gate dielectric is a first selector gate dielectric, and the quantum dot device further includes:
a second quantum dot gate electrode above the quantum well stack; a second selector above the second quantum dot gate electrode, wherein the second selector includes a selector material; a second selector gate electrode; and a second selector gate dielectric between the selector material of the second selector and the second selector gate electrode; wherein the second selector gate electrode is materially continuous with the first selector gate electrode. 9. The quantum dot device of claim 8, wherein the quantum dot device further includes:
a third quantum dot gate electrode above the quantum well stack; a third selector above the third quantum dot gate electrode, wherein the third selector includes a selector material; a third selector gate electrode; and a third selector gate dielectric between the selector material of the third selector and the third selector gate electrode; wherein the third selector gate electrode of the second selector is not materially continuous with the first selector gate electrode. 10. The quantum dot device of claim 1, wherein the selector material includes an oxide material, a chalcogenide material, a group IV element, a group VI element, or an ovonic material. 11. The quantum dot device of claim 1, wherein a bit line is coupled to the second contact. 12. The quantum dot device of claim 11, wherein a word line is coupled to an accumulation region. 13. A method of manufacturing a quantum dot device, comprising:
forming a quantum well stack; forming an array of quantum dot gate electrodes above the quantum well stack; and forming an array of selectors above the array of quantum dot gate electrodes. 14. The method of claim 13, wherein forming the array of quantum dot gate electrodes and forming the array of selectors includes:
depositing a quantum dot gate electrode material above the quantum well stack; depositing a selector material above the quantum dot gate electrode material; and simultaneously patterning the quantum dot gate electrode material and the selector material to form the array of quantum dot gate electrodes and the array of selectors. 15-19. (canceled) 20. A quantum computing device, comprising:
a quantum processing device, wherein the quantum processing device includes: a quantum well stack, an array of quantum dot gate electrodes above the quantum well stack, and an associated array of selectors above the array of quantum dot gate electrodes, wherein the array of quantum dot gate electrodes and the array of selectors are each arranged in a grid, and the grids have a same pitch. 21. The quantum computing device of claim 20, further comprising:
a non-quantum processing device, coupled to the quantum processing device, to control electrical signals applied to the quantum dot gate electrodes; and a memory device to store data generated by the quantum processing device. 22. The quantum computing device of claim 20, further comprising:
a plurality of word/bit lines, wherein different individual word/bit lines electrically connect contacts in different individual rows of selectors in the array of selectors. 23. The quantum computing device of claim 22, wherein the plurality of word/bit lines is a plurality of first word/bit lines, and the quantum computing device further includes:
a plurality of second word/bit lines, wherein different individual second word/bit lines electrically connect portions of the quantum well stack under quantum dot gate electrodes in different individual columns of quantum dot gate electrodes in the array of quantum dot gate electrodes. 24. The quantum computing device of claim 23, further comprising:
a plurality of gate lines, wherein different individual gate lines electrically connect selector material in different individual rows of selectors in the array of selectors. 25. The quantum computing device of claim 23, further comprising:
a plurality of gate lines, wherein different individual gate lines electrically connect selector material in different individual columns of selectors in the array of selectors. | 3,600 |
345,432 | 16,643,357 | 3,679 | A tire has a tread that comprises a rubber composition based on at least, an elastomer matrix; a reinforcing filler comprising more than 150 phr of a reinforcing inorganic filler; and a plasticizing agent comprising more than 30 phr of at least one liquid plasticizer exhibiting a glass transition temperature less than −70° C. | 1-22. (canceled) 23. A tire having a tread that comprises a rubber composition based on at least:
an elastomer matrix; a reinforcing filler comprising more than 150 phr of a reinforcing inorganic filler; and a plasticizing agent comprising more than 30 phr of at least one liquid plasticizer exhibiting a glass transition temperature less than −70° C. 24. The tire according to claim 23, wherein the elastomer matrix comprises more than 50 phr of a first diene elastomer which is a styrene-butadiene copolymer, and comprises 0 to less than 50 phr of a second diene elastomer which is different from the first diene elastomer. 25. The tire according to claim 24, wherein the styrene-butadiene copolymer exhibits a styrene unit of less than 30% by weight per 100% by weight of the styrene-butadiene copolymer. 26. The tire composition according to claim 24, wherein the first diene elastomer exhibits a glass transition temperature of less than −40° C. 27. The tire according to claim 24, wherein the elastomer matrix comprises 55 to 100 phr of the first diene elastomer and 0 to 45 phr of the second diene elastomer. 28. The tire according to claim 24, wherein the second diene elastomer is selected from the group consisting of polybutadienes, synthetic polyisoprenes, natural rubber, butadiene copolymers other than the first diene elastomer, isoprene copolymers and mixtures thereof. 29. The tire according to claim 24, wherein the second diene elastomer is a polybutadiene. 30. The tire according to claim 23, wherein the reinforcing filler comprises more than 200 phr of the reinforcing inorganic filler. 31. The tire according to claim 23, wherein the reinforcing inorganic filler predominately comprises silica. 32. The tire according to claim 23, wherein the reinforcing filler comprises less than 40 phr of carbon black. 33. The tire according to claim 23, wherein the plasticizing agent comprises more than 60 phr of the liquid plasticizer. 34. The tire according to claim 23, wherein the liquid plasticizer exhibits a glass transition temperature of less than −80° C. 35. The tire according to claim 23, wherein the liquid plasticizer is selected from the group consisting of at least one phosphate plasticizer and mixtures thereof. 36. The tire according to claim 35, wherein the plasticizing agent comprises 0 to 50 phr of at least one liquid plasticizer other than the at least one phosphate plasticizer. 37. The tire according to claim 36, wherein the at least one liquid plasticizer other than the at least one phosphate plasticizer is selected from the group consisting of liquid diene polymers, polyolefinic oils, naphthenic oils, paraffinic oils, Distillate Aromatic Extracts (DAE) oils, Medium Extracted Solvates (MES) oils, Treated Distillate Aromatic Extracts (TDAE) oils, Residual Aromatic Extracts (RAE) oils, Treated Residual Aromatic Extracts (TRAE) oils, Safety Residual Aromatic Extracts (SRAE) oils, mineral oils, vegetable oils, ether plasticizers, ester plasticizers other than phosphate plasticizers, sulphonate plasticizers and mixtures thereof. 38. The tire according to claim 23, wherein the plasticizing agent further comprises more than 40 phr of at least one hydrocarbon resin exhibiting a glass transition temperature of more than 20° C. 39. The tire according to the claim 38, wherein the at least one hydrocarbon resin is selected from the group consisting of cyclopentadiene homopolymer or copolymer resins, dicyclopentadiene homopolymer or copolymer resins, terpene homopolymer or copolymer resins, C5 fraction homopolymer or copolymer resins, C9 fraction homopolymer or copolymer resins, alpha-methyl styrene homopolymer or copolymer resins, and mixtures thereof. 40. The tire according to claim 23, wherein the total content of plasticizing agent is more than 70 phr. 41. The tire according to claim 23, wherein a ratio of the total content of plasticizing agent to the total content of reinforcing filler is between 0.6 and 1.7. 42. The tire according to claim 1, wherein the tire is a snow tire. | A tire has a tread that comprises a rubber composition based on at least, an elastomer matrix; a reinforcing filler comprising more than 150 phr of a reinforcing inorganic filler; and a plasticizing agent comprising more than 30 phr of at least one liquid plasticizer exhibiting a glass transition temperature less than −70° C.1-22. (canceled) 23. A tire having a tread that comprises a rubber composition based on at least:
an elastomer matrix; a reinforcing filler comprising more than 150 phr of a reinforcing inorganic filler; and a plasticizing agent comprising more than 30 phr of at least one liquid plasticizer exhibiting a glass transition temperature less than −70° C. 24. The tire according to claim 23, wherein the elastomer matrix comprises more than 50 phr of a first diene elastomer which is a styrene-butadiene copolymer, and comprises 0 to less than 50 phr of a second diene elastomer which is different from the first diene elastomer. 25. The tire according to claim 24, wherein the styrene-butadiene copolymer exhibits a styrene unit of less than 30% by weight per 100% by weight of the styrene-butadiene copolymer. 26. The tire composition according to claim 24, wherein the first diene elastomer exhibits a glass transition temperature of less than −40° C. 27. The tire according to claim 24, wherein the elastomer matrix comprises 55 to 100 phr of the first diene elastomer and 0 to 45 phr of the second diene elastomer. 28. The tire according to claim 24, wherein the second diene elastomer is selected from the group consisting of polybutadienes, synthetic polyisoprenes, natural rubber, butadiene copolymers other than the first diene elastomer, isoprene copolymers and mixtures thereof. 29. The tire according to claim 24, wherein the second diene elastomer is a polybutadiene. 30. The tire according to claim 23, wherein the reinforcing filler comprises more than 200 phr of the reinforcing inorganic filler. 31. The tire according to claim 23, wherein the reinforcing inorganic filler predominately comprises silica. 32. The tire according to claim 23, wherein the reinforcing filler comprises less than 40 phr of carbon black. 33. The tire according to claim 23, wherein the plasticizing agent comprises more than 60 phr of the liquid plasticizer. 34. The tire according to claim 23, wherein the liquid plasticizer exhibits a glass transition temperature of less than −80° C. 35. The tire according to claim 23, wherein the liquid plasticizer is selected from the group consisting of at least one phosphate plasticizer and mixtures thereof. 36. The tire according to claim 35, wherein the plasticizing agent comprises 0 to 50 phr of at least one liquid plasticizer other than the at least one phosphate plasticizer. 37. The tire according to claim 36, wherein the at least one liquid plasticizer other than the at least one phosphate plasticizer is selected from the group consisting of liquid diene polymers, polyolefinic oils, naphthenic oils, paraffinic oils, Distillate Aromatic Extracts (DAE) oils, Medium Extracted Solvates (MES) oils, Treated Distillate Aromatic Extracts (TDAE) oils, Residual Aromatic Extracts (RAE) oils, Treated Residual Aromatic Extracts (TRAE) oils, Safety Residual Aromatic Extracts (SRAE) oils, mineral oils, vegetable oils, ether plasticizers, ester plasticizers other than phosphate plasticizers, sulphonate plasticizers and mixtures thereof. 38. The tire according to claim 23, wherein the plasticizing agent further comprises more than 40 phr of at least one hydrocarbon resin exhibiting a glass transition temperature of more than 20° C. 39. The tire according to the claim 38, wherein the at least one hydrocarbon resin is selected from the group consisting of cyclopentadiene homopolymer or copolymer resins, dicyclopentadiene homopolymer or copolymer resins, terpene homopolymer or copolymer resins, C5 fraction homopolymer or copolymer resins, C9 fraction homopolymer or copolymer resins, alpha-methyl styrene homopolymer or copolymer resins, and mixtures thereof. 40. The tire according to claim 23, wherein the total content of plasticizing agent is more than 70 phr. 41. The tire according to claim 23, wherein a ratio of the total content of plasticizing agent to the total content of reinforcing filler is between 0.6 and 1.7. 42. The tire according to claim 1, wherein the tire is a snow tire. | 3,600 |
345,433 | 16,643,340 | 3,679 | This communication apparatus C is provided with: a first communication unit which, after establishing a link necessary for first near field communication with a communication counterpart existing within a first communication available range, performs the first near field communication with the link-established communication counterpart; and a second communication unit which performs second near field communication with a communication counterpart existing within a second communication available range that is narrower than the first communication available range. And when it is detected that any one among a plurality of communication counterparts with which links are established has entered the second communication available range, the communication apparatus C limits the transmission and reception of data through the first near field communication with communication counterparts other than the communication counterpart detected to have entered the second communication available range, while maintaining the establishment of each link with each of the plurality of link-established communication counterparts. | 1. A communication apparatus comprising:
first communication circuitry that establishes a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performs the first near field communication with the communication partner for which the link is established; second communication circuitry that performs second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range; at least one memory configured to store program code; and at least one processor configured to access the program code and operate as instructed by the program code, the program code including: detection code configured to cause at least one of the at least one processor to detect that any one of a plurality of communication partners for which the link is established has entered the second communicable range; and communication control code configured to cause at least one of the at least one processor to, in a case where at least one of the at least one processor detects that the communication partner has entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. 2. The communication apparatus according to claim 1, wherein, in a case where at least one of the at least one processor detects that the communication partner whose transmission and reception of data by the first near field communication is restricted has entered the second communicable range, while maintaining the establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to remove restriction of the transmission and reception of data with the communication partner whose entrance to the second communicable range has been further detected, and restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose restriction of the transmission and reception of data has been removed. 3. The communication apparatus according to claim 1, wherein the communication control code is configured to cause at least one of the at least one processor to not respond to a predetermined command by the first near field communication from the communication partner whose transmission and reception of data by the first near field communication is restricted. 4. The communication apparatus according to claim 1, further comprising a battery that supplies power to each unit comprised in the communication apparatus,
wherein, in a case where a state in which the first near field communication is not performed with any of the plurality of communication partners for which the link is established continues for a predetermined time, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to switch a power consumption mode of the battery from a normal mode to a power saving mode, and thereafter, in a case where the detection code causes at least one of the at least one processor to detect that any one of the plurality of communication partners for which the link is established has entered the second communicable range, the communication control code causes at least one of the at least one processor to switch the power consumption mode of the battery from the power saving mode to the normal mode, and restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entrance to the second communicable range has been detected. 5. The communication apparatus according to claim 4, wherein, in a case where the state in which the first near field communication is not performed with any of the plurality of communication partners for which the link is established continues for the predetermined time, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to switch a power consumption mode of the battery from a normal mode to a power saving mode, and remove the restriction with all the communication partners whose transmission and reception of data by the first near field communication has been restricted. 6. The communication apparatus according to claim 1, wherein, in a case where the detection code causes at least one of the at least one processor to detect that the communication partner has entered the second communicable range, the communication control code causes at least one of the at least one processor to acquire a remaining power amount of a battery of the communication partner whose entrance to the second communicable range has been detected, and in a case where the remaining power amount acquired is less than a threshold, the communication control code causes at least one of the at least one processor to notify that the remaining power amount of the battery of the communication partner is small. 7. A communication method performed by a computer, the communication method comprising:
establishing a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performing the first near field communication with the communication partner for which the link is established; performing second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range; detecting that any one of a plurality of communication partners for which the link is established has entered the second communicable range; and in a case where it is detected that the communication partner has entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restricting transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. 8. A non-transitory computer readable memory having stored thereon a communication processing program configured to cause a computer comprising: a first communication circuit that establishes a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performs the first near field communication with the communication partner for which the link is established; and a second communication circuit that performs second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range, to:
detect that any one of a plurality of communication partners for which the link is established has entered the second communicable range, and in a case where the communication partner has been detected to have entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. | This communication apparatus C is provided with: a first communication unit which, after establishing a link necessary for first near field communication with a communication counterpart existing within a first communication available range, performs the first near field communication with the link-established communication counterpart; and a second communication unit which performs second near field communication with a communication counterpart existing within a second communication available range that is narrower than the first communication available range. And when it is detected that any one among a plurality of communication counterparts with which links are established has entered the second communication available range, the communication apparatus C limits the transmission and reception of data through the first near field communication with communication counterparts other than the communication counterpart detected to have entered the second communication available range, while maintaining the establishment of each link with each of the plurality of link-established communication counterparts.1. A communication apparatus comprising:
first communication circuitry that establishes a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performs the first near field communication with the communication partner for which the link is established; second communication circuitry that performs second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range; at least one memory configured to store program code; and at least one processor configured to access the program code and operate as instructed by the program code, the program code including: detection code configured to cause at least one of the at least one processor to detect that any one of a plurality of communication partners for which the link is established has entered the second communicable range; and communication control code configured to cause at least one of the at least one processor to, in a case where at least one of the at least one processor detects that the communication partner has entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. 2. The communication apparatus according to claim 1, wherein, in a case where at least one of the at least one processor detects that the communication partner whose transmission and reception of data by the first near field communication is restricted has entered the second communicable range, while maintaining the establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to remove restriction of the transmission and reception of data with the communication partner whose entrance to the second communicable range has been further detected, and restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose restriction of the transmission and reception of data has been removed. 3. The communication apparatus according to claim 1, wherein the communication control code is configured to cause at least one of the at least one processor to not respond to a predetermined command by the first near field communication from the communication partner whose transmission and reception of data by the first near field communication is restricted. 4. The communication apparatus according to claim 1, further comprising a battery that supplies power to each unit comprised in the communication apparatus,
wherein, in a case where a state in which the first near field communication is not performed with any of the plurality of communication partners for which the link is established continues for a predetermined time, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to switch a power consumption mode of the battery from a normal mode to a power saving mode, and thereafter, in a case where the detection code causes at least one of the at least one processor to detect that any one of the plurality of communication partners for which the link is established has entered the second communicable range, the communication control code causes at least one of the at least one processor to switch the power consumption mode of the battery from the power saving mode to the normal mode, and restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entrance to the second communicable range has been detected. 5. The communication apparatus according to claim 4, wherein, in a case where the state in which the first near field communication is not performed with any of the plurality of communication partners for which the link is established continues for the predetermined time, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, the communication control code causes at least one of the at least one processor to switch a power consumption mode of the battery from a normal mode to a power saving mode, and remove the restriction with all the communication partners whose transmission and reception of data by the first near field communication has been restricted. 6. The communication apparatus according to claim 1, wherein, in a case where the detection code causes at least one of the at least one processor to detect that the communication partner has entered the second communicable range, the communication control code causes at least one of the at least one processor to acquire a remaining power amount of a battery of the communication partner whose entrance to the second communicable range has been detected, and in a case where the remaining power amount acquired is less than a threshold, the communication control code causes at least one of the at least one processor to notify that the remaining power amount of the battery of the communication partner is small. 7. A communication method performed by a computer, the communication method comprising:
establishing a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performing the first near field communication with the communication partner for which the link is established; performing second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range; detecting that any one of a plurality of communication partners for which the link is established has entered the second communicable range; and in a case where it is detected that the communication partner has entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restricting transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. 8. A non-transitory computer readable memory having stored thereon a communication processing program configured to cause a computer comprising: a first communication circuit that establishes a link necessary for first near field communication with a communication partner existing in a first communicable range, and then performs the first near field communication with the communication partner for which the link is established; and a second communication circuit that performs second near field communication with a communication partner existing in a second communicable range narrower than the first communicable range, to:
detect that any one of a plurality of communication partners for which the link is established has entered the second communicable range, and in a case where the communication partner has been detected to have entered the second communicable range, while maintaining establishment of the link with each of the plurality of communication partners for which the link is established, restrict transmission and reception of data by the first near field communication with the communication partners other than the communication partner whose entry into the second communicable range has been detected. | 3,600 |
345,434 | 16,643,323 | 3,679 | The present invention relates to a tip applicator and a cosmetic ingredient applying device having the same. According to the present invention, the tip applicator, which applies a cosmetic substance to a user's skin, includes: a body having a given shape; and a plurality of functional surfaces formed on the side periphery of the body, wherein two functional surfaces adjacent to each other among the plurality of functional surfaces have different widths on at least a portion thereof in a direction parallel with a circumferential direction of the body. | 1. A tip applicator for applying a cosmetic substance to a user's skin, comprising:
a body having a given shape; and a plurality of functional surfaces formed on the side periphery of the body, wherein at least two functional surfaces of the plurality of functional surfaces have different functions from each other. 2. The tip applicator according to claim 1, wherein at least any one of the plurality of functional surfaces is a flocked surface having a plurality of small fibers formed thereon by means of flocking. 3. The tip applicator according to claim 1, wherein the at least two functional surfaces of the plurality of functional surfaces are flocked surfaces having a plurality of small fibers formed thereon by means of flocking, any one of the at least two functional surfaces having the fibers having a first length, and the other having the fibers having a second length relatively longer than the first length. 4. The tip applicator according to claim 1, wherein the flocked surfaces and the non-flocked surfaces of the plurality of functional surfaces are arranged alternately in a circumferential direction of the body. 5. The tip applicator according to claim 1, wherein at least any one of the plurality of functional surfaces comprises both of a flocked portion having a plurality of small fibers formed thereon by means of flocking and a non-flocked portion. 6. The tip applicator according to claim 5, wherein the flocked portion is located closer to a free end portion of the body than the non-flocked portion. 7. The tip applicator according to claim 5, wherein the at least one functional surface has at least one boundary line defining the flocked portion and the non-flocked portion, and the boundary line is any one selected from a linear line, curved line, oval, circle, closed loop, and combined shapes thereof. 8. The tip applicator according to claim 1, wherein each functional surface becomes small in width from one end portion thereof toward the other end portion thereof in a longitudinal direction of the body. 9. The tip applicator according to claim 8, wherein the two functional surfaces adjacent to each other have relatively large portions in width located opposite to each other in the longitudinal direction of the body. 10. The tip applicator according to claim 1, wherein the plurality of functional surfaces have the same sectional shapes as each other. 11. The tip applicator according to claim 1, wherein the at least two functional surfaces of the plurality of functional surfaces are made of different materials from each other. 12. A tip applicator for applying a cosmetic substance to a user's skin, comprising:
a body having a given shape; and a first functional surface and a second functional surface formed on the side periphery of the body in a longitudinal direction of the body, wherein at least a portion of the first functional surface and the second functional surface has different widths from each other along a direction vertical to the longitudinal direction of the body. 13. The tip applicator according to claim 12, wherein the first functional surface and the second functional surface are adjacent to each other on the side periphery of the body. 14. The tip applicator according to claim 12, wherein at least a portion of the first functional surface is formed of a plane. 15. The tip applicator according to claim 14, wherein the plane is a slant surface inclined toward an imaginary linear line parallel with the longitudinal direction of the body. 16. The tip applicator according to claim 14, wherein at least a portion of the second functional surface is formed of a plane, and the plane is a slant surface inclined toward an imaginary linear line parallel with the longitudinal direction of the body. 17. The tip applicator according to claim 12, wherein the first functional surface is a flocked surface having a plurality of small fibers formed thereon by means of flocking, and the second functional surface comprises both of a flocked portion having a plurality of small fibers formed thereon by means of flocking and a non-flocked portion. 18. The tip applicator according to claim 12, wherein the body further comprises a third functional surface formed on the opposite side to the first functional surface and a fourth functional surface formed on the opposite side to the second functional surface, and the first functional surface, the second functional surface, the third functional surface and the fourth functional surfaces are sequentially arranged along the circumferential direction of the body. 19. The tip applicator according to claim 12, wherein the first functional surface and the second functional surface become small in width from one end portion thereof toward the other end portion thereof in the longitudinal direction of the body, and the first functional surface and the second functional surface have relatively large portions in width located opposite to each other in the longitudinal direction of the body. 20. (canceled) 21. A cosmetic ingredient applying device, comprising:
a container for storing a given amount of cosmetic substance therein; and the tip applicator as defined in claim 1 to apply the cosmetic substance to a user's skin. | The present invention relates to a tip applicator and a cosmetic ingredient applying device having the same. According to the present invention, the tip applicator, which applies a cosmetic substance to a user's skin, includes: a body having a given shape; and a plurality of functional surfaces formed on the side periphery of the body, wherein two functional surfaces adjacent to each other among the plurality of functional surfaces have different widths on at least a portion thereof in a direction parallel with a circumferential direction of the body.1. A tip applicator for applying a cosmetic substance to a user's skin, comprising:
a body having a given shape; and a plurality of functional surfaces formed on the side periphery of the body, wherein at least two functional surfaces of the plurality of functional surfaces have different functions from each other. 2. The tip applicator according to claim 1, wherein at least any one of the plurality of functional surfaces is a flocked surface having a plurality of small fibers formed thereon by means of flocking. 3. The tip applicator according to claim 1, wherein the at least two functional surfaces of the plurality of functional surfaces are flocked surfaces having a plurality of small fibers formed thereon by means of flocking, any one of the at least two functional surfaces having the fibers having a first length, and the other having the fibers having a second length relatively longer than the first length. 4. The tip applicator according to claim 1, wherein the flocked surfaces and the non-flocked surfaces of the plurality of functional surfaces are arranged alternately in a circumferential direction of the body. 5. The tip applicator according to claim 1, wherein at least any one of the plurality of functional surfaces comprises both of a flocked portion having a plurality of small fibers formed thereon by means of flocking and a non-flocked portion. 6. The tip applicator according to claim 5, wherein the flocked portion is located closer to a free end portion of the body than the non-flocked portion. 7. The tip applicator according to claim 5, wherein the at least one functional surface has at least one boundary line defining the flocked portion and the non-flocked portion, and the boundary line is any one selected from a linear line, curved line, oval, circle, closed loop, and combined shapes thereof. 8. The tip applicator according to claim 1, wherein each functional surface becomes small in width from one end portion thereof toward the other end portion thereof in a longitudinal direction of the body. 9. The tip applicator according to claim 8, wherein the two functional surfaces adjacent to each other have relatively large portions in width located opposite to each other in the longitudinal direction of the body. 10. The tip applicator according to claim 1, wherein the plurality of functional surfaces have the same sectional shapes as each other. 11. The tip applicator according to claim 1, wherein the at least two functional surfaces of the plurality of functional surfaces are made of different materials from each other. 12. A tip applicator for applying a cosmetic substance to a user's skin, comprising:
a body having a given shape; and a first functional surface and a second functional surface formed on the side periphery of the body in a longitudinal direction of the body, wherein at least a portion of the first functional surface and the second functional surface has different widths from each other along a direction vertical to the longitudinal direction of the body. 13. The tip applicator according to claim 12, wherein the first functional surface and the second functional surface are adjacent to each other on the side periphery of the body. 14. The tip applicator according to claim 12, wherein at least a portion of the first functional surface is formed of a plane. 15. The tip applicator according to claim 14, wherein the plane is a slant surface inclined toward an imaginary linear line parallel with the longitudinal direction of the body. 16. The tip applicator according to claim 14, wherein at least a portion of the second functional surface is formed of a plane, and the plane is a slant surface inclined toward an imaginary linear line parallel with the longitudinal direction of the body. 17. The tip applicator according to claim 12, wherein the first functional surface is a flocked surface having a plurality of small fibers formed thereon by means of flocking, and the second functional surface comprises both of a flocked portion having a plurality of small fibers formed thereon by means of flocking and a non-flocked portion. 18. The tip applicator according to claim 12, wherein the body further comprises a third functional surface formed on the opposite side to the first functional surface and a fourth functional surface formed on the opposite side to the second functional surface, and the first functional surface, the second functional surface, the third functional surface and the fourth functional surfaces are sequentially arranged along the circumferential direction of the body. 19. The tip applicator according to claim 12, wherein the first functional surface and the second functional surface become small in width from one end portion thereof toward the other end portion thereof in the longitudinal direction of the body, and the first functional surface and the second functional surface have relatively large portions in width located opposite to each other in the longitudinal direction of the body. 20. (canceled) 21. A cosmetic ingredient applying device, comprising:
a container for storing a given amount of cosmetic substance therein; and the tip applicator as defined in claim 1 to apply the cosmetic substance to a user's skin. | 3,600 |
345,435 | 16,643,341 | 3,679 | An embodiment comprises: a housing; a bobbin disposed in the housing; a first coil disposed on the bobbin; a magnet disposed at the housing; an elastic part coupled to the bobbin and the housing; a circuit board disposed under the housing and comprising a pad part; a base disposed under the circuit board; a terminal disposed on the base; and a support part, one end of which is coupled to the elastic part and the other end of which is coupled to the terminal, wherein the pad part comprises: a first pad disposed beneath the circuit board; a second pad on the circuit board; and a third pad connecting the first pad and the second pad. | 1-10. (canceled) 11. A lens moving apparatus comprising:
a housing; a bobbin disposed in the housing; a first coil disposed at the bobbin; a magnet disposed at the housing; an elastic member coupled both to the bobbin and to the housing; a circuit board disposed under the housing and including a pad portion; a base disposed under the circuit board; a terminal disposed at the base; and a support, which is coupled at one end thereof to the elastic member and at a remaining end thereof to the terminal, wherein the pad portion comprises a first pad disposed at a lower portion of the circuit board, a second pad disposed at an upper portion of the circuit board and a third pad connecting the first pad to the second pad. 12. The lens moving apparatus according to claim 11, wherein the terminal comprises a first coupler coupled to the remaining end of the support and a second coupler coupled to the pad portion of the circuit board. 13. The lens moving apparatus according to claim 12, wherein the circuit board has a groove formed at a position corresponding to the second coupler of the terminal, and a portion of the third pad is disposed in the groove. 14. The lens moving apparatus according to claim 12, wherein the circuit board has a through via formed at a position corresponding to the second coupler of the terminal, and a portion of the third pad is disposed in the through via. 15. The lens moving apparatus according to claim 11, wherein the circuit board comprises a first insulation layer, a first conductive layer disposed on an upper surface of the first insulation layer, a second conductive layer disposed on a lower surface of the first insulation layer, and a third insulation layer disposed on a lower surface of the second conductive layer,
wherein the first pad is disposed on the lower surface of the second conductive layer, and the second pad is disposed on the upper surface of the first conductive layer, and wherein a lower surface of the first pad is disposed higher than a lower surface of the third insulation layer of the circuit board. 16. The lens moving apparatus according to claim 15, wherein a surface area of the first pad is larger than a surface area of the second pad. 17. The lens moving apparatus according to claim 12, further comprising solder disposed between the first pad and the second coupler. 18. The lens moving apparatus according to claim 17, wherein the solder is disposed between the second pad and the third pad. 19. The lens moving apparatus according to claim 11, wherein the first pad faces the terminal in an optical axis direction. 20. The lens moving apparatus according to claim 11, wherein the elastic member comprises a first elastic member disposed on an upper surface of the bobbin and a second elastic member disposed on a lower surface of the bobbin, and
wherein the support is coupled to the first elastic member. 21. The lens moving apparatus according to claim 11, wherein the third pad is disposed on a side surface of the circuit board. 22. A lens moving apparatus comprising:
a housing; a bobbin disposed in the housing; a first coil disposed at the bobbin; a magnet disposed at the housing; an elastic member coupled both to the bobbin and to the housing; a circuit board disposed under the housing and including a pad portion; a base disposed under the circuit board; a terminal disposed at the base; and a support, which is coupled at one end thereof to the elastic member and at a remaining end thereof to the terminal, wherein the terminal comprises:
a first coupler coupled to the remaining end of the support;
a second coupler coupled to the pad portion of the circuit board; and
a connector connecting a portion of one side surface of the first coupler to a portion of one side surface of the second coupler, and
wherein a width of the connector is less than a length of the one side surface of the first coupler and a length of the one side surface of the second coupler. 23. The lens moving apparatus according to claim 22, wherein a lower surface of the second coupler is positioned higher than an upper surface of the first coupler with respect to a lower surface of the base. 24. The lens moving apparatus according to claim 22, wherein the connector comprises a curved portion or a bent portion. 25. The lens moving apparatus according to claim 22, wherein a horizontal distance between the first coupler and the second coupler is less than a length of the second coupler in a horizontal direction, the horizontal direction being perpendicular to a width direction of the connector. 26. The lens moving apparatus according to claim 22, wherein a surface area of an upper surface of the connector is larger than a surface area of an upper surface of the second coupler, and
wherein a surface area of an upper surface of the first coupler is larger than the surface area of the upper surface of the second coupler. 27. The lens moving apparatus according to claim 25, wherein a length of the connector is less than the length of the second coupler in the horizontal direction, and
wherein the length of the connector is a distance between a first coupling region of the connector connected to a first side surface of the first coupler and a second coupling region of the connector connected to a first side surface of the second coupler. 28. The lens moving apparatus according to claim 22, wherein the second coupler is disposed between the base and the circuit board,
wherein the first coupler is disposed lower than the second coupler, and wherein the connector comprises a curved portion or a bent portion. 29. The lens moving apparatus according to claim 22, wherein the base comprises a protrusion projecting from a lower surface thereof, and
wherein the terminal comprises a hole coupled to the protrusion of the base. 30. A camera module comprising:
a lens; a lens moving apparatus for mounting the lens according to claim 11; and an image sensor. | An embodiment comprises: a housing; a bobbin disposed in the housing; a first coil disposed on the bobbin; a magnet disposed at the housing; an elastic part coupled to the bobbin and the housing; a circuit board disposed under the housing and comprising a pad part; a base disposed under the circuit board; a terminal disposed on the base; and a support part, one end of which is coupled to the elastic part and the other end of which is coupled to the terminal, wherein the pad part comprises: a first pad disposed beneath the circuit board; a second pad on the circuit board; and a third pad connecting the first pad and the second pad.1-10. (canceled) 11. A lens moving apparatus comprising:
a housing; a bobbin disposed in the housing; a first coil disposed at the bobbin; a magnet disposed at the housing; an elastic member coupled both to the bobbin and to the housing; a circuit board disposed under the housing and including a pad portion; a base disposed under the circuit board; a terminal disposed at the base; and a support, which is coupled at one end thereof to the elastic member and at a remaining end thereof to the terminal, wherein the pad portion comprises a first pad disposed at a lower portion of the circuit board, a second pad disposed at an upper portion of the circuit board and a third pad connecting the first pad to the second pad. 12. The lens moving apparatus according to claim 11, wherein the terminal comprises a first coupler coupled to the remaining end of the support and a second coupler coupled to the pad portion of the circuit board. 13. The lens moving apparatus according to claim 12, wherein the circuit board has a groove formed at a position corresponding to the second coupler of the terminal, and a portion of the third pad is disposed in the groove. 14. The lens moving apparatus according to claim 12, wherein the circuit board has a through via formed at a position corresponding to the second coupler of the terminal, and a portion of the third pad is disposed in the through via. 15. The lens moving apparatus according to claim 11, wherein the circuit board comprises a first insulation layer, a first conductive layer disposed on an upper surface of the first insulation layer, a second conductive layer disposed on a lower surface of the first insulation layer, and a third insulation layer disposed on a lower surface of the second conductive layer,
wherein the first pad is disposed on the lower surface of the second conductive layer, and the second pad is disposed on the upper surface of the first conductive layer, and wherein a lower surface of the first pad is disposed higher than a lower surface of the third insulation layer of the circuit board. 16. The lens moving apparatus according to claim 15, wherein a surface area of the first pad is larger than a surface area of the second pad. 17. The lens moving apparatus according to claim 12, further comprising solder disposed between the first pad and the second coupler. 18. The lens moving apparatus according to claim 17, wherein the solder is disposed between the second pad and the third pad. 19. The lens moving apparatus according to claim 11, wherein the first pad faces the terminal in an optical axis direction. 20. The lens moving apparatus according to claim 11, wherein the elastic member comprises a first elastic member disposed on an upper surface of the bobbin and a second elastic member disposed on a lower surface of the bobbin, and
wherein the support is coupled to the first elastic member. 21. The lens moving apparatus according to claim 11, wherein the third pad is disposed on a side surface of the circuit board. 22. A lens moving apparatus comprising:
a housing; a bobbin disposed in the housing; a first coil disposed at the bobbin; a magnet disposed at the housing; an elastic member coupled both to the bobbin and to the housing; a circuit board disposed under the housing and including a pad portion; a base disposed under the circuit board; a terminal disposed at the base; and a support, which is coupled at one end thereof to the elastic member and at a remaining end thereof to the terminal, wherein the terminal comprises:
a first coupler coupled to the remaining end of the support;
a second coupler coupled to the pad portion of the circuit board; and
a connector connecting a portion of one side surface of the first coupler to a portion of one side surface of the second coupler, and
wherein a width of the connector is less than a length of the one side surface of the first coupler and a length of the one side surface of the second coupler. 23. The lens moving apparatus according to claim 22, wherein a lower surface of the second coupler is positioned higher than an upper surface of the first coupler with respect to a lower surface of the base. 24. The lens moving apparatus according to claim 22, wherein the connector comprises a curved portion or a bent portion. 25. The lens moving apparatus according to claim 22, wherein a horizontal distance between the first coupler and the second coupler is less than a length of the second coupler in a horizontal direction, the horizontal direction being perpendicular to a width direction of the connector. 26. The lens moving apparatus according to claim 22, wherein a surface area of an upper surface of the connector is larger than a surface area of an upper surface of the second coupler, and
wherein a surface area of an upper surface of the first coupler is larger than the surface area of the upper surface of the second coupler. 27. The lens moving apparatus according to claim 25, wherein a length of the connector is less than the length of the second coupler in the horizontal direction, and
wherein the length of the connector is a distance between a first coupling region of the connector connected to a first side surface of the first coupler and a second coupling region of the connector connected to a first side surface of the second coupler. 28. The lens moving apparatus according to claim 22, wherein the second coupler is disposed between the base and the circuit board,
wherein the first coupler is disposed lower than the second coupler, and wherein the connector comprises a curved portion or a bent portion. 29. The lens moving apparatus according to claim 22, wherein the base comprises a protrusion projecting from a lower surface thereof, and
wherein the terminal comprises a hole coupled to the protrusion of the base. 30. A camera module comprising:
a lens; a lens moving apparatus for mounting the lens according to claim 11; and an image sensor. | 3,600 |
345,436 | 16,643,365 | 2,814 | The present invention may provide an organic electroluminescent device which exhibits low driving voltage as well as high efficiency by including an electron transporting layer material having an improved electron transporting ability. | 1.-13. (canceled) 14. An organic electrolumiminescent device, comprising:
a stack structure in which an anode, a hole transporting area; an emissive layer; an electron transporting area; and a cathode are sequentially stacked, wherein the electron transporting area comprises an electron transporting layer and an electron injection layer, wherein the electron transporting layer comprises a compound represented by the following Chemical Formula 1: 15. The organic electroluminescent device of claim 14, wherein the compound represented by Chemical Formula 1 is represented by the following. Chemical Formula 2 or 3: 16. The organic electroluminescent device of claim 14,
wherein Ar1 to Ar4 are each independently selected from the group consisting of a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, wherein the alkyl group, the aryl group, the heteroaryl group, the aryloxy group, the arylphosphine oxide group and the arylamine group of Ar1 to Ar4 are each independently substituted or unsubstituted with one or more kinds of substituents selected from the group consisting of deuterium, halogen, a cyano group, a nitro group, a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, and wherein when the substituents are plural in number, the substituents are the same as or different from each other, 17. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 has a LUMO of 2.5 eV or more. 18. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 has an energy difference (EHOMO−ELUMO) between HOMO and LUMO of 3.2 eV or more. 19. The organic electroluminescent device of claim 14,
wherein the election transporting area is co-deposited with an n-type dopant. 20. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 is represented by one of the following ET-01 to ET-21: 21. An organic electroluminescent device, comprising:
a stack structure in which an anode, a hole transporting area; an emissive layer; an electron transporting area; and a cathode are sequentially stacked, wherein the electron transporting area comprises an auxiliary electron transporting layer, an electron transporting layer and an electron injection layer, wherein the electron transporting layer comprises a compound represented by the following, Chemical Formula 1: 22. The organic electroluminescent device of claim 21, wherein the compound represented by Chemical Formula 1 is represented by the following Chemical Formula 2 or 3: 23. The organic electroluminescent device of claim 21,
wherein Ar1 to Ar4 are each independently selected from the group consisting of a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, wherein the alkyl group, the aryl group, the heteroaryl group, the aryloxy group, the arylphosphine oxide group and the arylamine group of Ar1 to Ar4 are each independently substituted or unsubstituted with one or more kinds of substituents selected from the group consisting of deuterium, halogen, a cyano group, a nitro group, a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, and wherein when the substituents are plural in number, the substituents are the same as or different from each other. 24. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 has a LUMO of 2.5 eV or more. 25. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 has an energy difference (EHOMO−ELUMO) between HOMO and LUMO of 3.2 eV or more. 26. The organic electroluminescent device of claim 21.
wherein the electron transporting area is co-deposited with an n-type dopant. 27. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 is represented by one of the following ET-01 to ET-21: 28. The organic electroluminescent device of claim 21,
wherein the auxiliary electron transporting has (i) an ionization potential of 5.5 eV or more, and (ii) EHOMO−ELUMO≥3.0 eV. 29. The organic electroluminescent device of claim 21, wherein the auxiliary electron transporting layer comprises a bipolar compound having both an electron withdrawing group (EWG) and an electron donating group (EDG), and wherein the bipolar compound has (iii) ΔEst<0.5 eV (ΔEst representing a difference between a singlet energy (S1) and a triplet energy (T1) of the compound). 30. The organic electroluminescent device of claim 29, wherein the bipolar compound comprises an EWG moiety represented by the following Chemical Formula 4: 31. The organic electroluminescent device of claim 30, wherein the moiety represented by Chemical Formula 4 is selected from the structure represented by the following Chemical Formula: 32. The organic electroluminescent device of claim 29, wherein the electron donating group (EDG) included in the bipolar compound is an EDG moiety having an electron donating property greater than that of the electron withdrawing group (EWG). | The present invention may provide an organic electroluminescent device which exhibits low driving voltage as well as high efficiency by including an electron transporting layer material having an improved electron transporting ability.1.-13. (canceled) 14. An organic electrolumiminescent device, comprising:
a stack structure in which an anode, a hole transporting area; an emissive layer; an electron transporting area; and a cathode are sequentially stacked, wherein the electron transporting area comprises an electron transporting layer and an electron injection layer, wherein the electron transporting layer comprises a compound represented by the following Chemical Formula 1: 15. The organic electroluminescent device of claim 14, wherein the compound represented by Chemical Formula 1 is represented by the following. Chemical Formula 2 or 3: 16. The organic electroluminescent device of claim 14,
wherein Ar1 to Ar4 are each independently selected from the group consisting of a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, wherein the alkyl group, the aryl group, the heteroaryl group, the aryloxy group, the arylphosphine oxide group and the arylamine group of Ar1 to Ar4 are each independently substituted or unsubstituted with one or more kinds of substituents selected from the group consisting of deuterium, halogen, a cyano group, a nitro group, a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, and wherein when the substituents are plural in number, the substituents are the same as or different from each other, 17. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 has a LUMO of 2.5 eV or more. 18. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 has an energy difference (EHOMO−ELUMO) between HOMO and LUMO of 3.2 eV or more. 19. The organic electroluminescent device of claim 14,
wherein the election transporting area is co-deposited with an n-type dopant. 20. The organic electroluminescent device of claim 14,
wherein the compound represented by Chemical Formula 1 is represented by one of the following ET-01 to ET-21: 21. An organic electroluminescent device, comprising:
a stack structure in which an anode, a hole transporting area; an emissive layer; an electron transporting area; and a cathode are sequentially stacked, wherein the electron transporting area comprises an auxiliary electron transporting layer, an electron transporting layer and an electron injection layer, wherein the electron transporting layer comprises a compound represented by the following, Chemical Formula 1: 22. The organic electroluminescent device of claim 21, wherein the compound represented by Chemical Formula 1 is represented by the following Chemical Formula 2 or 3: 23. The organic electroluminescent device of claim 21,
wherein Ar1 to Ar4 are each independently selected from the group consisting of a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, wherein the alkyl group, the aryl group, the heteroaryl group, the aryloxy group, the arylphosphine oxide group and the arylamine group of Ar1 to Ar4 are each independently substituted or unsubstituted with one or more kinds of substituents selected from the group consisting of deuterium, halogen, a cyano group, a nitro group, a C1 to C40 alkyl group, a C6 to C60 aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C6 to C60 aryloxy group, a C6 to C60 arylphosphine oxide group and a C6 to C60 arylamine group, and wherein when the substituents are plural in number, the substituents are the same as or different from each other. 24. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 has a LUMO of 2.5 eV or more. 25. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 has an energy difference (EHOMO−ELUMO) between HOMO and LUMO of 3.2 eV or more. 26. The organic electroluminescent device of claim 21.
wherein the electron transporting area is co-deposited with an n-type dopant. 27. The organic electroluminescent device of claim 21,
wherein the compound represented by Chemical Formula 1 is represented by one of the following ET-01 to ET-21: 28. The organic electroluminescent device of claim 21,
wherein the auxiliary electron transporting has (i) an ionization potential of 5.5 eV or more, and (ii) EHOMO−ELUMO≥3.0 eV. 29. The organic electroluminescent device of claim 21, wherein the auxiliary electron transporting layer comprises a bipolar compound having both an electron withdrawing group (EWG) and an electron donating group (EDG), and wherein the bipolar compound has (iii) ΔEst<0.5 eV (ΔEst representing a difference between a singlet energy (S1) and a triplet energy (T1) of the compound). 30. The organic electroluminescent device of claim 29, wherein the bipolar compound comprises an EWG moiety represented by the following Chemical Formula 4: 31. The organic electroluminescent device of claim 30, wherein the moiety represented by Chemical Formula 4 is selected from the structure represented by the following Chemical Formula: 32. The organic electroluminescent device of claim 29, wherein the electron donating group (EDG) included in the bipolar compound is an EDG moiety having an electron donating property greater than that of the electron withdrawing group (EWG). | 2,800 |
345,437 | 16,643,363 | 2,814 | The present invention can predict the occurrence of target-patient problem behavior prior the occurrence of such problem behavior. A biological information processing system includes: a feature calculation unit that calculates, from input biological information of the target patient, detection-use feature time-series data which indicates a feature related to the target patient: and an agitation detection unit that processes the detection-use feature time-series data on the basis of a pre-acquired discrimination parameter, that calculates the current agitation score of the target patient, and that detects the current agitation state of the target patient prior to the target-patient problem behavior. | 1. A biological information processing system comprising:
a feature calculation unit configured to calculate, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and an agitation detection unit configured to process the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, to calculate a current agitation score of the target patient, and to detect a current agitation state of the target patient prior to a problem behavior of the target patient. 2. The biological information processing system as claimed in claim 1, comprising a storage unit configured to store the discrimination parameter,
wherein the storage unit is configured to store the discrimination parameter which is calculated on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 3. The biological information processing system as claimed in claim 1, wherein the agitation detection unit is configured to calculate the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data from the feature calculation unit. 4. The biological information processing system as claimed in claim 3, wherein the agitation detection unit is configured to calculate the current agitation score of the target patient by computation processing including an operation of multiplying the discrimination parameter by the detection-use feature time-series data from the feature calculation unit. 5. The biological information processing system as claimed in claim 1, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 6. The biological information processing system as claimed in claim 1, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. 7. The biological information processing system as claimed in claim 1, wherein the agitation detection unit is configured to detect the current agitation state of the target patient using additional information related to the target patient in addition to the detection-use feature time-series data. 8. (canceled) 9. A biological information processing method comprising:
calculating, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and processing the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, calculating a current agitation score of the target patient, and detecting a current agitation state of the target patient prior to a problem behavior of the target patient. 10. The biological information processing method as claimed in claim 9, comprising calculating the discrimination parameter on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 11. (canceled) 12. A non-transitory computer readable recording medium recording a computer program which causes a computer to execute the steps of:
calculating, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and processing the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, calculating a current agitation score of the target patient, and detecting a current agitation state of the target patient prior to a problem behavior of the target patient. 13. (canceled) 14. The biological information processing method as claimed in claim 9, wherein the calculating the current agitation score of the target patient calculates the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data. 15. The biological information processing method as claimed in claim 14, wherein the calculating the current agitation score of the target patient calculates the current agitation score of the target patient by computation processing including an operation for multiplying the discrimination parameter by the detection-use feature time-series data. 16. The biological information processing method as claimed in claim 9, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 17. The biological information processing method as claimed in claim 9, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. 18. The biological information processing method as claimed in claim 9, wherein the detecting the current agitation state of the target patient detects the current agitation state of the target patient using additional information related to the target patient in addition to the detection-use feature time-series data. 19. The non-transitory computer readable recording medium as claimed in claim 12, wherein the computer program causes the computer to execute the step of calculating the discrimination parameter on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 20. The non-transitory computer readable recording medium as claimed in claim 12, wherein the computer program causes the computer to execute the step of calculating the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data. 21. The non-transitory computer readable recording medium as claimed in claim 20, wherein the computer program causes the computer to execute the step of calculating the current agitation score of the target patient by computation processing including an operation for multiplying the discrimination parameter by the detection-use feature time-series data. 22. The non-transitory computer readable recording medium as claimed in claim 12, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 23. The non-transitory computer readable recording medium as claimed in claim 12, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. | The present invention can predict the occurrence of target-patient problem behavior prior the occurrence of such problem behavior. A biological information processing system includes: a feature calculation unit that calculates, from input biological information of the target patient, detection-use feature time-series data which indicates a feature related to the target patient: and an agitation detection unit that processes the detection-use feature time-series data on the basis of a pre-acquired discrimination parameter, that calculates the current agitation score of the target patient, and that detects the current agitation state of the target patient prior to the target-patient problem behavior.1. A biological information processing system comprising:
a feature calculation unit configured to calculate, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and an agitation detection unit configured to process the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, to calculate a current agitation score of the target patient, and to detect a current agitation state of the target patient prior to a problem behavior of the target patient. 2. The biological information processing system as claimed in claim 1, comprising a storage unit configured to store the discrimination parameter,
wherein the storage unit is configured to store the discrimination parameter which is calculated on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 3. The biological information processing system as claimed in claim 1, wherein the agitation detection unit is configured to calculate the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data from the feature calculation unit. 4. The biological information processing system as claimed in claim 3, wherein the agitation detection unit is configured to calculate the current agitation score of the target patient by computation processing including an operation of multiplying the discrimination parameter by the detection-use feature time-series data from the feature calculation unit. 5. The biological information processing system as claimed in claim 1, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 6. The biological information processing system as claimed in claim 1, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. 7. The biological information processing system as claimed in claim 1, wherein the agitation detection unit is configured to detect the current agitation state of the target patient using additional information related to the target patient in addition to the detection-use feature time-series data. 8. (canceled) 9. A biological information processing method comprising:
calculating, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and processing the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, calculating a current agitation score of the target patient, and detecting a current agitation state of the target patient prior to a problem behavior of the target patient. 10. The biological information processing method as claimed in claim 9, comprising calculating the discrimination parameter on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 11. (canceled) 12. A non-transitory computer readable recording medium recording a computer program which causes a computer to execute the steps of:
calculating, from input biological information of a target patient, detection-use feature time-series data indicative of a feature related to the target patient; and processing the detection-use feature time-series data on the basis of a discrimination parameter which is preliminarily acquired, calculating a current agitation score of the target patient, and detecting a current agitation state of the target patient prior to a problem behavior of the target patient. 13. (canceled) 14. The biological information processing method as claimed in claim 9, wherein the calculating the current agitation score of the target patient calculates the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data. 15. The biological information processing method as claimed in claim 14, wherein the calculating the current agitation score of the target patient calculates the current agitation score of the target patient by computation processing including an operation for multiplying the discrimination parameter by the detection-use feature time-series data. 16. The biological information processing method as claimed in claim 9, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 17. The biological information processing method as claimed in claim 9, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. 18. The biological information processing method as claimed in claim 9, wherein the detecting the current agitation state of the target patient detects the current agitation state of the target patient using additional information related to the target patient in addition to the detection-use feature time-series data. 19. The non-transitory computer readable recording medium as claimed in claim 12, wherein the computer program causes the computer to execute the step of calculating the discrimination parameter on the basis of a first feature time-series data for learning processing, obtained from biological information in an agitation state and a second feature time-series data for learning processing, obtained from biological information in a non-agitation state. 20. The non-transitory computer readable recording medium as claimed in claim 12, wherein the computer program causes the computer to execute the step of calculating the current agitation score of the target patient using the discrimination parameter and the detection-use feature time-series data. 21. The non-transitory computer readable recording medium as claimed in claim 20, wherein the computer program causes the computer to execute the step of calculating the current agitation score of the target patient by computation processing including an operation for multiplying the discrimination parameter by the detection-use feature time-series data. 22. The non-transitory computer readable recording medium as claimed in claim 12, wherein the discrimination parameter comprises a linear parameter which is obtained by a linear machine learning technique or a non-linear parameter which is obtained by a non-linear machine learning technique. 23. The non-transitory computer readable recording medium as claimed in claim 12, wherein the biological information comprises information selected from the group consisting of a heartbeat, breathing, blood pressure, body temperature, a level of consciousness, skin temperature, skin conductance response, an electrocardiographic waveform, and an electroencephalographic waveform. | 2,800 |
345,438 | 16,643,339 | 2,814 | Durable and scratch resistant articles including low-reflectance optical coating with gradient portion. In some embodiments, an article comprises: a substrate comprising a first major surface; and an optical coating disposed over the first major surface. The optical coating comprises: a second major surface; a thickness; and a first gradient portion. A refractive index of the optical coating varies along a thickness of the optical coating. The difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater. The absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion. The article exhibits a single side photopic average light reflectance of 3% or less, and a maximum hardness from 10 GPa to 30 GPa. | 1. An article comprising:
a substrate comprising a first major surface; and an optical coating disposed over the first major surface, the optical coating comprising:
a second major surface opposite the first major surface,
a thickness in a direction normal to the second major surface, and
a first gradient portion,
wherein: a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface; the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater; the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion; wherein the article exhibits: a single side photopic average light reflectance of 3% or less, measured at the second major surface, and a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface; wherein slope is measured along the thickness over a refractive index change of 0.04. 2. The article of claim 1, wherein the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater. 3. (canceled) 4. The article of claim 1, wherein the article exhibits a photopic average transmittance of 80% or more, measured at the second major surface. 5. The article of claim 1, wherein:
everywhere along the thickness of the first gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.001/nm to 0.02/nm. 6-8. (canceled) 9. The article of claim 1, wherein the optical coating further comprises a high hardness portion, wherein:
the thickness of the high hardness portion is 200 nm or more; the average index of refraction in the high hardness portion is 1.6 or more; and the maximum hardness of the high hardness portion is 10 GPa or more, wherein maximum hardness is measured by indenting the thick high hardness portion with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more. 10. (canceled) 11. The article of claim 9, wherein for 95% or more of the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 12. The article of claim 9, wherein:
everywhere along the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 13. The article of claim 9, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
the first gradient portion; and the high hardness portion in contact with the first gradient portion; wherein, where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less. 14. The article of claim 9, wherein the optical coating further comprises a second gradient portion disposed between the high hardness portion and the substrate, wherein the second gradient portion is in contact with the high hardness portion, and wherein:
the difference between the maximum refractive index of the second gradient portion and the minimum refractive index of the second gradient portion is 0.05 or greater; everywhere along the thickness of the second gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.1/nm or less. 15. The article of claim 14, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the refractive index of the second gradient portion monotonically decreases along the thickness in a direction moving away from the second major surface. 16. The article of claim 14, wherein the optical coating consists of the first gradient portion, the high hardness portion, and the second gradient portion, and wherein the optical coating is in direct contact with the substrate, and wherein the second major surface is an outer surface. 17. (canceled) 18. The article of claim 1, wherein the articles exhibit a single side reflected color range for all viewing angles from 0 to 60 degrees, measured at the second major surface, that comprises all a* and all b* points comprising absolute values of 20 or less. 19-21. (canceled) 22. The article of claim 1, wherein the article comprises a single side average photopic average light reflectance of 2% or less, measured at the second major surface. 23-26. (canceled) 27. The article of claim 1, wherein the article exhibits an average transmittance or average reflectance comprising an average oscillation amplitude of 10 percentage points or less, over the optical wavelength regime. 28. The article of claim 1, wherein optical coating comprises a thickness in the range from about 0.5 μm to about 3 μm. 29. The article of claim 9, wherein the cumulative thickness of any parts of the optical coating between the high hardness portion and the second major surface comprising a RI of 1.6 or less is 200 nm or less. 30. The article of claim 1, wherein the article comprises a maximum hardness in the range from about 12 GPa to about 30 Gpa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface. 31. (canceled) 32. The article of claim 1, wherein the optical coating comprises a compositional gradient, the compositional gradient comprising at least two of Si, Al, N, and O. 33. The article of claim 1, wherein the optical coating comprises a gradient selected from at least one of a porosity gradient, a density gradient and an elastic modulus gradient. 34-38. (canceled) 39. A method of forming an article comprising:
obtaining a substrate comprising a first major surface and comprising an amorphous substrate or a crystalline substrate; disposing an optical coating on the first major surface, the optical coating comprising a second major surface opposite the first major surface and a thickness in a direction normal to the second major surface, creating a refractive index gradient along at least a first gradient portion of the thickness of the optical coating, wherein:
a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface;
the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater;
the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion;
wherein the article exhibits:
a single side photopic average light reflectance of 3% or less, measured at the second major surface, and
a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface;
wherein slope is measured along the thickness over a refractive index change of 0.04. 40-41. (canceled) | Durable and scratch resistant articles including low-reflectance optical coating with gradient portion. In some embodiments, an article comprises: a substrate comprising a first major surface; and an optical coating disposed over the first major surface. The optical coating comprises: a second major surface; a thickness; and a first gradient portion. A refractive index of the optical coating varies along a thickness of the optical coating. The difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater. The absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion. The article exhibits a single side photopic average light reflectance of 3% or less, and a maximum hardness from 10 GPa to 30 GPa.1. An article comprising:
a substrate comprising a first major surface; and an optical coating disposed over the first major surface, the optical coating comprising:
a second major surface opposite the first major surface,
a thickness in a direction normal to the second major surface, and
a first gradient portion,
wherein: a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface; the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater; the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion; wherein the article exhibits: a single side photopic average light reflectance of 3% or less, measured at the second major surface, and a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface; wherein slope is measured along the thickness over a refractive index change of 0.04. 2. The article of claim 1, wherein the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater. 3. (canceled) 4. The article of claim 1, wherein the article exhibits a photopic average transmittance of 80% or more, measured at the second major surface. 5. The article of claim 1, wherein:
everywhere along the thickness of the first gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.001/nm to 0.02/nm. 6-8. (canceled) 9. The article of claim 1, wherein the optical coating further comprises a high hardness portion, wherein:
the thickness of the high hardness portion is 200 nm or more; the average index of refraction in the high hardness portion is 1.6 or more; and the maximum hardness of the high hardness portion is 10 GPa or more, wherein maximum hardness is measured by indenting the thick high hardness portion with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more. 10. (canceled) 11. The article of claim 9, wherein for 95% or more of the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 12. The article of claim 9, wherein:
everywhere along the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 13. The article of claim 9, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
the first gradient portion; and the high hardness portion in contact with the first gradient portion; wherein, where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less. 14. The article of claim 9, wherein the optical coating further comprises a second gradient portion disposed between the high hardness portion and the substrate, wherein the second gradient portion is in contact with the high hardness portion, and wherein:
the difference between the maximum refractive index of the second gradient portion and the minimum refractive index of the second gradient portion is 0.05 or greater; everywhere along the thickness of the second gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.1/nm or less. 15. The article of claim 14, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the refractive index of the second gradient portion monotonically decreases along the thickness in a direction moving away from the second major surface. 16. The article of claim 14, wherein the optical coating consists of the first gradient portion, the high hardness portion, and the second gradient portion, and wherein the optical coating is in direct contact with the substrate, and wherein the second major surface is an outer surface. 17. (canceled) 18. The article of claim 1, wherein the articles exhibit a single side reflected color range for all viewing angles from 0 to 60 degrees, measured at the second major surface, that comprises all a* and all b* points comprising absolute values of 20 or less. 19-21. (canceled) 22. The article of claim 1, wherein the article comprises a single side average photopic average light reflectance of 2% or less, measured at the second major surface. 23-26. (canceled) 27. The article of claim 1, wherein the article exhibits an average transmittance or average reflectance comprising an average oscillation amplitude of 10 percentage points or less, over the optical wavelength regime. 28. The article of claim 1, wherein optical coating comprises a thickness in the range from about 0.5 μm to about 3 μm. 29. The article of claim 9, wherein the cumulative thickness of any parts of the optical coating between the high hardness portion and the second major surface comprising a RI of 1.6 or less is 200 nm or less. 30. The article of claim 1, wherein the article comprises a maximum hardness in the range from about 12 GPa to about 30 Gpa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface. 31. (canceled) 32. The article of claim 1, wherein the optical coating comprises a compositional gradient, the compositional gradient comprising at least two of Si, Al, N, and O. 33. The article of claim 1, wherein the optical coating comprises a gradient selected from at least one of a porosity gradient, a density gradient and an elastic modulus gradient. 34-38. (canceled) 39. A method of forming an article comprising:
obtaining a substrate comprising a first major surface and comprising an amorphous substrate or a crystalline substrate; disposing an optical coating on the first major surface, the optical coating comprising a second major surface opposite the first major surface and a thickness in a direction normal to the second major surface, creating a refractive index gradient along at least a first gradient portion of the thickness of the optical coating, wherein:
a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface;
the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.05 or greater;
the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion;
wherein the article exhibits:
a single side photopic average light reflectance of 3% or less, measured at the second major surface, and
a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface;
wherein slope is measured along the thickness over a refractive index change of 0.04. 40-41. (canceled) | 2,800 |
345,439 | 16,643,367 | 2,814 | A polymer material for a lithium secondary battery having ionic conductivity and electronic conductivity at the same time, and a method for preparing the same. The polymer material includes a polythiophene-based polymer and a conductive polymer, and the polymer material may be formed by forming a polythiophene-based polymer, forming a conductive polymer, and heat-treating the polythiophene-based polymer and the conductive polymer. | 1. A polymer material for a lithium secondary battery comprising:
a polythiophene-based polymer represented by the following Formula 1: 2. The polymer material for the lithium secondary battery according to claim 1, wherein the conductive polymer comprises poly-(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). 3. The polymer material for the lithium secondary battery according to claim 1, wherein the polythiophene-based polymer and the conductive polymer are contained in a weight ratio of 95:5 to 80:20. 4. The polymer material for the lithium secondary battery according to claim 1, wherein the polymer material has an ionic conductivity of 10−6 S/cm to 10−4 S/cm. 5. The polymer material for the lithium secondary battery according to claim 1, wherein the polymer material has an electron conductivity of 10−8 S/cm to 10−2 S/cm. 6. A positive electrode for the lithium secondary battery comprising the polymer material according to claim 1. 7. A lithium secondary battery comprising the positive electrode according to claim 6. 8. A method for preparing the polymer material for the lithium secondary battery according to claim 1, comprising:
(a) forming a polythiophene-based polymer represented by the following Formula 1; (b) forming a conductive polymer; and (c) heat treating the polythiophene-based polymer and the conductive polymer: 9. The method for preparing the polymer material for the lithium secondary battery according to claim 8, wherein the step (a) comprises,
(a1) adding methanol and sulfuric acid to thiophene acetic acid to form thiophene methyl acetate; (a2) adding iron chloride to thiophene methyl acetate to form polythiophene methyl acetate; (a3) adding sodium hydroxide to the polythiophene methyl acetate to form polythiophene sodium acetate; (a4) adding hydrogen chloride to the polythiophene sodium acetate to form polythiophene acetic acid; and (a5) adding polyethylene glycol to the polythiophene acetic acid to form poly(3-polyethylene glycol thiophene). 10. The method for preparing the polymer material for the lithium secondary battery according to claim 8, wherein in the step (c), the heat treatment is performed at 120° C. to 250° C. 11. A polythiophene-based polymer represented by the following Formula 1: 12. A method for preparing the polythiophene-based polymer according to claim 11, wherein the method comprises,
adding methanol and sulfuric acid to thiophene acetic acid to form thiophene methyl acetate; adding iron chloride to thiophene methyl acetate to form polythiophene methyl acetate; adding sodium hydroxide to the polythiophene methyl acetate to form polythiophene sodium acetate; adding hydrogen chloride to the polythiophene sodium acetate to form polythiophene acetic acid; and adding polyethylene glycol to the polythiophene acetic acid to form poly(3-polyethylene glycol thiophene). | A polymer material for a lithium secondary battery having ionic conductivity and electronic conductivity at the same time, and a method for preparing the same. The polymer material includes a polythiophene-based polymer and a conductive polymer, and the polymer material may be formed by forming a polythiophene-based polymer, forming a conductive polymer, and heat-treating the polythiophene-based polymer and the conductive polymer.1. A polymer material for a lithium secondary battery comprising:
a polythiophene-based polymer represented by the following Formula 1: 2. The polymer material for the lithium secondary battery according to claim 1, wherein the conductive polymer comprises poly-(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). 3. The polymer material for the lithium secondary battery according to claim 1, wherein the polythiophene-based polymer and the conductive polymer are contained in a weight ratio of 95:5 to 80:20. 4. The polymer material for the lithium secondary battery according to claim 1, wherein the polymer material has an ionic conductivity of 10−6 S/cm to 10−4 S/cm. 5. The polymer material for the lithium secondary battery according to claim 1, wherein the polymer material has an electron conductivity of 10−8 S/cm to 10−2 S/cm. 6. A positive electrode for the lithium secondary battery comprising the polymer material according to claim 1. 7. A lithium secondary battery comprising the positive electrode according to claim 6. 8. A method for preparing the polymer material for the lithium secondary battery according to claim 1, comprising:
(a) forming a polythiophene-based polymer represented by the following Formula 1; (b) forming a conductive polymer; and (c) heat treating the polythiophene-based polymer and the conductive polymer: 9. The method for preparing the polymer material for the lithium secondary battery according to claim 8, wherein the step (a) comprises,
(a1) adding methanol and sulfuric acid to thiophene acetic acid to form thiophene methyl acetate; (a2) adding iron chloride to thiophene methyl acetate to form polythiophene methyl acetate; (a3) adding sodium hydroxide to the polythiophene methyl acetate to form polythiophene sodium acetate; (a4) adding hydrogen chloride to the polythiophene sodium acetate to form polythiophene acetic acid; and (a5) adding polyethylene glycol to the polythiophene acetic acid to form poly(3-polyethylene glycol thiophene). 10. The method for preparing the polymer material for the lithium secondary battery according to claim 8, wherein in the step (c), the heat treatment is performed at 120° C. to 250° C. 11. A polythiophene-based polymer represented by the following Formula 1: 12. A method for preparing the polythiophene-based polymer according to claim 11, wherein the method comprises,
adding methanol and sulfuric acid to thiophene acetic acid to form thiophene methyl acetate; adding iron chloride to thiophene methyl acetate to form polythiophene methyl acetate; adding sodium hydroxide to the polythiophene methyl acetate to form polythiophene sodium acetate; adding hydrogen chloride to the polythiophene sodium acetate to form polythiophene acetic acid; and adding polyethylene glycol to the polythiophene acetic acid to form poly(3-polyethylene glycol thiophene). | 2,800 |
345,440 | 16,643,377 | 2,814 | The present invention relates to a method of TNF-α-related disease by subcutaneously administering an antibody binding to TNF-α (anti-TNF-α antibody). A treatment method, composition, kit or use according to the present invention reduces the time for administration and the time for patients to stay in hospitals, thereby improving patient convenience and the quality of life of the patient. This provides the advantage of improving the patient's satisfaction. | 1. A method for treatment of TNF-α-related disease, comprising a step of administering to a patient a pharmaceutical composition comprising an anti-TNF-α antibody or its antigen binding fragment, wherein the anti-TNF-α antibody or its antigen binding fragment is administered subcutaneously to the patient at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. 2. The method of claim 1, wherein the TNF-α-related disease is selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. 3. The method of claim 2, wherein the TNF-α-related disease is rheumatoid arthritis. 4. The method of claim 3, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 90 to 180 mg. 5. The method of claim 2, wherein the TNF-α-related disease is selected from the group consisting of ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. 6. The method of claim 5, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 120 to 240 mg. 7. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 80 to 100 mg, 110 to 130 mg, 170 to 190 mg, or 230 to 250 mg. 8. The method of claim 7, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 90 mg, 120 mg, 180 mg or 240 mg. 9. The method of claim 1, further comprising a step of determining the dose according to the body weight of the patient, wherein the anti-TNF-α antibody or its antigen binding fragment is administered at a dose of 90 to 180 mg when the body weight of the patient is less than 80 kg, and is administered at a dose of 190 to 270 mg when the body weight of the patient is more than 80 kg. 10. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at intervals of 1, 2, 3, 4, 5, 6, 7 or 8 weeks. 11. The method of claim 10, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at intervals of 2 or 4 weeks. 12. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is co-administered with a disease-modifying anti rheumatic drug (DMARD). 13. The method of claim 12, wherein the disease-modifying anti rheumatic drug (DMARD) is selected from the group consisting of methotrexate, leflunomide, sulfasalazine and hydroxychloroquine. 14. The method of claim 1, wherein the patient is a patient who has been administered at least once intravenously with the anti-TNF-α antibody or its antigen-binding fragment before the subcutaneous administration. 15. The method of claim 14, wherein the patient is a patient who has been administered intravenously with the anti-TNF-α antibody or its antigen-binding fragment at a dose of 1 to 10 mg/kg for each administration. 16. The method of claim 14, wherein the first subcutaneous administration is performed 2 to 8 weeks after the last intravenous administration. 17. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 3 to 16 μg/mL after it is administered subcutaneously to the patient. 18. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 9 to 32 μg/mL after it is administered subcutaneously to the patient. 19. The method of claim 1, wherein the patient after the subcutaneous administration has one or more of the following characteristics:
a) a decrease in DAS28 (Disease Activity Score in 28 joints) of at least 2.0; or b) a decrease in CDAI (Crohn's disease activity index) of at least 70. 20. The method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics:
a) a patient who has an inadequate response to disease-modifying anti rheumatic drugs (DMARDs), including methotrexate; b) a patient who has not previously been treated with methotrexate and other DMARDs; c) a patient who exhibits elevated serologic indicators associated with severe axial-predominant symptoms and inflammation, which show no proper response to common therapies; or d) a patient who does not respond to, or is contraindicated to, or has intolerance to methotrexate, cyclosporine, or systemic therapies including psoralen ultraviolet A therapy (PUVA). 21. The method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics:
a) a patient who has an inadequate response to, or has intolerance to, or is contraindicated for treatment with corticosteroids, 6-mercaptopurine, azathioprine or immunosuppressants; or b) a patient who does not respond to common therapies, including antibiotic, excretion or immunosuppressive therapies. 22. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light-chain variable region comprising a CDR1 domain comprising an amino acid sequence of SEQ ID NO: 1, a CDR2 domain comprising an amino acid sequence of SEQ ID NO: 2, and a CDR3 domain comprising an amino acid sequence of SEQ ID NO: 3; and
a heavy-chain variable region comprising a CDR1 domain comprising an amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising an amino acid sequence of SEQ ID NO: 5, and a CDR3 domain comprising an amino acid sequence of SEQ ID NO: 6. 23. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light-chain variable region comprising an amino acid sequence of SEQ ID NO: 7; and
a heavy-chain variable region comprising an amino acid sequence of SEQ ID NO: 8. 24. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light chain comprising an amino acid sequence of SEQ ID NO: 9; and
a heavy chain comprising an amino acid sequence of SEQ ID NO: 10. 25. The method of claim 1, wherein the anti-TNF-α antibody is infliximab. 26. The method of claim 1, wherein the composition comprising the anti-TNF-α antibody or its antigen binding fragment contains: (A) 90 to 180 mg/ml of the anti-TNFα antibody or its antibody binding fragment; (B) 0.02 to 0.1% (w/v) of polysorbate; (C) 1 to 10% (w/v) of sorbitol; and (D) 1 to 50 mM of a buffer comprising acetate. 27. The method of claim 1, wherein the composition comprising the anti-TNF-α antibody or its antigen binding fragment is filled in a pre-filled syringe or an auto-injector before administration to the patient. 28. A pharmaceutical composition for treatment of TNF-α-related disease, comprising an anti-TNF-α antibody or its antigen binding fragment, wherein the anti-TNF-α antibody or its antigen binding fragment is to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. 29. A kit comprising:
(a) a pharmaceutical composition comprising an anti-TNF-α antibody or its antigen binding fragment; and (b) instructions that direct the pharmaceutical composition to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks in order to treat a patient having TNF-α-related disease. 30. Use of an anti-TNF-α antibody or its antigen binding fragment in preparation of a pharmaceutical composition to be administered subcutaneously to a patient in order to treat TNF-α-related disease, wherein the anti-TNF-α antibody or its antigen binding fragment is to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. | The present invention relates to a method of TNF-α-related disease by subcutaneously administering an antibody binding to TNF-α (anti-TNF-α antibody). A treatment method, composition, kit or use according to the present invention reduces the time for administration and the time for patients to stay in hospitals, thereby improving patient convenience and the quality of life of the patient. This provides the advantage of improving the patient's satisfaction.1. A method for treatment of TNF-α-related disease, comprising a step of administering to a patient a pharmaceutical composition comprising an anti-TNF-α antibody or its antigen binding fragment, wherein the anti-TNF-α antibody or its antigen binding fragment is administered subcutaneously to the patient at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. 2. The method of claim 1, wherein the TNF-α-related disease is selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. 3. The method of claim 2, wherein the TNF-α-related disease is rheumatoid arthritis. 4. The method of claim 3, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 90 to 180 mg. 5. The method of claim 2, wherein the TNF-α-related disease is selected from the group consisting of ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. 6. The method of claim 5, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 120 to 240 mg. 7. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 80 to 100 mg, 110 to 130 mg, 170 to 190 mg, or 230 to 250 mg. 8. The method of claim 7, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at a dose of 90 mg, 120 mg, 180 mg or 240 mg. 9. The method of claim 1, further comprising a step of determining the dose according to the body weight of the patient, wherein the anti-TNF-α antibody or its antigen binding fragment is administered at a dose of 90 to 180 mg when the body weight of the patient is less than 80 kg, and is administered at a dose of 190 to 270 mg when the body weight of the patient is more than 80 kg. 10. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at intervals of 1, 2, 3, 4, 5, 6, 7 or 8 weeks. 11. The method of claim 10, wherein the anti-TNF-α antibody or its antigen binding fragment is administered to the patient at intervals of 2 or 4 weeks. 12. The method of claim 1, wherein the anti-TNF-α antibody or its antigen binding fragment is co-administered with a disease-modifying anti rheumatic drug (DMARD). 13. The method of claim 12, wherein the disease-modifying anti rheumatic drug (DMARD) is selected from the group consisting of methotrexate, leflunomide, sulfasalazine and hydroxychloroquine. 14. The method of claim 1, wherein the patient is a patient who has been administered at least once intravenously with the anti-TNF-α antibody or its antigen-binding fragment before the subcutaneous administration. 15. The method of claim 14, wherein the patient is a patient who has been administered intravenously with the anti-TNF-α antibody or its antigen-binding fragment at a dose of 1 to 10 mg/kg for each administration. 16. The method of claim 14, wherein the first subcutaneous administration is performed 2 to 8 weeks after the last intravenous administration. 17. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 3 to 16 μg/mL after it is administered subcutaneously to the patient. 18. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 9 to 32 μg/mL after it is administered subcutaneously to the patient. 19. The method of claim 1, wherein the patient after the subcutaneous administration has one or more of the following characteristics:
a) a decrease in DAS28 (Disease Activity Score in 28 joints) of at least 2.0; or b) a decrease in CDAI (Crohn's disease activity index) of at least 70. 20. The method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics:
a) a patient who has an inadequate response to disease-modifying anti rheumatic drugs (DMARDs), including methotrexate; b) a patient who has not previously been treated with methotrexate and other DMARDs; c) a patient who exhibits elevated serologic indicators associated with severe axial-predominant symptoms and inflammation, which show no proper response to common therapies; or d) a patient who does not respond to, or is contraindicated to, or has intolerance to methotrexate, cyclosporine, or systemic therapies including psoralen ultraviolet A therapy (PUVA). 21. The method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics:
a) a patient who has an inadequate response to, or has intolerance to, or is contraindicated for treatment with corticosteroids, 6-mercaptopurine, azathioprine or immunosuppressants; or b) a patient who does not respond to common therapies, including antibiotic, excretion or immunosuppressive therapies. 22. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light-chain variable region comprising a CDR1 domain comprising an amino acid sequence of SEQ ID NO: 1, a CDR2 domain comprising an amino acid sequence of SEQ ID NO: 2, and a CDR3 domain comprising an amino acid sequence of SEQ ID NO: 3; and
a heavy-chain variable region comprising a CDR1 domain comprising an amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising an amino acid sequence of SEQ ID NO: 5, and a CDR3 domain comprising an amino acid sequence of SEQ ID NO: 6. 23. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light-chain variable region comprising an amino acid sequence of SEQ ID NO: 7; and
a heavy-chain variable region comprising an amino acid sequence of SEQ ID NO: 8. 24. The method of claim 1, wherein the anti-TNF-α antibody or its antigen-binding fragment comprises:
a light chain comprising an amino acid sequence of SEQ ID NO: 9; and
a heavy chain comprising an amino acid sequence of SEQ ID NO: 10. 25. The method of claim 1, wherein the anti-TNF-α antibody is infliximab. 26. The method of claim 1, wherein the composition comprising the anti-TNF-α antibody or its antigen binding fragment contains: (A) 90 to 180 mg/ml of the anti-TNFα antibody or its antibody binding fragment; (B) 0.02 to 0.1% (w/v) of polysorbate; (C) 1 to 10% (w/v) of sorbitol; and (D) 1 to 50 mM of a buffer comprising acetate. 27. The method of claim 1, wherein the composition comprising the anti-TNF-α antibody or its antigen binding fragment is filled in a pre-filled syringe or an auto-injector before administration to the patient. 28. A pharmaceutical composition for treatment of TNF-α-related disease, comprising an anti-TNF-α antibody or its antigen binding fragment, wherein the anti-TNF-α antibody or its antigen binding fragment is to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. 29. A kit comprising:
(a) a pharmaceutical composition comprising an anti-TNF-α antibody or its antigen binding fragment; and (b) instructions that direct the pharmaceutical composition to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks in order to treat a patient having TNF-α-related disease. 30. Use of an anti-TNF-α antibody or its antigen binding fragment in preparation of a pharmaceutical composition to be administered subcutaneously to a patient in order to treat TNF-α-related disease, wherein the anti-TNF-α antibody or its antigen binding fragment is to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks. | 2,800 |
345,441 | 16,643,346 | 2,814 | Fuel compositions comprising at least 10 ppm by weight of a succinic ester acid amine salt or a succinamide acid amine salt (both “amine salt(s)”). The amine salt is the product of (a) and (b), wherein: (a) is an amine with (i) at least one tertiary nitrogen and (ii) at least one hydroxy alkyl functional group and/or at least one secondary amine functionality; and (b) is a hydrocarbyl-substituted succinic acid/or anhydride. The molar ratio of (a) to (b) may range from 3:1 to 1:3. The fuel composition may comprise gasoline, oxygenate, or mixtures thereof. Methods and uses for reducing carbonaceous deposits in an engine comprising operating the engine using the fuel composition having an amine salt therein. | 1. A fuel composition comprising gasoline, oxygenate, or mixtures thereof and a succinic ester acid amine salt or a succinamide acid amine salt (both “amine salt(s)”) that is the product of (a) and (b), wherein:
(a) is an amine with (i) at least one tertiary nitrogen and (ii) at least one hydroxy alkyl functionality and/or at least one secondary amine functionality;
(b) is a hydrocarbyl-substituted succinic acid and/or anhydride; and 2. The fuel composition of claim 1, wherein the molar ratio of (a) to (b) ranges from 3:1 to 1:3. 3. The fuel composition of claim 1, wherein at least a portion of the amine salt has the formula (I): 4. The fuel composition of claim 1, wherein at least a portion of the amine salt has the formula (II): 5. The fuel composition of claim 3 or 4, wherein R1 is a C8 to C25 or C12 to C16 hydrocarbyl group. 6. The fuel composition of claim 3, wherein the amine salt is the product of N,N-methyldiethanolamine and hexadecenylsuccinic anhydride. 7. The fuel composition of claim 4, wherein the amine salt is the product of N1-(3-(dimethylamino)propyl)-N3,N3-dimethylpropane-1,3-diamine and hexadecenylsuccinic anhydride. 8. The fuel composition of claim 1, wherein the amine is an alkoxylated fatty amine. 9. The fuel composition of claim 1, further comprising an alkoxylated fatty amine in addition to the amine used to make the reaction product of the amine salt. 10. The fuel composition of claim 8 or 9, wherein said alkoxylated fatty amine has the formula (III): 11. The fuel composition of claim 1, wherein said amine salt has a concentration of at least 12 ppm, 25 ppm, or 50 ppm, based on a total weight of said fuel composition. 12. The fuel composition of claim 1, wherein said fuel composition comprises 0.1 vol % to 100 vol % oxygenate, based on a total volume of said fuel composition. 13. The fuel composition of claim 1, wherein said fuel composition comprises 0.1 vol % to 100 vol % gasoline, based on a total volume of said fuel composition. 14. The fuel composition of claim 12, wherein said oxygenate is ethanol. 15. A method of reducing carbonaceous deposits in an engine, said method comprising operating said engine using the fuel composition of claim 1. 16. The method of claim 15, wherein said amine salt is present in an amount of at least 20 ppm to 100 ppm (keep clean), or at least 100 ppm to 500 ppm (clean-up). 17. The method of claim 15, wherein said engine is an internal combustion gasoline engine. 18. The method of claim 17, wherein said internal combustion gasoline engine, is a gasoline direct injection (“GDI”) engine, a port fuel injection (“PFI”) engine, a homogeneous charge compression ignition (“HCCI”) engine, or a combination thereof. 19. The method of claim 15, wherein said amine salt is added to said fuel using an onboard dosing system. 20-23. (canceled) | Fuel compositions comprising at least 10 ppm by weight of a succinic ester acid amine salt or a succinamide acid amine salt (both “amine salt(s)”). The amine salt is the product of (a) and (b), wherein: (a) is an amine with (i) at least one tertiary nitrogen and (ii) at least one hydroxy alkyl functional group and/or at least one secondary amine functionality; and (b) is a hydrocarbyl-substituted succinic acid/or anhydride. The molar ratio of (a) to (b) may range from 3:1 to 1:3. The fuel composition may comprise gasoline, oxygenate, or mixtures thereof. Methods and uses for reducing carbonaceous deposits in an engine comprising operating the engine using the fuel composition having an amine salt therein.1. A fuel composition comprising gasoline, oxygenate, or mixtures thereof and a succinic ester acid amine salt or a succinamide acid amine salt (both “amine salt(s)”) that is the product of (a) and (b), wherein:
(a) is an amine with (i) at least one tertiary nitrogen and (ii) at least one hydroxy alkyl functionality and/or at least one secondary amine functionality;
(b) is a hydrocarbyl-substituted succinic acid and/or anhydride; and 2. The fuel composition of claim 1, wherein the molar ratio of (a) to (b) ranges from 3:1 to 1:3. 3. The fuel composition of claim 1, wherein at least a portion of the amine salt has the formula (I): 4. The fuel composition of claim 1, wherein at least a portion of the amine salt has the formula (II): 5. The fuel composition of claim 3 or 4, wherein R1 is a C8 to C25 or C12 to C16 hydrocarbyl group. 6. The fuel composition of claim 3, wherein the amine salt is the product of N,N-methyldiethanolamine and hexadecenylsuccinic anhydride. 7. The fuel composition of claim 4, wherein the amine salt is the product of N1-(3-(dimethylamino)propyl)-N3,N3-dimethylpropane-1,3-diamine and hexadecenylsuccinic anhydride. 8. The fuel composition of claim 1, wherein the amine is an alkoxylated fatty amine. 9. The fuel composition of claim 1, further comprising an alkoxylated fatty amine in addition to the amine used to make the reaction product of the amine salt. 10. The fuel composition of claim 8 or 9, wherein said alkoxylated fatty amine has the formula (III): 11. The fuel composition of claim 1, wherein said amine salt has a concentration of at least 12 ppm, 25 ppm, or 50 ppm, based on a total weight of said fuel composition. 12. The fuel composition of claim 1, wherein said fuel composition comprises 0.1 vol % to 100 vol % oxygenate, based on a total volume of said fuel composition. 13. The fuel composition of claim 1, wherein said fuel composition comprises 0.1 vol % to 100 vol % gasoline, based on a total volume of said fuel composition. 14. The fuel composition of claim 12, wherein said oxygenate is ethanol. 15. A method of reducing carbonaceous deposits in an engine, said method comprising operating said engine using the fuel composition of claim 1. 16. The method of claim 15, wherein said amine salt is present in an amount of at least 20 ppm to 100 ppm (keep clean), or at least 100 ppm to 500 ppm (clean-up). 17. The method of claim 15, wherein said engine is an internal combustion gasoline engine. 18. The method of claim 17, wherein said internal combustion gasoline engine, is a gasoline direct injection (“GDI”) engine, a port fuel injection (“PFI”) engine, a homogeneous charge compression ignition (“HCCI”) engine, or a combination thereof. 19. The method of claim 15, wherein said amine salt is added to said fuel using an onboard dosing system. 20-23. (canceled) | 2,800 |
345,442 | 16,643,379 | 2,814 | A larvae counter comprising a first container for receiving water, eggs of insects and/or larvae, a second container in fluid communication with the first container for receiving water and larvae from the first container, and a larvae counting module in fluid communication with the second container for receiving water and larvae from the second container and counting the larvae. | 1. A larvae counter comprising:
a first container for receiving water, eggs of insects and/or larvae, the first container having an outlet for dispensing larvae and water from the first container; a second container in fluid communication with the first container for receiving larvae and water from the first container; and a larvae counting module in fluid communication with the second container for receiving larvae from the second container and counting the larvae; wherein the second container comprises a channel in fluid communication with the larvae counting module, the channel comprises a plurality of openings disposed along the longitudinal surface of the channel that is away from the second container and configured for directing larvae from the second container into the larvae counting module; and wherein the larvae counting module comprises a passage for single larva to pass through and a detector positioned proximate the passage for detecting each larva passing through the passage. 2. The larvae counter of claim 1, wherein the channel is configured to direct larva one at a time from the second container into the passage of the larvae counting module. 3. The larvae counter of claim 2, wherein the channel is connected to a water outlet of the second container positioned at the base of the second container, the channel includes an outlet valve for regulating flow rate of water through the water outlet of the second container. 4. The larvae counter of claim 1, wherein the channel has a diameter of 3 mm sufficient for a single larva to pass through the channel. 5. The larvae counter of claim 1, wherein the passage has a diameter of 1.0 mm to 6.0 mm. 6. The larvae counter of claim 1, wherein the larvae counting module comprises a funnel having an upper portion and a lower portion, the upper portion being wider than the lower portion, the lower portion defines the passage for single larva to pass through and wherein the lower portion has an open end for water and larvae to pass through and out of the larvae counter after the larvae are counted. 7. The larvae counter of claim 1, wherein the detector is an image capturing device having an image sensor, the image sensor detects and transmits information about the larva to a processor unit to keep track and count the larva. 8. The larvae counter of claim 1, wherein the detector is an optical counter having a light sensor for detecting change of intensity of light when larvae passes through. 9. The larvae counter of claim 1, wherein the larvae counting module is provided with a counter light source positioned opposite the detector for facilitating the detection of larvae passing through the passage. 10. The larvae counter of claim 1, wherein the second container further comprises a water inlet positioned at the top of the second container for receiving water and larvae from the first container. 11. The larvae counter of claim 10, wherein the second container is in fluid communication with the first container via a conduit, the conduit comprises:
a first end and a second end, the first end having a funnel mouth for receiving larvae and water from the first container and the second end is removably attached to the water inlet of the second container. 12. The larvae counter of claim 11, wherein the conduit is positioned tilted at an angle with respect to a horizontal plane for facilitating flow of water and larvae from the first container to the second container. 13. The larvae counter of claim 1, wherein the second container further comprises a needle valve for controlling air flow into the second container. 14. The larvae counter of claim 1, wherein the first container, the second container and the larvae counting module are made of glass. 15. The larvae counter of claim 1, wherein the first container is provided with at least one light source positioned at the bottom of the first container for stimulating larvae to separate from the eggs. 16. The larvae counter of claim of 1, wherein the second container is provided with a plurality of light sources positioned along the side walls of the second container and/or the bottom of the second container for controlling larvae distribution inside the second container. 17. The larvae counter of claim 1, wherein the larvae counting module is provided with at least one light source positioned along the passage. 18. The larvae counter of claim 1, wherein the first container, the second container, the channel and the lower portion of the larvae counting module defining the passage are each provided with at least one valve for regulating the flow rate of water and larvae movement from one place to another. 19. The larvae counter of claim 6, wherein the larvae counting module further comprises at least one water inlet positioned proximate to an open end of the lower portion of the larvae counting module for flushing remaining larvae in the passage out of the larvae counter. 20. The larvae counter of claim 1, wherein the first container further comprises smooth inner periphery walls. 21. (canceled) 22. (canceled) 23. (canceled) 24. (canceled) 25. (canceled) 26. (canceled) 27. (canceled) 28. (canceled) 29. (canceled) 30. (canceled) 31. (canceled) 32. (canceled) | A larvae counter comprising a first container for receiving water, eggs of insects and/or larvae, a second container in fluid communication with the first container for receiving water and larvae from the first container, and a larvae counting module in fluid communication with the second container for receiving water and larvae from the second container and counting the larvae.1. A larvae counter comprising:
a first container for receiving water, eggs of insects and/or larvae, the first container having an outlet for dispensing larvae and water from the first container; a second container in fluid communication with the first container for receiving larvae and water from the first container; and a larvae counting module in fluid communication with the second container for receiving larvae from the second container and counting the larvae; wherein the second container comprises a channel in fluid communication with the larvae counting module, the channel comprises a plurality of openings disposed along the longitudinal surface of the channel that is away from the second container and configured for directing larvae from the second container into the larvae counting module; and wherein the larvae counting module comprises a passage for single larva to pass through and a detector positioned proximate the passage for detecting each larva passing through the passage. 2. The larvae counter of claim 1, wherein the channel is configured to direct larva one at a time from the second container into the passage of the larvae counting module. 3. The larvae counter of claim 2, wherein the channel is connected to a water outlet of the second container positioned at the base of the second container, the channel includes an outlet valve for regulating flow rate of water through the water outlet of the second container. 4. The larvae counter of claim 1, wherein the channel has a diameter of 3 mm sufficient for a single larva to pass through the channel. 5. The larvae counter of claim 1, wherein the passage has a diameter of 1.0 mm to 6.0 mm. 6. The larvae counter of claim 1, wherein the larvae counting module comprises a funnel having an upper portion and a lower portion, the upper portion being wider than the lower portion, the lower portion defines the passage for single larva to pass through and wherein the lower portion has an open end for water and larvae to pass through and out of the larvae counter after the larvae are counted. 7. The larvae counter of claim 1, wherein the detector is an image capturing device having an image sensor, the image sensor detects and transmits information about the larva to a processor unit to keep track and count the larva. 8. The larvae counter of claim 1, wherein the detector is an optical counter having a light sensor for detecting change of intensity of light when larvae passes through. 9. The larvae counter of claim 1, wherein the larvae counting module is provided with a counter light source positioned opposite the detector for facilitating the detection of larvae passing through the passage. 10. The larvae counter of claim 1, wherein the second container further comprises a water inlet positioned at the top of the second container for receiving water and larvae from the first container. 11. The larvae counter of claim 10, wherein the second container is in fluid communication with the first container via a conduit, the conduit comprises:
a first end and a second end, the first end having a funnel mouth for receiving larvae and water from the first container and the second end is removably attached to the water inlet of the second container. 12. The larvae counter of claim 11, wherein the conduit is positioned tilted at an angle with respect to a horizontal plane for facilitating flow of water and larvae from the first container to the second container. 13. The larvae counter of claim 1, wherein the second container further comprises a needle valve for controlling air flow into the second container. 14. The larvae counter of claim 1, wherein the first container, the second container and the larvae counting module are made of glass. 15. The larvae counter of claim 1, wherein the first container is provided with at least one light source positioned at the bottom of the first container for stimulating larvae to separate from the eggs. 16. The larvae counter of claim of 1, wherein the second container is provided with a plurality of light sources positioned along the side walls of the second container and/or the bottom of the second container for controlling larvae distribution inside the second container. 17. The larvae counter of claim 1, wherein the larvae counting module is provided with at least one light source positioned along the passage. 18. The larvae counter of claim 1, wherein the first container, the second container, the channel and the lower portion of the larvae counting module defining the passage are each provided with at least one valve for regulating the flow rate of water and larvae movement from one place to another. 19. The larvae counter of claim 6, wherein the larvae counting module further comprises at least one water inlet positioned proximate to an open end of the lower portion of the larvae counting module for flushing remaining larvae in the passage out of the larvae counter. 20. The larvae counter of claim 1, wherein the first container further comprises smooth inner periphery walls. 21. (canceled) 22. (canceled) 23. (canceled) 24. (canceled) 25. (canceled) 26. (canceled) 27. (canceled) 28. (canceled) 29. (canceled) 30. (canceled) 31. (canceled) 32. (canceled) | 2,800 |
345,443 | 16,643,355 | 2,814 | A method for purification of a sulfatase using metal chelating chromatography without using tags such as His-tag, etc. is disclosed. An embodiment provides a method for purifying a sulfatase including the steps of: (a) providing a sulfatase-containing solution comprising one or a plurality of impurities; (b) performing a first chromatographic separation of the sulfatase-containing solution using a metal affinity chromatography resin; (c) performing a second chromatographic separation using a cation exchange chromatography resin; and (d) performing a final chromatographic separation using an anion exchange chromatography resin, wherein the impurities are removed thereby. | 1. A method for purifying a sulfatase comprising the steps of:
(a) providing a sulfatase-containing solution comprising one or a plurality of impurities; (b) performing a first chromatographic separation of the sulfatase-containing solution using a metal affinity chromatography resin; (c) performing a second chromatographic separation using a cation exchange chromatography resin; and (d) performing a final chromatographic separation using an anion exchange chromatography resin, wherein the impurities are removed thereby. 2. The method of claim 1, wherein the metal affinity chromatography resin is charged with a divalent metal cation. 3. The method of claim 2, wherein the divalent metal is zinc. 4. The method of claim 1, wherein the cation exchange chromatography resin is selected from the group consisting of a strong cation exchange chromatography resin and a multimodal cation exchange chromatography resin. 5. The method of claim 1, further comprising the step of performing a third chromatographic separation using a cation exchange chromatography resin,
wherein the resin used in the second chromatographic separation step is a strong cation exchange chromatography resin; and wherein the resin used in the third chromatographic separation step is a multimodal cation exchange chromatography resin. 6. The method of claim 1, wherein the anion exchange chromatography resin is selected from the group consisting of a strong anion exchange chromatography resin and a weak anion exchange chromatography resin. 7. The method of claim 1, wherein the sulfatase has a metal ion selected from the group consisting of a calcium ion, a ferrous ion, a ferric ion, and a zinc ion in its active site. 8. The method of claim 1, wherein the sulfatase is selected from the group consisting of heparan-N-sulfatase, arylsulfatase A (ASA, or human lysosomal cerebroside-3-sulfate 3-sulfohydrolase), arylsulfatase B (ASB, or human lysosomal N-acetylgalactosamine-4-sulfate 4-sulfohydrolase), human oestrone/dehydroepiandrosterone sulfatase, human lysosomal (N-acetyl)galactosamine-6-sulfatase (GALNS), aryl sulfatase from P. aeruginosa, and sulfatase/hydrolase from B. caryophylli PG2952 (BcPMH). 9. The method of claim 1, further comprising a step of low pH virus inactivation. 10. The method of claim 9, wherein the low pH virus inactivation step is performed
after the first chromatographic separation step and before the second chromatographic separation step; or after the second chromatographic separation step and before the final chromatographic separation step. 11. The method of claim 5, further comprising a step of low pH virus inactivation. 12. The method of claim 11, wherein the low pH virus inactivation step is performed
after the first chromatographic separation step and before the second chromatographic separation step; or after the second chromatographic separation step and before the third chromatographic separation step. 13. The method of claim 1, further comprising a step of virus filtration. 14. The method of claim 13, wherein the virus filtration step is performed after the final chromatographic separation step. 15. The method of claim 1, wherein the sulfatase-containing solution is selected from the group consisting of a cell culture harvest and partially purified intermediate solutions. | A method for purification of a sulfatase using metal chelating chromatography without using tags such as His-tag, etc. is disclosed. An embodiment provides a method for purifying a sulfatase including the steps of: (a) providing a sulfatase-containing solution comprising one or a plurality of impurities; (b) performing a first chromatographic separation of the sulfatase-containing solution using a metal affinity chromatography resin; (c) performing a second chromatographic separation using a cation exchange chromatography resin; and (d) performing a final chromatographic separation using an anion exchange chromatography resin, wherein the impurities are removed thereby.1. A method for purifying a sulfatase comprising the steps of:
(a) providing a sulfatase-containing solution comprising one or a plurality of impurities; (b) performing a first chromatographic separation of the sulfatase-containing solution using a metal affinity chromatography resin; (c) performing a second chromatographic separation using a cation exchange chromatography resin; and (d) performing a final chromatographic separation using an anion exchange chromatography resin, wherein the impurities are removed thereby. 2. The method of claim 1, wherein the metal affinity chromatography resin is charged with a divalent metal cation. 3. The method of claim 2, wherein the divalent metal is zinc. 4. The method of claim 1, wherein the cation exchange chromatography resin is selected from the group consisting of a strong cation exchange chromatography resin and a multimodal cation exchange chromatography resin. 5. The method of claim 1, further comprising the step of performing a third chromatographic separation using a cation exchange chromatography resin,
wherein the resin used in the second chromatographic separation step is a strong cation exchange chromatography resin; and wherein the resin used in the third chromatographic separation step is a multimodal cation exchange chromatography resin. 6. The method of claim 1, wherein the anion exchange chromatography resin is selected from the group consisting of a strong anion exchange chromatography resin and a weak anion exchange chromatography resin. 7. The method of claim 1, wherein the sulfatase has a metal ion selected from the group consisting of a calcium ion, a ferrous ion, a ferric ion, and a zinc ion in its active site. 8. The method of claim 1, wherein the sulfatase is selected from the group consisting of heparan-N-sulfatase, arylsulfatase A (ASA, or human lysosomal cerebroside-3-sulfate 3-sulfohydrolase), arylsulfatase B (ASB, or human lysosomal N-acetylgalactosamine-4-sulfate 4-sulfohydrolase), human oestrone/dehydroepiandrosterone sulfatase, human lysosomal (N-acetyl)galactosamine-6-sulfatase (GALNS), aryl sulfatase from P. aeruginosa, and sulfatase/hydrolase from B. caryophylli PG2952 (BcPMH). 9. The method of claim 1, further comprising a step of low pH virus inactivation. 10. The method of claim 9, wherein the low pH virus inactivation step is performed
after the first chromatographic separation step and before the second chromatographic separation step; or after the second chromatographic separation step and before the final chromatographic separation step. 11. The method of claim 5, further comprising a step of low pH virus inactivation. 12. The method of claim 11, wherein the low pH virus inactivation step is performed
after the first chromatographic separation step and before the second chromatographic separation step; or after the second chromatographic separation step and before the third chromatographic separation step. 13. The method of claim 1, further comprising a step of virus filtration. 14. The method of claim 13, wherein the virus filtration step is performed after the final chromatographic separation step. 15. The method of claim 1, wherein the sulfatase-containing solution is selected from the group consisting of a cell culture harvest and partially purified intermediate solutions. | 2,800 |
345,444 | 16,643,368 | 2,814 | Durable and scratch resistant articles including an optical coating with a gradient. An article comprises: a substrate; and an optical coating having a thickness and a first gradient portion. A refractive index of the optical coating varies along a thickness of the optical coating. The difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater. The absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion. The article exhibits an average single-surface reflectance of 15% to 98% over the wavelength range 400 nm-700 nm. The article also exhibits a maximum hardness in the range from about 10 GPa to about 30 GPa. | 1. An article comprising:
a substrate comprising a first major surface; and an optical coating disposed over the first major surface, the optical coating comprising:
a second major surface opposite the first major surface,
a thickness in a direction normal to the second major surface, and
a first gradient portion, 2. The article of claim 1, wherein the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.3 or greater. 3. The article of claim 1, wherein the article exhibits an average transmittance of 5% to 90%, measured at the second major surface. 4-5. (canceled). 6. The article of claim 1, wherein:
everywhere along the thickness of the first gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.001/nm to 0.02/nm. 7. (canceled) 8. The article of claim 1, wherein the optical coating further comprises a high hardness portion, wherein:
the thickness of the high hardness portion is 200 nm or more; the average index of refraction in the high hardness portion is 1.6 or more; and the maximum hardness of the high hardness portion is 10 GPa or more, wherein maximum hardness is measured by indenting the thick high hardness portion with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more. 9. (canceled) 10. The article of claim 8, wherein for 95% or more of the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 11. The article of claim 8, wherein:
everywhere along the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 12. The article of claim 8, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
the first gradient portion; and the high hardness portion in contact with the first gradient portion; wherein, where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less. 13. The article of claim 8, wherein the optical coating further comprises a second gradient portion disposed between the high hardness portion and the substrate, wherein the second gradient portion is in contact with the high hardness portion, and wherein:
the difference between the maximum refractive index of the second gradient portion and the minimum refractive index of the second gradient portion is 0.05 or greater; everywhere along the thickness of the second gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.1/nm or less. 14. The article of claim 8, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the optical coating further comprises a multilayer interference stack comprising discrete layers disposed between the high hardness portion and the substrate. 15. The article of claim 8, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the optical coating further comprises a second gradient portion that oscillates across the thickness of the gradient portion as a function of distance from the substrate. 16. The article of claim 8, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
a multilayer interference stack comprising discrete layers; the high hardness portion in contact with the multilayer interference stack; the first gradient portion in contact with the high hardness portion; wherein:
where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less;
the refractive index of the first gradient portion monotonically decreases along the thickness in a direction moving away from the second major surface. 17-21. (canceled) 22. The article of claim 1, wherein the article exhibits a single side reflected color range for all viewing angles from 0 to 60 degrees, measured at the second major surface, that comprises all a* points and all b* points comprising values of 5 or less. 23-25. (canceled) 26. The article of claim 1, wherein the article exhibits a maximum visible reflectance between 30% to 80%. 27. The article of claim 1, wherein the article exhibits an average photopic reflectance between 15% to 50%. 28. (canceled) 29. The article of claim 1, wherein the article exhibits an average transmittance or average reflectance comprising an average oscillation amplitude of 20 percentage points or less, over the optical wavelength regime. 30. The article of claim 1, wherein optical coating comprises a thickness in the range from about 0.5 μm to about 3 μm. 31. The article of claim 8, wherein the cumulative thickness of any parts of the optical coating between the high hardness portion and the second major surface comprising a RI of 1.6 or less is 200 nm or less. 32-33. (canceled) 34. The article of claim 1, wherein the optical coating comprises a compositional gradient, the compositional gradient comprising at least two of Si, Al, N, and O. 35-40. (canceled) 41. A method of forming an article comprising:
obtaining a substrate comprising a first major surface and comprising an amorphous substrate or a crystalline substrate; disposing an optical coating on the first major surface, the optical coating comprising a second major surface opposite the first major surface and a thickness in a direction normal to the second major surface, creating a refractive index gradient along at least a first gradient portion of the thickness of the optical coating, wherein:
a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface;
the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater;
the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion;
wherein the article exhibits:
an average single-surface reflectance of 15% to 98% over the wavelength range 400 nm-700 nm, measured at the second major surface; and
a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface;
wherein slope is measured along the thickness over a refractive index change of 0.04. 42-43. (canceled) | Durable and scratch resistant articles including an optical coating with a gradient. An article comprises: a substrate; and an optical coating having a thickness and a first gradient portion. A refractive index of the optical coating varies along a thickness of the optical coating. The difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater. The absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion. The article exhibits an average single-surface reflectance of 15% to 98% over the wavelength range 400 nm-700 nm. The article also exhibits a maximum hardness in the range from about 10 GPa to about 30 GPa.1. An article comprising:
a substrate comprising a first major surface; and an optical coating disposed over the first major surface, the optical coating comprising:
a second major surface opposite the first major surface,
a thickness in a direction normal to the second major surface, and
a first gradient portion, 2. The article of claim 1, wherein the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.3 or greater. 3. The article of claim 1, wherein the article exhibits an average transmittance of 5% to 90%, measured at the second major surface. 4-5. (canceled). 6. The article of claim 1, wherein:
everywhere along the thickness of the first gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.001/nm to 0.02/nm. 7. (canceled) 8. The article of claim 1, wherein the optical coating further comprises a high hardness portion, wherein:
the thickness of the high hardness portion is 200 nm or more; the average index of refraction in the high hardness portion is 1.6 or more; and the maximum hardness of the high hardness portion is 10 GPa or more, wherein maximum hardness is measured by indenting the thick high hardness portion with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more. 9. (canceled) 10. The article of claim 8, wherein for 95% or more of the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 11. The article of claim 8, wherein:
everywhere along the thickness of the high hardness portion, the difference between the maximum refractive index of the high hardness portion and the minimum refractive index of the high hardness portion is 0.05 or less. 12. The article of claim 8, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
the first gradient portion; and the high hardness portion in contact with the first gradient portion; wherein, where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less. 13. The article of claim 8, wherein the optical coating further comprises a second gradient portion disposed between the high hardness portion and the substrate, wherein the second gradient portion is in contact with the high hardness portion, and wherein:
the difference between the maximum refractive index of the second gradient portion and the minimum refractive index of the second gradient portion is 0.05 or greater; everywhere along the thickness of the second gradient portion, the absolute value of the slope of the refractive index of the optical coating is 0.1/nm or less. 14. The article of claim 8, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the optical coating further comprises a multilayer interference stack comprising discrete layers disposed between the high hardness portion and the substrate. 15. The article of claim 8, wherein:
the refractive index of the first gradient portion monotonically increases along the thickness in a direction moving away from the second major surface; the optical coating further comprises a second gradient portion that oscillates across the thickness of the gradient portion as a function of distance from the substrate. 16. The article of claim 8, wherein the optical coating comprises, in order, along the direction of the thickness from the second major surface toward the first major surface:
a multilayer interference stack comprising discrete layers; the high hardness portion in contact with the multilayer interference stack; the first gradient portion in contact with the high hardness portion; wherein:
where the high hardness portion contacts the first gradient portion, the difference between the refractive index of the high hardness portion and the maximum refractive index of the first gradient portion is 0.05 or less;
the refractive index of the first gradient portion monotonically decreases along the thickness in a direction moving away from the second major surface. 17-21. (canceled) 22. The article of claim 1, wherein the article exhibits a single side reflected color range for all viewing angles from 0 to 60 degrees, measured at the second major surface, that comprises all a* points and all b* points comprising values of 5 or less. 23-25. (canceled) 26. The article of claim 1, wherein the article exhibits a maximum visible reflectance between 30% to 80%. 27. The article of claim 1, wherein the article exhibits an average photopic reflectance between 15% to 50%. 28. (canceled) 29. The article of claim 1, wherein the article exhibits an average transmittance or average reflectance comprising an average oscillation amplitude of 20 percentage points or less, over the optical wavelength regime. 30. The article of claim 1, wherein optical coating comprises a thickness in the range from about 0.5 μm to about 3 μm. 31. The article of claim 8, wherein the cumulative thickness of any parts of the optical coating between the high hardness portion and the second major surface comprising a RI of 1.6 or less is 200 nm or less. 32-33. (canceled) 34. The article of claim 1, wherein the optical coating comprises a compositional gradient, the compositional gradient comprising at least two of Si, Al, N, and O. 35-40. (canceled) 41. A method of forming an article comprising:
obtaining a substrate comprising a first major surface and comprising an amorphous substrate or a crystalline substrate; disposing an optical coating on the first major surface, the optical coating comprising a second major surface opposite the first major surface and a thickness in a direction normal to the second major surface, creating a refractive index gradient along at least a first gradient portion of the thickness of the optical coating, wherein:
a refractive index of the optical coating varies along a thickness of the optical coating between the first major surface and the second major surface;
the difference between the maximum refractive index of the first gradient portion and the minimum refractive index of the first gradient portion is 0.1 or greater;
the absolute value of the slope of the refractive index of the first gradient portion is 0.1/nm or less everywhere along the thickness of the first gradient portion;
wherein the article exhibits:
an average single-surface reflectance of 15% to 98% over the wavelength range 400 nm-700 nm, measured at the second major surface; and
a maximum hardness in the range from about 10 GPa to about 30 GPa, wherein maximum hardness is measured on the second major surface by indenting the second major surface with a Berkovich indenter to form an indent comprising an indentation depth of about 100 nm or more from the surface of the second major surface;
wherein slope is measured along the thickness over a refractive index change of 0.04. 42-43. (canceled) | 2,800 |
345,445 | 16,643,371 | 2,814 | A display panel has pixel regions each includes sub-pixel regions, one of the sub-pixel regions is a white sub-pixel region, and remaining sub-pixel regions are color sub-pixel regions. The display panel includes signal lines and at least one filter group. The signal lines include two signal lines, a portion of each of the two signal lines is disposed between one white sub-pixel region and an adjacent color sub-pixel region, and there is a space between the two signal lines. Each filter group includes a first filter block and a second filter block, and a light transmission wavelength range of the first filter block does not overlap with that of the second filter block. An overlapping portion of the first filter block and the second filter block that are in one filter group covers a portion of the space disposed between the white sub-pixel region and the adjacent color sub-pixel region. | 1. A display panel, having a plurality of pixel regions arranged in an array, each pixel region including a plurality of sub-pixel regions, one of the plurality of sub-pixel regions being a white sub-pixel region, and remaining sub-pixel regions being color sub-pixel regions; and
the display panel comprising: a plurality of signal lines, wherein the plurality of signal lines include two signal lines that are adjacent to each other, a portion of each of the two signal lines is disposed between one white sub-pixel region and an adjacent color sub-pixel region, and there is a space between the two signal lines; and at least one filter group, wherein each filter group includes a first filter block and a second filter block that are disposed in a stack, and a light transmission wavelength range of the first filter block does not overlap with a light transmission wavelength range of the second filter block; wherein an overlapping portion of the first filter block and the second filter block that are in one filter group covers a portion of the space disposed between the white sub-pixel region and the adjacent color sub-pixel region. 2. The display panel according to claim 1,
further comprising a plurality of color filter films, at least one portion of each color filter film being disposed in a corresponding color sub-pixel region; wherein in the filter group, a material of one of the first filter block and the second filter block is the same as a material of an adjacent color filter film. 3. The display panel according to claim 2, wherein a material of the first filter block in the filter group is the same as a material of the adjacent color filter film, and the first filter block is connected to the adjacent color filter film; and
the color filter film includes a portion connected to the first filter block, and the portion covers a portion of one signal line proximate to the color filter film in the two signal lines; or the first filter block includes a portion connected to the color filter film, and the portion covers a portion of one signal line proximate to the color filter film in the two signal lines. 4. The display panel according to claim 1, wherein in each pixel region, the remaining sub-pixel regions include a first color sub-pixel region, a second color sub-pixel region, and a third color sub-pixel region; and
the display panel further comprises: a plurality of first color filter films, at least one portion of each first color filter film being disposed in a corresponding first color sub-pixel region; a plurality of second color filter films, at least one portion of each second color filter film being disposed in a corresponding second color sub-pixel region; and a plurality of third color filter films, at least one portion of each third color filter film being disposed in a corresponding third color sub-pixel region, wherein colors of each first color filter film, each second color filter film, and each third color filter film are different from each other. 5. The display panel according to claim 4, wherein
a material of the first filter block is the same as a material of any one of each first color filter film, each second color filter film, and each third color filter film; and a material of the second filter block is the same as a material of any one of each first color filter film, each second color filter film, and each third color filter film, and the material of the second filter block is different from the material of the first filter block in a same filter group. 6. The display panel according to claim 5, wherein a color sub-pixel region adjacent to each white sub-pixel region is a third color sub-pixel region; and
a material of the first filter block in the filter group is the same as a material of an adjacent third color filter film. 7. The display panel according to claim 6, wherein the first filter block is connected to the adjacent third color filter film, wherein
the third color filter film includes a portion connected to the first filter block, and the portion covers a portion of one signal line proximate to the third color sub-pixel region in the two signal lines; or the first filter block includes a portion connected to the third color filter film, and the portion covers a portion of one signal line proximate to the third color sub-pixel region in the two signal lines. 8. The display panel according to claim 1, wherein a portion of the second filter block in the filter group covers a portion of one signal line proximate to the white sub-pixel region in the two signal lines. 9. The display panel according to claim 1, further comprising:
a substrate, wherein the plurality of signal lines and the at least one filter group are disposed on the substrate, and the second filter block in each filter group is disposed on a side of the first filter block in a same filter group away from the substrate; and a transparent insulating layer at least covering each second filter block. 10. The display panel according to claim 9, further comprising:
a plurality of white organic light-emitting diodes disposed on a side of the transparent insulating layer away from the substrate, wherein each white organic light-emitting diode is disposed in a corresponding sub-pixel region, a light emission direction of each white organic light-emitting diode is directed toward the substrate, and light-emitting layers of two adjacent white organic light-emitting diodes are connected. 11. The display panel according to claim 4, wherein in a row direction or a column direction in which the plurality of pixel regions are arranged, sub-pixel regions in each pixel region are arranged in an order of the first color sub-pixel region, the second color sub-pixel region, the white sub-pixel region, and the third color sub-pixel region. 12. The display panel according to claim 4, wherein the first color filter film includes a red filter film, the second color filter film includes a green filter film, and the third color filter film includes a blue filter film. 13. The display panel according to claim 1, wherein the plurality of signal lines include a plurality of data lines. 14. The display panel according to claim 1, wherein the plurality of signal lines include a plurality of gate lines. 15. The display panel according to claim 1, further comprising a common power line partially disposed between the white sub-pixel region and another adjacent color sub-pixel region. 16. The display panel according to claim 4, wherein a color sub-pixel region adjacent to each white sub-pixel region is a third color sub-pixel region; and
the plurality of signal lines further include another two signal lines that are adjacent to each other, a portion of each of the two signal lines is disposed between one first color sub-pixel region and an adjacent second color sub-pixel region, and there is a space between the two signal lines; wherein one first color filter film disposed in the first color sub-pixel region covers a portion of one signal line proximate to the first color sub-pixel region in the two signal lines, and extends to the other signal line in the two signal lines; and one second color filter film disposed in the second color sub-pixel region covers a portion of one signal line proximate to the second color sub-pixel region in the two signal lines, and extends to the other signal line in the two signal lines. 17. The display panel according to claim 3, wherein the first filter block and the adjacent color filter film are connected to each other so as to form a whole structure. 18. The display panel according to claim 7, wherein the first filter block and the adjacent third color filter film are connected to each other so as to form a whole structure. 19. The display panel according to claim 10, further comprising a driving transistor electrically connected to each white organic light-emitting diode. | A display panel has pixel regions each includes sub-pixel regions, one of the sub-pixel regions is a white sub-pixel region, and remaining sub-pixel regions are color sub-pixel regions. The display panel includes signal lines and at least one filter group. The signal lines include two signal lines, a portion of each of the two signal lines is disposed between one white sub-pixel region and an adjacent color sub-pixel region, and there is a space between the two signal lines. Each filter group includes a first filter block and a second filter block, and a light transmission wavelength range of the first filter block does not overlap with that of the second filter block. An overlapping portion of the first filter block and the second filter block that are in one filter group covers a portion of the space disposed between the white sub-pixel region and the adjacent color sub-pixel region.1. A display panel, having a plurality of pixel regions arranged in an array, each pixel region including a plurality of sub-pixel regions, one of the plurality of sub-pixel regions being a white sub-pixel region, and remaining sub-pixel regions being color sub-pixel regions; and
the display panel comprising: a plurality of signal lines, wherein the plurality of signal lines include two signal lines that are adjacent to each other, a portion of each of the two signal lines is disposed between one white sub-pixel region and an adjacent color sub-pixel region, and there is a space between the two signal lines; and at least one filter group, wherein each filter group includes a first filter block and a second filter block that are disposed in a stack, and a light transmission wavelength range of the first filter block does not overlap with a light transmission wavelength range of the second filter block; wherein an overlapping portion of the first filter block and the second filter block that are in one filter group covers a portion of the space disposed between the white sub-pixel region and the adjacent color sub-pixel region. 2. The display panel according to claim 1,
further comprising a plurality of color filter films, at least one portion of each color filter film being disposed in a corresponding color sub-pixel region; wherein in the filter group, a material of one of the first filter block and the second filter block is the same as a material of an adjacent color filter film. 3. The display panel according to claim 2, wherein a material of the first filter block in the filter group is the same as a material of the adjacent color filter film, and the first filter block is connected to the adjacent color filter film; and
the color filter film includes a portion connected to the first filter block, and the portion covers a portion of one signal line proximate to the color filter film in the two signal lines; or the first filter block includes a portion connected to the color filter film, and the portion covers a portion of one signal line proximate to the color filter film in the two signal lines. 4. The display panel according to claim 1, wherein in each pixel region, the remaining sub-pixel regions include a first color sub-pixel region, a second color sub-pixel region, and a third color sub-pixel region; and
the display panel further comprises: a plurality of first color filter films, at least one portion of each first color filter film being disposed in a corresponding first color sub-pixel region; a plurality of second color filter films, at least one portion of each second color filter film being disposed in a corresponding second color sub-pixel region; and a plurality of third color filter films, at least one portion of each third color filter film being disposed in a corresponding third color sub-pixel region, wherein colors of each first color filter film, each second color filter film, and each third color filter film are different from each other. 5. The display panel according to claim 4, wherein
a material of the first filter block is the same as a material of any one of each first color filter film, each second color filter film, and each third color filter film; and a material of the second filter block is the same as a material of any one of each first color filter film, each second color filter film, and each third color filter film, and the material of the second filter block is different from the material of the first filter block in a same filter group. 6. The display panel according to claim 5, wherein a color sub-pixel region adjacent to each white sub-pixel region is a third color sub-pixel region; and
a material of the first filter block in the filter group is the same as a material of an adjacent third color filter film. 7. The display panel according to claim 6, wherein the first filter block is connected to the adjacent third color filter film, wherein
the third color filter film includes a portion connected to the first filter block, and the portion covers a portion of one signal line proximate to the third color sub-pixel region in the two signal lines; or the first filter block includes a portion connected to the third color filter film, and the portion covers a portion of one signal line proximate to the third color sub-pixel region in the two signal lines. 8. The display panel according to claim 1, wherein a portion of the second filter block in the filter group covers a portion of one signal line proximate to the white sub-pixel region in the two signal lines. 9. The display panel according to claim 1, further comprising:
a substrate, wherein the plurality of signal lines and the at least one filter group are disposed on the substrate, and the second filter block in each filter group is disposed on a side of the first filter block in a same filter group away from the substrate; and a transparent insulating layer at least covering each second filter block. 10. The display panel according to claim 9, further comprising:
a plurality of white organic light-emitting diodes disposed on a side of the transparent insulating layer away from the substrate, wherein each white organic light-emitting diode is disposed in a corresponding sub-pixel region, a light emission direction of each white organic light-emitting diode is directed toward the substrate, and light-emitting layers of two adjacent white organic light-emitting diodes are connected. 11. The display panel according to claim 4, wherein in a row direction or a column direction in which the plurality of pixel regions are arranged, sub-pixel regions in each pixel region are arranged in an order of the first color sub-pixel region, the second color sub-pixel region, the white sub-pixel region, and the third color sub-pixel region. 12. The display panel according to claim 4, wherein the first color filter film includes a red filter film, the second color filter film includes a green filter film, and the third color filter film includes a blue filter film. 13. The display panel according to claim 1, wherein the plurality of signal lines include a plurality of data lines. 14. The display panel according to claim 1, wherein the plurality of signal lines include a plurality of gate lines. 15. The display panel according to claim 1, further comprising a common power line partially disposed between the white sub-pixel region and another adjacent color sub-pixel region. 16. The display panel according to claim 4, wherein a color sub-pixel region adjacent to each white sub-pixel region is a third color sub-pixel region; and
the plurality of signal lines further include another two signal lines that are adjacent to each other, a portion of each of the two signal lines is disposed between one first color sub-pixel region and an adjacent second color sub-pixel region, and there is a space between the two signal lines; wherein one first color filter film disposed in the first color sub-pixel region covers a portion of one signal line proximate to the first color sub-pixel region in the two signal lines, and extends to the other signal line in the two signal lines; and one second color filter film disposed in the second color sub-pixel region covers a portion of one signal line proximate to the second color sub-pixel region in the two signal lines, and extends to the other signal line in the two signal lines. 17. The display panel according to claim 3, wherein the first filter block and the adjacent color filter film are connected to each other so as to form a whole structure. 18. The display panel according to claim 7, wherein the first filter block and the adjacent third color filter film are connected to each other so as to form a whole structure. 19. The display panel according to claim 10, further comprising a driving transistor electrically connected to each white organic light-emitting diode. | 2,800 |
345,446 | 16,643,383 | 2,814 | In accordance with an embodiment of the present invention, an optical switch includes a photoconductor body including a first edge and an opposite second edge, a first end and an opposite second end. The first edge is configured to receive an electrical input signal and the second edge is configured to deliver an electrical output signal. The photoconductor body is configured to have an electrically ON state that is activated by an optical signal and an electrically OFF state that is activated by an absence of the optical signal. A direction from the first end to the second end defines a longitudinal direction. The direction from the first edge to the second edge defines a first direction that is orthogonal to the longitudinal direction. A first dimension between the first edge and the second edge along the first direction decreases from the first end to the second end. | 1-12. (canceled) 13. An optical switch comprising:
a photoconductor body comprising a first edge and an opposite second edge, a first end and an opposite second end, the first edge configured to receive an electrical input signal and the second edge configured to deliver an electrical output signal, the photoconductor body being configured to have an electrically ON state that is activated by an optical signal and an electrically OFF state that is activated by an absence of the optical signal, wherein a direction from the first end to the second end defines a longitudinal direction, wherein the direction from the first edge to the second edge defines a first direction that is orthogonal to the longitudinal direction, wherein a first dimension between the first edge and the second edge along the first direction decreases from the first end to the second end. 14. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases gradually. 15. The switch as claimed in claim 13, wherein the photoconductor body comprises a second dimension along a second direction that is orthogonal to the first direction and the longitudinal direction, and wherein the second dimension remains constant along the longitudinal direction. 16. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases stepwise along the longitudinal direction so that the first dimension decreases substantially linearly along the longitudinal direction. 17. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases stepwise along the longitudinal direction so that the first dimension decreases substantially exponentially along the longitudinal direction. 18. The switch as claimed in claim 17, wherein the first dimension between the first edge and the second edge decreases exponentially with the product of the absorption coefficient of the photoconductor body and a distance from the first end in the longitudinal direction. 19. The switch as claimed in claim 13, wherein the photoconductor body comprises a plurality of portions that are arranged along the longitudinal direction between the first end and the second end, the portions being configured such that the respective first dimension between the first edge and the second edge decreases from the first end to the second end. 20. The switch as claimed in claim 13, wherein the optical signal is delivered at the first end and the photoconductor body is configured to propagate the optical signal along the longitudinal direction. 21. The switch as claimed in claim 13, further comprising a silicon-on-insulator substrate that includes a semiconductor film disposed on a buried insulating layer, the buried insulating layer being disposed on a carrier substrate, and the semiconductor film comprising the photoconductor body. 22. An integrated electronic circuit comprising:
an input terminal configured to receive an analog electronic signal; an output terminal configured to deliver a sampled signal; and an optical switch comprising a photoconductor body that comprises a first series of contacts coupled to the input terminal and a second series of contacts coupled to the output terminal, the switch configured to have an electrically ON state coupling the first series of contacts to the second series of contact in response to an optical signal, the switch configured to have an electrically OFF state decoupling the first series of contacts from the second series of contact in response to an absence of the optical signal, wherein the photoconductor body comprises a first end configured to receive the optical signal, and an opposite second end, wherein a first distance between one of the first series of contacts to one of the second series of contacts at the first end is different from a second distance between another one of the first series of contacts to another one of the second series of contacts at the second end. 23. The circuit as claimed in claim 22, further comprising:
a capacitor coupled between the second series of contacts and a reference potential node. 24. The circuit as claimed in claim 22, wherein the integrated electronic circuit is a sample-and-hold circuit. 25. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies substantially linearly along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 26. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies substantially exponentially along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 27. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies in a stepwise manner along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 28. The switch as claimed in claim 27, wherein a step height between adjacent steps in the stepwise manner varies in a direction from the first end to the second end. 29. The switch as claimed in claim 27, wherein a step height between adjacent steps in the stepwise manner decreases in a direction from the first end to the second end. 30. An optical switch comprising:
a photoconductor body comprising a first end configured to receive an optical signal, and an opposite second end, a first edge and an opposite second edge; an input terminal configured to receive an electrical input signal at the first edge; an output terminal configured to deliver an electrical output signal at the second edge; and a control node configured to switch the optical switch between an electrically ON state coupling the input terminal to the output terminal and electrically OFF state decoupling the input terminal from the output terminal based on a presence or absence of the optical signal at the first end, wherein a first distance between the first edge and the second edge at the first end is different from a second distance between the first edge and the second edge at the second end. 31. The switch as claimed in claim 30, wherein the photoconductor body further comprises a first series of contacts at the first edge coupled to the input terminal and a second series of contacts at the second edge coupled to the output terminal. 32. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies substantially linearly from the first distance to the second distance. 33. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies substantially exponentially from the first distance to the second distance. 34. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies in a stepwise manner from the first distance to the second distance. 35. The switch as claimed in claim 34, wherein a step height between adjacent steps in the stepwise manner varies in a direction from the first end to the second end. 36. The switch as claimed in claim 34, wherein a step height between adjacent steps in the stepwise manner decreases in a direction from the first end to the second end. 37. The switch as claimed in claim 30, wherein the first distance is smaller than the second distance. | In accordance with an embodiment of the present invention, an optical switch includes a photoconductor body including a first edge and an opposite second edge, a first end and an opposite second end. The first edge is configured to receive an electrical input signal and the second edge is configured to deliver an electrical output signal. The photoconductor body is configured to have an electrically ON state that is activated by an optical signal and an electrically OFF state that is activated by an absence of the optical signal. A direction from the first end to the second end defines a longitudinal direction. The direction from the first edge to the second edge defines a first direction that is orthogonal to the longitudinal direction. A first dimension between the first edge and the second edge along the first direction decreases from the first end to the second end.1-12. (canceled) 13. An optical switch comprising:
a photoconductor body comprising a first edge and an opposite second edge, a first end and an opposite second end, the first edge configured to receive an electrical input signal and the second edge configured to deliver an electrical output signal, the photoconductor body being configured to have an electrically ON state that is activated by an optical signal and an electrically OFF state that is activated by an absence of the optical signal, wherein a direction from the first end to the second end defines a longitudinal direction, wherein the direction from the first edge to the second edge defines a first direction that is orthogonal to the longitudinal direction, wherein a first dimension between the first edge and the second edge along the first direction decreases from the first end to the second end. 14. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases gradually. 15. The switch as claimed in claim 13, wherein the photoconductor body comprises a second dimension along a second direction that is orthogonal to the first direction and the longitudinal direction, and wherein the second dimension remains constant along the longitudinal direction. 16. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases stepwise along the longitudinal direction so that the first dimension decreases substantially linearly along the longitudinal direction. 17. The switch as claimed in claim 13, wherein the first dimension between the first edge and the second edge decreases stepwise along the longitudinal direction so that the first dimension decreases substantially exponentially along the longitudinal direction. 18. The switch as claimed in claim 17, wherein the first dimension between the first edge and the second edge decreases exponentially with the product of the absorption coefficient of the photoconductor body and a distance from the first end in the longitudinal direction. 19. The switch as claimed in claim 13, wherein the photoconductor body comprises a plurality of portions that are arranged along the longitudinal direction between the first end and the second end, the portions being configured such that the respective first dimension between the first edge and the second edge decreases from the first end to the second end. 20. The switch as claimed in claim 13, wherein the optical signal is delivered at the first end and the photoconductor body is configured to propagate the optical signal along the longitudinal direction. 21. The switch as claimed in claim 13, further comprising a silicon-on-insulator substrate that includes a semiconductor film disposed on a buried insulating layer, the buried insulating layer being disposed on a carrier substrate, and the semiconductor film comprising the photoconductor body. 22. An integrated electronic circuit comprising:
an input terminal configured to receive an analog electronic signal; an output terminal configured to deliver a sampled signal; and an optical switch comprising a photoconductor body that comprises a first series of contacts coupled to the input terminal and a second series of contacts coupled to the output terminal, the switch configured to have an electrically ON state coupling the first series of contacts to the second series of contact in response to an optical signal, the switch configured to have an electrically OFF state decoupling the first series of contacts from the second series of contact in response to an absence of the optical signal, wherein the photoconductor body comprises a first end configured to receive the optical signal, and an opposite second end, wherein a first distance between one of the first series of contacts to one of the second series of contacts at the first end is different from a second distance between another one of the first series of contacts to another one of the second series of contacts at the second end. 23. The circuit as claimed in claim 22, further comprising:
a capacitor coupled between the second series of contacts and a reference potential node. 24. The circuit as claimed in claim 22, wherein the integrated electronic circuit is a sample-and-hold circuit. 25. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies substantially linearly along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 26. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies substantially exponentially along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 27. The switch as claimed in claim 22, wherein a distance measured along a first direction between the first series of contacts to the second series of contacts varies in a stepwise manner along a longitudinal direction from the first end to the second end, the first direction being orthogonal to the longitudinal direction. 28. The switch as claimed in claim 27, wherein a step height between adjacent steps in the stepwise manner varies in a direction from the first end to the second end. 29. The switch as claimed in claim 27, wherein a step height between adjacent steps in the stepwise manner decreases in a direction from the first end to the second end. 30. An optical switch comprising:
a photoconductor body comprising a first end configured to receive an optical signal, and an opposite second end, a first edge and an opposite second edge; an input terminal configured to receive an electrical input signal at the first edge; an output terminal configured to deliver an electrical output signal at the second edge; and a control node configured to switch the optical switch between an electrically ON state coupling the input terminal to the output terminal and electrically OFF state decoupling the input terminal from the output terminal based on a presence or absence of the optical signal at the first end, wherein a first distance between the first edge and the second edge at the first end is different from a second distance between the first edge and the second edge at the second end. 31. The switch as claimed in claim 30, wherein the photoconductor body further comprises a first series of contacts at the first edge coupled to the input terminal and a second series of contacts at the second edge coupled to the output terminal. 32. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies substantially linearly from the first distance to the second distance. 33. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies substantially exponentially from the first distance to the second distance. 34. The switch as claimed in claim 30, wherein a distance between the first edge and the second edge varies in a stepwise manner from the first distance to the second distance. 35. The switch as claimed in claim 34, wherein a step height between adjacent steps in the stepwise manner varies in a direction from the first end to the second end. 36. The switch as claimed in claim 34, wherein a step height between adjacent steps in the stepwise manner decreases in a direction from the first end to the second end. 37. The switch as claimed in claim 30, wherein the first distance is smaller than the second distance. | 2,800 |
345,447 | 16,643,350 | 2,814 | The Lactobacillus curvatus strain deposited as DSM18775 is used as a biopreservative culture in a wide range of meat products due to its production of bacteriocin. The present invention relates to Lactobacillus curvatus strains having an extended lag phase of at least 24 hours at 30° C. relative to DSM18775. In a presently preferred embodiment, the strains are mutants of DSM18775, such as the Lactobacillus curvatus strain deposited as DSM32590 and the Lactobacillus curvatus strain deposited as DSM 32591. Further, the invention relates to a method for inhibiting Listeria in a food product comprising adding bacteria of a Lactobacillus curvatus strain according to the invention to a food product in a concentration of at least 105 CFU/g. | 1. A mutant Lactobacillus curvatus strain which is a mutant of the Lactobacillus curvatus strain deposited at the Deutsche Sammlung von Mikroorganismen and Zellkulturen wherein (DSMZ) under accession number DSM 18775, wherein the strain has an extended lag phase of at least 24 hours at 30° C. relative to DSM 18775. 2. A Lactobacillus curvatus strain according to claim 1 wherein the extended lag phase is at least 48 hours at 30° C. relative to DSM 18775. 3. (canceled) 4. A mutant Lactobacillus curvatus strain according to claim 1, deposited at the DSMZ under accession number DSM 32590. 5. A Lactobacillus curvatus strain according to claim 1, deposited at the DSMZ under accession number DSM 32591. 6. A composition comprising bacteria of a mutant Lactobacillus curvatus strain according to claim 1. 7. The composition according to claim 6, comprising bacteria of the mutant Lactobacillus curvatus strain DSM 32590 and bacteria of the mutant Lactobacillus curvatus strain DSM 32591. 8. The composition according to claim 6, wherein the mutant Lactobacillus curvatus strain is present in the composition at a concentration of at least 105 CFU/g. 9. The composition according to claim 6, wherein the bacteria of the mutant Lactobacillus curvatus strain are the only bacteria present in the composition. 10. The composition according to claim 6, wherein the composition further comprises bacteria of one or more species selected from Pediococcus acidilactici, Lactobacillus sakei, Lactococcus lactis, Leuconostoc carnosum, and Staphylococcus carnosus. 11. The composition according to claim 10, wherein the bacteria of one or more of the species selected from Pediococcus acidilactici, Lactobacillus sakei, Lactococcus lactis, Leuconostoc carnosum, and Staphylococcus carnosus is selected from Pediococcus acidilactici deposited at the DSMZ under accession number DSM 28307, Lactobacillus sakei deposited at the DSMZ under accession number DSM 14022, Lactococcus lactis deposited at the DSMZ under accession number DSM 11037, and Leuconostoc carnosum LC1043. 12. A method for inhibiting the amount of spoilage or pathogenic bacteria in a food product, comprising adding bacteria of a mutant Lactobacillus curvatus strain according to claim 1 to a food product at a concentration of at least 105 CFU/g. 13. The method according to claim 12, wherein the pathogenic bacteria is Listeria. 14. A method for inhibiting the amount of spoilage or pathogenic bacteria in a food product, comprising adding a composition according to claim 6 to a food product in an amount to provide the mutant Lactobacillus curvatus strain at a concentration of at least 105 CFU/g. 15. The method according to claim 14, wherein the pathogenic bacteria is Listeria. | The Lactobacillus curvatus strain deposited as DSM18775 is used as a biopreservative culture in a wide range of meat products due to its production of bacteriocin. The present invention relates to Lactobacillus curvatus strains having an extended lag phase of at least 24 hours at 30° C. relative to DSM18775. In a presently preferred embodiment, the strains are mutants of DSM18775, such as the Lactobacillus curvatus strain deposited as DSM32590 and the Lactobacillus curvatus strain deposited as DSM 32591. Further, the invention relates to a method for inhibiting Listeria in a food product comprising adding bacteria of a Lactobacillus curvatus strain according to the invention to a food product in a concentration of at least 105 CFU/g.1. A mutant Lactobacillus curvatus strain which is a mutant of the Lactobacillus curvatus strain deposited at the Deutsche Sammlung von Mikroorganismen and Zellkulturen wherein (DSMZ) under accession number DSM 18775, wherein the strain has an extended lag phase of at least 24 hours at 30° C. relative to DSM 18775. 2. A Lactobacillus curvatus strain according to claim 1 wherein the extended lag phase is at least 48 hours at 30° C. relative to DSM 18775. 3. (canceled) 4. A mutant Lactobacillus curvatus strain according to claim 1, deposited at the DSMZ under accession number DSM 32590. 5. A Lactobacillus curvatus strain according to claim 1, deposited at the DSMZ under accession number DSM 32591. 6. A composition comprising bacteria of a mutant Lactobacillus curvatus strain according to claim 1. 7. The composition according to claim 6, comprising bacteria of the mutant Lactobacillus curvatus strain DSM 32590 and bacteria of the mutant Lactobacillus curvatus strain DSM 32591. 8. The composition according to claim 6, wherein the mutant Lactobacillus curvatus strain is present in the composition at a concentration of at least 105 CFU/g. 9. The composition according to claim 6, wherein the bacteria of the mutant Lactobacillus curvatus strain are the only bacteria present in the composition. 10. The composition according to claim 6, wherein the composition further comprises bacteria of one or more species selected from Pediococcus acidilactici, Lactobacillus sakei, Lactococcus lactis, Leuconostoc carnosum, and Staphylococcus carnosus. 11. The composition according to claim 10, wherein the bacteria of one or more of the species selected from Pediococcus acidilactici, Lactobacillus sakei, Lactococcus lactis, Leuconostoc carnosum, and Staphylococcus carnosus is selected from Pediococcus acidilactici deposited at the DSMZ under accession number DSM 28307, Lactobacillus sakei deposited at the DSMZ under accession number DSM 14022, Lactococcus lactis deposited at the DSMZ under accession number DSM 11037, and Leuconostoc carnosum LC1043. 12. A method for inhibiting the amount of spoilage or pathogenic bacteria in a food product, comprising adding bacteria of a mutant Lactobacillus curvatus strain according to claim 1 to a food product at a concentration of at least 105 CFU/g. 13. The method according to claim 12, wherein the pathogenic bacteria is Listeria. 14. A method for inhibiting the amount of spoilage or pathogenic bacteria in a food product, comprising adding a composition according to claim 6 to a food product in an amount to provide the mutant Lactobacillus curvatus strain at a concentration of at least 105 CFU/g. 15. The method according to claim 14, wherein the pathogenic bacteria is Listeria. | 2,800 |
345,448 | 16,643,392 | 2,814 | Disclosed is a surface foreign substance detector for a transparent or translucent film. The surface foreign substance detector for a transparent or translucent film according to the present invention comprises: an optical unit; an optical housing accommodating the optical unit therein; a light emission unit emitting light to the film; and a film holder providing a loading surface such that the film can be loaded thereon and made of a light-absorbing material capable of absorbing light or reflecting the light at a predetermined ratio or less. According to the present invention, the holder supporter is manufactured by using a material capable of generating a predetermined electrostatic force or more between the holder supporter and the foreign substances floating in a surrounding space to prevent foreign substances floating or scattered in a surrounding work space from being moved to the film side, thereby improving detection reliability. | 1. A surface foreign substance detector of a transparent or translucent film which detects foreign substances attached onto the surface of the film, the surface foreign substance detector comprising:
an optical unit; an optical housing accommodating the optical unit therein and formed in a through shape; a light emission unit provided at a lower side of the optical housing to emit the light toward the film; and a film holder provided to be spaced apart from the lower side of the light emission unit to provide a loading surface so that the film is able to be loaded thereon and formed of a light-absorbing material capable of absorbing the light or reflect the light at a predetermined ratio or less, wherein a guide groove is provided on an upper surface of the film holder to guide the loading position of the film and a through hole is provided in the guide groove to transmit the light emitted from the light emission unit. 2. The surface foreign substance detector of claim 1, further comprising:
a holder supporter configured to support the film holder from the lower portion of the film holder, wherein the holder supporter is made of a material capable of generating a predetermined electric force or more between the holder supporter and the foreign substances floating in a surrounding space. 3. The surface foreign substance detector of claim 1, further comprising:
a light blocking plate provided below the light emission unit to block light emitted from a surrounding light source from being transmitted to the film side, wherein the light blocking plate is provided to extend to the outside of the light emission unit at a predetermined length or more and made of a light-absorbing material capable of absorbing light or reflecting the light at a predetermined ratio or less. 4. The surface foreign substance detector of claim 3, wherein the film holder and the light blocking plate are made of the same material and formed by sand-blasting and then black-anodizing the surface thereof. 5. The surface foreign substance detector of claim 3, wherein the optical housing and the light blocking plate are made of a thermally conductive material having a predetermined thermal conductivity or more, respectively, and emit the heat generated from the light emission unit to the outside. 6. The surface foreign substance detector of claim 1, wherein the light emission unit includes
a light emission body having an empty space formed in a central region corresponding to an arrangement position of the film; a plurality of light sources provided in sections of the light emission body to emit the light to the film in a plurality of directions; and a plurality of light diffusion plates diffusing the light emitted from the plurality of light sources. 7. The surface foreign substance detector of claim 6, wherein while the film is disposed on the film holder, the plurality of light sources is positioned above the film and light emission angles of the plurality of light sources for the film are in the range of 5° to 30°. 8. The surface foreign substance detector of claim 1, wherein a foreign substance fall prevention film made of a transparent material is further provided below the optical housing to prevent foreign substances generated in the optical housing from falling onto the film. 9. The surface foreign substance detector of claim 8, wherein the foreign substance fall prevention film is made of any one of glass, quartz, and acryl and installed interchangeably in the optical housing. 10. The surface foreign substance detector of claim 1, wherein the film holder is formed in a hollow cube, a hollow cylinder, a hollow polyhedron, and the like, and the film holder has a predetermined inner area depth or more so that the light emitted from the light emission unit passes through the film to be reflected or scattered on its inner bottom surface, and then is not introduced within a focal length of the optical unit again. | Disclosed is a surface foreign substance detector for a transparent or translucent film. The surface foreign substance detector for a transparent or translucent film according to the present invention comprises: an optical unit; an optical housing accommodating the optical unit therein; a light emission unit emitting light to the film; and a film holder providing a loading surface such that the film can be loaded thereon and made of a light-absorbing material capable of absorbing light or reflecting the light at a predetermined ratio or less. According to the present invention, the holder supporter is manufactured by using a material capable of generating a predetermined electrostatic force or more between the holder supporter and the foreign substances floating in a surrounding space to prevent foreign substances floating or scattered in a surrounding work space from being moved to the film side, thereby improving detection reliability.1. A surface foreign substance detector of a transparent or translucent film which detects foreign substances attached onto the surface of the film, the surface foreign substance detector comprising:
an optical unit; an optical housing accommodating the optical unit therein and formed in a through shape; a light emission unit provided at a lower side of the optical housing to emit the light toward the film; and a film holder provided to be spaced apart from the lower side of the light emission unit to provide a loading surface so that the film is able to be loaded thereon and formed of a light-absorbing material capable of absorbing the light or reflect the light at a predetermined ratio or less, wherein a guide groove is provided on an upper surface of the film holder to guide the loading position of the film and a through hole is provided in the guide groove to transmit the light emitted from the light emission unit. 2. The surface foreign substance detector of claim 1, further comprising:
a holder supporter configured to support the film holder from the lower portion of the film holder, wherein the holder supporter is made of a material capable of generating a predetermined electric force or more between the holder supporter and the foreign substances floating in a surrounding space. 3. The surface foreign substance detector of claim 1, further comprising:
a light blocking plate provided below the light emission unit to block light emitted from a surrounding light source from being transmitted to the film side, wherein the light blocking plate is provided to extend to the outside of the light emission unit at a predetermined length or more and made of a light-absorbing material capable of absorbing light or reflecting the light at a predetermined ratio or less. 4. The surface foreign substance detector of claim 3, wherein the film holder and the light blocking plate are made of the same material and formed by sand-blasting and then black-anodizing the surface thereof. 5. The surface foreign substance detector of claim 3, wherein the optical housing and the light blocking plate are made of a thermally conductive material having a predetermined thermal conductivity or more, respectively, and emit the heat generated from the light emission unit to the outside. 6. The surface foreign substance detector of claim 1, wherein the light emission unit includes
a light emission body having an empty space formed in a central region corresponding to an arrangement position of the film; a plurality of light sources provided in sections of the light emission body to emit the light to the film in a plurality of directions; and a plurality of light diffusion plates diffusing the light emitted from the plurality of light sources. 7. The surface foreign substance detector of claim 6, wherein while the film is disposed on the film holder, the plurality of light sources is positioned above the film and light emission angles of the plurality of light sources for the film are in the range of 5° to 30°. 8. The surface foreign substance detector of claim 1, wherein a foreign substance fall prevention film made of a transparent material is further provided below the optical housing to prevent foreign substances generated in the optical housing from falling onto the film. 9. The surface foreign substance detector of claim 8, wherein the foreign substance fall prevention film is made of any one of glass, quartz, and acryl and installed interchangeably in the optical housing. 10. The surface foreign substance detector of claim 1, wherein the film holder is formed in a hollow cube, a hollow cylinder, a hollow polyhedron, and the like, and the film holder has a predetermined inner area depth or more so that the light emitted from the light emission unit passes through the film to be reflected or scattered on its inner bottom surface, and then is not introduced within a focal length of the optical unit again. | 2,800 |
345,449 | 16,643,380 | 2,814 | Provided is a method for manufacturing a cooling device and a motor housing cooling device manufactured using same, the method including the steps of: making a cooling pipe and forming the cooling pipe to a shape capable of being buried in a housing body; filling the cooling pipe with a support material; making a portion divided from the housing body as a jig body so as to support the cooling pipe against the jib body in an injection mold of the housing body; locating the cooling pipe in the injection mold of the housing body in such a manner as to be supported against the jig body and injection-molding the housing body; and after the injection molding, removing the support material from the cooling pipe. | 1. A method for manufacturing a cooling device for circulating a cooling fluid along a cooling pipe, the method comprising the steps of:
making the cooling pipe and forming the cooling pipe to a shape capable of being buried in a housing body; filling the cooling pipe with a support material; making a portion divided from the housing body as a jig body so as to support the cooling pipe against the jib body in an injection mold of the housing body; locating the cooling pipe in the injection mold of the housing body in such a manner as to be supported against the jig body and injection-molding the housing body; and after the injection molding, removing the support material from the cooling pipe. 2. The method according to claim 1, wherein the cooling pipe is a helix cooling pipe formed by winding a single pipe helixly with respect to the housing body. 3. The method according to claim 1, wherein the cooling pipe is a U-shaped cooling pipe formed by bending a single pipe in form of zigzag to have a circular shape in a plane direction. 4. The method according to claim 1, wherein one or a plurality of jig bodies is provided, and the plurality of jig bodies have widths whose portions are smaller than original body widths thereof, so that facing portions of the jig bodies have sufficient gaps therebetween. 5. The method according to claim 1, wherein, the jig body has a plurality of injection grooves formed on the surface thereof to allow a liquid material of the housing body to be injected thereinto. 6. The method according to claim 1, wherein the support rial is made of at least one selected from the group consisting of a water soluble material, non-organic grains or powder, heat-resistant grains or powder, and heat-resistant fibers, and after molding the housing body, water is injected into the cooling pipe to remove the support material from the cooling pipe. 7. The method according to claim 1, wherein the cooling pipe is coupled to a vibration absorbing pipe, and a vibration absorbing material as a support material is filled in the vibration absorbing pipe, so that the vibration absorbing pipe is buried in the housing body, together with the cooling pipe, through the injection molding of the housing body, and after the molding, the support material inside the cooling pipe is removed, while the vibration absorbing material inside the vibration absorbing pipe is being not removed. 8. The method according to claim 1, wherein the cooling pipe is coupled to a vibration absorbing pipe, and the support material is filled in the vibration absorbing material as well as the cooling pipe, so that the vibration absorbing pipe is buried in the housing body, together with the cooling pipe, through the injection molding of the housing body, and after the molding, the support material inside the cooling pipe and the vibration absorbing pipe is removed, while a vibration absorbing material is being filled in the vibration absorbing pipe from which the support material is removed. 9. The method according to claim 1, wherein the cooling device is configured to allow the cooling pipe to be buried in the housing body having an accommodation space formed therein to locate a motor therein and to allow the cooling fluid to be circulated through the cooling pipe so that the motor becomes cool. 10. A motor housing cooling device comprising:
a motor housing having a housing body having an accommodation space formed therein to locate a motor therein and a cover adapted to close the housing body; a helix cooling pipe buried helixly in the housing body in a longitudinal direction of the housing body in such a manner as to allow a cooling fluid to flow therealong; and a vibration absorbing pipe adapted to absorb vibrations and having a pipe-shaped body coupled to the side periphery of the helix cooling pipe and a vibration absorbing material filled in the body, wherein after the helix cooling pipe is filled with a removable support material and the vibration absorbing pipe with the vibration absorbing material, the helix cooling pipe and the vibration absorbing pipe are located in a housing body injection mold in such a manner as to mold the housing body with the helix cooling pipe and the vibration absorbing pipe buried therein by means of insert injection molding, and after molding, the support material filled in the helix cooling pipe is removed to allow the cooling fluid to be circulated through the helix cooling pipe so that the motor becomes cool. 11. The motor housing cooling device according to claim 10, wherein the helix cooling pipe is configured to allow a sectional shape of the cooling fluid flowing therethrough to become circular or rectangular. 12. The motor housing cooling device according to claim 10, wherein the vibration absorbing pipe has a sectional shape of a circle or rectangle in a radial direction thereof. 13. The motor housing cooling device according to claim 10, further comprising a coupling member whose one end portion is coupled to the side peripheral surface of the helix cooling pipe and whose other end portion is coupled to the side peripheral surface of the vibration absorbing pipe to allow the vibration absorbing pipe to be coupled to the helix cooling pipe in such a manner as to be spaced apart from the side peripheral surface of the helix cooling pipe. 14. The motor housing cooling device according to claim 10, wherein the vibration absorbing pipe is coupled to an inner or outer peripheral surface of the helix cooling pipe in such a manner as to be helixly formed correspondingly to the helix cooling pipe. 15. The motor housing cooling device according to claim 10, wherein the support material is made of at least one selected from the group consisting of a water soluble material, non-organic grains or powder, heat-resistant grains or powder, and heat-resistant fibers, and after molding the housing body, water injected into the cooling pipe to remove the support material from the cooling pipe. 16. The motor housing cooling device according to claim 10, wherein the helix cooling pipe and the vibration absorbing pipe are extrusion-molded unitarily with each other by means of the coupling member and are formed to helix pipes to be buried in the housing body so that the helix pipes are formed to hollow portions of the housing body by means of the insert injection molding. 17. A motor housing cooling device comprising:
a motor housing having a housing body having an accommodation space formed therein to locate a motor therein and a cover adapted to close the housing body; a U-shaped cooling pipe buried in form of zigzag in the housing body in an up and down direction of the housing body in such a manner as to allow a cooling fluid to flow therealong; and vibration absorbing pipes adapted to absorb vibrations, each vibration absorbing pipe having a pipe-shaped body coupled to the side periphery of the U-shaped cooling pipe and a vibration absorbing material filled in the body, wherein after the U-shaped cooling pipe is filled with a removable support material and the vibration absorbing pipes are filled with the vibration absorbing material, the U-shaped cooling pipe and the vibration absorbing pipes are located in a housing body injection mold in such a manner as to allow the U-shaped cooling pipe and the vibration absorbing pipes to be supported against a jig body made by dividing a portion of the housing body and to allow the housing body to be molded by means of insert injection molding, and after molding, the support material filled in the U-shaped cooling pipe is removed to provide the housing body where the U-shaped cooling pipe and the vibration absorbing pipes are buried in form of hollow portions, so that the motor becomes cool through circulation of the cooling fluid along the U-shaped cooling pipe. 18. The motor housing cooling device according to claim 17, wherein the U-shaped cooling pipe comprises:
a plurality of linear pipes erected in up and down directions in such a manner as to be spaced apart from each other at given intervals; and curved pipes bent to allow both end portions thereof to communicate with tops and undersides of the linear pipes adjacent to each other. 19. The motor housing cooling device according to claim 18, wherein bodies of the vibration absorbing pipes are coupled to the side peripheral surface of the U-shaped cooling pipe in such a manner as to be spaced apart therefrom by means of coupling members. 20. The motor housing cooling device according to claim 18, wherein the vibration absorbing pipes are coupled to inner or outer peripheral surfaces of the linear pipes in such a manner as to be erected in up and down directions correspondingly to the linear pipes. | Provided is a method for manufacturing a cooling device and a motor housing cooling device manufactured using same, the method including the steps of: making a cooling pipe and forming the cooling pipe to a shape capable of being buried in a housing body; filling the cooling pipe with a support material; making a portion divided from the housing body as a jig body so as to support the cooling pipe against the jib body in an injection mold of the housing body; locating the cooling pipe in the injection mold of the housing body in such a manner as to be supported against the jig body and injection-molding the housing body; and after the injection molding, removing the support material from the cooling pipe.1. A method for manufacturing a cooling device for circulating a cooling fluid along a cooling pipe, the method comprising the steps of:
making the cooling pipe and forming the cooling pipe to a shape capable of being buried in a housing body; filling the cooling pipe with a support material; making a portion divided from the housing body as a jig body so as to support the cooling pipe against the jib body in an injection mold of the housing body; locating the cooling pipe in the injection mold of the housing body in such a manner as to be supported against the jig body and injection-molding the housing body; and after the injection molding, removing the support material from the cooling pipe. 2. The method according to claim 1, wherein the cooling pipe is a helix cooling pipe formed by winding a single pipe helixly with respect to the housing body. 3. The method according to claim 1, wherein the cooling pipe is a U-shaped cooling pipe formed by bending a single pipe in form of zigzag to have a circular shape in a plane direction. 4. The method according to claim 1, wherein one or a plurality of jig bodies is provided, and the plurality of jig bodies have widths whose portions are smaller than original body widths thereof, so that facing portions of the jig bodies have sufficient gaps therebetween. 5. The method according to claim 1, wherein, the jig body has a plurality of injection grooves formed on the surface thereof to allow a liquid material of the housing body to be injected thereinto. 6. The method according to claim 1, wherein the support rial is made of at least one selected from the group consisting of a water soluble material, non-organic grains or powder, heat-resistant grains or powder, and heat-resistant fibers, and after molding the housing body, water is injected into the cooling pipe to remove the support material from the cooling pipe. 7. The method according to claim 1, wherein the cooling pipe is coupled to a vibration absorbing pipe, and a vibration absorbing material as a support material is filled in the vibration absorbing pipe, so that the vibration absorbing pipe is buried in the housing body, together with the cooling pipe, through the injection molding of the housing body, and after the molding, the support material inside the cooling pipe is removed, while the vibration absorbing material inside the vibration absorbing pipe is being not removed. 8. The method according to claim 1, wherein the cooling pipe is coupled to a vibration absorbing pipe, and the support material is filled in the vibration absorbing material as well as the cooling pipe, so that the vibration absorbing pipe is buried in the housing body, together with the cooling pipe, through the injection molding of the housing body, and after the molding, the support material inside the cooling pipe and the vibration absorbing pipe is removed, while a vibration absorbing material is being filled in the vibration absorbing pipe from which the support material is removed. 9. The method according to claim 1, wherein the cooling device is configured to allow the cooling pipe to be buried in the housing body having an accommodation space formed therein to locate a motor therein and to allow the cooling fluid to be circulated through the cooling pipe so that the motor becomes cool. 10. A motor housing cooling device comprising:
a motor housing having a housing body having an accommodation space formed therein to locate a motor therein and a cover adapted to close the housing body; a helix cooling pipe buried helixly in the housing body in a longitudinal direction of the housing body in such a manner as to allow a cooling fluid to flow therealong; and a vibration absorbing pipe adapted to absorb vibrations and having a pipe-shaped body coupled to the side periphery of the helix cooling pipe and a vibration absorbing material filled in the body, wherein after the helix cooling pipe is filled with a removable support material and the vibration absorbing pipe with the vibration absorbing material, the helix cooling pipe and the vibration absorbing pipe are located in a housing body injection mold in such a manner as to mold the housing body with the helix cooling pipe and the vibration absorbing pipe buried therein by means of insert injection molding, and after molding, the support material filled in the helix cooling pipe is removed to allow the cooling fluid to be circulated through the helix cooling pipe so that the motor becomes cool. 11. The motor housing cooling device according to claim 10, wherein the helix cooling pipe is configured to allow a sectional shape of the cooling fluid flowing therethrough to become circular or rectangular. 12. The motor housing cooling device according to claim 10, wherein the vibration absorbing pipe has a sectional shape of a circle or rectangle in a radial direction thereof. 13. The motor housing cooling device according to claim 10, further comprising a coupling member whose one end portion is coupled to the side peripheral surface of the helix cooling pipe and whose other end portion is coupled to the side peripheral surface of the vibration absorbing pipe to allow the vibration absorbing pipe to be coupled to the helix cooling pipe in such a manner as to be spaced apart from the side peripheral surface of the helix cooling pipe. 14. The motor housing cooling device according to claim 10, wherein the vibration absorbing pipe is coupled to an inner or outer peripheral surface of the helix cooling pipe in such a manner as to be helixly formed correspondingly to the helix cooling pipe. 15. The motor housing cooling device according to claim 10, wherein the support material is made of at least one selected from the group consisting of a water soluble material, non-organic grains or powder, heat-resistant grains or powder, and heat-resistant fibers, and after molding the housing body, water injected into the cooling pipe to remove the support material from the cooling pipe. 16. The motor housing cooling device according to claim 10, wherein the helix cooling pipe and the vibration absorbing pipe are extrusion-molded unitarily with each other by means of the coupling member and are formed to helix pipes to be buried in the housing body so that the helix pipes are formed to hollow portions of the housing body by means of the insert injection molding. 17. A motor housing cooling device comprising:
a motor housing having a housing body having an accommodation space formed therein to locate a motor therein and a cover adapted to close the housing body; a U-shaped cooling pipe buried in form of zigzag in the housing body in an up and down direction of the housing body in such a manner as to allow a cooling fluid to flow therealong; and vibration absorbing pipes adapted to absorb vibrations, each vibration absorbing pipe having a pipe-shaped body coupled to the side periphery of the U-shaped cooling pipe and a vibration absorbing material filled in the body, wherein after the U-shaped cooling pipe is filled with a removable support material and the vibration absorbing pipes are filled with the vibration absorbing material, the U-shaped cooling pipe and the vibration absorbing pipes are located in a housing body injection mold in such a manner as to allow the U-shaped cooling pipe and the vibration absorbing pipes to be supported against a jig body made by dividing a portion of the housing body and to allow the housing body to be molded by means of insert injection molding, and after molding, the support material filled in the U-shaped cooling pipe is removed to provide the housing body where the U-shaped cooling pipe and the vibration absorbing pipes are buried in form of hollow portions, so that the motor becomes cool through circulation of the cooling fluid along the U-shaped cooling pipe. 18. The motor housing cooling device according to claim 17, wherein the U-shaped cooling pipe comprises:
a plurality of linear pipes erected in up and down directions in such a manner as to be spaced apart from each other at given intervals; and curved pipes bent to allow both end portions thereof to communicate with tops and undersides of the linear pipes adjacent to each other. 19. The motor housing cooling device according to claim 18, wherein bodies of the vibration absorbing pipes are coupled to the side peripheral surface of the U-shaped cooling pipe in such a manner as to be spaced apart therefrom by means of coupling members. 20. The motor housing cooling device according to claim 18, wherein the vibration absorbing pipes are coupled to inner or outer peripheral surfaces of the linear pipes in such a manner as to be erected in up and down directions correspondingly to the linear pipes. | 2,800 |
345,450 | 16,643,396 | 2,814 | A video device includes at least one of an input connector and an output connector connectible with a video-signal cable, wherein the input connector is connected to a first resistor coupled with a predetermined potential and oppositely connected to a first signal line of the video-signal cable connected to a second resistor of a second video device, and wherein the output connector is connected to a third resistor coupled with a ground potential and oppositely connected to a second signal line of the video-signal cable connected to a fourth resistor of a third video device; and a connection determination part configured to determine a normal connection of the video-signal cable connected to the input connector based on a potential of the first signal line or to determine a normal connection of the video-signal cable connected to the output connector based on a potential of the second signal line. | 1. A video device comprising:
at least one of an input connector coupled with a video-signal cable configured to transmit a video signal and an output connector coupled with the video-signal cable, wherein a first resistor is provided in connection with the input connector while a third resistor is provided in connection with the output connector, wherein when the input connector is provided and normally connected to other video device through the video-signal cable, a first signal line, corresponding to one of a plurality of signal lines connected to the input connector, is connected to a first potential via a second resistor and a first switch included in the other video device in which the first switch is closed upon turning on a main power source of the other video device, wherein the first signal line is further connected to a second potential different from the first potential via the first resistor, and wherein when the output connector is provided and normally connected to the other video device through the video-signal cable, a second signal line, corresponding to one of a plurality of signal lines connected to the output connector, is connected to a third potential via a fourth resistor and a second switch included in the other video device in which the second switch is closed upon turning on the main power source of the other video device, wherein the second signal line is further connected to a fourth potential different from the third potential via the third resistor; and a connection determination part configured to determine whether or not the video-signal cable is connected normally based on a potential of the first signal line or a potential of the second signal line. 2. The video device according to claim 1, wherein the connection determination part is configured to determine a normal connection of the video-signal cable when the potential of the first signal line corresponds to a partial potential which is produced by dividing a potential difference between the first potential and the second potential by a series circuit consisting of the first resistor and the second resistor or when the potential of the second signal line corresponds to a partial potential which is produced by dividing a potential difference between the third potential and the fourth potential by a series circuit consisting of the third resistor and the fourth resistor, and wherein the connection determination part is configured not to determine the normal connection of the video-signal cable without conformity with the partial potential. 3. The video device according to claim 1, further comprising a third switch configured to close or open a connection between the first resistor and the second potential wherein the third switch is closed upon turning on a main power source of the video device, or a fourth switch configured to close or open an connection between the third resistor and the fourth potential wherein the fourth switch is closed upon turning on the main power source of the video device. 4. The video device according to claim 1, wherein the input connector and the output connector are each configured of a DP connector. 5. A video device comprising at least one of an input connector and an output connector connectible to a video-signal cable, further comprising:
at least one of a first switch and a second switch which are each closed upon turning on a main power source of the video device; at least one of a first signal line which is connected to the input connector and which is connected to a first resistor joining the first switch coupled with a first-potential signal line and a second signal line which is connected to the output connector and which is connected to a second resistor joining the second switch coupled with a second-potential signal line and a connection determination part configured to determine whether or not the video-signal cable is normally connected to the input connector based on a potential of the first signal line and/or configured to determine whether or not the video-signal cable is normally connected to the output connector based on a potential of the second signal line. 6. The video device according to claim 5, wherein the connection determination part is further configured to determine that the video-signal cable is normally connected to the input connector when the potential of the first signal line is equal to a predetermined potential, and wherein the connection determination part is further configured to determine that the video-signal cable is normally connected to the output connector when the potential of the second signal line is equal to the predetermined potential. 7. The video device according to claim 6, wherein the predetermined potential is lower than the first potential but higher than the second potential. 8. The video device according to claim 5, wherein a resistance of the first resistor is larger than a resistance of the second resistor. 9. The video device according to claim 5, wherein the first resistor comprises a pullup resistor while the second resistor comprises a pulldown resistor. 10. The video device according to claim 5, wherein a signal type allocated to the first terminal is identical to a signal type allocated to the second terminal. 11. The video device according to claim 5, wherein the connection determination part is further configured to display a predetermined image on a display part of the video device upon determining that the video-signal cable is not normally connected to the input connector and/or the output connector. 12. A connection determination method for a video device comprising an input connector and an output connector connectible to a video-signal cable, comprising:
closing a first switch, which is connected to a first signal line coupled with a first terminal of the input connector via a first resistor and further connected to a first-potential signal line, upon turning on a main power source of the video device; closing a second switch, which is connected to a second signal line coupled with a second terminal of the output connector via a second resistor and further connected to a second-potential signal line, upon turning on the main power source of the video device; determining whether or not the video-signal cable is normally connected to the input connector based on a potential of the first signal line; and determining whether or not the video-signal cable is normally connected to the output connector based on a potential of the second signal line. 13. A video device comprising at least one of an input connector and an output connector each connectible to a video-signal cable, wherein the input connector is connected to a first resistor coupled with a predetermined potential and oppositely connected to a first signal line of the video-signal cable while the output connector is connected to a third resistor coupled with a ground potential and oppositely connected to a second signal line of the video-signal cable. 14. The video device according to claim 13, wherein the video-signal cable connected to the input connector is connected to a second video device in which the first signal line is connected to a second resistor and a first switch coupled with another ground potential, and wherein the first switch is closed when power is applied to the second video device. 15. The video device according to claim 13, wherein the video-signal cable connected to the output connector is connected to a third video device in which the second signal line is connected to a fourth resistor and a second switch coupled with another predetermined potential, and wherein the second switch is closed when power is applied to the third video device. 16. The video device according to 14, wherein the first resistor is configured of a pullup resistor while the second resistor is configured of a pull-down resistor. | A video device includes at least one of an input connector and an output connector connectible with a video-signal cable, wherein the input connector is connected to a first resistor coupled with a predetermined potential and oppositely connected to a first signal line of the video-signal cable connected to a second resistor of a second video device, and wherein the output connector is connected to a third resistor coupled with a ground potential and oppositely connected to a second signal line of the video-signal cable connected to a fourth resistor of a third video device; and a connection determination part configured to determine a normal connection of the video-signal cable connected to the input connector based on a potential of the first signal line or to determine a normal connection of the video-signal cable connected to the output connector based on a potential of the second signal line.1. A video device comprising:
at least one of an input connector coupled with a video-signal cable configured to transmit a video signal and an output connector coupled with the video-signal cable, wherein a first resistor is provided in connection with the input connector while a third resistor is provided in connection with the output connector, wherein when the input connector is provided and normally connected to other video device through the video-signal cable, a first signal line, corresponding to one of a plurality of signal lines connected to the input connector, is connected to a first potential via a second resistor and a first switch included in the other video device in which the first switch is closed upon turning on a main power source of the other video device, wherein the first signal line is further connected to a second potential different from the first potential via the first resistor, and wherein when the output connector is provided and normally connected to the other video device through the video-signal cable, a second signal line, corresponding to one of a plurality of signal lines connected to the output connector, is connected to a third potential via a fourth resistor and a second switch included in the other video device in which the second switch is closed upon turning on the main power source of the other video device, wherein the second signal line is further connected to a fourth potential different from the third potential via the third resistor; and a connection determination part configured to determine whether or not the video-signal cable is connected normally based on a potential of the first signal line or a potential of the second signal line. 2. The video device according to claim 1, wherein the connection determination part is configured to determine a normal connection of the video-signal cable when the potential of the first signal line corresponds to a partial potential which is produced by dividing a potential difference between the first potential and the second potential by a series circuit consisting of the first resistor and the second resistor or when the potential of the second signal line corresponds to a partial potential which is produced by dividing a potential difference between the third potential and the fourth potential by a series circuit consisting of the third resistor and the fourth resistor, and wherein the connection determination part is configured not to determine the normal connection of the video-signal cable without conformity with the partial potential. 3. The video device according to claim 1, further comprising a third switch configured to close or open a connection between the first resistor and the second potential wherein the third switch is closed upon turning on a main power source of the video device, or a fourth switch configured to close or open an connection between the third resistor and the fourth potential wherein the fourth switch is closed upon turning on the main power source of the video device. 4. The video device according to claim 1, wherein the input connector and the output connector are each configured of a DP connector. 5. A video device comprising at least one of an input connector and an output connector connectible to a video-signal cable, further comprising:
at least one of a first switch and a second switch which are each closed upon turning on a main power source of the video device; at least one of a first signal line which is connected to the input connector and which is connected to a first resistor joining the first switch coupled with a first-potential signal line and a second signal line which is connected to the output connector and which is connected to a second resistor joining the second switch coupled with a second-potential signal line and a connection determination part configured to determine whether or not the video-signal cable is normally connected to the input connector based on a potential of the first signal line and/or configured to determine whether or not the video-signal cable is normally connected to the output connector based on a potential of the second signal line. 6. The video device according to claim 5, wherein the connection determination part is further configured to determine that the video-signal cable is normally connected to the input connector when the potential of the first signal line is equal to a predetermined potential, and wherein the connection determination part is further configured to determine that the video-signal cable is normally connected to the output connector when the potential of the second signal line is equal to the predetermined potential. 7. The video device according to claim 6, wherein the predetermined potential is lower than the first potential but higher than the second potential. 8. The video device according to claim 5, wherein a resistance of the first resistor is larger than a resistance of the second resistor. 9. The video device according to claim 5, wherein the first resistor comprises a pullup resistor while the second resistor comprises a pulldown resistor. 10. The video device according to claim 5, wherein a signal type allocated to the first terminal is identical to a signal type allocated to the second terminal. 11. The video device according to claim 5, wherein the connection determination part is further configured to display a predetermined image on a display part of the video device upon determining that the video-signal cable is not normally connected to the input connector and/or the output connector. 12. A connection determination method for a video device comprising an input connector and an output connector connectible to a video-signal cable, comprising:
closing a first switch, which is connected to a first signal line coupled with a first terminal of the input connector via a first resistor and further connected to a first-potential signal line, upon turning on a main power source of the video device; closing a second switch, which is connected to a second signal line coupled with a second terminal of the output connector via a second resistor and further connected to a second-potential signal line, upon turning on the main power source of the video device; determining whether or not the video-signal cable is normally connected to the input connector based on a potential of the first signal line; and determining whether or not the video-signal cable is normally connected to the output connector based on a potential of the second signal line. 13. A video device comprising at least one of an input connector and an output connector each connectible to a video-signal cable, wherein the input connector is connected to a first resistor coupled with a predetermined potential and oppositely connected to a first signal line of the video-signal cable while the output connector is connected to a third resistor coupled with a ground potential and oppositely connected to a second signal line of the video-signal cable. 14. The video device according to claim 13, wherein the video-signal cable connected to the input connector is connected to a second video device in which the first signal line is connected to a second resistor and a first switch coupled with another ground potential, and wherein the first switch is closed when power is applied to the second video device. 15. The video device according to claim 13, wherein the video-signal cable connected to the output connector is connected to a third video device in which the second signal line is connected to a fourth resistor and a second switch coupled with another predetermined potential, and wherein the second switch is closed when power is applied to the third video device. 16. The video device according to 14, wherein the first resistor is configured of a pullup resistor while the second resistor is configured of a pull-down resistor. | 2,800 |
345,451 | 16,643,360 | 2,814 | A head-up display apparatus in which display light emitted by a display device to express an image is reflected by a reflecting part, and a virtual image corresponding to the reflected image is displayed. The apparatus includes: a reflecting-part holder provided with a pair of rotary shaft parts protruding at both ends thereof, the rotary shaft parts retaining the reflecting part; a pair of bearings rotatably supporting the pair of rotary shaft parts; and a pair of bearing holders retaining the pair of bearings in a housing; first supported parts protruding in the radial direction of the bearings provided to the bearing holders, and the housing provided with a hole-shaped first support part in which the first supported part of one bearing holder is positioned, and an elongated-hole-shaped second support part elongated in an axial direction in which the first supported part of the other bearing holder is positioned. | 1. A head-up display apparatus for reflecting, by a reflecting part, display light emitted by a display device to express an image and displaying a virtual image corresponding to the image by the display light reflected by the reflecting part, comprising:
a reflecting-part holder provided with a pair of rotary shaft parts protruding at both ends of the reflecting-part holder, the reflecting-part holder for retaining the reflecting part; a pair of bearings for rotatably supporting the pair of rotary shaft parts respectively; and a pair of bearing holders for retaining the pair of bearings in a housing respectively, wherein a first supported part protruding in a radial direction of each of the bearings is provided to each of the bearing holders, and the housing includes a hole-shaped first support part in which the first supported part of one of the bearing holders is positioned, and an elongated-hole-shaped second support part along an axial direction of the rotary shaft parts in which the first supported part of the other of the bearing holders is positioned. 2. The head-up display apparatus according to claim 1, wherein
at least one of the pair of bearing holders is provided with a second supported part to be positioned in the housing, the second supported part being arranged and protruding in a direction intersecting with the axial direction of the rotary shaft parts, and the housing includes an elongated-hole-shaped third support part along a direction intersecting with the axial direction, the second supported part being positioned in the third support part. 3. The head-up display apparatus according to claim 2, wherein
a bearing holder having a same shape as the one of the bearing holders provided with the second supported part is arranged as a bearing holder on the opposite side, and the housing includes an elongated-hole-shaped fourth support part wider than the second supported part along the axial direction of the rotary shaft parts, the second supported part of the bearing holder on the opposite side being positioned in the fourth support part. 4. The head-up display apparatus according to claim 1, wherein the rotary shaft parts are provided separately from the reflecting-part holder. | A head-up display apparatus in which display light emitted by a display device to express an image is reflected by a reflecting part, and a virtual image corresponding to the reflected image is displayed. The apparatus includes: a reflecting-part holder provided with a pair of rotary shaft parts protruding at both ends thereof, the rotary shaft parts retaining the reflecting part; a pair of bearings rotatably supporting the pair of rotary shaft parts; and a pair of bearing holders retaining the pair of bearings in a housing; first supported parts protruding in the radial direction of the bearings provided to the bearing holders, and the housing provided with a hole-shaped first support part in which the first supported part of one bearing holder is positioned, and an elongated-hole-shaped second support part elongated in an axial direction in which the first supported part of the other bearing holder is positioned.1. A head-up display apparatus for reflecting, by a reflecting part, display light emitted by a display device to express an image and displaying a virtual image corresponding to the image by the display light reflected by the reflecting part, comprising:
a reflecting-part holder provided with a pair of rotary shaft parts protruding at both ends of the reflecting-part holder, the reflecting-part holder for retaining the reflecting part; a pair of bearings for rotatably supporting the pair of rotary shaft parts respectively; and a pair of bearing holders for retaining the pair of bearings in a housing respectively, wherein a first supported part protruding in a radial direction of each of the bearings is provided to each of the bearing holders, and the housing includes a hole-shaped first support part in which the first supported part of one of the bearing holders is positioned, and an elongated-hole-shaped second support part along an axial direction of the rotary shaft parts in which the first supported part of the other of the bearing holders is positioned. 2. The head-up display apparatus according to claim 1, wherein
at least one of the pair of bearing holders is provided with a second supported part to be positioned in the housing, the second supported part being arranged and protruding in a direction intersecting with the axial direction of the rotary shaft parts, and the housing includes an elongated-hole-shaped third support part along a direction intersecting with the axial direction, the second supported part being positioned in the third support part. 3. The head-up display apparatus according to claim 2, wherein
a bearing holder having a same shape as the one of the bearing holders provided with the second supported part is arranged as a bearing holder on the opposite side, and the housing includes an elongated-hole-shaped fourth support part wider than the second supported part along the axial direction of the rotary shaft parts, the second supported part of the bearing holder on the opposite side being positioned in the fourth support part. 4. The head-up display apparatus according to claim 1, wherein the rotary shaft parts are provided separately from the reflecting-part holder. | 2,800 |
345,452 | 16,643,349 | 2,814 | A plating apparatus for depositing metal on a substrate, comprising a membrane frame (14), a catholyte inlet pipe (30) and a center cap (40). The membrane frame (14) has a center passage (144) which passes through the center of the membrane frame (14). The catholyte inlet pipe (30) is connected to the center passage (144) of the membrane frame (14). The center cap (40) is fixed at the center of the membrane frame (14) and covers over the center passage (144) of the membrane frame (14). The top of the center cap (40) has a plurality of first holes (42). The catholyte inlet pipe (30) supplies catholyte to the center cap (40) through the center passage (144) of the membrane frame (14), and the catholyte is supplied to a center area of the substrate through the first holes (42) of the center cap (40). | 1. A plating apparatus for depositing metal on a substrate, comprising:
a membrane frame, having a center passage which passes through the center of the membrane frame; a catholyte inlet pipe, connecting to the center passage of the membrane frame; a center cap, fixed at the center of the membrane frame and covering over the center passage of the membrane frame, the top of the center cap having a plurality of first holes; wherein the catholyte inlet pipe supplies catholyte to the center cap through the center passage of the membrane frame, and the catholyte is supplied to a center area of the substrate through the first holes of the center cap. 2. The plating apparatus according to claim 1, wherein the flow of the catholyte supplied to the center cap is adjustable and controlled independently. 3. The plating apparatus according to claim 1, wherein the center cap has a through-hole defined at the center of the center cap, an adjustable member is inserted in the through-hole of the center cap and located at a top end of the center passage of the membrane frame, the adjustable member is configured to regulate the flow of the catholyte supplied to the center cap. 4. The plating apparatus according to claim 3, wherein the adjustable member has a base body and a blocking component formed at the bottom of the base body. 5. The plating apparatus according to claim 4, wherein the top of the base body defines a groove-shaped opening for conveniently rotating the adjustable member, the adjustable member is capable of moving upward or downward in the through-hole of the center cap for adjusting the size of a gap formed between the blocking component and the center passage, the catholyte is supplied to the center cap through the gap. 6. The plating apparatus according to claim 3, wherein the adjustable member is a set screw. 7. The plating apparatus according to claim 1, wherein the diameter of the first holes or the density of the first holes is same. 8. The plating apparatus according to claim 1, wherein the diameter of the first holes or the density of the first holes is different. 9. The plating apparatus according to claim 1, wherein the diameter of the first holes gradually increases from the center to edge of the center cap or the density of the first holes gradually increases from the center to edge of the center cap. 10. The plating apparatus according to claim 1, wherein the center cap has a side wall, the side wall of the center cap has a plurality of second holes, the opening direction of every second hole is obliquely upward. 11. The plating apparatus according to claim 1, wherein the membrane frame has a catholyte inlet, the catholyte inlet is connected to the catholyte inlet pipe and the center passage,
the membrane frame has a plurality of branch pipes extending from the center to edge of the membrane frame, every branch pipe is connected to the catholyte inlet, every branch pipe has a plurality of spray holes. 12. The plating apparatus according to claim 11, wherein the diameter or the density of the plurality of spray holes on each branch pipe is same. 13. The plating apparatus according to claim 11, wherein the diameter or the density of the plurality of spray holes on each branch pipe is different. 14. The plating apparatus according to claim 11, wherein the diameter or the density of the spray holes gradually increases from the center to edge of the membrane frame. 15. The plating apparatus according to claim 11, wherein the opening direction of every spray hole is tilted relative to a vertical plane. 16. The plating apparatus according to claim 15, wherein the plurality of spray holes on each branch pipe is divided into two groups, the opening directions of the two groups of spray holes are opposite. 17. The plating apparatus according to claim 1, further comprising at least one diffusion plate having a plurality of apertures, the at least one diffusion plate being fixed on the membrane frame. 18. The plating apparatus according to claim 17, wherein the apertures on the diffusion plate are of uniform size and the density of the apertures distributed on the diffusion plate is uniform. 19. The plating apparatus according to claim 17, wherein the density of the apertures distributed on the diffusion plate is uniform, but the diameter of the apertures distributed at the center region of the diffusion plate is larger than the diameter of the apertures distributed at the edge region of the diffusion plate. 20. The plating apparatus according to claim 17, wherein the number of the diffusion plates is two, the two diffusion plates are respectively defined as a first diffusion plate and a second diffusion plate, the first diffusion plate is set above the second diffusion plate, a distance is formed between the two diffusion plates. 21. The plating apparatus according to claim 20, wherein the density of the apertures distributed on the first diffusion plate is greater than the density of the apertures distributed on the second diffusion plate. 22. The plating apparatus according to claim 20, further comprising an annular middle plate being set between the two diffusion plates, the middle plate having a plurality of convex portions and a plurality of concave portions at the inner edge of the middle plate. 23. The plating apparatus according to claim 22, wherein the convex portion and the concave portion are arranged alternately. 24. The plating apparatus according to claim 22, wherein half of the apertures distributed at the edge of the first diffusion plate are blocked by the convex portions of the middle plate and the other half of the apertures distributed at the edge of the first diffusion plate are not blocked. 25. The plating apparatus according to claim 1, further comprising an anode chamber and a cathode chamber, the anode chamber and the cathode chamber being separated by a membrane which is positioned on the membrane frame. 26. The plating apparatus according to claim 25, wherein the anode chamber has a side wall, the side wall of the anode chamber defines a plurality of discharge holes, every discharge hole is connected to a discharge passage. 27. The plating apparatus according to claim 26, wherein the anode chamber is divided into multiple anode zones and every two adjacent anode zones are separated by a vertically arranged partition, every anode zone accommodates an annular anode, every anode zone has an independent anolyte inlet and an independent anolyte outlet. 28. The plating apparatus according to claim 27, wherein there is a distance between the top of the partitions and the membrane for gas bubbles passing through, the gas bubbles in the anode zones are collected and guided by the membrane to the discharge holes and discharged out from the discharge passages. 29. The plating apparatus according to claim 28, further comprising a third valve which is set on an anolyte inlet pipe connected to the anolyte inlet, and a second valve which is set on a discharge pipe connected to the discharge passage, wherein the anode electrolyte is supplied to the anode zones through the anolyte inlet pipes and the anolyte inlets and then discharged through the discharge holes, discharge passages and the discharge pipes. 30. The plating apparatus according to claim 27, further comprising a fourth valve which is set on an anolyte outlet pipe connected to the anolyte outlet, wherein the anode electrolyte in the anode zones is drained through the anolyte outlets and the anolyte outlet pipes. 31. The plating apparatus according to claim 28, further comprising a first valve which is set on a DIW inlet pipe and a fifth valve which is set on a DIW outlet pipe, wherein the DIW inlet pipe is connected to the discharge passage, the DIW outlet pipe is connected to the anolyte outlet, wherein DIW is supplied to the anode zones to flush the annular anodes through the DIW inlet pipes, the discharge passages and the discharge holes and then drained through the anolyte outlets and the DIW outlet pipes. 32. The plating apparatus according to claim 25, wherein the cathode chamber has an inner side wall and an outer side wall, a recess trough is formed between the inner side wall and the outer side wall, the top of the inner side wall has notches, the bottom of the recess trough has catholyte outlets, the electrolyte of the cathode chamber flows through the notches to be received in the recess trough and drained through the catholyte outlet. 33. The plating apparatus according to claim 25, further comprising a substrate rinse nozzle being positioned in the cathode chamber for cleaning plated film of the substrate. 34. The plating apparatus according to claim 25, further comprising a shroud fixed on the top of the cathode chamber. 35. The plating apparatus according to claim 34, wherein the shroud has a collecting groove, a drain passage is connected to the collecting groove, liquid in the collecting groove is drained through the drain passage. 36. The plating apparatus according to claim 35, wherein a side wall of the shroud defines a cleaning liquid inlet for cleaning the collecting groove. 37. The plating apparatus according to claim 25, further comprising a gas vent connecting to the cathode chamber for gas exhaust. 38. The plating apparatus according to claim 34, further comprising a chuck cleaning nozzle positioned above the shroud for cleaning a chuck which holds the substrate for plating. 39. The plating apparatus according to claim 38, wherein the chuck has a plurality of upright columns. 40. The plating apparatus according to claim 39, further comprising a controller having a timer, an on-off valve being set on a supply pipeline which is connected to the chuck cleaning nozzle for supplying cleaning liquid to the chuck cleaning nozzle,
wherein the controller is configured to control the on-off valve based on the timer to: close the on-off valve during the period that each of the upright columns passes the chuck cleaning nozzle to stop spraying the cleaning liquid; and open the on-off valve after the upright column has passed the chuck cleaning nozzle to spray the cleaning liquid. | A plating apparatus for depositing metal on a substrate, comprising a membrane frame (14), a catholyte inlet pipe (30) and a center cap (40). The membrane frame (14) has a center passage (144) which passes through the center of the membrane frame (14). The catholyte inlet pipe (30) is connected to the center passage (144) of the membrane frame (14). The center cap (40) is fixed at the center of the membrane frame (14) and covers over the center passage (144) of the membrane frame (14). The top of the center cap (40) has a plurality of first holes (42). The catholyte inlet pipe (30) supplies catholyte to the center cap (40) through the center passage (144) of the membrane frame (14), and the catholyte is supplied to a center area of the substrate through the first holes (42) of the center cap (40).1. A plating apparatus for depositing metal on a substrate, comprising:
a membrane frame, having a center passage which passes through the center of the membrane frame; a catholyte inlet pipe, connecting to the center passage of the membrane frame; a center cap, fixed at the center of the membrane frame and covering over the center passage of the membrane frame, the top of the center cap having a plurality of first holes; wherein the catholyte inlet pipe supplies catholyte to the center cap through the center passage of the membrane frame, and the catholyte is supplied to a center area of the substrate through the first holes of the center cap. 2. The plating apparatus according to claim 1, wherein the flow of the catholyte supplied to the center cap is adjustable and controlled independently. 3. The plating apparatus according to claim 1, wherein the center cap has a through-hole defined at the center of the center cap, an adjustable member is inserted in the through-hole of the center cap and located at a top end of the center passage of the membrane frame, the adjustable member is configured to regulate the flow of the catholyte supplied to the center cap. 4. The plating apparatus according to claim 3, wherein the adjustable member has a base body and a blocking component formed at the bottom of the base body. 5. The plating apparatus according to claim 4, wherein the top of the base body defines a groove-shaped opening for conveniently rotating the adjustable member, the adjustable member is capable of moving upward or downward in the through-hole of the center cap for adjusting the size of a gap formed between the blocking component and the center passage, the catholyte is supplied to the center cap through the gap. 6. The plating apparatus according to claim 3, wherein the adjustable member is a set screw. 7. The plating apparatus according to claim 1, wherein the diameter of the first holes or the density of the first holes is same. 8. The plating apparatus according to claim 1, wherein the diameter of the first holes or the density of the first holes is different. 9. The plating apparatus according to claim 1, wherein the diameter of the first holes gradually increases from the center to edge of the center cap or the density of the first holes gradually increases from the center to edge of the center cap. 10. The plating apparatus according to claim 1, wherein the center cap has a side wall, the side wall of the center cap has a plurality of second holes, the opening direction of every second hole is obliquely upward. 11. The plating apparatus according to claim 1, wherein the membrane frame has a catholyte inlet, the catholyte inlet is connected to the catholyte inlet pipe and the center passage,
the membrane frame has a plurality of branch pipes extending from the center to edge of the membrane frame, every branch pipe is connected to the catholyte inlet, every branch pipe has a plurality of spray holes. 12. The plating apparatus according to claim 11, wherein the diameter or the density of the plurality of spray holes on each branch pipe is same. 13. The plating apparatus according to claim 11, wherein the diameter or the density of the plurality of spray holes on each branch pipe is different. 14. The plating apparatus according to claim 11, wherein the diameter or the density of the spray holes gradually increases from the center to edge of the membrane frame. 15. The plating apparatus according to claim 11, wherein the opening direction of every spray hole is tilted relative to a vertical plane. 16. The plating apparatus according to claim 15, wherein the plurality of spray holes on each branch pipe is divided into two groups, the opening directions of the two groups of spray holes are opposite. 17. The plating apparatus according to claim 1, further comprising at least one diffusion plate having a plurality of apertures, the at least one diffusion plate being fixed on the membrane frame. 18. The plating apparatus according to claim 17, wherein the apertures on the diffusion plate are of uniform size and the density of the apertures distributed on the diffusion plate is uniform. 19. The plating apparatus according to claim 17, wherein the density of the apertures distributed on the diffusion plate is uniform, but the diameter of the apertures distributed at the center region of the diffusion plate is larger than the diameter of the apertures distributed at the edge region of the diffusion plate. 20. The plating apparatus according to claim 17, wherein the number of the diffusion plates is two, the two diffusion plates are respectively defined as a first diffusion plate and a second diffusion plate, the first diffusion plate is set above the second diffusion plate, a distance is formed between the two diffusion plates. 21. The plating apparatus according to claim 20, wherein the density of the apertures distributed on the first diffusion plate is greater than the density of the apertures distributed on the second diffusion plate. 22. The plating apparatus according to claim 20, further comprising an annular middle plate being set between the two diffusion plates, the middle plate having a plurality of convex portions and a plurality of concave portions at the inner edge of the middle plate. 23. The plating apparatus according to claim 22, wherein the convex portion and the concave portion are arranged alternately. 24. The plating apparatus according to claim 22, wherein half of the apertures distributed at the edge of the first diffusion plate are blocked by the convex portions of the middle plate and the other half of the apertures distributed at the edge of the first diffusion plate are not blocked. 25. The plating apparatus according to claim 1, further comprising an anode chamber and a cathode chamber, the anode chamber and the cathode chamber being separated by a membrane which is positioned on the membrane frame. 26. The plating apparatus according to claim 25, wherein the anode chamber has a side wall, the side wall of the anode chamber defines a plurality of discharge holes, every discharge hole is connected to a discharge passage. 27. The plating apparatus according to claim 26, wherein the anode chamber is divided into multiple anode zones and every two adjacent anode zones are separated by a vertically arranged partition, every anode zone accommodates an annular anode, every anode zone has an independent anolyte inlet and an independent anolyte outlet. 28. The plating apparatus according to claim 27, wherein there is a distance between the top of the partitions and the membrane for gas bubbles passing through, the gas bubbles in the anode zones are collected and guided by the membrane to the discharge holes and discharged out from the discharge passages. 29. The plating apparatus according to claim 28, further comprising a third valve which is set on an anolyte inlet pipe connected to the anolyte inlet, and a second valve which is set on a discharge pipe connected to the discharge passage, wherein the anode electrolyte is supplied to the anode zones through the anolyte inlet pipes and the anolyte inlets and then discharged through the discharge holes, discharge passages and the discharge pipes. 30. The plating apparatus according to claim 27, further comprising a fourth valve which is set on an anolyte outlet pipe connected to the anolyte outlet, wherein the anode electrolyte in the anode zones is drained through the anolyte outlets and the anolyte outlet pipes. 31. The plating apparatus according to claim 28, further comprising a first valve which is set on a DIW inlet pipe and a fifth valve which is set on a DIW outlet pipe, wherein the DIW inlet pipe is connected to the discharge passage, the DIW outlet pipe is connected to the anolyte outlet, wherein DIW is supplied to the anode zones to flush the annular anodes through the DIW inlet pipes, the discharge passages and the discharge holes and then drained through the anolyte outlets and the DIW outlet pipes. 32. The plating apparatus according to claim 25, wherein the cathode chamber has an inner side wall and an outer side wall, a recess trough is formed between the inner side wall and the outer side wall, the top of the inner side wall has notches, the bottom of the recess trough has catholyte outlets, the electrolyte of the cathode chamber flows through the notches to be received in the recess trough and drained through the catholyte outlet. 33. The plating apparatus according to claim 25, further comprising a substrate rinse nozzle being positioned in the cathode chamber for cleaning plated film of the substrate. 34. The plating apparatus according to claim 25, further comprising a shroud fixed on the top of the cathode chamber. 35. The plating apparatus according to claim 34, wherein the shroud has a collecting groove, a drain passage is connected to the collecting groove, liquid in the collecting groove is drained through the drain passage. 36. The plating apparatus according to claim 35, wherein a side wall of the shroud defines a cleaning liquid inlet for cleaning the collecting groove. 37. The plating apparatus according to claim 25, further comprising a gas vent connecting to the cathode chamber for gas exhaust. 38. The plating apparatus according to claim 34, further comprising a chuck cleaning nozzle positioned above the shroud for cleaning a chuck which holds the substrate for plating. 39. The plating apparatus according to claim 38, wherein the chuck has a plurality of upright columns. 40. The plating apparatus according to claim 39, further comprising a controller having a timer, an on-off valve being set on a supply pipeline which is connected to the chuck cleaning nozzle for supplying cleaning liquid to the chuck cleaning nozzle,
wherein the controller is configured to control the on-off valve based on the timer to: close the on-off valve during the period that each of the upright columns passes the chuck cleaning nozzle to stop spraying the cleaning liquid; and open the on-off valve after the upright column has passed the chuck cleaning nozzle to spray the cleaning liquid. | 2,800 |
345,453 | 16,643,369 | 2,814 | A method for determining the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method includes: | 1. A method for determining the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method including:
calculating a value of the line resistance of said electrical line; and determining the state of said electrical line as a function of said calculated line resistance value. 2. The method as claimed in claim 1, in which said calculating the line resistance value includes:
a first measurement substep, when said cell of said battery is not charging or discharging, of measuring an open circuit first voltage value between said first and second input terminals; a closing substep, at a first time, in which the monitoring unit connects said first and second input terminals via a resistive electrical branch the electrical resistance value of which is predetermined; a second measurement substep, at a second separated from said first time by a duration between a predetermined minimum duration and a predetermined maximum duration, of measuring a closed circuit second voltage value between said first and second input terminals; and a substep of estimating said line resistance value of said electrical line as a function of said predetermined electrical resistance value and said first and second measured voltage values. 3. The method as claimed in claim 2, in which:
said minimum duration is predetermined so that said second measurement substep is carried out under static electrical conditions; and said maximum duration is predetermined so that the absolute value of the voltage between said positive and negative terminals of said cell does not vary by more than 1% between the first measurement substep and the second measurement substep. 4. The method as claimed in claim 2, in which, during the closing substep, each resistive electrical branch is a balancing electrical branch of a cell. 5. The method as claimed in claim 1, further including comparing the calculated line resistance value with an electrical resistance threshold value and in which the state of said electrical line is determined as a function of the result of said comparison. 6. The method as claimed in claim 5, further including measuring a temperature representative of the ambient temperature of said electrical line and in which said electrical resistance threshold value is predetermined as a function of that representative temperature. 7. A method of issuing an alert regarding the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method of issuing an alert including:
determining the state of said electrical line using a determination method as claimed in claim 5; and sending an alert signal if the line resistance value is greater than said electrical resistance threshold value. 8. A unit for monitoring states of charge of a plurality of cells of a battery, each cell being connected to said monitoring unit by an electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said monitoring unit being designed:
to calculate a line resistance value of each electrical line; to determine the state of said electrical lines as a function of said calculated line resistance values. 9. A system for electric or hybrid motor vehicles, including:
a battery comprising a plurality of cells; and a monitoring unit according to claim 8 for said battery. 10. An electric or hybrid motor vehicle including:
a system according to claim 9; and an electric motor supplied with current by said battery of said system. | A method for determining the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method includes:1. A method for determining the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method including:
calculating a value of the line resistance of said electrical line; and determining the state of said electrical line as a function of said calculated line resistance value. 2. The method as claimed in claim 1, in which said calculating the line resistance value includes:
a first measurement substep, when said cell of said battery is not charging or discharging, of measuring an open circuit first voltage value between said first and second input terminals; a closing substep, at a first time, in which the monitoring unit connects said first and second input terminals via a resistive electrical branch the electrical resistance value of which is predetermined; a second measurement substep, at a second separated from said first time by a duration between a predetermined minimum duration and a predetermined maximum duration, of measuring a closed circuit second voltage value between said first and second input terminals; and a substep of estimating said line resistance value of said electrical line as a function of said predetermined electrical resistance value and said first and second measured voltage values. 3. The method as claimed in claim 2, in which:
said minimum duration is predetermined so that said second measurement substep is carried out under static electrical conditions; and said maximum duration is predetermined so that the absolute value of the voltage between said positive and negative terminals of said cell does not vary by more than 1% between the first measurement substep and the second measurement substep. 4. The method as claimed in claim 2, in which, during the closing substep, each resistive electrical branch is a balancing electrical branch of a cell. 5. The method as claimed in claim 1, further including comparing the calculated line resistance value with an electrical resistance threshold value and in which the state of said electrical line is determined as a function of the result of said comparison. 6. The method as claimed in claim 5, further including measuring a temperature representative of the ambient temperature of said electrical line and in which said electrical resistance threshold value is predetermined as a function of that representative temperature. 7. A method of issuing an alert regarding the state of an electrical line connecting a cell of a battery to a monitoring unit of said battery, said electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said method of issuing an alert including:
determining the state of said electrical line using a determination method as claimed in claim 5; and sending an alert signal if the line resistance value is greater than said electrical resistance threshold value. 8. A unit for monitoring states of charge of a plurality of cells of a battery, each cell being connected to said monitoring unit by an electrical line including a first electrical branch connecting a positive terminal of said cell to a first input terminal of said monitoring unit and a second electrical branch connecting a negative terminal of said cell to a second input terminal of said monitoring unit, said monitoring unit being designed:
to calculate a line resistance value of each electrical line; to determine the state of said electrical lines as a function of said calculated line resistance values. 9. A system for electric or hybrid motor vehicles, including:
a battery comprising a plurality of cells; and a monitoring unit according to claim 8 for said battery. 10. An electric or hybrid motor vehicle including:
a system according to claim 9; and an electric motor supplied with current by said battery of said system. | 2,800 |
345,454 | 16,643,345 | 2,814 | Compounds of general formula IA, IB and IC outlined below, including pharmaceutically acceptable salts, solvates and hydrates thereof. Such compounds and pharmaceutical compositions comprising them may be used in medical conditions involving Ran GTPase. | 1. A compound of general formula IA below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 2. A compound according to claim 1 having the general formula IIA below 3. A compound according to claim 2 having the general formula IIIA below 4. A compound according to claim 2 or 3, wherein X is O. 5. A compound according to any one of claims 2 to 4, wherein Z is (C═S)NH2 or 6. A compound according to any one of claims 2 to 5, wherein X1, X2 and X3 are each O. 7. A compound according to any one of claims 2 to 6, wherein n, m1, m2 and m3 are each 1. 8. A compound according to any one of claims 3 to 7, wherein R1, R2 and R3 are each independently a halogen atom; and I1, I2 and I3 are each 1. 9. A compound according to claim 1, wherein Q is the tetrahydrofuran ring. 10. A compound according to claim 1, which is selected from the group of compounds depicted in the Table 1 below 11. A compound according to claim 1, which is compound M36 depicted below 12. A compound according to claim 1, which is compound M88 depicted below 13. A compound of general formula IB below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 14. A compound according to claim 13 having the general formula IIB or IIB′ below 15. A compound according to claim 13 or 14 having the general formula IIIB or IIIB′ below 16. A compound according to claim 14 or 15, wherein n1, n2, n3, m1, m2, and m3 are each 1. 17. A compound according to any one of claims 14 to 16, wherein X1, X2 and X3 in IIB or IIIB are each N, and Y1, Y2 and Y3 in IIB′ or IIIB′ are each O. 18. A compound according to any one of claims 14 to 17, wherein Q1, Q2 and Q3 are each independently is a 5 or 6-member ring, optionally the ring comprises one or more heteroatoms selected from O, N, S and Se, and/or optionally the ring is substituted with one or more groups selected from C1 to C6 alkoxy and halogens. 19. A compound according to claim 13, wherein Q is the benzene ring. 20. A compound according to claim 13, which is selected from the group of compounds depicted in the Table 2 below 21. A compound according to claim 13, which is compound M51 depicted below 22. A compound according to claim 13, which is compound M55 depicted below 23. A compound according to claim 13, which is compound M66 depicted below 24. A compound of general formula IC below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 25. A compound according to claim 24 having the general formula IIC below 26. A compound according to claim 25, having the general formula IIIC below 27. A compound according to any one of claims 24 to 26, wherein L1 is (CH2)n wherein n is an integer from 0 to 12. 28. A compound according to claim 25 or 26, wherein Q2 is a cycloalkyl or alkylaryl. 29. A compound according to claim 24, wherein Q is the piperazine ring. 30. A compound according to claim 24, which is selected from the group of compounds depicted in the Table 3 or Table 4 below 31. A compound according to claim 24, which is compound R20 depicted below 32. A compound according to claim 24, which is compound QR20 depicted below 33. A compound according to claim 24 having the general formula IIC′ below 34. A compound according to claim 33 having the general formula IIIC′ below 35. A compound according to claim 34 having the general formula IVC′ below 36. A compound according to claim 34, wherein L1 and L2 are each independently (CH2)n wherein n is an integer from 0 to 12. 37. A compound according to claim 36, wherein n1 and n2 are each independently an integer from 1 to 3. 38. A compound according to claim 36, wherein R1 and R3 are each independently an alkoxy or a halogen. 39. A compound according to claim 36, wherein R2 is N(HNC═X)2(Ph-halogen(s))2 wherein X is O or S. 40. A compound according to claim 24, wherein Q is the piperazine ring. 41. A compound according to claim 24, which is selected from the group of compounds depicted in the Table 5 below 42. A compound according to claim 35, which is compound R28 depicted below 43. A pharmaceutical composition comprising a compound as defined in any one of claims 1 to 42, and a pharmaceutically acceptable carrier. 44. A kit comprising a compound as defined in any one of claims 1 to 42 and/or a pharmaceutical composition as defined in claim 43, another therapeutic agent, and instructions for use in the treatment of a medical condition involving Ran GTPase. 45. A kit according to claim 44, wherein the other therapeutic agent comprises a DNA damaging agent such as carboplatin and/or an inhibitor of poly ADP ribase polymerase (PARP) such as olaparib. 46. A compound according to any one of claims 1 to 42, which inhibits Ran GTPase. 47. A method of treating a medical condition involving Ran GTPase, comprising administering to a subject a therapeutically effective amount of a compound as defined in any one of claims 1 to 42 or a pharmaceutical composition as defined in claim 43. 48. A method of treating a medical condition involving Ran GTPase, comprising administering to a subject a therapeutically effective amount of compound M26, V188, 1292 or a pharmaceutical composition comprising same. 49. A method according to claim 47 or 48, wherein the medical condition is a medical condition with immune disorder. 50. A method according to any one of claims 47 to 49, wherein the medical condition is cancer including ovarian cancer, breast cancer, pancreatic cancer, colorectal cancer and a cancer embodying aneuploidy. 51. A method according to any one of claims 47 to 50, further comprising treating the subject with a second therapy. 52. A method according to claim 51, wherein the second therapy comprises a DNA damaging agent such as carboplatin and/or an inhibitor of poly ADP ribase polymerase (PARP) such as olaparib. 53. A method according to any one of claims 47 to 51, wherein the compound is administered orally, intravenously, intra-arterially, subcutaneously, topically or intramuscularly. 54. A method according to claim 50, wherein the cancer is primary or multi-drug resistant, metastatic and/or recurrent. 55. A method according to claim 50 or 54, wherein the method comprises inhibiting cancer growth, killing cancer cells, reducing tumor burden, reducing tumor size, improving the subject's quality of life and/or prolonging the subject's length of life. 56. A method according to any one of claims 43 to 50, wherein the subject is human. 57. A method according to any one of claims 47 to 56, wherein the subject is a non-human animal. 58. Use of a compound as defined in any one of claims 1 to 42 or a pharmaceutical composition as defined in claim 43, for treating in a subject, a medical condition involving Ran GTPase. 59. Use of compound M26, V188, 1292 or a pharmaceutical composition comprising same, for treating in a subject, a medical condition involving Ran GTPase. 60. Use of a compound as defined in any one of claims 1 to 42, in the manufacture of a medicament for treating a medical condition involving Ran GTPase. 61. Use of compound M26, V188 or 1292, in the manufacture of a medicament for treating a medical condition involving Ran GTPase. 62. A compound as defined in any one of claims 1 to 42, for use in the treatment of a medical condition that involves Ran GTPase. 63. A pharmaceutical composition as defined in claim 43, for use in the treatment of a medical condition that involves Ran GTPase. | Compounds of general formula IA, IB and IC outlined below, including pharmaceutically acceptable salts, solvates and hydrates thereof. Such compounds and pharmaceutical compositions comprising them may be used in medical conditions involving Ran GTPase.1. A compound of general formula IA below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 2. A compound according to claim 1 having the general formula IIA below 3. A compound according to claim 2 having the general formula IIIA below 4. A compound according to claim 2 or 3, wherein X is O. 5. A compound according to any one of claims 2 to 4, wherein Z is (C═S)NH2 or 6. A compound according to any one of claims 2 to 5, wherein X1, X2 and X3 are each O. 7. A compound according to any one of claims 2 to 6, wherein n, m1, m2 and m3 are each 1. 8. A compound according to any one of claims 3 to 7, wherein R1, R2 and R3 are each independently a halogen atom; and I1, I2 and I3 are each 1. 9. A compound according to claim 1, wherein Q is the tetrahydrofuran ring. 10. A compound according to claim 1, which is selected from the group of compounds depicted in the Table 1 below 11. A compound according to claim 1, which is compound M36 depicted below 12. A compound according to claim 1, which is compound M88 depicted below 13. A compound of general formula IB below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 14. A compound according to claim 13 having the general formula IIB or IIB′ below 15. A compound according to claim 13 or 14 having the general formula IIIB or IIIB′ below 16. A compound according to claim 14 or 15, wherein n1, n2, n3, m1, m2, and m3 are each 1. 17. A compound according to any one of claims 14 to 16, wherein X1, X2 and X3 in IIB or IIIB are each N, and Y1, Y2 and Y3 in IIB′ or IIIB′ are each O. 18. A compound according to any one of claims 14 to 17, wherein Q1, Q2 and Q3 are each independently is a 5 or 6-member ring, optionally the ring comprises one or more heteroatoms selected from O, N, S and Se, and/or optionally the ring is substituted with one or more groups selected from C1 to C6 alkoxy and halogens. 19. A compound according to claim 13, wherein Q is the benzene ring. 20. A compound according to claim 13, which is selected from the group of compounds depicted in the Table 2 below 21. A compound according to claim 13, which is compound M51 depicted below 22. A compound according to claim 13, which is compound M55 depicted below 23. A compound according to claim 13, which is compound M66 depicted below 24. A compound of general formula IC below, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate thereof 25. A compound according to claim 24 having the general formula IIC below 26. A compound according to claim 25, having the general formula IIIC below 27. A compound according to any one of claims 24 to 26, wherein L1 is (CH2)n wherein n is an integer from 0 to 12. 28. A compound according to claim 25 or 26, wherein Q2 is a cycloalkyl or alkylaryl. 29. A compound according to claim 24, wherein Q is the piperazine ring. 30. A compound according to claim 24, which is selected from the group of compounds depicted in the Table 3 or Table 4 below 31. A compound according to claim 24, which is compound R20 depicted below 32. A compound according to claim 24, which is compound QR20 depicted below 33. A compound according to claim 24 having the general formula IIC′ below 34. A compound according to claim 33 having the general formula IIIC′ below 35. A compound according to claim 34 having the general formula IVC′ below 36. A compound according to claim 34, wherein L1 and L2 are each independently (CH2)n wherein n is an integer from 0 to 12. 37. A compound according to claim 36, wherein n1 and n2 are each independently an integer from 1 to 3. 38. A compound according to claim 36, wherein R1 and R3 are each independently an alkoxy or a halogen. 39. A compound according to claim 36, wherein R2 is N(HNC═X)2(Ph-halogen(s))2 wherein X is O or S. 40. A compound according to claim 24, wherein Q is the piperazine ring. 41. A compound according to claim 24, which is selected from the group of compounds depicted in the Table 5 below 42. A compound according to claim 35, which is compound R28 depicted below 43. A pharmaceutical composition comprising a compound as defined in any one of claims 1 to 42, and a pharmaceutically acceptable carrier. 44. A kit comprising a compound as defined in any one of claims 1 to 42 and/or a pharmaceutical composition as defined in claim 43, another therapeutic agent, and instructions for use in the treatment of a medical condition involving Ran GTPase. 45. A kit according to claim 44, wherein the other therapeutic agent comprises a DNA damaging agent such as carboplatin and/or an inhibitor of poly ADP ribase polymerase (PARP) such as olaparib. 46. A compound according to any one of claims 1 to 42, which inhibits Ran GTPase. 47. A method of treating a medical condition involving Ran GTPase, comprising administering to a subject a therapeutically effective amount of a compound as defined in any one of claims 1 to 42 or a pharmaceutical composition as defined in claim 43. 48. A method of treating a medical condition involving Ran GTPase, comprising administering to a subject a therapeutically effective amount of compound M26, V188, 1292 or a pharmaceutical composition comprising same. 49. A method according to claim 47 or 48, wherein the medical condition is a medical condition with immune disorder. 50. A method according to any one of claims 47 to 49, wherein the medical condition is cancer including ovarian cancer, breast cancer, pancreatic cancer, colorectal cancer and a cancer embodying aneuploidy. 51. A method according to any one of claims 47 to 50, further comprising treating the subject with a second therapy. 52. A method according to claim 51, wherein the second therapy comprises a DNA damaging agent such as carboplatin and/or an inhibitor of poly ADP ribase polymerase (PARP) such as olaparib. 53. A method according to any one of claims 47 to 51, wherein the compound is administered orally, intravenously, intra-arterially, subcutaneously, topically or intramuscularly. 54. A method according to claim 50, wherein the cancer is primary or multi-drug resistant, metastatic and/or recurrent. 55. A method according to claim 50 or 54, wherein the method comprises inhibiting cancer growth, killing cancer cells, reducing tumor burden, reducing tumor size, improving the subject's quality of life and/or prolonging the subject's length of life. 56. A method according to any one of claims 43 to 50, wherein the subject is human. 57. A method according to any one of claims 47 to 56, wherein the subject is a non-human animal. 58. Use of a compound as defined in any one of claims 1 to 42 or a pharmaceutical composition as defined in claim 43, for treating in a subject, a medical condition involving Ran GTPase. 59. Use of compound M26, V188, 1292 or a pharmaceutical composition comprising same, for treating in a subject, a medical condition involving Ran GTPase. 60. Use of a compound as defined in any one of claims 1 to 42, in the manufacture of a medicament for treating a medical condition involving Ran GTPase. 61. Use of compound M26, V188 or 1292, in the manufacture of a medicament for treating a medical condition involving Ran GTPase. 62. A compound as defined in any one of claims 1 to 42, for use in the treatment of a medical condition that involves Ran GTPase. 63. A pharmaceutical composition as defined in claim 43, for use in the treatment of a medical condition that involves Ran GTPase. | 2,800 |
345,455 | 16,643,362 | 2,814 | A display substrate and a method for manufacturing the same, a display panel and a display device are provided. The display substrate includes a base substrate, a display component on the base substrate, and an encapsulation layer covering the display component, where the encapsulation layer includes an organic layer and an inorganic layer that are stacked alternately. A detection capacitor is further provided in a peripheral region of the display substrate. The detection capacitor includes a first electrode plate on a side of the encapsulation layer close to the base substrate, and a second electrode plate on a side of the encapsulation layer away from the base substrate. | 1. A display substrate, comprising:
a base substrate; a display component on the base substrate; and an encapsulation layer covering the display component, wherein the encapsulation layer comprises an organic layer and an inorganic layer that are stacked, a detection capacitor is further provided in a peripheral region of the display substrate, and the peripheral region is a region between an effective display area and a frame of the display substrate; and the detection capacitor comprises a first electrode plate on a side of the encapsulation layer close to the base substrate, and a second electrode plate on a side of the encapsulation layer away from the base substrate. 2. The display substrate according to claim 1, wherein the first electrode plate and the second electrode plate of the detection capacitor are made of a metal material. 3. The display substrate according to claim 1, wherein the display component comprises a source-drain metal layer pattern or an anode layer; and
the first electrode plate and the source-drain metal layer pattern of the display component are made of a same material and on a same layer, or the first electrode plate and the anode layer of the display component are made of a same material and on a same layer. 4. The display substrate according to claim 1, further comprising a touch electrode on the side of the encapsulation layer away from the base substrate, wherein the second electrode plate of the detection capacitor and the touch electrode are made of a same material and on a same layer. 5. The display substrate according to claim 4, wherein the second electrode plate comprises a structure of a Ti layer, an Al layer and the Ti layer that are laminated. 6. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the first blocking structure onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 7. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the effective display area of the display substrate onto the base substrate and an orthographic projection of the first blocking structure onto the base substrate. 8. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the frame of the display substrate onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 9. The display substrate according to claim 6, wherein an orthographic projection of the first electrode plate onto the base substrate covers the orthographic projection of the first blocking structure onto the base substrate and the orthographic projection of the second blocking structure onto the base substrate. 10. The display substrate according to claim 1, wherein the first electrode plate is of a ring shape and around the peripheral region of the display substrate, and a shape of the second electrode plate corresponds to a shape of the first electrode plate. 11. The display substrate according to claim 1, wherein the encapsulation layer comprises a first inorganic layer, the organic layer, and a second inorganic layer that are sequentially stacked. 12. A display panel, comprising the display substrate according to claim 1. 13. A display device, comprising the display panel according to claim 12. 14. A method for manufacturing a display substrate, wherein the display substrate comprises a base substrate and a display component on the base substrate, and the method comprises:
forming a first electrode plate of a detection capacitor in a peripheral region of the display substrate, the peripheral region being a region between an effective display area and a frame of the display substrate; forming an encapsulation layer covering the display component; and forming a second electrode plate of the detection capacitor on a side of the encapsulation layer away from the base substrate. 15. The method according to claim 14, wherein the display component comprises a source-drain metal layer pattern or an anode layer, and forming the first electrode plate of the detection capacitor comprises:
forming the first electrode plate and the source-drain metal layer pattern of the display component simultaneously through one patterning process; or forming the first electrode plate and the anode layer of the display component simultaneously through one patterning process. 16. The method according to claim 14, wherein the display substrate further comprises a touch electrode, and forming the second electrode plate of the detection capacitor comprises:
forming the second electrode plate and the touch electrode simultaneously through one patterning process. 17. The method according to claim 14, wherein the display substrate further comprises a first blocking structure and a second blocking structure, and orthographic projections of the first electrode plate and second electrode of the detection capacitor onto the base substrate are between an orthographic projection of the first blocking structure onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 18. The display substrate according to claim 1, wherein the display component comprises a source-drain metal layer pattern and an anode layer; and
the first electrode plate and the source-drain metal layer pattern of the display component are made of a same material and on a same layer, or the first electrode plate and the anode layer of the display component are made of a same material and on a same layer. 19. The display substrate according to claim 4, wherein the touch electrode comprises a plurality of first touch electrodes, a plurality of second touch electrodes and a plurality of metal bridges, an extending direction of the plurality of first touch electrodes is perpendicular to an extending direction of the plurality of the second touch electrodes, and each of the plurality of metal bridges is configured to connect two adjacent second electrodes. 20. The display substrate according to claim 19, wherein the plurality of first touch electrodes and the plurality of second touch electrodes are on a same layer, the second electrode plate of the detection capacitor is made of a same material and on a same layer as the plurality of first touch electrodes and the plurality of second touch electrodes, or the second electrode plate of the detection capacitor is made of a same material and on a same layer as the plurality of metal bridges. | A display substrate and a method for manufacturing the same, a display panel and a display device are provided. The display substrate includes a base substrate, a display component on the base substrate, and an encapsulation layer covering the display component, where the encapsulation layer includes an organic layer and an inorganic layer that are stacked alternately. A detection capacitor is further provided in a peripheral region of the display substrate. The detection capacitor includes a first electrode plate on a side of the encapsulation layer close to the base substrate, and a second electrode plate on a side of the encapsulation layer away from the base substrate.1. A display substrate, comprising:
a base substrate; a display component on the base substrate; and an encapsulation layer covering the display component, wherein the encapsulation layer comprises an organic layer and an inorganic layer that are stacked, a detection capacitor is further provided in a peripheral region of the display substrate, and the peripheral region is a region between an effective display area and a frame of the display substrate; and the detection capacitor comprises a first electrode plate on a side of the encapsulation layer close to the base substrate, and a second electrode plate on a side of the encapsulation layer away from the base substrate. 2. The display substrate according to claim 1, wherein the first electrode plate and the second electrode plate of the detection capacitor are made of a metal material. 3. The display substrate according to claim 1, wherein the display component comprises a source-drain metal layer pattern or an anode layer; and
the first electrode plate and the source-drain metal layer pattern of the display component are made of a same material and on a same layer, or the first electrode plate and the anode layer of the display component are made of a same material and on a same layer. 4. The display substrate according to claim 1, further comprising a touch electrode on the side of the encapsulation layer away from the base substrate, wherein the second electrode plate of the detection capacitor and the touch electrode are made of a same material and on a same layer. 5. The display substrate according to claim 4, wherein the second electrode plate comprises a structure of a Ti layer, an Al layer and the Ti layer that are laminated. 6. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the first blocking structure onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 7. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the effective display area of the display substrate onto the base substrate and an orthographic projection of the first blocking structure onto the base substrate. 8. The display substrate according to claim 1, further comprising a first blocking structure and a second blocking structure that are in the peripheral region of the display substrate, wherein an orthographic projection of the second electrode plate onto the base substrate is between an orthographic projection of the frame of the display substrate onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 9. The display substrate according to claim 6, wherein an orthographic projection of the first electrode plate onto the base substrate covers the orthographic projection of the first blocking structure onto the base substrate and the orthographic projection of the second blocking structure onto the base substrate. 10. The display substrate according to claim 1, wherein the first electrode plate is of a ring shape and around the peripheral region of the display substrate, and a shape of the second electrode plate corresponds to a shape of the first electrode plate. 11. The display substrate according to claim 1, wherein the encapsulation layer comprises a first inorganic layer, the organic layer, and a second inorganic layer that are sequentially stacked. 12. A display panel, comprising the display substrate according to claim 1. 13. A display device, comprising the display panel according to claim 12. 14. A method for manufacturing a display substrate, wherein the display substrate comprises a base substrate and a display component on the base substrate, and the method comprises:
forming a first electrode plate of a detection capacitor in a peripheral region of the display substrate, the peripheral region being a region between an effective display area and a frame of the display substrate; forming an encapsulation layer covering the display component; and forming a second electrode plate of the detection capacitor on a side of the encapsulation layer away from the base substrate. 15. The method according to claim 14, wherein the display component comprises a source-drain metal layer pattern or an anode layer, and forming the first electrode plate of the detection capacitor comprises:
forming the first electrode plate and the source-drain metal layer pattern of the display component simultaneously through one patterning process; or forming the first electrode plate and the anode layer of the display component simultaneously through one patterning process. 16. The method according to claim 14, wherein the display substrate further comprises a touch electrode, and forming the second electrode plate of the detection capacitor comprises:
forming the second electrode plate and the touch electrode simultaneously through one patterning process. 17. The method according to claim 14, wherein the display substrate further comprises a first blocking structure and a second blocking structure, and orthographic projections of the first electrode plate and second electrode of the detection capacitor onto the base substrate are between an orthographic projection of the first blocking structure onto the base substrate and an orthographic projection of the second blocking structure onto the base substrate. 18. The display substrate according to claim 1, wherein the display component comprises a source-drain metal layer pattern and an anode layer; and
the first electrode plate and the source-drain metal layer pattern of the display component are made of a same material and on a same layer, or the first electrode plate and the anode layer of the display component are made of a same material and on a same layer. 19. The display substrate according to claim 4, wherein the touch electrode comprises a plurality of first touch electrodes, a plurality of second touch electrodes and a plurality of metal bridges, an extending direction of the plurality of first touch electrodes is perpendicular to an extending direction of the plurality of the second touch electrodes, and each of the plurality of metal bridges is configured to connect two adjacent second electrodes. 20. The display substrate according to claim 19, wherein the plurality of first touch electrodes and the plurality of second touch electrodes are on a same layer, the second electrode plate of the detection capacitor is made of a same material and on a same layer as the plurality of first touch electrodes and the plurality of second touch electrodes, or the second electrode plate of the detection capacitor is made of a same material and on a same layer as the plurality of metal bridges. | 2,800 |
345,456 | 16,643,393 | 2,814 | Disclosed are compounds and compositions for the activation or induction of expression of a pattern recognition receptor (e.g., STING, RIG-I, MDA5), and methods of use thereof. | 1. A compound of Formula (I): 2. The compound of claim 1, wherein the compound is a compound of Formula (I-a), (I-b), (I-c), or (I-d): 3. The compound of claim 1, wherein Z is O. 4. The compound of claim 1, wherein Z is S. 5. The compound of claim 1, wherein B1 is a purinyl nucleobase and B2 is a pyrimidinyl nucleobase; or B2 is a purinyl nucleobase and B1 is a pyrimidinyl nucleobase. 6. The compound of claim 1, wherein B1 is adenosinyl or guanosinyl and B2 is cytosinyl, thyminyl, or uracilyl; or B2 is adenosinyl or guanosinyl and B1 is cytosinyl, thyminyl, or uracilyl. 7. The compound of claim 1, wherein B1 is adenosinyl, and B2 is uracilyl; or B2 is adenosinyl, and B1 is uracilyl. 8-10. (canceled) 11. The compound of claim 1, wherein each of R1 and R2 is independently hydrogen, halo, or OR7. 12. The compound of claim 1, wherein each of R1 and R2 is independently halo. 13. (canceled) 14. The compound of claim 1, wherein each of X1 and X2 is independently O. 15. The compound of claim 1, wherein each of Y1 and Y2 is independently O or S. 16. The compound of claim 1, wherein one of Y1 or Y2 is O and the other of Y1 or Y2 is S. 17. (canceled) 18. (canceled) 19. The compound of claim 1, wherein each of L1 and L2 is independently C1-C6 alkyl. 20. The compound of claim 1, wherein each of R3 and R4 is independently hydrogen, aryl, or heteroaryl, wherein aryl and heteroaryl is optionally substituted with 1-5 R8. 21. The compound of claim 1, wherein R3 is aryl or heteroaryl, each of which is optionally substituted with 1-5 R8, and R4 is hydrogen. 22. The compound of claim 1, wherein R3 is phenyl substituted with 1 R8 and R4 is hydrogen. 23. The compound of claim 1, wherein each of R3 and R4 is independently phenyl substituted with 1 R8. 24. The compound of claim 1, wherein each of Y1 and Y2 is O and each of R3 and R4 is independently hydrogen. 25. The compound of claim 1, wherein Y2 is O and R4 is hydrogen. 26. (canceled) 27. The compound of claim 1, wherein Y1 is S and R3 is substituted with 1 R8. 28. The compound of claim 1, wherein R8 is C(O)-aryl optionally substituted by 1-5 R9. 29. The compound of claim 1, wherein R8 is OC(O)-aryl optionally substituted by 1-5 R9. 30. The compound of claim 28, wherein R9 is O—C1-C12 alkyl. 31. The compound of claim 1, wherein the compound is selected from the following table: 32. A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 33. The method of claim 32, wherein the cancer is a cancer of the breast, bone, brain, cervix, colon, gastrointestinal tract, eye, gall bladder, lymph nodes, blood, lung, liver, skin, mouth, prostate, ovary, penis, pancreas, uterus, testicles, stomach, thymus, thyroid, or other part of the body. 34. The method of claim 33, wherein the cancer is a cancer of the liver. 35-38. (canceled) 39. The method of claim 32, further comprising administering an effective amount of an additional agent. 40. The method of claim 39, wherein the additional agent comprises methotrexate, 5-fluorouracil, doxorubicin, vincristine, bleomycin, vinblastine, dacarbazine, toposide, cisplatin, epirubicin, or sorafenib tosylate. 41. A method of inducing the expression of a pattern recognition receptors (PRRs) for immune-modulation in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 42. A method of inducing the expression of a pattern recognition receptors for immunomodulation and inducing a therapeutic response in a subject having cancer, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 43. A method of inducing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 44. The method of claim 43, wherein the immune response comprises antitumoral immunity. 45. The method of claim 43, wherein the immune response comprises induction of a PRR. 46. A method of treating a microbial infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 47. A method of inducing the expression of a pattern recognition receptor in a subject suffering from a microbial infection, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 48. A method of treating a viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 49. The method of claim 48, wherein the viral infection is Hepatitis C virus, Norovirus, Junin virus, Respiratory syncytial virus, or Dengue virus. | Disclosed are compounds and compositions for the activation or induction of expression of a pattern recognition receptor (e.g., STING, RIG-I, MDA5), and methods of use thereof.1. A compound of Formula (I): 2. The compound of claim 1, wherein the compound is a compound of Formula (I-a), (I-b), (I-c), or (I-d): 3. The compound of claim 1, wherein Z is O. 4. The compound of claim 1, wherein Z is S. 5. The compound of claim 1, wherein B1 is a purinyl nucleobase and B2 is a pyrimidinyl nucleobase; or B2 is a purinyl nucleobase and B1 is a pyrimidinyl nucleobase. 6. The compound of claim 1, wherein B1 is adenosinyl or guanosinyl and B2 is cytosinyl, thyminyl, or uracilyl; or B2 is adenosinyl or guanosinyl and B1 is cytosinyl, thyminyl, or uracilyl. 7. The compound of claim 1, wherein B1 is adenosinyl, and B2 is uracilyl; or B2 is adenosinyl, and B1 is uracilyl. 8-10. (canceled) 11. The compound of claim 1, wherein each of R1 and R2 is independently hydrogen, halo, or OR7. 12. The compound of claim 1, wherein each of R1 and R2 is independently halo. 13. (canceled) 14. The compound of claim 1, wherein each of X1 and X2 is independently O. 15. The compound of claim 1, wherein each of Y1 and Y2 is independently O or S. 16. The compound of claim 1, wherein one of Y1 or Y2 is O and the other of Y1 or Y2 is S. 17. (canceled) 18. (canceled) 19. The compound of claim 1, wherein each of L1 and L2 is independently C1-C6 alkyl. 20. The compound of claim 1, wherein each of R3 and R4 is independently hydrogen, aryl, or heteroaryl, wherein aryl and heteroaryl is optionally substituted with 1-5 R8. 21. The compound of claim 1, wherein R3 is aryl or heteroaryl, each of which is optionally substituted with 1-5 R8, and R4 is hydrogen. 22. The compound of claim 1, wherein R3 is phenyl substituted with 1 R8 and R4 is hydrogen. 23. The compound of claim 1, wherein each of R3 and R4 is independently phenyl substituted with 1 R8. 24. The compound of claim 1, wherein each of Y1 and Y2 is O and each of R3 and R4 is independently hydrogen. 25. The compound of claim 1, wherein Y2 is O and R4 is hydrogen. 26. (canceled) 27. The compound of claim 1, wherein Y1 is S and R3 is substituted with 1 R8. 28. The compound of claim 1, wherein R8 is C(O)-aryl optionally substituted by 1-5 R9. 29. The compound of claim 1, wherein R8 is OC(O)-aryl optionally substituted by 1-5 R9. 30. The compound of claim 28, wherein R9 is O—C1-C12 alkyl. 31. The compound of claim 1, wherein the compound is selected from the following table: 32. A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 33. The method of claim 32, wherein the cancer is a cancer of the breast, bone, brain, cervix, colon, gastrointestinal tract, eye, gall bladder, lymph nodes, blood, lung, liver, skin, mouth, prostate, ovary, penis, pancreas, uterus, testicles, stomach, thymus, thyroid, or other part of the body. 34. The method of claim 33, wherein the cancer is a cancer of the liver. 35-38. (canceled) 39. The method of claim 32, further comprising administering an effective amount of an additional agent. 40. The method of claim 39, wherein the additional agent comprises methotrexate, 5-fluorouracil, doxorubicin, vincristine, bleomycin, vinblastine, dacarbazine, toposide, cisplatin, epirubicin, or sorafenib tosylate. 41. A method of inducing the expression of a pattern recognition receptors (PRRs) for immune-modulation in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 42. A method of inducing the expression of a pattern recognition receptors for immunomodulation and inducing a therapeutic response in a subject having cancer, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 43. A method of inducing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 44. The method of claim 43, wherein the immune response comprises antitumoral immunity. 45. The method of claim 43, wherein the immune response comprises induction of a PRR. 46. A method of treating a microbial infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 47. A method of inducing the expression of a pattern recognition receptor in a subject suffering from a microbial infection, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 48. A method of treating a viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 49. The method of claim 48, wherein the viral infection is Hepatitis C virus, Norovirus, Junin virus, Respiratory syncytial virus, or Dengue virus. | 2,800 |
345,457 | 16,643,342 | 2,814 | A medical information processing system comprises: an input unit that receives input of electronic chart information for a patient being treated; a machine learning unit that refers to an electronic chart information group for each patient, the information group being obtained on the basis of an inpatient of an acute care facility, and performs machine learning about the discharge destination, from the acute care facility, of each patient; and a discharge-destination prediction unit that predicts the discharge destination of the patient being treated from the received electronic chart information of the patient being treated, on the basis of the learning results obtained from the machine learning unit. | 1. A medical information processing system, comprising:
an input unit configured to receive input of electronic medical chart information on a subject patient; a machine learning unit configured to machine-learn a transition destination of each patient from an acute care medical facility by referring to an electronic medical chart information group of each patient obtained from inpatients of the acute care medical facility; and a transition destination prediction unit configured to predict, using a learning result obtained by the machine learning unit, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 2. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to receive the electronic medical chart information on the subject patient, and to select, by using the learning result, the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to other facility has a higher likelihood. 3. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to select, when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 4. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to receive, at least data on a family structure living with a patient in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, to predict, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and to classify the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. 5. A medical information processing method, comprising:
machine learning, a transition destination of each patient from the acute care medical facility based on an electronic medical chart information group of each patient obtained from inpatients of an acute care medical facility; receiving input of electronic medical chart information on a subject patient; and predicting, using a machine learning result, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 6. The medical information processing method according to claim 5, wherein the predicting of the transition destination includes receiving the electronic medical chart information on the subject patient, and selecting, using the machine learning result the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to another facility has a higher likelihood. 7. The medical information processing method according to claim 5, wherein, the predicting of the transition destination includes selecting when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 8. The medical information processing method according to claim 5, wherein the predicting of the transition destination includes receiving at least data on a cohabiting family structure in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, predicting, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and classifying the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. 9. A recording medium having stored thereon, in a non-transitory manner, a program for causing a processor of an information processing system to operate as:
an input unit configured to receive input of electronic medical chart information on a subject patient; a machine learning unit configured to machine-learn a transition destination of each patient from an acute care medical facility by referring to an electronic medical chart information group of each patient obtained from inpatients of the acute care medical facility; and a transition destination prediction unit configured to predict, using a learning result obtained by the machine learning unit, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 10. The recording medium according to claim 9, wherein the processor is caused to operate so as to receive the electronic medical chart information on the subject patient, and to select, using the learning result, the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to other facility has a higher likelihood. 11. The recording medium according to claim 9, wherein the processor is caused to operate so as to select, when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 12. The recording medium according to claim 9, wherein the processor is caused to operate so as to receive, at least data on a family structure living with a patient in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, to predict, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and to classify the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. | A medical information processing system comprises: an input unit that receives input of electronic chart information for a patient being treated; a machine learning unit that refers to an electronic chart information group for each patient, the information group being obtained on the basis of an inpatient of an acute care facility, and performs machine learning about the discharge destination, from the acute care facility, of each patient; and a discharge-destination prediction unit that predicts the discharge destination of the patient being treated from the received electronic chart information of the patient being treated, on the basis of the learning results obtained from the machine learning unit.1. A medical information processing system, comprising:
an input unit configured to receive input of electronic medical chart information on a subject patient; a machine learning unit configured to machine-learn a transition destination of each patient from an acute care medical facility by referring to an electronic medical chart information group of each patient obtained from inpatients of the acute care medical facility; and a transition destination prediction unit configured to predict, using a learning result obtained by the machine learning unit, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 2. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to receive the electronic medical chart information on the subject patient, and to select, by using the learning result, the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to other facility has a higher likelihood. 3. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to select, when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 4. The medical information processing system according to claim 1, wherein the transition destination prediction unit is configured to receive, at least data on a family structure living with a patient in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, to predict, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and to classify the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. 5. A medical information processing method, comprising:
machine learning, a transition destination of each patient from the acute care medical facility based on an electronic medical chart information group of each patient obtained from inpatients of an acute care medical facility; receiving input of electronic medical chart information on a subject patient; and predicting, using a machine learning result, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 6. The medical information processing method according to claim 5, wherein the predicting of the transition destination includes receiving the electronic medical chart information on the subject patient, and selecting, using the machine learning result the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to another facility has a higher likelihood. 7. The medical information processing method according to claim 5, wherein, the predicting of the transition destination includes selecting when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 8. The medical information processing method according to claim 5, wherein the predicting of the transition destination includes receiving at least data on a cohabiting family structure in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, predicting, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and classifying the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. 9. A recording medium having stored thereon, in a non-transitory manner, a program for causing a processor of an information processing system to operate as:
an input unit configured to receive input of electronic medical chart information on a subject patient; a machine learning unit configured to machine-learn a transition destination of each patient from an acute care medical facility by referring to an electronic medical chart information group of each patient obtained from inpatients of the acute care medical facility; and a transition destination prediction unit configured to predict, using a learning result obtained by the machine learning unit, the transition destination of the subject patient from the received electronic medical chart information on the subject patient. 10. The recording medium according to claim 9, wherein the processor is caused to operate so as to receive the electronic medical chart information on the subject patient, and to select, using the learning result, the transition destination of the subject patient based on which of discharge to a home, transfer to a convalescent hospital, and transfer to other facility has a higher likelihood. 11. The recording medium according to claim 9, wherein the processor is caused to operate so as to select, when selecting any one of a home, a convalescent hospital, and other facility as the transition destination of the subject patient, a convalescent hospital or other facility that satisfies a condition in a case in which a probability that a home is not selectable as the transition destination is higher than a threshold value. 12. The recording medium according to claim 9, wherein the processor is caused to operate so as to receive, at least data on a family structure living with a patient in the electronic medical chart information for a patient having emergency as a hospitalization category input as the electronic medical chart information on the subject patient, to predict, using the learning result, the transition destination after hospitalization by emergency transport of the subject patient, and to classify the transition destination as discharge to a home, transfer to a convalescent hospital, or transfer to other facility. | 2,800 |
345,458 | 16,643,399 | 2,814 | The present invention relates to a hard film having improved wear resistance and improved toughness. A hard film according to the present invention is formed by using a PVD method on a surface of a base material, wherein: the hard film includes a first hard layer and a second hard layer; the first hard layer has a thickness of approximately 0.1-3.0 μm and is composed of Ti1-aAlaN (0.3≤a≤0.7), and has a single phase structure; and the second hard layer has a thickness of approximately 0.5-10 μm and is composed of Ti1-a-bAlaMebN (0.3≤a≤0.7, 0≤b≤0.05, the Me being at least one selected from V, Zr, Si, Nb, Cr, Mo, Hf, Ta and W); according to an XRD phase analysis method, a ratio ([200]/[111]) of the intensity of a [200] peak to the intensity of a [111] peak is approximately 1.5 or higher; the second hard layer preferentially grows in a [200] direction; the [200] peak is located at approximately 42.7°-44.6° and is composed of three phases, and the [111] peak is located at approximately 37.0°-38.5° and is composed of three phases; and when a peak having a largest intensity among the peaks of the three phases is a main peak and remaining peaks are sub-peaks, a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [200] face is approximately 2 or higher, and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [111] face is approximately 2 or higher. | 1. A hard film formed by using a PVD method on a surface of a base material, the hard film comprising a first hard layer and a second hard layer, wherein:
the first hard layer has a thickness of approximately 0.1-3.0 μm and comprises Ti1-aAlaN (0.3≤a≤0.7), and has a single phase structure; the second hard layer has a thickness of approximately 0.5-10 μm and is composed of Ti1-a-bAlaMebN (0.3≤a≤0.7, 0≤b≤0.05, and the Me is at least one selected from V, Zr, Si, Nb, Cr, Mo, Hf, Ta and W); according to an XRD phase analysis method, a ratio ([200]/[111]) of an intensity of a [200] peak to an intensity of a [111] peak is approximately 1.5 or higher; the second hard layer preferentially grows in a [200] direction; the [200] peak is located at approximately 42.7°-44.6° and comprises three phases; the [111] peak is located at approximately 37.0°-38.5° and comprises three phases; when a peak having a largest intensity among the peaks of the three phases is a main peak and remaining peaks are sub-peaks, a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [200] face is approximately 2 or higher; and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [111] face is approximately 2 or higher. 2. The hard film of claim 1, wherein a third hard layer having a structure of a single layer including one or more compounds selected from Al1-xCrxN (0.3≤x≤0.7), Al1-yTiyN (0.3≤y≤0.7), and Al2O3, or a composite layer structure in which at least two single layers are laminated, is formed on the second hard layer. 3. The hard film of claim 1, wherein a fourth hard layer is formed between the first hard layer and the second hard layer, the fourth hard layer having a structure of a single layer including one or more compounds selected from Al1-xCrxN (0.3≤x≤0.7), Al1-yTiyN (0.3≤y≤0.7), and Al2O3, or a composite layer structure in which at least two single layers are laminated. 4. The hard film of claim 1, wherein
a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks of the [200] face is approximately 3-8, and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks of the [111] face is approximately 4-7. | The present invention relates to a hard film having improved wear resistance and improved toughness. A hard film according to the present invention is formed by using a PVD method on a surface of a base material, wherein: the hard film includes a first hard layer and a second hard layer; the first hard layer has a thickness of approximately 0.1-3.0 μm and is composed of Ti1-aAlaN (0.3≤a≤0.7), and has a single phase structure; and the second hard layer has a thickness of approximately 0.5-10 μm and is composed of Ti1-a-bAlaMebN (0.3≤a≤0.7, 0≤b≤0.05, the Me being at least one selected from V, Zr, Si, Nb, Cr, Mo, Hf, Ta and W); according to an XRD phase analysis method, a ratio ([200]/[111]) of the intensity of a [200] peak to the intensity of a [111] peak is approximately 1.5 or higher; the second hard layer preferentially grows in a [200] direction; the [200] peak is located at approximately 42.7°-44.6° and is composed of three phases, and the [111] peak is located at approximately 37.0°-38.5° and is composed of three phases; and when a peak having a largest intensity among the peaks of the three phases is a main peak and remaining peaks are sub-peaks, a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [200] face is approximately 2 or higher, and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [111] face is approximately 2 or higher.1. A hard film formed by using a PVD method on a surface of a base material, the hard film comprising a first hard layer and a second hard layer, wherein:
the first hard layer has a thickness of approximately 0.1-3.0 μm and comprises Ti1-aAlaN (0.3≤a≤0.7), and has a single phase structure; the second hard layer has a thickness of approximately 0.5-10 μm and is composed of Ti1-a-bAlaMebN (0.3≤a≤0.7, 0≤b≤0.05, and the Me is at least one selected from V, Zr, Si, Nb, Cr, Mo, Hf, Ta and W); according to an XRD phase analysis method, a ratio ([200]/[111]) of an intensity of a [200] peak to an intensity of a [111] peak is approximately 1.5 or higher; the second hard layer preferentially grows in a [200] direction; the [200] peak is located at approximately 42.7°-44.6° and comprises three phases; the [111] peak is located at approximately 37.0°-38.5° and comprises three phases; when a peak having a largest intensity among the peaks of the three phases is a main peak and remaining peaks are sub-peaks, a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [200] face is approximately 2 or higher; and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks in a [111] face is approximately 2 or higher. 2. The hard film of claim 1, wherein a third hard layer having a structure of a single layer including one or more compounds selected from Al1-xCrxN (0.3≤x≤0.7), Al1-yTiyN (0.3≤y≤0.7), and Al2O3, or a composite layer structure in which at least two single layers are laminated, is formed on the second hard layer. 3. The hard film of claim 1, wherein a fourth hard layer is formed between the first hard layer and the second hard layer, the fourth hard layer having a structure of a single layer including one or more compounds selected from Al1-xCrxN (0.3≤x≤0.7), Al1-yTiyN (0.3≤y≤0.7), and Al2O3, or a composite layer structure in which at least two single layers are laminated. 4. The hard film of claim 1, wherein
a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks of the [200] face is approximately 3-8, and a ratio (main peak/sub-peaks) of the intensity of the main peak to the intensities of the sub-peaks of the [111] face is approximately 4-7. | 2,800 |
345,459 | 16,643,361 | 2,814 | Disclosed are a method for manufacturing a coil, a coil, and an electronic device. The method includes: bonding a first side of a metal sheet onto a laser-transmitting substrate by an adhesive layer; cutting a coil pattern on a second side of the metal sheet by the laser to form a coil running through the two sides of the metal sheet on the metal sheet; bonding the second side of the metal sheet onto an adhesive tape; transmitting the laser through the laser-transmitting substrate to act on the adhesive layer to detach the laser-transmitting substrate and the adhesive layer from the first side of the metal sheet; exposing the coil pattern on the first side of the metal sheet; and forming an encapsulation layer on the coil to encapsulate the first side of the coil. | 1. A method for manufacturing a coil, comprising:
(a) bonding a first side of a metal sheet onto a laser-transmitting substrate by an adhesive layer; (b) cutting a coil pattern on a second side of the metal sheet by a laser transmission to form a coil running through the two first and second sides of the metal sheet; (c) bonding the second side of the metal sheet onto an adhesive tape; (d) transmitting the laser transmission through the laser-transmitting substrate to act on the adhesive layer to detach the laser-transmitting substrate; (e) removing the adhesive layer to expose the coil pattern on the first side of the metal sheet; and (d) forming an encapsulation layer on the coil to encapsulate the first side of the coil. 2. The method of claim 1, wherein the adhesive layer is made from polyimide, benzocyclobutene, polybenzoxazole, epoxy resin, silica gel, an acrylic adhesive, a photoresist, parylene, polyamide or polyurethane. 3. The method of claim 1, wherein the laser-transmitting substrate is made of laser-transmitting glass or laser-transmitting sapphire. 4. The method of claim 1, wherein the adhesive tape is a UV tape, and an adhesive tape frame is further disposed at each of two ends of the UV tape. 5. The method of claim 1, wherein the encapsulation layer is made from polyimide, benzocyclobutene, polybenzoxazole, epoxy resin, silica gel, an acrylic adhesive, a photoresist, parylene, polyamide or polyurethane. 6. The method of claim 1, wherein the encapsulation layer is formed on the coil by means of whirl coating, spray coating, dispensing, printing or vapor deposition. 7. The method of claim 1, wherein the cutting further comprises cutting the metal sheet by the laser to form an external pad. 8. The method of claim 1, wherein the metal sheet is made of a copper foil. 9. A coil manufactured by the method of claim 1. 10. An electronic device comprising the coil of claim 9. | Disclosed are a method for manufacturing a coil, a coil, and an electronic device. The method includes: bonding a first side of a metal sheet onto a laser-transmitting substrate by an adhesive layer; cutting a coil pattern on a second side of the metal sheet by the laser to form a coil running through the two sides of the metal sheet on the metal sheet; bonding the second side of the metal sheet onto an adhesive tape; transmitting the laser through the laser-transmitting substrate to act on the adhesive layer to detach the laser-transmitting substrate and the adhesive layer from the first side of the metal sheet; exposing the coil pattern on the first side of the metal sheet; and forming an encapsulation layer on the coil to encapsulate the first side of the coil.1. A method for manufacturing a coil, comprising:
(a) bonding a first side of a metal sheet onto a laser-transmitting substrate by an adhesive layer; (b) cutting a coil pattern on a second side of the metal sheet by a laser transmission to form a coil running through the two first and second sides of the metal sheet; (c) bonding the second side of the metal sheet onto an adhesive tape; (d) transmitting the laser transmission through the laser-transmitting substrate to act on the adhesive layer to detach the laser-transmitting substrate; (e) removing the adhesive layer to expose the coil pattern on the first side of the metal sheet; and (d) forming an encapsulation layer on the coil to encapsulate the first side of the coil. 2. The method of claim 1, wherein the adhesive layer is made from polyimide, benzocyclobutene, polybenzoxazole, epoxy resin, silica gel, an acrylic adhesive, a photoresist, parylene, polyamide or polyurethane. 3. The method of claim 1, wherein the laser-transmitting substrate is made of laser-transmitting glass or laser-transmitting sapphire. 4. The method of claim 1, wherein the adhesive tape is a UV tape, and an adhesive tape frame is further disposed at each of two ends of the UV tape. 5. The method of claim 1, wherein the encapsulation layer is made from polyimide, benzocyclobutene, polybenzoxazole, epoxy resin, silica gel, an acrylic adhesive, a photoresist, parylene, polyamide or polyurethane. 6. The method of claim 1, wherein the encapsulation layer is formed on the coil by means of whirl coating, spray coating, dispensing, printing or vapor deposition. 7. The method of claim 1, wherein the cutting further comprises cutting the metal sheet by the laser to form an external pad. 8. The method of claim 1, wherein the metal sheet is made of a copper foil. 9. A coil manufactured by the method of claim 1. 10. An electronic device comprising the coil of claim 9. | 2,800 |
345,460 | 16,643,373 | 2,814 | Embodiments of the present application provide a method and apparqatus for determining a trajectory of a human target. The method includes: extracting a target feature of a to-be-tracked human target in a to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. It can be seen that in this solution, a face image is not required for determining a trajectory of a person. Even if the acquired face image is not clear, the accuracy of determining the trajectory of the person will not be reduced. Therefore, by the solution of the present application, the accuracy of determining the trajectory of the person is improved. | 1. A method for determining a trajectory of a human target, comprising:
obtaining a to-be-processed image; extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; wherein an acquisition attribute corresponding to one target feature in the correspondence is an acquisition attribute of an image containing the target feature, and the acquisition attribute contains an acquisition location; and determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. 2. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
extracting a facial feature of the to-be-tracked human target in the to-be-processed image, as a to-be-searched facial feature; searching for an acquisition attribute corresponding to the to-be-searched facial feature based on a pre-established correspondence between facial features and acquisition attributes; wherein an acquisition attribute corresponding to one facial feature in the correspondence is an acquisition attribute of an image containing the facial feature. 3. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
extracting a facial feature of the to-be-tracked human target in the to-be-processed image as a to-be-searched facial feature; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute matching the to-be-searched target feature and the to-be-searched facial feature as the acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence among target features, facial features and acquisition attributes; wherein one pair of target feature and facial feature in the correspondence belongs to the same human target, and an acquisition feature corresponding to one pair of target feature and facial feature in the correspondence is an acquisition attribute of an image containing the target feature and the facial feature. 4. The method according to claim 1, wherein the step of extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature comprises:
extracting an original target feature of the to-be-tracked human target in the to-be-processed image, and calculating a hash value of the original target feature as a to-be-searched hash value; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes. 5. The method according to claim 4, wherein the step of searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes comprises:
calculating a similarity between each hash value comprised in the pre-established correspondence between hash values and acquisition attributes and the to-be-searched hash value, respectively; and determining an acquisition attribute corresponding to a hash value whose similarity with the to-be-searched hash value meets a preset condition. 6. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
determining an acquisition attribute of the to-be-processed image as the to-be-searched acquisition attribute; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching the pre-established correspondence between target attributes and acquisition attributes for a target acquisition attribute whose difference from the to-be-searched acquisition attribute is less than a preset threshold, and a target feature corresponding to the target acquisition attribute as a to-be-matched target feature; determining whether the to-be-matched target feature matches the to-be-searched target feature; when the to-be-matched target feature matches the to-be-searched target feature, using the target acquisition attribute as the acquisition attribute corresponding to the to-be-searched target feature. 7. The method according to claim 1, wherein the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises:
searching the pre-established correspondence between target features and acquisition attributes for a target feature group matching the to-be-searched target feature; wherein the target feature group is composed of target features belonging to the same human target; and using an acquisition attribute corresponding to each target feature comprised in the target feature group as the acquisition attribute corresponding to the to-be-searched target feature. 8. The method according to any one of claims 1 7 claim 1, wherein, the acquisition attribute further comprises acquisition time. 9-16. (canceled) 17. An electronic device, comprising a processor and a memory wherein,
the memory is configured to store a computer program, the processor is configured to execute the program stored on the memory to perform steps of: obtaining a to-be-processed image; extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; wherein an acquisition attribute corresponding to one target feature in the correspondence is an acquisition attribute of an image containing the target feature, and the acquisition attribute contains an acquisition location; and determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. 18. The device according to claim 17, wherein, the processor is further configured to perform steps of:
after obtaining the to-be-processed image, extracting a facial feature of the to-be-tracked human target in the to-be-processed image, as a to-be-searched facial feature; searching for an acquisition attribute corresponding to the to-be-searched facial feature based on a pre-established correspondence between facial features and acquisition attributes; wherein an acquisition attribute corresponding to one facial feature in the correspondence is an acquisition attribute of an image containing the facial feature. 19. The device according to claim 17, wherein, the processor is further configured to perform a step of: extracting a facial feature of the to-be-tracked human target in the to-be-processed image as a to-be-searched facial feature;
the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute matching the to-be-searched target feature and the to-be-searched facial feature as the acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence among target features, facial features and acquisition attributes; wherein one pair of target feature and facial feature in the correspondence belongs to the same human target, and an acquisition feature corresponding to one pair of target feature and facial feature in the correspondence is an acquisition attribute of an image containing the target feature and the facial feature. 20. The device according to claim 17, wherein, the step of extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature comprises:
extracting an original target feature of the to-be-tracked human target in the to-be-processed image, and calculating a hash value of the original target feature as a to-be-searched hash value; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes. 21. The device according to claim 20, wherein, the step of searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes comprises:
calculating a similarity between each hash value comprised in the pre-established correspondence between hash values and acquisition attributes and the to-be-searched hash value, respectively; and determining an acquisition attribute corresponding to a hash value whose similarity with the to-be-searched hash value meets a preset condition. 22. The device according to claim 17, wherein, the processor is further configured to perform a step of: after obtaining the to-be-processed image, determining an acquisition attribute of the to-be-processed image as the to-be-searched acquisition attribute;
the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching the pre-established correspondence between target attributes and acquisition attributes for a target acquisition attribute whose difference from the to-be-searched acquisition attribute is less than a preset threshold, and a target feature corresponding to the target acquisition attribute as a to-be-matched target feature; determining whether the to-be-matched target feature matches the to-be-searched target feature; when the to-be-matched target feature matches the to-be-searched target feature, using the target acquisition attribute as the acquisition attribute corresponding to the to-be-searched target feature. 23. The device according to claim 17, wherein, the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises:
searching the pre-established correspondence between target features and acquisition attributes for a target feature group matching the to-be-searched target feature; wherein the target feature group is composed of target features belonging to the same human target; and using an acquisition attribute corresponding to each target feature comprised in the target feature group as the acquisition attribute corresponding to the to-be-searched target feature. 24. The device according to claim 17, wherein, the acquisition attribute further comprises acquisition time. | Embodiments of the present application provide a method and apparqatus for determining a trajectory of a human target. The method includes: extracting a target feature of a to-be-tracked human target in a to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. It can be seen that in this solution, a face image is not required for determining a trajectory of a person. Even if the acquired face image is not clear, the accuracy of determining the trajectory of the person will not be reduced. Therefore, by the solution of the present application, the accuracy of determining the trajectory of the person is improved.1. A method for determining a trajectory of a human target, comprising:
obtaining a to-be-processed image; extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; wherein an acquisition attribute corresponding to one target feature in the correspondence is an acquisition attribute of an image containing the target feature, and the acquisition attribute contains an acquisition location; and determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. 2. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
extracting a facial feature of the to-be-tracked human target in the to-be-processed image, as a to-be-searched facial feature; searching for an acquisition attribute corresponding to the to-be-searched facial feature based on a pre-established correspondence between facial features and acquisition attributes; wherein an acquisition attribute corresponding to one facial feature in the correspondence is an acquisition attribute of an image containing the facial feature. 3. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
extracting a facial feature of the to-be-tracked human target in the to-be-processed image as a to-be-searched facial feature; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute matching the to-be-searched target feature and the to-be-searched facial feature as the acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence among target features, facial features and acquisition attributes; wherein one pair of target feature and facial feature in the correspondence belongs to the same human target, and an acquisition feature corresponding to one pair of target feature and facial feature in the correspondence is an acquisition attribute of an image containing the target feature and the facial feature. 4. The method according to claim 1, wherein the step of extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature comprises:
extracting an original target feature of the to-be-tracked human target in the to-be-processed image, and calculating a hash value of the original target feature as a to-be-searched hash value; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes. 5. The method according to claim 4, wherein the step of searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes comprises:
calculating a similarity between each hash value comprised in the pre-established correspondence between hash values and acquisition attributes and the to-be-searched hash value, respectively; and determining an acquisition attribute corresponding to a hash value whose similarity with the to-be-searched hash value meets a preset condition. 6. The method according to claim 1, wherein after obtaining the to-be-processed image, the method further comprises:
determining an acquisition attribute of the to-be-processed image as the to-be-searched acquisition attribute; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching the pre-established correspondence between target attributes and acquisition attributes for a target acquisition attribute whose difference from the to-be-searched acquisition attribute is less than a preset threshold, and a target feature corresponding to the target acquisition attribute as a to-be-matched target feature; determining whether the to-be-matched target feature matches the to-be-searched target feature; when the to-be-matched target feature matches the to-be-searched target feature, using the target acquisition attribute as the acquisition attribute corresponding to the to-be-searched target feature. 7. The method according to claim 1, wherein the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises:
searching the pre-established correspondence between target features and acquisition attributes for a target feature group matching the to-be-searched target feature; wherein the target feature group is composed of target features belonging to the same human target; and using an acquisition attribute corresponding to each target feature comprised in the target feature group as the acquisition attribute corresponding to the to-be-searched target feature. 8. The method according to any one of claims 1 7 claim 1, wherein, the acquisition attribute further comprises acquisition time. 9-16. (canceled) 17. An electronic device, comprising a processor and a memory wherein,
the memory is configured to store a computer program, the processor is configured to execute the program stored on the memory to perform steps of: obtaining a to-be-processed image; extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature; searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes; wherein an acquisition attribute corresponding to one target feature in the correspondence is an acquisition attribute of an image containing the target feature, and the acquisition attribute contains an acquisition location; and determining a trajectory of the to-be-tracked human target based on the found acquisition attribute. 18. The device according to claim 17, wherein, the processor is further configured to perform steps of:
after obtaining the to-be-processed image, extracting a facial feature of the to-be-tracked human target in the to-be-processed image, as a to-be-searched facial feature; searching for an acquisition attribute corresponding to the to-be-searched facial feature based on a pre-established correspondence between facial features and acquisition attributes; wherein an acquisition attribute corresponding to one facial feature in the correspondence is an acquisition attribute of an image containing the facial feature. 19. The device according to claim 17, wherein, the processor is further configured to perform a step of: extracting a facial feature of the to-be-tracked human target in the to-be-processed image as a to-be-searched facial feature;
the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute matching the to-be-searched target feature and the to-be-searched facial feature as the acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence among target features, facial features and acquisition attributes; wherein one pair of target feature and facial feature in the correspondence belongs to the same human target, and an acquisition feature corresponding to one pair of target feature and facial feature in the correspondence is an acquisition attribute of an image containing the target feature and the facial feature. 20. The device according to claim 17, wherein, the step of extracting a target feature of a to-be-tracked human target in the to-be-processed image as a to-be-searched target feature comprises:
extracting an original target feature of the to-be-tracked human target in the to-be-processed image, and calculating a hash value of the original target feature as a to-be-searched hash value; the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes. 21. The device according to claim 20, wherein, the step of searching for an acquisition attribute corresponding to the to-be-searched hash value based on a pre-established correspondence between hash values and acquisition attributes comprises:
calculating a similarity between each hash value comprised in the pre-established correspondence between hash values and acquisition attributes and the to-be-searched hash value, respectively; and determining an acquisition attribute corresponding to a hash value whose similarity with the to-be-searched hash value meets a preset condition. 22. The device according to claim 17, wherein, the processor is further configured to perform a step of: after obtaining the to-be-processed image, determining an acquisition attribute of the to-be-processed image as the to-be-searched acquisition attribute;
the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises: searching the pre-established correspondence between target attributes and acquisition attributes for a target acquisition attribute whose difference from the to-be-searched acquisition attribute is less than a preset threshold, and a target feature corresponding to the target acquisition attribute as a to-be-matched target feature; determining whether the to-be-matched target feature matches the to-be-searched target feature; when the to-be-matched target feature matches the to-be-searched target feature, using the target acquisition attribute as the acquisition attribute corresponding to the to-be-searched target feature. 23. The device according to claim 17, wherein, the step of searching for an acquisition attribute corresponding to the to-be-searched target feature based on a pre-established correspondence between target features and acquisition attributes comprises:
searching the pre-established correspondence between target features and acquisition attributes for a target feature group matching the to-be-searched target feature; wherein the target feature group is composed of target features belonging to the same human target; and using an acquisition attribute corresponding to each target feature comprised in the target feature group as the acquisition attribute corresponding to the to-be-searched target feature. 24. The device according to claim 17, wherein, the acquisition attribute further comprises acquisition time. | 2,800 |
345,461 | 16,643,388 | 2,814 | An eyeglass lens piece (10) configured for both forward and rearward viewing by a user comprises at least one curved transparent section extending in front of, above, between and below the user's eyes and a distance laterally from the sides of said user's eyes to the approximate sides of the user's head, a housing (11) arranged at an edge in the lower section (12) of the lens piece (10), projecting from the lens piece, and a mirror (15) arranged in the housing in a position offset from the curved transparent section. | 1. An eyeglass lens piece (10) configured for both forward and rearward viewing by a user, comprising:
at least one curved transparent section (13) extending in front of, above, between and below the user's eyes and a distance laterally from the sides of said user's eyes to the approximate sides of the user's head, a housing (11) arranged in an edge section (12) of the lens piece (10), projecting from the lens piece, and a mirror (15) arranged in the housing in a position offset from the curved transparent section. 2. An eyeglass lens piece (10) according to claim 1, where the housing projects a distance allowing the mirror to be offset 0-1 cm with respect to the surface of the lens piece, allowing a depth of field required for a rearview. 3. Eyeglass lens piece (10) according to claim 1, where there are one or two housings, arranged at one or both side edges of the laterally extended section of the curved transparent section. 4. Eyeglass lens piece (10) according to claim 1, where the curved transparent section is substantially spheroidal curved. 5. Eyeglass lens piece (10) according to claim 1, where the curved transparent section and the housing is one integrated unit. 6. Eyeglass lens piece (10) according to claim 1, where the mirror is arranged in the housing with an angle relative to the curvature of the curved transparent section. 7. Eyeglass lens piece (10) according to claim 6, where the curved transparent section has a symmetry axis and the mirror is arranged in the housing to be substantially perpendicular to the symmetry axis. 8. Eyeglass lens piece according to claim 1 comprising an angular adjustment mechanism (16) arranged in the housing and connecting the mirror (15) adjustable to the housing (11). 9. An eyeglass lens piece according to claim 8, where the housing projects a distance, which combined with the angular adjustment mechanism, offsets the mirror 1-2 cm with respect to the outer surface of the lens piece, allowing a depth of field required for a rearview. 10. Eyeglasses comprising a lens piece according to any of the previous claims, said eyeglass lens piece adapted by a supporting means on the head and centered a predetermined space distance in front of the user's eyes. | An eyeglass lens piece (10) configured for both forward and rearward viewing by a user comprises at least one curved transparent section extending in front of, above, between and below the user's eyes and a distance laterally from the sides of said user's eyes to the approximate sides of the user's head, a housing (11) arranged at an edge in the lower section (12) of the lens piece (10), projecting from the lens piece, and a mirror (15) arranged in the housing in a position offset from the curved transparent section.1. An eyeglass lens piece (10) configured for both forward and rearward viewing by a user, comprising:
at least one curved transparent section (13) extending in front of, above, between and below the user's eyes and a distance laterally from the sides of said user's eyes to the approximate sides of the user's head, a housing (11) arranged in an edge section (12) of the lens piece (10), projecting from the lens piece, and a mirror (15) arranged in the housing in a position offset from the curved transparent section. 2. An eyeglass lens piece (10) according to claim 1, where the housing projects a distance allowing the mirror to be offset 0-1 cm with respect to the surface of the lens piece, allowing a depth of field required for a rearview. 3. Eyeglass lens piece (10) according to claim 1, where there are one or two housings, arranged at one or both side edges of the laterally extended section of the curved transparent section. 4. Eyeglass lens piece (10) according to claim 1, where the curved transparent section is substantially spheroidal curved. 5. Eyeglass lens piece (10) according to claim 1, where the curved transparent section and the housing is one integrated unit. 6. Eyeglass lens piece (10) according to claim 1, where the mirror is arranged in the housing with an angle relative to the curvature of the curved transparent section. 7. Eyeglass lens piece (10) according to claim 6, where the curved transparent section has a symmetry axis and the mirror is arranged in the housing to be substantially perpendicular to the symmetry axis. 8. Eyeglass lens piece according to claim 1 comprising an angular adjustment mechanism (16) arranged in the housing and connecting the mirror (15) adjustable to the housing (11). 9. An eyeglass lens piece according to claim 8, where the housing projects a distance, which combined with the angular adjustment mechanism, offsets the mirror 1-2 cm with respect to the outer surface of the lens piece, allowing a depth of field required for a rearview. 10. Eyeglasses comprising a lens piece according to any of the previous claims, said eyeglass lens piece adapted by a supporting means on the head and centered a predetermined space distance in front of the user's eyes. | 2,800 |
345,462 | 16,643,353 | 2,814 | An embodiment of a semiconductor package apparatus may include technology to identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system, and complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. Other embodiments are disclosed and claimed | 1-24. (canceled) 25. An electronic processing system, comprising:
a processor; a multi-channel memory system communicatively coupled to the processor; and logic communicatively coupled to the processor to:
identify a partial set of populated memory channels from a full set of populated memory channels of the multi-channel memory system, and
complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 26. The system of claim 25, wherein the logic is further to:
identify one memory channel for the partial set of populated memory channels. 27. The system of claim 26, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 28. The system of claim 26, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 29. The system of claim 26, wherein the logic is further to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 30. The system of claim 25, wherein the logic is further to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. 31. A semiconductor package apparatus, comprising:
a substrate; and logic coupled to the substrate, wherein the logic is at least partly implemented in one or more of configurable logic and fixed-functionality hardware logic, the logic coupled to the substrate to:
identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system, and
complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 32. The apparatus of claim 31, wherein the logic is further to:
identify one memory channel for the partial set of populated memory channels. 33. The apparatus of claim 32, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 34. The apparatus of claim 32, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 35. The apparatus of claim 32, wherein the logic is further to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 36. The apparatus of claim 31, wherein the logic is further to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. 37. A method of booting an operating system, comprising:
identifying a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system; and completing a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 38. The method of claim 37, further comprising:
identifying one memory channel for the partial set of populated memory channels. 39. The method of claim 38, further comprising:
identifying a first populated memory channel of the multi-channel memory system as the one memory channel. 40. The method of claim 38, further comprising:
identifying a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 41. The method of claim 38, further comprising:
identifying a least populated memory channel of the multi-channel memory system as the one memory channel. 42. The method of claim 37, further comprising:
onlining the other populated memory channels of the full set of populated memory channels after the first boot is completed. 43. At least one computer readable medium, comprising a set of instructions, which when executed by a computing device, cause the computing device to:
identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system; and complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 44. The at least one computer readable medium of claim 43, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify one memory channel for the partial set of populated memory channels. 45. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 46. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 47. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 48. The at least one computer readable medium of claim 43, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. | An embodiment of a semiconductor package apparatus may include technology to identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system, and complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. Other embodiments are disclosed and claimed1-24. (canceled) 25. An electronic processing system, comprising:
a processor; a multi-channel memory system communicatively coupled to the processor; and logic communicatively coupled to the processor to:
identify a partial set of populated memory channels from a full set of populated memory channels of the multi-channel memory system, and
complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 26. The system of claim 25, wherein the logic is further to:
identify one memory channel for the partial set of populated memory channels. 27. The system of claim 26, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 28. The system of claim 26, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 29. The system of claim 26, wherein the logic is further to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 30. The system of claim 25, wherein the logic is further to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. 31. A semiconductor package apparatus, comprising:
a substrate; and logic coupled to the substrate, wherein the logic is at least partly implemented in one or more of configurable logic and fixed-functionality hardware logic, the logic coupled to the substrate to:
identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system, and
complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 32. The apparatus of claim 31, wherein the logic is further to:
identify one memory channel for the partial set of populated memory channels. 33. The apparatus of claim 32, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 34. The apparatus of claim 32, wherein the logic is further to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 35. The apparatus of claim 32, wherein the logic is further to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 36. The apparatus of claim 31, wherein the logic is further to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. 37. A method of booting an operating system, comprising:
identifying a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system; and completing a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 38. The method of claim 37, further comprising:
identifying one memory channel for the partial set of populated memory channels. 39. The method of claim 38, further comprising:
identifying a first populated memory channel of the multi-channel memory system as the one memory channel. 40. The method of claim 38, further comprising:
identifying a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 41. The method of claim 38, further comprising:
identifying a least populated memory channel of the multi-channel memory system as the one memory channel. 42. The method of claim 37, further comprising:
onlining the other populated memory channels of the full set of populated memory channels after the first boot is completed. 43. At least one computer readable medium, comprising a set of instructions, which when executed by a computing device, cause the computing device to:
identify a partial set of populated memory channels from a full set of populated memory channels of a multi-channel memory system; and complete a first boot of an operating system with only the identified partial set of memory channels of the multi-channel memory system. 44. The at least one computer readable medium of claim 43, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify one memory channel for the partial set of populated memory channels. 45. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a first populated memory channel of the multi-channel memory system as the one memory channel. 46. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a first populated memory channel of the multi-channel memory system with fewer memory components than a threshold as the one memory channel. 47. The at least one computer readable medium of claim 44, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
identify a least populated memory channel of the multi-channel memory system as the one memory channel. 48. The at least one computer readable medium of claim 43, comprising a further set of instructions, which when executed by the computing device, cause the computing device to:
online the other populated memory channels of the full set of populated memory channels after the first boot is completed. | 2,800 |
345,463 | 16,643,374 | 2,814 | A terminal is disclosed including a receiver that receives a signal of a downlink shared channel; and a transmitter that transmits Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. In other aspects, a radio communication method and a base station are also disclosed. | 1-6. (canceled) 7. A terminal, comprising:
a receiver that receives a signal of a downlink shared channel; and a transmitter that transmits Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. 8. The terminal according to claim 7, wherein
the receiver receives a higher layer signal including information indicating the plurality of time resource candidates. 9. The terminal according to claim 8, wherein:
the receiver receives downlink control information, and the downlink control information provides a value indicating the time resource for transmission of the ACK/NACK information, the time resource being among the plurality of time resource candidates. 10. The terminal according to claim 9, wherein
the higher layer signal includes information on a symbol of the time resource indicated by the downlink control information, the symbol being for transmission of the ACK/NACK information. 11. A radio communication method, comprising:
receiving a signal of a downlink shared channel; and transmitting Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. 12. A base station, comprising:
a transmitter that transmits a signal of a downlink shared channel; and a receiver that receives Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. | A terminal is disclosed including a receiver that receives a signal of a downlink shared channel; and a transmitter that transmits Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. In other aspects, a radio communication method and a base station are also disclosed.1-6. (canceled) 7. A terminal, comprising:
a receiver that receives a signal of a downlink shared channel; and a transmitter that transmits Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. 8. The terminal according to claim 7, wherein
the receiver receives a higher layer signal including information indicating the plurality of time resource candidates. 9. The terminal according to claim 8, wherein:
the receiver receives downlink control information, and the downlink control information provides a value indicating the time resource for transmission of the ACK/NACK information, the time resource being among the plurality of time resource candidates. 10. The terminal according to claim 9, wherein
the higher layer signal includes information on a symbol of the time resource indicated by the downlink control information, the symbol being for transmission of the ACK/NACK information. 11. A radio communication method, comprising:
receiving a signal of a downlink shared channel; and transmitting Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. 12. A base station, comprising:
a transmitter that transmits a signal of a downlink shared channel; and a receiver that receives Acknowledgement (ACK)/Negative Acknowledgement (NACK) information for the signal of the downlink shared channel using an uplink control channel in a time resource included in a plurality of time resource candidates. | 2,800 |
345,464 | 16,643,381 | 2,814 | The present invention provides a method for detecting cancer in a simple and highly accurate manner, and a reagent that can be used in the method. According to the present invention, cancer (excluding castration-resistant prostate cancer) is detected by measuring the intact growth and differentiation factor (GDF15) propeptide level, the GDF15 propeptide fragment level, or the total of the intact GDF15 propeptide level and the GDF15 propeptide fragment level, in a sample. The above described method for detecting cancer includes a method for detecting one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, and a method for distinguishing and detecting non-small cell lung cancer and small cell lung cancer. Further, a reagent for detecting cancer includes an antibody that specifically recognizes GDF15 propeptide. | 1. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the intact growth and differentiation factor 15 (GDF15) propeptide level in a sample. 2. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the GDF15 propeptide fragment level in a sample. 3. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the total of the intact GDF15 propeptide level and the GDF15 propeptide fragment level in a sample. 4. The method for detecting cancer according to claim 1, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 5. The method according to claim 2, wherein the GDF15 propeptide fragment(s) include(s) the following GDF15 propeptide fragment(s) (A) and/or (B):
(A) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the lysine at the 58th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto; (B) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the glutamic acid at the 74th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto. 6. The method according to claim 1, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 7. The method according to claim 1, wherein the measurement is carried out using mass spectrometry. 8. (canceled) 9. The method for detecting cancer according to claim 2, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 10. The method according to claim 2, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 11. The method according to claim 2, wherein the measurement is carried out using mass spectrometry. 12. The method for detecting cancer according to claim 3, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 13. The method according to claim 3, wherein the GDF15 propeptide fragment(s) include(s) the following GDF15 propeptide fragment(s) (A) and/or (B):
(A) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the lysine at the 58th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto; (B) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the glutamic acid at the 74th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto. 14. The method according to claim 3, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 15. The method according to claim 3, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. | The present invention provides a method for detecting cancer in a simple and highly accurate manner, and a reagent that can be used in the method. According to the present invention, cancer (excluding castration-resistant prostate cancer) is detected by measuring the intact growth and differentiation factor (GDF15) propeptide level, the GDF15 propeptide fragment level, or the total of the intact GDF15 propeptide level and the GDF15 propeptide fragment level, in a sample. The above described method for detecting cancer includes a method for detecting one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, and a method for distinguishing and detecting non-small cell lung cancer and small cell lung cancer. Further, a reagent for detecting cancer includes an antibody that specifically recognizes GDF15 propeptide.1. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the intact growth and differentiation factor 15 (GDF15) propeptide level in a sample. 2. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the GDF15 propeptide fragment level in a sample. 3. A method for detecting cancer (excluding castration-resistant prostate cancer), which comprises measuring the total of the intact GDF15 propeptide level and the GDF15 propeptide fragment level in a sample. 4. The method for detecting cancer according to claim 1, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 5. The method according to claim 2, wherein the GDF15 propeptide fragment(s) include(s) the following GDF15 propeptide fragment(s) (A) and/or (B):
(A) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the lysine at the 58th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto; (B) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the glutamic acid at the 74th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto. 6. The method according to claim 1, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 7. The method according to claim 1, wherein the measurement is carried out using mass spectrometry. 8. (canceled) 9. The method for detecting cancer according to claim 2, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 10. The method according to claim 2, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 11. The method according to claim 2, wherein the measurement is carried out using mass spectrometry. 12. The method for detecting cancer according to claim 3, wherein the detected cancer is one or more selected from the group consisting of stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer and esophageal cancer, or wherein non-small cell lung cancer and small cell lung cancer are distinguished to be detected. 13. The method according to claim 3, wherein the GDF15 propeptide fragment(s) include(s) the following GDF15 propeptide fragment(s) (A) and/or (B):
(A) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the lysine at the 58th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto; (B) a GDF15 propeptide fragment having the following properties: contains an amino acid sequence from the glutamic acid at the 74th residue to at least the aspartic acid at the 167th residue in the GDF15 amino acid sequence of SEQ ID NO:2, or a sequence having an identity of not less than 80% thereto. 14. The method according to claim 3, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. 15. The method according to claim 3, wherein the measurement is carried out by an antigen-antibody reaction using an antibody that recognizes GDF15 propeptide. | 2,800 |
345,465 | 16,643,389 | 2,814 | An output system according to one aspect of the present invention includes a magnet disposed on an axis of a pointer of a gauge, first and second magnetic sensors that are each configured to have a sensitivity axial direction, and an output unit configured to output indicated value information generated based on detection values of the magnetic sensors. Also, first and second directions are set to intersect each other on the axis of the pointer, and the first magnetic sensor is disposed such that the sensitivity axial direction thereof extends in the first direction, and the second magnetic sensor is disposed such that the sensitivity axial direction thereof extends in the second direction. | 1. An output system for outputting a value indicated by a pointer of a gauge that has an axis and is configured to rotate around the axis, the output system comprising:
a magnet disposed on the axis of the pointer; a first magnetic sensor and a second magnetic sensor that are each configured to have a sensitivity axial direction in which magnetic field detection sensitivity is at the maximum; and an output unit configured to output indicated value information relating to the value indicated by the pointer, the indicated value information being generated based on values that are respectively detected by the first magnetic sensor and the second magnetic sensor, wherein a first direction and a second direction are set to intersect each other on the axis of the pointer, the first magnetic sensor is disposed such that the sensitivity axial direction of the first magnetic sensor extends in the first direction, and the second magnetic sensor is disposed such that the sensitivity axial direction of the second magnetic sensor extends in the second direction. 2. The output system according to claim 1,
wherein the first direction and the second direction are set to be orthogonal to each other on the axis of the pointer. 3. The output system according to claim 1,
wherein the output unit is configured to output the indicated value information to an external device through wireless communication. 4. The output system according to claim 1,
wherein the magnet is formed into a circular shape. 5. A gauge comprising:
an axis; a dial that includes a scale provided in an arc shape around the axis; a pointer configured to rotate around the axis on the dial; a main body portion whose upper end portion is open and that includes an internal space and houses the dial and the pointer in the internal space in a state in which the scale faces the upper end portion side; a transparent cover for covering the upper end portion of the main body portion in a state in which the dial and the pointer are visually recognizable; and the output system according to claim 1, wherein the magnet is disposed on the axis of the pointer, and the first magnetic sensor, the second magnetic sensor, and the output unit are attached near a center of a surface of the transparent cover on the internal space side in a state in which the scale of the dial is not concealed. 6. The gauge according to claim 5,
wherein the output system further includes one or more substrates for disposing the first magnetic sensor, the second magnetic sensor, and the output unit, and the one or more substrates each include a window portion for visually recognizing the magnet. | An output system according to one aspect of the present invention includes a magnet disposed on an axis of a pointer of a gauge, first and second magnetic sensors that are each configured to have a sensitivity axial direction, and an output unit configured to output indicated value information generated based on detection values of the magnetic sensors. Also, first and second directions are set to intersect each other on the axis of the pointer, and the first magnetic sensor is disposed such that the sensitivity axial direction thereof extends in the first direction, and the second magnetic sensor is disposed such that the sensitivity axial direction thereof extends in the second direction.1. An output system for outputting a value indicated by a pointer of a gauge that has an axis and is configured to rotate around the axis, the output system comprising:
a magnet disposed on the axis of the pointer; a first magnetic sensor and a second magnetic sensor that are each configured to have a sensitivity axial direction in which magnetic field detection sensitivity is at the maximum; and an output unit configured to output indicated value information relating to the value indicated by the pointer, the indicated value information being generated based on values that are respectively detected by the first magnetic sensor and the second magnetic sensor, wherein a first direction and a second direction are set to intersect each other on the axis of the pointer, the first magnetic sensor is disposed such that the sensitivity axial direction of the first magnetic sensor extends in the first direction, and the second magnetic sensor is disposed such that the sensitivity axial direction of the second magnetic sensor extends in the second direction. 2. The output system according to claim 1,
wherein the first direction and the second direction are set to be orthogonal to each other on the axis of the pointer. 3. The output system according to claim 1,
wherein the output unit is configured to output the indicated value information to an external device through wireless communication. 4. The output system according to claim 1,
wherein the magnet is formed into a circular shape. 5. A gauge comprising:
an axis; a dial that includes a scale provided in an arc shape around the axis; a pointer configured to rotate around the axis on the dial; a main body portion whose upper end portion is open and that includes an internal space and houses the dial and the pointer in the internal space in a state in which the scale faces the upper end portion side; a transparent cover for covering the upper end portion of the main body portion in a state in which the dial and the pointer are visually recognizable; and the output system according to claim 1, wherein the magnet is disposed on the axis of the pointer, and the first magnetic sensor, the second magnetic sensor, and the output unit are attached near a center of a surface of the transparent cover on the internal space side in a state in which the scale of the dial is not concealed. 6. The gauge according to claim 5,
wherein the output system further includes one or more substrates for disposing the first magnetic sensor, the second magnetic sensor, and the output unit, and the one or more substrates each include a window portion for visually recognizing the magnet. | 2,800 |
345,466 | 16,643,372 | 2,814 | Various examples are provided for modular prosthetic devices and their use. In one example, a device includes a chassis assembly including a joint portion; and an interchangeable module that can be removably attached to the chassis assembly. The interchangeable modules can be configured for use in a wide variety of applications. The interchangeable modules can be quickly exchanged for different activities. | 1. A modular prosthetic device, comprising:
a chassis assembly comprising a joint portion; and an interchangeable module configured to be removably attached to the chassis assembly. 2. The device of claim 1, wherein the chassis assembly is secured to a user by attaching the chassis assembly to an existing osseous implant or existing prosthetic socket. 3. The device of claim 1, wherein the chassis assembly comprises the joint portion, a structural frame, and a mounting portion. 4. The device of claim 3, wherein the chassis assembly is secured at a proximal end to the joint portion and the mount portion is secured to a distal end of the chassis assembly. 5. The device of claim 3, wherein the structural frame accepts the interchangeable module, the interchangeable module secured to the chassis assembly via complementary mating slots and tabs on the structural frame and the interchangeable module. 6. The device of claim 5, wherein the interchangeable module is further secured to the joint portion via a locking mechanism, wherein the locking mechanism is engaged with the joint portion via a lever and locking wedge. 7. The device of claim 6, wherein the locking mechanism comprises a top snap configured to engage with the locking wedge to secure the joint portion to the interchangeable module. 8. The device of claim 7, wherein the top snap is coupled to a damping mechanism of the interchangeable module. 9. The device of claim 8, wherein the damping mechanism is a piston assembly. 10. The device of claim 3, wherein the chassis assembly is configured to accept removable prosthetic modules attached to the mounting portion. 11. The device of claim 1, where the interchangeable module comprises a damper driven mechanism. 12. The device of claim 1, wherein the modular prosthetic device is selected from a leg, a lower leg, an arm, and a forearm. 13. The device of claim 1, wherein the joint portion is securely attached to an existing osseous implant or existing prosthetic socket. 14. The device of claim 1, wherein:
the joint portion comprises a rotatable mounting plate configured to be secured to an implant or prosthetic socket of a user; and the interchangeable module comprises a locking mechanism configured to engage an open cavity of the rotatable mounting plate to secure it in a load bearing position. 15. The device of claim 14, wherein the locking mechanism comprises a pair of flanges configured to engage with a surface of the open cavity to secure the rotatable mounting plate in the load bearing position. 16. The device of claim 15, wherein the pair of flanges tilt inward towards each other to facilitate insertion in the open cavity, and flex outward to engage with the surface of the open cavity. 17. The device of claim 16, wherein the rotatable mounting plate comprises a locking wedge that forces the pair of flanges to flex outward when inserted between the pair of flanges. 18. The device of claim 17, wherein the rotatable mounting plate comprises a lever that forces the locking wedge between the pair of flanges when rotated from an extend position to a locked position. 19. The device of claim 14, wherein the chassis assembly comprises an anchor on a module mounting surface at a distal end of the chassis assembly, and the interchangeable module comprises a corresponding recess configured to align with the anchor when the interchangeable module is inserted into the chassis assembly. 20. The device of claim 20, wherein the interchangeable module and structural frame of the chassis assembly comprise mounting ridges and mounting grooves configured to secure the interchangeable module in the structural frame. | Various examples are provided for modular prosthetic devices and their use. In one example, a device includes a chassis assembly including a joint portion; and an interchangeable module that can be removably attached to the chassis assembly. The interchangeable modules can be configured for use in a wide variety of applications. The interchangeable modules can be quickly exchanged for different activities.1. A modular prosthetic device, comprising:
a chassis assembly comprising a joint portion; and an interchangeable module configured to be removably attached to the chassis assembly. 2. The device of claim 1, wherein the chassis assembly is secured to a user by attaching the chassis assembly to an existing osseous implant or existing prosthetic socket. 3. The device of claim 1, wherein the chassis assembly comprises the joint portion, a structural frame, and a mounting portion. 4. The device of claim 3, wherein the chassis assembly is secured at a proximal end to the joint portion and the mount portion is secured to a distal end of the chassis assembly. 5. The device of claim 3, wherein the structural frame accepts the interchangeable module, the interchangeable module secured to the chassis assembly via complementary mating slots and tabs on the structural frame and the interchangeable module. 6. The device of claim 5, wherein the interchangeable module is further secured to the joint portion via a locking mechanism, wherein the locking mechanism is engaged with the joint portion via a lever and locking wedge. 7. The device of claim 6, wherein the locking mechanism comprises a top snap configured to engage with the locking wedge to secure the joint portion to the interchangeable module. 8. The device of claim 7, wherein the top snap is coupled to a damping mechanism of the interchangeable module. 9. The device of claim 8, wherein the damping mechanism is a piston assembly. 10. The device of claim 3, wherein the chassis assembly is configured to accept removable prosthetic modules attached to the mounting portion. 11. The device of claim 1, where the interchangeable module comprises a damper driven mechanism. 12. The device of claim 1, wherein the modular prosthetic device is selected from a leg, a lower leg, an arm, and a forearm. 13. The device of claim 1, wherein the joint portion is securely attached to an existing osseous implant or existing prosthetic socket. 14. The device of claim 1, wherein:
the joint portion comprises a rotatable mounting plate configured to be secured to an implant or prosthetic socket of a user; and the interchangeable module comprises a locking mechanism configured to engage an open cavity of the rotatable mounting plate to secure it in a load bearing position. 15. The device of claim 14, wherein the locking mechanism comprises a pair of flanges configured to engage with a surface of the open cavity to secure the rotatable mounting plate in the load bearing position. 16. The device of claim 15, wherein the pair of flanges tilt inward towards each other to facilitate insertion in the open cavity, and flex outward to engage with the surface of the open cavity. 17. The device of claim 16, wherein the rotatable mounting plate comprises a locking wedge that forces the pair of flanges to flex outward when inserted between the pair of flanges. 18. The device of claim 17, wherein the rotatable mounting plate comprises a lever that forces the locking wedge between the pair of flanges when rotated from an extend position to a locked position. 19. The device of claim 14, wherein the chassis assembly comprises an anchor on a module mounting surface at a distal end of the chassis assembly, and the interchangeable module comprises a corresponding recess configured to align with the anchor when the interchangeable module is inserted into the chassis assembly. 20. The device of claim 20, wherein the interchangeable module and structural frame of the chassis assembly comprise mounting ridges and mounting grooves configured to secure the interchangeable module in the structural frame. | 2,800 |
345,467 | 16,643,387 | 2,814 | Included are a multiplexing unit configured to map a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and map a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and a transmitter configured to transmit the PUSCH with the PTRS and the DMRS mapped to the resources of the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a symbol position different from the symbol position that overlaps. | 1. A terminal apparatus for communicating with a base station apparatus, the terminal apparatus comprising:
a multiplexing unit configured to map a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and map a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and a transmitter configured to transmit the PUSCH with the PTRS and the DMRS mapped to the resources for the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a symbol position different from the symbol position that overlaps. 2. The terminal apparatus according to claim 1, wherein
in the case that the symbol position of the PTRS overlaps with the symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a different symbol position in a same subcarrier. 3. A communication method for a terminal apparatus for communicating with a base station apparatus, the communication method comprising the steps of:
mapping a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and mapping a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and transmitting the PUSCH with the PTRS and the DMRS mapped to the resources for the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the PTRS is mapped to a resource of the resources at a symbol position different from the symbol position that overlaps. 4. The communication method according to claim 3, wherein
in the case that the symbol position of the PTRS overlaps with the symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a different symbol position in a same subcarrier. | Included are a multiplexing unit configured to map a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and map a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and a transmitter configured to transmit the PUSCH with the PTRS and the DMRS mapped to the resources of the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a symbol position different from the symbol position that overlaps.1. A terminal apparatus for communicating with a base station apparatus, the terminal apparatus comprising:
a multiplexing unit configured to map a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and map a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and a transmitter configured to transmit the PUSCH with the PTRS and the DMRS mapped to the resources for the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a symbol position different from the symbol position that overlaps. 2. The terminal apparatus according to claim 1, wherein
in the case that the symbol position of the PTRS overlaps with the symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a different symbol position in a same subcarrier. 3. A communication method for a terminal apparatus for communicating with a base station apparatus, the communication method comprising the steps of:
mapping a Phase Tracking Reference Signal (PTRS) to resources for a Physical Uplink Shared Channel (PUSCH) according to a first pattern, and mapping a Demodulation Reference Signal (DMRS) to the resources for the PUSCH according to a second pattern; and transmitting the PUSCH with the PTRS and the DMRS mapped to the resources for the PUSCH, wherein in a case that a symbol position of the PTRS overlaps with a symbol position of the DMRS, the PTRS is mapped to a resource of the resources at a symbol position different from the symbol position that overlaps. 4. The communication method according to claim 3, wherein
in the case that the symbol position of the PTRS overlaps with the symbol position of the DMRS, the multiplexing unit maps the PTRS to a resource of the resources at a different symbol position in a same subcarrier. | 2,800 |
345,468 | 16,643,385 | 2,814 | Antenna suitable to be integrated in a printed circuit board, | 1. Antenna suitable to be integrated in a printed circuit board, which is an electromagnetically coupled antenna that comprises:
a body of dielectric material of a substantially planar design having a bottom side and top side; a bottom metallized layer on the bottom side of the body, which layer is provided with a slot; a top metallized layer on the top side of the body, which layer is provided with a T-shaped slot; wherein both the above slots, as well as the top and bottom metallized layer surrounding the slots, are provided on symmetrically opposite sides of the body; wherein electrically conductive strands are provided in the body, which strands extend substantially vertically from the bottom side to the top side, and electrically connect the bottom metallized layer with the top metallized layer; wherein the strands are disposed in such a way as to collectively form a row that delimits an inner volume of the body; wherein a feeding line of electrically conductive material is provided inside the body,
the feeding line extending in a plane between the bottom side and the top side,
wherein the feeding line has a distal section extending within the inner volume of the body delimited by the strands, which distal section has a curled shape in the plane in which it extends. 2. Antenna according to claim 1, further provided with an additional body of dielectric material which covers the T-shaped slot in the top metallized layer. 3. Antenna according to claim 1, wherein the contour of the T-shaped slot in the top metallized layer is composed of two longitudinal slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot. 4. Antenna according to claim 1, wherein the distance between adjacent strands in a row is in the range of 1 up to 2 times the thickness of a single strand. 5. Antenna according to claim 1, which is suitable to be used in the frequency range between 4.9 and 6 GHz. 6. Antenna according to claim 5, wherein the bottom metallized layer is provided with a slot having a rectangular, preferably square shape. 7. Antenna according to claim 5, wherein the curled shape is an L-shape, so that the final part of the distal section of the feeding line is oriented substantially orthogonal to a proximal section of the feeding line. 8. Antenna according to claim 7, wherein the L-shape is of a rectangular design, which comprises two longitudinal sections having an orthogonal orientation. 9. Antenna according to claim 8, wherein the first longitudinal section comprises a proximal section of the feeding line, and the second longitudinal section comprises the end part of the distal section of the feeding line, wherein the length of the first longitudinal section (L1) is in the range of 2 to 4 times the length of the second longitudinal section (L2). 10. Antenna according to claim 5, wherein the T-shaped slot comprises a first, horizontally oriented slot having a cross-directional width halfway its length, denoted as Hw, in a range of 0.60 up to 0.90 mm. 11. Antenna according to claim 5, wherein the T-shaped slot comprises a second, vertically oriented slot having a cross-directional width halfway its length, denoted as Vw, in a range of 3.00 mm up to 4.00 mm. 12. Antenna according to claim 5, wherein the contour of the T-shaped slot in the top metallized layer is composed of two slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot,
wherein the contours of the first and second slot are each defined by the following formula: 13. Antenna according to claim 12, wherein the following parameters are applied:
for i=1
m1=6
n1_1=38
n2_1=19
for i=2
m2=6
n1_2=24
n2_2=47.5
with L2=3.15 mm Hw=0.84 Vw=3.38 ai=1 bi=1 14. Antenna according to claim 12, wherein the following parameters are applied:
for i=1
m1=6
n1_1=38
n2_1=79
for i=2
m2=6
n1_2=24
n2_2=47.5
with L2=3.15 mm Hw=0.84 Vw=3.38 ai=1 bi=1 15. Antenna according to claim 1, which is suitable to be used in the frequency range between 2.4 and 2.5 GHz. 16. Antenna according to claim 15, wherein the bottom metallized layer is provided with a T-shaped slot, which preferably is identical to the slot in the top metallized layer. 17. Antenna according to claim 15, wherein the curled shape of the feeding line is a G-shape, preferably a rectangular G-shape which comprises four or five longitudinal sections of which consecutive sections have an orthogonal orientation. 18. Antenna according to claim 15,
wherein the feeding line comprises four or five longitudinal sections of which consecutive sections have an orthogonal orientation,
wherein the first longitudinal section comprises a proximal section of the feeding line, and the fourth or fifth longitudinal section constitutes the end part of the distal section of the feeding line,
wherein the length of the first longitudinal section (L1) is in the range of 2 to 4 times the length of the second longitudinal section (L2). 19. Antenna according to claim 15, wherein the feeding line has a width in the range of 0.25 to 2.0 mm. 20. Antenna according to claim 15, wherein the T-shaped slot comprises a first, horizontally oriented slot having a cross-directional width halfway its length, denoted as Hw, in a range of 1.20 to 1.40 mm. 21. Antenna according to claim 15, wherein the T-shaped slot comprises a second, vertically oriented slot having a cross-directional width halfway its length, denoted as Vw, in a range of 2.5-3.0 mm. 22. Antenna according to claim 1, wherein the contour of the T-shaped slot in the top metallized layer is composed of two slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot,
wherein the contours of the first and second slot are each defined by the following formula: 23. Antenna according to claim 22, wherein the following parameters are applied:
for i=1
a1=0.5
b1=4.1
m1=4
n1_1=103
n2_1=33
n3_1=59
for i=2
a2 7.3
b2 3.7
m2=4
n1_2=33
n2_2=48
n3_2=49
with Hw=1.23 Vw=2.76 24. Antenna according to claim 22, wherein the following parameters are applied:
for i=1
a1=7.6
b1=3.8
m1=4
n1_1=89.8
n2_1=87
n3_1=88
for i=2
a2=7.7
b2=7.8
m2=4
n1_2=81.9
n2_2=82
n3_2=91
with Hw=1.38 Vw=2.76 25. A printed circuit board which is provided with an antenna according to claim 1, wherein a part of the board, and preferably a part of the circumferential edge of the board, constitutes the body of dielectric material of the antenna. | Antenna suitable to be integrated in a printed circuit board,1. Antenna suitable to be integrated in a printed circuit board, which is an electromagnetically coupled antenna that comprises:
a body of dielectric material of a substantially planar design having a bottom side and top side; a bottom metallized layer on the bottom side of the body, which layer is provided with a slot; a top metallized layer on the top side of the body, which layer is provided with a T-shaped slot; wherein both the above slots, as well as the top and bottom metallized layer surrounding the slots, are provided on symmetrically opposite sides of the body; wherein electrically conductive strands are provided in the body, which strands extend substantially vertically from the bottom side to the top side, and electrically connect the bottom metallized layer with the top metallized layer; wherein the strands are disposed in such a way as to collectively form a row that delimits an inner volume of the body; wherein a feeding line of electrically conductive material is provided inside the body,
the feeding line extending in a plane between the bottom side and the top side,
wherein the feeding line has a distal section extending within the inner volume of the body delimited by the strands, which distal section has a curled shape in the plane in which it extends. 2. Antenna according to claim 1, further provided with an additional body of dielectric material which covers the T-shaped slot in the top metallized layer. 3. Antenna according to claim 1, wherein the contour of the T-shaped slot in the top metallized layer is composed of two longitudinal slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot. 4. Antenna according to claim 1, wherein the distance between adjacent strands in a row is in the range of 1 up to 2 times the thickness of a single strand. 5. Antenna according to claim 1, which is suitable to be used in the frequency range between 4.9 and 6 GHz. 6. Antenna according to claim 5, wherein the bottom metallized layer is provided with a slot having a rectangular, preferably square shape. 7. Antenna according to claim 5, wherein the curled shape is an L-shape, so that the final part of the distal section of the feeding line is oriented substantially orthogonal to a proximal section of the feeding line. 8. Antenna according to claim 7, wherein the L-shape is of a rectangular design, which comprises two longitudinal sections having an orthogonal orientation. 9. Antenna according to claim 8, wherein the first longitudinal section comprises a proximal section of the feeding line, and the second longitudinal section comprises the end part of the distal section of the feeding line, wherein the length of the first longitudinal section (L1) is in the range of 2 to 4 times the length of the second longitudinal section (L2). 10. Antenna according to claim 5, wherein the T-shaped slot comprises a first, horizontally oriented slot having a cross-directional width halfway its length, denoted as Hw, in a range of 0.60 up to 0.90 mm. 11. Antenna according to claim 5, wherein the T-shaped slot comprises a second, vertically oriented slot having a cross-directional width halfway its length, denoted as Vw, in a range of 3.00 mm up to 4.00 mm. 12. Antenna according to claim 5, wherein the contour of the T-shaped slot in the top metallized layer is composed of two slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot,
wherein the contours of the first and second slot are each defined by the following formula: 13. Antenna according to claim 12, wherein the following parameters are applied:
for i=1
m1=6
n1_1=38
n2_1=19
for i=2
m2=6
n1_2=24
n2_2=47.5
with L2=3.15 mm Hw=0.84 Vw=3.38 ai=1 bi=1 14. Antenna according to claim 12, wherein the following parameters are applied:
for i=1
m1=6
n1_1=38
n2_1=79
for i=2
m2=6
n1_2=24
n2_2=47.5
with L2=3.15 mm Hw=0.84 Vw=3.38 ai=1 bi=1 15. Antenna according to claim 1, which is suitable to be used in the frequency range between 2.4 and 2.5 GHz. 16. Antenna according to claim 15, wherein the bottom metallized layer is provided with a T-shaped slot, which preferably is identical to the slot in the top metallized layer. 17. Antenna according to claim 15, wherein the curled shape of the feeding line is a G-shape, preferably a rectangular G-shape which comprises four or five longitudinal sections of which consecutive sections have an orthogonal orientation. 18. Antenna according to claim 15,
wherein the feeding line comprises four or five longitudinal sections of which consecutive sections have an orthogonal orientation,
wherein the first longitudinal section comprises a proximal section of the feeding line, and the fourth or fifth longitudinal section constitutes the end part of the distal section of the feeding line,
wherein the length of the first longitudinal section (L1) is in the range of 2 to 4 times the length of the second longitudinal section (L2). 19. Antenna according to claim 15, wherein the feeding line has a width in the range of 0.25 to 2.0 mm. 20. Antenna according to claim 15, wherein the T-shaped slot comprises a first, horizontally oriented slot having a cross-directional width halfway its length, denoted as Hw, in a range of 1.20 to 1.40 mm. 21. Antenna according to claim 15, wherein the T-shaped slot comprises a second, vertically oriented slot having a cross-directional width halfway its length, denoted as Vw, in a range of 2.5-3.0 mm. 22. Antenna according to claim 1, wherein the contour of the T-shaped slot in the top metallized layer is composed of two slots of which a first slot forms a horizontally oriented slot of which the middle part is connected to the top end of a second slot which forms a vertically oriented slot,
wherein the contours of the first and second slot are each defined by the following formula: 23. Antenna according to claim 22, wherein the following parameters are applied:
for i=1
a1=0.5
b1=4.1
m1=4
n1_1=103
n2_1=33
n3_1=59
for i=2
a2 7.3
b2 3.7
m2=4
n1_2=33
n2_2=48
n3_2=49
with Hw=1.23 Vw=2.76 24. Antenna according to claim 22, wherein the following parameters are applied:
for i=1
a1=7.6
b1=3.8
m1=4
n1_1=89.8
n2_1=87
n3_1=88
for i=2
a2=7.7
b2=7.8
m2=4
n1_2=81.9
n2_2=82
n3_2=91
with Hw=1.38 Vw=2.76 25. A printed circuit board which is provided with an antenna according to claim 1, wherein a part of the board, and preferably a part of the circumferential edge of the board, constitutes the body of dielectric material of the antenna. | 2,800 |
345,469 | 16,643,382 | 3,792 | A device and method for rejuvenating skin includes a power supply adapted to generate a voltage and an applicator. The applicator includes a first node and a second node, wherein the first node is adapted to be configurable between a positive electrode or electrically isolated from the power supply, and wherein the second node is adapted to be configurable between a negative electrode or electrically isolated from the power supply. The power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode. | 1. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage; an applicator comprising a first node and a second node, wherein the first node is adapted to be configurable between a positive electrode electrically coupled to the power supply or electrically isolated from the power supply, and wherein the second node is adapted to be configurable between a negative electrode electrically coupled to the power supply or electrically isolated from the power supply; and wherein the power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode. 2. The device of claim 1, further comprising a voltage control adapted to modulate a frequency of the voltage. 3. The device of claim 2, wherein the voltage control is further adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 4. The device of claim 2, wherein the voltage control is further adapted to modulate at least one selected from an amplitude, pulse rate, pulse sweep, and duty cycle of the voltage. 5. The device of claim 1, wherein the applicator further comprises a convex surface, wherein the first node and the second node are disposed on the convex surface. 6. The device of claim 1, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period of positive voltage through the first node followed by a second period of no voltage through the first node. 7. The device of claim 2, wherein the device further comprises a network interface. 8. The device of claim 2, wherein the device further comprises a wireless interface. 9. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage; an applicator comprising a plurality of nodes, wherein each node is adapted to be configurable between a positive electrode electrically coupled to the power supply, a negative electrode electrically coupled to the power supply, or electrically isolated from the power supply; and wherein the power supply delivers a current through each node configured as a positive electrode and current returns to the power supply through each node configured as a negative electrode. 10. The device of claim 9, further comprising a voltage control adapted to modulate a frequency of the voltage. 11. The device of claim 10, wherein the voltage control is adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 12. The device of claim 10, wherein the voltage control is further adapted to modulate at least one selected from an amplitude, pulse rate, pulse sweep, and duty cycle of the voltage. 13. The device claim 9, wherein the applicator further comprises a convex surface, wherein each node is disposed on the convex surface. 14. The device of claim 9, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period of positive voltage through at least one of the electrodes followed by a second period of no voltage through any of the electrodes. 15-21. (canceled) 22. The device as claimed in claim 26, wherein said control applies said output to at least one of said nodes to activate that node and not to at least one other node to allow that other node to float. 23. The device as claimed in claim 26 wherein said control applies said output to at least one of said nodes to activate that node and allows that node to float to discharge that node. 24. (canceled) 25. (canceled) 26. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage and having at least two output terminals, said power supply providing said particular polarity between one of said output terminals and ground an applicator comprising a plurality of spaced apart electrically conductive nodes; and a control adapted to selectively connect each of said nodes with said at least one output terminal of said power supply and selectively to allow each of said nodes to float with respect to said at least one output wherein said at least one output terminal comprises at least two output terminals, and an opposite polarity between other of said output terminals and ground, wherein said control is adapted to selectively connect each of said nodes with one of said output terminals, the other of said output terminals or to float, wherein said plurality of said nodes comprise a plurality of first nodes, a plurality of second nodes, and a plurality of third nodes, wherein at least some of said third nodes are between one of said first nodes and said one of said second nodes, said wherein said control is adapted to selectively connect said first nodes with said one output terminal, said second nodes with said other of said output terminals and said third nodes to float in order to define a first pattern wherein only said first and second nodes are activated. 27. The device as claimed in claim 26, wherein said control is adapted to connect alternating ones of said electrodes with said one output terminal and said second output terminal to define a second pattern wherein all of said nodes are activated. 28. The device of claim 26, further comprising a voltage control adapted to modulate a frequency of the voltage. 29. The device of claim 28, wherein the voltage control is adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 30. The device of claim 26, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period positive voltage through at least one output terminal followed by a second period of no voltage through any of the output terminals. 31. A method for stimulating skin with a device, the device having a power supply adapted to generate a voltage and an applicator comprising a first node and a second node, the method comprising:
configuring the first node as a positive electrode electrically coupled to the power supply or electrically isolated from the power supply, and configuring the second node as a negative electrode coupled to the power supply or electrically isolated from the power supply; and wherein the power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode. 32. A method for stimulating skin with a device, the device having a power supply adapted to generate a voltage and having at least one output terminal, said power supply providing a particular polarity between said output terminal and ground and an applicator comprising a plurality of spaced apart electrically conductive nodes, the method comprising:
selectively connect each of said nodes with said at least one output terminal of said power supply and selectively allowing each of said nodes to float with respect to said at least one output terminal. | A device and method for rejuvenating skin includes a power supply adapted to generate a voltage and an applicator. The applicator includes a first node and a second node, wherein the first node is adapted to be configurable between a positive electrode or electrically isolated from the power supply, and wherein the second node is adapted to be configurable between a negative electrode or electrically isolated from the power supply. The power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode.1. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage; an applicator comprising a first node and a second node, wherein the first node is adapted to be configurable between a positive electrode electrically coupled to the power supply or electrically isolated from the power supply, and wherein the second node is adapted to be configurable between a negative electrode electrically coupled to the power supply or electrically isolated from the power supply; and wherein the power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode. 2. The device of claim 1, further comprising a voltage control adapted to modulate a frequency of the voltage. 3. The device of claim 2, wherein the voltage control is further adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 4. The device of claim 2, wherein the voltage control is further adapted to modulate at least one selected from an amplitude, pulse rate, pulse sweep, and duty cycle of the voltage. 5. The device of claim 1, wherein the applicator further comprises a convex surface, wherein the first node and the second node are disposed on the convex surface. 6. The device of claim 1, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period of positive voltage through the first node followed by a second period of no voltage through the first node. 7. The device of claim 2, wherein the device further comprises a network interface. 8. The device of claim 2, wherein the device further comprises a wireless interface. 9. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage; an applicator comprising a plurality of nodes, wherein each node is adapted to be configurable between a positive electrode electrically coupled to the power supply, a negative electrode electrically coupled to the power supply, or electrically isolated from the power supply; and wherein the power supply delivers a current through each node configured as a positive electrode and current returns to the power supply through each node configured as a negative electrode. 10. The device of claim 9, further comprising a voltage control adapted to modulate a frequency of the voltage. 11. The device of claim 10, wherein the voltage control is adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 12. The device of claim 10, wherein the voltage control is further adapted to modulate at least one selected from an amplitude, pulse rate, pulse sweep, and duty cycle of the voltage. 13. The device claim 9, wherein the applicator further comprises a convex surface, wherein each node is disposed on the convex surface. 14. The device of claim 9, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period of positive voltage through at least one of the electrodes followed by a second period of no voltage through any of the electrodes. 15-21. (canceled) 22. The device as claimed in claim 26, wherein said control applies said output to at least one of said nodes to activate that node and not to at least one other node to allow that other node to float. 23. The device as claimed in claim 26 wherein said control applies said output to at least one of said nodes to activate that node and allows that node to float to discharge that node. 24. (canceled) 25. (canceled) 26. A skin rejuvenation device, the device comprising:
a power supply adapted to generate a voltage and having at least two output terminals, said power supply providing said particular polarity between one of said output terminals and ground an applicator comprising a plurality of spaced apart electrically conductive nodes; and a control adapted to selectively connect each of said nodes with said at least one output terminal of said power supply and selectively to allow each of said nodes to float with respect to said at least one output wherein said at least one output terminal comprises at least two output terminals, and an opposite polarity between other of said output terminals and ground, wherein said control is adapted to selectively connect each of said nodes with one of said output terminals, the other of said output terminals or to float, wherein said plurality of said nodes comprise a plurality of first nodes, a plurality of second nodes, and a plurality of third nodes, wherein at least some of said third nodes are between one of said first nodes and said one of said second nodes, said wherein said control is adapted to selectively connect said first nodes with said one output terminal, said second nodes with said other of said output terminals and said third nodes to float in order to define a first pattern wherein only said first and second nodes are activated. 27. The device as claimed in claim 26, wherein said control is adapted to connect alternating ones of said electrodes with said one output terminal and said second output terminal to define a second pattern wherein all of said nodes are activated. 28. The device of claim 26, further comprising a voltage control adapted to modulate a frequency of the voltage. 29. The device of claim 28, wherein the voltage control is adapted to modulate the frequency of the voltage between 1,000 Hz and 350,000 Hz. 30. The device of claim 26, wherein the power supply is adapted to deliver a periodic voltage comprising of a first period positive voltage through at least one output terminal followed by a second period of no voltage through any of the output terminals. 31. A method for stimulating skin with a device, the device having a power supply adapted to generate a voltage and an applicator comprising a first node and a second node, the method comprising:
configuring the first node as a positive electrode electrically coupled to the power supply or electrically isolated from the power supply, and configuring the second node as a negative electrode coupled to the power supply or electrically isolated from the power supply; and wherein the power supply delivers a current through the first node when the first node is configured as the positive electrode and current returns to the power supply through the second node when the second node is configured to be the negative electrode. 32. A method for stimulating skin with a device, the device having a power supply adapted to generate a voltage and having at least one output terminal, said power supply providing a particular polarity between said output terminal and ground and an applicator comprising a plurality of spaced apart electrically conductive nodes, the method comprising:
selectively connect each of said nodes with said at least one output terminal of said power supply and selectively allowing each of said nodes to float with respect to said at least one output terminal. | 3,700 |
345,470 | 16,643,347 | 3,792 | The purpose of the present invention is to provide a novel compound which has antibacterial activity against Mycobacterium avium and Mycobacterium intracellulare that are causative bacteria of MAC infection and which is different in backbone structure from known drugs for treatment of MAC infection. One aspect of the present invention relates to a compound of Formula (I) [where R1 has the same meaning as described in the specification and claims] or a salt thereof, or a solvate thereof. Another aspect of the present invention relates to a method for producing the compound of Formula (I) or a salt thereof, or a solvate thereof, and a therapeutic agent for Mycobacterium avium complex infection (MAC infection), which comprises the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an active ingredient. | 1. A compound of Formula (I): 2. The compound according to claim 1, wherein R1 is substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or 3. The compound according to claim 1, wherein R1 is 2-methylpropan-1-en-yl. 4. A method for producing the compound or a salt thereof, or a solvate thereof according to claim 1, which comprises:
a compound accumulation step of culturing in a medium a microorganism which is Streptomyces OPMA40551 strain (Accession No. NITE BP-02510) or a variant thereof capable of producing the compound of Formula (I) to accumulate the compound of Formula (I) in the medium; and a compound purification step of purifying, from a culture broth of the microorganism, the compound of Formula (I) obtained in the compound accumulation step. 5. A microorganism which is Streptomyces OPMA40551 strain (Accession No. NITE BP-02510) or a variant thereof capable of producing the compound of Formula (I) according to claim 1. 6.-8. (canceled) 9. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to claim 1, and one or more pharmaceutically acceptable carriers. 10. The pharmaceutical composition according to claim 9 for use in preventing or treating Mycobacterium avium complex infection (MAC infection). 11. A method for preventing or treating a symptom, disease and/or disorder which is an infection with one or more bacteria, which comprises administering an effective amount of the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to according to claim 1 to a subject in need of prevention or treatment of the symptom, disease and/or disorder. 12. The method according to claim 11, wherein the symptom, disease and/or disorder which is an infection with one or more bacteria is one or more symptoms, diseases and/or disorders selected from the group consisting of Mycobacterium avium complex infection (MAC infection) and tuberculosis. | The purpose of the present invention is to provide a novel compound which has antibacterial activity against Mycobacterium avium and Mycobacterium intracellulare that are causative bacteria of MAC infection and which is different in backbone structure from known drugs for treatment of MAC infection. One aspect of the present invention relates to a compound of Formula (I) [where R1 has the same meaning as described in the specification and claims] or a salt thereof, or a solvate thereof. Another aspect of the present invention relates to a method for producing the compound of Formula (I) or a salt thereof, or a solvate thereof, and a therapeutic agent for Mycobacterium avium complex infection (MAC infection), which comprises the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an active ingredient.1. A compound of Formula (I): 2. The compound according to claim 1, wherein R1 is substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or 3. The compound according to claim 1, wherein R1 is 2-methylpropan-1-en-yl. 4. A method for producing the compound or a salt thereof, or a solvate thereof according to claim 1, which comprises:
a compound accumulation step of culturing in a medium a microorganism which is Streptomyces OPMA40551 strain (Accession No. NITE BP-02510) or a variant thereof capable of producing the compound of Formula (I) to accumulate the compound of Formula (I) in the medium; and a compound purification step of purifying, from a culture broth of the microorganism, the compound of Formula (I) obtained in the compound accumulation step. 5. A microorganism which is Streptomyces OPMA40551 strain (Accession No. NITE BP-02510) or a variant thereof capable of producing the compound of Formula (I) according to claim 1. 6.-8. (canceled) 9. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to claim 1, and one or more pharmaceutically acceptable carriers. 10. The pharmaceutical composition according to claim 9 for use in preventing or treating Mycobacterium avium complex infection (MAC infection). 11. A method for preventing or treating a symptom, disease and/or disorder which is an infection with one or more bacteria, which comprises administering an effective amount of the compound or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to according to claim 1 to a subject in need of prevention or treatment of the symptom, disease and/or disorder. 12. The method according to claim 11, wherein the symptom, disease and/or disorder which is an infection with one or more bacteria is one or more symptoms, diseases and/or disorders selected from the group consisting of Mycobacterium avium complex infection (MAC infection) and tuberculosis. | 3,700 |
345,471 | 16,643,386 | 2,493 | The present invention relates to a control system for a network device. The control system comprises a network device for connecting to a network and transmitting status information of the network device; a host server for receiving the status information via the network and transmitting action information related to the network device, wherein the action information includes at least an action command; and a Message Queuing Telemetry Transport (MQTT) server for receiving the action information from the host server, and transmitting the action information to the network device, wherein the network device executes the action command according to the received action information. | 1. A control system for a network device, the control system comprising:
a network device for connecting to a network and transmitting a status information of the network device; a host server for receiving the status information and an action information related to the network device via the network, wherein the action information includes an action command; and a Message Queuing Telemetry Transport (MQTT) server for receiving the action information from the host server and transmitting the received action information to the network device; wherein the network device executes the action command included in the action information according to the action information. 2. The control system according to claim 1, wherein after the network device executes the action command, the network device updates the status information to the host server via the network. 3. The control system according to claim 1, wherein the network device performs a security determination according to the action information and the status information to execute the action command included in the action information. 4. The control system according to claim 1, wherein the host server receives the action information from a user equipment that has obtained authentication from the server, and transmits the action information to the MQTT server, and the action information includes the encrypted action command and a related password message. 5. The control system according to claim 1, wherein the network device includes a communication platform for connecting to the network, and the control system further comprising:
at least one sensor for obtaining at least one sensing information; and a processor for generating a corresponding status information according to the at least one sensing information, and transmitting the corresponding status information to the host server with an encrypted communication protocol via the communication platform. 6. The control system according to claim 1, wherein the action information includes an encrypted action command and a related password message. 7. A control method for a network device, the control method comprising:
(a) a network device transmitting a status information to a host server by connecting to a network; (b) the host server receiving the status information and an action information related to the network device, wherein the action information includes an action command; (c) a Message Queuing Telemetry Transport (MQTT) server receiving the action information transmitted by the host server; (d) the MQTT server transmitting the action information received from the host server to the network device; and (e) the network device executing the action command included in the action information according to the received action information. 8. The control method according to claim 7, further comprising:
(f) the network device updating the status information to the host server via the network according to the executed action command. 9. The control method according to claim 7, wherein the step (e) comprising:
the network device performing a security determination according to the received action information and the status information to execute the action command included in the action information. 10. The control method according to claim 7, wherein the step (b) comprising:
the host server receiving an authentication request from an user equipment; the host server displaying the status information on the user equipment; and the user equipment receiving an action request related to the action command and transmitting the action information including the action command to the host server. 11. The control method according to claim 7, wherein the step (a) comprising:
obtaining at least one sensing information of at least one sensor; generating corresponding status information according to the at least one sensing information; and the network device connecting to the network via a communication platform, and transmitting the status information to the host server with an encrypted communication protocol. 12. The control method according to claim 7, wherein the action information includes an encrypted action command and a related password message. 13. A network device connecting to a host server and a Message Queuing Telemetry Transport (MQTT) server via a network for command and message transmissions, the network device comprising:
a communication platform for connecting to the network; a storage device for storing at least one sensing information obtained from at least one sensor; and a control device for generating a corresponding status information according to the at least one sensing information, transmitting the corresponding status information to the host server via the communication platform, and receiving an action information transmitted from the MQTT server via the communication platform, and executing an action command included in the action information. 14. The network device according to claim 13, wherein after executing the action command, the control device transmits an updated status information to the host server via the communication platform. 15. The network device according to claim 13, wherein the control device performs a security determination according to the action information and the status information to execute the action command included in the action information. 16. The network device according to claim 13, wherein the status information is displayed on an user equipment authenticated by the host server, the user equipment receives an action request related to the action command, and transmits the action information to the MQTT server via the host server. 17. The network device according to claim 13, wherein the communication platform transmits the status information to the host server with an encrypted communication protocol. 18. The network device according to claim 13, wherein the action information further includes an encrypted action command and a related password message. 19. The network device according to claim 13, wherein the network device and the at least one sensor are installed in a motor vehicle, and the action command is executed for identifying the motor vehicle, leasing the motor vehicle, starting the motor vehicle, turning off the motor vehicle, or returning the motor vehicle. | The present invention relates to a control system for a network device. The control system comprises a network device for connecting to a network and transmitting status information of the network device; a host server for receiving the status information via the network and transmitting action information related to the network device, wherein the action information includes at least an action command; and a Message Queuing Telemetry Transport (MQTT) server for receiving the action information from the host server, and transmitting the action information to the network device, wherein the network device executes the action command according to the received action information.1. A control system for a network device, the control system comprising:
a network device for connecting to a network and transmitting a status information of the network device; a host server for receiving the status information and an action information related to the network device via the network, wherein the action information includes an action command; and a Message Queuing Telemetry Transport (MQTT) server for receiving the action information from the host server and transmitting the received action information to the network device; wherein the network device executes the action command included in the action information according to the action information. 2. The control system according to claim 1, wherein after the network device executes the action command, the network device updates the status information to the host server via the network. 3. The control system according to claim 1, wherein the network device performs a security determination according to the action information and the status information to execute the action command included in the action information. 4. The control system according to claim 1, wherein the host server receives the action information from a user equipment that has obtained authentication from the server, and transmits the action information to the MQTT server, and the action information includes the encrypted action command and a related password message. 5. The control system according to claim 1, wherein the network device includes a communication platform for connecting to the network, and the control system further comprising:
at least one sensor for obtaining at least one sensing information; and a processor for generating a corresponding status information according to the at least one sensing information, and transmitting the corresponding status information to the host server with an encrypted communication protocol via the communication platform. 6. The control system according to claim 1, wherein the action information includes an encrypted action command and a related password message. 7. A control method for a network device, the control method comprising:
(a) a network device transmitting a status information to a host server by connecting to a network; (b) the host server receiving the status information and an action information related to the network device, wherein the action information includes an action command; (c) a Message Queuing Telemetry Transport (MQTT) server receiving the action information transmitted by the host server; (d) the MQTT server transmitting the action information received from the host server to the network device; and (e) the network device executing the action command included in the action information according to the received action information. 8. The control method according to claim 7, further comprising:
(f) the network device updating the status information to the host server via the network according to the executed action command. 9. The control method according to claim 7, wherein the step (e) comprising:
the network device performing a security determination according to the received action information and the status information to execute the action command included in the action information. 10. The control method according to claim 7, wherein the step (b) comprising:
the host server receiving an authentication request from an user equipment; the host server displaying the status information on the user equipment; and the user equipment receiving an action request related to the action command and transmitting the action information including the action command to the host server. 11. The control method according to claim 7, wherein the step (a) comprising:
obtaining at least one sensing information of at least one sensor; generating corresponding status information according to the at least one sensing information; and the network device connecting to the network via a communication platform, and transmitting the status information to the host server with an encrypted communication protocol. 12. The control method according to claim 7, wherein the action information includes an encrypted action command and a related password message. 13. A network device connecting to a host server and a Message Queuing Telemetry Transport (MQTT) server via a network for command and message transmissions, the network device comprising:
a communication platform for connecting to the network; a storage device for storing at least one sensing information obtained from at least one sensor; and a control device for generating a corresponding status information according to the at least one sensing information, transmitting the corresponding status information to the host server via the communication platform, and receiving an action information transmitted from the MQTT server via the communication platform, and executing an action command included in the action information. 14. The network device according to claim 13, wherein after executing the action command, the control device transmits an updated status information to the host server via the communication platform. 15. The network device according to claim 13, wherein the control device performs a security determination according to the action information and the status information to execute the action command included in the action information. 16. The network device according to claim 13, wherein the status information is displayed on an user equipment authenticated by the host server, the user equipment receives an action request related to the action command, and transmits the action information to the MQTT server via the host server. 17. The network device according to claim 13, wherein the communication platform transmits the status information to the host server with an encrypted communication protocol. 18. The network device according to claim 13, wherein the action information further includes an encrypted action command and a related password message. 19. The network device according to claim 13, wherein the network device and the at least one sensor are installed in a motor vehicle, and the action command is executed for identifying the motor vehicle, leasing the motor vehicle, starting the motor vehicle, turning off the motor vehicle, or returning the motor vehicle. | 2,400 |
345,472 | 16,643,390 | 1,656 | In alternative embodiments, provided are compositions and methods for making a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. In alternative embodiments, the compositions and methods comprise recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. Also provided are compositions and methods for displaying or immobilizing proteins on a methanotrophic S-layer. In alternative embodiments, provided are compositions and methods comprising recombinant methylotrophic or methanotrophic bacteria comprising assembled or self-assembled recombinant or isolated chimeric S-layer polypeptides. In alternative embodiments, provided are compositions and methods using recombinant methylotrophic or methanotrophic bacteria, optionally a Methylomicrobium alcaliphilum, optionally a M. alcaliphilum sp. 20Z, for ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid), for the production or synthesis of a protein, e.g., an ectoine, or an enzyme, e.g., a lipase. | 1. A method for making a chimeric polypeptide comprising an S-layer polypeptide, or a self-aggregating or self-assembling fragment thereof, and a heterologous polypeptide or peptide, the method comprising recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide is on the carboxy terminal end of the heterologous polypeptide or peptide, and optionally the recombinant or isolated chimeric polypeptide has assembled or is self-assembled to form a monomolecular layer. 2. A method for displaying or immobilizing proteins on a methanotrophic S-layer protein, or a self-aggregating or self-assembling fragment thereof, comprising recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide or a self-aggregating or self-assembling fragment thereof and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide or self-aggregating or self-assembling fragment thereof is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof has assembled or is self-assembled to form a monomolecular layer. 3. A recombinant or isolated chimeric S-layer polypeptide, wherein the recombinant or isolated chimeric S-layer polypeptide comprises an S-layer polypeptide or self-aggregating or self-assembling fragment thereof and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide has assembled or is self-assembled to form a monomolecular layer. 4. A recombinant or isolated monomolecular layer comprising a chimeric S-layer polypeptide, wherein the recombinant or isolated chimeric S-layer polypeptide comprises an S-layer polypeptide or a self-aggregating or self-assembling fragment thereof, and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide self-aggregating or self-assembling fragment thereof is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide self-aggregating or self-assembling fragment thereof has assembled or is self-assembled to form a monomolecular layer. 5. A recombinant or genetically engineered methylotrophic or methanotrophic bacteria comprising the recombinant or isolated chimeric S-layer polypeptide or a self-aggregating or self-assembling fragment thereof of claim 3,
wherein optionally the recombinant or chimeric polypeptide has assembled or is self-assembled to form a monomolecular layer on the extracellular surface of the recombinant methylotrophic or methanotrophic bacteria, and optionally the heterologous polypeptide or peptide is at least partially exposed, or is fully exposed, to an extracellular environment or milieu. 6. The recombinant or isolated chimeric S-layer polypeptide of claim 3, wherein the S-layer polypeptide or self-aggregating or self-assembling fragment thereof comprises or is a lipoprotein. 7. The recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof of claim 3, wherein the methylotrophic or methanotrophic bacteria is selected the group consisting of a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, and a Methylosinus bacteria; or, the S-layer polypeptide is derived from a methylotrophic or methanotrophic bacteria, or a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, or a Methylosinus bacteria. 8. The recombinant or isolated chimeric S-layer polypeptide self-aggregating or self-assembling fragment thereof of claim 3, wherein the methylotrophic or methanotrophic bacteria is a Methylomicrobium alcaliphilum (M. alcaliphilum), or a M. alcaliphilum sp. 20Z. 9. The method, or the recombinant or isolated chimeric S-layer polypeptide of claim 3, wherein the chimeric polypeptide, or the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, is expressed on the surface of a methylotrophic or methanotrophic bacteria, and the heterologous polypeptide, or the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, is at least in part exposed to an extracellular environment or milieu. 10. The recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, of claim 3, wherein the methanotrophic S-layer polypeptide or self-assembling fragment thereof is isolated from the methylotrophic or methanotrophic bacteria. 11. The method, or the recombinant or isolated chimeric S-layer polypeptide, of claim 3, wherein the heterologous polypeptide or peptide, or recombinant or isolated chimeric S-layer polypeptide, comprises or is an enzyme, a structural protein, a fluorescent or a chemiluminescent protein, a ligand, a receptor, an antibody or antigen binding protein, or an antigen, a tolerogen or an immunogen. 12. The recombinant or isolated chimeric S-layer polypeptide of claim 11, wherein the enzyme is an industrial enzyme, or the enzyme is a lipase, a protease, a nitrogenase, a hydrogenase, a monooxygenase, an amylase, an isomerase, a cellulase or hemicellulase, a laccase, an epimerase, a decarboxylase, a glucanase or a fl-glucanase, a glucosidase, a phosphorylase, a phosphatase, a halogenase or a dehalogenase, a GlcNAc transferase, an N-acetylglucosamine, a GlcNAc transferase, a neuraminidase or sialidase, a nuclease, a peroxidase or an oxidase, or a metalloproteinase. 13. The recombinant or isolated chimeric S-layer polypeptide, of claim 3, wherein the chimeric protein, the recombinant or isolated chimeric S-layer polypeptide or self-assembling fragment thereof, the recombinant or isolated monomolecular layer, or the recombinant methylotrophic or methanotrophic bacteria, act as or are used as or used for: an ultrafiltration membrane; an affinity structure; nitrogen fixation; converting carbon dioxide into methane; methane uptake or methane oxidation; converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an anchor for extracellular production of a small molecule or a protein (optionally an enzyme or a structural protein), an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical. 14. A membrane or an enzyme membrane; an ultrafiltration membrane; an affinity structure; a composition or device for nitrogen fixation; a composition or device for converting carbon dioxide into methane; a composition or device for methane uptake or methane oxidation; a composition or device for converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an implant; an anchor for extracellular production of a small molecule or a protein (optionally an enzyme or a structural protein), an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical, comprising:
A recombinant or isolated chimeric S-layer polypeptide of claim 3. 15. A recombinant methylotrophic or methanotrophic bacteria, optionally a Methylomicrobium alcaliphilum (M. alcaliphilum), optionally a M. alcaliphilum sp. 20Z, for ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid) production or synthesis, wherein:
(a) the recombinant or engineered methylotrophic or methanotrophic bacteria comprises an ectoine biosynthetic gene cluster organized as one operon (ectABC-ask), wherein the operon comprises genes encoding: a diaminobutyric acid (DABA) aminotransferase (EctB); a DABA acetyltransferase (EctA), and an ectoine synthase (EctC); and (b) the recombinant or engineered methylotrophic or methanotrophic bacteria: (i) is engineered to lack or not express a functional EctR1 repressor; (ii) comprises an isocitrate lyase/malate synthase fusion (transcriptionally controlled by a hps promoter (Phps); and/or, (iii) comprises one or more of the genetic modifications set forth in Table 1. 16. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein a doeA-gene encoding ectoine hydrolase is deleted or mutated such that a functional ectoine hydrolase is not expressed. 17. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein the recombinant methylotrophic or methanotrophic bacteria further comprises an exogenous nucleic acid capable of expressing a methanotrophic lipase, or a functional lipase fragment thereof, in the recombinant methylotrophic or methanotrophic bacteria. 18. The recombinant methylotrophic or methanotrophic bacteria of claim 17, wherein:
(a) the recombinant bacteria is engineered such that the ectoine and/or the lipase, or the functional lipase fragment thereof, is expressed as an S layer protein chimeric polypeptide, optionally as a lipase-S protein fusion protein, wherein optionally the S-layer protein is positioned at the amino terminus; (b) the methylotrophic or methanotrophic bacteria is selected the group consisting of a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, and a Methylosinus bacteria; or (c) the methylotrophic or methanotrophic bacteria further comprises the ability to express: a heterologous or exogenous protein or enzyme, optionally an industrial enzyme; or a chimeric protein comprising an S-layer protein and the heterologous or exogenous protein or enzyme, wherein optionally the protein or enzyme is a lipase, a protease, a nitrogenase, a hydrogenase, a monooxygenase, an amylase, an isomerase, a cellulase or hemicellulase, a laccase, an epimerase, a decarboxylase, a glucanase or a fl-glucanase, a glucosidase, a phosphorylase, a phosphatase, a halogenase or a dehalogenase, a GlcNAc transferase, an N-acetylglucosamine, a GlcNAc transferase, a neuraminidase or sialidase, a nuclease, a peroxidase or an oxidase, or a metalloproteinase. 19-20. (canceled) 21. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein the recombinant methylotrophic or methanotrophic bacteria, act as or are used as or used for: an ultrafiltration membrane; an affinity structure; nitrogen fixation; converting carbon dioxide into methane; methane uptake or methane oxidation; converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an anchor for extracellular production of a small molecule or a protein, an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical,
wherein optionally the protein comprises an enzyme or a structural protein. 22. A membrane or an enzyme membrane; an ultrafiltration membrane; an affinity structure; a composition or device for nitrogen fixation; a composition or device for converting carbon dioxide into methane; a composition or device for methane uptake or methane oxidation; a composition or device for converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an implant; an anchor for extracellular production of a small molecule or a protein, an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical,
