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Surface profile measurement |
An imaging system scans a light source output over an object to be imaged, and receives the reflected signal in a multi-region light detector, wherein different regions of the object to be imaged are imaged onto different regions of the detector by the receiving optics, and wherein different regions of the light detector can be actuated separately. The light source scanning is synchronised with the actuation of the light detector so that a region of the detector imaging the region of object being illuminated by the light source is actuated. The time of flight of light signals from the light source to the actuated portion of the detector is calculated for all scanning directions, to enable a three dimensional image of the object to be constructed. |
1. An imaging system comprising: a light source; means for scanning the light from the light source over an object to be imaged; stationary receiving optics for receiving light reflected from the object to be imaged; a multi-region light detector for detecting light received from the receiving optics, wherein different regions of the object to be imaged are imaged onto different regions of the detector by the receiving optics, and wherein different regions of the light detector can be actuated separately; control means to synchronise the light source scanning and the actuation of the light detector so that a region of the detector imaging the region of the object being illuminated by the light source is actuated; and processing means for measuring the time of flight of light signals from the light source to the actuated portion of the detector for all scanning directions. 2. An imaging system as claimed in claim 1, wherein the or each light source is a pulsed laser or light emitting diode or diodes. 3. An imaging system as claimed in claim 1, wherein the light source is a laser or light emitting diode or diodes having a modulated output. 4. An imaging system as claimed in any preceding claim, wherein the means for scanning comprises: a reflector for directing the light from the light source to an object to be imaged; and a drive mechanism for controlling movement of the reflector for scanning the light from the light source over the object to be imaged. 5. An imaging system comprising: a plurality of light sources, each light source being directed to an object to be imaged; stationary receiving optics for receiving light reflected from the object to be imaged; a multi-region light detector for detecting light received from the receiving optics, wherein each light source is imaged by the receiving optics onto a different region of the light detector, wherein the different regions of the light detector can be actuated separately; control means to synchronise the operation of individual light sources and the operation of the light detector so that the region of the detector imaging the region of the object being illuminated by an operating light source is actuated; and processing means for measuring the time of flight of light signals from the operating light source to the actuated portion of the detector for all scanning directions. 6. An imaging system as claimed in claim 5, wherein each light source comprises a pulsed laser or light emitting diode or diodes. 7. An imaging system as claimed in claim 5, wherein the light source is a laser or light emitting diode or diodes having a modulated output. 8. An imaging system comprising: a light source directed to an object to be imaged; stationary receiving optics for receiving light reflected from the object to be imaged; a multi-region light detector for detecting light received from the receiving optics; control means to synchronise the operation of the light source and the operation of the light detector so that a region of the detector is actuated synchronously with an allocated operation of the light source; and processing means for measuring the time of flight of light signals from the light source to the actuated portion of the detector. 9. An imaging system as claimed in claim 8, wherein all regions of the light detector are actuated in parallel. 10. An imaging system as claimed in claim 8, wherein different regions of the light detector can be actuated separately. 11. An imaging system as claimed in claim 10, wherein different sub-regions of the light detector are actuated in sequence, a different operation of the light source being allocated to each sub-region. 12. An imaging system as claimed in claim 10 or 11, wherein each sub region comprises a row or column of detector pixels of a pixel array. 13. An imaging system as claimed in any one of claims 8 to 12, wherein the light source comprises a pulsed laser or light emitting diode or diodes. 14. An imaging system as claimed in any one of claims 8 to 12, wherein the light source is a laser or light emitting diode or diodes having a modulated output. 15. An imaging system as claimed in any preceding claim, wherein the light detector comprises a photodiode array. 16. An imaging system as claimed in claim 15, wherein the photodiode array is operable in two modes, a first mode in which light signals from all photodiodes in the array are read out in sequence, and a second mode in which light signals from selected photodiodes or sub-groups of photodiodes in the array are read out in a sequence. 17. An imaging system as claimed in claim 15 or 16, wherein the processing means is integrated onto the same substrate as the photodiode array. 18. An imaging system as claimed in any one of claims 15 to 17, wherein multiple channels of time of flight measurement circuitry are integrated onto the same substrate as the photodiode array and configured to process signals from different actuated portions of the photodiode array in parallel. 19. An imaging system as claimed in any preceding claim, wherein the processing means uses cross-correlation for measuring the time of flight of light signals from the light source to the actuated portion of the detector. 20. A method of obtaining an image of an object comprising: scanning a light source signal over the object by directing a light source output in a plurality of scanning directions in sequence, and detecting reflected light received from the object using a two dimensional light detector array; determining the regions of the light detector array which are illuminated for each scanning direction; scanning the light source signal over the object again, and detecting reflected light received from the object using only the determined regions of the light detector array; calculating the time of flight of light pulses from the light source to the detector for each scanning direction; and obtaining a 3D profile from the time of flight calculations. 21. A method as claimed in claim 20, wherein the scanning of the light source is synchronised with the actuation of selected regions of the light detector array. 22. A method as claimed in claim 20 or 21 wherein the light source signal comprises a pulsed laser output or output of a light emitting diode or diodes. 23. A method as claimed in claim 20 or 21, wherein the light source signal comprises a modulated output of a laser or light emitting diode or diodes. 24. A method as claimed in claim 23, wherein calculating the time of flight uses cross-correlation. |
Supported double layer structure for displaying a nucleic acid associated with a protein |
The invention concerns novel biosensors, in particular a support for displaying nucleic acids and for detecting both the presence of nucleic acids in a sample and the linkage between proteins and nucleic acids, as well as the linkage between a ligand and a protein linked to a nucleic acid. |
1. A cell for displaying a nucleic acid, comprising: a support which is substantially flat on an atomic scale, a protein III having an unequivocal three-dimensional structure, a nucleic acid IV linked to said protein III, the nucleic acid-protein assembly being laterally mobile relative to said support, such that the hybridization of a target nucleic acid to said nucleic acid IV or the change in conformation of said nucleic acid IV can be detected via the geometric reorganization of the nucleic acid-protein assembly. 2. The cell as claimed in claim 1, characterized in that said protein III is chosen from the group consisting of proteins having a redox center and proteins having an anisotropic optical absorption property. 3. The cell as claimed in one of claims 1 and 2, comprising: a support which is substantially flat on an atomic scale, to which is attached a hydrophobic monolayer I, on which is present a monolayer II comprising phospholipids, a bridging molecule having a hydrophobic end which can interact with the monolayer II, and an end which is chemically functionalized so as to form a stable bond with a protein III, a protein III having an unequivocal three-dimensional structure, said protein III being laterally mobile in said layer II, a nucleic acid IV unequivocally attached to said protein III, preferably via a molecular arm. 4. The cell as claimed in one of claims 1 to 3, characterized in that the nucleic acid is attached to said protein via a covalent bond. 5. The cell as claimed in one of claims 1 to 3, characterized in that the nucleic acid is attached to said protein via a reversible bond. 6. The cell as claimed in one of claims 1 to 3, characterized in that the nucleic acid IV is attached to said protein III via a compound chosen from: a spacer arm connecting two identical or different, chemically reactive residues of the nucleic acid IV and of the protein III, chosen from the group consisting of thiols, amines, amides and arginines; a metal complex such as cis-platinum, trans-platinum, europium, or a complex of nickel, of copper or of ruthenium coordinated, firstly, with an amino residue or a group of amino residues of said protein III and, secondly, with one or more natural or modified bases of the nucleic acid IV, a covalent or noncovalent protein complex involving the nucleic acid IV. 7. The cell as claimed in one of claims 1 to 6, characterized in that said protein III has undergone a modification which introduces a unique site for effecting said bond [lacuna] said nucleic acid IV in an unequivocal manner. 8. The cell as claimed in claim 7, characterized in that said modification consists of a mutation of said protein so as to leave remaining or to introduce just one unique predetermined amino acid. 9. The cell as claimed in claim 8, characterized in that said predetermined amino acid is a cysteine. 10. The cell as claimed in one of claims 3 to 9, characterized in that said protein is attached to a phospholipid of the layer II. 11. The cell as claimed in claim 10, characterized in that said bond is a covalent bond, for example via acylation, farnesylation, via a GPI (glycosyl-phosphatidylinositol) anchoring sequence or via the attachment of a phospholipid to a specific residue of the protein III by any artificial method. 12. The cell as claimed in claim 10 or 11, characterized in that said bond is a reversible bond, for example via an arm capable of linking a metal chelate on one side and an amino acid or a group of amino acids on the other. 13. The cell as claimed in one of claims 10 to 12, characterized in that said protein is linked to a modified phospholipid of the layer II, said phospholipid having a chelate-binding zone. 14. The cell as claimed in one of claims 3 to 9, characterized in that said protein has a hydrophobic tail which allows it to be anchored in the layer II. 15. The cell as claimed in one of claims 3 to 14, characterized in that the phospholipids of the layer II have hydrophobic tails chosen such that said layer is not in the crystalline state, but in the fluid state at the temperature for use. 16. The cell as claimed in claim 15, characterized in that said hydrophobic tails are greater than or equal to 14 carbon atoms in chain length, said chain possibly having unsaturations, such that said layer II is in the fluid state at the temperature for use. 17. The cell as claimed in one of claims 3 to 16, characterized in that said phospholipids of the layer II have polar heads, chosen from the group consisting of neutral polar heads carrying no charges, polar heads which are neutral overall but which carry opposite charges (zwitterionic polar heads), or polar heads carrying an overall negative charge. 18. The cell as claimed in one of claims 3 to 17, characterized in that said layer I comprises hydrophobic elements with a chain length of approximately 2 to 2.5 nm, for example of between 12 and 20 carbon atoms, preferably between 14 and 18 carbon atoms. 19. The cell as claimed in one of claims 3 to 18, characterized in that said layer I comprises phospholipids linked to said support via their polar heads. 20. The cell as claimed in one of claims 3 to 18, characterized in that said layer I comprises hydrophobic elements linked to said support via a covalent bond, for example an alkyl-thiol bond or an alkyl-siloxane bond. 21. The cell as claimed in one of claims 1 to 20, characterized in that the flatness of said support is such that the difference in height between two zones separated by less than 100 nm is less than or equal to 10 nm, preferably less than or equal to 3 nm, more preferably less than or equal to 2 nm. 22. The cell as claimed in one of claims 1 to 21, characterized in that said support consists of a material chosen from the group consisting of glass covered with a layer of gold, cleaved mica, silicon or any other monocrystalline material. 23. The cell as claimed in one of claims 1 to 22, characterized in that it comprises several identical or different proteins linked to identical or different nucleic acids. 24. A support for detecting nucleic acids, displaying a plurality of cells as claimed in one of claims 1 to 23. 25. The support as claimed in claim 24, characterized in that it comprises a system for measuring current, impedance or potential. 26. The support as claimed in claim 24, characterized in that it comprises, between each cell, an integrated optical device capable of measuring the absorbance of a cell in two cross directions and of deducing therefrom its state of organization (anisotropy) or of disorganization (isotropy). 27. The support as claimed in claim 24, characterized in that it comprises a surface alternating conducting and reflecting zones and nonconducting and transparent zones. 28. A method for identifying the presence of a test nucleic acid in a sample, comprising the steps of: a) bringing said sample into contact with a cell as claimed in one of claims 1 to 23, under conditions which allow the hybridization of said test nucleic acid to a nucleic acid attached to a protein of said cell, b) detecting the hybridization of said test nucleic acid to said nucleic acid attached to said protein. 29. A method for identifying the binding of a protein to a nucleic acid, and/or its activity on the conformation of said nucleic acid, comprising the steps of: a) bringing said protein into contact with a nucleic acid attached to a protein, in a cell as claimed in one of claims 1 to 23, b) detecting the binding of said protein to said nucleic acid, and/or its activity on the conformation of said nucleic acid. 30. A method for identifying the binding of a ligand to a protein attached to a nucleic acid attached to a protein in a cell as claimed in one of claims 1 to 23, comprising the steps of: a) bringing said ligand into contact with said protein, b) detecting the binding of said ligand to said protein. 31. A method for identifying the binding of a compound to a nucleic acid, and/or its activity on the conformation of said nucleic acid, comprising the steps of: a) bringing said compound into contact with a nucleic acid attached to a protein, in a cell as claimed in one of claims 1 to 23, b) detecting the binding of said compound to said nucleic acid, and/or its activity on the conformation of said nucleic acid. 32. The method of identification as claimed in one of claims 28 to 31, characterized in that the detection is carried out via an optical (absorbance, fluorescence), electrical, electron-based, surface plasmon resonance, energy transfer, radiolabeling, diffraction (optical, electron, X-ray, neutron diffraction) or microscopy (direct optical or fluorescence microscopy, electron microscopy, near-field microscopy, atomic force microscopy) system. |
Server-based browser system |
A server-based browser system provides a server-based browser and a client system browser. The client browser reports the position of a user click on its display screen, hotspot ID, or URL to the server-side browser which retrieves a Document Object Model (DOM) model and view tree for the client and finds the location on the Web page that the user clicked on using the coordinates or hotspot ID received from the client. If there is a script associated with the location, it is executed and the resulting page location is requested from the appropriate server. If there is a URL associated with the location, it is requested from the appropriate server. The response Web page HTML definition is parsed and a DOM tree model is created which is used to create a view tree model. The server-side browser retrieves a style sheet, layout algorithms, and device constraints for the client device and lays out the view model using them onto a virtual page and determines the visual content. Textual and positional information are highly compressed and formatted into a stream and sent to the client browser which decodes the stream and displays the page to the user using the textual and positional information. |
1. A process for providing a server-based Web browser that interacts with a plurality of client device types, comprising the steps of: (a) providing browsing means on a server for accepting a Web page from a Web server, said browsing means comprising Web page layout means for laying out said Web page in a two-dimensional virtual page, said Web page layout means determining what information is visible on said virtual page, said Web page layout means calculating positioning of said visible information within said Web page, and said browsing means creating a compressed stream containing said visible information and the positioning information of said visible information; (b) providing client browsing means on a client system for accepting compressed streams representing display pages; and (c) providing means on said server for sending said compressed stream to said client browsing means; wherein said client browsing means decompresses said compressed stream and displays said visible information using said positioning information. 2. The process of claim 1, wherein said browsing means comprises: a database of style sheets on a storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; and a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 3. The process of claim 1, wherein said step of providing browsing means further comprises the sub-steps of: parsing said Web page's HTML code to create a Document Object Model (DOM) tree; creating a view tree using said DOM tree; and storing said DOM tree and said view tree on a storage device for said client system. 4. The process of claim 3, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 5. The process of claim 4, wherein said step of providing browsing means further comprises the sub-steps of: retrieving a DOM tree and view tree from said storage device for said client system; determining the location of said position or hotspot ID on said Web page using said view tree; finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 6. The process of claim 3, wherein said step of providing browsing means further comprises the sub-step of: saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. 7. A process for providing a cross platform Web browser that interacts with a plurality of client device types, comprising the steps of: (a) providing browsing means on a server for accepting a Web page from a Web server; said step pf providing browsing means further comprising the sub-steps of: parsing said Web page's HTML code to create a Document Object Model (DOM) tree; creating a view tree using said DOM tree; providing Web page layout means for laying out said Web page in a two-dimensional virtual page; wherein said Web page layout means determines what information is visible on said virtual page; wherein said Web page layout means removes unnecessary structural information and retains visible information in said view tree; and storing said DOM tree and said view tree on a storage device for said client system; wherein said browsing means creates a compressed stream containing said DOM tree and said view tree; (b) providing client browsing means on a client system for accepting compressed streams; and (c) providing means on said server for sending said compressed stream to said client browsing means; wherein said client browsing means decompresses said compressed stream and displays said visible information using said DOM tree and said view tree. 8. The process of claim 7, wherein said browsing means comprises: a database of style sheets on said storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; and a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 9. The process of claim 7, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 10. The process of claim 9, wherein said step of providing browsing means further comprises the sub-steps of: retrieving a DOM tree and view tree from said storage device for said client system; determining the location of said position or hotspot ID on said Web page using said view tree; and finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 11. The process of claim 7, wherein said step of providing browsing means further comprising the sub-step of: saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. 