wherein optionally the protein comprises an enzyme or a structural protein, comprising: a recombinant or isolated chimeric S-layer polypeptide of claim 3. | In alternative embodiments, provided are compositions and methods for making a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. In alternative embodiments, the compositions and methods comprise recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. Also provided are compositions and methods for displaying or immobilizing proteins on a methanotrophic S-layer. In alternative embodiments, provided are compositions and methods comprising recombinant methylotrophic or methanotrophic bacteria comprising assembled or self-assembled recombinant or isolated chimeric S-layer polypeptides. In alternative embodiments, provided are compositions and methods using recombinant methylotrophic or methanotrophic bacteria, optionally a Methylomicrobium alcaliphilum, optionally a M. alcaliphilum sp. 20Z, for ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid), for the production or synthesis of a protein, e.g., an ectoine, or an enzyme, e.g., a lipase.1. A method for making a chimeric polypeptide comprising an S-layer polypeptide, or a self-aggregating or self-assembling fragment thereof, and a heterologous polypeptide or peptide, the method comprising recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide is on the carboxy terminal end of the heterologous polypeptide or peptide, and optionally the recombinant or isolated chimeric polypeptide has assembled or is self-assembled to form a monomolecular layer. 2. A method for displaying or immobilizing proteins on a methanotrophic S-layer protein, or a self-aggregating or self-assembling fragment thereof, comprising recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide or a self-aggregating or self-assembling fragment thereof and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide or self-aggregating or self-assembling fragment thereof is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof has assembled or is self-assembled to form a monomolecular layer. 3. A recombinant or isolated chimeric S-layer polypeptide, wherein the recombinant or isolated chimeric S-layer polypeptide comprises an S-layer polypeptide or self-aggregating or self-assembling fragment thereof and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide has assembled or is self-assembled to form a monomolecular layer. 4. A recombinant or isolated monomolecular layer comprising a chimeric S-layer polypeptide, wherein the recombinant or isolated chimeric S-layer polypeptide comprises an S-layer polypeptide or a self-aggregating or self-assembling fragment thereof, and a heterologous polypeptide or peptide,
wherein optionally the S-layer polypeptide self-aggregating or self-assembling fragment thereof is on the carboxy terminal end of the heterologous polypeptide or peptide, wherein optionally the recombinant or isolated chimeric S-layer polypeptide self-aggregating or self-assembling fragment thereof has assembled or is self-assembled to form a monomolecular layer. 5. A recombinant or genetically engineered methylotrophic or methanotrophic bacteria comprising the recombinant or isolated chimeric S-layer polypeptide or a self-aggregating or self-assembling fragment thereof of claim 3,
wherein optionally the recombinant or chimeric polypeptide has assembled or is self-assembled to form a monomolecular layer on the extracellular surface of the recombinant methylotrophic or methanotrophic bacteria, and optionally the heterologous polypeptide or peptide is at least partially exposed, or is fully exposed, to an extracellular environment or milieu. 6. The recombinant or isolated chimeric S-layer polypeptide of claim 3, wherein the S-layer polypeptide or self-aggregating or self-assembling fragment thereof comprises or is a lipoprotein. 7. The recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof of claim 3, wherein the methylotrophic or methanotrophic bacteria is selected the group consisting of a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, and a Methylosinus bacteria; or, the S-layer polypeptide is derived from a methylotrophic or methanotrophic bacteria, or a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, or a Methylosinus bacteria. 8. The recombinant or isolated chimeric S-layer polypeptide self-aggregating or self-assembling fragment thereof of claim 3, wherein the methylotrophic or methanotrophic bacteria is a Methylomicrobium alcaliphilum (M. alcaliphilum), or a M. alcaliphilum sp. 20Z. 9. The method, or the recombinant or isolated chimeric S-layer polypeptide of claim 3, wherein the chimeric polypeptide, or the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, is expressed on the surface of a methylotrophic or methanotrophic bacteria, and the heterologous polypeptide, or the recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, is at least in part exposed to an extracellular environment or milieu. 10. The recombinant or isolated chimeric S-layer polypeptide or self-aggregating or self-assembling fragment thereof, of claim 3, wherein the methanotrophic S-layer polypeptide or self-assembling fragment thereof is isolated from the methylotrophic or methanotrophic bacteria. 11. The method, or the recombinant or isolated chimeric S-layer polypeptide, of claim 3, wherein the heterologous polypeptide or peptide, or recombinant or isolated chimeric S-layer polypeptide, comprises or is an enzyme, a structural protein, a fluorescent or a chemiluminescent protein, a ligand, a receptor, an antibody or antigen binding protein, or an antigen, a tolerogen or an immunogen. 12. The recombinant or isolated chimeric S-layer polypeptide of claim 11, wherein the enzyme is an industrial enzyme, or the enzyme is a lipase, a protease, a nitrogenase, a hydrogenase, a monooxygenase, an amylase, an isomerase, a cellulase or hemicellulase, a laccase, an epimerase, a decarboxylase, a glucanase or a fl-glucanase, a glucosidase, a phosphorylase, a phosphatase, a halogenase or a dehalogenase, a GlcNAc transferase, an N-acetylglucosamine, a GlcNAc transferase, a neuraminidase or sialidase, a nuclease, a peroxidase or an oxidase, or a metalloproteinase. 13. The recombinant or isolated chimeric S-layer polypeptide, of claim 3, wherein the chimeric protein, the recombinant or isolated chimeric S-layer polypeptide or self-assembling fragment thereof, the recombinant or isolated monomolecular layer, or the recombinant methylotrophic or methanotrophic bacteria, act as or are used as or used for: an ultrafiltration membrane; an affinity structure; nitrogen fixation; converting carbon dioxide into methane; methane uptake or methane oxidation; converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an anchor for extracellular production of a small molecule or a protein (optionally an enzyme or a structural protein), an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical. 14. A membrane or an enzyme membrane; an ultrafiltration membrane; an affinity structure; a composition or device for nitrogen fixation; a composition or device for converting carbon dioxide into methane; a composition or device for methane uptake or methane oxidation; a composition or device for converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an implant; an anchor for extracellular production of a small molecule or a protein (optionally an enzyme or a structural protein), an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical, comprising:
A recombinant or isolated chimeric S-layer polypeptide of claim 3. 15. A recombinant methylotrophic or methanotrophic bacteria, optionally a Methylomicrobium alcaliphilum (M. alcaliphilum), optionally a M. alcaliphilum sp. 20Z, for ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid) production or synthesis, wherein:
(a) the recombinant or engineered methylotrophic or methanotrophic bacteria comprises an ectoine biosynthetic gene cluster organized as one operon (ectABC-ask), wherein the operon comprises genes encoding: a diaminobutyric acid (DABA) aminotransferase (EctB); a DABA acetyltransferase (EctA), and an ectoine synthase (EctC); and (b) the recombinant or engineered methylotrophic or methanotrophic bacteria: (i) is engineered to lack or not express a functional EctR1 repressor; (ii) comprises an isocitrate lyase/malate synthase fusion (transcriptionally controlled by a hps promoter (Phps); and/or, (iii) comprises one or more of the genetic modifications set forth in Table 1. 16. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein a doeA-gene encoding ectoine hydrolase is deleted or mutated such that a functional ectoine hydrolase is not expressed. 17. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein the recombinant methylotrophic or methanotrophic bacteria further comprises an exogenous nucleic acid capable of expressing a methanotrophic lipase, or a functional lipase fragment thereof, in the recombinant methylotrophic or methanotrophic bacteria. 18. The recombinant methylotrophic or methanotrophic bacteria of claim 17, wherein:
(a) the recombinant bacteria is engineered such that the ectoine and/or the lipase, or the functional lipase fragment thereof, is expressed as an S layer protein chimeric polypeptide, optionally as a lipase-S protein fusion protein, wherein optionally the S-layer protein is positioned at the amino terminus; (b) the methylotrophic or methanotrophic bacteria is selected the group consisting of a Methylococcus, a Methylomonas, a Methylomicrobium, a Methylobacter, a Methylomarinum, a Methylovulum, a Methylocaldum, a Methylothermus, a Methylomarinovum, a Methylosphaera, a Methylocystis, and a Methylosinus bacteria; or (c) the methylotrophic or methanotrophic bacteria further comprises the ability to express: a heterologous or exogenous protein or enzyme, optionally an industrial enzyme; or a chimeric protein comprising an S-layer protein and the heterologous or exogenous protein or enzyme, wherein optionally the protein or enzyme is a lipase, a protease, a nitrogenase, a hydrogenase, a monooxygenase, an amylase, an isomerase, a cellulase or hemicellulase, a laccase, an epimerase, a decarboxylase, a glucanase or a fl-glucanase, a glucosidase, a phosphorylase, a phosphatase, a halogenase or a dehalogenase, a GlcNAc transferase, an N-acetylglucosamine, a GlcNAc transferase, a neuraminidase or sialidase, a nuclease, a peroxidase or an oxidase, or a metalloproteinase. 19-20. (canceled) 21. The recombinant methylotrophic or methanotrophic bacteria of claim 15, wherein the recombinant methylotrophic or methanotrophic bacteria, act as or are used as or used for: an ultrafiltration membrane; an affinity structure; nitrogen fixation; converting carbon dioxide into methane; methane uptake or methane oxidation; converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an anchor for extracellular production of a small molecule or a protein, an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical,
wherein optionally the protein comprises an enzyme or a structural protein. 22. A membrane or an enzyme membrane; an ultrafiltration membrane; an affinity structure; a composition or device for nitrogen fixation; a composition or device for converting carbon dioxide into methane; a composition or device for methane uptake or methane oxidation; a composition or device for converting nitrogen gas to ammonia; a membrane of an enzyme membrane; a micro-carrier; a biosensor; a diagnostic device; a biocompatible surface; a vaccine; a device or composition for targeting, delivery and/or encapsulation; an implant; an anchor for extracellular production of a small molecule or a protein, an enzymatic system for a bioremediation or a bio-mitigation, or a pharmaceutical or a protein-based biopharmaceutical,
wherein optionally the protein comprises an enzyme or a structural protein, comprising: a recombinant or isolated chimeric S-layer polypeptide of claim 3. | 1,600 |
345,473 | 16,643,358 | 1,656 | Provided is a glycated hemoglobin oxidase with small measurement error or without deviation of the measured value from the true value regarding a sample containing glycated abnormal hemoglobin. Provided are a glycated hemoglobin oxidase comprising an amino acid sequence in which the amino acid at the position corresponding to position 113, 109, 106, or 102 of the amino acid sequence of SEQ ID NO: 1 is substituted with an amino acid other than a positively-charged amino acid, such as glutamic acid, alanine, or aspartic acid as well as a method and a reagent kit for measurement of glycated hemoglobin using such glycated hemoglobin oxidase. The glycated hemoglobin is capable of reacting with various genotypes and enables highly accurate measurement of glycated hemoglobin in a sample containing glycated abnormal hemoglobin. | 1. A method for measurement of HbS1c or HbC1c in a sample comprising a step of allowing glycated hemoglobin oxidase to act on a sample that can contain HbS1c or HbC1c. 2. The method according to claim 1, wherein the amount of a reduced compound generated by the action of the glycated hemoglobin oxidase is measured. 3. The method according to claim 2, wherein the reduced compound to be measured is hydrogen peroxide. 4. The method according to claim 1, wherein the glycated hemoglobin oxidase has properties (a) and/or (b):
(a) the ratio of activity on HbS1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbS1c/HbA1c), is 0.45 or more; and (b) the ratio of activity on HbC1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbC1c/HbA1c), is 0.15 or more. 5. The method according to claim 1, wherein the glycated hemoglobin oxidase has an optimal pH range of 6 to 8, an operative pH range of 5 to 9, an optimal temperature range of 25° C. to 40° C., and a molecular weight of about 45 to 55 KDa on SDS-PAGE. 6. The method according to claim 1, wherein the glycated hemoglobin oxidase is a glycated hemoglobin oxidase variant selected from the group consisting of (i) to (viii) below:
(i) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (ii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 109 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 106 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iv) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 102 of the amino acid sequence of SEQ ID NO: I is modified into an amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having a substitution, deletion, or addition of 1 or several amino acids at positions other than those corresponding to positions 113, 109, 106, and 102 of the amino acid sequence of SEQ ID NO: 1; (vi) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid; (vii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 90% or higher sequence identity between the amino acid sequence of the homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of the homologous region of the corresponding positions of the glycated hemoglobin oxidase; and (viii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 50% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 70% or higher sequence identity between the amino acid sequence of a homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of a homologous region of the corresponding positions of the glycated hemoglobin oxidase, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid. 7. Glycated hemoglobin oxidase for measurement of HbS1c or HbC1c in a sample. 8. The glycated hemoglobin oxidase according to claim 7, which is allowed to act on HbS1c or HbC1c and used to measure the amount of the reduced compound generated. 9. The glycated hemoglobin oxidase according to claim 8, wherein the reduced compound generated is hydrogen peroxide. 10. The glycated hemoglobin oxidase according to claim 7, which has properties (a) and/or (b):
(a) the ratio of activity on HbS1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbS1c/HbA1c), is 0.45 or more; and (b) the ratio of activity on HbC1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbC1c/HbA1c), is 0.15 or more. 11. The glycated hemoglobin oxidase according to claim 7, which has an optimal pH range of 6 to 8, an operative pH range of 5 to 9, an optimal temperature range of 25° C. to 40° C., and a molecular weight of about 45 to 55 KDa on SDS-PAGE. 12. The glycated hemoglobin oxidase according to claim 7, which is selected from the group consisting of (i) to (viii) below:
(i) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (ii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 109 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 106 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iv) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 102 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having a substitution, deletion, or addition of 1 or several amino acids at positions other than those corresponding to positions 113, 109, 106, and 102 of the amino acid sequence of SEQ ID NO: 1; (vi) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid; (vii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 90% or higher sequence identity between the amino acid sequence of the homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of the homologous region of the corresponding positions of the glycated hemoglobin oxidase; and (viii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 50% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 70% or higher sequence identity between the amino acid sequence of a homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of a homologous region of the corresponding positions of the glycated hemoglobin oxidase, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid. 13. The glycated hemoglobin oxidase according to claim 7, based on an amadoriase of the genus Coniochaeta, Eupenicillium, Pyrenochaeta, Arthrinium, Curvularia, Neocosmospora, Cryptococcus, Phaeosphaeria, Aspergillus, Emericella, Ulocladium, or Penicillium. 14. The glycated hemoglobin oxidase according to claim 13, wherein the amadoriase is derived from Coniochaeta sp., Eupenicillium terrenum, Pyrenochaeta sp., Arthrinium sp., Curvularia clavata, Neocosmospora vasinfecta, Cryptococcus neoformans, Phaeosphaeria nodorum, Aspergillus nidulans, Emericella nidulans, Ulocladium sp., Penicillium janthinelum, or Penicillium chrysogenum. 15. A reagent composition for measurement of HbS1c or HbC1c comprising the glycated hemoglobin oxidase according to claim 7. 16. A gene encoding the glycated hemoglobin oxidase according to claim 7. 17. A vector comprising the gene according to claim 16. 18. A host cell comprising the vector according to claim 17. 19. A method for producing glycated hemoglobin oxidase comprising the following steps:
(i) culturing the host cell according to claim 18 under conditions where the glycated hemoglobin oxidase can be expressed; and (ii) isolating the glycated hemoglobin oxidase from a culture product or culture solution. 20. A method for producing glycated hemoglobin oxidase by modifying an amadoriase or A1c oxidase comprising the following steps:
(i) obtaining an amadoriase gene or A1c oxidase gene; (ii) integrating the amadoriase gene or A1c oxidase gene into a vector, transforming the host cell, expressing the amadoriase or A1c oxidase, and isolating the expressed product; (iii) measuring the relative activity (HbS1c/HbA1c) and/or the relative activity (HbC1c/HbA1c) of the expressed product; (iv) modifying the amadoriase gene or A1c oxidase gene such that, when the amino acid sequence of the amadoriase or A1c oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113, 109, 106, or 102 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) integrating the modified gene into a vector, transforming a host cell, expressing the modified amadoriase or A1c oxidase, and isolating the expressed product; (vi) measuring the relative activity (HbS1c/HbA1c) and/or the relative activity (HbC1c/HbA1c) of the expressed product of the modified amadoriase or A1c oxidase and comparing the measured values with the values measured in step (iii); (vii) when the relative activity (HbS1/HbA1c) of the modified amadoriase or A1c oxidase is 1.1 times or greater than the relative activity (HbS1c/HbA1c) of the amadoriase or A1c oxidase before modification and/or the relative activity (HbC1c/HbA1c) of the modified amadoriase or A1c oxidase is 1.1 times or greater than the relative activity (HbC1c/HbA1c) of the amadoriase or A1c oxidase before modification, designating the modified amadoriase or A1c oxidase as a glycated hemoglobin oxidase; and (viii) repeating steps (iv) to (vi) on the glycated hemoglobin oxidase of step (vii), according to need. | Provided is a glycated hemoglobin oxidase with small measurement error or without deviation of the measured value from the true value regarding a sample containing glycated abnormal hemoglobin. Provided are a glycated hemoglobin oxidase comprising an amino acid sequence in which the amino acid at the position corresponding to position 113, 109, 106, or 102 of the amino acid sequence of SEQ ID NO: 1 is substituted with an amino acid other than a positively-charged amino acid, such as glutamic acid, alanine, or aspartic acid as well as a method and a reagent kit for measurement of glycated hemoglobin using such glycated hemoglobin oxidase. The glycated hemoglobin is capable of reacting with various genotypes and enables highly accurate measurement of glycated hemoglobin in a sample containing glycated abnormal hemoglobin.1. A method for measurement of HbS1c or HbC1c in a sample comprising a step of allowing glycated hemoglobin oxidase to act on a sample that can contain HbS1c or HbC1c. 2. The method according to claim 1, wherein the amount of a reduced compound generated by the action of the glycated hemoglobin oxidase is measured. 3. The method according to claim 2, wherein the reduced compound to be measured is hydrogen peroxide. 4. The method according to claim 1, wherein the glycated hemoglobin oxidase has properties (a) and/or (b):
(a) the ratio of activity on HbS1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbS1c/HbA1c), is 0.45 or more; and (b) the ratio of activity on HbC1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbC1c/HbA1c), is 0.15 or more. 5. The method according to claim 1, wherein the glycated hemoglobin oxidase has an optimal pH range of 6 to 8, an operative pH range of 5 to 9, an optimal temperature range of 25° C. to 40° C., and a molecular weight of about 45 to 55 KDa on SDS-PAGE. 6. The method according to claim 1, wherein the glycated hemoglobin oxidase is a glycated hemoglobin oxidase variant selected from the group consisting of (i) to (viii) below:
(i) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (ii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 109 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 106 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iv) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 102 of the amino acid sequence of SEQ ID NO: I is modified into an amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having a substitution, deletion, or addition of 1 or several amino acids at positions other than those corresponding to positions 113, 109, 106, and 102 of the amino acid sequence of SEQ ID NO: 1; (vi) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid; (vii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 90% or higher sequence identity between the amino acid sequence of the homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of the homologous region of the corresponding positions of the glycated hemoglobin oxidase; and (viii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 50% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 70% or higher sequence identity between the amino acid sequence of a homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of a homologous region of the corresponding positions of the glycated hemoglobin oxidase, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid. 7. Glycated hemoglobin oxidase for measurement of HbS1c or HbC1c in a sample. 8. The glycated hemoglobin oxidase according to claim 7, which is allowed to act on HbS1c or HbC1c and used to measure the amount of the reduced compound generated. 9. The glycated hemoglobin oxidase according to claim 8, wherein the reduced compound generated is hydrogen peroxide. 10. The glycated hemoglobin oxidase according to claim 7, which has properties (a) and/or (b):
(a) the ratio of activity on HbS1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbS1c/HbA1c), is 0.45 or more; and (b) the ratio of activity on HbC1c-type αF8P to activity on HbA1c-type αF8P; i.e., the relative activity (HbC1c/HbA1c), is 0.15 or more. 11. The glycated hemoglobin oxidase according to claim 7, which has an optimal pH range of 6 to 8, an operative pH range of 5 to 9, an optimal temperature range of 25° C. to 40° C., and a molecular weight of about 45 to 55 KDa on SDS-PAGE. 12. The glycated hemoglobin oxidase according to claim 7, which is selected from the group consisting of (i) to (viii) below:
(i) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (ii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 109 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iii) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 106 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, alanine, aspartic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (iv) a glycated hemoglobin oxidase variant, wherein, when the amino acid sequence of the glycated hemoglobin oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 102 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having a substitution, deletion, or addition of 1 or several amino acids at positions other than those corresponding to positions 113, 109, 106, and 102 of the amino acid sequence of SEQ ID NO: 1; (vi) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid; (vii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 70% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 90% or higher sequence identity between the amino acid sequence of the homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of the homologous region of the corresponding positions of the glycated hemoglobin oxidase; and (viii) the glycated hemoglobin oxidase variant as defined in (i), (ii), (iii), or (iv) comprising an amino acid sequence having 50% or higher sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 45 over the full length and having 70% or higher sequence identity between the amino acid sequence of a homologous region of SEQ ID NO: 1 or SEQ ID NO: 45 and the amino acid sequence of a homologous region of the corresponding positions of the glycated hemoglobin oxidase, wherein the amino acid at the position corresponding to position 60 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 239 of SEQ ID NO: 1 is tryptophan, phenylalanine, or tyrosine, the amino acid at the position corresponding to position 282 of SEQ ID NO: 1 is glutamic acid, the amino acid at the position corresponding to position 376 of SEQ ID NO: 1 is glycine, the amino acid at the position corresponding to position 418 of SEQ ID NO: 1 is arginine, and the amino acid sequence of the positions corresponding to positions 15 to 20 of SEQ ID NO: 1 is Gly-Xaa-Gly-Xaa-Xaa-Gly, wherein Xaa indicates any amino acid. 13. The glycated hemoglobin oxidase according to claim 7, based on an amadoriase of the genus Coniochaeta, Eupenicillium, Pyrenochaeta, Arthrinium, Curvularia, Neocosmospora, Cryptococcus, Phaeosphaeria, Aspergillus, Emericella, Ulocladium, or Penicillium. 14. The glycated hemoglobin oxidase according to claim 13, wherein the amadoriase is derived from Coniochaeta sp., Eupenicillium terrenum, Pyrenochaeta sp., Arthrinium sp., Curvularia clavata, Neocosmospora vasinfecta, Cryptococcus neoformans, Phaeosphaeria nodorum, Aspergillus nidulans, Emericella nidulans, Ulocladium sp., Penicillium janthinelum, or Penicillium chrysogenum. 15. A reagent composition for measurement of HbS1c or HbC1c comprising the glycated hemoglobin oxidase according to claim 7. 16. A gene encoding the glycated hemoglobin oxidase according to claim 7. 17. A vector comprising the gene according to claim 16. 18. A host cell comprising the vector according to claim 17. 19. A method for producing glycated hemoglobin oxidase comprising the following steps:
(i) culturing the host cell according to claim 18 under conditions where the glycated hemoglobin oxidase can be expressed; and (ii) isolating the glycated hemoglobin oxidase from a culture product or culture solution. 20. A method for producing glycated hemoglobin oxidase by modifying an amadoriase or A1c oxidase comprising the following steps:
(i) obtaining an amadoriase gene or A1c oxidase gene; (ii) integrating the amadoriase gene or A1c oxidase gene into a vector, transforming the host cell, expressing the amadoriase or A1c oxidase, and isolating the expressed product; (iii) measuring the relative activity (HbS1c/HbA1c) and/or the relative activity (HbC1c/HbA1c) of the expressed product; (iv) modifying the amadoriase gene or A1c oxidase gene such that, when the amino acid sequence of the amadoriase or A1c oxidase is aligned with the amino acid sequence of SEQ ID NO: 1, the amino acid at the position corresponding to position 113, 109, 106, or 102 of the amino acid sequence of SEQ ID NO: 1 is modified into an amino acid selected from the group consisting of glutamic acid, aspartic acid, alanine, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; (v) integrating the modified gene into a vector, transforming a host cell, expressing the modified amadoriase or A1c oxidase, and isolating the expressed product; (vi) measuring the relative activity (HbS1c/HbA1c) and/or the relative activity (HbC1c/HbA1c) of the expressed product of the modified amadoriase or A1c oxidase and comparing the measured values with the values measured in step (iii); (vii) when the relative activity (HbS1/HbA1c) of the modified amadoriase or A1c oxidase is 1.1 times or greater than the relative activity (HbS1c/HbA1c) of the amadoriase or A1c oxidase before modification and/or the relative activity (HbC1c/HbA1c) of the modified amadoriase or A1c oxidase is 1.1 times or greater than the relative activity (HbC1c/HbA1c) of the amadoriase or A1c oxidase before modification, designating the modified amadoriase or A1c oxidase as a glycated hemoglobin oxidase; and (viii) repeating steps (iv) to (vi) on the glycated hemoglobin oxidase of step (vii), according to need. | 1,600 |
345,474 | 16,643,394 | 3,643 | The invention relates to a greenhouse, specifically a closed greenhouse environment suitable for use in dry environments which regulates the conditions of the growing environment whilst minimising heat and water loss. The greenhouse is especially suitable for use with macrophyte growing systems. | 1. A greenhouse comprising:
A first sub-assembly, the first sub-assembly comprising:
a rail; and
a first clamping means;
the greenhouse further comprising; a cover configured to at least partially allow light therethrough; and a liner; wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. 2. A greenhouse according to claim 1, wherein the first clamping means comprises;
a first receiving portion within the rail and a first insert configured to be received in the first receiving portion. 3. A greenhouse according to claim 2, wherein the first receiving portion and the first insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 4-6. (canceled) 7. A greenhouse according to claim 2, wherein the first receiving portion and the first insert are elongate. 8. A greenhouse according to claim 2, wherein the first sub-assembly further comprises a second clamping means spaced from the first clamping means. 9. A greenhouse according to claim 8, wherein the second clamping means comprises a second receiving portion in the rail and a second insert configured to be received in the second receiving portion. 10. A greenhouse according to claim 9, wherein the second receiving portion and the second insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 11-13. (canceled) 14. A greenhouse according to claim 9, wherein the second receiving portion and the second insert are elongate. 15. (canceled) 16. A greenhouse according to claim 1, wherein at least a portion of the cover and the liner are clamped by the first clamping means. 17-19. (canceled) 20. A greenhouse according to claim 1, further comprising a truss. 21. (canceled) 22. A greenhouse according to claim 20, wherein the truss comprises;
a first anchoring member positioned at a first end of the greenhouse; a second anchoring member at a second end of the greenhouse; and a connection member suspended between the first and second anchoring members; wherein, in use, the connection member cooperates with the cover in order to hold the cover in position. 23-24. (canceled) 25. A greenhouse according to claim 1, further comprising a supporting frame over or under which the cover can be stretched. 26-34. (canceled) 35. A greenhouse according to claim 1, wherein the rail further comprises an inner bar disposed between the first and a second clamping means, the inner bar comprising one or more inner bar features. 36. A greenhouse according to claim 35, wherein the inner bar further comprises one or more carriages, moveable along the inner bar, to which the one or more inner bar features may be affixed. 37. A greenhouse according to claim 35, wherein the inner bar comprises one or more inner bar features selected from the group consisting of: sensors, sprinklers, cameras, collection means, heat exchangers, lights or combinations thereof. 38. A greenhouse sub-assembly, the sub-assembly comprising:
a rail,
a first and a second clamping means, and
a bridging portion disposed between the first and second clamping means. 39. A greenhouse sub-assembly according to claim 38, wherein the first and the second clamping means each comprise a first and a second receiving portion each adapted to receive a first and a second insert respectively. 40. (canceled) 41. A greenhouse sub-assembly according to claim 38, wherein the bridging portion is adapted to promote condensation thereon. 42. (canceled) 43. A greenhouse sub-assembly according to claim 38, wherein the rail comprises a recess configured for to collect precipitation from the bridging portion. 44-52. (canceled) 53. A greenhouse comprising:
a cover configured to at least partially allow light therethrough; and a liner; and a first sub-assembly, wherein the first sub-assembly comprises:
a plurality of means for holding the cover and/or liner in position; and
a first clamping means;
wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. | The invention relates to a greenhouse, specifically a closed greenhouse environment suitable for use in dry environments which regulates the conditions of the growing environment whilst minimising heat and water loss. The greenhouse is especially suitable for use with macrophyte growing systems.1. A greenhouse comprising:
A first sub-assembly, the first sub-assembly comprising:
a rail; and
a first clamping means;
the greenhouse further comprising; a cover configured to at least partially allow light therethrough; and a liner; wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. 2. A greenhouse according to claim 1, wherein the first clamping means comprises;
a first receiving portion within the rail and a first insert configured to be received in the first receiving portion. 3. A greenhouse according to claim 2, wherein the first receiving portion and the first insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 4-6. (canceled) 7. A greenhouse according to claim 2, wherein the first receiving portion and the first insert are elongate. 8. A greenhouse according to claim 2, wherein the first sub-assembly further comprises a second clamping means spaced from the first clamping means. 9. A greenhouse according to claim 8, wherein the second clamping means comprises a second receiving portion in the rail and a second insert configured to be received in the second receiving portion. 10. A greenhouse according to claim 9, wherein the second receiving portion and the second insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 11-13. (canceled) 14. A greenhouse according to claim 9, wherein the second receiving portion and the second insert are elongate. 15. (canceled) 16. A greenhouse according to claim 1, wherein at least a portion of the cover and the liner are clamped by the first clamping means. 17-19. (canceled) 20. A greenhouse according to claim 1, further comprising a truss. 21. (canceled) 22. A greenhouse according to claim 20, wherein the truss comprises;
a first anchoring member positioned at a first end of the greenhouse; a second anchoring member at a second end of the greenhouse; and a connection member suspended between the first and second anchoring members; wherein, in use, the connection member cooperates with the cover in order to hold the cover in position. 23-24. (canceled) 25. A greenhouse according to claim 1, further comprising a supporting frame over or under which the cover can be stretched. 26-34. (canceled) 35. A greenhouse according to claim 1, wherein the rail further comprises an inner bar disposed between the first and a second clamping means, the inner bar comprising one or more inner bar features. 36. A greenhouse according to claim 35, wherein the inner bar further comprises one or more carriages, moveable along the inner bar, to which the one or more inner bar features may be affixed. 37. A greenhouse according to claim 35, wherein the inner bar comprises one or more inner bar features selected from the group consisting of: sensors, sprinklers, cameras, collection means, heat exchangers, lights or combinations thereof. 38. A greenhouse sub-assembly, the sub-assembly comprising:
a rail,
a first and a second clamping means, and
a bridging portion disposed between the first and second clamping means. 39. A greenhouse sub-assembly according to claim 38, wherein the first and the second clamping means each comprise a first and a second receiving portion each adapted to receive a first and a second insert respectively. 40. (canceled) 41. A greenhouse sub-assembly according to claim 38, wherein the bridging portion is adapted to promote condensation thereon. 42. (canceled) 43. A greenhouse sub-assembly according to claim 38, wherein the rail comprises a recess configured for to collect precipitation from the bridging portion. 44-52. (canceled) 53. A greenhouse comprising:
a cover configured to at least partially allow light therethrough; and a liner; and a first sub-assembly, wherein the first sub-assembly comprises:
a plurality of means for holding the cover and/or liner in position; and
a first clamping means;
wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. | 3,600 |
345,475 | 16,643,391 | 3,643 | The invention relates to a greenhouse, specifically a closed greenhouse environment suitable for use in dry environments which regulates the conditions of the growing environment whilst minimising heat and water loss. The greenhouse is especially suitable for use with macrophyte growing systems. | 1. A greenhouse comprising:
A first sub-assembly, the first sub-assembly comprising:
a rail; and
a first clamping means;
the greenhouse further comprising; a cover configured to at least partially allow light therethrough; and a liner; wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. 2. A greenhouse according to claim 1, wherein the first clamping means comprises;
a first receiving portion within the rail and a first insert configured to be received in the first receiving portion. 3. A greenhouse according to claim 2, wherein the first receiving portion and the first insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 4-6. (canceled) 7. A greenhouse according to claim 2, wherein the first receiving portion and the first insert are elongate. 8. A greenhouse according to claim 2, wherein the first sub-assembly further comprises a second clamping means spaced from the first clamping means. 9. A greenhouse according to claim 8, wherein the second clamping means comprises a second receiving portion in the rail and a second insert configured to be received in the second receiving portion. 10. A greenhouse according to claim 9, wherein the second receiving portion and the second insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 11-13. (canceled) 14. A greenhouse according to claim 9, wherein the second receiving portion and the second insert are elongate. 15. (canceled) 16. A greenhouse according to claim 1, wherein at least a portion of the cover and the liner are clamped by the first clamping means. 17-19. (canceled) 20. A greenhouse according to claim 1, further comprising a truss. 21. (canceled) 22. A greenhouse according to claim 20, wherein the truss comprises;
a first anchoring member positioned at a first end of the greenhouse; a second anchoring member at a second end of the greenhouse; and a connection member suspended between the first and second anchoring members; wherein, in use, the connection member cooperates with the cover in order to hold the cover in position. 23-24. (canceled) 25. A greenhouse according to claim 1, further comprising a supporting frame over or under which the cover can be stretched. 26-34. (canceled) 35. A greenhouse according to claim 1, wherein the rail further comprises an inner bar disposed between the first and a second clamping means, the inner bar comprising one or more inner bar features. 36. A greenhouse according to claim 35, wherein the inner bar further comprises one or more carriages, moveable along the inner bar, to which the one or more inner bar features may be affixed. 37. A greenhouse according to claim 35, wherein the inner bar comprises one or more inner bar features selected from the group consisting of: sensors, sprinklers, cameras, collection means, heat exchangers, lights or combinations thereof. 38. A greenhouse sub-assembly, the sub-assembly comprising:
a rail,
a first and a second clamping means, and
a bridging portion disposed between the first and second clamping means. 39. A greenhouse sub-assembly according to claim 38, wherein the first and the second clamping means each comprise a first and a second receiving portion each adapted to receive a first and a second insert respectively. 40. (canceled) 41. A greenhouse sub-assembly according to claim 38, wherein the bridging portion is adapted to promote condensation thereon. 42. (canceled) 43. A greenhouse sub-assembly according to claim 38, wherein the rail comprises a recess configured for to collect precipitation from the bridging portion. 44-52. (canceled) 53. A greenhouse comprising:
a cover configured to at least partially allow light therethrough; and a liner; and a first sub-assembly, wherein the first sub-assembly comprises:
a plurality of means for holding the cover and/or liner in position; and
a first clamping means;
wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. | The invention relates to a greenhouse, specifically a closed greenhouse environment suitable for use in dry environments which regulates the conditions of the growing environment whilst minimising heat and water loss. The greenhouse is especially suitable for use with macrophyte growing systems.1. A greenhouse comprising:
A first sub-assembly, the first sub-assembly comprising:
a rail; and
a first clamping means;
the greenhouse further comprising; a cover configured to at least partially allow light therethrough; and a liner; wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. 2. A greenhouse according to claim 1, wherein the first clamping means comprises;
a first receiving portion within the rail and a first insert configured to be received in the first receiving portion. 3. A greenhouse according to claim 2, wherein the first receiving portion and the first insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 4-6. (canceled) 7. A greenhouse according to claim 2, wherein the first receiving portion and the first insert are elongate. 8. A greenhouse according to claim 2, wherein the first sub-assembly further comprises a second clamping means spaced from the first clamping means. 9. A greenhouse according to claim 8, wherein the second clamping means comprises a second receiving portion in the rail and a second insert configured to be received in the second receiving portion. 10. A greenhouse according to claim 9, wherein the second receiving portion and the second insert cooperate by means of a snap-fit connection; or
wherein the first receiving portion and the first insert cooperate by means of an interference-fit connection. 11-13. (canceled) 14. A greenhouse according to claim 9, wherein the second receiving portion and the second insert are elongate. 15. (canceled) 16. A greenhouse according to claim 1, wherein at least a portion of the cover and the liner are clamped by the first clamping means. 17-19. (canceled) 20. A greenhouse according to claim 1, further comprising a truss. 21. (canceled) 22. A greenhouse according to claim 20, wherein the truss comprises;
a first anchoring member positioned at a first end of the greenhouse; a second anchoring member at a second end of the greenhouse; and a connection member suspended between the first and second anchoring members; wherein, in use, the connection member cooperates with the cover in order to hold the cover in position. 23-24. (canceled) 25. A greenhouse according to claim 1, further comprising a supporting frame over or under which the cover can be stretched. 26-34. (canceled) 35. A greenhouse according to claim 1, wherein the rail further comprises an inner bar disposed between the first and a second clamping means, the inner bar comprising one or more inner bar features. 36. A greenhouse according to claim 35, wherein the inner bar further comprises one or more carriages, moveable along the inner bar, to which the one or more inner bar features may be affixed. 37. A greenhouse according to claim 35, wherein the inner bar comprises one or more inner bar features selected from the group consisting of: sensors, sprinklers, cameras, collection means, heat exchangers, lights or combinations thereof. 38. A greenhouse sub-assembly, the sub-assembly comprising:
a rail,
a first and a second clamping means, and
a bridging portion disposed between the first and second clamping means. 39. A greenhouse sub-assembly according to claim 38, wherein the first and the second clamping means each comprise a first and a second receiving portion each adapted to receive a first and a second insert respectively. 40. (canceled) 41. A greenhouse sub-assembly according to claim 38, wherein the bridging portion is adapted to promote condensation thereon. 42. (canceled) 43. A greenhouse sub-assembly according to claim 38, wherein the rail comprises a recess configured for to collect precipitation from the bridging portion. 44-52. (canceled) 53. A greenhouse comprising:
a cover configured to at least partially allow light therethrough; and a liner; and a first sub-assembly, wherein the first sub-assembly comprises:
a plurality of means for holding the cover and/or liner in position; and
a first clamping means;
wherein the first sub-assembly, the cover and the liner cooperate with each other so as to form a closed system. | 3,600 |
345,476 | 16,643,378 | 3,643 | A composition comprising the following: A) coated polymer particles, and wherein the polymer particles are formed from a first composition comprising an ethylene-based polymer that comprises the following properties: a density from 0.854 to 0.860 g/cc, and a melt index (I2) from 4.0 to 15.0 g/10 min; and wherein the polymer particles comprise a coating on at least a portion of the total surface of the polymer particles, and wherein the coating is formed from a powder composition comprising at least one inorganic powder, and at least one organic powder selected from a metal stearate and/or a polymer powder, and wherein the weight ratio of the total amount of the inorganic powder to the total amount of the organic powder is from 3.0 to 50.0; B) optionally, a propylene-based polymer. | 1. A composition comprising the following:
A) coated polymer particles, and wherein the polymer particles are formed from a first composition comprising an ethylene-based polymer that comprises the following properties: a density from 0.854 to 0.860 g/cc, and a melt index (I2) from 4.0 to 15.0 g/10 min; and wherein the polymer particles comprise a coating on at least a portion of the total surface of the polymer particles, and wherein the coating is formed from a powder composition comprising at least one inorganic powder, and at least one organic powder selected from a metal stearate and/or a polymer powder, and wherein the weight ratio of the total amount of the inorganic powder to the total amount of the organic powder is from 3.0 to 50.0; B) optionally, a propylene-based polymer. 2. The composition of claim 1, comprising the propylene-based polymer of component B. 3. The composition of claim 2, wherein the propylene-based polymer of component B has a MFR from 20 to 120 g/10 min, and a density from 0.880 to 0.920 g/cc. 4. The composition of claim 2, wherein composition has a MFR ≥30 g/10 min. 5. The composition of claim 2, wherein composition has a MFR from 30 to 60 g/10 min. 6. The composition of claim 2, wherein composition comprises ≥50 wt % component B, and ≤50 wt % component A, wherein each wt % based on the weight of the composition. 7. The composition of claim 1, wherein, for component A, the first composition comprises ≥95 wt % of the ethylene-based polymer, based on the weight of the first composition. 8. The composition of claim 1, wherein, for component A, the ethylene-based polymer is an ethylene/alpha-olefin interpolymer. 9. The composition of claim 1, wherein, for component A, the organic powder is a metal stearate. 10. The composition of claim 1, wherein, for component A, the inorganic powder is selected from the group consisting of the following: talc, mica, calcium carbonate, finely divided silica, fumed silica, quartz, and combinations thereof. 11. The composition of claim 1, wherein, for component A, the coated polymer particles further comprise a binder. 12. The composition of claim 11, wherein the binder is a silicone fluid. 13. An article comprising at least one component formed from the composition of claim 1. | A composition comprising the following: A) coated polymer particles, and wherein the polymer particles are formed from a first composition comprising an ethylene-based polymer that comprises the following properties: a density from 0.854 to 0.860 g/cc, and a melt index (I2) from 4.0 to 15.0 g/10 min; and wherein the polymer particles comprise a coating on at least a portion of the total surface of the polymer particles, and wherein the coating is formed from a powder composition comprising at least one inorganic powder, and at least one organic powder selected from a metal stearate and/or a polymer powder, and wherein the weight ratio of the total amount of the inorganic powder to the total amount of the organic powder is from 3.0 to 50.0; B) optionally, a propylene-based polymer.1. A composition comprising the following:
A) coated polymer particles, and wherein the polymer particles are formed from a first composition comprising an ethylene-based polymer that comprises the following properties: a density from 0.854 to 0.860 g/cc, and a melt index (I2) from 4.0 to 15.0 g/10 min; and wherein the polymer particles comprise a coating on at least a portion of the total surface of the polymer particles, and wherein the coating is formed from a powder composition comprising at least one inorganic powder, and at least one organic powder selected from a metal stearate and/or a polymer powder, and wherein the weight ratio of the total amount of the inorganic powder to the total amount of the organic powder is from 3.0 to 50.0; B) optionally, a propylene-based polymer. 2. The composition of claim 1, comprising the propylene-based polymer of component B. 3. The composition of claim 2, wherein the propylene-based polymer of component B has a MFR from 20 to 120 g/10 min, and a density from 0.880 to 0.920 g/cc. 4. The composition of claim 2, wherein composition has a MFR ≥30 g/10 min. 5. The composition of claim 2, wherein composition has a MFR from 30 to 60 g/10 min. 6. The composition of claim 2, wherein composition comprises ≥50 wt % component B, and ≤50 wt % component A, wherein each wt % based on the weight of the composition. 7. The composition of claim 1, wherein, for component A, the first composition comprises ≥95 wt % of the ethylene-based polymer, based on the weight of the first composition. 8. The composition of claim 1, wherein, for component A, the ethylene-based polymer is an ethylene/alpha-olefin interpolymer. 9. The composition of claim 1, wherein, for component A, the organic powder is a metal stearate. 10. The composition of claim 1, wherein, for component A, the inorganic powder is selected from the group consisting of the following: talc, mica, calcium carbonate, finely divided silica, fumed silica, quartz, and combinations thereof. 11. The composition of claim 1, wherein, for component A, the coated polymer particles further comprise a binder. 12. The composition of claim 11, wherein the binder is a silicone fluid. 13. An article comprising at least one component formed from the composition of claim 1. | 3,600 |
345,477 | 16,643,375 | 3,643 | The present invention is directed to an improved purification process using additive and activated carbon for purifying resorbable polymers suitable for industrial manufacturing. The metal catalyst concentration in the purified resorbable polymers of this invention is preferably less than 1 ppm. The method can be used to obtain high molecular weight polymers that are substantially metal free. | 1. A method of reducing the residual tin content in a tin containing resorbable polymer to less than 1 ppm, comprising:
(d) dissolving a polymer in an organic solvent to produce a polymer solution; (e) combining the polymer solution with activated carbon and an additive; wherein said method results in the formation of a purified polymer; and (f) recovering the purified polymer by anti-solvent precipitation. 2. The method of claim 1, wherein the polymer is linear. 3. The method of claim 2, wherein the additive is up to 20 wt % of the solvent, and activated carbon is up to 9 wt % of the linear polymer. 4. The method of claim 1, wherein the polymer is branched. 5. The method of claim 4, wherein the additive is up to 20 wt % of the solvent, and activated carbon is between 50-100 wt % of the branched polymer. 6. The method of claim 1, wherein the additive and activated carbon is exposed to the polymer solution for 2 to 4 hours 7. The method of claim 1, wherein the additive is lactic acid, glycolic acid, or water. 8. A purified polyester which is a branched or a linear polylactide-glycolide having a weight averaged molecular weight of 5 to 315 kDa, a polydispersity Mw/Mn of 1.5 to 2.5, prepared by the process of ring-opening polymerization of lactide and glycolide in the presence of tin (II)-(2-ethylhexanoate) or tin chloride followed by treatment with activated carbon and an additive. 9. The purified polyester of claim 8, wherein the additive is lactic acid, glycolic acid, or water. 10. The purified polyester of claim 8 having a D,L-lactide/glycolide molar ratio of 100-50/0-50. 11. The purified polyester of claim 8 having a D,L-lactide/caprolactone molar ratio of 100-90/0-10. 12. The purified polyester of claim 8 having a terpolymer of lactide, glycolide, and caprolactone. 13. The purified polyester of claim 8, wherein the purified polyester is poly(D,L-lactide), poly(D,L-lactide-co-glycolide) with more than 50 mole % D,L-lactide content, poly(D,L-lactide-co-caprolactone) with more than 10 mole % D,L-lactide content, poly(L-lactide-co-caprolactone) with more than 50 mole % L-lactide content, poly(D,L-lactide-co-trimethylene carbonate) with more than 50 mole % D,L-lactide content, poly(D,L-lactide-co-dioxanone) with more than 50 mole % D,L-lactide content, or poly(D,L-lactide-co-glycolide-co-caprolactone) with less than 50 mole % glycolide content. 14. The purified polyester of claim 8 having an acid number comparable to standard polylactide. 15. The purified polyester of claim 8 having improved thermal stability compared to standard polylactide. | The present invention is directed to an improved purification process using additive and activated carbon for purifying resorbable polymers suitable for industrial manufacturing. The metal catalyst concentration in the purified resorbable polymers of this invention is preferably less than 1 ppm. The method can be used to obtain high molecular weight polymers that are substantially metal free.1. A method of reducing the residual tin content in a tin containing resorbable polymer to less than 1 ppm, comprising:
(d) dissolving a polymer in an organic solvent to produce a polymer solution; (e) combining the polymer solution with activated carbon and an additive; wherein said method results in the formation of a purified polymer; and (f) recovering the purified polymer by anti-solvent precipitation. 2. The method of claim 1, wherein the polymer is linear. 3. The method of claim 2, wherein the additive is up to 20 wt % of the solvent, and activated carbon is up to 9 wt % of the linear polymer. 4. The method of claim 1, wherein the polymer is branched. 5. The method of claim 4, wherein the additive is up to 20 wt % of the solvent, and activated carbon is between 50-100 wt % of the branched polymer. 6. The method of claim 1, wherein the additive and activated carbon is exposed to the polymer solution for 2 to 4 hours 7. The method of claim 1, wherein the additive is lactic acid, glycolic acid, or water. 8. A purified polyester which is a branched or a linear polylactide-glycolide having a weight averaged molecular weight of 5 to 315 kDa, a polydispersity Mw/Mn of 1.5 to 2.5, prepared by the process of ring-opening polymerization of lactide and glycolide in the presence of tin (II)-(2-ethylhexanoate) or tin chloride followed by treatment with activated carbon and an additive. 9. The purified polyester of claim 8, wherein the additive is lactic acid, glycolic acid, or water. 10. The purified polyester of claim 8 having a D,L-lactide/glycolide molar ratio of 100-50/0-50. 11. The purified polyester of claim 8 having a D,L-lactide/caprolactone molar ratio of 100-90/0-10. 12. The purified polyester of claim 8 having a terpolymer of lactide, glycolide, and caprolactone. 13. The purified polyester of claim 8, wherein the purified polyester is poly(D,L-lactide), poly(D,L-lactide-co-glycolide) with more than 50 mole % D,L-lactide content, poly(D,L-lactide-co-caprolactone) with more than 10 mole % D,L-lactide content, poly(L-lactide-co-caprolactone) with more than 50 mole % L-lactide content, poly(D,L-lactide-co-trimethylene carbonate) with more than 50 mole % D,L-lactide content, poly(D,L-lactide-co-dioxanone) with more than 50 mole % D,L-lactide content, or poly(D,L-lactide-co-glycolide-co-caprolactone) with less than 50 mole % glycolide content. 14. The purified polyester of claim 8 having an acid number comparable to standard polylactide. 15. The purified polyester of claim 8 having improved thermal stability compared to standard polylactide. | 3,600 |
345,478 | 16,643,415 | 3,643 | A method of manufacturing a TFT substrate and a manufacturing apparatus of a TFT substrate are provided. The method of manufacturing a TFT substrate comprises: forming active switches on a substrate; forming transparent electrode layer on the active switches; and forming a pixel layer on the transparent electrode layer. The step of forming the active switches on the substrate comprises: forming a metal layer on the substrate; bombarding the metal layer with hydrogen ions; and forming a protection layer on the metal layer. | 1. A method of manufacturing a TFT substrate, comprising:
providing a substrate; forming a first metal layer on the substrate; dissociating hydrogen into hydrogen atoms; ionizing the hydrogen atoms into hydrogen ions; bombarding the first metal layer with the hydrogen ions to form scan lines and gates of active switches; forming a first protection layer and a semiconductor layer on the first metal layer; forming a second metal layer on the semiconductor layer; bombarding the second metal layer with the hydrogen ions to form data lines, and sources and drains of the active switches; forming a second protection layer on the second metal layer; and forming a transparent electrode layer connected to the drain on the second protection layer. 2. The method according to claim 1, wherein the step of bombarding the second metal layer with the hydrogen ions comprises:
dissociating the hydrogen into hydrogen atoms; ionizing the hydrogen atoms into hydrogen ions; and bombarding the metal layer with the hydrogen ions. 3. The method according to claim 1, wherein the second protection layer is provided with an opening, and the transparent electrode layer is connected to the second metal layer through the opening. 4. The method according to claim 1, wherein the first metal layer and the second metal layer are made of copper, aluminum, silver, gold or an alloy of the above-mentioned metals. 5. The method according to claim 1, wherein each of the first protection layer and the second protection layer is a silicon nitride layer and/or a silicon oxide layer. 6. The method according to claim 5, wherein the first protection layer and the second protection layer are stacked in two layers. 7. The method according to claim 5, wherein the first protection layer and the second protection layer are made of the same material. 8. The method according to claim 5, wherein the first protection layer and the second protection layer are made of different materials. 9. A method of manufacturing a TFT substrate, comprising:
providing a substrate; forming a metal layer on the substrate; bombarding the metal layer with hydrogen ions; and forming a protection layer on the metal layer; wherein the substrate is disposed with an active switch, a scan line and a data line perpendicular to the scan line, the active switch comprises a metal layer, a scan line and a data line coupled to the active switch, and the metal layer comprises a first metal layer, a second metal layer, a scan line and a data line. 10. The method according to claim 9, wherein the step of bombarding the metal layer with the hydrogen ions comprises:
dissociating hydrogen into hydrogen atoms; ionizing the hydrogen atoms into the hydrogen ions; and bombarding the metal layer with the hydrogen ions. 11. The method according to claim 9, wherein the protection layer comprises a first protection layer and a second protection layer, the first metal layer is disposed on the substrate, the first protection layer is disposed on the first metal layer, the second metal layer is disposed on the first protection layer, and the second protection layer is disposed on the second metal layer. 12. The method according to claim 11, wherein a transparent electrode layer is formed on the second protection layer, the second protection layer is provided with an opening, and the transparent electrode layer is connected to the second metal layer through the opening. 13. The method according to claim 11, wherein the step of forming the metal layer on the substrate comprises forming the first metal layer on the substrate;
the step of bombarding the metal layer with the hydrogen ions comprises bombarding the first metal layer with the hydrogen ions; and the step of forming the protection layer on the metal layer comprises forming the first protection layer on the first metal layer. 14. The method according to claim 11, wherein the step of forming the metal layer on the substrate comprises forming the second metal layer on the first protection layer;
the step of bombarding the metal layer with the hydrogen ions comprises bombarding the second metal layer with the hydrogen ions; and the step of forming the protection layer on the metal layer comprises forming the second protection layer on the second metal layer. 15. The method according to claim 12, wherein the method comprises:
forming the first metal layer on the substrate; bombarding the first metal layer with the hydrogen ions to form the scan lines and gates of the active switches; forming the first protection layer, a semiconductor layer, and the second metal layer on the first metal layer; bombarding the second metal layer with the hydrogen ions to form the data lines, and sources and drains of the active switches; forming the second protection layer on the second metal layer; and forming the transparent electrode layer connected to the drains on the second protection layer. 16. The method according to claim 12, wherein the method comprises:
forming the first metal layer on the substrate; bombarding the first metal layer with the hydrogen ions to form the scan lines and gates of the active switches; forming the first protection layer and a semiconductor layer on the first metal layer; forming the second metal layer on the semiconductor layer; bombarding the second metal layer with the hydrogen ions to form the data lines, and sources and drains of the active switches; forming the second protection layer on the second metal layer; and forming the transparent electrode layer connected to the drains on the second protection layer. 17. The method according to claim 9, wherein the first metal layer and the second metal layer are made of copper, aluminum, silver, gold or an alloy of the above-mentioned metals. 18. The method according to claim 11, wherein each of the first protection layer and the second protection layer is a silicon nitride layer and/or a silicon oxide layer. 19. The method according to claim 18, wherein the first protection layer and the second protection layer are stacked in two layers. 20. A manufacturing apparatus of a TFT substrate, comprising:
a gas inlet configured to inject hydrogen and air; a dissociating device configured to dissociate the hydrogen into hydrogen ions; a gas outlet configured to release the hydrogen ions to bombard a metal layer; and a coating device configured to form a protection layer on the metal layer; wherein the manufacturing apparatus further comprises a housing, the gas inlet and the gas outlet are disposed on the housing, the dissociating device is disposed inside the housing, the dissociating device comprises a high voltage electrode and a ceramic electrode, the dissociating device is connected to the gas inlet through a cooling sleeve, the housing comprises an anti-electrostatic board, and the gas outlet is disposed on the anti-electrostatic board. | A method of manufacturing a TFT substrate and a manufacturing apparatus of a TFT substrate are provided. The method of manufacturing a TFT substrate comprises: forming active switches on a substrate; forming transparent electrode layer on the active switches; and forming a pixel layer on the transparent electrode layer. The step of forming the active switches on the substrate comprises: forming a metal layer on the substrate; bombarding the metal layer with hydrogen ions; and forming a protection layer on the metal layer.1. A method of manufacturing a TFT substrate, comprising:
providing a substrate; forming a first metal layer on the substrate; dissociating hydrogen into hydrogen atoms; ionizing the hydrogen atoms into hydrogen ions; bombarding the first metal layer with the hydrogen ions to form scan lines and gates of active switches; forming a first protection layer and a semiconductor layer on the first metal layer; forming a second metal layer on the semiconductor layer; bombarding the second metal layer with the hydrogen ions to form data lines, and sources and drains of the active switches; forming a second protection layer on the second metal layer; and forming a transparent electrode layer connected to the drain on the second protection layer. 2. The method according to claim 1, wherein the step of bombarding the second metal layer with the hydrogen ions comprises:
dissociating the hydrogen into hydrogen atoms; ionizing the hydrogen atoms into hydrogen ions; and bombarding the metal layer with the hydrogen ions. 3. The method according to claim 1, wherein the second protection layer is provided with an opening, and the transparent electrode layer is connected to the second metal layer through the opening. 4. The method according to claim 1, wherein the first metal layer and the second metal layer are made of copper, aluminum, silver, gold or an alloy of the above-mentioned metals. 5. The method according to claim 1, wherein each of the first protection layer and the second protection layer is a silicon nitride layer and/or a silicon oxide layer. 6. The method according to claim 5, wherein the first protection layer and the second protection layer are stacked in two layers. 7. The method according to claim 5, wherein the first protection layer and the second protection layer are made of the same material. 8. The method according to claim 5, wherein the first protection layer and the second protection layer are made of different materials. 9. A method of manufacturing a TFT substrate, comprising:
providing a substrate; forming a metal layer on the substrate; bombarding the metal layer with hydrogen ions; and forming a protection layer on the metal layer; wherein the substrate is disposed with an active switch, a scan line and a data line perpendicular to the scan line, the active switch comprises a metal layer, a scan line and a data line coupled to the active switch, and the metal layer comprises a first metal layer, a second metal layer, a scan line and a data line. 10. The method according to claim 9, wherein the step of bombarding the metal layer with the hydrogen ions comprises:
dissociating hydrogen into hydrogen atoms; ionizing the hydrogen atoms into the hydrogen ions; and bombarding the metal layer with the hydrogen ions. 11. The method according to claim 9, wherein the protection layer comprises a first protection layer and a second protection layer, the first metal layer is disposed on the substrate, the first protection layer is disposed on the first metal layer, the second metal layer is disposed on the first protection layer, and the second protection layer is disposed on the second metal layer. 12. The method according to claim 11, wherein a transparent electrode layer is formed on the second protection layer, the second protection layer is provided with an opening, and the transparent electrode layer is connected to the second metal layer through the opening. 13. The method according to claim 11, wherein the step of forming the metal layer on the substrate comprises forming the first metal layer on the substrate;
the step of bombarding the metal layer with the hydrogen ions comprises bombarding the first metal layer with the hydrogen ions; and the step of forming the protection layer on the metal layer comprises forming the first protection layer on the first metal layer. 14. The method according to claim 11, wherein the step of forming the metal layer on the substrate comprises forming the second metal layer on the first protection layer;
the step of bombarding the metal layer with the hydrogen ions comprises bombarding the second metal layer with the hydrogen ions; and the step of forming the protection layer on the metal layer comprises forming the second protection layer on the second metal layer. 15. The method according to claim 12, wherein the method comprises:
forming the first metal layer on the substrate; bombarding the first metal layer with the hydrogen ions to form the scan lines and gates of the active switches; forming the first protection layer, a semiconductor layer, and the second metal layer on the first metal layer; bombarding the second metal layer with the hydrogen ions to form the data lines, and sources and drains of the active switches; forming the second protection layer on the second metal layer; and forming the transparent electrode layer connected to the drains on the second protection layer. 16. The method according to claim 12, wherein the method comprises:
forming the first metal layer on the substrate; bombarding the first metal layer with the hydrogen ions to form the scan lines and gates of the active switches; forming the first protection layer and a semiconductor layer on the first metal layer; forming the second metal layer on the semiconductor layer; bombarding the second metal layer with the hydrogen ions to form the data lines, and sources and drains of the active switches; forming the second protection layer on the second metal layer; and forming the transparent electrode layer connected to the drains on the second protection layer. 17. The method according to claim 9, wherein the first metal layer and the second metal layer are made of copper, aluminum, silver, gold or an alloy of the above-mentioned metals. 18. The method according to claim 11, wherein each of the first protection layer and the second protection layer is a silicon nitride layer and/or a silicon oxide layer. 19. The method according to claim 18, wherein the first protection layer and the second protection layer are stacked in two layers. 20. A manufacturing apparatus of a TFT substrate, comprising:
a gas inlet configured to inject hydrogen and air; a dissociating device configured to dissociate the hydrogen into hydrogen ions; a gas outlet configured to release the hydrogen ions to bombard a metal layer; and a coating device configured to form a protection layer on the metal layer; wherein the manufacturing apparatus further comprises a housing, the gas inlet and the gas outlet are disposed on the housing, the dissociating device is disposed inside the housing, the dissociating device comprises a high voltage electrode and a ceramic electrode, the dissociating device is connected to the gas inlet through a cooling sleeve, the housing comprises an anti-electrostatic board, and the gas outlet is disposed on the anti-electrostatic board. | 3,600 |
345,479 | 16,643,422 | 3,643 | Porous and microporous parts prepared by additive manufacturing as disclosed herein are useful in medical and non-medical applications. The parts are prepared from a composition containing both a solvent soluble component and a solvent insoluble component. After a part is printed by an additive manufacturing process it is exposed to solvent to extract solvent soluble component away from the printed part, resulting in a part having surface cavities. | 1. A composition comprising an additive in a polymer phase, wherein:
a) the additive is soluble in a solvent; b) the polymer phase comprises an organic polymer and is essentially insoluble in the solvent; c) the composition is a solid at temperatures below 25° C. and a viscous fluid with a Melt Flow Index of 2.5-30 g/10 min at a temperature above 50° C.; and d) the composition has a weight percent of the additive based on the weight of the composition and a weight percent of the polymer phase based on the weight of the composition, where the sum of the weight percent of the additive and the weight percent of the polymer phase is greater than 90%. 2. The composition of claim 1 in a form of a monofilament. 3. The composition of claim 2 wherein the monofilament is an undrawn monofilament. 4. The composition of claim 2 wherein the monofilament has an orientation factor of less than 50%. 5. The composition of claim 2 wherein the monofilament has a diameter of 1-5 mm. 6. (canceled) 7. (canceled) 8. The composition of claim 1 in a form of a powder or granule. 9. The composition of claim 1 wherein the additive comprises an inorganic salt. 10. The composition of claim 1 wherein the additive comprises a water-soluble organic compound. 11. The composition of claim 10 wherein the water-soluble organic compound is polyethyeleneglycol. 12. The composition of claim 1 wherein the polymer phase comprises a bioabsorbable polymer. 13. The composition of claim 12 wherein the polymer phase comprises a bioabsorbable polymer comprising segments selected from polyester, polyanhydride, poly(hydroxybutyrate) and polyether. 14. The composition of claim 1 wherein the polymer phase comprises a non-bioabsorbable polymer. 15. The composition of claim 12 wherein the polymer phase comprises a non-bioabsorbable polymer selected from polyethylene, nylon, thermoplastic polyurethane, polypropylene, polyetheretherketone, polyaryletherketone and polyethylene terephthalate. 16. The composition of claim 1 wherein the weight percent of the additive in the composition is 1-60%. 17. The composition of claim 1 where the solvent is water, the additive is soluble in water and the polymer phase is insoluble in water. 18. An assembly comprising the monofilament of claim 2 and further comprising a spool, where the monofilament is wrapped around the spool. 19. (canceled) 20. A method of forming a composition of claim 2 comprising:
a) combining the additive and the polymer phase to form a composition;
b) heating the composition to form a molten composition;
c) extruding the molten composition to form an undrawn monofilament; and
d) sterilizing the undrawn monofilament. 21. A method of forming an assembly of claim 18 comprising:
a) providing a composition according to claim 1 in a molten form;
b) extruding the molten form of the composition to form an undrawn monofilament;
c) winding the undrawn monofilament onto a spool; and
d) packaging the spool with monofilament wound thereon. 22. A method of additive manufacturing, the method comprising:
a) melting a solid composition to provide a molten composition, the molten composition comprising an additive and a polymer phase according to claim 1; b) performing additive manufacturing to form an article from the molten composition; and c) contacting the article with a solvent, where the additive is soluble in the solvent, under conditions which at least partially dissolves the additive but not the polymer phase, to form a porous form of the article. 23. (canceled) 24. (canceled) 25. (canceled) 26. (canceled) 27. (canceled) 28. (canceled) 29. A method of additive manufacturing, the method comprising:
a) providing a composition comprising an additive in a polymer phase according to claim 1; b) extruding the composition into a monofilament fiber; c) melting the monofilament fiber to provide a molten composition; d) performing additive manufacturing to form an article from the molten composition; e) contacting the article with a solvent, where the additive is soluble in the solvent, under conditions which at least partially dissolves the additive but not the polymer phase, to form a porous form of the article; and | Porous and microporous parts prepared by additive manufacturing as disclosed herein are useful in medical and non-medical applications. The parts are prepared from a composition containing both a solvent soluble component and a solvent insoluble component. After a part is printed by an additive manufacturing process it is exposed to solvent to extract solvent soluble component away from the printed part, resulting in a part having surface cavities.1. A composition comprising an additive in a polymer phase, wherein:
a) the additive is soluble in a solvent; b) the polymer phase comprises an organic polymer and is essentially insoluble in the solvent; c) the composition is a solid at temperatures below 25° C. and a viscous fluid with a Melt Flow Index of 2.5-30 g/10 min at a temperature above 50° C.; and d) the composition has a weight percent of the additive based on the weight of the composition and a weight percent of the polymer phase based on the weight of the composition, where the sum of the weight percent of the additive and the weight percent of the polymer phase is greater than 90%. 2. The composition of claim 1 in a form of a monofilament. 3. The composition of claim 2 wherein the monofilament is an undrawn monofilament. 4. The composition of claim 2 wherein the monofilament has an orientation factor of less than 50%. 5. The composition of claim 2 wherein the monofilament has a diameter of 1-5 mm. 6. (canceled) 7. (canceled) 8. The composition of claim 1 in a form of a powder or granule. 9. The composition of claim 1 wherein the additive comprises an inorganic salt. 10. The composition of claim 1 wherein the additive comprises a water-soluble organic compound. 11. The composition of claim 10 wherein the water-soluble organic compound is polyethyeleneglycol. 12. The composition of claim 1 wherein the polymer phase comprises a bioabsorbable polymer. 13. The composition of claim 12 wherein the polymer phase comprises a bioabsorbable polymer comprising segments selected from polyester, polyanhydride, poly(hydroxybutyrate) and polyether. 14. The composition of claim 1 wherein the polymer phase comprises a non-bioabsorbable polymer. 15. The composition of claim 12 wherein the polymer phase comprises a non-bioabsorbable polymer selected from polyethylene, nylon, thermoplastic polyurethane, polypropylene, polyetheretherketone, polyaryletherketone and polyethylene terephthalate. 16. The composition of claim 1 wherein the weight percent of the additive in the composition is 1-60%. 17. The composition of claim 1 where the solvent is water, the additive is soluble in water and the polymer phase is insoluble in water. 18. An assembly comprising the monofilament of claim 2 and further comprising a spool, where the monofilament is wrapped around the spool. 19. (canceled) 20. A method of forming a composition of claim 2 comprising:
a) combining the additive and the polymer phase to form a composition;
b) heating the composition to form a molten composition;
c) extruding the molten composition to form an undrawn monofilament; and
d) sterilizing the undrawn monofilament. 21. A method of forming an assembly of claim 18 comprising:
a) providing a composition according to claim 1 in a molten form;
b) extruding the molten form of the composition to form an undrawn monofilament;
c) winding the undrawn monofilament onto a spool; and
d) packaging the spool with monofilament wound thereon. 22. A method of additive manufacturing, the method comprising:
a) melting a solid composition to provide a molten composition, the molten composition comprising an additive and a polymer phase according to claim 1; b) performing additive manufacturing to form an article from the molten composition; and c) contacting the article with a solvent, where the additive is soluble in the solvent, under conditions which at least partially dissolves the additive but not the polymer phase, to form a porous form of the article. 23. (canceled) 24. (canceled) 25. (canceled) 26. (canceled) 27. (canceled) 28. (canceled) 29. A method of additive manufacturing, the method comprising:
a) providing a composition comprising an additive in a polymer phase according to claim 1; b) extruding the composition into a monofilament fiber; c) melting the monofilament fiber to provide a molten composition; d) performing additive manufacturing to form an article from the molten composition; e) contacting the article with a solvent, where the additive is soluble in the solvent, under conditions which at least partially dissolves the additive but not the polymer phase, to form a porous form of the article; and | 3,600 |
345,480 | 16,643,397 | 3,643 | The present disclosure relates to an artificial intelligence (AI) system for simulating functions, such as recognition and determination, of the human brain by using a machine learning algorithm such as deep learning, and an application thereof. Provided are an automatic cooking device and method for selectively emitting light of different wavelength bands to a food material, identifying the food material by obtaining information about the food material, based on reflected light, and controlling a cooking process of the food material. | 1. An automatic cooking device comprising:
a light emitter configured to emit light of different wavelength bands; a photographing unit including an image sensor; a memory storing computer executable instructions; at least one processor configured to execute the computer executable instructions to control the light emitter and the photographing unit to obtain information about a kind of a food material by performing vision recognition based on a captured image of the food material, obtain characteristic information of the food material by performing spectroscopic analysis based on light reflected by emitting light of a wavelength band selected according to the information about the kind of the food material, and control a cooking process of the food material, based on the information about the kind of the food material and the characteristic information of the food material; and a cooker configured to operate according to the cooking process of the food material. 2. The automatic cooking device of claim 1, wherein the at least one processor is further configured to:
select a wavelength band corresponding to the information about the kind of the food material; identify an amount of light of the selected wavelength band according to a position of the food material and an intensity of external light and emit the light of the selected wavelength band to the food material; perform calibration according to the position of the food material and the intensity of the external light during the spectroscopic analysis based on the reflected light; and obtain characteristic information of the food material. 3. The automatic cooking device of claim 1, wherein the at least one processor is further configured to obtain an optimum recipe using the food material and control the cooking process according to the recipe by comparing the information about the kind of the food material and the characteristic information of the food material before cooking with a database of food material information. 4. The automatic cooking device of claim 1, wherein the at least one processor is further configured to estimate a cooked state of the food material or an end of a cooking time by selectively emitting light of a wavelength band used for obtaining predefined sensing information according to a progress of the cooking process of the food material. 5. The automatic cooking device of claim 1, wherein the at least one processor is further configured to control the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and volume change information regarding the difference between a volume of the food material before cooking and the volume of the food material when heated. 6. The automatic cooking device of claim 1, further comprising a probe configured to obtain information about an internal temperature and composition of the food material, and
wherein the at least one processor is further configured to control the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the information about the internal temperature and composition of the food material. 7. The automatic cooking device of claim 6, wherein the at least one processor is further configured to identify a position of the probe by using the photographing unit and inform a user about the position of the probe to correct the position of the probe. 8. An automatic cooking method comprising:
obtaining information about a kind of a food material by performing vision recognition based on a captured image of the food material; obtaining characteristic information of the food material by performing spectroscopic analysis based on light reflected by emitting, to the food material, light of a wavelength band selected according to the information about the kind of the food material; and controlling a cooking process of the food material, based on the information about the kind of the food material and the characteristic information of the food material, wherein the information about the kind of the food material and the characteristic information of the food material are obtained by a light emitter which emits light of different wavelength bands and a photographing unit including an image sensor. 9. The automatic cooking method of claim 8, wherein the obtaining of the characteristic information of the food material by performing the spectroscopic analysis comprises:
selecting a wavelength band according to the information about the kind of the food material; emitting light of the selected wavelength band to the food material by determining an amount of the light according to a position of the food material and an intensity of external light; performing calibration according to the position of the food material and the intensity of the external light during the spectroscopic analysis based on the reflected light; and obtaining the characteristic information of the food material. 10. The automatic cooking method of claim 8, wherein the controlling of the cooking process of the food material comprises:
obtaining an optimal recipe using the food material by comparing the information about the kind of the food material and the characteristic information of the food material before cooking with a database of food material information; and controlling the cooking process according to the obtained recipe. 11. The automatic cooking method of claim 8, wherein the controlling of the cooking process of the food material comprises estimating a cooked state of the food material or an end of a cooking time by selectively emitting light of a wavelength band used for obtaining predefined sensing information according to a progress of the cooking process of the food material. 12. The automatic cooking method of claim 8, further comprising obtaining volume change information regarding the difference between a volume of the food material before cooking and the volume of the food material when heated, and
wherein the controlling of the cooking process of the food material comprises controlling the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the volume change information. 13. The automatic cooking method of claim 8, further comprising obtaining information about an internal temperature and composition of the food material by using a probe configured to obtain the information about the internal temperature and composition of the food material, and
wherein the controlling of the cooking process of the food material comprises controlling the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the information about the internal temperature and composition of the food material. 14. The automatic cooking method of claim 13, wherein the obtaining of the information about the internal temperature and composition of the food material comprises:
identifying a position of the probe and informing a user about the position of the probe to change the position of the probe; and obtaining the information about the internal temperature and composition of the food material at the changed position of the probe. 15. A non-transitory computer-readable recording medium storing a program for executing the method of claim 8 in a computer. | The present disclosure relates to an artificial intelligence (AI) system for simulating functions, such as recognition and determination, of the human brain by using a machine learning algorithm such as deep learning, and an application thereof. Provided are an automatic cooking device and method for selectively emitting light of different wavelength bands to a food material, identifying the food material by obtaining information about the food material, based on reflected light, and controlling a cooking process of the food material.1. An automatic cooking device comprising:
a light emitter configured to emit light of different wavelength bands; a photographing unit including an image sensor; a memory storing computer executable instructions; at least one processor configured to execute the computer executable instructions to control the light emitter and the photographing unit to obtain information about a kind of a food material by performing vision recognition based on a captured image of the food material, obtain characteristic information of the food material by performing spectroscopic analysis based on light reflected by emitting light of a wavelength band selected according to the information about the kind of the food material, and control a cooking process of the food material, based on the information about the kind of the food material and the characteristic information of the food material; and a cooker configured to operate according to the cooking process of the food material. 2. The automatic cooking device of claim 1, wherein the at least one processor is further configured to:
select a wavelength band corresponding to the information about the kind of the food material; identify an amount of light of the selected wavelength band according to a position of the food material and an intensity of external light and emit the light of the selected wavelength band to the food material; perform calibration according to the position of the food material and the intensity of the external light during the spectroscopic analysis based on the reflected light; and obtain characteristic information of the food material. 3. The automatic cooking device of claim 1, wherein the at least one processor is further configured to obtain an optimum recipe using the food material and control the cooking process according to the recipe by comparing the information about the kind of the food material and the characteristic information of the food material before cooking with a database of food material information. 4. The automatic cooking device of claim 1, wherein the at least one processor is further configured to estimate a cooked state of the food material or an end of a cooking time by selectively emitting light of a wavelength band used for obtaining predefined sensing information according to a progress of the cooking process of the food material. 5. The automatic cooking device of claim 1, wherein the at least one processor is further configured to control the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and volume change information regarding the difference between a volume of the food material before cooking and the volume of the food material when heated. 6. The automatic cooking device of claim 1, further comprising a probe configured to obtain information about an internal temperature and composition of the food material, and
wherein the at least one processor is further configured to control the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the information about the internal temperature and composition of the food material. 7. The automatic cooking device of claim 6, wherein the at least one processor is further configured to identify a position of the probe by using the photographing unit and inform a user about the position of the probe to correct the position of the probe. 8. An automatic cooking method comprising:
obtaining information about a kind of a food material by performing vision recognition based on a captured image of the food material; obtaining characteristic information of the food material by performing spectroscopic analysis based on light reflected by emitting, to the food material, light of a wavelength band selected according to the information about the kind of the food material; and controlling a cooking process of the food material, based on the information about the kind of the food material and the characteristic information of the food material, wherein the information about the kind of the food material and the characteristic information of the food material are obtained by a light emitter which emits light of different wavelength bands and a photographing unit including an image sensor. 9. The automatic cooking method of claim 8, wherein the obtaining of the characteristic information of the food material by performing the spectroscopic analysis comprises:
selecting a wavelength band according to the information about the kind of the food material; emitting light of the selected wavelength band to the food material by determining an amount of the light according to a position of the food material and an intensity of external light; performing calibration according to the position of the food material and the intensity of the external light during the spectroscopic analysis based on the reflected light; and obtaining the characteristic information of the food material. 10. The automatic cooking method of claim 8, wherein the controlling of the cooking process of the food material comprises:
obtaining an optimal recipe using the food material by comparing the information about the kind of the food material and the characteristic information of the food material before cooking with a database of food material information; and controlling the cooking process according to the obtained recipe. 11. The automatic cooking method of claim 8, wherein the controlling of the cooking process of the food material comprises estimating a cooked state of the food material or an end of a cooking time by selectively emitting light of a wavelength band used for obtaining predefined sensing information according to a progress of the cooking process of the food material. 12. The automatic cooking method of claim 8, further comprising obtaining volume change information regarding the difference between a volume of the food material before cooking and the volume of the food material when heated, and
wherein the controlling of the cooking process of the food material comprises controlling the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the volume change information. 13. The automatic cooking method of claim 8, further comprising obtaining information about an internal temperature and composition of the food material by using a probe configured to obtain the information about the internal temperature and composition of the food material, and
wherein the controlling of the cooking process of the food material comprises controlling the cooking process of the food material by identifying a cooked state of the food material, based on the characteristic information of the food material and the information about the internal temperature and composition of the food material. 14. The automatic cooking method of claim 13, wherein the obtaining of the information about the internal temperature and composition of the food material comprises:
identifying a position of the probe and informing a user about the position of the probe to change the position of the probe; and obtaining the information about the internal temperature and composition of the food material at the changed position of the probe. 15. A non-transitory computer-readable recording medium storing a program for executing the method of claim 8 in a computer. | 3,600 |
345,481 | 16,643,420 | 3,643 | There is provided a compound of formula (I), wherein L1 to L3′, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease. | 1. A compound of formula I, 2. A compound as claimed in claim 1, wherein X represents —O—, —N(Rx)— or —CH2—. 3. A compound as claimed in claim 2, wherein the —[CR3R4]-L1-X— linker has one of the following structures: 4. A compound as claimed in claim 1, wherein L2 represents —C(═O)—. 5. A compound as claimed in claim 1, wherein R1 and R2 independently represent hydrogen, halogen, —OR7, or C1-4 alkyl optionally substituted by one or more halo atoms. 6. A compound as claimed in claim 1, wherein A represents an aryl or heteroaryl group, each of which is optionally substituted by one or more Q1 groups. 7. A compound as claimed in claim 1, wherein B represents an aryl or heteroaryl group, each of which is optionally substituted by one or more Q2 substituents. 8. A compound as claimed in claim 1, wherein the compound is an antagonist of OX1R and/or OX1R/OX2R selected from the group consisting of:
3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R)-3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S)-3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; (3S)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; (3R)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; 3-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-[(4-fluorophenoxy)methyl]-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; 3-[(4-fluorophenoxy)methyl]-2-[5-(2-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; 3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S)-3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R)-3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; 3-(3-fluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(2-fluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-bromophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(3,4-difluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-(4-methylphenoxymethyl)-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-[5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; 2-(2-chloro-5-phenyl-1,3-thiazole-4-carbonyl)-3-[(4-fluorophenoxy)methyl]-2-azabicyclo[3.1.1]heptane; 3-[(4-fluorophenoxy)methyl]-2-(2-methoxy-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 2-(2-cyclopropyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-[(4-fluorophenoxy)methyl]-2-azabicyclo[3.1.1]heptane; 6-fluoro-2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}-1,3-benzothiazole; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; 2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoline; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-[({7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl}oxy)methyl]-2-azabicyclo[3.1.1]heptane; 2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoxaline; N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}isoquinolin-3-amine; N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinolin-2-amine; 6-fluoro-N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; (3S,4R)-4-fluoro-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4S)-4-fluoro-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; 1-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 7-chloro-2-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoxaline; 3-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3R,4R)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3R,4S)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3S,4S)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3S,4R)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-3-{[(5-methylpyridin-2-yl)oxy]methyl}-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-6-fluoro-2-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methoxy)-1,3-benzothiazole; Racemic mixture of trans-3-[(3,4-difluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-2′-(3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-6′-methyl-2,3′-bipyridine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-{6-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]pyridine-2-carbonyl}-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-2-[3-(5-fluoropyrimidin-2-yl)-6-methylpyridine-2-carbonyl]-4-methyl-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrazin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1H-pyrazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)isoquinolin-3-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-1H-pyrazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrazin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinazolin-2-amine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(6-methylpyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(5-methylpyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-2-[5-(5-chloropyridin-3-yl)-2-methyl-1,3-thiazole-4-carbonyl]-3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(2H-1,2,3-triazol-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(1H-pyrazol-1-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(2H-1,2,3-triazol-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl}-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(6-methylpyridin-3-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyrazine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-1H-1,2,3-triazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of trans-5-chloro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of trans-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinazolin-2-amine; Racemic mixture of trans-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; Racemic mixture of cis-5-chloro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of cis-5-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinolin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-({(3R,4S)-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-({(3S,4R)-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; N-{(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; N-{(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-{[2-(3-ethoxy-6-methylpyridine-2-carbonyl)-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoro-1,3-benzothiazol-2-amine; Racemic mixture of cis-3-(3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3S,4R)-3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3R,4S)-3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-5-fluoro-6-methyl-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; Racemic mixture of cis-6,7-difluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-4-fluoro-N-({4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)aniline; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrido[2,3-b]pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoroquinoxalin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoroquinoxalin-2-amine; N-{[(3R,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoroquinoxalin-2-amine; Racemic mixture of cis-N-{[4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-5-methyl-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrazin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzoxazol-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzoxazol-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-3-{4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl}-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3S,4R)-4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3R,4S)-4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-3-[4-methyl-3-({[5-(trifluoromethyl)pyrazin-2-yl]amino}methyl)-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-3-(3-{[(6-fluoroquinoxalin-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]oxazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]oxazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]oxazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[4-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyridazin-3-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R) or (3R,4S)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S) or (3S,4R)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[4-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-N-({2-[2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R) or (3R,4S)-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S) or (3S,4R)-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-cyclopropylpyrazin-2-amine; Racemic mixture of cis-5-cyclopropyl-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-cyclopropylpyrimidin-2-amine; and Racemic mixture of cis 5-cyclopropyl-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrimidin-2-amine. 9. (canceled) 10. A pharmaceutical formulation comprising a compound of formula I, as defined in claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 11-12. (canceled) 13. A method of treating or preventing a disease or disorder in which antagonism of the orexin-1 and/or orexin-2 receptors is desired and/or required, comprising administering a therapeutically effective amount of a compound of formula I as defined in claim 1, or a pharmaceutically-acceptable salt, solvate or prodrug thereof, to a patient suffering from, or susceptible to, such a condition. 14. The method as claimed in claim 13, wherein the disease or disorder is selected from the group consisting of substance dependence, addiction, an anxiety disorder, a panic disorder, binge eating, a compulsive disorder, an impulse control disorder, cognitive impairment, and Alzheimer's disease. 15. The method, as claimed in claim 14, wherein the disease or disorder is binge eating, alcohol addiction, nicotine addiction, or cocaine addiction. 16. The pharmaceutical formulation as claimed in claim 10, further comprising a second therapeutic agent that is useful in the treatment of a disease or disorder in which antagonism of the orexin-1 and/or orexin-2 receptors is desired and/or required, 17. (canceled) | There is provided a compound of formula (I), wherein L1 to L3′, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease.1. A compound of formula I, 2. A compound as claimed in claim 1, wherein X represents —O—, —N(Rx)— or —CH2—. 3. A compound as claimed in claim 2, wherein the —[CR3R4]-L1-X— linker has one of the following structures: 4. A compound as claimed in claim 1, wherein L2 represents —C(═O)—. 5. A compound as claimed in claim 1, wherein R1 and R2 independently represent hydrogen, halogen, —OR7, or C1-4 alkyl optionally substituted by one or more halo atoms. 6. A compound as claimed in claim 1, wherein A represents an aryl or heteroaryl group, each of which is optionally substituted by one or more Q1 groups. 7. A compound as claimed in claim 1, wherein B represents an aryl or heteroaryl group, each of which is optionally substituted by one or more Q2 substituents. 8. A compound as claimed in claim 1, wherein the compound is an antagonist of OX1R and/or OX1R/OX2R selected from the group consisting of:
3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R)-3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S)-3-[(4-fluorophenoxy)methyl]-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-(4-fluorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(pyrimidin-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(1,3-thiazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-{[6-methyl-3-(1,3-thiazol-2-yl)pyridin-2-yl]carbonyl}-2-azabicyclo[3.1.1]heptane; 3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3S)-3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; (3R)-3-{[(5-chloropyridin-2-yl)oxy]methyl}-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-2-azabicyclo[3.1.1]heptane; 2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; (3S)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; (3R)-2-{[5-methyl-2-(pyrimidin-2-yl)phenyl]carbonyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; 3-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-[(4-fluorophenoxy)methyl]-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; 3-[(4-fluorophenoxy)methyl]-2-[5-(2-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; 3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S)-3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R)-3-[2-(4-fluorophenoxy)ethyl]-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; 3-(3-fluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(2-fluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-bromophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(3,4-difluorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-(4-methylphenoxymethyl)-2-azabicyclo[3.1.1]heptane; 3-(4-chlorophenoxymethyl)-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-2-[5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; 2-(2-chloro-5-phenyl-1,3-thiazole-4-carbonyl)-3-[(4-fluorophenoxy)methyl]-2-azabicyclo[3.1.1]heptane; 3-[(4-fluorophenoxy)methyl]-2-(2-methoxy-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 2-(2-cyclopropyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-[(4-fluorophenoxy)methyl]-2-azabicyclo[3.1.1]heptane; 6-fluoro-2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}-1,3-benzothiazole; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; 2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoline; 2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-3-[({7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl}oxy)methyl]-2-azabicyclo[3.1.1]heptane; 2-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoxaline; N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}isoquinolin-3-amine; N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinolin-2-amine; 6-fluoro-N-{[2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; (3S,4R)-4-fluoro-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4S)-4-fluoro-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[5-methyl-2-(pyrimidin-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptane; 3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; 1-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 7-chloro-2-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}quinoxaline; 3-{[4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3R,4R)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3R,4S)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3S,4S)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; 3-{[(3S,4R)-4-methyl-2-(2-methyl-5-phenyl-1,3-thiazole-4-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methoxy}isoquinoline; (3R,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-(4-fluorophenoxymethyl)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-3-{[(5-methylpyridin-2-yl)oxy]methyl}-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1,3-thiazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-6-fluoro-2-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methoxy)-1,3-benzothiazole; Racemic mixture of trans-3-[(3,4-difluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-2′-(3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-6′-methyl-2,3′-bipyridine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-{6-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]pyridine-2-carbonyl}-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-chlorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-2-[3-(5-fluoropyrimidin-2-yl)-6-methylpyridine-2-carbonyl]-4-methyl-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrazin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(1H-pyrazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)isoquinolin-3-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-1H-pyrazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyrazin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinazolin-2-amine; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(6-methylpyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(5-methylpyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-2-[5-(5-chloropyridin-3-yl)-2-methyl-1,3-thiazole-4-carbonyl]-3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(2H-1,2,3-triazol-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(1H-pyrazol-1-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-{[(5-chloropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3S,4S)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; (3R,4R)-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(pyridin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(2H-1,2,3-triazol-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-3-({[5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{[(5-fluoropyridin-2-yl)oxy]methyl}-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-{3-[(4-fluorophenoxy)methyl]-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl}-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[2-methyl-5-(6-methylpyridin-3-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyrazine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of cis-3-[(4-fluorophenoxy)methyl]-4-methyl-2-[6-methyl-3-(4-methyl-1H-1,2,3-triazol-1-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptane; Racemic mixture of trans-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of trans-5-chloro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of trans-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinazolin-2-amine; Racemic mixture of trans-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; Racemic mixture of cis-5-chloro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of cis-5-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinolin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-({(3R,4S)-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-({(3S,4R)-4-methyl-2-[2-methyl-5-(pyrimidin-2-yl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; 6-fluoro-N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; N-{(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; N-{(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoro-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-{[2-(3-ethoxy-6-methylpyridine-2-carbonyl)-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoro-1,3-benzothiazol-2-amine; Racemic mixture of cis-3-(3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3S,4R)-3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3R,4S)-3-{[(6-fluoro-1,3-benzothiazol-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzothiazol-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzothiazol-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-5-fluoro-6-methyl-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}quinoxalin-2-amine; Racemic mixture of cis-6,7-difluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-4-fluoro-N-({4-methyl-2-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)aniline; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrido[2,3-b]pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-fluoroquinoxalin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoroquinoxalin-2-amine; N-{[(3R,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-6-fluoroquinoxalin-2-amine; Racemic mixture of cis-N-{[4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-(1-methyl-4-phenyl-1H-pyrazole-3-carbonyl)-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-amine; N-{[(3S,4R)-4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; N-{[(3R,4S)-4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyridin-2-amine; Racemic mixture of cis-5-methyl-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrazin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzoxazol-2-amine; 6-fluoro-N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; 6-fluoro-N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-6-fluoro-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)quinoxalin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-1,3-benzoxazol-2-amine; N-{[(3S,4R)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; N-{[(3R,4S)-4-methyl-2-[6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-1,3-benzoxazol-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-3-{4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl}-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3S,4R)-4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; 3-[(3R,4S)-4-methyl-3-[({[1,3]thiazolo[5,4-b]pyridin-2-yl}amino)methyl]-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]thiazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-3-[4-methyl-3-({[5-(trifluoromethyl)pyrazin-2-yl]amino}methyl)-2-azabicyclo[3.1.1]heptane-2-carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-3-(3-{[(6-fluoroquinoxalin-2-yl)amino]methyl}-4-methyl-2-azabicyclo[3.1.1]heptane-2-carbonyl)-4-(2H-1,2,3-triazol-2-yl)benzonitrile; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-[1,3]oxazolo[5,4-b]pyridin-2-amine; N-{[(3S,4R)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]oxazolo[5,4-b]pyridin-2-amine; N-{[(3R,4S)-2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-[1,3]oxazolo[5,4-b]pyridin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[1-methyl-4-(pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[4-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-6-(trifluoromethyl)pyridazin-3-amine; Racemic mixture of cis-N-({4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R) or (3R,4S)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S) or (3S,4R)-4-methyl-2-[6-methyl-3-(pyrimidin-2-yl)pyridine-2-carbonyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[4-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine; Racemic mixture of cis-N-({2-[2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3S,4R) or (3R,4S)-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; N-{[(3R,4S) or (3S,4R)-4-methyl-2-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-2-azabicyclo[3.1.1]heptan-3-yl]methyl}-5-(trifluoromethyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-cyclopropylpyrazin-2-amine; Racemic mixture of cis-5-cyclopropyl-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrazin-2-amine; Racemic mixture of cis-N-({2-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)-5-cyclopropylpyrimidin-2-amine; and Racemic mixture of cis 5-cyclopropyl-N-({2-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-4-methyl-2-azabicyclo[3.1.1]heptan-3-yl}methyl)pyrimidin-2-amine. 9. (canceled) 10. A pharmaceutical formulation comprising a compound of formula I, as defined in claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 11-12. (canceled) 13. A method of treating or preventing a disease or disorder in which antagonism of the orexin-1 and/or orexin-2 receptors is desired and/or required, comprising administering a therapeutically effective amount of a compound of formula I as defined in claim 1, or a pharmaceutically-acceptable salt, solvate or prodrug thereof, to a patient suffering from, or susceptible to, such a condition. 14. The method as claimed in claim 13, wherein the disease or disorder is selected from the group consisting of substance dependence, addiction, an anxiety disorder, a panic disorder, binge eating, a compulsive disorder, an impulse control disorder, cognitive impairment, and Alzheimer's disease. 15. The method, as claimed in claim 14, wherein the disease or disorder is binge eating, alcohol addiction, nicotine addiction, or cocaine addiction. 16. The pharmaceutical formulation as claimed in claim 10, further comprising a second therapeutic agent that is useful in the treatment of a disease or disorder in which antagonism of the orexin-1 and/or orexin-2 receptors is desired and/or required, 17. (canceled) | 3,600 |
345,482 | 16,643,435 | 2,625 | The invention relates to a touch panel device comprising a touch input surface, at least one sensor that serves to monitor a contact and/or a load applied to the touch input surface, a tactile response generation unit that is rigidly connected to the touch input surface, and a control unit that serves to process a signal from the sensor and control the tactile response generation unit on the basis of the monitored contact and/or load, wherein the tactile response generation unit comprises a housing, said housing comprising magnetically conducting material, an electrically conducting coil arranged fixedly within the housing, and a core comprising magnetically conducting material, wherein the core is arranged within the coil, such that the core is movable along a long axis of the coil. | 1. A touch panel device comprising:
a touch input surface; at least one sensor that serves to monitor at least one of a contact or a load applied to the touch input surface; a tactile response generation unit that is rigidly connected to the touch input surface; and a control unit configured to process a signal from the sensor and to control the tactile response generation unit on a basis of the at least one of the monitored contact or the monitored load, wherein the tactile response generation unit comprises;
a housing, said housing comprising magnetically conducting material;
an electrically conducting coil arranged fixedly within the housing; and
a core comprising magnetically conducting material, wherein the core is arranged within the coil, such that the core is movable along a long axis of the coil. 2. The touch panel device according to claim 1, wherein the control unit is configured to initiate a current in the coil such that when a magnetically conducting portion of the core is asymmetrically positioned with respect to the coil, the core begins an oscillating movement with respect to the coil. 3. The touch panel device according to claim 1, wherein the core comprises a material having a lower relative permeability than a magnetically conducting material comprised in the core. 4. The touch panel device according to claim 1, further comprising:
a spring mechanism attached to at least one of the housing or the coil and configured to apply a spring force to the core such that the core returns to an initial position when a current applied to the coil is set to zero. 5. The touch panel device according to at claim 1, wherein the tactile response generation unit is configured to prevent the core from coming into direct contact with the touch input surface. 6. The touch panel device according to at claim 1, wherein the rigid connection between the tactile response generation unit and the touch input surface is configured to transfer a mechanical vibration caused by an oscillating movement of the tactile response generation unit to the touch input surface. 7. The touch panel device according to claim 1, further comprising a device housing, wherein the touch input surface is elastically connected to the device housing. 8. The touch panel device according to claim 7, wherein the connection between the device housing and the touch input surface comprises a damping element. 9. The touch panel device according to claim 1, wherein the sensor for monitoring the load applied to the touch input surface is arranged between the touch input surface and a wall of a device housing. 10. The touch panel device according to claim 1, wherein the signal from the sensor comprises information regarding a location of the contact on the touch input surface, and wherein the control unit is configured to determine a magnitude of separation between the location of the contact and at least one of the tactile response generation unit or the rigid connection that connects the tactile response generation unit to the touch input surface, and wherein the control unit controls the tactile response generation unit on a basis of the determined magnitude of separation. | The invention relates to a touch panel device comprising a touch input surface, at least one sensor that serves to monitor a contact and/or a load applied to the touch input surface, a tactile response generation unit that is rigidly connected to the touch input surface, and a control unit that serves to process a signal from the sensor and control the tactile response generation unit on the basis of the monitored contact and/or load, wherein the tactile response generation unit comprises a housing, said housing comprising magnetically conducting material, an electrically conducting coil arranged fixedly within the housing, and a core comprising magnetically conducting material, wherein the core is arranged within the coil, such that the core is movable along a long axis of the coil.1. A touch panel device comprising:
a touch input surface; at least one sensor that serves to monitor at least one of a contact or a load applied to the touch input surface; a tactile response generation unit that is rigidly connected to the touch input surface; and a control unit configured to process a signal from the sensor and to control the tactile response generation unit on a basis of the at least one of the monitored contact or the monitored load, wherein the tactile response generation unit comprises;
a housing, said housing comprising magnetically conducting material;
an electrically conducting coil arranged fixedly within the housing; and
a core comprising magnetically conducting material, wherein the core is arranged within the coil, such that the core is movable along a long axis of the coil. 2. The touch panel device according to claim 1, wherein the control unit is configured to initiate a current in the coil such that when a magnetically conducting portion of the core is asymmetrically positioned with respect to the coil, the core begins an oscillating movement with respect to the coil. 3. The touch panel device according to claim 1, wherein the core comprises a material having a lower relative permeability than a magnetically conducting material comprised in the core. 4. The touch panel device according to claim 1, further comprising:
a spring mechanism attached to at least one of the housing or the coil and configured to apply a spring force to the core such that the core returns to an initial position when a current applied to the coil is set to zero. 5. The touch panel device according to at claim 1, wherein the tactile response generation unit is configured to prevent the core from coming into direct contact with the touch input surface. 6. The touch panel device according to at claim 1, wherein the rigid connection between the tactile response generation unit and the touch input surface is configured to transfer a mechanical vibration caused by an oscillating movement of the tactile response generation unit to the touch input surface. 7. The touch panel device according to claim 1, further comprising a device housing, wherein the touch input surface is elastically connected to the device housing. 8. The touch panel device according to claim 7, wherein the connection between the device housing and the touch input surface comprises a damping element. 9. The touch panel device according to claim 1, wherein the sensor for monitoring the load applied to the touch input surface is arranged between the touch input surface and a wall of a device housing. 10. The touch panel device according to claim 1, wherein the signal from the sensor comprises information regarding a location of the contact on the touch input surface, and wherein the control unit is configured to determine a magnitude of separation between the location of the contact and at least one of the tactile response generation unit or the rigid connection that connects the tactile response generation unit to the touch input surface, and wherein the control unit controls the tactile response generation unit on a basis of the determined magnitude of separation. | 2,600 |
345,483 | 16,643,398 | 2,625 | This invention relates generally to methods for assessing telomeres, including methods of measuring the length of a telomere and methods for detecting extension of a telomere and methods for measuring telomere extension, and associated systems. | 1. A method for measuring the length of a telomere, comprising:
stretching genomic DNA on to a surface of a support at a uniform stretching rate; hybridizing a telomere-specific probe to the DNA to obtain a probe-DNA hybrid; and detecting the probe-DNA hybrid to thereby determine the length of a telomere. 2. The method of claim 1, wherein the length of the telomere is determined by visualizing and measuring the absolute length of the probe-DNA hybrid. 3. The method of claim 1, wherein the length of the telomere is determined by measuring the intensity of a detectable signal on the telomere-specific probe within the probe-DNA hybrid. 4. A method for detecting extension of a telomere, comprising:
contacting a cell with a nucleotide analogue under conditions sufficient for DNA synthesis and incorporation of the nucleotide analogue into the genomic DNA of the cell; isolating the genomic DNA from the cell; stretching the genomic DNA on to a surface of a support at a uniform stretching rate; hybridizing a telomere-specific probe to the DNA to obtain a probe-DNA hybrid; and detecting the probe-DNA hybrid and the nucleotide analogue to thereby determine whether telomere extension has occurred, wherein the presence of a probe-DNA hybrid comprising the nucleotide analogue is indicative of the extension of a telomere. 5. The method of claim 4, further comprising measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension. 6. The method of claim 5, wherein measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension is performed by visualizing and measuring the absolute length of the probe-DNA hybrid. 7. The method of claim 5, wherein measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension is performed by measuring the intensity of a detectable signal on the telomere-specific probe within the probe-DNA hybrid. 8. The method of any one of claims 4 to 7, further comprising contacting the cell with an agent that inhibits or promotes telomere extension. 9. The method of any one of claims 1 to 8, wherein the uniform stretching rate is between 0.1 kb/μm and 10 kb/μm, between 0.5 kb/μm and 5 kb/μm, or between 1 kb/μm and 3 kb/μm. 10. The method of any one of claims 1 to 9, wherein the uniform stretching rate is between 1.5 kb/μm and 2.5 kb/μm. 11. The method of any one of claims 1 to 10, wherein the uniform stretching rate is 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3 or 2.4 kb/μm. 12. The method of any one of claims 1 to 11, wherein the genomic DNA is stretched on to the surface by molecular combing. 13. The method of any one of claims 1 to 12, wherein the genomic DNA is stretched on to the surface by a molecular combing machine. 14. The method of any one of claims 1 to 13, wherein the telomere-specific probe hybridizes to one or more telomere repeat units. 15. The method of claim 14, wherein the genomic DNA is human genomic DNA and the telomere repeat unit comprises the sequence TTAGGG. 16. The method of any one of claims 1 to 15, wherein the telomere-specific probe is a nucleic acid probe comprising the sequence CCCTAA or TTAGGG. 17. The method of any one of claims 1 to 16, wherein the telomere-specific probe is a peptide nucleic acid (PNA) probe. 18. The method of any one of claims 1 to 17, wherein the telomere-specific probe comprises a visually-detectable label. 19. The method of claim 18, wherein the visually-detectable label is a fluorescent label. 20. The method of any one of claims 4 to 19, wherein the nucleotide analogue comprises a visually-detectable label. 21. The method of claim 20, wherein the visually-detectable label is applied to the analogue after incorporation of the analogue into the DNA. 22. The method of claim 20, wherein the nucleotide analogue comprises the visually-detectable label prior to incorporation of the analogue into the DNA. 23. The method of any one of claims 20 to 22, wherein the visually-detectable label is a fluorescent label. 24. The method of any one of claim 4 to 21 or 23, wherein the nucleotide analogue is a thymidine analogue selected from among chlorodeoxyuridine (CldU), bromoeoxyuridine (BrdU), iododeoxyuridine (IdU) and ethynyldeoxyuridine (EdU). 25. The method of any one of claim 4 to 20, 22 or 23, wherein the nucleotide analogue is a fluorescent analogue selected from 2-aminopurine (2AP), pyrrolo-C (PyC), 1,3-diaza-2-oxophenothiazine (tC), 1,3-diaza-2-oxophenoxazine (tC°) and 7-nitro-1,3-diaza-2-oxophenothiazine (tCnitro). 26. The method of any one of claims 1 to 25, further comprising staining the genomic DNA. 27. The method of claim 26, wherein the genomic DNA is stained with a fluorescent dye. 28. The method of claim 27, wherein the fluorescent dye is selected from among YOYO-1, TOTO-1, POPO-1, BOBO-1 and JOJO-1. 29. The method of any one of claims 1 to 3, wherein the genomic DNA is obtained from frozen, fresh, or fixed cells or tissue. 30. The method of any one of claims 1 to 3, wherein the method first comprises a step of extracting genomic DNA from cells or tissue. 31. The method of claim 30, wherein the cells or tissue are frozen, fixed or fresh. 32. The method of any one of claims 1 to 31, wherein the support is a glass support. 33. The method of claim 32, wherein the glass support is silanized. 34. The method of claim 32 or 33, wherein the glass support is coated with vinyl silane. 35. The method of any one of claims 32 to 34, wherein the glass support is a microscope slide or coverslip. 36. The method of any one of claims 1 to 35, wherein at least a portion of the method is automated. 37. A method for measuring the length of a telomere, the method including, in one or more processing devices:
receiving image data captured by an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detecting a probe-DNA hybrid in the one or more images; measuring a length of the probe-DNA hybrid in the one or more images; and, using the measured length to determine a telomere length indicator indicative of the telomere length. 38. A method according to claim 37, wherein the method includes detecting a probe-DNA hybrid in accordance with pixel parameters of image pixels of the image, the pixel parameters including at least one of:
a pixel colour; a pixel intensity; a pixel brightness; a pixel hue; and, a pixel saturation. 39. A method according to claim 37 or claim 38, wherein the method includes determining the length of the probe-DNA hybrid by at least one of:
region growing; and,
edge detection. 40. A method according to any one of the claims 37 to 39, wherein the method includes:
detecting candidate features in the image using the pixel parameters; and,
detecting a probe-DNA hybrid at least partially in accordance with the candidate features. 41. A method according to claim 40, wherein the method includes:
determining an extent of a candidate feature; and, detecting a probe-DNA hybrid in accordance with the determined extent. 42. A method according to claim 41, wherein the method includes:
comparing the extent to one or more thresholds; and, detecting a probe-DNA hybrid in accordance with results of the comparison. 43. A method according to claim 41 or claim 42, wherein the method includes determining the extent by at least one of:
region growing; and,
edge detection. 44. A method according to any one of the claims 41 to 43, wherein the method includes:
selectively excluding candidate features in accordance with at least one of:
candidate feature size;
candidate feature location; and,
candidate feature orientation; and,
detecting a probe-DNA hybrid from the remaining candidate features. 45. A method according to any one of the claims 37 to 44, wherein the method includes:
performing enhancement to generate an enhanced image using at least one of:
contrast enhancement;
hue enhancement;
intensity enhancement;
brightness enhancement;
colour enhancement; and,
saturation enhancement; and,
detecting a probe-DNA hybrid using the enhanced image. 46. A method according to any one of the claims 37 to 45, wherein the image data includes a plurality of images and wherein the method includes:
forming a composite image from the plurality of images; and,
detecting a probe-DNA hybrid using the composite image. 47. A method according to any one of the claims 37 to 46, wherein the method includes:
measuring a length of plurality of probe-DNA hybrids; and,
statistically analyzing the measured lengths to determine at least one of:
a telomere length; and,
a telomere length distribution. 48. A system for measuring the length of a telomere, the system including, one or more processing devices that:
receive image data from an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detect a probe-DNA hybrid in the one or more images; measure a length of the probe-DNA hybrid in the one or more images; and, use the measured length to determine a telomere length indicator indicative of the telomere length. 49. A system according to claim 48, wherein the one or more processing devices:
generate an indicator indicative of at least one of: a telomere length; and, a telomere length distribution; and, at least one of display and store the indicator. 50. A system according to claim 48 or claim 49, wherein the one or more processing devices control the imaging device to capture the one or more images. 51. A system according to any one of the claims 48 to 50, wherein the support is mounted on a stage, and the one or more processing devices control actuators to thereby relatively move the stage and imaging device to thereby capture the one or more images. 52. A system according to any one of the claims 48 to 51, wherein the system includes:
a molecular combing machine that stretches the genomic DNA on to the surface;
an applicator that applies the telomere-specific probe to the surface; and,
at least one transport mechanism for transporting the substrate from the molecular combing to the applicator and from the applicator to the stage. 53. A system according to claim 52, wherein the one or more processing devices control at least one of:
the molecular combing machine; the applicator; and, the at least one transport mechanism. 54. A computer program product including computer executable code, which when executed by a suitably programmed processing system causes the processing system to:
receive image data from an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detect a probe-DNA hybrid in the one or more images; measure a length of the probe-DNA hybrid in the one or more images; and, use the measured length to determine a telomere length indicator indicative of the telomere length. | This invention relates generally to methods for assessing telomeres, including methods of measuring the length of a telomere and methods for detecting extension of a telomere and methods for measuring telomere extension, and associated systems.1. A method for measuring the length of a telomere, comprising:
stretching genomic DNA on to a surface of a support at a uniform stretching rate; hybridizing a telomere-specific probe to the DNA to obtain a probe-DNA hybrid; and detecting the probe-DNA hybrid to thereby determine the length of a telomere. 2. The method of claim 1, wherein the length of the telomere is determined by visualizing and measuring the absolute length of the probe-DNA hybrid. 3. The method of claim 1, wherein the length of the telomere is determined by measuring the intensity of a detectable signal on the telomere-specific probe within the probe-DNA hybrid. 4. A method for detecting extension of a telomere, comprising:
contacting a cell with a nucleotide analogue under conditions sufficient for DNA synthesis and incorporation of the nucleotide analogue into the genomic DNA of the cell; isolating the genomic DNA from the cell; stretching the genomic DNA on to a surface of a support at a uniform stretching rate; hybridizing a telomere-specific probe to the DNA to obtain a probe-DNA hybrid; and detecting the probe-DNA hybrid and the nucleotide analogue to thereby determine whether telomere extension has occurred, wherein the presence of a probe-DNA hybrid comprising the nucleotide analogue is indicative of the extension of a telomere. 5. The method of claim 4, further comprising measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension. 6. The method of claim 5, wherein measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension is performed by visualizing and measuring the absolute length of the probe-DNA hybrid. 7. The method of claim 5, wherein measuring the length of the extension, the length of the telomere with the extension and/or the length of the telomere excluding the extension is performed by measuring the intensity of a detectable signal on the telomere-specific probe within the probe-DNA hybrid. 8. The method of any one of claims 4 to 7, further comprising contacting the cell with an agent that inhibits or promotes telomere extension. 9. The method of any one of claims 1 to 8, wherein the uniform stretching rate is between 0.1 kb/μm and 10 kb/μm, between 0.5 kb/μm and 5 kb/μm, or between 1 kb/μm and 3 kb/μm. 10. The method of any one of claims 1 to 9, wherein the uniform stretching rate is between 1.5 kb/μm and 2.5 kb/μm. 11. The method of any one of claims 1 to 10, wherein the uniform stretching rate is 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3 or 2.4 kb/μm. 12. The method of any one of claims 1 to 11, wherein the genomic DNA is stretched on to the surface by molecular combing. 13. The method of any one of claims 1 to 12, wherein the genomic DNA is stretched on to the surface by a molecular combing machine. 14. The method of any one of claims 1 to 13, wherein the telomere-specific probe hybridizes to one or more telomere repeat units. 15. The method of claim 14, wherein the genomic DNA is human genomic DNA and the telomere repeat unit comprises the sequence TTAGGG. 16. The method of any one of claims 1 to 15, wherein the telomere-specific probe is a nucleic acid probe comprising the sequence CCCTAA or TTAGGG. 17. The method of any one of claims 1 to 16, wherein the telomere-specific probe is a peptide nucleic acid (PNA) probe. 18. The method of any one of claims 1 to 17, wherein the telomere-specific probe comprises a visually-detectable label. 19. The method of claim 18, wherein the visually-detectable label is a fluorescent label. 20. The method of any one of claims 4 to 19, wherein the nucleotide analogue comprises a visually-detectable label. 21. The method of claim 20, wherein the visually-detectable label is applied to the analogue after incorporation of the analogue into the DNA. 22. The method of claim 20, wherein the nucleotide analogue comprises the visually-detectable label prior to incorporation of the analogue into the DNA. 23. The method of any one of claims 20 to 22, wherein the visually-detectable label is a fluorescent label. 24. The method of any one of claim 4 to 21 or 23, wherein the nucleotide analogue is a thymidine analogue selected from among chlorodeoxyuridine (CldU), bromoeoxyuridine (BrdU), iododeoxyuridine (IdU) and ethynyldeoxyuridine (EdU). 25. The method of any one of claim 4 to 20, 22 or 23, wherein the nucleotide analogue is a fluorescent analogue selected from 2-aminopurine (2AP), pyrrolo-C (PyC), 1,3-diaza-2-oxophenothiazine (tC), 1,3-diaza-2-oxophenoxazine (tC°) and 7-nitro-1,3-diaza-2-oxophenothiazine (tCnitro). 26. The method of any one of claims 1 to 25, further comprising staining the genomic DNA. 27. The method of claim 26, wherein the genomic DNA is stained with a fluorescent dye. 28. The method of claim 27, wherein the fluorescent dye is selected from among YOYO-1, TOTO-1, POPO-1, BOBO-1 and JOJO-1. 29. The method of any one of claims 1 to 3, wherein the genomic DNA is obtained from frozen, fresh, or fixed cells or tissue. 30. The method of any one of claims 1 to 3, wherein the method first comprises a step of extracting genomic DNA from cells or tissue. 31. The method of claim 30, wherein the cells or tissue are frozen, fixed or fresh. 32. The method of any one of claims 1 to 31, wherein the support is a glass support. 33. The method of claim 32, wherein the glass support is silanized. 34. The method of claim 32 or 33, wherein the glass support is coated with vinyl silane. 35. The method of any one of claims 32 to 34, wherein the glass support is a microscope slide or coverslip. 36. The method of any one of claims 1 to 35, wherein at least a portion of the method is automated. 37. A method for measuring the length of a telomere, the method including, in one or more processing devices:
receiving image data captured by an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detecting a probe-DNA hybrid in the one or more images; measuring a length of the probe-DNA hybrid in the one or more images; and, using the measured length to determine a telomere length indicator indicative of the telomere length. 38. A method according to claim 37, wherein the method includes detecting a probe-DNA hybrid in accordance with pixel parameters of image pixels of the image, the pixel parameters including at least one of:
a pixel colour; a pixel intensity; a pixel brightness; a pixel hue; and, a pixel saturation. 39. A method according to claim 37 or claim 38, wherein the method includes determining the length of the probe-DNA hybrid by at least one of:
region growing; and,
edge detection. 40. A method according to any one of the claims 37 to 39, wherein the method includes:
detecting candidate features in the image using the pixel parameters; and,
detecting a probe-DNA hybrid at least partially in accordance with the candidate features. 41. A method according to claim 40, wherein the method includes:
determining an extent of a candidate feature; and, detecting a probe-DNA hybrid in accordance with the determined extent. 42. A method according to claim 41, wherein the method includes:
comparing the extent to one or more thresholds; and, detecting a probe-DNA hybrid in accordance with results of the comparison. 43. A method according to claim 41 or claim 42, wherein the method includes determining the extent by at least one of:
region growing; and,
edge detection. 44. A method according to any one of the claims 41 to 43, wherein the method includes:
selectively excluding candidate features in accordance with at least one of:
candidate feature size;
candidate feature location; and,
candidate feature orientation; and,
detecting a probe-DNA hybrid from the remaining candidate features. 45. A method according to any one of the claims 37 to 44, wherein the method includes:
performing enhancement to generate an enhanced image using at least one of:
contrast enhancement;
hue enhancement;
intensity enhancement;
brightness enhancement;
colour enhancement; and,
saturation enhancement; and,
detecting a probe-DNA hybrid using the enhanced image. 46. A method according to any one of the claims 37 to 45, wherein the image data includes a plurality of images and wherein the method includes:
forming a composite image from the plurality of images; and,
detecting a probe-DNA hybrid using the composite image. 47. A method according to any one of the claims 37 to 46, wherein the method includes:
measuring a length of plurality of probe-DNA hybrids; and,
statistically analyzing the measured lengths to determine at least one of:
a telomere length; and,
a telomere length distribution. 48. A system for measuring the length of a telomere, the system including, one or more processing devices that:
receive image data from an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detect a probe-DNA hybrid in the one or more images; measure a length of the probe-DNA hybrid in the one or more images; and, use the measured length to determine a telomere length indicator indicative of the telomere length. 49. A system according to claim 48, wherein the one or more processing devices:
generate an indicator indicative of at least one of: a telomere length; and, a telomere length distribution; and, at least one of display and store the indicator. 50. A system according to claim 48 or claim 49, wherein the one or more processing devices control the imaging device to capture the one or more images. 51. A system according to any one of the claims 48 to 50, wherein the support is mounted on a stage, and the one or more processing devices control actuators to thereby relatively move the stage and imaging device to thereby capture the one or more images. 52. A system according to any one of the claims 48 to 51, wherein the system includes:
a molecular combing machine that stretches the genomic DNA on to the surface;
an applicator that applies the telomere-specific probe to the surface; and,
at least one transport mechanism for transporting the substrate from the molecular combing to the applicator and from the applicator to the stage. 53. A system according to claim 52, wherein the one or more processing devices control at least one of:
the molecular combing machine; the applicator; and, the at least one transport mechanism. 54. A computer program product including computer executable code, which when executed by a suitably programmed processing system causes the processing system to:
receive image data from an imaging device, the image data being indicative of one or more images of at least part of a surface of a support, the surface having stretched genomic DNA hybridized to a telomere-specific probe attached thereto; detect a probe-DNA hybrid in the one or more images; measure a length of the probe-DNA hybrid in the one or more images; and, use the measured length to determine a telomere length indicator indicative of the telomere length. | 2,600 |
345,484 | 16,643,407 | 2,625 | An internal combustion engine (1) has a variable compression ratio mechanism (2) that varies a mechanical compression ratio and a variable valve timing mechanism (7) that varies a valve timing of an intake valve (4). When there is a demand to execute reference position learning (step 21) for system calibration of the variable valve timing mechanism (7), the execution of the reference position learning is permitted on the condition that the mechanical compression ratio is higher than a threshold value VCRth (step 22). When any anomaly is present in the variable compression ratio mechanism (2), the reference position learning of the variable valve timing mechanism (7) is prohibited (steps 23 and 25). | 1. A control method for an internal combustion engine,
the internal combustion engine comprising:
a variable compression ratio mechanism that varies a mechanical compression ratio of the internal combustion engine; and
a variable valve timing mechanism that varies a closing timing of an intake valve, the internal combustion engine having a possibility of combustion instability in a state that the mechanical compression ratio is low and the closing timing of the intake valve is on a retard side,
the control method comprising:
setting a target compression ratio of the variable compression ratio mechanism and a target control position of the variable valve timing mechanism according to operating conditions of the internal combustion engine;
judging whether or not an anomaly is present in the variable compression ratio mechanism, wherein the setting includes:
when the variable compression ratio mechanism is judged as normal, setting the target control position of the variable valve timing mechanism by using a current value of the mechanical compression ratio as a parameter; and
when it is judged that any anomaly is present in the variable compression ratio mechanism, setting the target control position of the variable valve timing mechanism by considering the mechanical compression ratio to be a maximum compression ratio value achievable by the variable compression ratio mechanism;
when there is a demand for a reference position learning operation of controlling the variable valve timing mechanism to a most retarded position and then learning a sensor value of the most retarded position as a reference position, permitting the execution of the reference position learning operation on the condition that the mechanical compression ratio controlled by the variable compression ratio mechanism is higher than a predetermined compression ratio threshold value, wherein the compression ratio threshold value is a value of the mechanical compression ratio at which no combustion instability occurs even when the variable valve timing mechanism is controlled to the most retarded position; and
prohibiting the execution of the reference position learning operation when it is judged that any anomaly is present in the variable compression ratio mechanism. 2. (canceled) 3. (canceled) 4. (canceled) 5. The control method for the internal combustion engine according to claim 1, wherein the variable compression ratio mechanism varies the mechanical compression ratio by changing a relative positional relationship of a piston and a cylinder. 6. A control device for an internal combustion engine,
the internal combustion engine comprising:
a variable compression ratio mechanism that varies a mechanical compression ratio of the internal combustion engine; and
a variable valve timing mechanism that varies a closing timing of an intake valve, the internal combustion engine having a possibility of combustion instability in a state that the mechanical compression ratio is low and the closing timing of the intake valve is on a retard side,
the control device comprising:
a compression ratio control section configured to set a target compression ratio of the variable compression ratio mechanism according to operating conditions of the internal combustion engine;
a valve timing control section configured to set a target control position of the variable valve timing mechanism according to operating conditions of the internal combustion engine;
a learning control section configured to, when there is a demand for a reference position learning operation of controlling the variable valve timing mechanism to a most retarded position and then learning a sensor value of the most retarded position as a reference position, execute the reference position learning operation on the condition that the mechanical compression ratio controlled by the variable compression ratio mechanism is higher than a predetermined compression ratio threshold value, and
an anomaly judgment section configured to judge whether or not an anomaly is present in the variable compression ratio mechanism,
wherein the compression ratio threshold value is a value of the mechanical compression ratio at which no combustion instability occurs even when the variable valve timing mechanism is controlled to the most retarded position,
wherein the valve timing control section is configured to:
when the anomaly judgment section judges that the variable compression ratio mechanism is normal, set the target control position of the variable valve timing mechanism by using a current value of the mechanical compression ratio as a parameter; and
when the anomaly judgment section judges that any anomaly is present in the variable compression ratio mechanism, set the target control position of the variable valve timing mechanism by considering the mechanical compression ratio to be a maximum compression ratio value achievable by the variable compression ratio mechanism, and
wherein the learning control section is configured to, when the anomaly judgment section judges that any anomaly is present in the variable compression ratio mechanism, prohibit the execution of the reference position learning operation. | An internal combustion engine (1) has a variable compression ratio mechanism (2) that varies a mechanical compression ratio and a variable valve timing mechanism (7) that varies a valve timing of an intake valve (4). When there is a demand to execute reference position learning (step 21) for system calibration of the variable valve timing mechanism (7), the execution of the reference position learning is permitted on the condition that the mechanical compression ratio is higher than a threshold value VCRth (step 22). When any anomaly is present in the variable compression ratio mechanism (2), the reference position learning of the variable valve timing mechanism (7) is prohibited (steps 23 and 25).1. A control method for an internal combustion engine,
the internal combustion engine comprising:
a variable compression ratio mechanism that varies a mechanical compression ratio of the internal combustion engine; and
a variable valve timing mechanism that varies a closing timing of an intake valve, the internal combustion engine having a possibility of combustion instability in a state that the mechanical compression ratio is low and the closing timing of the intake valve is on a retard side,
the control method comprising:
setting a target compression ratio of the variable compression ratio mechanism and a target control position of the variable valve timing mechanism according to operating conditions of the internal combustion engine;
judging whether or not an anomaly is present in the variable compression ratio mechanism, wherein the setting includes:
when the variable compression ratio mechanism is judged as normal, setting the target control position of the variable valve timing mechanism by using a current value of the mechanical compression ratio as a parameter; and
when it is judged that any anomaly is present in the variable compression ratio mechanism, setting the target control position of the variable valve timing mechanism by considering the mechanical compression ratio to be a maximum compression ratio value achievable by the variable compression ratio mechanism;
when there is a demand for a reference position learning operation of controlling the variable valve timing mechanism to a most retarded position and then learning a sensor value of the most retarded position as a reference position, permitting the execution of the reference position learning operation on the condition that the mechanical compression ratio controlled by the variable compression ratio mechanism is higher than a predetermined compression ratio threshold value, wherein the compression ratio threshold value is a value of the mechanical compression ratio at which no combustion instability occurs even when the variable valve timing mechanism is controlled to the most retarded position; and
prohibiting the execution of the reference position learning operation when it is judged that any anomaly is present in the variable compression ratio mechanism. 2. (canceled) 3. (canceled) 4. (canceled) 5. The control method for the internal combustion engine according to claim 1, wherein the variable compression ratio mechanism varies the mechanical compression ratio by changing a relative positional relationship of a piston and a cylinder. 6. A control device for an internal combustion engine,
the internal combustion engine comprising:
a variable compression ratio mechanism that varies a mechanical compression ratio of the internal combustion engine; and
a variable valve timing mechanism that varies a closing timing of an intake valve, the internal combustion engine having a possibility of combustion instability in a state that the mechanical compression ratio is low and the closing timing of the intake valve is on a retard side,
the control device comprising:
a compression ratio control section configured to set a target compression ratio of the variable compression ratio mechanism according to operating conditions of the internal combustion engine;
a valve timing control section configured to set a target control position of the variable valve timing mechanism according to operating conditions of the internal combustion engine;
a learning control section configured to, when there is a demand for a reference position learning operation of controlling the variable valve timing mechanism to a most retarded position and then learning a sensor value of the most retarded position as a reference position, execute the reference position learning operation on the condition that the mechanical compression ratio controlled by the variable compression ratio mechanism is higher than a predetermined compression ratio threshold value, and
an anomaly judgment section configured to judge whether or not an anomaly is present in the variable compression ratio mechanism,
wherein the compression ratio threshold value is a value of the mechanical compression ratio at which no combustion instability occurs even when the variable valve timing mechanism is controlled to the most retarded position,
wherein the valve timing control section is configured to:
when the anomaly judgment section judges that the variable compression ratio mechanism is normal, set the target control position of the variable valve timing mechanism by using a current value of the mechanical compression ratio as a parameter; and
when the anomaly judgment section judges that any anomaly is present in the variable compression ratio mechanism, set the target control position of the variable valve timing mechanism by considering the mechanical compression ratio to be a maximum compression ratio value achievable by the variable compression ratio mechanism, and
wherein the learning control section is configured to, when the anomaly judgment section judges that any anomaly is present in the variable compression ratio mechanism, prohibit the execution of the reference position learning operation. | 2,600 |
345,485 | 16,643,395 | 2,625 | A display includes a display panel and at least one display driver chip. The display panel includes a display area and a non-display area surrounding the display area. The display area includes a planar area and a curved bending area located on at least one side of the planar area, where a longitudinal direction of each data signal line is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged, and each data signal line extends to a non-display area on the side of the curved bending area of the display area. The display driver chip is connected to data signal lines by using a chip-on-film, and the display driver chip is located in concave space. | 1. A display, comprising:
a display panel, wherein a plurality of data signal lines and gate scanning lines crossed in a grid shape are arranged on the display panel, and wherein the display panel comprises:
a display area comprising:
a planar area; and
a curved bending area located on at least one side of the planar area, wherein a longitudinal direction of each of the data signal lines is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged; and
a non-display area surrounding the display area, wherein each of the data signal lines extends to the non-display area on the side of the curved bending area of the display area; and
a display driver chip coupled to the display panel using a chip-on-film to the data signal lines that extend to the non-display area, wherein the chip-on-film is bent in a concave space formed by the curved bending area of the display area, and wherein the display driver chip is located in the concave space. 2. The display of claim 1, wherein the display area comprises two curved bending areas, and wherein the two curved bending areas are arranged on two opposite sides of the planar area. 3. The display of claim 2, further comprising two display driver chips, wherein one of the two display driver chips is connected to part of the data signal lines using a first chip-on-film, and wherein the other one of the two display driver chips is connected to remaining data signal lines by a second chip-on-film. 4. The display of claim 1, wherein the chip-on-film comprises a connecting portion connected to the data signal wherein a first bending portion is connected to the connecting portion, and wherein the first bending portion is located in the concave space. 5. The display of claim 4, wherein the display driver chip is disposed at the first bending portion. 6. The display of claim 4, wherein the chip-on-film further comprises a second bending portion connected to the first bending portion, wherein the second bending portion is located in the concave space, and wherein the display driver chip is disposed at the second bending portion. 7. The display of claim 1, wherein the chip-on-film is a single-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces away from the display panel. 8. The display of claim 1, wherein the chip-on-film is a double-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces toward or away from the display panel. 9. A mobile terminal, comprising:
a housing; a middle frame disposed in the housing; a mainboard disposed on the middle frame; and a display disposed on the middle frame and comprising:
a display panel, wherein a plurality of data signal lines and gate scanning lines crossed in a grid shape are arranged on the display panel, and wherein the display panel comprises:
a display area comprising:
a planar area; and
a curved bending area located on at least one side of the planar area, wherein a longitudinal direction of each of the data signal lines is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged; and
a non-display area surrounding the display area, wherein each of the data signal lines extends to the non-display area on the side of the curved bending area of the display area; and
a display driver chip connected to the mainboard using a flexible circuit board and connected using a chip-on-film to the data signal lines that extend to the non-display area, wherein the chip-on-film is bent in a concave space formed by the curved bending area of the display area, and wherein the display driver chip is located in the concave space. 10. The mobile terminal of claim 9, wherein the middle frame comprises a groove configured to accommodate the chip-on-film. 11. The mobile terminal of claim 9, wherein the display area comprises two curved bending areas, and wherein the two curved bending areas are arranged on two opposite sides of the planar area. 12. The mobile terminal of claim 11, further comprising two display driver chips, wherein one of the two display driver chips is connected to part of the data signal lines by a first chip-on-film, and wherein the other one of the two display driver chips is connected to remaining data signal lines by a second chip-on-film. 13. The mobile terminal of claim 9, wherein the chip-on-film comprises a connecting portion connected to the data signal lines, wherein a first bending portion is connected to the connecting portion, and wherein the first bending portion is located in the concave space. 14. The mobile terminal of claim 13, wherein the display driver chip is disposed at the first bending portion. 15. The mobile terminal of claim 13, wherein the chip-on-film further comprises a second bending portion connected to the first bending portion, wherein the second bending portion is located in the concave space, and wherein the display driver chip is disposed at the second bending portion. 16. The mobile terminal of claim 9, wherein the chip-on-film is a single-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces away from the display panel. 17. The mobile terminal of claim 9, wherein the chip-on-film is a double-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces toward or away from the display panel. 18. The mobile terminal of claim 9, wherein the chip-on-film is a double layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on film that faces toward the display panel. 19. The mobile terminal of claim 9, wherein the chip-on-film is a double layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on film that faces away from the display panel. 20. The mobile terminal of claim 9, wherein the display further comprises gate on array (GOA) circuits coupled to the display driver chips. | A display includes a display panel and at least one display driver chip. The display panel includes a display area and a non-display area surrounding the display area. The display area includes a planar area and a curved bending area located on at least one side of the planar area, where a longitudinal direction of each data signal line is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged, and each data signal line extends to a non-display area on the side of the curved bending area of the display area. The display driver chip is connected to data signal lines by using a chip-on-film, and the display driver chip is located in concave space.1. A display, comprising:
a display panel, wherein a plurality of data signal lines and gate scanning lines crossed in a grid shape are arranged on the display panel, and wherein the display panel comprises:
a display area comprising:
a planar area; and
a curved bending area located on at least one side of the planar area, wherein a longitudinal direction of each of the data signal lines is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged; and
a non-display area surrounding the display area, wherein each of the data signal lines extends to the non-display area on the side of the curved bending area of the display area; and
a display driver chip coupled to the display panel using a chip-on-film to the data signal lines that extend to the non-display area, wherein the chip-on-film is bent in a concave space formed by the curved bending area of the display area, and wherein the display driver chip is located in the concave space. 2. The display of claim 1, wherein the display area comprises two curved bending areas, and wherein the two curved bending areas are arranged on two opposite sides of the planar area. 3. The display of claim 2, further comprising two display driver chips, wherein one of the two display driver chips is connected to part of the data signal lines using a first chip-on-film, and wherein the other one of the two display driver chips is connected to remaining data signal lines by a second chip-on-film. 4. The display of claim 1, wherein the chip-on-film comprises a connecting portion connected to the data signal wherein a first bending portion is connected to the connecting portion, and wherein the first bending portion is located in the concave space. 5. The display of claim 4, wherein the display driver chip is disposed at the first bending portion. 6. The display of claim 4, wherein the chip-on-film further comprises a second bending portion connected to the first bending portion, wherein the second bending portion is located in the concave space, and wherein the display driver chip is disposed at the second bending portion. 7. The display of claim 1, wherein the chip-on-film is a single-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces away from the display panel. 8. The display of claim 1, wherein the chip-on-film is a double-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces toward or away from the display panel. 9. A mobile terminal, comprising:
a housing; a middle frame disposed in the housing; a mainboard disposed on the middle frame; and a display disposed on the middle frame and comprising:
a display panel, wherein a plurality of data signal lines and gate scanning lines crossed in a grid shape are arranged on the display panel, and wherein the display panel comprises:
a display area comprising:
a planar area; and
a curved bending area located on at least one side of the planar area, wherein a longitudinal direction of each of the data signal lines is perpendicular to a longitudinal direction of the side of the planar area on which the curved bending area is arranged; and
a non-display area surrounding the display area, wherein each of the data signal lines extends to the non-display area on the side of the curved bending area of the display area; and
a display driver chip connected to the mainboard using a flexible circuit board and connected using a chip-on-film to the data signal lines that extend to the non-display area, wherein the chip-on-film is bent in a concave space formed by the curved bending area of the display area, and wherein the display driver chip is located in the concave space. 10. The mobile terminal of claim 9, wherein the middle frame comprises a groove configured to accommodate the chip-on-film. 11. The mobile terminal of claim 9, wherein the display area comprises two curved bending areas, and wherein the two curved bending areas are arranged on two opposite sides of the planar area. 12. The mobile terminal of claim 11, further comprising two display driver chips, wherein one of the two display driver chips is connected to part of the data signal lines by a first chip-on-film, and wherein the other one of the two display driver chips is connected to remaining data signal lines by a second chip-on-film. 13. The mobile terminal of claim 9, wherein the chip-on-film comprises a connecting portion connected to the data signal lines, wherein a first bending portion is connected to the connecting portion, and wherein the first bending portion is located in the concave space. 14. The mobile terminal of claim 13, wherein the display driver chip is disposed at the first bending portion. 15. The mobile terminal of claim 13, wherein the chip-on-film further comprises a second bending portion connected to the first bending portion, wherein the second bending portion is located in the concave space, and wherein the display driver chip is disposed at the second bending portion. 16. The mobile terminal of claim 9, wherein the chip-on-film is a single-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces away from the display panel. 17. The mobile terminal of claim 9, wherein the chip-on-film is a double-layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on-film that faces toward or away from the display panel. 18. The mobile terminal of claim 9, wherein the chip-on-film is a double layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on film that faces toward the display panel. 19. The mobile terminal of claim 9, wherein the chip-on-film is a double layer chip-on-film, and wherein the display driver chip is located on one side of the chip-on film that faces away from the display panel. 20. The mobile terminal of claim 9, wherein the display further comprises gate on array (GOA) circuits coupled to the display driver chips. | 2,600 |
345,486 | 16,643,408 | 2,192 | A firmware update method including receiving a first message from an update server, where the first message includes first data and a signature of the first data, verifying the first message, and obtaining digest data included in the first data after the first message is successfully verified. The digest data includes digest information of a differential installation package between a first installation package and a second installation package and at least one of, digest information of the first installation package, or digest information of the second installation package A second message is received from the update server and includes the differential installation package. The digest data is verified, and firmware of an embedded universal integrated circuit card (eUICC) is updated based on the differential installation package after the digest data is successfully verified. | 1. A firmware update method implemented by a user equipment, the firmware update method comprising:
receiving a first message from an update server, wherein the first message comprises first data and a signature of the first data; verifying the first message; obtaining digest data from the first data after the first message is successfully verified, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment; receiving a second message from the update server, wherein the second message comprises the differential installation package; verifying the digest data; and updating firmware of an embedded universal integrated circuit card (eUICC) based on the differential installation package after the digest data is successfully verified. 2. The firmware update method of claim 1, further comprising:
obtaining fourth digest information of a third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; comparing the fourth digest information with the second digest information; obtaining fifth digest information of the differential installation package comprised in the second message when the fourth digest information is the same as the second digest information; comparing the first digest information with the fifth digest information; and determining that the digest data is successfully verified when the first digest information is the same as the fifth digest information. 3. The firmware update method of claim 1, further comprising:
obtaining fourth digest information of the differential installation package in the second message; comparing the first digest information with the fourth digest information; obtaining a third installation package and fifth digest information of the third installation package when the first digest information is the same as the fourth digest information, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; combining the third installation package with the differential installation package; obtaining a fourth installation package and sixth digest information of the fourth installation package; comparing the sixth digest information with the third digest information; and determining that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 4. The firmware update method of claim 1, further comprising:
obtaining a third installation package and fourth digest information of the third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; comparing the fourth digest information with the second digest information; obtaining fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; comparing the first digest information with the fifth digest information; when the first digest information is the same as the fifth digest information:
combining the third installation package with the differential installation package; and
obtaining a fourth installation package and sixth digest information of the fourth installation package;
comparing the sixth digest information with the third digest information; and determining that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 5. The firmware update method of claim 1, wherein the differential installation package and the digest data are stored in the update server. 6. The firmware update method of claim 1, wherein before receiving the first message, the firmware update method further comprises:
receiving a target event record and an address of the update server from an event management server based on an eUICC identity of the user equipment, wherein the target event record instructs the user equipment to perform a firmware update operation; sending a third message to the update server based on the address of the update server, wherein the third message comprises the eUICC identity; and receiving the first message from the update server based on the eUICC identity. 7. The firmware update method of claim 1, wherein before receiving the second message, the firmware update method further comprises:
sending a fourth message to the update server on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information, and wherein the fourth message enables the update server to search a pre-generated software package list based on the eUICC information to obtain the differential installation package comprised in the second message; and receiving the second message from the update server after the fourth message is successfully verified. 8. The firmware update method of claim 1, wherein after updating the firmware of the eUICC, the firmware update method further comprises:
obtaining fourth digest information of an installation package corresponding to an updated firmware version of the eUICC; and storing the fourth digest information. 9.-14. (canceled) 15. A firmware update method implemented by an update server, the firmware update method comprising:
sending a first message to a user equipment, wherein the first message comprises first data and a signature of the first data, wherein the first data comprises digest data, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment; and sending a second message comprising the differential installation package to the user equipment to enable the user equipment to update firmware of an embedded universal integrated circuit card (eUICC) based on the digest data using the differential installation package. 16. The firmware update method of claim 15, further comprising storing the differential installation package and the digest data. 17. The firmware update method of claim 15, wherein before sending the first message, the firmware update method further comprises:
receiving a third message from the user equipment based on a pre-obtained address of the update server, wherein the third message comprises an eUICC identity of the user equipment; determining the first message based on the eUICC identity; and sending the first message to the user equipment. 18. The firmware update method of claim 15, wherein before sending the second message, the firmware update method further comprises:
receiving a fourth message from the user equipment based on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information; verifying the fourth message; searching a pre-generated software package list based on the eUICC information to obtain the differential installation package; and the second message to the user equipment, wherein the second message comprises the differential installation package. 19. A user equipment, comprising:
a receiver configured to receive a first message from an update server, wherein the first message comprises first data and a signature of the first data; a processor coupled to the receiver and configured to:
verify the first message; and
obtain digest data from the first data after the first message is successfully verified, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment,
wherein the receiver is further configured to receive a second message from the update server, wherein the second message comprises the differential installation package, and wherein the processor is further configured to;
verify the digest data; and
update firmware of an embedded universal integrated circuit card (eUICC) based on the differential installation package after the digest data is successfully verified. 20. The user equipment of claim 19, wherein the process is further configured to
obtain fourth digest information of a third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; compare the fourth digest information with the second digest information; obtain fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; compare the first digest information with the fifth digest information; and determine that the digest data is successfully verified when the first digest information is the same as the fifth digest information. 21. The user equipment of claim 19, wherein the processor is further configured to:
obtain fourth digest information of the differential installation package in the second message; compare the first digest information with the fourth digest information; obtain a third installation package and fifth digest information of the third installation package when the first digest information is the same as the fourth digest information, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; combine the third installation package with the differential installation package; obtain a fourth installation package and sixth digest information of the fourth installation package; compare the sixth digest information with the third digest information; and determine that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 22. The user equipment of claim 19, wherein the processor is further configured to:
obtain a third installation package and fourth digest information of the third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; compare the fourth digest information with the second digest information; obtain fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; compare the first digest information with the fifth digest information; when the first digest information is the same as the fifth digest information:
combine the third installation package with the differential installation package; and
obtain a fourth installation package and sixth digest information of the fourth installation package;
compare the sixth digest information with the third digest information; and determine that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 23. The user equipment of claim 19, wherein the differential installation package and the digest data are stored in the update server. 24. The user equipment of claim 19, wherein receiver is further configured to receive a target event record and an address of the update server from an event management server based on an eUICC identity of the user equipment, wherein the target event record instructs the user equipment to perform a firmware update operation, wherein the user equipment further comprises a transmitter coupled to the receiver and the processor and configured to send a third message to the update server based on the address of the update server, wherein the third message comprises the eUICC identity, and wherein the receiver is further configured to receive the first message from the update server based on the eUICC identity. 25. The user equipment of claim 19, further comprising a transmitter coupled to the receiver and the processor and configured to send a fourth message to the update server based on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information, wherein the fourth message enables the update server to search a pre-generated software package list based on the eUICC information to obtain the differential installation package in the second message, and wherein the receiver is further configured to receive the second message from the update server after the fourth message is successfully verified. 26. The user equipment of claim 19, wherein the processor is further configured to:
obtain fourth digest information of an installation package corresponding to a updated firmware version of the eUICC; and store the fourth digest information. 27.-56. (canceled) | A firmware update method including receiving a first message from an update server, where the first message includes first data and a signature of the first data, verifying the first message, and obtaining digest data included in the first data after the first message is successfully verified. The digest data includes digest information of a differential installation package between a first installation package and a second installation package and at least one of, digest information of the first installation package, or digest information of the second installation package A second message is received from the update server and includes the differential installation package. The digest data is verified, and firmware of an embedded universal integrated circuit card (eUICC) is updated based on the differential installation package after the digest data is successfully verified.1. A firmware update method implemented by a user equipment, the firmware update method comprising:
receiving a first message from an update server, wherein the first message comprises first data and a signature of the first data; verifying the first message; obtaining digest data from the first data after the first message is successfully verified, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment; receiving a second message from the update server, wherein the second message comprises the differential installation package; verifying the digest data; and updating firmware of an embedded universal integrated circuit card (eUICC) based on the differential installation package after the digest data is successfully verified. 2. The firmware update method of claim 1, further comprising:
obtaining fourth digest information of a third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; comparing the fourth digest information with the second digest information; obtaining fifth digest information of the differential installation package comprised in the second message when the fourth digest information is the same as the second digest information; comparing the first digest information with the fifth digest information; and determining that the digest data is successfully verified when the first digest information is the same as the fifth digest information. 3. The firmware update method of claim 1, further comprising:
obtaining fourth digest information of the differential installation package in the second message; comparing the first digest information with the fourth digest information; obtaining a third installation package and fifth digest information of the third installation package when the first digest information is the same as the fourth digest information, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; combining the third installation package with the differential installation package; obtaining a fourth installation package and sixth digest information of the fourth installation package; comparing the sixth digest information with the third digest information; and determining that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 4. The firmware update method of claim 1, further comprising:
obtaining a third installation package and fourth digest information of the third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; comparing the fourth digest information with the second digest information; obtaining fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; comparing the first digest information with the fifth digest information; when the first digest information is the same as the fifth digest information:
combining the third installation package with the differential installation package; and
obtaining a fourth installation package and sixth digest information of the fourth installation package;
comparing the sixth digest information with the third digest information; and determining that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 5. The firmware update method of claim 1, wherein the differential installation package and the digest data are stored in the update server. 6. The firmware update method of claim 1, wherein before receiving the first message, the firmware update method further comprises:
receiving a target event record and an address of the update server from an event management server based on an eUICC identity of the user equipment, wherein the target event record instructs the user equipment to perform a firmware update operation; sending a third message to the update server based on the address of the update server, wherein the third message comprises the eUICC identity; and receiving the first message from the update server based on the eUICC identity. 7. The firmware update method of claim 1, wherein before receiving the second message, the firmware update method further comprises:
sending a fourth message to the update server on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information, and wherein the fourth message enables the update server to search a pre-generated software package list based on the eUICC information to obtain the differential installation package comprised in the second message; and receiving the second message from the update server after the fourth message is successfully verified. 8. The firmware update method of claim 1, wherein after updating the firmware of the eUICC, the firmware update method further comprises:
obtaining fourth digest information of an installation package corresponding to an updated firmware version of the eUICC; and storing the fourth digest information. 9.-14. (canceled) 15. A firmware update method implemented by an update server, the firmware update method comprising:
sending a first message to a user equipment, wherein the first message comprises first data and a signature of the first data, wherein the first data comprises digest data, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment; and sending a second message comprising the differential installation package to the user equipment to enable the user equipment to update firmware of an embedded universal integrated circuit card (eUICC) based on the digest data using the differential installation package. 16. The firmware update method of claim 15, further comprising storing the differential installation package and the digest data. 17. The firmware update method of claim 15, wherein before sending the first message, the firmware update method further comprises:
receiving a third message from the user equipment based on a pre-obtained address of the update server, wherein the third message comprises an eUICC identity of the user equipment; determining the first message based on the eUICC identity; and sending the first message to the user equipment. 18. The firmware update method of claim 15, wherein before sending the second message, the firmware update method further comprises:
receiving a fourth message from the user equipment based on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information; verifying the fourth message; searching a pre-generated software package list based on the eUICC information to obtain the differential installation package; and the second message to the user equipment, wherein the second message comprises the differential installation package. 19. A user equipment, comprising:
a receiver configured to receive a first message from an update server, wherein the first message comprises first data and a signature of the first data; a processor coupled to the receiver and configured to:
verify the first message; and
obtain digest data from the first data after the first message is successfully verified, wherein the digest data comprises first digest information of a differential installation package between a first installation package and a second installation package and at least one of second digest information of the first installation package or third digest information of the second installation package, wherein the first installation package corresponds to a current firmware version of the user equipment, and wherein the second installation package corresponds to an updated firmware version of the user equipment,
wherein the receiver is further configured to receive a second message from the update server, wherein the second message comprises the differential installation package, and wherein the processor is further configured to;
verify the digest data; and
update firmware of an embedded universal integrated circuit card (eUICC) based on the differential installation package after the digest data is successfully verified. 20. The user equipment of claim 19, wherein the process is further configured to
obtain fourth digest information of a third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; compare the fourth digest information with the second digest information; obtain fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; compare the first digest information with the fifth digest information; and determine that the digest data is successfully verified when the first digest information is the same as the fifth digest information. 21. The user equipment of claim 19, wherein the processor is further configured to:
obtain fourth digest information of the differential installation package in the second message; compare the first digest information with the fourth digest information; obtain a third installation package and fifth digest information of the third installation package when the first digest information is the same as the fourth digest information, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; combine the third installation package with the differential installation package; obtain a fourth installation package and sixth digest information of the fourth installation package; compare the sixth digest information with the third digest information; and determine that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 22. The user equipment of claim 19, wherein the processor is further configured to:
obtain a third installation package and fourth digest information of the third installation package, wherein the third installation package is locally stored by the user equipment and corresponding to the current firmware version of the user equipment; compare the fourth digest information with the second digest information; obtain fifth digest information of the differential installation package in the second message when the fourth digest information is the same as the second digest information; compare the first digest information with the fifth digest information; when the first digest information is the same as the fifth digest information:
combine the third installation package with the differential installation package; and
obtain a fourth installation package and sixth digest information of the fourth installation package;
compare the sixth digest information with the third digest information; and determine that the digest data is successfully verified when the sixth digest information is the same as the third digest information. 23. The user equipment of claim 19, wherein the differential installation package and the digest data are stored in the update server. 24. The user equipment of claim 19, wherein receiver is further configured to receive a target event record and an address of the update server from an event management server based on an eUICC identity of the user equipment, wherein the target event record instructs the user equipment to perform a firmware update operation, wherein the user equipment further comprises a transmitter coupled to the receiver and the processor and configured to send a third message to the update server based on the address of the update server, wherein the third message comprises the eUICC identity, and wherein the receiver is further configured to receive the first message from the update server based on the eUICC identity. 25. The user equipment of claim 19, further comprising a transmitter coupled to the receiver and the processor and configured to send a fourth message to the update server based on a pre-obtained address of the update server, wherein the fourth message comprises second data, a signature of the second data, and eUICC information, wherein the fourth message enables the update server to search a pre-generated software package list based on the eUICC information to obtain the differential installation package in the second message, and wherein the receiver is further configured to receive the second message from the update server after the fourth message is successfully verified. 26. The user equipment of claim 19, wherein the processor is further configured to:
obtain fourth digest information of an installation package corresponding to a updated firmware version of the eUICC; and store the fourth digest information. 27.-56. (canceled) | 2,100 |
345,487 | 16,643,404 | 2,192 | The device is comprised of oblong main body and the cup, which locks the front end of the main body. A casing of the main body is shaped as a tube. A puncture mechanism with a lancet leading unit, a puncture depth regulation mechanism and used lancet removal mechanism are installed in the casing. They compose a mechanism unit, which components are installed in a mechanism body, fastened inside the casing. The lancet leading mechanism is comprised of a lancet socket with guide, that goes through the opening in the transversal partition of the mechanism body, and lancet chamber. The guide is linked with the front end of a driving sleeve, sliding and rotary fitted in the mechanism body. Between the transversal partition and the driving sleeve there is the return spring. Between the driving sleeve and a button there is the drive spring. At the end of the casing there is the button, sliding and rotary fitted. The tension in the drive spring is released by a springy latch of the driving sleeve, that cooperates with a stop surface of the mechanism body and an activating surface of the button. The puncture depth regulation mechanism is comprised of the button rotary coupled with the driving sleeve and limiting steps limiting the movement of a bumper of the driving sleeve. | 1. A skin puncturing device, which is comprised of oblong main body, a cup closing the front end of the main body, placed against patient's skin and which has an opening for the puncturing a lancet blade, a puncturing mechanism with a lancet guiding mechanism, a drive spring of the lancet guiding mechanism, return spring of the lancet guiding mechanism, a button for tensioning the drive spring in the back part of the main body with a member releasing the drive spring tension as well as having a puncture depth regulation mechanism and a used lancet removal mechanism, characterized in that the main body have a casing in form of a tube with longitudinal axis as well as front and back ends opened, while the puncturing mechanism, the puncture depth regulation mechanism and the used lancet removal mechanism form the mechanism unit installed inside the main body, elements of the mechanism unit are placed inside the mechanism body, permanently fixed inside the casing, the front end of the mechanism body is generally flush with the front end of the casing its back end is located inside the casing, the lancet guiding mechanism is comprised of the lancet socket with oblong guide that passes through the opening in the transverse partition of the mechanism body and finished in the front end with the lancet chamber, which in the back end is linked with the front end of the driving sleeve, the driving sleeve is rotary and sliding fitted in the back part of the mechanism body, the return spring is placed between the transverse partition and the end of the driving sleeve, linked with guide of the lancet socket, the drive spring is placed between the driving sleeve and the button, the button is rotary and sliding fitted in the back end of the casing, the member releasing the drive spring tension is a springy latch of the driving sleeve, cooperating with a stop surface of the mechanism body and an activating surface of the button, whereas the puncture depth regulation mechanism is comprised of the button rotary coupled with the driving sleeve and of limiting steps limiting the movement of bumper of the driving sleeve. 2. The puncturing device according to claim 1, characterized in that the button is equipped with at least one latch, defining a sequence of angular positions of the button upon its rotation in relation to the casing and a sequence of anti-rotary channels, placed opposite the oblong fin of the mechanism body in any angular position of the button defined by the latch, whereas the button is linked with two side sliders, sliding fitted inside channels of the mechanism body, front latches of the side sliders reach inside the mechanism body, inside the mechanism body a driver setting is rotary fitted, in which the driver with notches for the front latches of the side sliders is sliding fitted in the axial direction, whereas the cup has a longitudinal channel for the lancet chamber, elements of the bayonet connector that cooperate with other components of the bayonet connector placed in the front part of the main body and at least one fin coupling the cup with the driver setting. 3. The puncturing device according to claim 1, characterized in that the used lancet removal mechanism is comprised of an ejector fitted sliding on the guide of the lancet socket between the lancet chamber and the driver, the throughfeed window for the ejector in the bottom of the lancet chamber, the button, the driving sleeve, the return spring and of the driver. 4. The puncturing device according to claim 1, characterized in that the cup is comprised of a cup sheath and a cup base permanently fixed inside of the sheath, whereas the axial channel, components of the bayonet fitting and at least one fin are integral elements of the cup base. 5. The puncturing device according to claim 2, characterized in that it is equipped with angular position indicator of the button in relation to the casing. 6. The puncturing device according to claim 5, characterized in that the angular position indicator of the button is a sequence of symbols of a consecutive angular positions of the button, located circumferentially on its side surface and a window in the casing, located above the said symbols on the released button. 7. The puncturing device according to claim 1, characterized in that the end of the button that protrudes from the casing and the cup have surfaces for the user's fingers, indicated with curvature change of the outer surface of the button and of the cup, whereas the outer surface of the casing has an elevated shape for improved gripping. | The device is comprised of oblong main body and the cup, which locks the front end of the main body. A casing of the main body is shaped as a tube. A puncture mechanism with a lancet leading unit, a puncture depth regulation mechanism and used lancet removal mechanism are installed in the casing. They compose a mechanism unit, which components are installed in a mechanism body, fastened inside the casing. The lancet leading mechanism is comprised of a lancet socket with guide, that goes through the opening in the transversal partition of the mechanism body, and lancet chamber. The guide is linked with the front end of a driving sleeve, sliding and rotary fitted in the mechanism body. Between the transversal partition and the driving sleeve there is the return spring. Between the driving sleeve and a button there is the drive spring. At the end of the casing there is the button, sliding and rotary fitted. The tension in the drive spring is released by a springy latch of the driving sleeve, that cooperates with a stop surface of the mechanism body and an activating surface of the button. The puncture depth regulation mechanism is comprised of the button rotary coupled with the driving sleeve and limiting steps limiting the movement of a bumper of the driving sleeve.1. A skin puncturing device, which is comprised of oblong main body, a cup closing the front end of the main body, placed against patient's skin and which has an opening for the puncturing a lancet blade, a puncturing mechanism with a lancet guiding mechanism, a drive spring of the lancet guiding mechanism, return spring of the lancet guiding mechanism, a button for tensioning the drive spring in the back part of the main body with a member releasing the drive spring tension as well as having a puncture depth regulation mechanism and a used lancet removal mechanism, characterized in that the main body have a casing in form of a tube with longitudinal axis as well as front and back ends opened, while the puncturing mechanism, the puncture depth regulation mechanism and the used lancet removal mechanism form the mechanism unit installed inside the main body, elements of the mechanism unit are placed inside the mechanism body, permanently fixed inside the casing, the front end of the mechanism body is generally flush with the front end of the casing its back end is located inside the casing, the lancet guiding mechanism is comprised of the lancet socket with oblong guide that passes through the opening in the transverse partition of the mechanism body and finished in the front end with the lancet chamber, which in the back end is linked with the front end of the driving sleeve, the driving sleeve is rotary and sliding fitted in the back part of the mechanism body, the return spring is placed between the transverse partition and the end of the driving sleeve, linked with guide of the lancet socket, the drive spring is placed between the driving sleeve and the button, the button is rotary and sliding fitted in the back end of the casing, the member releasing the drive spring tension is a springy latch of the driving sleeve, cooperating with a stop surface of the mechanism body and an activating surface of the button, whereas the puncture depth regulation mechanism is comprised of the button rotary coupled with the driving sleeve and of limiting steps limiting the movement of bumper of the driving sleeve. 2. The puncturing device according to claim 1, characterized in that the button is equipped with at least one latch, defining a sequence of angular positions of the button upon its rotation in relation to the casing and a sequence of anti-rotary channels, placed opposite the oblong fin of the mechanism body in any angular position of the button defined by the latch, whereas the button is linked with two side sliders, sliding fitted inside channels of the mechanism body, front latches of the side sliders reach inside the mechanism body, inside the mechanism body a driver setting is rotary fitted, in which the driver with notches for the front latches of the side sliders is sliding fitted in the axial direction, whereas the cup has a longitudinal channel for the lancet chamber, elements of the bayonet connector that cooperate with other components of the bayonet connector placed in the front part of the main body and at least one fin coupling the cup with the driver setting. 3. The puncturing device according to claim 1, characterized in that the used lancet removal mechanism is comprised of an ejector fitted sliding on the guide of the lancet socket between the lancet chamber and the driver, the throughfeed window for the ejector in the bottom of the lancet chamber, the button, the driving sleeve, the return spring and of the driver. 4. The puncturing device according to claim 1, characterized in that the cup is comprised of a cup sheath and a cup base permanently fixed inside of the sheath, whereas the axial channel, components of the bayonet fitting and at least one fin are integral elements of the cup base. 5. The puncturing device according to claim 2, characterized in that it is equipped with angular position indicator of the button in relation to the casing. 6. The puncturing device according to claim 5, characterized in that the angular position indicator of the button is a sequence of symbols of a consecutive angular positions of the button, located circumferentially on its side surface and a window in the casing, located above the said symbols on the released button. 7. The puncturing device according to claim 1, characterized in that the end of the button that protrudes from the casing and the cup have surfaces for the user's fingers, indicated with curvature change of the outer surface of the button and of the cup, whereas the outer surface of the casing has an elevated shape for improved gripping. | 2,100 |
345,488 | 16,643,406 | 2,192 | An end surface incident-type light receiving element according to an aspect of the present disclosure is made of a semiconductor material, and includes an upper surface and a lower surface that are opposite to each other in the vertical direction, and an end surface that couples the upper surface and the lower surface and is to be arranged on a light source side, the light source side being a side from which the light source emits light. At least a portion of the end surface is inclined relative to the vertical direction such that the lower surface side is arranged closer to the light source than the upper surface side is. The lower surface is provided with one or more grooves. The inclined surfaces on the end surface side of one or more grooves are arranged so as to reflect incident light that is emitted from the light source and passes through the end surface. A light receiving region for receiving the light reflected by the inclined surfaces on the end surface side of the one or more grooves is provided on the upper surface side. | 1. An end surface incident-type light receiving element made of a semiconductor material, comprising:
an upper surface and a lower surface that are opposite to each other in a vertical direction; and an end surface that couples the upper surface and the lower surface and is to be arranged on a light source side, the side being a side from which the light source emits light, wherein at least a portion of the end surface is inclined relative to the vertical direction in a state in which a portion on the lower surface side of the inclined portion is arranged closer to the light source than a portion on the upper surface side of the inclined portion is, the lower surface is provided with one or more grooves, inclined surfaces on the end surface side of the one or more grooves are arranged so as to reflect incident light that is emitted from the light source and passes through the end surface, and a light receiving region for receiving the light reflected by the inclined surfaces on the end surface side of the one or more grooves is provided on the upper surface side. 2. The end surface incident-type light receiving element according to claim 1,
wherein the entire region of the end surface is inclined relative to the vertical direction. 3. The end surface incident-type light receiving element according to claim 1,
wherein a portion on the upper surface side of the end surface is inclined relative to the vertical direction, and the remainder of the end surface is formed extending in the vertical direction. 4. The end surface incident-type light receiving element according to claim 3,
a lower end of the inclined portion on the upper surface side is located at a position that is as high as upper ends of the one or more grooves or is higher than upper ends of the one or more grooves. 5. The end surface incident-type light receiving element according to claim 3,
wherein an inclination angle A1 of the inclined portion on the upper surface side and inclination angles A2 of the inclined surfaces of the one or more grooves are set to satisfy Formula 1: 6. The end surface incident-type light receiving element according to claim 1,
wherein the portion of the end surface that is inclined relative to the vertical direction is formed in a flat shape. 7. The end surface incident-type light receiving element according to claim 1,
wherein the portion of the end surface that is inclined relative to the vertical direction is formed in a curved shape to condense the incident light emitted from the light source on at least one of the inclined surfaces on the end surface side of the one or more grooves. 8. The end surface incident-type light receiving element according to claim 1,
wherein the lower surface is provided with a plurality of the grooves, and the plurality of the grooves are arranged in a direction in which the light is incident. 9. The end surface incident-type light receiving element according to claim 1,
wherein a metal film is formed on the outer sides of the inclined surfaces on the end surface side of the one or more grooves. | An end surface incident-type light receiving element according to an aspect of the present disclosure is made of a semiconductor material, and includes an upper surface and a lower surface that are opposite to each other in the vertical direction, and an end surface that couples the upper surface and the lower surface and is to be arranged on a light source side, the light source side being a side from which the light source emits light. At least a portion of the end surface is inclined relative to the vertical direction such that the lower surface side is arranged closer to the light source than the upper surface side is. The lower surface is provided with one or more grooves. The inclined surfaces on the end surface side of one or more grooves are arranged so as to reflect incident light that is emitted from the light source and passes through the end surface. A light receiving region for receiving the light reflected by the inclined surfaces on the end surface side of the one or more grooves is provided on the upper surface side.1. An end surface incident-type light receiving element made of a semiconductor material, comprising:
an upper surface and a lower surface that are opposite to each other in a vertical direction; and an end surface that couples the upper surface and the lower surface and is to be arranged on a light source side, the side being a side from which the light source emits light, wherein at least a portion of the end surface is inclined relative to the vertical direction in a state in which a portion on the lower surface side of the inclined portion is arranged closer to the light source than a portion on the upper surface side of the inclined portion is, the lower surface is provided with one or more grooves, inclined surfaces on the end surface side of the one or more grooves are arranged so as to reflect incident light that is emitted from the light source and passes through the end surface, and a light receiving region for receiving the light reflected by the inclined surfaces on the end surface side of the one or more grooves is provided on the upper surface side. 2. The end surface incident-type light receiving element according to claim 1,
wherein the entire region of the end surface is inclined relative to the vertical direction. 3. The end surface incident-type light receiving element according to claim 1,
wherein a portion on the upper surface side of the end surface is inclined relative to the vertical direction, and the remainder of the end surface is formed extending in the vertical direction. 4. The end surface incident-type light receiving element according to claim 3,
a lower end of the inclined portion on the upper surface side is located at a position that is as high as upper ends of the one or more grooves or is higher than upper ends of the one or more grooves. 5. The end surface incident-type light receiving element according to claim 3,
wherein an inclination angle A1 of the inclined portion on the upper surface side and inclination angles A2 of the inclined surfaces of the one or more grooves are set to satisfy Formula 1: 6. The end surface incident-type light receiving element according to claim 1,
wherein the portion of the end surface that is inclined relative to the vertical direction is formed in a flat shape. 7. The end surface incident-type light receiving element according to claim 1,
wherein the portion of the end surface that is inclined relative to the vertical direction is formed in a curved shape to condense the incident light emitted from the light source on at least one of the inclined surfaces on the end surface side of the one or more grooves. 8. The end surface incident-type light receiving element according to claim 1,
wherein the lower surface is provided with a plurality of the grooves, and the plurality of the grooves are arranged in a direction in which the light is incident. 9. The end surface incident-type light receiving element according to claim 1,
wherein a metal film is formed on the outer sides of the inclined surfaces on the end surface side of the one or more grooves. | 2,100 |
345,489 | 16,643,384 | 2,192 | The present invention relates to a method for producing a mesophilic fermented dairy product by fermenting a milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain in the presence of at least one Bacillus subtilis subsp. natto or Bacillus coagulans strain. | 1. A method for producing a mesophilic fermented dairy product, comprising:
(a) providing a milk substrate, (b) fermenting said milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, wherein step (b) is conducted in the presence of at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 2. The method of claim 1, wherein the fat content of the milk substrate is between 16% and 22%. 3. The method of claim 1, wherein the fermenting in step (b) is performed at a temperature ranging from 25° C. to 35° C. 4. The method of claim 1, wherein the milk substrate is cream. 5. The method of claim 1, wherein said mesophilic lactic acid bacterium starter culture does not comprise an EPS-producing lactic acid bacterium. 6. The method of claim 1, wherein said Bacillus subtilis subsp. natto strain is selected from the Bacillus subtilis subsp. natto strains deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number DSM 32588, accession number DSM32589, and accession number DSM 32606. 7. The method of claim 1, wherein said Bacillus strain is added to the milk substrate at a concentration of 107 to 108 CFU/ml milk substrate. 8. The method of claim 1, wherein said Bacillus strain produces vitamin K. 9. The method of claim 1, wherein the method produces a mesophilic fermented dairy product selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. 10. The method of claim 1, wherein fermenting step (b) results in an increase of shear stress, gel stiffness and/or gel firmness of at least 10% relative to fermenting the milk substrate with the mesophilic lactic acid bacterium starter culture in the absence of the Bacillus strain. 11. A composition for producing a mesophilic fermented dairy product, comprising:
(a) a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, and (b) at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 12. The composition of claim 11, wherein said Lactococcus lactis strain is selected from the group consisting of Lactococcus lactis subsp. lactis strains and Lactococcus lactis subsp. cremoris strains. 13. The composition of claim 11, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM32589, and DSM 32606. 14. A mesophilic fermented dairy product obtained by the method according to claim 10. 15. A mesophilic fermented dairy product, comprising
(a) at least one Lactococcus lactis strain; (b) at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 16. The mesophilic fermented dairy product of claim 14, wherein said product is selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. 17. The mesophilic fermented dairy product of claim 16, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM 32589, and DSM 32606. 18. A method for increasing the shear stress, gel stiffness and/or gel firmness of a mesophilic fermented dairy product, comprising fermenting a milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, in the presence of at least one Bacillus strain selected from a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 19. A method according to claim 18, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM 32589, and DSM 32606. 20. A method according to claim 18, wherein said mesophilic fermented dairy product is selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. | The present invention relates to a method for producing a mesophilic fermented dairy product by fermenting a milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain in the presence of at least one Bacillus subtilis subsp. natto or Bacillus coagulans strain.1. A method for producing a mesophilic fermented dairy product, comprising:
(a) providing a milk substrate, (b) fermenting said milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, wherein step (b) is conducted in the presence of at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 2. The method of claim 1, wherein the fat content of the milk substrate is between 16% and 22%. 3. The method of claim 1, wherein the fermenting in step (b) is performed at a temperature ranging from 25° C. to 35° C. 4. The method of claim 1, wherein the milk substrate is cream. 5. The method of claim 1, wherein said mesophilic lactic acid bacterium starter culture does not comprise an EPS-producing lactic acid bacterium. 6. The method of claim 1, wherein said Bacillus subtilis subsp. natto strain is selected from the Bacillus subtilis subsp. natto strains deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number DSM 32588, accession number DSM32589, and accession number DSM 32606. 7. The method of claim 1, wherein said Bacillus strain is added to the milk substrate at a concentration of 107 to 108 CFU/ml milk substrate. 8. The method of claim 1, wherein said Bacillus strain produces vitamin K. 9. The method of claim 1, wherein the method produces a mesophilic fermented dairy product selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. 10. The method of claim 1, wherein fermenting step (b) results in an increase of shear stress, gel stiffness and/or gel firmness of at least 10% relative to fermenting the milk substrate with the mesophilic lactic acid bacterium starter culture in the absence of the Bacillus strain. 11. A composition for producing a mesophilic fermented dairy product, comprising:
(a) a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, and (b) at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 12. The composition of claim 11, wherein said Lactococcus lactis strain is selected from the group consisting of Lactococcus lactis subsp. lactis strains and Lactococcus lactis subsp. cremoris strains. 13. The composition of claim 11, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM32589, and DSM 32606. 14. A mesophilic fermented dairy product obtained by the method according to claim 10. 15. A mesophilic fermented dairy product, comprising
(a) at least one Lactococcus lactis strain; (b) at least one Bacillus strain selected from the group consisting of a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 16. The mesophilic fermented dairy product of claim 14, wherein said product is selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. 17. The mesophilic fermented dairy product of claim 16, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM 32589, and DSM 32606. 18. A method for increasing the shear stress, gel stiffness and/or gel firmness of a mesophilic fermented dairy product, comprising fermenting a milk substrate with a mesophilic lactic acid bacterium starter culture comprising at least one Lactococcus lactis strain, in the presence of at least one Bacillus strain selected from a Bacillus subtilis subsp. natto strain and a Bacillus coagulans strain. 19. A method according to claim 18, wherein said Bacillus subtilis subsp. natto strain is selected from the group consisting of strains DSM 32588, DSM 32589, and DSM 32606. 20. A method according to claim 18, wherein said mesophilic fermented dairy product is selected from the group consisting of sour cream, sour milk, buttermilk, cultured milk, smetana, quark, tvarog, fresh cheese and cream cheese. | 2,100 |
345,490 | 16,643,366 | 2,192 | The present invention provides a hard capsule comprising an outer and one inner capsule, wherein the outer capsule comprises a hydrophobic liquid and the inner capsule which comprises a composition comprising uncoated microorganisms and optionally at least one desiccant. The composition may comprise a filtrate composed of viable fecal bacteria useful forfecal microbiota transplantation (FMT) or a mixture of one or more different types of microorganisms isolated from intestinal microbiome, such as bacteria, archaea, virus, or fungi such as yeast. The composition may comprise a desiccant, preferably a food approved component which is degradable in the gastrointestinal tract. The hydrophobic liquid, if present, is preferably at least one edible oil. Also provided are methods of treating or preventing a dysbiosis in a human subject, comprising administering to the human subject at least one capsule of the invention. | 1. A hard capsule comprising an outer and one inner capsule, wherein the outer capsule comprises a hydrophobic liquid and the inner capsule which comprises a composition comprising uncoated microorganisms and optionally at least one desiccant. 2. A capsule according to claim 1, wherein the composition comprises at least one bacterium, archaea, fungus, or virus. 3. A capsule according to claim 1 or 2, wherein the composition comprises fecal microbiota. 4. A capsule according to claim 1 or 2, wherein the composition comprises no more than 20 different types of microorganisms. 5. A capsule according to claim 4, wherein the composition comprises no more than different types of bacteria. 6. A capsule according to any one of claims 1 to 5, wherein the hydrophobic liquid is at least one edible oil. 7. A capsule according to claim 6, wherein the at least one edible oil is sunflower oil, olive oil, rapeseed oil, maize oil, soya oil, linseed oil, groundnut oil, sesame oil, rice oil, thistle oil, grape seed oil, peanut oil, coconut oil, and fish oil. 8. A capsule according to any one of claims 1 to 7, wherein the edible oil comprises at least one antioxidant. 9. A capsule according to claim 8, wherein the at least one antioxidant is ascorbyl palmitate (E304), tocopherol-rich extract (E306), alpha-tocopherol (E307), gamma-tocopherol (E308), delta-tocopherol (E309), propyl gallate (E310), octyl gallate (E311), dodecyl gallate (E312), β-carotenoids, tertiary-butyl hydroxyquinone (TBHA) (E319), butylated hydroxyanisole (BHA) (E320), butylated hydroxytolvene (BHT) (E321), lecithin (E322), 4-hexylresorcinol (E586), or combinations thereof. 10. A capsule according to any one of claims 1 to 9, wherein the composition comprises at least one desiccant. 11. A capsule according to claim 10, wherein the desiccant is a food approved component which is degradable in the gastrointestinal tract. 12. A capsule according to any one of claims 1 to 11, wherein the desiccant is starch, such as potato starch, corn starch, rice starch, wheat starch, or cassava starch. 13. A capsule according to any one of claims 1 to 12, wherein the composition comprises at least one cryoprotectant. 14. A capsule according to claim 13, wherein the cryoprotectant is glycerol, carbohydrate, water soluble antioxidants as e.g. sodium ascorbate, glutathione, riboflavin, L-cysteine, or salts or combinations thereof. 15. A capsule according to any one of claims 1 to 14 for the use in the prevention or treatment of an infection or a disease, disorder or condition associated with a dysbiosis. | The present invention provides a hard capsule comprising an outer and one inner capsule, wherein the outer capsule comprises a hydrophobic liquid and the inner capsule which comprises a composition comprising uncoated microorganisms and optionally at least one desiccant. The composition may comprise a filtrate composed of viable fecal bacteria useful forfecal microbiota transplantation (FMT) or a mixture of one or more different types of microorganisms isolated from intestinal microbiome, such as bacteria, archaea, virus, or fungi such as yeast. The composition may comprise a desiccant, preferably a food approved component which is degradable in the gastrointestinal tract. The hydrophobic liquid, if present, is preferably at least one edible oil. Also provided are methods of treating or preventing a dysbiosis in a human subject, comprising administering to the human subject at least one capsule of the invention.1. A hard capsule comprising an outer and one inner capsule, wherein the outer capsule comprises a hydrophobic liquid and the inner capsule which comprises a composition comprising uncoated microorganisms and optionally at least one desiccant. 2. A capsule according to claim 1, wherein the composition comprises at least one bacterium, archaea, fungus, or virus. 3. A capsule according to claim 1 or 2, wherein the composition comprises fecal microbiota. 4. A capsule according to claim 1 or 2, wherein the composition comprises no more than 20 different types of microorganisms. 5. A capsule according to claim 4, wherein the composition comprises no more than different types of bacteria. 6. A capsule according to any one of claims 1 to 5, wherein the hydrophobic liquid is at least one edible oil. 7. A capsule according to claim 6, wherein the at least one edible oil is sunflower oil, olive oil, rapeseed oil, maize oil, soya oil, linseed oil, groundnut oil, sesame oil, rice oil, thistle oil, grape seed oil, peanut oil, coconut oil, and fish oil. 8. A capsule according to any one of claims 1 to 7, wherein the edible oil comprises at least one antioxidant. 9. A capsule according to claim 8, wherein the at least one antioxidant is ascorbyl palmitate (E304), tocopherol-rich extract (E306), alpha-tocopherol (E307), gamma-tocopherol (E308), delta-tocopherol (E309), propyl gallate (E310), octyl gallate (E311), dodecyl gallate (E312), β-carotenoids, tertiary-butyl hydroxyquinone (TBHA) (E319), butylated hydroxyanisole (BHA) (E320), butylated hydroxytolvene (BHT) (E321), lecithin (E322), 4-hexylresorcinol (E586), or combinations thereof. 10. A capsule according to any one of claims 1 to 9, wherein the composition comprises at least one desiccant. 11. A capsule according to claim 10, wherein the desiccant is a food approved component which is degradable in the gastrointestinal tract. 12. A capsule according to any one of claims 1 to 11, wherein the desiccant is starch, such as potato starch, corn starch, rice starch, wheat starch, or cassava starch. 13. A capsule according to any one of claims 1 to 12, wherein the composition comprises at least one cryoprotectant. 14. A capsule according to claim 13, wherein the cryoprotectant is glycerol, carbohydrate, water soluble antioxidants as e.g. sodium ascorbate, glutathione, riboflavin, L-cysteine, or salts or combinations thereof. 15. A capsule according to any one of claims 1 to 14 for the use in the prevention or treatment of an infection or a disease, disorder or condition associated with a dysbiosis. | 2,100 |
345,491 | 16,643,401 | 2,192 | The present invention relates to a process for producing a fermented milk product comprising the steps of: 1) adding a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate, to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product. | 1. A process for producing a fermented milk product comprising the steps of
1) adding a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate, to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product. 2. A process according to claim 1, wherein the lactose-deficient strains are capable of metabolizing a non-lactose carbohydrate selected from the group consisting of sucrose, galactose and glucose. 3. A process according to any of the preceding claims, wherein non-lactose carbohydrate is added to the milk base at the start of the fermentation step. 4. A process according to claim 3, wherein the non-lactose carbohydrate is added to the milk base in an amount measured so as to become depleted at the target pH and hence result in stopping the growth of the lactic acid bacteria and in stopping the fermentation. 5. A process according to any of the preceding claims, wherein the Streptococcus thermophilus lactose-deficient strain is selected from the group consisting of:
(a) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2014 Jun. 12 under the accession no. DSM 28952;
(ii) a strain derived from DSM 28952, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal;
(b) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2014 Jun. 12 under the accession no. DSM 28953;
(ii) a strain derived from DSM 28953, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal;
(c) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2017 Aug. 22 under the accession no. DSM 32599;
(ii) a strain derived from DSM 32599, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal; and
(d) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2017 Aug. 22 under the accession no. DSM 32600; and
(ii) a strain derived from DSM 32600, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal. 6. A process according to any of the preceding claims, wherein the Lactococcus lactis strain is selected from the group consisting of a Lactococcus lactis subsp. cremoris strain and a Lactococcus lactis subsp. lactis strain. 7. A process according to any of the preceding claims, wherein the starter culture further contains one or more strains selected from the group consisting of Lactococcus lactis subsp. lactis biovar. diacetylactis, Leuconostoc spp. and Bifidobacterium spp. 8. A process according to any of the preceding claims, wherein the fermented milk product produced is selected from the group consisting of buttermilk, sour milk, cultured milk, Smetana, sour cream, thick cream, cultured cream, ymer, fermented whey, Kefir, Yakult and fresh cheese, such as Quark, tvarog and cream cheese. 9. A process according to any of the preceding claims, wherein the lactose-deficient Lactococcus lactis strain is selected from the group consisting of
1) the strain deposited at DSMZ under the accession number DSM 32398, 2) the strain deposited at DSMZ under the accession number DSM 18882, 3) the strain deposited at DSMZ under the accession number DSM 32399, 4) the strain deposited at DSMZ under the accession number DSM 18893, 5) the strain deposited at DSMZ under the accession number DSM 32601, 6) the strain deposited at DSMZ under the accession number DSM 32602, 7) the strain deposited at DSMZ under the accession number DSM 32603, 8) the strain deposited at DSMZ under the accession number DSM 32604, 9) the strain deposited at DSMZ under the accession number DSM 32605, 10) the strain deposited at DSMZ under the accession number DSM 32829, 11) the strain deposited at DSMZ under the accession number DSM 32830, 12) the strain deposited at DSMZ under the accession number DSM 32832, and 13) a mutant of any of strains 1) to 12). 10. A composition of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain and at least one lactose-deficient Lactococcus lactis. 11. A fermented milk product produced by the process of claims 1-9. 12. Use in a process for producing a fermented milk product comprising the steps of
1) adding a starter culture of lactic acid bacteria strain to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product,
of
3) a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate. 13. Use according to claim 12 to increase the texture of the fermented milk product as compared to using a starter culture comprising at least one lactose-positive Streptococcus thermophilus strain, which is capable of metabolizing lactose, and at least one lactose-positive Lactococcus lactis strain, which is capable of metabolizing lactose. | The present invention relates to a process for producing a fermented milk product comprising the steps of: 1) adding a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate, to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product.1. A process for producing a fermented milk product comprising the steps of
1) adding a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate, to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product. 2. A process according to claim 1, wherein the lactose-deficient strains are capable of metabolizing a non-lactose carbohydrate selected from the group consisting of sucrose, galactose and glucose. 3. A process according to any of the preceding claims, wherein non-lactose carbohydrate is added to the milk base at the start of the fermentation step. 4. A process according to claim 3, wherein the non-lactose carbohydrate is added to the milk base in an amount measured so as to become depleted at the target pH and hence result in stopping the growth of the lactic acid bacteria and in stopping the fermentation. 5. A process according to any of the preceding claims, wherein the Streptococcus thermophilus lactose-deficient strain is selected from the group consisting of:
(a) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2014 Jun. 12 under the accession no. DSM 28952;
(ii) a strain derived from DSM 28952, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal;
(b) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2014 Jun. 12 under the accession no. DSM 28953;
(ii) a strain derived from DSM 28953, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal;
(c) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2017 Aug. 22 under the accession no. DSM 32599;
(ii) a strain derived from DSM 32599, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal; and
(d) (i) the strain deposited with DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, D-38124 Braunschweig, on 2017 Aug. 22 under the accession no. DSM 32600; and
(ii) a strain derived from DSM 32600, wherein the derived strain is further characterized as having the ability to generate white colonies on a medium containing lactose and X-Gal. 6. A process according to any of the preceding claims, wherein the Lactococcus lactis strain is selected from the group consisting of a Lactococcus lactis subsp. cremoris strain and a Lactococcus lactis subsp. lactis strain. 7. A process according to any of the preceding claims, wherein the starter culture further contains one or more strains selected from the group consisting of Lactococcus lactis subsp. lactis biovar. diacetylactis, Leuconostoc spp. and Bifidobacterium spp. 8. A process according to any of the preceding claims, wherein the fermented milk product produced is selected from the group consisting of buttermilk, sour milk, cultured milk, Smetana, sour cream, thick cream, cultured cream, ymer, fermented whey, Kefir, Yakult and fresh cheese, such as Quark, tvarog and cream cheese. 9. A process according to any of the preceding claims, wherein the lactose-deficient Lactococcus lactis strain is selected from the group consisting of
1) the strain deposited at DSMZ under the accession number DSM 32398, 2) the strain deposited at DSMZ under the accession number DSM 18882, 3) the strain deposited at DSMZ under the accession number DSM 32399, 4) the strain deposited at DSMZ under the accession number DSM 18893, 5) the strain deposited at DSMZ under the accession number DSM 32601, 6) the strain deposited at DSMZ under the accession number DSM 32602, 7) the strain deposited at DSMZ under the accession number DSM 32603, 8) the strain deposited at DSMZ under the accession number DSM 32604, 9) the strain deposited at DSMZ under the accession number DSM 32605, 10) the strain deposited at DSMZ under the accession number DSM 32829, 11) the strain deposited at DSMZ under the accession number DSM 32830, 12) the strain deposited at DSMZ under the accession number DSM 32832, and 13) a mutant of any of strains 1) to 12). 10. A composition of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain and at least one lactose-deficient Lactococcus lactis. 11. A fermented milk product produced by the process of claims 1-9. 12. Use in a process for producing a fermented milk product comprising the steps of
1) adding a starter culture of lactic acid bacteria strain to a milk base, and 2) fermenting the milk for a period of time until a target pH is reached to obtain a fermented milk product,
of
3) a starter culture of lactic acid bacteria comprising at least one lactose-deficient Streptococcus thermophilus strain, which is capable of metabolizing a non-lactose carbohydrate, and at least one lactose-deficient Lactococcus lactis strain, which is capable of metabolizing the non-lactose carbohydrate. 13. Use according to claim 12 to increase the texture of the fermented milk product as compared to using a starter culture comprising at least one lactose-positive Streptococcus thermophilus strain, which is capable of metabolizing lactose, and at least one lactose-positive Lactococcus lactis strain, which is capable of metabolizing lactose. | 2,100 |
345,492 | 16,643,403 | 2,192 | Provided herein are methods for determining if a subject is at risk for developing a toxicity, e.g., neurotoxicity, following administration of a therapy, such as an immunotherapy or cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy based on the expression, in a sample obtained from the subject, of one or more genes or gene products that are associated with and/or correlate to a risk of developing toxicity following administration of the therapy. In some aspects, the sample is a sample obtained from the subject prior to receiving the therapy. Also provided are methods for treating a subject having a disease or condition, such as acute lymphoblastic leukemia (ALL), according to a particular treatment regimen, in some cases involving administration of the immunotherapy or cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the methods. | 1. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising:
(1) assessing the presence, absence or level of expression of one or more gene products or portions thereof in a sample from a subject that is a candidate for receiving a immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein:
the one or more gene products is associated with a risk of developing neurotoxicity following administration of the immunotherapy; and
the sample does not comprise the immunotherapy and/or is obtained from the subject prior to receiving the immunotherapy; and
(2) comparing the presence, absence or level of expression of the one or more gene products or portions thereof to a gene reference value, wherein the comparison indicates the risk or likely risk of the subject developing a neurotoxicity, optionally a specified grade or severity of neurotoxicity, following administration of the therapy to the subject. 2. The method of claim 1, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 3. The method of claim 1 or claim 2, wherein:
(a) at least one of the one or more gene products is from a first group of gene products that negatively correlate to a risk of developing neurotoxicity; and/or
(b) at least one of the one or more gene products is from a second group of gene products that positively correlates to a risk of developing neurotoxicity. 4. The method of claim 3, wherein:
the at least one gene product is from (a) and is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAP5, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS 1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof; and/or the at least one gene product is from (b) and is selected from PINLYP, PCDHGA12, ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof. 5. A method of assessing a risk of toxicity following administration of an immunotherapy, the method comprising:
(1) assessing the presence, absence or level of expression of one or more gene products or a portion thereof in a sample from a subject that is a candidate for receiving a immunotherapy for treating a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein:
(a) at least one of the one or more gene products is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof, optionally wherein said one or more gene products negatively correlate to a risk of developing neurotoxicity; and/or
(b) at least one of the one or more gene products is selected from ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof, optionally wherein said one or more gene products positively correlates to a risk of developing neurotoxicity; and
(2) comparing the presence, absence or level of expression of the one or more gene product to a gene reference value, wherein the comparison indicates whether the subject is or is likely at risk of developing a neurotoxicity or grade or severity thereof following administration of the immunotherapy when administered to the subject. 6. The method of claim 5, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 7. The method of any of claims 1-6, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 8. The method of claim 5, claim 6 or claim 7, wherein the sample does not comprise the immunotherapy, and/or is obtained from the subject prior to receiving the immunotherapy, optionally wherein the immunotherapy is a cell therapy. 9. The method of any of claims 1-8, wherein the sample does not contain cells genetically engineered with the recombinant receptor. 10. The method of any of claims 3-9, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one gene product of (a) is at or below a gene reference value and/or the at least one gene product of (b) is at or above a gene reference value; or the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if the at least one gene product of (a) is above a gene reference value and/or the at least one gene product of (b) is below a gene reference value. 11. The method of claim 10, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 12. The method of claim 10, wherein if the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 13. The method of claim 11 or claim 12, further comprising administering the therapeutic regimen to the selected subject. 14. A method of treatment, the method comprising administering a therapeutic regimen to a subject that is a candidate for receiving an immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein the administration is carried out following or based on the results of assessing the presence, absence or level of expression, from a sample from the subject, of one or more gene products or portion thereof, wherein:
(a) at least one of the one or more gene products is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAP5, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS 1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof; and/or (b) at least one of the one or more gene products is selected from ASAP2, ATP9A, CCNA1, CDHR3, CECR2, DLX1, DPYSL3, EHD4, FMNL2, GGA2, HHIPL1, HMX3, IGF2BP1, IL3RA, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TNKS1BP1, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof, wherein the presence, absence or level of the one or more gene products from (a) negatively correlate to a risk that the subject is or is likely to develop neurotoxicity following administration of the immunotherapy when it is administered, and expression of the at least one or more gene products from (b) positively correlates to a risk that the subject is or is likely to develop neurotoxicity following administration of the immunotherapy when it is administered. 15. The method of claim 14, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 16. The method of claim 14 or 15, wherein the sample is obtained from the subject prior to receiving the immunotherapy and/or the sample does not comprise the immunotherapy. 17. The method of any of claims 14-16, wherein the results of assessing the presence, absence or level of expression of the one or more gene products or portions thereof comprises a comparison to a gene reference value, wherein the comparison indicates the risk or likely risk of the subject developing neurotoxicity following administration of the immunotherapy when administered to the subject. 18. The method of claim 17, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 19. The method of any of claims 14-18, wherein if the assessing indicates the subject is or is likely to develop neurotoxicity following administration of the immunotherapy, the therapeutic regimen comprises administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 20. The method of any of claims 14-18, wherein if the assessing indicates the subject is not or is likely not to develop neurotoxicity following administration of the immunotherapy, the therapeutic regimen comprises administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 21. The method of any of claims 3-20, wherein the at least one gene product is from (a) and is a gene product associated with a PH+ or Ph-like molecular subtype of ALL. 22. The method of claim 21, wherein the at least one gene product is selected from CCL17, ADGRF1, BMPR1B, CA6, CCR6, CD99, CHN2, CRLF2, DENND3, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, PTP4A3, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2, IL2RA, or WNT9A, or is a portion or fragment of any of the foregoing. 23. A method of treatment, the method comprising:
selecting a subject that exhibits a Philadelphia chromosome (Ph+) and/or Ph chromosome-like (Ph-like) molecular subtype of acute lymphoblastic leukemia (ALL); and administering to the subject an immunotherapy that binds to an antigen associated with the ALL. 24. The method of claim 23, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 25. The method of claim 23 or claim 24, wherein:
the selected subject exhibits one or more of (9;22)(q34;q11) chromosomal abnormality; deletion or mutation of IKZF1 transcription factor; a kinase-activating alteration, optionally a rearrangement involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2; a sequence mutation involving FLT3, IL7R, SH2B3, TYK2, IL2RB, NTRK3, DGKH, KRAS, NRAS, PTPN11, NF1; and/or comprises a Ph-like gene expression signature; or
the subject is selected based on one or more of the presence of (9;22)(q34;q11) chromosomal abnormality, deletion or mutation of IKZF1 transcription factor; a kinase-activating alteration, optionally a rearrangement involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2; a sequence mutation involving FLT3, IL7R, SH2B3, TYK2, IL2RB, NTRK3, DGKH, KRAS, NRAS, PTPN11, NF1; and/or the presence of a Ph-like gene expression signature. 26. The method of claim 25, wherein the Ph-like gene signature is based on comparison of the presence, absence or level of expression, in a sample from the subject, of at least one gene product to a reference gene value, said at least one gene product is selected from:
(a) CCL17, ADGRF1, BMPR1B, CA6, CCR6, CD99, CHN2, CRLF2, DENND3, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, PTP4A3, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2, IL2RA, or WNT9A or a portion or fragment of any of the foregoing; and/or (b) ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28 or is a portion or fragment of any of the foregoing, wherein the comparison indicates the subject exhibits a Ph-like molecular subtype of ALL if the at least one gene product of (a) is above a gene reference value and/or the at least one gene product of (b) is below a gene reference value. 27. The method of claim 26, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 28. The method of any of claims 21, 22, 26 and 27, wherein the at least one gene product selected from (a) is ADGRF1, BMPR1B, CA6, CD99, CHN2, CRLF2, DENND3, ENAM, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2 or WNT9A, or is a portion of fragment of any of the foregoing. 29. The method of any of claims 3-22 and 26-28, wherein the at least one gene product selected from (a) is ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A or is a portion or fragment of any of the foregoing. 30. The method of any of claims 3-22 and 26-29, wherein the at least one gene product selected from (b) is ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28 or is a portion or fragment of any of the foregoing. 31. The method of any of claims 1-30, wherein the subject is a human and/or the one or more gene products is human. 32. The method of any of claims 3-22 and 26-31, wherein at least one of the one or more gene products is from (a) and at least one of the one or more gene products is from (b). 33. The method of any of claims 3-22 and 26-32, wherein the one or more gene product comprises at least one gene product from (a) that is IGJ (JCHAIN), MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing. 34. The method of any of claims 3-22 and 26-33, wherein the one or more gene products comprises at least one gene product from (a) that is CCL17 or a portion or fragment thereof. 35. The method of any of claims 3-22 and 26-34, wherein the one or more gene products comprises at least one gene product from (b) that is PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 36. The method of any of claims 3-22 and 26-35, wherein the one or more gene products comprise at least one gene product from (b) that is PINLYP or PCDHGA12 or a portion or fragment of any of the foregoing. 37. The method of any of claims 13-36, wherein:
greater than or greater than about 30%, 35%, 40%, or 50% of the subjects treated according to the method do not exhibit any grade of cytokine release syndrome (CRS) or neurotoxicity; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit severe CRS, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 CRS; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit cerebral edema. 38. The method of any of claims 13-37, wherein:
prior to initiation of administration of the dose of cells, the subject has not been administered an agent or treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity; and/or the subject is not administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof, within a period of time following administration of the dose, which period of time is optionally at or about 1, 2, 3, 4, 5 days or is optionally at or about 6, 7, 8, 9, 10, 11 days or is optionally 1 or 2 or 3 or 4 weeks; and/or the subject is not administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof, following administration of the dose, prior to or unless the subject exhibits a sign or symptom of the toxicity and/or prior to or unless the subject exhibits a sign or symptom of the toxicity other than a fever, optionally wherein the fever is not a sustained fever or the fever is or has been reduced or reduced by more than 1° C. after treatment with an antipyretic; and/or the administration and any follow-up is carried out on an outpatient basis and/or without admitting the subject to a hospital and/or without an overnight stay at a hospital and/or without requiring admission to or an overnight stay at a hospital, optionally unless or until the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic. 39. The method of any of claims 13-38, wherein:
prior to initiation of administration of the dose of cells, the subject has not been administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone; the subject is not administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone, within a period of time following administration of the dose, which period of time is optionally at or about 1, 2, 3, 4, 5 days or is optionally at or about 6, 7, 8, 9, 10, 11 days or is optionally 1 or 2 or 3 or 4 weeks; and/or the subject is not administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone, following administration of the cell dose, prior to, or unless, the subject exhibits a sign or symptom of a toxicity, optionally a neurotoxicity or CRS, and/or prior to, or unless, the subject exhibits a sign or symptom of a toxicity, optionally a neurotoxicity or CRS, other than a fever, optionally wherein the fever is not a sustained fever or the fever is or has been reduced or reduced by more than 1° C. after treatment with an antipyretic; and/or the administration and any follow-up is carried out on an outpatient basis and/or without admitting the subject to a hospital and/or without an overnight stay at a hospital and/or without requiring admission to or an overnight stay at a hospital, optionally unless or until the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic. 40. The method of any of claims 13-39, wherein:
the administration is carried out on an outpatient basis and/or without requiring admission to or an overnight stay at a hospital; and if the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic, the subject is admitted to the hospital or to an overnight stay at a hospital and/or is administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof. 41. The method of any of claims 1-40, wherein the neurotoxicity comprises severe neurotoxicity, optionally at or above grade 4 or grade 5 or at least prolonged grade 3 neurotoxicity. 42. The method of any of claims 1-41, wherein the ALL is adult ALL or pediatric ALL. 43. The method of any of claims 1-42, wherein the sample is or comprises a bone marrow sample, blood sample, plasma sample, or serum sample. 44. The method of any of claims 1-43, wherein the sample is or comprises a bone marrow aspirate. 45. The method of any of claims 1-43, wherein the sample is or comprises a serum or plasma sample. 46. The method of any of claims 1-45, wherein the presence, absence or level of expression of one, two, three, four, five, six, seven, eight, nine, ten or more gene products is assessed or compared. 47. The method of any of claims 1-46, wherein the one or more gene products or portion or fragment thereof is a polynucleotide or a portion thereof. 48. The method of claim 47, wherein the polynucleotide is an RNA. 49. The method of any of claims 1-46, wherein the one or more gene products or portions thereof comprise a protein or a portion thereof. 50. The method of claim 49, wherein the one or more gene products is a gene product from (s) selected from CCL17, ENG, SELE, ICAM3, or IL6R. 51. The method of any of claims 3-50, wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is above the highest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the at least one gene product as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 52. The method of claim 51, further wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the at least one gene product observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the at least one gene product measured as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the same disease or condition, wherein each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 53. The method of any of claims 3-70, wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is above the highest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 54. The method of claim 53, further wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the at least one gene product observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a plurality of control samples, wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the same disease or condition, wherein each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 55. The method of any of claims 3-54, wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% below the average level, concentration or amount, and/or is within a standard deviation below the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is below the lowest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; iii) is below the lowest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 56. The method of claim 55, further wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b) is:
above the highest level, concentration, or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such level, concentration or amount, measured in at least one sample from among a second plurality of control samples; and/or above the level, concentration or amount of the at least one gene product measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples, wherein the second plurality of control samples are a plurality of control samples obtained from a group of subjects prior to receiving the immunotherapy for treating the disease or condition, wherein each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 57. The method of any of claims 3-54, wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% below the average level, concentration or amount, and/or is within a standard deviation below the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is below the lowest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below such lowest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; iii) is below the lowest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group has ALL that is not Philadelphia chromosome positive (PH+) or Philadelphia-like (Ph-like) subtype of ALL. 58. The method of claim 57, further wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b) is:
above the highest level, concentration, or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such level, concentration or amount, measured in at least one sample from among a second plurality of control samples; and/or is above the level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a second plurality of control samples, wherein the second plurality of control samples are a plurality of control samples obtained from a group of subjects prior to receiving the immunotherapy for treating the same disease or condition, wherein each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 59. The method of any of claims 51-58, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a bone marrow sample or aspirate or is a plasma sample. 60. The method of any of claims 51-59, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 61. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising
(a) assessing the level or amount of one or more proteins or portions thereof in a biological sample from a subject that is a candidate for receiving a immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein at least one of the one the one or more proteins or portions thereof are selected from CCL17, ENG, SELE, ICAM3, or IL6R; and (b) comparing the level or amount of the one or more proteins or portions thereof to a reference value, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one of the one or more proteins or portions thereof is at or below the reference value; or
the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if at least one of the one or more protein or portions thereof is above the reference value. 62. The method of claim 61, wherein the biological sample is a plasma sample. 63. The method of claim 61 or claim 62, wherein at least one of the one or more proteins or portions thereof is CCL17. 64. The method of any of claims 61-63, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 65. The method of any of claims 61-64, wherein the sample does not comprise the immunotherapy, and/or is obtained from the subject prior to receiving the immunotherapy. 66. The method of any of claims 61-65, wherein the reference value for the one or more protein or portion thereof, or each of the reference values individually for each of the one or more protein or portion thereof, is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the one or more protein or portion thereof in a plurality of control samples; ii) is above the highest level, concentration or amount of the one or more protein or portion thereof, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the one or more protein or portion thereof as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein (1) each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition; or (2) each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 67. The method of claim 66, further wherein the reference value for the one or more protein or portion thereof, or each of the gene reference values individually for each of the one or more protein or portion thereof, is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the one or more protein or portion thereof observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the one or more protein or portion thereof as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples, wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the ALL, wherein (1) each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition, or (2) each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 68. The method of claim 66 or claim 67, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a plasma sample. 69. The method of any of claims 66-68, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 70. The method of any of claims 61-69, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 71. The method of any of claims 61-69, wherein if the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 72. The method of any of claims 61-71, further comprising administering the therapeutic regimen to the selected subject. 73. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising
(a) assessing the level or amount of one or more proteins or portions thereof in a biological sample from a subject that received an immunotherapy for treatment of a disease or condition, wherein:
at least one of the one the one or more proteins or portions thereof are selected from CCL27, ENG, FAS, 1-309, ICAM3, NSE, P-Selectin, Resistin, S100(3, Thrombomodulin or vWF; and
(b) comparing the level or amount of the one or more proteins or portions thereof to a reference value, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one of the one or more proteins or portions thereof is at or below the reference value; or
the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if at least one of the one or more protein or portions thereof is above the reference value. 74. The method of claim 73, wherein the biological sample is a plasma sample. 75. The method of claim 73 or claim 74, wherein the biological sample is obtained or collected from the subject no more than 4 days, no more than 3 days, no more than 2 days or no more than 1 day, after initiation of administration of the immunotherapy and/or before the subject exhibits a sign or symptom of the toxicity and/or before the subjects develops a sustained fever. 76. The method of any of claims 73-75, wherein at least one of the one or more proteins or portions thereof is ENG or ICAM3. 77. The method of any of claims 73-76, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 78. The method of any of claims 73-77, wherein the reference value for the one or more protein or portion thereof, or each of the reference values individually for each of the one or more protein or portion thereof, is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the one or more protein or portion thereof in a plurality of control samples; ii) is above the highest level, concentration or amount of the one or more protein or portion thereof, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the one or more protein or portion thereof as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects after receiving a immunotherapy for treating ALL, wherein (1) each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition; or (2) each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 79. The method of claim 78, further wherein the reference value for the one or more protein or portion thereof, or each of the gene reference values individually for each of the one or more protein or portion thereof, is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the one or more protein or portion thereof observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the one or more protein or portion thereof as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples,
wherein the second plurality of control samples is obtained from a group of subjects after receiving the same immunotherapy for treating the ALL, wherein (1) each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition, or (2) each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 80. The method of claim 78 or claim 79, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a plasma sample. 81. The method of any of claims 78-80, wherein the control sample or each of the plurality of control samples had been obtained or collected from the subject no more than 4 days, no more than 3 days, no more than 2 days or no more than 1 day, after initiation of administration of the immunotherapy and/or before the subject exhibits a sign or symptom of the toxicity and/or before the subjects develops a sustained fever. 82. The method of any of claims 78-81, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 83. The method of any of claims 73-83, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, administering to the subject an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy. 84. The method of claim 83, wherein administration of the agent is to be administered within one, two, or three days of and/or at first fever following, the initiation of administration of the immunotherapy to the subject. 85. The method of any of claims 1-88, wherein the immunotherapy specifically binds to an antigen associated with the disease or condition or expressed in cells of the environment of a lesion associated with the disease or condition. 86. The method of claim 85, wherein the antigen is CD19, CD20, CD22 or CD123. 87. The method of any of claim 1-86, wherein the immunotherapy is a T cell-engaging therapy comprising a bispecific antibody, wherein at least one binding portion specifically binds to a T cell antigen and a second binding portion binds to the antigen associated with the disease or condition or expressed in cells of the environment of a lesion associated with the disease or condition. 88. The method of claim 87, wherein the T cell antigen is CD3. 89. The method of claim 87 or 88, wherein the second binding portion binds CD19. 90. The method of any of claims 87-89, wherein the bispecific antibody is blinatumomab. 91. The method of any of claims 1-86, wherein the immunotherapy is a cell therapy, wherein the cell therapy comprises genetically engineered cells expressing a recombinant receptor. 92. The method of claim 91, wherein the genetically engineered cells comprise T cells or NK cells. 93. The method of claim 91 or claim 92, wherein the engineered cells comprise T cells. 94. The method of any of claims 1-86 and 91-93, wherein the immunotherapy is a T cell therapy comprising genetically engineered T cells expressing a recombinant receptor. 95. The method of claim 94, wherein the T cells comprise CD4+ and/or CD8+ T cells 96. The method of any of claims 91-95, wherein the recombinant receptor is a T cell receptor or a functional non-T cell receptor. 97. The method of any of claims 91-96, wherein the recombinant receptor is a chimeric antigen receptor (CAR). 98. The method of any of claims 91-97, wherein the recombinant receptor is an anti-CD19 CAR. 99. The method of claim 97 or 98, wherein the CAR comprises an extracellular antigen-recognition domain that specifically binds to the antigen and an intracellular signaling domain comprising an ITAM, wherein optionally, the intracellular signaling domain comprises an intracellular domain of a CD3-zeta (CDζ) chain; and/or wherein the CAR further comprises a costimulatory signaling region, which optionally comprises a signaling domain of CD28 or 4-1BB. 100. The method of any of claims 91-99, wherein the risk or likely risk of the subject developing neurotoxicity following administration of the cell therapy is further based on the value of a parameter that indicates or correlates with the degree of recombinant receptor-dependent, optionally CAR-dependent, activity of the composition, wherein if the value of the parameter is at or greater than a threshold value the subject is at risk of developing neurotoxicity following administration of the immunotherapy when administered to the subject. 101. The method of claim 100, wherein the recombinant receptor-dependent activity comprises a measure of the production or accumulation of one or more of a proinflammatory cytokine, or a normalized value thereof. 102. The method of claim 101, wherein the proinflammatory cytokine is TNF-alpha, IFN-gamma, IL-2, IL-10, or a combination thereof. 103. The method of any of claims 91-103, wherein the immunotherapy comprises the administration of from or from about 1×105 to 1×108 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs), from or from about 5×105 to 1×107 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs) or from or from about 1×106 to 1×107 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs), each inclusive. 104. The method of claim 19 or claim 70, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 2×106 to 5×107 total recombinant receptor-expressing cells, inclusive, or that is from or from about 2×105 cells/kg to 5×105 cells/kg total recombinant receptor-expressing cells, inclusive. 105. The method of claim 20 or claim 71, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 1×107 to 2.0×108 total recombinant receptor-expressing cells, inclusive, or that is from or from about 1×106 cells/kg to 2×106 cells/kg total recombinant receptor-expressing cells, inclusive. 106. The method of claim 23-30, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 1×107 to 2.0×108 total recombinant receptor-expressing cells, inclusive, or the subject is administered a dose that is from or from about 1×106 cells/kg to 2×106 cells/kg total recombinant receptor-expressing cells, inclusive. 107. The method of any of claims 1-106, wherein the subject is an adult human subject. 108. The method of any of claims 1-106, wherein the subject is a pediatric human subject. 109. A kit, comprising reagents for detecting the expression of two or more gene products or portions thereof in a sample, wherein the two or more gene products are encoded by two or more of CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, ZNF415, ENG, SELE, ICAM3, PCDHGA9, FMNL1, or IL6R, or a portion or a fragment of any of the forgoing. 110. The kit of claim 109, wherein the two or more gene products are human gene products. 111. The kit of claim 109 or 110, wherein the kit comprises reagents for detecting the expression of at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 gene products. 112. The kit of any of claims 109-111, wherein at least one of the two or more gene products is from a first group of gene products that negatively correlate to a risk of developing neurotoxicity, wherein the first group comprises gene products encoded by CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCL17, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 113. The kit of any of claims 109-112, wherein at least one of the two or more gene products is a gene product encoded by ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, JCHAIN, MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A, or is a portion or a fragment of any of the forgoing. 114. The kit of any of claims 109-113, wherein at least one of the two or more gene products is a gene product encoded by JCHAIN, MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing. 115. The kit of any of claims 109-112, wherein at least one of the two or more gene products is a gene product encoded by CCL17, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 116. The kit of any of claims 109-115, wherein at least one of the two or more gene products is a gene product encoded by CCL17 or is a portion or fragment thereof. 117. The kit of any of claims 109-116, wherein at least one of the two or more gene products is from a second group of gene products that positively correlate to a risk of developing neurotoxicity, wherein the second group comprises gene products encoded by ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGBS, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, and ZNF415, or portions or a fragments of any of the forgoing. 118. The kit of any of claims 109-117, wherein at least one of the two or more gene products is a gene product encoded by ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGBS, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28, or is a portion or fragment of any of the foregoing. 119. The kit of any of claims 109-118, wherein at least one of the two or more gene products is a gene product encoded by PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 120. The kit of any of claims 109-119, wherein at least one of the two or more gene products is a gene product encoded by PINLYP or PCDHGA12, or a portion or fragment of any of the foregoing. 121. The kit of any of claims 109-119 wherein:
at least one of the two or more gene products is a gene product, or a portion or fragment thereof, from a first group of gene products that negatively correlate to a risk of developing neurotoxicity selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCL17, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing; and
at least one of the gene products is a gene product, or a portion or fragment thereof, from a second group of gene products that positively correlate to a risk of developing neurotoxicity selected from ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGBS, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, and ZNF415, or portions or a fragments of any of the forgoing. 122. The kit of claim 121, wherein the at least one of the gene products from the first group is a gene product encoded by ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, JCHAIN, MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A, or is a portion or a fragment of any of the forgoing;
and wherein the at least one of the gene products from the second group is a gene product encoded by ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGBS, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28, or is a portion or fragment of any of the foregoing. 123. The kit of claim 121 or 122, wherein the at least one of the gene products from the first group is a gene product encoded by JCHAIN, MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing; and
wherein the at least one of the gene products from the second group is a gene product encoded by PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 124. The kit of any of claims 121-123, wherein:
the at least one of the gene products from the first group is a gene product encoded by CCL17 or is a portion or fragment thereof; and the at least one of the gene products from the second group is a gene product encoded by PINLYP or PCDHGA12, or a portion or fragment thereof. 125. The kit of any of claims 109-124, wherein the two or more gene products are or comprise mRNA. 126. The kit of claim 125, wherein the reagents comprise one or more oligonucleotide and/or polynucleotide probes that are to, bind to, and/or are capable of binding to the one or more mRNA gene products. 127. The kit of any of claims 109-124, wherein the two or more gene products are or comprise proteins or variants or fragments thereof. 128. The kit of claim 127, wherein the two or more gene products are selected from CCL17, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 129. The kit of claim 128, wherein the reagents are or comprise antibodies or antigen binding fragments or variants thereof, wherein the antibodies or the antigen binding fragments or variants thereof bind to and/or are capable of binding to the protein gene products. 130. The kit of any of claims 109-129, further comprising an immunotherapy. 131. The kit of claim 130, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 132. The kit of any of claims 109-131, for use in connection the method of any of claims 1-108. 133. An article of manufacture, comprising a kit of any one of claims 109-134, and instructions for using the reagents to assay a biological sample from a subject that is a candidate for treatment, optionally with an immunotherapy. 134. The article of manufacture of claims 133, wherein the instructions specify carrying out the method of any of claims 1-108. 135. An article of manufacture comprising an immunotherapy and instructions for administering the immunotherapy to a subject that exhibits a Philadelphia chromosome (Ph+) and/or Ph chromosome-like (Ph-like) molecular subtype of acute lymphoblastic leukemia (ALL). 136. The article of manufacture of claim 135, wherein the immunotherapy is a immunotherapy or is a T cell-engaging therapy, optionally wherein the immunotherapy comprises cells engineered to express a recombinant receptor. | Provided herein are methods for determining if a subject is at risk for developing a toxicity, e.g., neurotoxicity, following administration of a therapy, such as an immunotherapy or cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy based on the expression, in a sample obtained from the subject, of one or more genes or gene products that are associated with and/or correlate to a risk of developing toxicity following administration of the therapy. In some aspects, the sample is a sample obtained from the subject prior to receiving the therapy. Also provided are methods for treating a subject having a disease or condition, such as acute lymphoblastic leukemia (ALL), according to a particular treatment regimen, in some cases involving administration of the immunotherapy or cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the methods.1. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising:
(1) assessing the presence, absence or level of expression of one or more gene products or portions thereof in a sample from a subject that is a candidate for receiving a immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein:
the one or more gene products is associated with a risk of developing neurotoxicity following administration of the immunotherapy; and
the sample does not comprise the immunotherapy and/or is obtained from the subject prior to receiving the immunotherapy; and
(2) comparing the presence, absence or level of expression of the one or more gene products or portions thereof to a gene reference value, wherein the comparison indicates the risk or likely risk of the subject developing a neurotoxicity, optionally a specified grade or severity of neurotoxicity, following administration of the therapy to the subject. 2. The method of claim 1, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 3. The method of claim 1 or claim 2, wherein:
(a) at least one of the one or more gene products is from a first group of gene products that negatively correlate to a risk of developing neurotoxicity; and/or
(b) at least one of the one or more gene products is from a second group of gene products that positively correlates to a risk of developing neurotoxicity. 4. The method of claim 3, wherein:
the at least one gene product is from (a) and is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAP5, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS 1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof; and/or the at least one gene product is from (b) and is selected from PINLYP, PCDHGA12, ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof. 5. A method of assessing a risk of toxicity following administration of an immunotherapy, the method comprising:
(1) assessing the presence, absence or level of expression of one or more gene products or a portion thereof in a sample from a subject that is a candidate for receiving a immunotherapy for treating a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein:
(a) at least one of the one or more gene products is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof, optionally wherein said one or more gene products negatively correlate to a risk of developing neurotoxicity; and/or
(b) at least one of the one or more gene products is selected from ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof, optionally wherein said one or more gene products positively correlates to a risk of developing neurotoxicity; and
(2) comparing the presence, absence or level of expression of the one or more gene product to a gene reference value, wherein the comparison indicates whether the subject is or is likely at risk of developing a neurotoxicity or grade or severity thereof following administration of the immunotherapy when administered to the subject. 6. The method of claim 5, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 7. The method of any of claims 1-6, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 8. The method of claim 5, claim 6 or claim 7, wherein the sample does not comprise the immunotherapy, and/or is obtained from the subject prior to receiving the immunotherapy, optionally wherein the immunotherapy is a cell therapy. 9. The method of any of claims 1-8, wherein the sample does not contain cells genetically engineered with the recombinant receptor. 10. The method of any of claims 3-9, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one gene product of (a) is at or below a gene reference value and/or the at least one gene product of (b) is at or above a gene reference value; or the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if the at least one gene product of (a) is above a gene reference value and/or the at least one gene product of (b) is below a gene reference value. 11. The method of claim 10, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 12. The method of claim 10, wherein if the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 13. The method of claim 11 or claim 12, further comprising administering the therapeutic regimen to the selected subject. 14. A method of treatment, the method comprising administering a therapeutic regimen to a subject that is a candidate for receiving an immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein the administration is carried out following or based on the results of assessing the presence, absence or level of expression, from a sample from the subject, of one or more gene products or portion thereof, wherein:
(a) at least one of the one or more gene products is selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAP5, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS 1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, or is a portion or fragment thereof; and/or (b) at least one of the one or more gene products is selected from ASAP2, ATP9A, CCNA1, CDHR3, CECR2, DLX1, DPYSL3, EHD4, FMNL2, GGA2, HHIPL1, HMX3, IGF2BP1, IL3RA, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TNKS1BP1, TTC28, PCDHGA9, FMNL1, or ZNF415 or is a portion or fragment thereof, wherein the presence, absence or level of the one or more gene products from (a) negatively correlate to a risk that the subject is or is likely to develop neurotoxicity following administration of the immunotherapy when it is administered, and expression of the at least one or more gene products from (b) positively correlates to a risk that the subject is or is likely to develop neurotoxicity following administration of the immunotherapy when it is administered. 15. The method of claim 14, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 16. The method of claim 14 or 15, wherein the sample is obtained from the subject prior to receiving the immunotherapy and/or the sample does not comprise the immunotherapy. 17. The method of any of claims 14-16, wherein the results of assessing the presence, absence or level of expression of the one or more gene products or portions thereof comprises a comparison to a gene reference value, wherein the comparison indicates the risk or likely risk of the subject developing neurotoxicity following administration of the immunotherapy when administered to the subject. 18. The method of claim 17, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 19. The method of any of claims 14-18, wherein if the assessing indicates the subject is or is likely to develop neurotoxicity following administration of the immunotherapy, the therapeutic regimen comprises administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 20. The method of any of claims 14-18, wherein if the assessing indicates the subject is not or is likely not to develop neurotoxicity following administration of the immunotherapy, the therapeutic regimen comprises administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 21. The method of any of claims 3-20, wherein the at least one gene product is from (a) and is a gene product associated with a PH+ or Ph-like molecular subtype of ALL. 22. The method of claim 21, wherein the at least one gene product is selected from CCL17, ADGRF1, BMPR1B, CA6, CCR6, CD99, CHN2, CRLF2, DENND3, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, PTP4A3, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2, IL2RA, or WNT9A, or is a portion or fragment of any of the foregoing. 23. A method of treatment, the method comprising:
selecting a subject that exhibits a Philadelphia chromosome (Ph+) and/or Ph chromosome-like (Ph-like) molecular subtype of acute lymphoblastic leukemia (ALL); and administering to the subject an immunotherapy that binds to an antigen associated with the ALL. 24. The method of claim 23, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 25. The method of claim 23 or claim 24, wherein:
the selected subject exhibits one or more of (9;22)(q34;q11) chromosomal abnormality; deletion or mutation of IKZF1 transcription factor; a kinase-activating alteration, optionally a rearrangement involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2; a sequence mutation involving FLT3, IL7R, SH2B3, TYK2, IL2RB, NTRK3, DGKH, KRAS, NRAS, PTPN11, NF1; and/or comprises a Ph-like gene expression signature; or
the subject is selected based on one or more of the presence of (9;22)(q34;q11) chromosomal abnormality, deletion or mutation of IKZF1 transcription factor; a kinase-activating alteration, optionally a rearrangement involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2; a sequence mutation involving FLT3, IL7R, SH2B3, TYK2, IL2RB, NTRK3, DGKH, KRAS, NRAS, PTPN11, NF1; and/or the presence of a Ph-like gene expression signature. 26. The method of claim 25, wherein the Ph-like gene signature is based on comparison of the presence, absence or level of expression, in a sample from the subject, of at least one gene product to a reference gene value, said at least one gene product is selected from:
(a) CCL17, ADGRF1, BMPR1B, CA6, CCR6, CD99, CHN2, CRLF2, DENND3, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, PTP4A3, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2, IL2RA, or WNT9A or a portion or fragment of any of the foregoing; and/or (b) ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28 or is a portion or fragment of any of the foregoing, wherein the comparison indicates the subject exhibits a Ph-like molecular subtype of ALL if the at least one gene product of (a) is above a gene reference value and/or the at least one gene product of (b) is below a gene reference value. 27. The method of claim 26, wherein each of the one or more gene products is individually compared to a gene reference value for the respective gene product. 28. The method of any of claims 21, 22, 26 and 27, wherein the at least one gene product selected from (a) is ADGRF1, BMPR1B, CA6, CD99, CHN2, CRLF2, DENND3, ENAM, GBP5, GLI2, IFITM1, IGJ (JCHAIN), LDB3, L0645744, MDF1C, MUC4, NRXN3, PON2, S100Z, SEMA6A, SLC37A3, SLC2A5, SPATS2L, TMEM154, TP53INP1, TTYH2 or WNT9A, or is a portion of fragment of any of the foregoing. 29. The method of any of claims 3-22 and 26-28, wherein the at least one gene product selected from (a) is ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, IGJ (JCHAIN), MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A or is a portion or fragment of any of the foregoing. 30. The method of any of claims 3-22 and 26-29, wherein the at least one gene product selected from (b) is ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGB5, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28 or is a portion or fragment of any of the foregoing. 31. The method of any of claims 1-30, wherein the subject is a human and/or the one or more gene products is human. 32. The method of any of claims 3-22 and 26-31, wherein at least one of the one or more gene products is from (a) and at least one of the one or more gene products is from (b). 33. The method of any of claims 3-22 and 26-32, wherein the one or more gene product comprises at least one gene product from (a) that is IGJ (JCHAIN), MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing. 34. The method of any of claims 3-22 and 26-33, wherein the one or more gene products comprises at least one gene product from (a) that is CCL17 or a portion or fragment thereof. 35. The method of any of claims 3-22 and 26-34, wherein the one or more gene products comprises at least one gene product from (b) that is PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 36. The method of any of claims 3-22 and 26-35, wherein the one or more gene products comprise at least one gene product from (b) that is PINLYP or PCDHGA12 or a portion or fragment of any of the foregoing. 37. The method of any of claims 13-36, wherein:
greater than or greater than about 30%, 35%, 40%, or 50% of the subjects treated according to the method do not exhibit any grade of cytokine release syndrome (CRS) or neurotoxicity; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit severe CRS, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 CRS; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity; and/or at least at or about 45, 50, 60, 65, 70, 75, 80, 85, 90, 95% or about 100% of subjects treated according to the method do not exhibit cerebral edema. 38. The method of any of claims 13-37, wherein:
prior to initiation of administration of the dose of cells, the subject has not been administered an agent or treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity; and/or the subject is not administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof, within a period of time following administration of the dose, which period of time is optionally at or about 1, 2, 3, 4, 5 days or is optionally at or about 6, 7, 8, 9, 10, 11 days or is optionally 1 or 2 or 3 or 4 weeks; and/or the subject is not administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof, following administration of the dose, prior to or unless the subject exhibits a sign or symptom of the toxicity and/or prior to or unless the subject exhibits a sign or symptom of the toxicity other than a fever, optionally wherein the fever is not a sustained fever or the fever is or has been reduced or reduced by more than 1° C. after treatment with an antipyretic; and/or the administration and any follow-up is carried out on an outpatient basis and/or without admitting the subject to a hospital and/or without an overnight stay at a hospital and/or without requiring admission to or an overnight stay at a hospital, optionally unless or until the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic. 39. The method of any of claims 13-38, wherein:
prior to initiation of administration of the dose of cells, the subject has not been administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone; the subject is not administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone, within a period of time following administration of the dose, which period of time is optionally at or about 1, 2, 3, 4, 5 days or is optionally at or about 6, 7, 8, 9, 10, 11 days or is optionally 1 or 2 or 3 or 4 weeks; and/or the subject is not administered an anti-IL-6 or anti-IL-6R antibody, optionally tocilizumab or siltuximab, and/or has not been administered a steroid, optionally dexamethasone, following administration of the cell dose, prior to, or unless, the subject exhibits a sign or symptom of a toxicity, optionally a neurotoxicity or CRS, and/or prior to, or unless, the subject exhibits a sign or symptom of a toxicity, optionally a neurotoxicity or CRS, other than a fever, optionally wherein the fever is not a sustained fever or the fever is or has been reduced or reduced by more than 1° C. after treatment with an antipyretic; and/or the administration and any follow-up is carried out on an outpatient basis and/or without admitting the subject to a hospital and/or without an overnight stay at a hospital and/or without requiring admission to or an overnight stay at a hospital, optionally unless or until the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic. 40. The method of any of claims 13-39, wherein:
the administration is carried out on an outpatient basis and/or without requiring admission to or an overnight stay at a hospital; and if the subject exhibits a sustained fever or a fever that is or has not been reduced or not reduced by more than 1° C. after treatment with an antipyretic, the subject is admitted to the hospital or to an overnight stay at a hospital and/or is administered an agent or treatment for the treatment or prevention or reduction or attenuation of a neurotoxicity and/or a cytokine release syndrome or risk thereof. 41. The method of any of claims 1-40, wherein the neurotoxicity comprises severe neurotoxicity, optionally at or above grade 4 or grade 5 or at least prolonged grade 3 neurotoxicity. 42. The method of any of claims 1-41, wherein the ALL is adult ALL or pediatric ALL. 43. The method of any of claims 1-42, wherein the sample is or comprises a bone marrow sample, blood sample, plasma sample, or serum sample. 44. The method of any of claims 1-43, wherein the sample is or comprises a bone marrow aspirate. 45. The method of any of claims 1-43, wherein the sample is or comprises a serum or plasma sample. 46. The method of any of claims 1-45, wherein the presence, absence or level of expression of one, two, three, four, five, six, seven, eight, nine, ten or more gene products is assessed or compared. 47. The method of any of claims 1-46, wherein the one or more gene products or portion or fragment thereof is a polynucleotide or a portion thereof. 48. The method of claim 47, wherein the polynucleotide is an RNA. 49. The method of any of claims 1-46, wherein the one or more gene products or portions thereof comprise a protein or a portion thereof. 50. The method of claim 49, wherein the one or more gene products is a gene product from (s) selected from CCL17, ENG, SELE, ICAM3, or IL6R. 51. The method of any of claims 3-50, wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is above the highest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the at least one gene product as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 52. The method of claim 51, further wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the at least one gene product observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the at least one gene product measured as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the same disease or condition, wherein each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 53. The method of any of claims 3-70, wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is above the highest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 54. The method of claim 53, further wherein the gene reference value for the at least one gene product of (a), or each of the gene reference values individually for each of the at least one or more gene product of (a), is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the at least one gene product observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a plurality of control samples, wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the same disease or condition, wherein each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 55. The method of any of claims 3-54, wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% below the average level, concentration or amount, and/or is within a standard deviation below the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is below the lowest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; iii) is below the lowest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 56. The method of claim 55, further wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b) is:
above the highest level, concentration, or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such level, concentration or amount, measured in at least one sample from among a second plurality of control samples; and/or above the level, concentration or amount of the at least one gene product measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples, wherein the second plurality of control samples are a plurality of control samples obtained from a group of subjects prior to receiving the immunotherapy for treating the disease or condition, wherein each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition. 57. The method of any of claims 3-54, wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b), is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% below the average level, concentration or amount, and/or is within a standard deviation below the average level, concentration or amount, of the at least one gene product in a plurality of control samples; ii) is below the lowest level, concentration or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below such lowest level, concentration or amount, as measured in at least one sample from among a plurality of control samples; iii) is below the lowest level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein each of the subjects of the group has ALL that is not Philadelphia chromosome positive (PH+) or Philadelphia-like (Ph-like) subtype of ALL. 58. The method of claim 57, further wherein the gene reference value for the at least one gene product of (b), or each of the gene reference values individually for each of the at least one or more gene product of (b) is:
above the highest level, concentration, or amount of the at least one gene product, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such level, concentration or amount, measured in at least one sample from among a second plurality of control samples; and/or is above the level, concentration or amount of the at least one gene product measured among more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from a second plurality of control samples, wherein the second plurality of control samples are a plurality of control samples obtained from a group of subjects prior to receiving the immunotherapy for treating the same disease or condition, wherein each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 59. The method of any of claims 51-58, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a bone marrow sample or aspirate or is a plasma sample. 60. The method of any of claims 51-59, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 61. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising
(a) assessing the level or amount of one or more proteins or portions thereof in a biological sample from a subject that is a candidate for receiving a immunotherapy for treatment of a disease or condition, wherein the disease or condition is acute lymphoblastic leukemia (ALL) or a subtype thereof, wherein at least one of the one the one or more proteins or portions thereof are selected from CCL17, ENG, SELE, ICAM3, or IL6R; and (b) comparing the level or amount of the one or more proteins or portions thereof to a reference value, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one of the one or more proteins or portions thereof is at or below the reference value; or
the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if at least one of the one or more protein or portions thereof is above the reference value. 62. The method of claim 61, wherein the biological sample is a plasma sample. 63. The method of claim 61 or claim 62, wherein at least one of the one or more proteins or portions thereof is CCL17. 64. The method of any of claims 61-63, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 65. The method of any of claims 61-64, wherein the sample does not comprise the immunotherapy, and/or is obtained from the subject prior to receiving the immunotherapy. 66. The method of any of claims 61-65, wherein the reference value for the one or more protein or portion thereof, or each of the reference values individually for each of the one or more protein or portion thereof, is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the one or more protein or portion thereof in a plurality of control samples; ii) is above the highest level, concentration or amount of the one or more protein or portion thereof, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the one or more protein or portion thereof as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects prior to receiving a immunotherapy for treating ALL, wherein (1) each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition; or (2) each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 67. The method of claim 66, further wherein the reference value for the one or more protein or portion thereof, or each of the gene reference values individually for each of the one or more protein or portion thereof, is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the one or more protein or portion thereof observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the one or more protein or portion thereof as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples, wherein the second plurality of control samples is obtained from a group of subjects prior to receiving the same immunotherapy for treating the ALL, wherein (1) each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition, or (2) each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 68. The method of claim 66 or claim 67, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a plasma sample. 69. The method of any of claims 66-68, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 70. The method of any of claims 61-69, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy, wherein administration of the agent is to be administered (i) prior to, (ii) within one, two, or three days of, (iii) concurrently with and/or (iv) at first fever following, the initiation of administration of the immunotherapy to the subject; ii. the immunotherapy at a reduced dose or at a dose that is not associated with risk of developing toxicity or severe toxicity, or is not associated with a risk of developing a toxicity or severe toxicity in a majority of subjects, and/or a majority of subjects having a disease or condition that the subject has or is suspected of having, following administration of the immunotherapy; iii. the immunotherapy in an in-patient setting and/or with admission to the hospital for one or more days, optionally wherein the immunotherapy is otherwise to be administered to subjects on an outpatient basis or without admission to the hospital for one or more days; or iv. an alternative therapeutic treatment other than the immunotherapy. 71. The method of any of claims 61-69, wherein if the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity, selecting the subject for administration of a therapeutic regimen, the therapeutic regimen comprising administering to the subject:
i. the immunotherapy, optionally at a non-reduced dose, optionally on an outpatient basis or without admission to the hospital for one or more days; ii. the immunotherapy, wherein administration of the immunotherapy does not comprise administering, prior to or concurrently with administering the immunotherapy and/or prior to the development of a sign or symptom of toxicity other than fever, an agent or treatment capable of treating, preventing, delaying, or attenuating the development of the toxicity; or iii. the immunotherapy in an outpatient setting and/or without admission of the subject to the hospital overnight or for one or more consecutive days and/or is without admission of the subject to the hospital for one or more days. 72. The method of any of claims 61-71, further comprising administering the therapeutic regimen to the selected subject. 73. A method of assessing a risk of a toxicity or a toxicity-related outcome, following administration of an immunotherapy, the method comprising
(a) assessing the level or amount of one or more proteins or portions thereof in a biological sample from a subject that received an immunotherapy for treatment of a disease or condition, wherein:
at least one of the one the one or more proteins or portions thereof are selected from CCL27, ENG, FAS, 1-309, ICAM3, NSE, P-Selectin, Resistin, S100(3, Thrombomodulin or vWF; and
(b) comparing the level or amount of the one or more proteins or portions thereof to a reference value, wherein:
the comparison indicates the subject is or is likely at risk of developing neurotoxicity if the at least one of the one or more proteins or portions thereof is at or below the reference value; or
the comparison indicates the subject is not or is likely not at risk of developing neurotoxicity if at least one of the one or more protein or portions thereof is above the reference value. 74. The method of claim 73, wherein the biological sample is a plasma sample. 75. The method of claim 73 or claim 74, wherein the biological sample is obtained or collected from the subject no more than 4 days, no more than 3 days, no more than 2 days or no more than 1 day, after initiation of administration of the immunotherapy and/or before the subject exhibits a sign or symptom of the toxicity and/or before the subjects develops a sustained fever. 76. The method of any of claims 73-75, wherein at least one of the one or more proteins or portions thereof is ENG or ICAM3. 77. The method of any of claims 73-76, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 78. The method of any of claims 73-77, wherein the reference value for the one or more protein or portion thereof, or each of the reference values individually for each of the one or more protein or portion thereof, is a value that:
i) is within 25%, within 20%, within 15%, within 10%, or within 5% above the average level, concentration or amount, and/or is within a standard deviation above the average level, concentration or amount, of the one or more protein or portion thereof in a plurality of control samples; ii) is above the highest level, concentration or amount of the one or more protein or portion thereof, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% above such highest level, concentration or amount, measured in at least one sample from among a plurality of control samples; and/or iii) is above the highest level, concentration or amount of the one or more protein or portion thereof as measured among more than 75%, 80%, 85%, 90%, or 95%, or 98% of samples from a plurality of control samples; wherein the plurality of control samples are a plurality of biological samples obtained from a group of subjects after receiving a immunotherapy for treating ALL, wherein (1) each of the subjects of the group went on to develop severe neurotoxicity, optionally grade 3 or higher, prolonged grade 3 or higher or grade 4 or 5 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition; or (2) each of the subjects of the group has ALL that is not Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 79. The method of claim 78, further wherein the reference value for the one or more protein or portion thereof, or each of the gene reference values individually for each of the one or more protein or portion thereof, is:
below the lowest level, concentration, or amount, optionally within 50%, within 25%, within 20%, within 15%, within 10%, or within 5% below the lowest level, concentration or amount, of the one or more protein or portion thereof observed in a sample from among a second plurality of control samples; and/or below the level, concentration or amount of the one or more protein or portion thereof as measured in more than 75%, 80%, 85%, 90%, 95%, or 98% of samples from among a second plurality of control samples,
wherein the second plurality of control samples is obtained from a group of subjects after receiving the same immunotherapy for treating the ALL, wherein (1) each of the subjects of the group did not develop severe neurotoxicity, optionally wherein each of the subjects developed grade 3 or less, grade 2 or less, or grade 1 or 0 neurotoxicity, after receiving the immunotherapy for treating the same disease or condition, or (2) each of the subjects has ALL that is Philadelphia chromosome positive (Ph+) or Philadelphia-like (Ph-like) subtype of ALL. 80. The method of claim 78 or claim 79, wherein the control sample or each of the plurality of control samples is the same type of biological sample being assessed from the subject, optionally is a plasma sample. 81. The method of any of claims 78-80, wherein the control sample or each of the plurality of control samples had been obtained or collected from the subject no more than 4 days, no more than 3 days, no more than 2 days or no more than 1 day, after initiation of administration of the immunotherapy and/or before the subject exhibits a sign or symptom of the toxicity and/or before the subjects develops a sustained fever. 82. The method of any of claims 78-81, wherein the plurality of control samples comprises at least 3, at least 10, at least 20, at least 50, or at least 100 control samples. 83. The method of any of claims 73-83, wherein if the comparison indicates the subject is or is likely to develop neurotoxicity, administering to the subject an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity and the immunotherapy. 84. The method of claim 83, wherein administration of the agent is to be administered within one, two, or three days of and/or at first fever following, the initiation of administration of the immunotherapy to the subject. 85. The method of any of claims 1-88, wherein the immunotherapy specifically binds to an antigen associated with the disease or condition or expressed in cells of the environment of a lesion associated with the disease or condition. 86. The method of claim 85, wherein the antigen is CD19, CD20, CD22 or CD123. 87. The method of any of claim 1-86, wherein the immunotherapy is a T cell-engaging therapy comprising a bispecific antibody, wherein at least one binding portion specifically binds to a T cell antigen and a second binding portion binds to the antigen associated with the disease or condition or expressed in cells of the environment of a lesion associated with the disease or condition. 88. The method of claim 87, wherein the T cell antigen is CD3. 89. The method of claim 87 or 88, wherein the second binding portion binds CD19. 90. The method of any of claims 87-89, wherein the bispecific antibody is blinatumomab. 91. The method of any of claims 1-86, wherein the immunotherapy is a cell therapy, wherein the cell therapy comprises genetically engineered cells expressing a recombinant receptor. 92. The method of claim 91, wherein the genetically engineered cells comprise T cells or NK cells. 93. The method of claim 91 or claim 92, wherein the engineered cells comprise T cells. 94. The method of any of claims 1-86 and 91-93, wherein the immunotherapy is a T cell therapy comprising genetically engineered T cells expressing a recombinant receptor. 95. The method of claim 94, wherein the T cells comprise CD4+ and/or CD8+ T cells 96. The method of any of claims 91-95, wherein the recombinant receptor is a T cell receptor or a functional non-T cell receptor. 97. The method of any of claims 91-96, wherein the recombinant receptor is a chimeric antigen receptor (CAR). 98. The method of any of claims 91-97, wherein the recombinant receptor is an anti-CD19 CAR. 99. The method of claim 97 or 98, wherein the CAR comprises an extracellular antigen-recognition domain that specifically binds to the antigen and an intracellular signaling domain comprising an ITAM, wherein optionally, the intracellular signaling domain comprises an intracellular domain of a CD3-zeta (CDζ) chain; and/or wherein the CAR further comprises a costimulatory signaling region, which optionally comprises a signaling domain of CD28 or 4-1BB. 100. The method of any of claims 91-99, wherein the risk or likely risk of the subject developing neurotoxicity following administration of the cell therapy is further based on the value of a parameter that indicates or correlates with the degree of recombinant receptor-dependent, optionally CAR-dependent, activity of the composition, wherein if the value of the parameter is at or greater than a threshold value the subject is at risk of developing neurotoxicity following administration of the immunotherapy when administered to the subject. 101. The method of claim 100, wherein the recombinant receptor-dependent activity comprises a measure of the production or accumulation of one or more of a proinflammatory cytokine, or a normalized value thereof. 102. The method of claim 101, wherein the proinflammatory cytokine is TNF-alpha, IFN-gamma, IL-2, IL-10, or a combination thereof. 103. The method of any of claims 91-103, wherein the immunotherapy comprises the administration of from or from about 1×105 to 1×108 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs), from or from about 5×105 to 1×107 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs) or from or from about 1×106 to 1×107 total recombinant receptor-expressing cells, total T cells, or total peripheral blood mononuclear cells (PBMCs), each inclusive. 104. The method of claim 19 or claim 70, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 2×106 to 5×107 total recombinant receptor-expressing cells, inclusive, or that is from or from about 2×105 cells/kg to 5×105 cells/kg total recombinant receptor-expressing cells, inclusive. 105. The method of claim 20 or claim 71, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 1×107 to 2.0×108 total recombinant receptor-expressing cells, inclusive, or that is from or from about 1×106 cells/kg to 2×106 cells/kg total recombinant receptor-expressing cells, inclusive. 106. The method of claim 23-30, wherein the immunotherapy is a cell therapy, said cell therapy comprising genetically engineered cells expressing a recombinant receptor, and the subject is administered a dose that is from or from about 1×107 to 2.0×108 total recombinant receptor-expressing cells, inclusive, or the subject is administered a dose that is from or from about 1×106 cells/kg to 2×106 cells/kg total recombinant receptor-expressing cells, inclusive. 107. The method of any of claims 1-106, wherein the subject is an adult human subject. 108. The method of any of claims 1-106, wherein the subject is a pediatric human subject. 109. A kit, comprising reagents for detecting the expression of two or more gene products or portions thereof in a sample, wherein the two or more gene products are encoded by two or more of CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGB5, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, ZNF415, ENG, SELE, ICAM3, PCDHGA9, FMNL1, or IL6R, or a portion or a fragment of any of the forgoing. 110. The kit of claim 109, wherein the two or more gene products are human gene products. 111. The kit of claim 109 or 110, wherein the kit comprises reagents for detecting the expression of at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 gene products. 112. The kit of any of claims 109-111, wherein at least one of the two or more gene products is from a first group of gene products that negatively correlate to a risk of developing neurotoxicity, wherein the first group comprises gene products encoded by CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AK5, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCL17, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 113. The kit of any of claims 109-112, wherein at least one of the two or more gene products is a gene product encoded by ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, JCHAIN, MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A, or is a portion or a fragment of any of the forgoing. 114. The kit of any of claims 109-113, wherein at least one of the two or more gene products is a gene product encoded by JCHAIN, MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing. 115. The kit of any of claims 109-112, wherein at least one of the two or more gene products is a gene product encoded by CCL17, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 116. The kit of any of claims 109-115, wherein at least one of the two or more gene products is a gene product encoded by CCL17 or is a portion or fragment thereof. 117. The kit of any of claims 109-116, wherein at least one of the two or more gene products is from a second group of gene products that positively correlate to a risk of developing neurotoxicity, wherein the second group comprises gene products encoded by ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGBS, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, and ZNF415, or portions or a fragments of any of the forgoing. 118. The kit of any of claims 109-117, wherein at least one of the two or more gene products is a gene product encoded by ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGBS, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28, or is a portion or fragment of any of the foregoing. 119. The kit of any of claims 109-118, wherein at least one of the two or more gene products is a gene product encoded by PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 120. The kit of any of claims 109-119, wherein at least one of the two or more gene products is a gene product encoded by PINLYP or PCDHGA12, or a portion or fragment of any of the foregoing. 121. The kit of any of claims 109-119 wherein:
at least one of the two or more gene products is a gene product, or a portion or fragment thereof, from a first group of gene products that negatively correlate to a risk of developing neurotoxicity selected from CCL17, ABCA9, ADAMTSL4, ADGRA2, ADGRF1, AKS, APOL1, ARHGAP27, ARID3B, CA6, CABP7, CCDC152, CCL17, CCR1, CCR6, CEP85L, CISH, CR2, ENAM, ENPP2, EPHA4, FTH1P11, FTH1P2, FTH1P8, GADD45A, GAS6, GBP3, GBP5, GBP6, GIMAP1-GIMAPS, GLI2, GPA33, GPRIN3, HSPA1A, IFITM1, IFITM3, IL15, IL2RA, JCHAIN, KIAA1257, LA16c-390H2.4, LAMB1, LDB3, LINC00623, LST1, LTB, LY6E, MAS1, MUC4, NLRC3, PLXNA4, PON2, PTGES3P1, PTP4A3, RNU1-1, RP11-345J4.6, RP11-421N8.1, RP11-51J9.5, RP11-51O6.1, RP11-552F3.9, RP11-686D22.9, RP11-723D22.3, RP11-723O4.6, RP13-512J5.1, RP4-620F22.2, RP5-940J5.9, RP6-109B7.5, RPL21P75, RYR2, SAMD9L, SEMA6A, SLC37A3, SNRPEP4, SOCS1, SPATS2L, SPON1, SV2C, TMEM154, TP53INP1, TNF, TRIM47, UST, WNT9A, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing; and
at least one of the gene products is a gene product, or a portion or fragment thereof, from a second group of gene products that positively correlate to a risk of developing neurotoxicity selected from ASAP2, ATP8B1, ATP9A, CCNA1, CDHR3, CECR2, CELF4, DLX1, DPYSL3, EHD4, FMNL2, GGA2, GPR176, HHIPL1, HOXA7, HMX3, IGF2BP1, IL3RA, IRX3, IRX5, KCNIP1, KIAA1644, LINC00092, LINC01483, MDFI, MIB1, MMP14, NOM1, OTOA, PCDHGA12, PCDHGA4, PCDHGA6, PCDHGB1, PCDHGBS, PCDHGB6, PINLYP, PPM1E, PRKD1, PROKR2, PRSS12, PRTG, PTCH1, RFX8, RP11-146B14.1, RP11-3P17.5, RP11-41O4.1, RP11-713N11.4, RP4-568B10.1, SERF1A, SEZ6L, SMURF1, TBC1D30, TCF12, TCP11, TM9SF3, TMPRSS15, TMSB15A, TNKS1BP1, TREM2, TTC28, PCDHGA9, FMNL1, and ZNF415, or portions or a fragments of any of the forgoing. 122. The kit of claim 121, wherein the at least one of the gene products from the first group is a gene product encoded by ADGRF1, CA6, CCL17, CCR6, ENAM, GAS6, GBP5, GLI2, IFITM1, JCHAIN, MUC4, PON2, PTP4A3, SEMA6A, SLC37A3, SPATS2L, TMEM154, TP53INP1, IL2RA, or WNT9A, or is a portion or a fragment of any of the forgoing;
and wherein the at least one of the gene products from the second group is a gene product encoded by ASAP2, FMNL2, GPR176, MDFI, PCDHGA12, PCDHGA6, PCDHGBS, PCDHGB6, PINLYP, PTCH1, ATP9A, HMX3, DPYSL3, ZNF415, IRX5, TMPRSS15, IL3RA, IGF2BP1, or TTC28, or is a portion or fragment of any of the foregoing. 123. The kit of claim 121 or 122, wherein the at least one of the gene products from the first group is a gene product encoded by JCHAIN, MUC4, CA6, WNT9A, ADGRF1 or CCL17, or a portion or fragment of any of the foregoing; and
wherein the at least one of the gene products from the second group is a gene product encoded by PINLYP, ASAP2, FMNL2, PTCH1, TTC28, PCDHGA6, PCDHGB6 or PCDHGA12, or a portion or fragment of any of the foregoing. 124. The kit of any of claims 121-123, wherein:
the at least one of the gene products from the first group is a gene product encoded by CCL17 or is a portion or fragment thereof; and the at least one of the gene products from the second group is a gene product encoded by PINLYP or PCDHGA12, or a portion or fragment thereof. 125. The kit of any of claims 109-124, wherein the two or more gene products are or comprise mRNA. 126. The kit of claim 125, wherein the reagents comprise one or more oligonucleotide and/or polynucleotide probes that are to, bind to, and/or are capable of binding to the one or more mRNA gene products. 127. The kit of any of claims 109-124, wherein the two or more gene products are or comprise proteins or variants or fragments thereof. 128. The kit of claim 127, wherein the two or more gene products are selected from CCL17, ENG, SELE, ICAM3, or IL6R, and portions or a fragments of any of the forgoing. 129. The kit of claim 128, wherein the reagents are or comprise antibodies or antigen binding fragments or variants thereof, wherein the antibodies or the antigen binding fragments or variants thereof bind to and/or are capable of binding to the protein gene products. 130. The kit of any of claims 109-129, further comprising an immunotherapy. 131. The kit of claim 130, wherein the immunotherapy is a cell therapy or is a T cell-engaging therapy, optionally wherein the cell therapy comprises cells engineered to express a recombinant receptor. 132. The kit of any of claims 109-131, for use in connection the method of any of claims 1-108. 133. An article of manufacture, comprising a kit of any one of claims 109-134, and instructions for using the reagents to assay a biological sample from a subject that is a candidate for treatment, optionally with an immunotherapy. 134. The article of manufacture of claims 133, wherein the instructions specify carrying out the method of any of claims 1-108. 135. An article of manufacture comprising an immunotherapy and instructions for administering the immunotherapy to a subject that exhibits a Philadelphia chromosome (Ph+) and/or Ph chromosome-like (Ph-like) molecular subtype of acute lymphoblastic leukemia (ALL). 136. The article of manufacture of claim 135, wherein the immunotherapy is a immunotherapy or is a T cell-engaging therapy, optionally wherein the immunotherapy comprises cells engineered to express a recombinant receptor. | 2,100 |
345,493 | 16,643,425 | 2,192 | A display substrate, a manufacturing method and a display device are provided. The display substrate includes a functional region and a peripheral region surrounding the functional region. A barrier structure is arranged at the peripheral region of the display substrate, and includes a plurality of barrier members spaced from each other in a direction away from the functional region. At least a part of the barrier member are made of metal. | 1. A display substrate, comprising a functional region and a peripheral region surrounding the functional region, wherein a barrier structure is arranged at the peripheral region of the display substrate, and comprises a plurality of barrier members spaced from each other in a direction away from the functional region, at least a part of the barrier member is made of metal, and thicknesses of the barrier members in a direction perpendicular to the display substrate gradually increase in the direction away from the functional region. 2. The display substrate according to claim 1, wherein each barrier member comprises a first sub-member and a second sub-member laminated one on another, the second sub-member is located at a surface of the first sub-member away from a base substrate of the display substrate, and an orthogonal projection of the second sub-member onto the base substrate is located within an orthogonal projection of the first sub-member onto the base substrate. 3. The display substrate according to claim 2, wherein the first sub-members of the barrier members are independent of each other, and the barrier structure further comprises a first connection layer configured to connect ends of the second sub-members away from the corresponding first sub-members. 4. The display substrate according to claim 3, wherein the barrier structure further comprises a plurality of third sub-members arranged at a side of the first connection layer away from the first sub-members and corresponding to the first sub-members in a one-to-one manner, and an orthogonal projection of each third sub-member onto the base substrate is located within the orthogonal projection of the corresponding first sub-member onto the base substrate. 5. The display substrate according to claim 4, wherein the barrier structure further comprises a second connection layer configured to connect ends of the third sub-members away from the corresponding first sub-members. 6. The display substrate according to claim 5, wherein the first sub-members, the second sub-members, the third sub-members, the first connection layer and/or the second connection layer surround the functional region. 7. The display substrate according to claim 5, wherein an orthogonal projection of each of the first sub-members, the second sub-members, the third sub-members, the first connection layer and/or the second connection layer onto the base substrate of the display substrate is of a wave shape. 8. The display substrate according to claim 4, wherein each first sub-member comprises a first sub-pattern and a second sub-pattern arranged at a same layer or different layers, and an orthogonal projection of the first sub-pattern onto the base substrate and an orthogonal projection of the second sub-pattern onto the base substrate together define at least one enclosed region. 9. The display substrate according to claim 2, wherein the first sub-members of the barrier members of barrier structure are arranged at different layers and gradually close to the base substrate in the direction away from the functional region, and thicknesses of the second sub-members in the direction perpendicular to the display substrate gradually increase in the direction away from the functional region. 10. The display substrate according to claim 9, wherein at least one of the plurality of first sub-members is created from a same layer and made of a same material as a first gate electrode layer of the display substrate, at least one of the plurality of first sub-members is created from a same layer and made of a same material as a second gate electrode layer of the display substrate, and/or at least one of the plurality of first sub-members is created from a same layer and made of a same material as a semiconductor layer of the display substrate. 11. The display substrate according to claim 5, wherein the first connection layer is created from a same layer and made of a same material as a source electrode layer and a drain electrode layer of the display substrate, and the second connection layer is created from a same layer and made of a same material as an anode layer of the display substrate. 12. The display substrate according to claim 5, further comprising:
a dielectric layer arranged at a side of each first sub-member away from the base substrate and provided with a plurality of first via-holes, the second sub-members being formed in the first via-holes in a one-to-one manner; and a planarization layer arranged at a side of the first connection layer away from the base substrate and provided with a plurality of second via-holes, the third sub-members being formed in the second via-holes in a one-to-one manner. 13. The display substrate according to claim 12, wherein the first connection layer is made of a same material as each second sub-member, and the second connection layer is made of a same material as each third sub-member. 14. A display device, comprising the display substrate according to claim 1. 15. A method of manufacturing the display substrate according to claim 1, comprising forming a barrier structure at a peripheral region of the display substrate, wherein the barrier structure of the display substrate comprises a plurality of barrier member, each barrier member comprises a first sub-member and a second sub-member, and the display substrate further comprises a first gate electrode layer, a second gate electrode layer, and a semiconductor layer, wherein the forming the barrier structure at the peripheral region of the display substrate comprises:
forming at least one of the plurality of first sub-members and the first gate electrode layer through a single patterning process; forming at least one of the plurality of first sub-members and the second gate electrode layer through a single patterning process; and/or forming at least one of the plurality of first sub-members and the semiconductor layer through a single patterning process, the first sub-members of the barrier members being spaced from each other; and forming each second sub-member at a surface of the corresponding first sub-member away from a base substrate of the display substrate, an orthogonal projection of each second sub-member onto the base substrate being located within an orthogonal projection of the corresponding first sub-member onto the base substrate. 16. The method according to claim 15, wherein the barrier structure further comprises a first connection layer, and the display substrate further comprises a dielectric layer, wherein prior to forming the second sub-members, the forming the barrier structure at the peripheral region of the display substrate further comprises:
forming the dielectric layer at a surface of each first sub-member away from the base substrate of the display substrate; and patterning the dielectric layer to form a plurality of first via-holes, and wherein the forming each second sub-member at the surface of the corresponding first sub-member away from the base substrate of the display substrate comprises forming the plurality of second sub-members and the first connection layer through a single patterning process, the plurality of second sub-members is located within the plurality of first via-holes in a one-to-one manner, and the first connection layer is configured to connect ends of the plurality of second sub-members away from the corresponding first sub-members. 17. The method according to claim 16, wherein the display substrate further comprises a source electrode layer and a drain electrode layer, and the forming the plurality of second sub-members and the first connection layer through a single patterning process comprises forming the plurality of second sub-members, the first connection layer, the source electrode layer and the drain electrode layer through a single patterning process. 18. The method according to claim 16 or 17, wherein the barrier structure further comprises a plurality of third sub-members and a second connection layer, and the display substrate further comprises a planarization layer, wherein subsequent to forming the first connection layer, the forming the barrier structure at the peripheral region of the display substrate further comprises:
forming the planarization layer at a surface of the first connection layer away from the base substrate of the display substrate;
patterning the planarization layer to form a plurality of second via-holes corresponding to the first sub-members in a one-to-one manner, an orthogonal of each second via-hole onto the base substrate being located within an orthogonal projection of the corresponding first sub-member onto the base substrate; and
forming the plurality of third sub-members and the second connection layer through a single patterning process, the plurality of third sub-members being located within the plurality of second via-holes in a one-to-one manner, and the second connection layer being configured to connect ends of the plurality of third sub-members away from the corresponding first sub-members. 19. The method according to claim 18, wherein the display substrate further comprises an anode layer, and the forming the plurality of third sub-members and the second connection layer through a single patterning process comprises forming the plurality of third sub-members, the second connection layer and the anode layer through a single patterning process. | A display substrate, a manufacturing method and a display device are provided. The display substrate includes a functional region and a peripheral region surrounding the functional region. A barrier structure is arranged at the peripheral region of the display substrate, and includes a plurality of barrier members spaced from each other in a direction away from the functional region. At least a part of the barrier member are made of metal.1. A display substrate, comprising a functional region and a peripheral region surrounding the functional region, wherein a barrier structure is arranged at the peripheral region of the display substrate, and comprises a plurality of barrier members spaced from each other in a direction away from the functional region, at least a part of the barrier member is made of metal, and thicknesses of the barrier members in a direction perpendicular to the display substrate gradually increase in the direction away from the functional region. 2. The display substrate according to claim 1, wherein each barrier member comprises a first sub-member and a second sub-member laminated one on another, the second sub-member is located at a surface of the first sub-member away from a base substrate of the display substrate, and an orthogonal projection of the second sub-member onto the base substrate is located within an orthogonal projection of the first sub-member onto the base substrate. 3. The display substrate according to claim 2, wherein the first sub-members of the barrier members are independent of each other, and the barrier structure further comprises a first connection layer configured to connect ends of the second sub-members away from the corresponding first sub-members. 4. The display substrate according to claim 3, wherein the barrier structure further comprises a plurality of third sub-members arranged at a side of the first connection layer away from the first sub-members and corresponding to the first sub-members in a one-to-one manner, and an orthogonal projection of each third sub-member onto the base substrate is located within the orthogonal projection of the corresponding first sub-member onto the base substrate. 5. The display substrate according to claim 4, wherein the barrier structure further comprises a second connection layer configured to connect ends of the third sub-members away from the corresponding first sub-members. 6. The display substrate according to claim 5, wherein the first sub-members, the second sub-members, the third sub-members, the first connection layer and/or the second connection layer surround the functional region. 7. The display substrate according to claim 5, wherein an orthogonal projection of each of the first sub-members, the second sub-members, the third sub-members, the first connection layer and/or the second connection layer onto the base substrate of the display substrate is of a wave shape. 8. The display substrate according to claim 4, wherein each first sub-member comprises a first sub-pattern and a second sub-pattern arranged at a same layer or different layers, and an orthogonal projection of the first sub-pattern onto the base substrate and an orthogonal projection of the second sub-pattern onto the base substrate together define at least one enclosed region. 9. The display substrate according to claim 2, wherein the first sub-members of the barrier members of barrier structure are arranged at different layers and gradually close to the base substrate in the direction away from the functional region, and thicknesses of the second sub-members in the direction perpendicular to the display substrate gradually increase in the direction away from the functional region. 10. The display substrate according to claim 9, wherein at least one of the plurality of first sub-members is created from a same layer and made of a same material as a first gate electrode layer of the display substrate, at least one of the plurality of first sub-members is created from a same layer and made of a same material as a second gate electrode layer of the display substrate, and/or at least one of the plurality of first sub-members is created from a same layer and made of a same material as a semiconductor layer of the display substrate. 11. The display substrate according to claim 5, wherein the first connection layer is created from a same layer and made of a same material as a source electrode layer and a drain electrode layer of the display substrate, and the second connection layer is created from a same layer and made of a same material as an anode layer of the display substrate. 12. The display substrate according to claim 5, further comprising:
a dielectric layer arranged at a side of each first sub-member away from the base substrate and provided with a plurality of first via-holes, the second sub-members being formed in the first via-holes in a one-to-one manner; and a planarization layer arranged at a side of the first connection layer away from the base substrate and provided with a plurality of second via-holes, the third sub-members being formed in the second via-holes in a one-to-one manner. 13. The display substrate according to claim 12, wherein the first connection layer is made of a same material as each second sub-member, and the second connection layer is made of a same material as each third sub-member. 14. A display device, comprising the display substrate according to claim 1. 15. A method of manufacturing the display substrate according to claim 1, comprising forming a barrier structure at a peripheral region of the display substrate, wherein the barrier structure of the display substrate comprises a plurality of barrier member, each barrier member comprises a first sub-member and a second sub-member, and the display substrate further comprises a first gate electrode layer, a second gate electrode layer, and a semiconductor layer, wherein the forming the barrier structure at the peripheral region of the display substrate comprises:
forming at least one of the plurality of first sub-members and the first gate electrode layer through a single patterning process; forming at least one of the plurality of first sub-members and the second gate electrode layer through a single patterning process; and/or forming at least one of the plurality of first sub-members and the semiconductor layer through a single patterning process, the first sub-members of the barrier members being spaced from each other; and forming each second sub-member at a surface of the corresponding first sub-member away from a base substrate of the display substrate, an orthogonal projection of each second sub-member onto the base substrate being located within an orthogonal projection of the corresponding first sub-member onto the base substrate. 16. The method according to claim 15, wherein the barrier structure further comprises a first connection layer, and the display substrate further comprises a dielectric layer, wherein prior to forming the second sub-members, the forming the barrier structure at the peripheral region of the display substrate further comprises:
forming the dielectric layer at a surface of each first sub-member away from the base substrate of the display substrate; and patterning the dielectric layer to form a plurality of first via-holes, and wherein the forming each second sub-member at the surface of the corresponding first sub-member away from the base substrate of the display substrate comprises forming the plurality of second sub-members and the first connection layer through a single patterning process, the plurality of second sub-members is located within the plurality of first via-holes in a one-to-one manner, and the first connection layer is configured to connect ends of the plurality of second sub-members away from the corresponding first sub-members. 17. The method according to claim 16, wherein the display substrate further comprises a source electrode layer and a drain electrode layer, and the forming the plurality of second sub-members and the first connection layer through a single patterning process comprises forming the plurality of second sub-members, the first connection layer, the source electrode layer and the drain electrode layer through a single patterning process. 18. The method according to claim 16 or 17, wherein the barrier structure further comprises a plurality of third sub-members and a second connection layer, and the display substrate further comprises a planarization layer, wherein subsequent to forming the first connection layer, the forming the barrier structure at the peripheral region of the display substrate further comprises:
forming the planarization layer at a surface of the first connection layer away from the base substrate of the display substrate;
patterning the planarization layer to form a plurality of second via-holes corresponding to the first sub-members in a one-to-one manner, an orthogonal of each second via-hole onto the base substrate being located within an orthogonal projection of the corresponding first sub-member onto the base substrate; and
forming the plurality of third sub-members and the second connection layer through a single patterning process, the plurality of third sub-members being located within the plurality of second via-holes in a one-to-one manner, and the second connection layer being configured to connect ends of the plurality of third sub-members away from the corresponding first sub-members. 19. The method according to claim 18, wherein the display substrate further comprises an anode layer, and the forming the plurality of third sub-members and the second connection layer through a single patterning process comprises forming the plurality of third sub-members, the second connection layer and the anode layer through a single patterning process. | 2,100 |
345,494 | 16,643,427 | 2,192 | The present disclosure provides a process for the preparation of ixazomib citrate. | 1. A process for preparing ixazomib citrate comprising:
a) reacting a compound of Formula II 2. The process according to claim 1, wherein the coupling agent is selected from dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), or combinations thereof. 3. The process according to claim 1, wherein the coupling agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. 4. The process according to claim 1, wherein the reacting in (a) is carried out in a solvent selected from dichloromethane, chloroform, carbon tetrachloride, diethyl ether, acetone, tetrahydrofuran, and combinations thereof. 5. The process according to claim 1, wherein the reacting in (a) is carried out in a base selected from pyridine, trimethylamine, triethylamine, diethylamine, diisopropylethylamine, triethanolamine, morphine, N-methyl morphine, and combinations thereof. 6. The process according to claim 1, wherein the reacting in (a) is carried out at about −5° C. to about 10° C. 7. The process according to claim 1, wherein the polar protic solvent in (b) is selected from methanol, ethanol, propanol, butanol, water, and a mixture thereof. 8. Ixazomib citrate prepared according to the process of claim 1 having HPLC purity more than 99.5%. 9. The process according to claim 1, wherein (a), (b), and (c) occur in a single pot process. | The present disclosure provides a process for the preparation of ixazomib citrate.1. A process for preparing ixazomib citrate comprising:
a) reacting a compound of Formula II 2. The process according to claim 1, wherein the coupling agent is selected from dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), or combinations thereof. 3. The process according to claim 1, wherein the coupling agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. 4. The process according to claim 1, wherein the reacting in (a) is carried out in a solvent selected from dichloromethane, chloroform, carbon tetrachloride, diethyl ether, acetone, tetrahydrofuran, and combinations thereof. 5. The process according to claim 1, wherein the reacting in (a) is carried out in a base selected from pyridine, trimethylamine, triethylamine, diethylamine, diisopropylethylamine, triethanolamine, morphine, N-methyl morphine, and combinations thereof. 6. The process according to claim 1, wherein the reacting in (a) is carried out at about −5° C. to about 10° C. 7. The process according to claim 1, wherein the polar protic solvent in (b) is selected from methanol, ethanol, propanol, butanol, water, and a mixture thereof. 8. Ixazomib citrate prepared according to the process of claim 1 having HPLC purity more than 99.5%. 9. The process according to claim 1, wherein (a), (b), and (c) occur in a single pot process. | 2,100 |
345,495 | 16,643,412 | 2,192 | A terminal device includes or connects to an external Hall device. The terminal device enters a to-be-connected state based on a Hall event generated by the Hall device, where terminal device is configured for connection to an externally device using a wireless communication protocol. The terminal device sends a trigger signal to enable the externally device to enter the to-be-connected state based on the trigger signal, and establishes the connection to the externally device using the wireless communication protocol. | 1. (canceled) 2. A pairing method implemented by a terminal device, wherein the terminal device is configured for connecting to a Hall device, and wherein the pairing method comprises:
entering a to-be-connected state based on a Hall event of the Hall device, wherein the terminal device is configured for connecting to an external device; sending a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and establishing a connection to the external device using a wireless communication protocol. 3. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is a security device; and requesting, in response to the identifying, a connection key from the external device using just works pairing. 4. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is not a security device; and requesting a connection key from the external device in a Link Key connection manner. 5. The pairing method of claim 2, further comprising determining whether the external device is a security device. 6. The pairing method of claim 5, wherein before determining whether the external device is the security device, the pairing method further comprises:
receiving mark information of the external device; determining whether the mark information is the same as prestored mark information; determining that the external device is the security device when the mark information is the same as the prestored mark information; and determining that the external device is not the security device when the mark information is different from the prestored mark information. 7. The pairing method of claim 2, wherein after establishing the connection, the pairing method further comprises breaking the connection to the externally-connected device based on a Hall disconnection event of the Hall device. 8. The pairing method of claim 7, wherein after breaking the connection, the pairing method further comprises deleting pairing information that is stored when the terminal device connects to the externally-connected device, and wherein the pairing information comprises at least one of address information of the externally-connected device, a service type of the externally-connected device, or a connection key used when the terminal device couples to the externally-connected device. 9. The pairing method of claim 2, wherein the trigger signal is a Hall signal. 10. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, wherein the pairing method further comprises:
turning on a BLUETOOTH switch and entering a BLUETOOTH discoverable state based on the Hall event; entering the BLUETOOTH discoverable state based on the Hall event; or turning on the BLUETOOTH switch based on the Hall event. 11.-34. (canceled) 35. A terminal device comprising:
a memory configured to store a computer program; and a processor coupled to the memory, wherein when executed by the processor, the computer program causes the terminal device to:
enter a to-be-connected state based on a Hall event of a Hall device, wherein the terminal device is configured to establish a connection to an external device;
send a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and
establish the connection to the external device using a wireless communication protocol. 36. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the computer program further causes the terminal device to:
identify that the external device is a security device; and request, in response to the identifying, a connection key from the external device in a using just works pairing. 37. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the computer program further causes the terminal device to:
identify that the external device is not a security device; and request, in response to the identifying, a connection key from the external device in a Link Key connection manner. 38. The terminal device of claim 35, wherein the computer program further causes the terminal device to determine whether the external device is a security device. 39. The terminal device of claim 38, wherein before determining whether the external device is a security device, the computer program further causes the terminal device to:
receive mark information of the external device; determine whether the mark information is the same as prestored mark information; determine that the external device is the security device when the mark information is the same as the prestored mark information; and determine that the external device is not the security device when the mark information is different from the prestored mark information. 40. The terminal device of claim 35, wherein after establishing the connection, the method further comprises breaking the connection to the externally-connected device based on a Hall disconnection event of the Hall device. 41. The terminal device of claim 40, wherein after breaking the connection, the computer program further causes the terminal device to delete pairing information that is stored when the terminal device connects to the externally-connected device, and wherein the pairing information comprises at least one of address information of the externally-connected device, a service type of the externally-connected device, or a connection key used when the terminal device connects to the externally-connected device. 42. The terminal device of claim 35, wherein the trigger signal is a Hall signal. 43. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein the computer program further causes the terminal device to:
turn on a BLUETOOTH switch and enter a BLUETOOTH discoverable state based on the Hall event; enter the BLUETOOTH discoverable state based on the Hall event; or turn on the BLUETOOTH switch based on the Hall event. 44. A pairing method implemented by a terminal device, wherein the terminal device comprises a Hall device, and wherein the pairing method comprises:
entering a to-be-connected state based on a Hall event of the Hall device; sending a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and establishing the coupling to the external device using a wireless communication protocol. 45. The pairing method of claim 44, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is a security device; and requesting, in response to the identifying, a connection key from the external device in a just works manner. | A terminal device includes or connects to an external Hall device. The terminal device enters a to-be-connected state based on a Hall event generated by the Hall device, where terminal device is configured for connection to an externally device using a wireless communication protocol. The terminal device sends a trigger signal to enable the externally device to enter the to-be-connected state based on the trigger signal, and establishes the connection to the externally device using the wireless communication protocol.1. (canceled) 2. A pairing method implemented by a terminal device, wherein the terminal device is configured for connecting to a Hall device, and wherein the pairing method comprises:
entering a to-be-connected state based on a Hall event of the Hall device, wherein the terminal device is configured for connecting to an external device; sending a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and establishing a connection to the external device using a wireless communication protocol. 3. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is a security device; and requesting, in response to the identifying, a connection key from the external device using just works pairing. 4. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is not a security device; and requesting a connection key from the external device in a Link Key connection manner. 5. The pairing method of claim 2, further comprising determining whether the external device is a security device. 6. The pairing method of claim 5, wherein before determining whether the external device is the security device, the pairing method further comprises:
receiving mark information of the external device; determining whether the mark information is the same as prestored mark information; determining that the external device is the security device when the mark information is the same as the prestored mark information; and determining that the external device is not the security device when the mark information is different from the prestored mark information. 7. The pairing method of claim 2, wherein after establishing the connection, the pairing method further comprises breaking the connection to the externally-connected device based on a Hall disconnection event of the Hall device. 8. The pairing method of claim 7, wherein after breaking the connection, the pairing method further comprises deleting pairing information that is stored when the terminal device connects to the externally-connected device, and wherein the pairing information comprises at least one of address information of the externally-connected device, a service type of the externally-connected device, or a connection key used when the terminal device couples to the externally-connected device. 9. The pairing method of claim 2, wherein the trigger signal is a Hall signal. 10. The pairing method of claim 2, wherein the wireless communication protocol is a BLUETOOTH protocol, wherein the pairing method further comprises:
turning on a BLUETOOTH switch and entering a BLUETOOTH discoverable state based on the Hall event; entering the BLUETOOTH discoverable state based on the Hall event; or turning on the BLUETOOTH switch based on the Hall event. 11.-34. (canceled) 35. A terminal device comprising:
a memory configured to store a computer program; and a processor coupled to the memory, wherein when executed by the processor, the computer program causes the terminal device to:
enter a to-be-connected state based on a Hall event of a Hall device, wherein the terminal device is configured to establish a connection to an external device;
send a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and
establish the connection to the external device using a wireless communication protocol. 36. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the computer program further causes the terminal device to:
identify that the external device is a security device; and request, in response to the identifying, a connection key from the external device in a using just works pairing. 37. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the computer program further causes the terminal device to:
identify that the external device is not a security device; and request, in response to the identifying, a connection key from the external device in a Link Key connection manner. 38. The terminal device of claim 35, wherein the computer program further causes the terminal device to determine whether the external device is a security device. 39. The terminal device of claim 38, wherein before determining whether the external device is a security device, the computer program further causes the terminal device to:
receive mark information of the external device; determine whether the mark information is the same as prestored mark information; determine that the external device is the security device when the mark information is the same as the prestored mark information; and determine that the external device is not the security device when the mark information is different from the prestored mark information. 40. The terminal device of claim 35, wherein after establishing the connection, the method further comprises breaking the connection to the externally-connected device based on a Hall disconnection event of the Hall device. 41. The terminal device of claim 40, wherein after breaking the connection, the computer program further causes the terminal device to delete pairing information that is stored when the terminal device connects to the externally-connected device, and wherein the pairing information comprises at least one of address information of the externally-connected device, a service type of the externally-connected device, or a connection key used when the terminal device connects to the externally-connected device. 42. The terminal device of claim 35, wherein the trigger signal is a Hall signal. 43. The terminal device of claim 35, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein the computer program further causes the terminal device to:
turn on a BLUETOOTH switch and enter a BLUETOOTH discoverable state based on the Hall event; enter the BLUETOOTH discoverable state based on the Hall event; or turn on the BLUETOOTH switch based on the Hall event. 44. A pairing method implemented by a terminal device, wherein the terminal device comprises a Hall device, and wherein the pairing method comprises:
entering a to-be-connected state based on a Hall event of the Hall device; sending a trigger signal to enable the external device to enter the to-be-connected state based on the trigger signal; and establishing the coupling to the external device using a wireless communication protocol. 45. The pairing method of claim 44, wherein the wireless communication protocol is a BLUETOOTH protocol, and wherein before establishing the connection, the pairing method further comprises:
identifying that the external device is a security device; and requesting, in response to the identifying, a connection key from the external device in a just works manner. | 2,100 |
345,496 | 16,643,450 | 3,761 | The present disclosure generally relates to devices and methods for brewing beverages. More specifically, aspects of the present disclosure include devices suitable for brewing coffee from coffee beans which have been ground by the device using a wet grinding process, and methods of brewing coffee using such a device. | 1. A pod adapted for use with a beverage brewing device, comprising:
an upper wall; a lower wall; one or more side walls connecting the upper wall and the lower wall to form a compartment; and a grinder attached to an inner surface of the compartment and adapted to grind an edible material; wherein at least a portion of the upper wall, the lower wall, and/or the one or more side walls comprises a filter adapted to allow fluid communication through the pod. 2. The pod of claim 1, wherein the grinder comprises a rotary grinder. 3. The pod of claim 1, wherein the grinder is a burr grinder. 4. The pod of any one of claims 1-3, wherein the grinder comprises a burr grinder or a rotary grinder adapted to grind coffee beans. 5. The pod of any one of claims 1-4, wherein the pod is configured to allow detachment of the filter from the container. 6. The pod of any one of claims 1-5, wherein the filter is attached to the container by at least one hinge or clasp. 7. The pod of any one of claims 1-6, wherein an outer surface of the pod is shaped to attach to a surface of a container and the container comprises one or more of the following:
a fluid reservoir; a motor configured to drive the grinder; a switch configured to activate the grinder; and/or a power source configured to power the grinder. 8. The pod of any one of claims 1-7, wherein an outer surface of the pod is shaped to attach to a surface of a container, the container comprises a fluid reservoir and is attached to a base, and the base comprises one or more of the following:
a motor configured to drive the grinder; a switch configured to activate the grinder; and/or a power source configured to power the grinder. 9. The pod of any one of claims 1-8, wherein the filter comprises:
a mesh filter; a solid support having one or more pores; and/or a porous material configured to allow fluid communication across the material while retaining edible material grinds. 10. The pod of any one of claims 1-9, wherein the pod further comprises:
a cap adapted to attach to the pod, the cap defining an upper wall of the pod. 11. The pod of any one of claims 1-10, wherein the pod comprises one or more of the following:
a pumping burr grinder; one or more interchangeable blades; one or more blades adapted to provide simultaneous grinding and mixing; a grinding element having at least one flat blade and at least one bent blade; and/or a grinding element having at least one flat blade, wherein the flat blade is substantially vertical or horizontal. 12. The pod of any one of claims 1-11, wherein the grinder comprises a “U”-shaped blade shaped to provide force to direct liquid laterally through at least one filter of the pod. 13. The pod of any one of claims 1-12, wherein the grinder is configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 14. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the pod is configured to attach to an inner surface of the bottom end of the container, and optionally, the top end; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 15. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a first base, adapted to allow the pod to attach to an upper surface of the first base; a second base, adapted to allow the first base to attach to an upper surface of the second base, wherein the second base comprises a power supply configured to power the grinder and a motor configured to operate the grinder; and a container, having a top end and a bottom end, wherein at least a portion of the bottom end comprises a filter adapted to allow fluid communication between the container and the pod; wherein the pod is configured to attach to an inner surface of the bottom end of the container. 16. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the container is configured to allow attachment of the pod to an inner surface of the top end and an inner surface of the bottom end of the container; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 17. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the container is configured to allow attachment of the pod to an inner surface of the bottom end of the container; a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder; and a scaffold extending along a vertical axis of the container, adapted to attach to the pod. 18. The beverage brewing device any one of claims 14-17, wherein the base and/or the container comprises at least one of the following:
a heating element adapted to heat or maintain the temperature of a liquid stored in the container; a switch configured to activate the grinder; or a power supply configured to power the grinder. 19. The beverage brewing device of any one of claims 14-17, further comprising a second container which comprises a fluid reservoir, where the device is configured to enable or block fluid communication between the container and the fluid reservoir of the second container in response to user input. 20. The beverage brewing device of claim 17, wherein the scaffold comprises a heating element adapted to heat or maintain the temperature of a liquid stored in the container 21. The beverage brewing device of claim 17, wherein the scaffold is further adapted to attach to a lid of the device. 22. The beverage brewing device of claim 21, wherein the lid is detachable. 23. A method of brewing a beverage, comprising:
placing an edible material in the pod of any one of claims 1-13; submerging the pod in a liquid, wherein the liquid is sufficient to fully or partially submerge the edible material; grinding the edible material; and generating a beverage by steeping the ground-up edible material in the liquid. 24. The method of claim 23, wherein the edible material comprises a plurality of coffee beans. 25. The method of claim 24, wherein the ground-up coffee is steeped for less than 5, 10, or 20 minutes. 26. The method of claim 24, wherein the ground-up coffee is steeped at a temperature of 0-25° C. 27. A method of brewing a coffee beverage, comprising:
placing an amount of coffee beans in the pod of any one of claims 1-13; placing the pod within a container; adding hot or cold water to the container; at least partially submerging the pod in the hot or cold water in the container; and generating coffee grinds by grinding the coffee beans using the grinder in the pod, wherein the grinding is subject to one or more selected parameters; and optionally, further steeping the coffee grinds in the hot or cold water. 28. The method of claim 27, wherein the amount of coffee beans placed in the pod is any one of the following: 20 g, 5-20 g, 10-30 g, 15-40 g, 20-50 g or >50 g. 29. The method of claim 27 or 28, further comprising:
attaching the pod to a scaffold prior to placing the pod in the container, wherein the scaffold is attached to an upper surface or a lower surface of the pod, and/or
a pod that attaches both to the bottom and top of the container. 30. The method of claim 27, wherein a volume of the hot or cold water added to the container is: 100-200 mL, 201-300 mL, 301-400 mL, 401-500 mL or >500 mL. 31. The method of claim 27, wherein the one or more selected parameters include:
a motor rotation speed parameter; a grinder run time parameter; a temperature parameter and/or a post-grinding steeping time parameter. 32. The method of claim 27, wherein steeping the coffee grinds in the hot or cold water comprises steeping for any one of the following durations of time: <5 minutes, 5-10 minutes, 10-20 minutes, 20-30 minutes or >30 minutes. 33. The method of claim 27, wherein adding the hot or cold water to the container comprises adding the hot or cold water having a temperature of: 0-5° C., 5-10° C., 10-20° C., 20-30° C., 30-50° C., 50-80° C. or 80-100° C. 34. A coffee composition comprising coffee beans ground and brewed in water with an approximately 6% w/v ratio of coffee beans or grounds to water, comprising one or more of the following:
at least 0.25% total fat; at least 0.1% saturated fat; and/or at least 0.1% polyunsaturated fat. 35. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising at least 140 mg/100 ml polyphenol content. 36. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising at least 65 mg/100 ml caffeine content. 37. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising a substantially brown color. 38. A coffee composition, generated by coffee grounds that have been exposed to oxygen only at levels of <1%. 39. A coffee composition comprising coffee beans ground and brewed in water with an approximately 6% w/v ratio of coffee beans or grounds to water, having any or all of the physical properties, amounts or concentrations required by claims 34-37, wherein the coffee composition has a particulate concentration of ≤10 mg/mL. 40. The coffee composition of any one of claims 34-38 wherein the ratio of coffee beans or grounds to water are at a ratio other than 6% but the relationship of the ratio to the physical property, amount or concentrations remains linear. 41. The coffee composition of any one of claims 34-38, wherein the coffee is brewed in water at a temperature of 0 to 25° C. 42. The coffee composition of any one of claims 34-38, wherein the coffee is brewed within 15 minutes. 43. The coffee composition of any one of claims 34-38, wherein the coffee is brewed within 15 minutes in water at a temperature of 0 to 25° C. 44. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; a second container adapted to attach to the bottom end of the first container, comprising a grinder and a filter; wherein the grinder is positioned within the second container; and a base adapted to attach to the bottom end of the first container, comprising a motor configured to operate the grinder. 45. The beverage brewing device of claim 44, wherein the grinder is a burr grinder or a rotary grinder. 46. The beverage brewing device of any one of claim 44 or 45, wherein the filter is a mesh filter comprising a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 47. The beverage brewing device of any one of claims 44-46, wherein the filter is a mesh filter attached to the second container by at least one hinge or clasp. 48. The beverage brewing device of any one of claims 44-47, wherein the grinder is a rotary grinder adapted to grind coffee beans. 49. The beverage brewing device of any one of claims 44-48, wherein the grinder comprises one or more blades. 50. The beverage brewing device of any one of claims 44-49, wherein the grinder comprises a “U”-shaped blade adapted to provide force to laterally direct liquid through at least one filter of the pod. 51. The beverage brewing device of any one of claims 44-50, wherein the device comprises a grinder configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 52. The beverage brewing device of any one of claims 44-51, wherein the second container is a pod or canister. 53. The beverage brewing device of any one of claims 44-52, wherein the first container is non-circular and adapted such that water emanating from a second container will have variable path lengths to the walls of the first container. 54. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; wherein a least a portion of the bottom end comprises a filter; a base adapted to attach to the bottom end of the first container, comprising a motor; and a second container comprising a top end, a bottom end, and a grinder positioned within the second container and configured to be operated by the motor; wherein the bottom end of the second container is adapted to attach to the base at a position. 55. The beverage brewing device of claim 54, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 56. The beverage brewing device of any one of claim 54 or 55, wherein the grinder is a burr grinder or a rotary grinder. 57. The beverage brewing device of any one of claims 54-56, wherein the filter is a mesh filter comprising a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 58. The beverage brewing device of any one of claims 54-57, wherein the grinder is a rotary grinder adapted to grind coffee beans. 59. A beverage brewing device, comprising:
a container, having a top end and a bottom end; a handle attached to an outside surface of the container and comprising a switch; a grinder, attached to an inside surface of the container at the bottom end; a repositionable filter attached to an inside surface of the container, configured to move into an open position or a closed position in response to operation of the switch; wherein the closed position prevents fluid communication between the container and the compartment; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 60. The beverage brewing device of claim 59, further comprising a means for locking the filter in a closed position, wherein the locking means is configured to unlock in response to operation of the switch. 61. The beverage brewing device of claim 59 or 60, wherein the repositionable filter is a mesh filter attached to the inside surface of the container by at least one hinge. 62. The beverage brewing device of any one of claims 59-61, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 63. The beverage brewing device of any one of claims 59-62, wherein the grinder is a burr grinder or a rotary grinder. 64. The beverage brewing device of any one of claims 59-63, wherein the repositionable filter comprises a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 65. The beverage brewing device of any one of claims 59-64, wherein the grinder is a rotary grinder adapted to grind coffee beans. 66. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; a second container, having a top end, a bottom end, and a side wall; wherein at least a portion of the side wall, the bottom end, and/or the top end comprises a filter; a grinder, attached to the second container at the bottom end; a partition positioned within the second container, which defines an upper chamber and a lower chamber, wherein the lower chamber contains the grinder; and a base adapted to attach to the bottom end of the second container, comprising a motor configured to operate the grinder. 67. The beverage brewing device of claim 66, wherein the filter comprises a majority of the surface area of the second container. 68. The beverage brewing device of claim 66 or 67, wherein the partition is adapted to prevent suction of air into the grinder during operation of the grinder. 69. The beverage brewing device of any one of claims 66-68, wherein the filter is structured as a cylinder or a conical cylinder. 70. The beverage brewing device of any one of claims 66-69, wherein the second container further comprises at least one attachment point configured to fasten or secure the filter in place 71. The beverage brewing device of any one of claims 66-70, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 72. The beverage brewing device of any one of claims 66-71, wherein the grinder is a burr grinder or a rotary grinder. 73. The beverage brewing device of any one of claims 66-72, wherein the filter comprises a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 74. The beverage brewing device of any one of claims 66-73, wherein the grinder is a rotary grinder adapted to grind coffee beans. 75. A beverage brewing device, comprising:
a container, having a top end and a bottom end; a grinder assembly configured to fit within the container, comprising:
an upper compartment having a top end, a bottom end, and a side wall, wherein at least a portion of the bottom end of the upper compartment comprises a filter, grating or valve and the sidewalls allow water to flow through into the container;
a detachable lower compartment having a bottom end and a side wall, wherein at least a portion of the side wall and/or the bottom end comprises a filter;
a grinder, attached to the lower compartment at the bottom end; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 76. The beverage brewing device of any one of claims 44-75, further comprising a heating element integrated into the device. 77. The beverage brewing device of claim 76, wherein:
the heating element is integrated into a base, compartment or container of the device; and/or the heating element is configured to heat or maintain the temperature of a liquid stored in a container or compartment of the device. 78. The beverage brewing device of any one of claims 44-77, wherein the grinder comprises one or more of the following:
a pumping burr grinder; one or more interchangeable blades; one or more blades adapted to provide simultaneous grinding and mixing; a grinding element having at least one flat blade and at least one bent blade; and/or a grinding element having at least one flat blade, wherein the flat blade is substantially vertical or horizontal. 79. The beverage brewing device of any one of claims 44-78, wherein the grinder comprises a “U”-shaped blade. 80. The beverage brewing device of any one of claims 44-78, wherein the grinder comprises a “U”-shaped blade adapted to provide force to laterally direct liquid through at least one filter of the pod. 81. The beverage brewing device of any one of claims 44-80, wherein the device comprises a grinder configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 82. A grinder assembly adapted to fit within a beverage brewing device, comprising:
a container adapted to store one or more edible materials; and a grinder; wherein the grinder is attached to an inside surface of the container. 83. The grinder assembly of claim 82, wherein the container comprises:
a sealed bottom end, a side wall attached to the bottom end, and an open end; and the grinder is attached to the inner surface of the sealed bottom end of the container. 84. The grinder assembly of claim 82 or 83, wherein the edible material comprises one or more coffee beans. 85. A method of brewing coffee, comprising:
providing a coffee brewing device comprising
a first container, having a top end and a bottom end;
a second container adapted to attach to the bottom end of the first container, comprising a grinder and a filter;
wherein the grinder is positioned within the second container; and
a base adapted to attach to the bottom end of the first container, comprising a motor configured to operate the grinder;
placing a plurality of coffee beans within the second container; adding liquid to the first container sufficient to fully or partially submerge the coffee beans in the second container; and generating coffee by grinding the submerged coffee beans and allowing soluble and/or extractable components of the coffee beans to dissolve or form an emulsion in the liquid. 86. The method of claim 85, wherein the liquid added to the container is at least:
0° C. to 100° C.; 0° C. to 20° C.; or 80° C. to 100° C.; when added to the container. 87. The method of claim 85 or 86, wherein the extractable components of the coffee beans are allowed to dissolve and/or form an emulsion in the liquid over a period of at least:
0.5 to 10 minutes;
10 to 30 minutes; or
30 to 90 minutes. 88. A method of brewing coffee comprising
at least partially submerging coffee beans in container comprising water, wherein there is an approximately 6% w/v ratio of coffee beans to water; and grinding the coffee beans to obtain coffee, 89. The method of claim 88, wherein the ratio of coffee beans to water are at a ratio other than 6% but the relationship of the ratio to total fat, saturated fat, polyunsaturated fat, polyphenol content, caffeine content, and/or a particulate concentration remains linear. 90. The method of any one of claims 88 and 89, wherein the water has a temperature of 0 to 25° C. 91. The method of any one of claims 88-90, wherein the coffee is brewed within 15 minutes. 92. The method of any one of claims 88 and 89, wherein the coffee is brewed within 15 minutes and the water has a temperature of 0 to 25° C. 93. The pod of any one of claims 1-13, wherein the pod comprises two or more filters with different pore sizes. 94. The pod of claims 93, wherein at least one of the filters has a pore size selected from or within the range of:
10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, or 100 μm; 10 μm-1,000 μm; 10-50 μm, 10-100 μm, 10-250 μm, 10-500 μm; 20-60 μm, 30-70 μm, 40-80 μm, 50-90 μm, 60-100 μm; or 100-200 μm, 200-300 μm, 300-400 μm, 400-500 μm, 500-600 μm, 600-700 μm, 700-800 μm, 800-900 μm, 900-1,000 μm. 95. The beverage brewing device of any one of claim 14-22 or 44-81, comprising the pod of any one of claim 93 or 94. 96. A beverage produced by the beverage brewing device of claim 95, wherein the beverage comprises coffee having at least 0.25% total fat, at least 0.1% saturated fat, at least 0.1% polyunsaturated fat, at least 140 mg/100 ml polyphenol content, at least 65 mg/100 ml caffeine content, a substantially brown color, and/or a particulate concentration of ≤10 mg/mL. | The present disclosure generally relates to devices and methods for brewing beverages. More specifically, aspects of the present disclosure include devices suitable for brewing coffee from coffee beans which have been ground by the device using a wet grinding process, and methods of brewing coffee using such a device.1. A pod adapted for use with a beverage brewing device, comprising:
an upper wall; a lower wall; one or more side walls connecting the upper wall and the lower wall to form a compartment; and a grinder attached to an inner surface of the compartment and adapted to grind an edible material; wherein at least a portion of the upper wall, the lower wall, and/or the one or more side walls comprises a filter adapted to allow fluid communication through the pod. 2. The pod of claim 1, wherein the grinder comprises a rotary grinder. 3. The pod of claim 1, wherein the grinder is a burr grinder. 4. The pod of any one of claims 1-3, wherein the grinder comprises a burr grinder or a rotary grinder adapted to grind coffee beans. 5. The pod of any one of claims 1-4, wherein the pod is configured to allow detachment of the filter from the container. 6. The pod of any one of claims 1-5, wherein the filter is attached to the container by at least one hinge or clasp. 7. The pod of any one of claims 1-6, wherein an outer surface of the pod is shaped to attach to a surface of a container and the container comprises one or more of the following:
a fluid reservoir; a motor configured to drive the grinder; a switch configured to activate the grinder; and/or a power source configured to power the grinder. 8. The pod of any one of claims 1-7, wherein an outer surface of the pod is shaped to attach to a surface of a container, the container comprises a fluid reservoir and is attached to a base, and the base comprises one or more of the following:
a motor configured to drive the grinder; a switch configured to activate the grinder; and/or a power source configured to power the grinder. 9. The pod of any one of claims 1-8, wherein the filter comprises:
a mesh filter; a solid support having one or more pores; and/or a porous material configured to allow fluid communication across the material while retaining edible material grinds. 10. The pod of any one of claims 1-9, wherein the pod further comprises:
a cap adapted to attach to the pod, the cap defining an upper wall of the pod. 11. The pod of any one of claims 1-10, wherein the pod comprises one or more of the following:
a pumping burr grinder; one or more interchangeable blades; one or more blades adapted to provide simultaneous grinding and mixing; a grinding element having at least one flat blade and at least one bent blade; and/or a grinding element having at least one flat blade, wherein the flat blade is substantially vertical or horizontal. 12. The pod of any one of claims 1-11, wherein the grinder comprises a “U”-shaped blade shaped to provide force to direct liquid laterally through at least one filter of the pod. 13. The pod of any one of claims 1-12, wherein the grinder is configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 14. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the pod is configured to attach to an inner surface of the bottom end of the container, and optionally, the top end; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 15. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a first base, adapted to allow the pod to attach to an upper surface of the first base; a second base, adapted to allow the first base to attach to an upper surface of the second base, wherein the second base comprises a power supply configured to power the grinder and a motor configured to operate the grinder; and a container, having a top end and a bottom end, wherein at least a portion of the bottom end comprises a filter adapted to allow fluid communication between the container and the pod; wherein the pod is configured to attach to an inner surface of the bottom end of the container. 16. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the container is configured to allow attachment of the pod to an inner surface of the top end and an inner surface of the bottom end of the container; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 17. A beverage brewing device, comprising:
the pod of any one of claims 1-13; a container, having a top end and a bottom end; wherein the container is configured to allow attachment of the pod to an inner surface of the bottom end of the container; a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder; and a scaffold extending along a vertical axis of the container, adapted to attach to the pod. 18. The beverage brewing device any one of claims 14-17, wherein the base and/or the container comprises at least one of the following:
a heating element adapted to heat or maintain the temperature of a liquid stored in the container; a switch configured to activate the grinder; or a power supply configured to power the grinder. 19. The beverage brewing device of any one of claims 14-17, further comprising a second container which comprises a fluid reservoir, where the device is configured to enable or block fluid communication between the container and the fluid reservoir of the second container in response to user input. 20. The beverage brewing device of claim 17, wherein the scaffold comprises a heating element adapted to heat or maintain the temperature of a liquid stored in the container 21. The beverage brewing device of claim 17, wherein the scaffold is further adapted to attach to a lid of the device. 22. The beverage brewing device of claim 21, wherein the lid is detachable. 23. A method of brewing a beverage, comprising:
placing an edible material in the pod of any one of claims 1-13; submerging the pod in a liquid, wherein the liquid is sufficient to fully or partially submerge the edible material; grinding the edible material; and generating a beverage by steeping the ground-up edible material in the liquid. 24. The method of claim 23, wherein the edible material comprises a plurality of coffee beans. 25. The method of claim 24, wherein the ground-up coffee is steeped for less than 5, 10, or 20 minutes. 26. The method of claim 24, wherein the ground-up coffee is steeped at a temperature of 0-25° C. 27. A method of brewing a coffee beverage, comprising:
placing an amount of coffee beans in the pod of any one of claims 1-13; placing the pod within a container; adding hot or cold water to the container; at least partially submerging the pod in the hot or cold water in the container; and generating coffee grinds by grinding the coffee beans using the grinder in the pod, wherein the grinding is subject to one or more selected parameters; and optionally, further steeping the coffee grinds in the hot or cold water. 28. The method of claim 27, wherein the amount of coffee beans placed in the pod is any one of the following: 20 g, 5-20 g, 10-30 g, 15-40 g, 20-50 g or >50 g. 29. The method of claim 27 or 28, further comprising:
attaching the pod to a scaffold prior to placing the pod in the container, wherein the scaffold is attached to an upper surface or a lower surface of the pod, and/or
a pod that attaches both to the bottom and top of the container. 30. The method of claim 27, wherein a volume of the hot or cold water added to the container is: 100-200 mL, 201-300 mL, 301-400 mL, 401-500 mL or >500 mL. 31. The method of claim 27, wherein the one or more selected parameters include:
a motor rotation speed parameter; a grinder run time parameter; a temperature parameter and/or a post-grinding steeping time parameter. 32. The method of claim 27, wherein steeping the coffee grinds in the hot or cold water comprises steeping for any one of the following durations of time: <5 minutes, 5-10 minutes, 10-20 minutes, 20-30 minutes or >30 minutes. 33. The method of claim 27, wherein adding the hot or cold water to the container comprises adding the hot or cold water having a temperature of: 0-5° C., 5-10° C., 10-20° C., 20-30° C., 30-50° C., 50-80° C. or 80-100° C. 34. A coffee composition comprising coffee beans ground and brewed in water with an approximately 6% w/v ratio of coffee beans or grounds to water, comprising one or more of the following:
at least 0.25% total fat; at least 0.1% saturated fat; and/or at least 0.1% polyunsaturated fat. 35. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising at least 140 mg/100 ml polyphenol content. 36. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising at least 65 mg/100 ml caffeine content. 37. A coffee composition comprising coffee beans ground and brewed in water at a 6% w/v ratio of coffee beans or grounds to water, comprising a substantially brown color. 38. A coffee composition, generated by coffee grounds that have been exposed to oxygen only at levels of <1%. 39. A coffee composition comprising coffee beans ground and brewed in water with an approximately 6% w/v ratio of coffee beans or grounds to water, having any or all of the physical properties, amounts or concentrations required by claims 34-37, wherein the coffee composition has a particulate concentration of ≤10 mg/mL. 40. The coffee composition of any one of claims 34-38 wherein the ratio of coffee beans or grounds to water are at a ratio other than 6% but the relationship of the ratio to the physical property, amount or concentrations remains linear. 41. The coffee composition of any one of claims 34-38, wherein the coffee is brewed in water at a temperature of 0 to 25° C. 42. The coffee composition of any one of claims 34-38, wherein the coffee is brewed within 15 minutes. 43. The coffee composition of any one of claims 34-38, wherein the coffee is brewed within 15 minutes in water at a temperature of 0 to 25° C. 44. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; a second container adapted to attach to the bottom end of the first container, comprising a grinder and a filter; wherein the grinder is positioned within the second container; and a base adapted to attach to the bottom end of the first container, comprising a motor configured to operate the grinder. 45. The beverage brewing device of claim 44, wherein the grinder is a burr grinder or a rotary grinder. 46. The beverage brewing device of any one of claim 44 or 45, wherein the filter is a mesh filter comprising a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 47. The beverage brewing device of any one of claims 44-46, wherein the filter is a mesh filter attached to the second container by at least one hinge or clasp. 48. The beverage brewing device of any one of claims 44-47, wherein the grinder is a rotary grinder adapted to grind coffee beans. 49. The beverage brewing device of any one of claims 44-48, wherein the grinder comprises one or more blades. 50. The beverage brewing device of any one of claims 44-49, wherein the grinder comprises a “U”-shaped blade adapted to provide force to laterally direct liquid through at least one filter of the pod. 51. The beverage brewing device of any one of claims 44-50, wherein the device comprises a grinder configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 52. The beverage brewing device of any one of claims 44-51, wherein the second container is a pod or canister. 53. The beverage brewing device of any one of claims 44-52, wherein the first container is non-circular and adapted such that water emanating from a second container will have variable path lengths to the walls of the first container. 54. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; wherein a least a portion of the bottom end comprises a filter; a base adapted to attach to the bottom end of the first container, comprising a motor; and a second container comprising a top end, a bottom end, and a grinder positioned within the second container and configured to be operated by the motor; wherein the bottom end of the second container is adapted to attach to the base at a position. 55. The beverage brewing device of claim 54, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 56. The beverage brewing device of any one of claim 54 or 55, wherein the grinder is a burr grinder or a rotary grinder. 57. The beverage brewing device of any one of claims 54-56, wherein the filter is a mesh filter comprising a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 58. The beverage brewing device of any one of claims 54-57, wherein the grinder is a rotary grinder adapted to grind coffee beans. 59. A beverage brewing device, comprising:
a container, having a top end and a bottom end; a handle attached to an outside surface of the container and comprising a switch; a grinder, attached to an inside surface of the container at the bottom end; a repositionable filter attached to an inside surface of the container, configured to move into an open position or a closed position in response to operation of the switch; wherein the closed position prevents fluid communication between the container and the compartment; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 60. The beverage brewing device of claim 59, further comprising a means for locking the filter in a closed position, wherein the locking means is configured to unlock in response to operation of the switch. 61. The beverage brewing device of claim 59 or 60, wherein the repositionable filter is a mesh filter attached to the inside surface of the container by at least one hinge. 62. The beverage brewing device of any one of claims 59-61, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 63. The beverage brewing device of any one of claims 59-62, wherein the grinder is a burr grinder or a rotary grinder. 64. The beverage brewing device of any one of claims 59-63, wherein the repositionable filter comprises a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 65. The beverage brewing device of any one of claims 59-64, wherein the grinder is a rotary grinder adapted to grind coffee beans. 66. A beverage brewing device, comprising:
a first container, having a top end and a bottom end; a second container, having a top end, a bottom end, and a side wall; wherein at least a portion of the side wall, the bottom end, and/or the top end comprises a filter; a grinder, attached to the second container at the bottom end; a partition positioned within the second container, which defines an upper chamber and a lower chamber, wherein the lower chamber contains the grinder; and a base adapted to attach to the bottom end of the second container, comprising a motor configured to operate the grinder. 67. The beverage brewing device of claim 66, wherein the filter comprises a majority of the surface area of the second container. 68. The beverage brewing device of claim 66 or 67, wherein the partition is adapted to prevent suction of air into the grinder during operation of the grinder. 69. The beverage brewing device of any one of claims 66-68, wherein the filter is structured as a cylinder or a conical cylinder. 70. The beverage brewing device of any one of claims 66-69, wherein the second container further comprises at least one attachment point configured to fasten or secure the filter in place 71. The beverage brewing device of any one of claims 66-70, wherein the base (a) further comprises a power supply connected to the motor; or (b) is connectable to an external power supply capable of powering the motor. 72. The beverage brewing device of any one of claims 66-71, wherein the grinder is a burr grinder or a rotary grinder. 73. The beverage brewing device of any one of claims 66-72, wherein the filter comprises a metallic sieve having one or more openings adapted to allow a liquid to pass through the filter. 74. The beverage brewing device of any one of claims 66-73, wherein the grinder is a rotary grinder adapted to grind coffee beans. 75. A beverage brewing device, comprising:
a container, having a top end and a bottom end; a grinder assembly configured to fit within the container, comprising:
an upper compartment having a top end, a bottom end, and a side wall, wherein at least a portion of the bottom end of the upper compartment comprises a filter, grating or valve and the sidewalls allow water to flow through into the container;
a detachable lower compartment having a bottom end and a side wall, wherein at least a portion of the side wall and/or the bottom end comprises a filter;
a grinder, attached to the lower compartment at the bottom end; and a base adapted to attach to the bottom end of the container, comprising a motor configured to operate the grinder. 76. The beverage brewing device of any one of claims 44-75, further comprising a heating element integrated into the device. 77. The beverage brewing device of claim 76, wherein:
the heating element is integrated into a base, compartment or container of the device; and/or the heating element is configured to heat or maintain the temperature of a liquid stored in a container or compartment of the device. 78. The beverage brewing device of any one of claims 44-77, wherein the grinder comprises one or more of the following:
a pumping burr grinder; one or more interchangeable blades; one or more blades adapted to provide simultaneous grinding and mixing; a grinding element having at least one flat blade and at least one bent blade; and/or a grinding element having at least one flat blade, wherein the flat blade is substantially vertical or horizontal. 79. The beverage brewing device of any one of claims 44-78, wherein the grinder comprises a “U”-shaped blade. 80. The beverage brewing device of any one of claims 44-78, wherein the grinder comprises a “U”-shaped blade adapted to provide force to laterally direct liquid through at least one filter of the pod. 81. The beverage brewing device of any one of claims 44-80, wherein the device comprises a grinder configured to perform filtration by repeatedly circulating liquid through at least one filter of the pod. 82. A grinder assembly adapted to fit within a beverage brewing device, comprising:
a container adapted to store one or more edible materials; and a grinder; wherein the grinder is attached to an inside surface of the container. 83. The grinder assembly of claim 82, wherein the container comprises:
a sealed bottom end, a side wall attached to the bottom end, and an open end; and the grinder is attached to the inner surface of the sealed bottom end of the container. 84. The grinder assembly of claim 82 or 83, wherein the edible material comprises one or more coffee beans. 85. A method of brewing coffee, comprising:
providing a coffee brewing device comprising
a first container, having a top end and a bottom end;
a second container adapted to attach to the bottom end of the first container, comprising a grinder and a filter;
wherein the grinder is positioned within the second container; and
a base adapted to attach to the bottom end of the first container, comprising a motor configured to operate the grinder;
placing a plurality of coffee beans within the second container; adding liquid to the first container sufficient to fully or partially submerge the coffee beans in the second container; and generating coffee by grinding the submerged coffee beans and allowing soluble and/or extractable components of the coffee beans to dissolve or form an emulsion in the liquid. 86. The method of claim 85, wherein the liquid added to the container is at least:
0° C. to 100° C.; 0° C. to 20° C.; or 80° C. to 100° C.; when added to the container. 87. The method of claim 85 or 86, wherein the extractable components of the coffee beans are allowed to dissolve and/or form an emulsion in the liquid over a period of at least:
0.5 to 10 minutes;
10 to 30 minutes; or
30 to 90 minutes. 88. A method of brewing coffee comprising
at least partially submerging coffee beans in container comprising water, wherein there is an approximately 6% w/v ratio of coffee beans to water; and grinding the coffee beans to obtain coffee, 89. The method of claim 88, wherein the ratio of coffee beans to water are at a ratio other than 6% but the relationship of the ratio to total fat, saturated fat, polyunsaturated fat, polyphenol content, caffeine content, and/or a particulate concentration remains linear. 90. The method of any one of claims 88 and 89, wherein the water has a temperature of 0 to 25° C. 91. The method of any one of claims 88-90, wherein the coffee is brewed within 15 minutes. 92. The method of any one of claims 88 and 89, wherein the coffee is brewed within 15 minutes and the water has a temperature of 0 to 25° C. 93. The pod of any one of claims 1-13, wherein the pod comprises two or more filters with different pore sizes. 94. The pod of claims 93, wherein at least one of the filters has a pore size selected from or within the range of:
10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, or 100 μm; 10 μm-1,000 μm; 10-50 μm, 10-100 μm, 10-250 μm, 10-500 μm; 20-60 μm, 30-70 μm, 40-80 μm, 50-90 μm, 60-100 μm; or 100-200 μm, 200-300 μm, 300-400 μm, 400-500 μm, 500-600 μm, 600-700 μm, 700-800 μm, 800-900 μm, 900-1,000 μm. 95. The beverage brewing device of any one of claim 14-22 or 44-81, comprising the pod of any one of claim 93 or 94. 96. A beverage produced by the beverage brewing device of claim 95, wherein the beverage comprises coffee having at least 0.25% total fat, at least 0.1% saturated fat, at least 0.1% polyunsaturated fat, at least 140 mg/100 ml polyphenol content, at least 65 mg/100 ml caffeine content, a substantially brown color, and/or a particulate concentration of ≤10 mg/mL. | 3,700 |
345,497 | 16,643,416 | 3,761 | A bending method and a bending device, wherein a composite bar comprising a bundle of reinforcing fibres embedded in a polymer matrix is bent at a bending point. To make it bendable, the composite bar is heated locally at the bending point using an ultrasonic device with a sonotrode. After the bending point has been heated, an infeeding movement between the composite bar and the sonotrode is used to deform a region of the composite bar at the bending point to create a deformed portion of which the outer dimensions are different from the outer dimensions of the bar portions of the composite bar adjoining the bending point. The two bar portions are then moved or angled away in relation to one another, and so the composite bar is curved at the bending point. Once the desired bending has been achieved, the composite bar is cured at the bending point. | 1. A bending method for bending at least one composite bar (11) at a bending location (21) that comprises a reinforcement fiber bundle (15) with multiple reinforcement fibers (14) embedded in a cured plastic matrix, the method comprising the following steps:
arranging a sonotrode (24) of an ultrasonic device (22) at a bending location (21), wherein two bar sections (11 a) of the at least one composite bar (11) that adjoin the bending location (21) extend in a first spatial direction (x), heating a plastic matrix (M) of the at least one composite bar (11) at the bending location (21) by coupling ultrasonic waves in the at least one composite bar (11) at the bending location (21), deforming the at least one composite bar (11) for formation of a deformed section (37) at the bending location (21) by an infeed movement between the sonotrode (24) and the at least one composite bar (11) in a second spatial direction (y) that is orientated radial to a bend that is to be created at the bending location (21), bending the at least one composite bar (11) at the bending location (21), curing the plastic matrix (M) at the bending location (21). 2. The bending method according to claim 1, wherein an orientation of the bar sections (11 a) of the at least one composite bar (11) remain unchanged relative to each other during the formation of the deformed section (37). 3. The bending method according to claim 1, wherein the deformed section (37) of the at least one composite bar (11) comprises a width (bz) in a third spatial direction (z) that is larger than a dimension (az) in the third spatial direction (z) of the bar sections (11 a) adjoining the bending location (21), wherein the third spatial direction (z) is orientated orthogonal to the first spatial direction (x) and the second spatial direction (y). 4. The bending method according to claim 1, wherein the deformed section (37) of the at least one composite bar (11) has a thickness (dy) in the second spatial direction (y) that is smaller than a dimension (ay) in the second spatial direction (y) of the bar sections (11 a) adjoining the bending location (21). 5. The bending method according to claim 1, wherein the at least one composite bar (11) has at the bending location (21) a bend inner side (BI) with an inner curvature and with reference to a center axis of the at least one composite bar (11) an opposite bend outer side (BA) with an outer curvature, wherein the inner curvature of the at least one composite bar (11) is larger than the outer curvature and wherein none of the reinforcement fibers (14) have a curvature at the bending location (21) that is larger than the inner curvature. 6. The bending method according to claim 1, further comprising emitting ultrasonic waves from the sonotrode (24) at least during phases during the infeed movement for formation of the deformed section (37) and/or during bending. 7. The bending method according to claim 1, further comprising supplying energy by a further energy source (44) at least during phases to the at least one composite bar (11) at the bending location (21) during bending. 8. The bending method according to claim 1, further comprising feedback controlling at least one of the following control parameters during the formation of the deformed section (37) and/or during bending:
an ultrasonic energy output during the infeed movement and/or during bending, a time duration during which ultrasonic waves are emitted during the infeed movement and/or during bending, a power of the emitted ultrasonic waves, a temperature of the at least one composite bar (11) at the deformed section (37) or at the bending location (21), a pressure force between the sonotrode (24) and the at least one composite bar (11), a position of the infeed movement, a bend or angle position of the bar sections adjoining the bending location. 9. The bending method according to claim 1 further comprising omitting the emission of ultrasonic waves by the sonotrode (24) during the infeed movement for formation of the deformed section (37) and/or during bending. 10. The bending method according to claim 1, further comprising feedback controlling at least one of the following control parameters of during the formation of the deformed section (37):
a relative position between the sonotrode (24) and the at least one composite bar (11), a velocity of the infeed movement, an acceleration of the infeed movement. 11. The bending method according to claim 1, wherein bending is carried out about a curved sonotrode surface (27) of the sonotrode (24), wherein the sonotrode surface (27) is curved about at least one axis that extends parallel to a third spatial direction (z), wherein the third spatial direction (z) is oriented orthogonal to the first spatial direction (x) and the second spatial direction (y). 12. The bending method according to claim 11, wherein the sonotrode surface (27) is in addition curved about at least one axis that extends parallel to the first spatial direction (x). 13. The bending method according to claim 1, further comprising keeping the sonotrode (24) stationary during bending. 14. The bending method according to claim 1, further comprising moving the sonotrode (24) in the second spatial direction (y) during bending. 15. The bending method according to claim 1, further comprising supplying a cooling medium (C) to the bending location (21) for curing the at least one composite bar (11). 16. The bending method according to claim 15, further comprising contacting the at least one composite bar (11) at the bending location (21) with a component within which a cooling medium flows and/or contacting the composite bar (11) directly with the cooling medium (C). 17. The bending method according to claim 1, wherein the plastic matrix (M) of the at least one composite bar (11) comprises a reversibly cross-linked plastic (K). 18. The bending method according to claim 1, wherein the plastic matrix (M) of the at least one composite bar (11) comprises a thermoplastic plastic (K). 19. A bending device (20) that is configured to bend at least one composite bar (11) at a bending location that comprises a reinforcement fiber bundle (15) with multiple reinforcement fibers embedded in a cured plastic matrix (M), wherein the two bar sections (11 a) of the at least one composite bar (11) adjoining the bending location (21) extend in a first spatial direction (x), the bending device comprising:
an ultrasonic device (22) comprising a sonotrode (24) and an ultrasound source (23), wherein the sonotrode (24) is moveable in a second spatial direction (y) orthogonal to the first spatial direction (x), a support device (31) for supporting the at least one composite bar (11) at a side opposite the sonotrode (24), wherein the bending device (20) is configured to carry out the bending method according to claim 1. 20. The bending device according to claim 19, further comprising at least one bending tool (41, 42, 43) is configured for bending the at least one composite bar (11) at the bending location (21). | A bending method and a bending device, wherein a composite bar comprising a bundle of reinforcing fibres embedded in a polymer matrix is bent at a bending point. To make it bendable, the composite bar is heated locally at the bending point using an ultrasonic device with a sonotrode. After the bending point has been heated, an infeeding movement between the composite bar and the sonotrode is used to deform a region of the composite bar at the bending point to create a deformed portion of which the outer dimensions are different from the outer dimensions of the bar portions of the composite bar adjoining the bending point. The two bar portions are then moved or angled away in relation to one another, and so the composite bar is curved at the bending point. Once the desired bending has been achieved, the composite bar is cured at the bending point.1. A bending method for bending at least one composite bar (11) at a bending location (21) that comprises a reinforcement fiber bundle (15) with multiple reinforcement fibers (14) embedded in a cured plastic matrix, the method comprising the following steps:
arranging a sonotrode (24) of an ultrasonic device (22) at a bending location (21), wherein two bar sections (11 a) of the at least one composite bar (11) that adjoin the bending location (21) extend in a first spatial direction (x), heating a plastic matrix (M) of the at least one composite bar (11) at the bending location (21) by coupling ultrasonic waves in the at least one composite bar (11) at the bending location (21), deforming the at least one composite bar (11) for formation of a deformed section (37) at the bending location (21) by an infeed movement between the sonotrode (24) and the at least one composite bar (11) in a second spatial direction (y) that is orientated radial to a bend that is to be created at the bending location (21), bending the at least one composite bar (11) at the bending location (21), curing the plastic matrix (M) at the bending location (21). 2. The bending method according to claim 1, wherein an orientation of the bar sections (11 a) of the at least one composite bar (11) remain unchanged relative to each other during the formation of the deformed section (37). 3. The bending method according to claim 1, wherein the deformed section (37) of the at least one composite bar (11) comprises a width (bz) in a third spatial direction (z) that is larger than a dimension (az) in the third spatial direction (z) of the bar sections (11 a) adjoining the bending location (21), wherein the third spatial direction (z) is orientated orthogonal to the first spatial direction (x) and the second spatial direction (y). 4. The bending method according to claim 1, wherein the deformed section (37) of the at least one composite bar (11) has a thickness (dy) in the second spatial direction (y) that is smaller than a dimension (ay) in the second spatial direction (y) of the bar sections (11 a) adjoining the bending location (21). 5. The bending method according to claim 1, wherein the at least one composite bar (11) has at the bending location (21) a bend inner side (BI) with an inner curvature and with reference to a center axis of the at least one composite bar (11) an opposite bend outer side (BA) with an outer curvature, wherein the inner curvature of the at least one composite bar (11) is larger than the outer curvature and wherein none of the reinforcement fibers (14) have a curvature at the bending location (21) that is larger than the inner curvature. 6. The bending method according to claim 1, further comprising emitting ultrasonic waves from the sonotrode (24) at least during phases during the infeed movement for formation of the deformed section (37) and/or during bending. 7. The bending method according to claim 1, further comprising supplying energy by a further energy source (44) at least during phases to the at least one composite bar (11) at the bending location (21) during bending. 8. The bending method according to claim 1, further comprising feedback controlling at least one of the following control parameters during the formation of the deformed section (37) and/or during bending:
an ultrasonic energy output during the infeed movement and/or during bending, a time duration during which ultrasonic waves are emitted during the infeed movement and/or during bending, a power of the emitted ultrasonic waves, a temperature of the at least one composite bar (11) at the deformed section (37) or at the bending location (21), a pressure force between the sonotrode (24) and the at least one composite bar (11), a position of the infeed movement, a bend or angle position of the bar sections adjoining the bending location. 9. The bending method according to claim 1 further comprising omitting the emission of ultrasonic waves by the sonotrode (24) during the infeed movement for formation of the deformed section (37) and/or during bending. 10. The bending method according to claim 1, further comprising feedback controlling at least one of the following control parameters of during the formation of the deformed section (37):
a relative position between the sonotrode (24) and the at least one composite bar (11), a velocity of the infeed movement, an acceleration of the infeed movement. 11. The bending method according to claim 1, wherein bending is carried out about a curved sonotrode surface (27) of the sonotrode (24), wherein the sonotrode surface (27) is curved about at least one axis that extends parallel to a third spatial direction (z), wherein the third spatial direction (z) is oriented orthogonal to the first spatial direction (x) and the second spatial direction (y). 12. The bending method according to claim 11, wherein the sonotrode surface (27) is in addition curved about at least one axis that extends parallel to the first spatial direction (x). 13. The bending method according to claim 1, further comprising keeping the sonotrode (24) stationary during bending. 14. The bending method according to claim 1, further comprising moving the sonotrode (24) in the second spatial direction (y) during bending. 15. The bending method according to claim 1, further comprising supplying a cooling medium (C) to the bending location (21) for curing the at least one composite bar (11). 16. The bending method according to claim 15, further comprising contacting the at least one composite bar (11) at the bending location (21) with a component within which a cooling medium flows and/or contacting the composite bar (11) directly with the cooling medium (C). 17. The bending method according to claim 1, wherein the plastic matrix (M) of the at least one composite bar (11) comprises a reversibly cross-linked plastic (K). 18. The bending method according to claim 1, wherein the plastic matrix (M) of the at least one composite bar (11) comprises a thermoplastic plastic (K). 19. A bending device (20) that is configured to bend at least one composite bar (11) at a bending location that comprises a reinforcement fiber bundle (15) with multiple reinforcement fibers embedded in a cured plastic matrix (M), wherein the two bar sections (11 a) of the at least one composite bar (11) adjoining the bending location (21) extend in a first spatial direction (x), the bending device comprising:
an ultrasonic device (22) comprising a sonotrode (24) and an ultrasound source (23), wherein the sonotrode (24) is moveable in a second spatial direction (y) orthogonal to the first spatial direction (x), a support device (31) for supporting the at least one composite bar (11) at a side opposite the sonotrode (24), wherein the bending device (20) is configured to carry out the bending method according to claim 1. 20. The bending device according to claim 19, further comprising at least one bending tool (41, 42, 43) is configured for bending the at least one composite bar (11) at the bending location (21). | 3,700 |
345,498 | 16,643,419 | 3,761 | Provided is a method for preparing an organic electronic device, comprising steps of: applying an ink composition on a substrate, on which an organic electronic element is formed; applying heat thereto before curing the applied ink composition; and curing the applied ink composition by irradiating with light having a wavelength in a range of 300 nm to 450 nm. Also provided is an organic electronic device, comprising a substrate, an organic electronic element formed on the substrate, and an organic layer sealing the entire surface of the organic electronic element, wherein after the organic layer is maintained at 110° C. for 30 minutes, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm. | 1. A method for preparing an organic electronic device device, comprising steps of
applying an ink composition on a substrate, on which an organic electronic element is formed; applying heat thereto before curing the applied ink composition; and curing the applied ink composition by irradiating with light having a wavelength in a range of 300 nm to 450 nm. 2. The method according to claim 1, further performing a step of applying heat after curing. 3. The method according to claim 1, wherein the step of applying heat proceeds at a temperature in a range of 20° C. to 230° C. 4. The method according to claim 1, wherein the step of applying heat proceeds for one time from 1 minute to 40 minutes. 5. The method according to claim 2, wherein the step of applying heat before curing proceeds at a temperature in a range of 20° C. to 110° C., and the step of applying heat after curing proceeds at a temperature in a range of 50° C. to 230° C. 6. The method according to claim 2, wherein the ratio (T2/T1) of the temperature (T2) for applying heat after curing to the temperature (T1) for applying heat before curing is in a range of 1.15 to 8. 7. The method according to claim 1, further comprising a step of planarizing the applied ink composition before curing. 8. The method according to claim 7, wherein the step of the planarizing proceeds for one time from 1 minute to 5 minutes. 9. The method according to claim 1, wherein the step of applying an ink composition comprises ejecting the ink composition using an inkjet apparatus. 10. The method according to claim 1, wherein the ink composition is a solventless type. 11. The method according to claim 1, wherein the ink composition is a photocurable composition. 12. The method according to claim 1, wherein after the applied ink composition is maintained at 110° C. for 30 minutes after curing, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm. 13. An organic electronic device, comprising a substrate, an organic electronic element formed on the substrate, and an organic layer sealing the entire surface of the organic electronic element, wherein after the organic layer is maintained at 110° C. for 30 minutes, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm. 14. The organic electronic device according to claim 13, further comprising an inorganic protective layer between the organic layer and the organic electronic element. 15. The organic electronic device according to claim 13, further comprising an inorganic layer formed on the organic layer. | Provided is a method for preparing an organic electronic device, comprising steps of: applying an ink composition on a substrate, on which an organic electronic element is formed; applying heat thereto before curing the applied ink composition; and curing the applied ink composition by irradiating with light having a wavelength in a range of 300 nm to 450 nm. Also provided is an organic electronic device, comprising a substrate, an organic electronic element formed on the substrate, and an organic layer sealing the entire surface of the organic electronic element, wherein after the organic layer is maintained at 110° C. for 30 minutes, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm.1. A method for preparing an organic electronic device device, comprising steps of
applying an ink composition on a substrate, on which an organic electronic element is formed; applying heat thereto before curing the applied ink composition; and curing the applied ink composition by irradiating with light having a wavelength in a range of 300 nm to 450 nm. 2. The method according to claim 1, further performing a step of applying heat after curing. 3. The method according to claim 1, wherein the step of applying heat proceeds at a temperature in a range of 20° C. to 230° C. 4. The method according to claim 1, wherein the step of applying heat proceeds for one time from 1 minute to 40 minutes. 5. The method according to claim 2, wherein the step of applying heat before curing proceeds at a temperature in a range of 20° C. to 110° C., and the step of applying heat after curing proceeds at a temperature in a range of 50° C. to 230° C. 6. The method according to claim 2, wherein the ratio (T2/T1) of the temperature (T2) for applying heat after curing to the temperature (T1) for applying heat before curing is in a range of 1.15 to 8. 7. The method according to claim 1, further comprising a step of planarizing the applied ink composition before curing. 8. The method according to claim 7, wherein the step of the planarizing proceeds for one time from 1 minute to 5 minutes. 9. The method according to claim 1, wherein the step of applying an ink composition comprises ejecting the ink composition using an inkjet apparatus. 10. The method according to claim 1, wherein the ink composition is a solventless type. 11. The method according to claim 1, wherein the ink composition is a photocurable composition. 12. The method according to claim 1, wherein after the applied ink composition is maintained at 110° C. for 30 minutes after curing, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm. 13. An organic electronic device, comprising a substrate, an organic electronic element formed on the substrate, and an organic layer sealing the entire surface of the organic electronic element, wherein after the organic layer is maintained at 110° C. for 30 minutes, the out-gas amount measured using Purge & Trap-gas chromatography/mass spectrometry is less than 150 ppm. 14. The organic electronic device according to claim 13, further comprising an inorganic protective layer between the organic layer and the organic electronic element. 15. The organic electronic device according to claim 13, further comprising an inorganic layer formed on the organic layer. | 3,700 |
345,499 | 16,643,409 | 3,761 | The present invention relates to novel thiophene compounds of general Formula I, and their stereoisomers tures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof along with process for their preparation. The present invention discloses compounds that are useful in the treatment and prevention of autoimmune diseases. | 1. A compound of Formula I represented by 2. The compound of Formula I as claimed in claim 1, wherein R1, R2, R3, R4, and R5 are each independently selected from a halogen group comprising F, Cl, Br and I. 3. The compounds of Formula I as claimed in claim 1, wherein at least one of the substituents selected from R1, R2, R3, R4, and R5 is a phenyl group optionally substituted by straight chain or branched C1-C5 alkyl, or straight chain or branched C1-C5 alkoxyalkyl. 4. The compound of Formula I as claimed in claim 1, wherein at least one of the substituents selected from R1, R2, R3, R4, and R5 is a C3-C7 aromatic or aliphatic heterocycle comprising at least one hetero atom selected from a group of O, N and S, wherein it is optionally substituted with C1-C5 alkyl, C2-C5 alkenyl or C1-C5 alkoxyalkyl. 5. The compound of Formula I as claimed in claim 1, wherein R6 and R7, together form a 3-7 membered aromatic or aliphatic heterocycle comprising at least one hetero atom selected from O, N and S, further wherein the heterocycle is optionally substituted with any substituent selected from the group comprising halogen, CF3, straight chain or branched C1-C5 alkyl, straight chain or branched C2-C5 alkenyl or straight chain or branched C1-C5 alkoxyalkyl. 6. The compound of Formula I as claimed in claim 1, wherein any two adjacent substituents selected from R1, R2, R3, R4 and R5, combine to form naphthalene. 7. The compound of Formula I as claimed in claim 1 wherein Rc, and Rd form a 3-7 membered aromatic or aliphatic heterocycle comprising at least one hetero atom selected from O, N and S, further wherein the heterocycle is optionally substituted with any substituent selected from the group of halogen, CF3, straight chain or branched C1-C5 alkyl, straight chain or branched C2-C5 alkenyl or straight chain or branched C1-C5 alkoxyalkyl. 8. The compound of Formula I as claimed in claim 1, wherein Rc, and Rd together form a heterocycle dioxidothiomorpholine. 9. The compound of Formula I and their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof, as claimed in claim 1 selected from:
N-butyl-2-(5-(4-chlorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-isopropoxypropyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(pyrrolidin-1-yl)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(4-fluorophenethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(3,5-dimethylmorpholino)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-cyclopentylacetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(4-fluorophenyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-(trifluoromethyl)phenyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3,5-difluorobenzyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-chlorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-Chlorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
2-(5-(4-Chlorophenyl)thiophen-2-yl)-N-(2-(dimethylamino)ethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide hydrochloride,
2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methyl-1-(4-methylpiperazin-1-yl)propan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methyl-N-(2-(piperidin-1-yl)ethyl)propenamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methylpropanamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one,
2-(5-(4-fluorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
N-(4-fluorophenethyl)-2-(5-(4-fluorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-fluorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(4-fluorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-fluorophenyl)thiophen-2-yl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(4-fluorophenethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
1-(4-methylpiperazin-1-yl)-2-(5-phenylthiophen-2-yl)ethan-1-one,
N-(4-fluorophenethyl)-2-(5-phenylthiophen-2-yl) acetamide,
N-(2-morpholinoethyl)-2-(5-phenylthiophen-2-yl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
2-(5-phenylthiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-phenylthiophen-2-yl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(2,4-dichlorophenyl)thiophen-2-yl)acetamide,
2-(5-(3-fluorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(3-fluorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)acetamide,
2-(5-(3-chlorophenyl)thiophen-2-l)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(3-chlorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(4-methoxyphenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholine ethyl)-2-(5-(4-(trifluoromethyl)phenyl)thiophen-2-yl) acetamide,
2-(5-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-morpholinopropyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl)acetamide,
2-(5-(3-bromophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholinoethyl)-2-(5-(3-morpholinophenyl)thiophen-2-yl)acetamide,
2-(5-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide, 2-(5-(3-(1-methyl-1H-pyrrol-2-yl)phenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholinoethyl)-2-(5-(3-(pyrazin-2-yl)phenyl)thiophen-2-yl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-morpholinoethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-thiomorpholinoethan-1-one,
2-(5-(3-(1-methyl-1H-imidazol-4-yl)phenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(3-morpholinopropyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-morpholinoethan-1-one,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-thiomorpholinoethan-1-one,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-(4-(4-fluorophenyl)piperidin-1-yl)ethan-1-one,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-morpholinoacetamide,
2-(5-(2,6-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl) acetamide,
2-(5-(2,6-dichlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(piperidin-1-yl)acetamide,
(1-(5-(4-chlorophenyl)thiophen-2-yl)cyclopropyl)(4-methylpiperazin-1-yl)methanone
(1-(5-(4-chlorophenyl)thiophen-2-yl)cyclobutyl)(4-methylpiperazin-1-yl)methanone,
(3-(5-(4-chlorophenyl)thiophen-2-yl)oxetan-3-yl)(4-methylpiperazin-1-yl)methanone,
(1-(5-(4-fluorophenyl)thiophen-2-yl)cyclopropyl)(4-methylpiperazin-1-yl)methanone,
(1-(5-(4-fluorophenyl)thiophen-2-yl)cyclobutyl)(4-methylpiperazin-1-yl)methanone,
(3-(5-(4-fluorophenyl)thiophen-2-yl)oxetan-3-yl)(4-methylpiperazin-1-yl)methanone,
N-butyl-2-(5-(naphthalen-1-yl)thiophen-2-yl)acetamide and
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-morpholinoacetamide. 10. A process for the preparation of the compounds of Formula I as claimed in claim 1, comprising the steps of:
a) Stirring thiophene acetonitrile in the presence of catalyst N-bromosuccinamide (NBS) in solvents selected from a group comprising dimethylformamide (DMF), dimethylsulfoxide (DMSO) and Tetrahydrofuran(THF); b) Reacting the resultant bromo thiophene acetonitrile obtained from Step a, with substituted phenylboronic acid in the presence of a solvent selected from toluene, benzene, dimethyl formamide, dioxane, tertiary butanol, potassium carbonate and triphenylphosphine palladium(0) or any Palladium (0) catalyst at a temperature of about 80° C. -100° C. for about 6-24 hours to obtain compounds of Formula II: 11. A pharmaceutical composition comprising an effective amount of one or more of the compounds as claimed in claim 1, and their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof, as an active ingredient along with a pharmaceutically acceptable carrier. 12. The process for preparing a pharmaceutical composition as claimed in claim 11, comprising the step of mixing at least one of the compounds of Formula I, with a pharmaceutically acceptable carrier. 13. Use of compound of Formula I as claimed in claim 1, for the treatment or prevention of autoimmune diseases. 14. A method of treating autoimmune diseases comprising administering a therapeutically effective amount of the compounds of Formula I as defined in claim 1 or their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof. 15. A method of treating skin autoimmune diseases as claimed in claim 14, comprising administering a therapeutically effective amount of a pharmaceutical composition or formulation comprising essentially of a compound of Formula I, or their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof. 16. The method of treating autoimmune diseases as claimed in claim 14, wherein the autoimmune diseases include but are not limited to type I diabetes, rheumatoid arthritis, multiple sclerosis, lupus, celiac diseases and pernicious anaemia. 17. The method of treating skin autoimmune diseases as claimed in claim 15, wherein the skin autoimmune diseases are from a group comprising psoriasis, lupus, vitiligo, scleroderma, dermatomyositis, epidermolysis bullosa, bullous pemphigoid, leukoderma, dermatitis, Koebner's phenomenon and any other skin autoimmune disease. 18. The method of treating skin autoimmune diseases as claimed in claim 17, wherein the disease is vitiligo. 19. The method of treating autoimmune diseases as claimed in claim 14, wherein the mode of administration may be selected from a group comprising of oral, parenteral, topical, transdermal, intravenous, rectal, sublingual and nasal, intramuscular, subcutaneous, intravenous and peridural administration. 20. The pharmaceutical composition as claimed in claim 11, wherein the composition is in the form of a formulation that is administered in unit-dosage forms such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or suspensions, injections, syrup, liquid, microemulsion, topical creams, ointments, suppositories, sachets, troches and lozenges and oil-water emulsions containing suitable quantities of the compound of Formula I or multiple-dosage forms. | The present invention relates to novel thiophene compounds of general Formula I, and their stereoisomers tures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof along with process for their preparation. The present invention discloses compounds that are useful in the treatment and prevention of autoimmune diseases.1. A compound of Formula I represented by 2. The compound of Formula I as claimed in claim 1, wherein R1, R2, R3, R4, and R5 are each independently selected from a halogen group comprising F, Cl, Br and I. 3. The compounds of Formula I as claimed in claim 1, wherein at least one of the substituents selected from R1, R2, R3, R4, and R5 is a phenyl group optionally substituted by straight chain or branched C1-C5 alkyl, or straight chain or branched C1-C5 alkoxyalkyl. 4. The compound of Formula I as claimed in claim 1, wherein at least one of the substituents selected from R1, R2, R3, R4, and R5 is a C3-C7 aromatic or aliphatic heterocycle comprising at least one hetero atom selected from a group of O, N and S, wherein it is optionally substituted with C1-C5 alkyl, C2-C5 alkenyl or C1-C5 alkoxyalkyl. 5. The compound of Formula I as claimed in claim 1, wherein R6 and R7, together form a 3-7 membered aromatic or aliphatic heterocycle comprising at least one hetero atom selected from O, N and S, further wherein the heterocycle is optionally substituted with any substituent selected from the group comprising halogen, CF3, straight chain or branched C1-C5 alkyl, straight chain or branched C2-C5 alkenyl or straight chain or branched C1-C5 alkoxyalkyl. 6. The compound of Formula I as claimed in claim 1, wherein any two adjacent substituents selected from R1, R2, R3, R4 and R5, combine to form naphthalene. 7. The compound of Formula I as claimed in claim 1 wherein Rc, and Rd form a 3-7 membered aromatic or aliphatic heterocycle comprising at least one hetero atom selected from O, N and S, further wherein the heterocycle is optionally substituted with any substituent selected from the group of halogen, CF3, straight chain or branched C1-C5 alkyl, straight chain or branched C2-C5 alkenyl or straight chain or branched C1-C5 alkoxyalkyl. 8. The compound of Formula I as claimed in claim 1, wherein Rc, and Rd together form a heterocycle dioxidothiomorpholine. 9. The compound of Formula I and their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof, as claimed in claim 1 selected from:
N-butyl-2-(5-(4-chlorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-isopropoxypropyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(pyrrolidin-1-yl)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(4-fluorophenethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(3,5-dimethylmorpholino)ethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-cyclopentylacetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(4-fluorophenyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-(trifluoromethyl)phenyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3,5-difluorobenzyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-chlorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-Chlorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
2-(5-(4-Chlorophenyl)thiophen-2-yl)-N-(2-(dimethylamino)ethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide hydrochloride,
2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methyl-1-(4-methylpiperazin-1-yl)propan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methyl-N-(2-(piperidin-1-yl)ethyl)propenamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-chlorophenyl)thiophen-2-yl)-2-methylpropanamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one,
2-(5-(4-fluorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
N-(4-fluorophenethyl)-2-(5-(4-fluorophenyl)thiophen-2-yl)acetamide,
2-(5-(4-fluorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(4-fluorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(4-fluorophenyl)thiophen-2-yl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(4-fluorophenethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
1-(4-methylpiperazin-1-yl)-2-(5-phenylthiophen-2-yl)ethan-1-one,
N-(4-fluorophenethyl)-2-(5-phenylthiophen-2-yl) acetamide,
N-(2-morpholinoethyl)-2-(5-phenylthiophen-2-yl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
2-(5-phenylthiophen-2-yl)-N-(2-(piperidin-1-yl)ethyl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-phenylthiophen-2-yl)acetamide,
N-(3-(1H-imidazol-1-yl)propyl)-2-(5-(2,4-dichlorophenyl)thiophen-2-yl)acetamide,
2-(5-(3-fluorophenyl)thiophen-2-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(3-fluorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)acetamide,
2-(5-(3-chlorophenyl)thiophen-2-l)-1-(4-methylpiperazin-1-yl)ethan-1-one,
2-(5-(3-chlorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
2-(5-(4-methoxyphenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholine ethyl)-2-(5-(4-(trifluoromethyl)phenyl)thiophen-2-yl) acetamide,
2-(5-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-N-(3-morpholinopropyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl)acetamide,
2-(5-(3-bromophenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholinoethyl)-2-(5-(3-morpholinophenyl)thiophen-2-yl)acetamide,
2-(5-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide, 2-(5-(3-(1-methyl-1H-pyrrol-2-yl)phenyl)thiophen-2-yl)-N-(2-morpholino ethyl) acetamide,
N-(2-morpholinoethyl)-2-(5-(3-(pyrazin-2-yl)phenyl)thiophen-2-yl)acetamide,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-morpholinoethan-1-one,
2-(5-(4-chlorophenyl)thiophen-2-yl)-1-thiomorpholinoethan-1-one,
2-(5-(3-(1-methyl-1H-imidazol-4-yl)phenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(3-morpholinopropyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl)acetamide,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-morpholinoethan-1-one,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-thiomorpholinoethan-1-one,
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-1-(4-(4-fluorophenyl)piperidin-1-yl)ethan-1-one,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-morpholinoacetamide,
2-(5-(2,6-dichlorophenyl)thiophen-2-yl)-N-(3-(1,1-dioxidothiomorpholino)propyl) acetamide,
2-(5-(2,6-dichlorophenyl)thiophen-2-yl)-N-(2-morpholinoethyl)acetamide,
2-(5-(2,4-dichlorophenyl)thiophen-2-yl)-N-(piperidin-1-yl)acetamide,
(1-(5-(4-chlorophenyl)thiophen-2-yl)cyclopropyl)(4-methylpiperazin-1-yl)methanone
(1-(5-(4-chlorophenyl)thiophen-2-yl)cyclobutyl)(4-methylpiperazin-1-yl)methanone,
(3-(5-(4-chlorophenyl)thiophen-2-yl)oxetan-3-yl)(4-methylpiperazin-1-yl)methanone,
(1-(5-(4-fluorophenyl)thiophen-2-yl)cyclopropyl)(4-methylpiperazin-1-yl)methanone,
(1-(5-(4-fluorophenyl)thiophen-2-yl)cyclobutyl)(4-methylpiperazin-1-yl)methanone,
(3-(5-(4-fluorophenyl)thiophen-2-yl)oxetan-3-yl)(4-methylpiperazin-1-yl)methanone,
N-butyl-2-(5-(naphthalen-1-yl)thiophen-2-yl)acetamide and
2-(5-(3,5-dichlorophenyl)thiophen-2-yl)-N-morpholinoacetamide. 10. A process for the preparation of the compounds of Formula I as claimed in claim 1, comprising the steps of:
a) Stirring thiophene acetonitrile in the presence of catalyst N-bromosuccinamide (NBS) in solvents selected from a group comprising dimethylformamide (DMF), dimethylsulfoxide (DMSO) and Tetrahydrofuran(THF); b) Reacting the resultant bromo thiophene acetonitrile obtained from Step a, with substituted phenylboronic acid in the presence of a solvent selected from toluene, benzene, dimethyl formamide, dioxane, tertiary butanol, potassium carbonate and triphenylphosphine palladium(0) or any Palladium (0) catalyst at a temperature of about 80° C. -100° C. for about 6-24 hours to obtain compounds of Formula II: 11. A pharmaceutical composition comprising an effective amount of one or more of the compounds as claimed in claim 1, and their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof, as an active ingredient along with a pharmaceutically acceptable carrier. 12. The process for preparing a pharmaceutical composition as claimed in claim 11, comprising the step of mixing at least one of the compounds of Formula I, with a pharmaceutically acceptable carrier. 13. Use of compound of Formula I as claimed in claim 1, for the treatment or prevention of autoimmune diseases. 14. A method of treating autoimmune diseases comprising administering a therapeutically effective amount of the compounds of Formula I as defined in claim 1 or their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof. 15. A method of treating skin autoimmune diseases as claimed in claim 14, comprising administering a therapeutically effective amount of a pharmaceutical composition or formulation comprising essentially of a compound of Formula I, or their stereoisomers (diastereoisomers, enantiomers), pure or mixed, racemic mixtures, geometrical isomers, tautomers, pharmaceutically acceptable salts, hydrates, solvates, solid forms and mixtures thereof. 16. The method of treating autoimmune diseases as claimed in claim 14, wherein the autoimmune diseases include but are not limited to type I diabetes, rheumatoid arthritis, multiple sclerosis, lupus, celiac diseases and pernicious anaemia. 17. The method of treating skin autoimmune diseases as claimed in claim 15, wherein the skin autoimmune diseases are from a group comprising psoriasis, lupus, vitiligo, scleroderma, dermatomyositis, epidermolysis bullosa, bullous pemphigoid, leukoderma, dermatitis, Koebner's phenomenon and any other skin autoimmune disease. 18. The method of treating skin autoimmune diseases as claimed in claim 17, wherein the disease is vitiligo. 19. The method of treating autoimmune diseases as claimed in claim 14, wherein the mode of administration may be selected from a group comprising of oral, parenteral, topical, transdermal, intravenous, rectal, sublingual and nasal, intramuscular, subcutaneous, intravenous and peridural administration. 20. The pharmaceutical composition as claimed in claim 11, wherein the composition is in the form of a formulation that is administered in unit-dosage forms such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or suspensions, injections, syrup, liquid, microemulsion, topical creams, ointments, suppositories, sachets, troches and lozenges and oil-water emulsions containing suitable quantities of the compound of Formula I or multiple-dosage forms. | 3,700 |
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