12. An apparatus for a server-based Web browser that interacts with a plurality of client device types, comprising: (a) browsing means on a server for accepting a Web page from a Web server, said browsing means further comprising Web page layout means for laying out said Web page in a two-dimensional virtual page, said Web page layout means determining what information is visible on said virtual page, and said Web page layout means calculating positioning of said visible information within said Web page; wherein said browsing means creates a compressed stream containing said visible information and the positioning information of said visible information; (b) client browsing means on a client system for accepting compressed streams representing display pages; and (c) means on said server for sending said compressed stream to said client browsing means; wherein said client browsing means decompresses said compressed stream and displays said visible information using said positioning information. 13. The apparatus of claim 12, wherein said browsing means further comprises: a database of style sheets on a storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; and a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 14. The apparatus of claim 12, wherein said browsing means further comprises: a module for parsing said Web page's HTML code to create a Document Object Model (DOM) tree; a module for creating a view tree using said DOM tree; and a module for storing said DOM tree and said view tree on a storage device for said client system. 15. The apparatus of claim 14, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 16. The apparatus of claim 15, wherein said browsing means further comprises: a module for retrieving a DOM tree and view tree from said storage device for said client system; a module for determining the location of said position or hotspot ID on said Web page using said view tree; a module for finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and a module for requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 17. The apparatus of claim 14, wherein said browsing means further comprises: a module for saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. 18. An apparatus for a cross platform Web browser that interacts with a plurality of client device types, comprising: (a) browsing means on a server for accepting a Web page from a Web server; said browsing means further comprising: a module for parsing said Web page's HTML code to create a Document Object Model (DOM) tree; a module for creating a view tree using said DOM tree; Web page layout means for laying out said Web page in a two-dimensional virtual page; wherein said Web page layout means determines what information is visible on said virtual page; wherein said Web page layout means removes unnecessary structural information and retains visible information in said view tree; and a module for storing said DOM tree and said view tree on a storage device for said client system; wherein said browsing means creates a compressed stream containing said DOM tree and said view tree; (b) client browsing means on a client system for accepting compressed streams; (c) means on said server for sending said compressed stream to said client browsing means; and wherein said client browsing means decompresses said compressed stream and displays said visible information using said DOM tree and said view tree. 19. The apparatus of claim 18, wherein said browsing means further comprises: a database of style sheets on said storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 20. The apparatus of claim 18, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 21. The apparatus of claim 20, wherein said browsing means further comprises: a module for retrieving a DOM tree and view tree from said storage device for said client system; a module for determining the location of said position or hotspot ID on said Web page using said view tree; a module for finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and a module for requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 22. The apparatus of claim 18, wherein said browsing means further comprises: a module for saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. 23. A program storage medium readable by a computer, tangibly embodying a program of instructions executable by the computer to perform method steps for a server-based Web browser that interacts with a plurality of client device types, comprising the steps of: (a) providing browsing means on a server for accepting a Web page from a Web server, said browsing means providing Web page layout means for laying out said Web page in a two-dimensional virtual page, said Web page layout means determining what information is visible on said virtual page, said Web page layout means calculating positioning of said visible information within said Web page; and said browsing means creating a compressed stream containing said visible information and the positioning information of said visible information; (b) providing client browsing means on a client system for accepting compressed streams representing display pages; and (c) providing means on said server for sending said compressed stream to said client browsing means; wherein said client browsing means decompresses said compressed stream and displays said visible information using said positioning information. 24. The program storage medium of claim 23, wherein said browsing means comprises: a database of style sheets on a storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; and a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 25. The program storage medium of claim 23, wherein said step of providing browsing means further comprising the sub-steps of: parsing said Web page's HTML code to create a Document Object Model (DOM) tree; creating a view tree using said DOM tree; and storing said DOM tree and said view tree on a storage device for said client system. 26. The program storage medium of claim 25, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 27. The program storage medium of claim 26, wherein said step of providing browsing means further comprising the sub-steps of: retrieving a DOM tree and view tree from said storage device for said client system; determining the location of said position or hotspot ID on said Web page using said view tree; finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 28. The program storage medium of claim 23, wherein said step of providing browsing means further comprising the step of: saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. 29. A program storage medium readable by a computer, tangibly embodying a program of instructions executable by the computer to perform method steps for a cross platform Web browser that interacts with a plurality of client device types, comprising the steps of: (a) providing browsing means on a server for accepting a Web page from a Web server; said step of providing browsing means further comprising the sub-steps of: parsing said Web page's HTML code to create a Document Object Model (DOM) tree; creating a view tree using said DOM tree; providing Web page layout means for laying out said Web page in a two-dimensional virtual page; wherein said Web page layout means determines what information is visible on said virtual page; wherein said Web page layout means removes unnecessary structural information and retains visible information in said view tree; and storing said DOM tree and said view tree on a storage device for said client system; wherein said browsing means creates a compressed stream containing said DOM tree and said view tree; (b) providing client browsing means on a client system for accepting compressed streams; and (c) providing means on said server for sending said compressed stream to said client browsing means; wherein said client browsing means decompresses said compressed stream and displays said visible information using said DOM tree and said view tree. 30. The program storage medium of claim 29, wherein said browsing means comprises: a database of style sheets on said storage device for supported client devices; a database of layout algorithms on said storage device for supported client devices; and a database of device constraint information on said storage device for supported client devices; wherein said Web page layout means retrieves a style sheet, layout algorithms, and device constraints from said storage device for said client system; and wherein said Web page layout means lays out said Web page based on said client system's style sheet, layout algorithms, and device constraints. 31. The program storage medium of claim 29, wherein said client browsing means accepts a URL from a user or determines a position or hotspot ID of a user's click or press on a display page, wherein said client browsing means sends said URL, said position, or said hotspot ID to said browsing means, and wherein said browsing means accepts said URL, said position, or said hotspot ID from said client browsing means. 32. The program storage medium of claim 31, wherein said step of providing browsing means further comprising the steps of: retrieving a DOM tree and view tree from said storage device for said client system; determining the location of said position or hotspot ID on said Web page using said view tree; finding a script or URL associated with the location using said DOM tree; wherein if a script is associated with the location then executing the script and determining the resulting URL; and requesting the Web page associated with said resulting URL or said associated URL from the appropriate server. 33. The program storage medium of claim 29, wherein said step of providing browsing means further comprises the sub-step of: saving said client system's state information on said storage device for a particular user; wherein said client system's state information includes Javascripts and cookies; and wherein said client system's state information allows said browsing means to track the current state of said client system and the particular user. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Technical Field The invention relates to Web browsing technology. More particularly, the invention relates to a system and method for fast delivery of and fast rendering of Web pages on a lightweight network device. 2. Description of the Prior Art A typical Web page today contains not only HTML content but also, by reference to, other content elements such as graphics and external style sheets. A browser acquires the referenced content elements by spawning worker threads that retrieve the data via multiple HTTP-TCP/IP connections. This model works well for desktop systems containing large amounts of processing power and RAM. However, it is usually not feasible for mobile, lightweight, embedded devices in which processing power and RAM are much limited. The process for proper HTML parsing, validation, and layout code is normally quite complex and requires large amount of CPU and RAM to execute. Size and manufacturing cost have been major concerns in providing embedded devices with a capacity to implement the process. Although embedded devices are getting more and more processing power and RAM, the requirements of a proper browser engine still outdistance the resources available to even the highest end of embedded devices. High levels of CPU usage are detrimental to the preservation of battery life, which is a very important consideration for today's mobile devices. Heavy loads in HTTP communications, HTML parsing, HTML validation and layout may largely shorten the battery life. Bandwidth usage is also a major constraint that must be considered in designing a browser model for embedded devices. Text based HTML content, although compressible, is already quite large with respect to the limited transmission speed of today's wireless networks. When image content designed for higher resolution and larger form factor display is included, one may quickly end up consuming a lot of wasted bandwidth transmitting redundant, not necessarily usable data to mobile devices. Although various browsing technologies have been already presented in the marketplace, many of them fail to meet the tight constraints and stringent requirements of the embedded devices. Writing a cross platform code base for these devices is an even bigger challenge, given the multitude of operating systems, memory models and processors available for embedded device manufacturers. It would be advantageous to provide a server-based browser system that offloads heavy weight components of a traditional browser to a back end server. It would further be advantageous to provide a server-based browser system that leaves a lightweight client device with a minimal task of implementing a customizable interface to display a pre-rendered representation of Web pages. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention provides a server-based browser system. The system offloads heavy weight components of a traditional browser to a back end server. In addition, the invention leaves a lightweight client device with a minimal task of implementing a customizable interface to display a pre-rendered representation of Web pages. A preferred embodiment of the invention provides a server-based browser and a client system browser. The client browser determines the position of a user click on its display screen and sends a navigation request containing the coordinates of the dick or a hotspot ID, to the server-side browser. The client browser will also accept a specific URL from a user and places the URL in the navigation request. The server-side browser retrieves a Document Object Model (DOM) model and view tree from a storage device for the client It then finds the location on the Web page that the user clicked on using the coordinates or hotspot ID received from the client. If there is a script associated with the location, it is executed and the resulting page location is requested from the appropriate server. If there is a URL associated with the location, it is requested from the appropriate server. The response Web page HTML page definition is parsed and a DOM tree model is created. The server-side browser uses the DOM tree and creates a two-dimensional view tree model, and stores both trees on the storage device. The server-side browser retrieves a style sheet, layout algorithms, and device constraints for the client device from the storage device. It lays out the view model using the style sheet, layout algorithms, and device constraints onto a virtual page. If the client browser is a subset of the server-side browser engine, then the DOM tree and view tree are compressed into a stream and sent to the client browser which decodes the stream, translates the DOM tree and view tree, and displays the page to the user. Otherwise, the server-side browser determines the visual content on the virtual page and the location of the visual content. Visual content and positional information are highly compressed and formatted into a stream and sent to the client browser which decodes the stream and displays the page to the user using the visual content and positional information. The DOM tree and view tree and all state information (including Javascripts and cookies) for the client are stored on the storage device by the server-side browser. Other aspects and advantages of the invention will become apparent from the following detailed description in combination with the accompanying drawings, illustrating, by way of example, the principles of the invention. |
Thiazolyl-substsituted carbocylic 1,3-diones as pesticidal agents |
The present invention relates to novel hetaryl-substituted carbocyclic 1,3-diones of the formula (I) in which A, B, Q1, Q2, Q3, Q4, G, m and Het are as defined in the description, to a plurality of processes for their preparation and to their use as pesticides, herbicides and fungicides. |
1. A compounds of the Formula (I) in which Het represents a nitrogen-containing 5-membered heterocycle, preferably selected from the group consisting of thiazolyl, which heterocycle is optionally substituted by halogen, alkyl, alkoxy, alkenyloxy, halogenoalkyl, halogenoalkoxy, halogenoalkenyloxy, cyano, nitro, alkylthio, alkylsulphinyl, alkylsulphonyl, optionally substituted phenyl or phenoxy, m represents the number 0 or 1, A represents hydrogen, represents in each case optionally halogen-substituted alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl, alkylthioalkyl, saturated or unsaturated, optionally substituted cycloalkyl in which optionally at least one ring atom is replaced by a heteroatom, or in each case optionally halogen-, alkyl-, halogenoalkyl-, alkoxy-, halogenoalkoxy-, cyano- or nitro-substituted aryl, arylalkyl or hetaryl, B represents hydrogen or alkyl, A and B together with the carbon atom to which they are attached represent a saturated or unsaturated, unsubstituted or substituted cycle which optionally contains at least one heteroatom, A and Q1 together represent optionally substituted alkanediyl in which two not directly adjacent carbon atoms optionally form a further optionally substituted cycle, Q1 represents hydrogen, alkyl, alkoxyalkyl, optionally substituted cycloalkyl (in which optionally one methylene group is replaced by oxygen or sulphur) or in each case optionally substituted phenyl, hetaryl, phenylalkyl or hetarylalkyl, Q2, Q3, Q4 independently of one another represent hydrogen or alkyl, Q1 and Q2 together with the carbon atom to which they are attached represent a saturated or unsaturated, unsubstituted or substituted cycle which optionally contains one heteroatom, G represents hydrogen (a) or represents one of the groups in which E represents a metal ion or an ammonium ion, L represents oxygen or sulphur, M represents oxygen or sulphur, R1 represents in each case optionally halogen-substituted alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, polyalkoxyalkyl or optionally halogen-, alkyl- or alkoxy-substituted cycloalkyl which may be interrupted by at least one heteroatom, in each case optionally substituted phenyl, phenylalkyl, hetaryl, phenoxyalkyl or hetaryloxyalkyl, R2 represents in each case optionally halogen-substituted alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl or represents in each case optionally substituted cycloalkyl, phenyl or benzyl, R3 represents in each case optionally substituted alkyl, halogenoalkyl, phenyl or benzyl, R4 and R5 independently of one another represent in each case optionally halogen-substituted alkyl, alkoxy, alkylamino, dialkylamino, alkylthio, alkenylthio, cycloalkylthio or represent in each case optionally substituted phenyl, benzyl, phenoxy or phenylthio, R6 and R7 independently of one another represent hydrogen, in each case optionally halogen-substituted alkyl, cycloalkyl, alkenyl, alkoxy, alkoxyalkyl, represent optionally substituted phenyl, represent optionally substituted benzyl, or together with the N atom to which they are attached represent a cycle which is optionally interrupted by oxygen or sulphur. 2. A compounds of the formula (I) according to claim 1, in which Het represents m represents the number 0 or 1, X represents hydrogen, halogen, C1-C6-alkyl, C1-C6-alkoxy, C3-C6-alkenyloxy, nitro or cyano, Y represents halogen, C1-C6-alkyl, C1-C6-halogenoalkyl, C1-C6-alkoxy, C1-C6-halogenoalkoxy or represents the groups V1 represents hydrogen, halogen, C1-C12-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, C1-C4-halogenoalkyl, C1-C4-halogenoalkoxy, nitro, cyano or represents phenyl, phenoxy, phenoxy-C1-C4-alkyl, phenyl-C1-C4-alkoxy, phenylthio-C1-C4-alkyl or phenyl-C1-C4-alkylthio, each of which is optionally mono- or polysubstituted by halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C4-halogenoalkyl, C1-C4-halogenoalkoxy, nitro or cyano, V2 and V3 independently of one another represent hydrogen, halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C4-halogenoalkyl or C1-C4-halogeno-alkoxy, V1 and V2 jointly together with the carbon atoms to which they are attached represent an optionally C1-C4-alkyl- or halogen-substituted 5- or 6-membered cycle in which optionally one or two carbon atoms may be replaced by oxygen, sulphur or nitrogen, A represents hydrogen or in each case optionally halogen-substituted C1-C12-alkyl, C3-C8-alkenyl, C1-C6-alkoxy-C1-C4-alkyl, optionally halogen-, C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkyl or C3-C6-cycloalkyl-C1-C4-alkyl, in which optionally one or two not directly adjacent ring members are replaced by oxygen and/or sulphur, or represents in each case optionally halogen-, C1-C6-alkyl-, C1-C6-halogenoalkyl-, C1-C6-alkoxy-, C1-C6-halogenoalkoxy-, cyano- or nitro-substituted phenyl, benzyl, hetaryl having 5 or 6 ring atoms or hetaryl-C1-C4-alkyl having 5 or 6 ring atoms, B represents hydrogen or C1-C6-alkyl, A, B and the carbon atom to which they are attached represent saturated C3-C10-cycloalkyl or unsaturated C5-C10-cycloalkyl in which optionally one ring member is replaced by oxygen or sulphur and which are optionally mono- or disubstituted by C1-C6-alkyl, C3-C8-cycloalkyl, C1-C6-halogenoalkyl, C1-C6-alkoxy, C1-C6-alkylthio, halogen or phenyl, A and Q1 together represent C3-C6-alkanediyl which is optionally mono- or disubstituted by identical or different substituents from the group consisting of C1-C4-alkyl and C1-C4-alkoxy, Q1 represents hydrogen, C1-C6-alkyl, C1-C6-alkoxy-C1-C2-alkyl, optionally fluorine-, chlorine-, C1-C4-alkyl-, C1-C2-halogenoalkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkyl in which optionally one methylene group is replaced by oxygen or sulphur or in each case optionally halogen-, C1-C4-alkyl-, C1-C4-alkoxy-, C1-C2-halogenoalkyl-, C1-C2-halogenoalkoxy-, cyano- or nitro-substituted phenyl, pyridyl, thienyl, thiazolyl, phenyl-C1-C4-alkyl, pyridyl-C1-C2-alkyl or thiazolyl-C1-C2-alkyl, Q2, Q3, Q4 independently of one another represent hydrogen or C1-C4-alkyl, Q1 and Q2 together with the carbon atom to which they are attached represent optionally C1-C6-alkyl-, C1-C6-alkoxy- or C1-C2-halogenoalkyl-substituted C3-C7-cycloalkyl in which optionally one ring member is replaced by oxygen or sulphur, G represents hydrogen (a) or represents one of the groups in which E represents a metal ion or an ammonium ion, L represents oxygen or sulphur and M represents oxygen or sulphur, R1 represents in each case optionally halogen-substituted C1-C20-alkyl, C2-C20-alkenyl, C1-C8-alkoxy-C1-C8-alkyl, C1-C8-alkylthio-C1-C8-alkyl, poly-C1-C8-alkoxy-C1-C8-alkyl or optinally halogen-, C1-C6-alkyl- or C1-C6-alkoxy-substituted C3-C8-cycloalkyl, in which optionally one or more not directly adjacent ring members are replaced by oxygen and/or sulphur, represents optionally halogen-, cyano-, nitro-, C1-C6-alkyl, C1-C6-alkoxy-, C1-C6-halogenoalkyl-, C1-C6-halogenoalkoxy-, C1-C6-alkylthio or C1-C6-alkylsulphonyl-substituted phenyl, represents optionally halogen-, nitro-, cyano-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-halogenoalkyl- or C1-C6-halogenoalkoxy-substituted phenyl-C1-C6-alkyl, represents optionally halogen-, C1-C6-alkyl- or trifluoromethyl-substituted 5- or 6-membered hetaryl, represents optionally halogen- or C1-C6-alkyl-substituted phenoxy-C1-C6-alkyl or represents optionally halogen-, amino- or C1-C6-alkyl-substituted 5- or 6-membered hetaryloxy-C1-C6-alkyl, R2 represents in each case optionally halogen-substituted C1-C20-alkyl, C2-C20-alkenyl, C1-C8-alkoxy-C2-C8-alkyl, poly-C1-C8-alkoxy-C2-C8-alkyl, represents optionally halogen-, C1-C6-alkyl- or C1-C6-alkoxy-substituted C3-C8-cycloalkyl or represents in each case optionally halogen-, cyano-, nitro-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-halogenoalkyl- or C1-C6-halogenoalkoxy-substituted phenyl or benzyl, R3 represents optionally halogeno-substituted C1-C8-alkyl or represents in each case optionally halogen-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C4-halogenoalkyl-, C1-C4-halogenoalkoxy-, cyano- or nitro-substituted phenyl or benzyl, R4 and R5 independently of one another represent in each case optionally halogen-substituted C1-C8-alkyl, C1-C8-alkoxy, C1-C8-alkylamino, di-(C1-C8-alkyl)amino, C1-C8-alkylthio, C2-C8-alkenylthio, C3-C7-cycloalkylthio or represent in each case optionally halogen-, nitro-, cyano-, C1-C4-alkoxy-, C1-C4-halogenoalkoxy-, C1-C4-alkylthio-, C1-C4-halogenoalkylthio-, C1-C4-alkyl- or C1-C4-halogenoalkyl-substituted phenyl, benzyl, phenoxy or phenylthio, R6 and R7 independently of one another represent hydrogen, represent in each case optionally halogen-substituted C1-C8-alkyl, C3-C8-cycloalkyl, C1-C8-alkoxy, C3-C8-alkenyl, C1-C8-alkoxy-C1-C8-alkyl, represent optionally halogen-, C1-C8-halogenoalkyl-, C1-C8-alkyl- or C1-C8-alkoxy-substituted phenyl, optionally halogen-, C1-C8-alkyl-, C1-C8-halogenoalkyl- or C1-C8-alkoxy-substituted benzyl or together with the nitrogen to which they are attached represent an optionally C1-C4-alkyl-substituted C3-C6-alkylene radical in which optionally one carbon atom is replaced by oxygen or sulphur. 3. A compound of the Formula (I) according to claim 1, in which Het represents m represents the number 0 or 1, X represents hydrogen, chlorine, bromine or C1-C4-alkyl, Y represents chlorine, bromine, C1-C4-alkyl, C1-C4-halogenoalkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy or the group V1 represents hydrogen, fluorine, chlorine, C1-C6-alkyl, C1-C4-alkoxy, C1-C2-halogenoalkyl, C1-C2-halogenoalkoxy, nitro, cyano or phenoxy which is optionally mono- or disubstituted by fluorine, chlorine, bromine, C1-C4-alkyl, C1-C4-alkoxy, C1-C2-halogenoalkyl, C1-C2-halogenoalkoxy, nitro or cyano, V2 represents hydrogen, fluorine, chlorine, bromine, C1-C4-alkyl, C1-C4-alkoxy, C1-C2-halogenoalkyl or C1-C2-halogenoalkoxy, V1 and V2 jointly, together with the carbon atoms to which they are attached, represent an optionally fluorine- or methyl-substituted 5- or 6-membered cycle in which optionally one or two carbon atoms may be replaced by oxygen, A represents hydrogen, represents C1-C8-alkyl or C1-C4-alkoxy-C1-C2-alkyl, each of which is optionally mono- to trisubstituted by fluorine, represents C5-C6-cycloalkyl or C3-C6-cycloalkyl-C1-C2-alkyl in which optionally one ring member is replaced by oxygen or sulphur, each of which radicals is optionally mono- or disubstituted by fluorine, chlorine, methyl, ethyl or methoxy, or represents phenyl or benzyl, each of which is optionally mono- or disubstituted by fluorine, chlorine, bromine, C1-C4-alkyl, C1-C2-halogenoalkyl, C1-C4-alkoxy or C1-C2-halogenoalkoxy, B represents hydrogen or C1-C4-alkyl, A, B and the carbon atom to which they are attached represent saturated C5-C6-cycloalkyl in which optionally one ring member is replaced by oxygen and which is optionally monosubstituted by C1-C4-alkyl, trifluoromethyl or C1-C4-alkoxy, with the proviso that in this case Q1 represents only hydrogen or C1-C4-alkyl, A and Q1 together represent C3-C4-alkanediyl which is optionally mono- or disubstituted by methyl, ethyl, methoxy or ethoxy, Q1 represents hydrogen, C1-C4-alkyl, C1-C4-alkoxy-C1-C2-alkyl, or optionally methyl- or methoxy-substituted C3-C6-cycloalkyl, in which optionally one methylene group is replaced by oxygen, or represents phenyl or benzyl, each of which is optionally mono- or disubstituted by fluorine, chlorine, bromine, C1-C4-alkyl, C1-C4-alkoxy, trifluoromethyl or trifluoromethoxy, Q2, Q3, Q4 independently of one another represent hydrogen, methyl or ethyl, Q1 and Q2 together with the carbon atom to which they are attached represent optionally C1-C4-alkyl- or C1-C4-alkoxy-substituted saturated C5-C6-cycloalkyl in which optionally one ring member is replaced by oxygen, with the proviso that in this case A only represents hydrogen or C1-C4-alkyl, G represents hydrogen (a) or represents one of the groups in which E represents a metal ion or an ammonium ion, L represents oxygen or sulphur and M represents oxygen or sulphur, R1 represents C1-C16-alkyl, C2-C16-alkenyl, C1-C4-alkoxy-C1-C2-alkyl, C1-C4-alkylthio-C1-C2-alkyl, each of which is optionally mono- to pentasubstituted by fluorine or chlorine, or C3-C6-cycloalkyl in which optionally one or two not directly adjacent ring members are replaced by oxygen and/or sulphur and which is optionally mono- or disubstituted by fluorine, chlorine, C1-C4-alkyl or C1-C5-alkoxy, represents phenyl which is optionally mono- or disubstituted by fluorine, chlorine, bromine, cyano, nitro, C1-C4-alkyl, C1-C4-alkoxy, trifluoromethyl or trifluoromethoxy, represents pyridyl or thienyl, each of which is optionally monosubstituted by fluorine, chlorine, bromine, methyl, ethyl or trifluoromethyl, R2 represents C1-C16-alkyl, C2-C16-alkenyl or C 1 -C4-alkoxy-C2-C4-alkyl, represents C3-C6-cycloalkyl which is optionally mono- or disubstituted by methyl, ethyl or methoxy, represents phenyl or benzyl, each of which is optionally mono- or disubstituted by fluorine, chlorine, bromine, cyano, nitro, C1-C4-alkyl, C1-C4-alkoxy, trifluoromethyl or trifluoromethoxy, R3 represents C1-C4-alkyl which is optionally mono- to pentasubstituted by fluorine or represents phenyl which is optionally mono- or disubstituted by fluorine, chlorine, bromine, C1-C4-alkyl, C1-C4-alkoxy, trifluoromethyl, trifluoromethoxy, cyano or nitro, R4 represents C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylamino, di-(C1-C6-alkyl)amino, C1-C6-alkylthio, or represents phenyl, benzyl, phenoxy or phenylthio, each of which is optionally mono- or disubstituted by fluorine, chlorine, bromine, nitro, cyano, C1-C3-alkoxy, trifluoromethoxy, C1-C3-alkyl or trifluoromethyl, R5 represents C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio, R6 represents hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C3-C6-alkenyl, C1-C6-alkoxy-C1-C6-alkyl, represents phenyl which is optionally mono- or disubstituted by fluorine, chlorine, bromine, trifluoromethyl, C1-C4-alkyl or C1-C4-alkoxy, represents benzyl which is optionally substituted by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl or methoxy, R7 represents hydrogen, C1-C6-alkyl or C3-C6-alkenyl, R6 and R7 together with nitrogen atom to which they are attached represent a C5-C6-alkylene radical in which optionally one methylene group is replaced by oxygen or sulphur and which is optionally mono- or disubstituted by methyl or ethyl. 4. A compound of the Formula (I) according to claim 1, in which Het represents m represents the number 0 or 1, X represents hydrogen, chlorine, bromine, methyl, ethyl, n-propyl or isopropyl, Y represents the group V1 represents hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethyl, trifluoromethoxy or 4-chlorophenoxy, V2 represents hydrogen, fluorine, chlorine, bromine, methyl, methoxy or trifluoromethyl, A represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxymethyl, ethoxymethyl, phenyl or cyclohexyl, B represents hydrogen, methyl or ethyl, A, B and the carbon atom to which they are attached represent saturated C5-C6-cycloalkyl in which optionally one ring member is replaced by oxygen and which is optionally monosubstituted by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, n-propoxy, n-butoxy or isobutoxy, with the provisio that in this case Q1 only represents hydrogen, A and Q1 together represent C3-C4-alkanediyl, Q1 represents hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclopentyl, cyclohexyl or 4-chlorophenyl, Q2, Q3, Q4 independently of one another represent hydrogen, methyl or ethyl, Q1 and Q2 together with the carbon atom to which they are attached represent optionally methyl-, ethyl-, methoxy-, ethoxy-, n-propoxy- or n-butoxy-substituted saturated C5-C6-cycloalkyl in which optionalloy one ring member is replaced by oxygen, with the proviso that in this case A only represents hydrogen, G represents hydrogen (a) or represents one of the groups in which E represents a metal ion or an ammonium ion, L represents oxygen or sulphur and M represents oxygen or sulphur, R1 represents in each case optionally fluorine- or chlorine-substituted C1-C8-alkyl, C2-C8-alkenyl, C1-C2-alkoxy-C1-C2-alkyl, C1-C2-alkylthio-C1-C2-alkyl or cyclopropyl or cyclohexyl, each of which is optionally monosubstituted by fluorine, chlorine, methyl, ethyl or methoxy, represents phenyl which is optionally monosubstituted by fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, methoxy, trifluoromethyl or trifluoromethoxy, represents thienyl or pyridyl, each of which is optionally monosubstituted by fluorine, chlorine, bromine or methyl, R2 represents C1-C8-alkyl, C2-C8-alkenyl or C1-C4-alkoxy-C2-alkyl, represents C3-C6-cycloalkyl which is optionally monosubstituted by methyl, ethyl or methoxy, represents phenyl or benzyl, each of which is optionally monosubstituted by fluorine, chlorine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, methoxy, trifluoromethyl or trifluoromethoxy, R3 represents methyl or ethyl, each of which is optionally trisubstituted by fluorine or represents phenyl which is optionally monosubstituted by fluorine, chlorine, bromine, methyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, cyano or nitro, R4 represents C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylamino, di-(C1-C4-alkyl)amino, C1-C4-alkylthio or represents phenyl, phenoxy or phenylthio, each of which is optionally monosubstituted by fluorine, chlorine, bromine, nitro, cyano, C1-C2-alkoxy, trifluoromethoxy or C1-C3-alkyl, R5 represents methyl, ethyl, methoxy, ethoxy, methylthio or ethylthio, R6 represents hydrogen, represents C1-C4-alkyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C3-C4-alkenyl or C1-C4-alkoxy-C1-C4-alkyl, R7 represents hydrogen, C1-C4-alkyl or C3-C4-alkenyl, R6 and R7 together with the nitrogen atom to which they are attached represent a C5-alkylene radical in which optionally one methylene group is replaced by oxygen. 5. A compound of the Formula (I) according to claim 1, in which Het represents m represents the number 0 or 1, X represents hydrogen, methyl or ethyl, Y represents the group V1 represents hydrogen, chlorine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl or represents 4-chloro-phenoxy, A represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, phenyl or cyclohexyl, B represents hydrogen, methyl or ethyl, A, B and the carbon atom to which they are attached represent saturated C5-C6-cycloalkyl in which optionally one ring member is replaced by oxygen and which is optionally monosubstituted by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, n-butoxy or isobutoxy, with the proviso that in this case Q1 only represents hydrogen, A and Q1 together represent C3-C4-alkanediyl, Q1 represents hydrogen, methyl, ethyl, n-propyl, isopropyl or 4-chlorophenyl, Q2 represents hydrogen, methyl or ethyl, Q3 represents hydrogen, Q4 represents hydrogen, Q1 and Q2 together with the carbon atom to which they are attached represent saturated C5-C6-cycloalkyl, with the proviso that in this case A only represents hydrogen, G represents hydrogen (a) or represents one of the groups in which L represents oxygen and M represents oxygen or sulphur, R1 represents C1-C8-alkyl, C1-C2-alkoxy-C1-C2-alkyl or cyclopropyl which is optionally monosubstituted by chlorine, represents phenyl which is optionally monosubstituted by chlorine, represents pyridyl which is optionally monosubstituted by chlorine, R2 represents C1-C8-alkyl, represents phenyl or benzyl, R3 represents methyl or ethyl, R6 and R7 together with the nitrogen atom to which they are attached represent a C5-alkylene radical in which optionally one methylene group is replaced by oxygen. 6. A process for preparing a compound of the Formula (I) according to claim 1, wherein to obtain (A) a compound of the Formula (I-1-a) in which A, B, Q1, Q2 and Het are as defined in claim 1, a compound of the Formula (II) in which A, B, Q1, Q2 and Het are as defined in claim 1 and R8 represents alkyl, is condensed intramolecularly, optionally in the presence of a diluent and in the presence of a base, (B) a compound of the Formula (I-2-a) in which A, B, Q1, Q2, Q3, Q4, and Het are as defined claim 1, a compound of the Formula (III) in which A, B, Q1, Q2, Q3, Q4 and Het are as defined in claim 1 and R8 represents alkyl, is condensed intramolecularly in the presence of a diluent and in the presence of a base, (C) a compound of the Formulae (I-1-b) or (I-2-b) in which A, B, Q1, Q2, Q3, Q4, m, R1 and Het are as defined in claim 1, a compound of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case (α) reacted with an acid halide of the Formula (IV) in which R1 is as defined in claim 1 and Hal represents halogen or (β) reacted with a carboxylic anhydride of the Formula (V) R1—CO—O—CO—R1 (V) in which R1 is as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of an acid binder; (D) a compound of the Formulae (I-1-c) or (I-2-c) in which A, B, Q1 , Q2, Q3, Q4, m, R2, M and Het are as defined in claim 1 and L represents oxygen, compounds of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case reacted with a chloroformic ester or a chloroformic thioester of the Formula (VI) R2—M—CO—Cl (VI) in which R2 and M are as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of an acid binder; (E) a compound of the Formulae (I-1-c) or (I-2-c) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m, R2, M and Het are as defined in claim 1 and L represents sulphur, compounds of the Formulae (I-1 -a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case reacted with a chloromonothioformic ester or a chlorodithioformic ester of the Formula (VII) in which M and R2 are as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of an acid binder and (F) a compound of the Formulae (I-1-d) or (I-2-d) in which A, B, Q1, Q2, Q3, Q4, m, R3 and Het are as defined in claim 1, compounds of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case reacted with a sulphonyl chloride of the Formula (VIII) R3—SO2—Cl (VIII) in which R3 is as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of an acid binder, (G) a compound of the Formulae (I-1-e) or (I-2-e) in which A, B, L, Q1, Q2, Q3, Q4, m, R4, R5 and Het are as defined in claim 1, compounds of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case reacted with a phosphorus compound of the Formula (IX) in which L, R4 and R5 are as defined in claim 1 and Hal represents halogen, optionally in the presence of a diluent and optionally in the presence of an acid binder, (H) a compound of the formulae (I-1-f) or (I-2-f) in which A, B, E, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1, compounds of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case reacted with a metal compound or an amine of the Formulae (X) and (XI), respectively, Me(OR11)t (X) in which Me represents a mono- or divalent metal, t represents the number 1 or 2 and R11, R12, R13 independently of one another represent hydrogen or alkyl, optionally in the presence of a diluent, (I) a compound of the Formulae (I-1-g) or (I-2-g) in which A, B, L, Q1, Q2, Q3, Q4, m, R6, R7 and Het are as defined in claim 1, compounds of the Formulae (I-1-a) or (I-2-a) shown above in this claim 6 in which A, B, Q1, Q2, Q3, Q4, m and Het are as defined in claim 1 are in each case (α) reacted with an isocyanater or isothiocyanater of the Formula (XII) R6—N═C═L (XII) in which R6 and L are as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of a catalyst, or (β) reacted with a carbamoyl chloride or a thiocarbamoyl chloride of the Formula (XIII) in which L, R6 and R7 are as defined in claim 1, optionally in the presence of a diluent and optionally in the presence of an acid binder. 7. A compound of the Formula (II) in which A, B, Q1, Q2 and Het are as defined in claim 1 and R8 represents alkyl. 8. A compound of the Formula (III) in which A, B, Q1, Q2, Q3, Q4, and Het are as defined in claim 1, and R8 represents alkyl. 9. A compound of the Formula (XIV) in which A, B, Het, Q1 and Q2 are as defined in claim 1. 10. A compound of the Formula (XV) in which A, B, Het, Q1 and Q2 are as defined claim 1 and R8 and R8′ represents alkyl. 11. A compound of the Formula (XIX) in which A, B, Het, Q1, Q2, Q3 and Q4 are as defined claim 1. 12. A compound of the Formula (XX) in which A, B, Het, Q1, Q2, Q3, and Q4are as defined in claim 1, R8 and R8 represent alkyl. 13. Pesticides, herbicides and fungicides comprising at least one compound of the Formula (I) according to claim 1. 14. A method for controlling animal pests, undesirable vegetation and/or fungi comprising allowing a compound of the Formula (I) according to claim 1 to act on pests, undesirable vegetation and/or fungi and/or their habitat. 15. canceled 16. A process for preparing pesticides, herbicides and/or fungicides comprising mixing one or more compounds of the Formula (I) according to claim 1 with one or more extenders and/or surfactants. 17. canceled. |
Reversible life raft comprising removable shelters |
Rescue and safety device, permitting the reversibility of a rescue raft, shelter (s)-tent (s), consists of an inflated grille provided with unlockable, spreadable and lockable openings, handles and safety belts. On this grille are fixed bags (11) containing membranes that expand into the shelter(s) (8) and the floor(s) (7). The whole is made to be removable, including the weight element, by a fastener system that is laid on two sides of a boat. The male fasteners are fixed to handles (4) and bags (11), the female fasteners are fixed on the rods and allow, if the raft expands inside out, it to be remounted in place. |
1. Rescue and safety device, permitting the reversibility of a survival raft, shelter (s)-tent (s), consists of an inflated grille, provided with handle and safety belts, whose meshes filled with netting, are provided with openings which can be unlocked, spreaded and locked, said device characterized in that the device is made to be totally reversible by fastening means distributed on two sides of the raft, in that it is composed of means allowing the weight element to fix, stabilize and to make it removable, in that it is composed of at least a bag (11) fixed removably to the grille (1), this bag comprises two membranes, said membranes expand into shelter (8), floor (7) extending on at least a mesh (6) of the grille (1), these membranes-shelters (8) form, by mean of a structure (12), (19), (37), a space which is reinforced by some means and whose sides (13), (18) are also created which have the possibility to expand and fix them to adjacent spaces, contained previously in other bags (11), and to fix also to the bottom of the grille (1), on rods, in order to establish common multiple cell spaces, in that said openings (3) in the netting (2) are openable from over side as well as from underside of the device, by some means, in that said bags (11), handles (4) are provided with fasteners being fixed with fasteners distributed on two sides of the raft, fasteners receiving the periphery of floors and shelters being also distributed on two sides of the raft, in that the bag (s) (11) as well as bases of shelters (8) and floors (7) are composed of ground engaging fasteners (14) with a peg pouch included in said bag, making the shelter (s) (8) with floor (7) independent. 2. Device according to claim 1, characterized in that said membrane forming shelter (8) expands into two parallelepipeds interconnected by a structure in the form of an H (12) with four panels (13) on its sides, said structure is folded following the movement of the center bar of the H which is rotated over half a turn on itself causing the whole of stops/upright posts to be in the form of a bundle with the membrane-shelter and the membrane-floor in front of the latter, being maintained inside a bag, said structure is reinforced when it is filled with water, gas/air or rods, pipes, on the sides of the H, panels of membranes in form of equilateral triangles (13) allow, when the structure is raised, to close sides of a refuge by fixing two said triangles one on the other, of each side, forming also an individual shelter and by fixing the periphery of the base of the shelter which is connected to the grille or to the ground. 3. Device according to claim 1, characterized in that said membranes from at least two bags (11), expand into at least two structures in the form of an H (12) interconnected each time by a center bar of the H which forms a roof, said structures are reinforced when they are filled with water, gas/air or rods, pipes, on the sides of each H, the panels of the membrane in the form of equilateral triangles (13) forming sides allow, when the structure is raised, to close said sides of the refuge, those sides are fixed along one after the other triangle (13) and connecting two triangles (13) of the structure at its end one above the other in order to form a multiple shelter in the form of a tunnel, said parallelepipeds being laid inside form inner raised walls, so that it can be fixed to disengage the space, the periphery of the shelter is fixed to the grille or to the ground. 4. Device according to claim 1, characterized in that a shelter (8) which consists of six structures in the form of an H (12), which expand each time by a center bar of the H forming a roof, said structures are reinforced when they are filled with water, gas/air or rods, pipes, the panels of the membrane in the form of equilateral triangles (13) allow, when the structure is raised, to close sides of the refuge, these sides panels are fixed on the lateral panels along one after the other triangle (13), roofs of the refuge are fixed once over side, once under side of the triangles of square or adjacent rectangular elements in order to establish the whole of several shelters, the inner walls also create of means allowing them to be disengaged, raised, it is the same for the ends used for inlet/outlet openings (38), the base of the shelter is fixed to the grille (1) or to the ground. 5. Device according to claim 1, characterized in that these stops/upright posts (22) consist of folds, which can receive a fluid, rods, pipes. 6. Device according to claim 1, characterized in that said structures in the form of an H (12), form spiders as a pyramid (19), the structure with three sides (37) as well as these membranes-shelters (8), floors (7) are doubled, which are inflated by an automatic air/gas generator or by an air/gas muscle-powered pump (20). 7. Device according to claim 1, characterized in that the surfaces of floors (7) are provided with button holes, slits (25), allowing the passage of handles (4). 8. Device according to claim 1, characterized in that said structures in the form of spiders (19) and said structures consisting of three sides (37) are provided with panels with accordions (17) for its extension to the adjacent space. 9. Device according to claim 1, characterized in that, a bag contains a telescopic mast with a sail and oars. |
<SOH> BACKGROUND ART <EOH>According to the technical background, the object of the document PCT/CH99/00619 is to provide a wider impact surface on the sea wherein an ordinary boat operates and permits someone stuck beneath the device, when it expands, to move onto the device and to stay there by means of unlockable, spreadable and lockable openings permitting shipwrecked persons to grasp the netting in order to rejoin one of the openings. It also allows, if required, the device to be caught by hand and feet through handles and to use safety belts. However, survivors are neither protected from the weather influences in cold sea, waves that can pass through the netting, nor the sunlight, and if the raft is opened inside out, shipwrecked persons do not have handles and safety belts. Also according to the technical background, the document DE 3210 590 A1, 23.03.82 discloses a device for use in open water, which is a multiple place buoy without netting, the tarpaulins of which cover a certain number of openings, and do not form a floor on all the surface. Shelters are provided, but they are located on certain units, they are fixed and they can't communicate to each other and they form multiple spaces. Children can slide in the openings, survivors can meet splashes, water can stagnate in the tarpaulins and form pockets there, and when survivors are below the shelter, it is going to create an unbalance and the multiple buoy will be returned, this situation can get worse at the, time of coupling units in a rough sea, because nothing guarantees that shelters are arranged head-to-tail in such way to balance loads. On the contrary, in the panic condition, unfortunately, it is impossible to perform such operation, many persons must be also exposed to weather influences. Rescue boats, which are available now in the market, are used only on a small surface, with a very limited number of persons on boards, aircraft glide paths, toboggans and require a skillful folding with a link system in the form of any press-studs so that they are opened in the common direction. |
<SOH> SUMMARY OF THE INVENTION <EOH>Therefore, the object of the invention is to provide a rescue and safety device that is able to overcome these drawbacks. The advantages of the invention reside in the fact that the rescue raft is made totally reversible by the use of male receiving fasteners distributed on both sides of the raft for forming removable floors, shelters which can be engaged by interconnecting several spaces or a single space at the selected location on the device without the requirement of the proper opening of the raft. This flexibility is realized by the following features: fasteners distributed on both sides of the boat, removable bags containing shelter and floor, removable handles and safety belts, removable weight element. By the selection of structures in the form of an H, with triangles, structures with three sides, those sides are provided with panels in the form of bellows, structures in the form of a spider provided with panels in the form of bellows. The invention will be better understood by reading the description of the embodiments given as non-restrictive examples with regards to the underlying figures. |
Digital video protection for authenticity verification |
A method and apparatus for verifying the authenticity and integrity of an ordered sequence of digital video frames, without having access to the original recording, by embedding therein a respective series of digital signatures based on a secret key, or keys, and on the video content of respective frames. Signatures are camouflaged by embedding in transform coefficients of a transformed representation of the video data in parts of the frame corresponding to motion. If there is sufficient motion to contain all of the signature bits, a supplementary technique embeds in high-texture areas of a frame. A final fall-back is to embed in a pre-defined default zone. A method of predicting when supplementary embedding is needed enables the process to be applied in a single pass allowing real-time operation. Verification is done during decoding by comparing, for identity, embedded signatures with signatures calculated anew using the method employed to embed. |
1. A method for verifying an authenticity and integrity of an ordered sequence of digital video frames, the video frames including respective data, the digital frames including Inter frames and Intra frames both including segments, the segments of the Inter frames including Inter segments and Intra segments, the segments of the Intra frames including Intra segments, the method comprising the steps of: a) providing at least one secret key; and b) protecting the sequence by embedding a respective calculated digital signature in at least one video frame to produce a protected sequence: i) each said calculated digital signature being dependent on the data of another video frame; and ii) each said calculated digital signature being generated using one of said at least one secret key. 2. The method of claim 1 wherein each said at least one signature is dependent on recording environment parameters. 3. The method of claim 1 wherein each said at least one signature is embedded in a respective video frame according to an embedding pattern. 4. The method of claim 1 wherein each said at least one signature is embedded in a respective video frame according to embedding criteria. 5. The method of claim 1 wherein a respective said signature is embedded in each digital video frame. 6. The method of claim 5 wherein each said signature is dependent on an immediately preceding video frame. 7. The method of claim 1 wherein the method is performed in a single pass. 8. The method of claim 1 further including the step of: c) compressing the video sequence into a bit stream according to a video compression standard. 9. The method of claim 8 wherein said video compression standard is a transform-based video compression standard. 10. The method of claim 9 wherein said transform-based video compression standard is a block-based video compression standard. 11. The method of claim 10 wherein said block-based video compression standard is a DCT-based video compression standard. 12. The method of claim 11 wherein said DCT-based video compression standard is selected from the group consisting of: an H.261 video compression standard, an H.263 video compression standard, an H.263+ video compression standard, an H.263L video compression standard, an MPEG1 video compression standard, an MPEG2 video compression standard, and an MPEG4 video compression standard. 13. The method of claim 12 wherein a syntax of said video compression standard includes a frame layer. 14. The method of claim 1 wherein said digital signature is generated using an encryption algorithm. 15. The method of claim 14 wherein said encryption algorithm is a Data Encryption Standard algorithm. 16. The method of claim 14 wherein said generation is done using a full cipher block chaining mode of said Data Encryption Standard. 17. The method of claim 1 further comprising the steps of c) dividing each segment into at least one macroblock, each said macroblock having an associated plurality of compression parameters, said compression parameters including: i) a transform coefficient; ii) a motion vector; and iii) a quantization level; and d) performing a transform on at least one respective frame thereby providing, for said respective frame, a plurality of transform coefficients wherein a respective said embedded digital signature is embedded. 18. The method of claim 17 further comprising the step of: e) quantizing said coefficients. 19. The method of claim 18 wherein only a single bit of said embedded digital signature is embedded in each said transform coefficient. 20. The method of claim 19 wherein said transform is a Discrete Cosine Transform. 21. The method of claim 17 wherein each said transform coefficient is chosen according to an embedding pattern. 22. The method of claim 19 wherein said only a single bit is embedded in a least-significant bit of said transform coefficient. 23. The method of claim 21 wherein said embedding pattern includes a plurality of pointers to said transform coefficients. 24. The method of claim 21 wherein a respective calculated digital signal is embedded in each of a plurality of video frames according to one of a plurality of types of said embedding patterns. 25. The method of claim 24 wherein said plurality of types of said embedding patterns includes an Inter embedding pattern. 26. The method of claim 25 wherein, for each said video frame wherein a respective calculated digital signal is embedded, said Inter embedding pattern is derived from said transform coefficients of another Inter frame by selecting therefrom a plurality of said transform coefficients of highest absolute value. 27. The method of claim 26 wherein said plurality is a number greater than or equal to a number of bits of said digital signature. 28. The method of claim 26 wherein a bit of said digital signature is embedded in a transform coefficient of a macroblock pointed to by said embedding pattern only if at least one embedding criterion is satisfied. 29. The method of claim 28 wherein said at least one embedding criterion includes that an absolute value of said associated transform coefficient exceeds a predetermined value. 30. The method of claim 28 wherein said at least one embedding criterion includes that an absolute value of said associated motion vector exceeds a predetermined value. 31. The method of claim 28 wherein said at least one embedding criterion includes that said associated quantization level be at most as great as a predetermined value. 32. The method of claim 25 wherein, if said frame is an Inter frame, then in an Intra macro-block in a said Inter frame, a said transform coefficient in a said Intra macroblock pointed to by said Inter embedding pattern is embedded only if an absolute value of said associated transform coefficient exceeds a predetermined value. 33. The method of claim 26 wherein said other Inter frame is an immediately preceding Inter frame. 34. The method of claim 24 wherein said plurality of types of said embedding patterns includes a default embedding pattern including a pre-defined default embedding zone. 35. The method of claim 34 wherein a said transform coefficient is embedded if pointed to by a pointer of said default embedding pattern. 36. The method of claim 34 wherein said plurality of pointers is a number greater than or equal to a number of bits of said digital signature and wherein each said pointer points to a respective defined location in said default embedding zone. 37. The method of claim 36 wherein said default embedding zone includes a series of locations located at an end of the digital video frame according to a raster scanning order. 38. The method of claim 24 wherein said plurality of types of said embedding patterns includes an Intra embedding pattern. 39. The method of claim 38 wherein, for each said video frame wherein a respective calculated digital signal is embedded, said Intra embedding pattern is derived from said transform coefficients of another Intra frame by selecting a plurality of said pointers to highest-textured said macroblocks in said other Intra frame. 40. The method of claim 39 wherein said another Intra frame is a nearest preceding Intra frame. 41. The method of claim 39 further comprising the step of: f) determining said highest-textured macroblocks by: i) calculating a pixel luminance variance of each said macroblock of said other frame; and ii) selecting said macroblocks having said plurality of highest said variances. 42. The method of claim 17 wherein, in a said Intra frame, a said transform coefficient in a said Intra macroblock is embedded only if an absolute value of said associated transform coefficient exceeds a predetermined value. 43. The method of claim 1 further comprising the steps of: f) dividing a bit stream of the digital video frame into a plurality of consecutive blocks of bits, each said block having an equal number of bits; g) dividing each said block into a plurality of consecutive words, each said word having an equal number of bits; and h) i) XOR-ing said words of a first said block to provide a first block word; ii) encrypting said first block word with said secret key, thereby obtaining an encrypted block word; iii) XOR-ing said first encrypted block word with said words of a second said block thereby obtaining a second encrypted block word; and vii) repeating steps (ii) and (iii) until said plurality of consecutive words have been exhausted, thereby obtaining said digital signature. 44. The method of claim 43 further including the step of padding said bit stream to enable said blocks to have equal size. 45. The method of claim 44 wherein said padding is done with zeroes. 46. The method of claim 44 further including the step of padding said blocks of bits to enable said words to have equal size. 47. The method of claim 46 wherein said padding is done with zeroes. 48. The method of claim 43 wherein said secret key includes selected data. 49. The method of claim 48 wherein said selected data includes identifying data. 50. The method of claim 49 wherein said identifying data is selected from the group consisting of information relating to a time of recording, a date of recording, and a recording channel number. 51. The method of claim 1 further comprising the step of i) confirming an authenticity and integrity of said protected sequence. 52. The method of claim 51 wherein said confirming includes i) extracting said embedded digital signature from each at least one frame of said protected sequence, thereby obtaining a frame signature; ii) calculating from each in at least one frame of said protected sequence a new digital signature, using said secret key, thereby obtaining a stream signature; and iii) inferring authenticity and integrity by comparing said extracted digital signatures with respective said new calculated signatures for identity. 53. The method of claim 6, wherein said new digital signature depends on data of another video frame. 54. The method of claim 52 wherein said frame signature in each frame of said protected sequence is extracted from a least-significant bit of said transform coefficients of claim 17 pointed to by said embedding patterns of claim 21 only if at least one criterion selected from a group consisting of: a) that an absolute value of a said associated transform coefficient exceeds a predetermined value; b) that an absolute value of a said associated motion vector exceeds a predetermined value; and c) that said associated quantization level be at most as great as a predetermined value; is satisfied. 55. The method of claim 52 wherein said stream signature is generated using an encryption algorithm. 56. The method of claim 52 wherein said authenticity and integrity are deemed confirmed if said frame signature is identical to said stream signature. 57. The method of claim 1 further comprising the step of: j) adding a dummy, final frame to the ordered sequence of frames for containing an embedded signature to verify an original final frame of the sequence. 58. In an ordered sequence of digital video frames, the sequence being compressed according to a video compression standard, the sequence including at least one Intra frame and the frames including segments, a method of predicting a plurality of highest-textured segments in a frame comprising the steps of: a) Counting non-zero transform coefficients in each segment of one of the at least one Intra frame; and b) Selecting a plurality of segments having highest said counts of said transform coefficients. 59. The method of claim 58 wherein the segments are macroblocks. 60. The method of claim 58 wherein the video compression standard is a transform-based video compression standard. 61. The method of claim 60 wherein said transform-based video compression standard is a block-based video compression standard. 62. The method of claim 60 wherein said block-based video compression standard is a DCT-based video compression standard. 63. The method of claim 62 wherein said DCT-based video compression standard is selected from the group consisting of: an H.261 video compression standard, an H.263 video compression standard, an H.263+ video compression standard, an H.263L video compression standard, an MPEG1 video compression standard, an MPEG2 video compression standard, an MPEG4 video compression standard. 64. The method of claim 58 wherein said one Intra frame is a nearest preceding Intra frame. 65. A method of protecting an authenticity and integrity of an ordered sequence of digital video frames, comprising the steps of: a) compressing the frames according to a transform-based video compression standard; and b) for at least one frame: (i) embedding bits of a digital signature in respective transform coefficients of said at least one frame, and (ii) prior to said embedding, predicting a number of mis-embeddings of said bits. 66. The method of claim 65 further comprising the steps of: c) counting a number of non-effective embeddings in another frame; and d) deriving the number of mis-embeddings from said number of non-effective embeddings. 67. The method of claim 66 wherein said deriving is effected according to: Mi=max[min{(Nj−κ), S}, 0] wherein Mi is the predicted number of mis-embeddings in the frame, Nj is said counted number of non-effective embeddings in the other frame, κ is a non negative constant at most as great as a number of locations pointed to by the embedding pattern, and S is a number of bits in the digital signature. 68. The method of claim 66 wherein said other frame is an immediately preceding frame. 69. An apparatus for embedding digital signatures into an input sequence of digital video frames comprising: a) a video encoder for compressing and encoding the input sequence to produce a compressed and encoded sequence; b) a digital-signature-generation unit for generating a digital signature for embedding into the frames of said compressed and encoded sequence; c) an embedding-pattern-generation unit for generating an embedding pattern; and d) a signature-embedding unit for embedding said digital signature into the frames of said compressed and encoded sequence according to said embedding pattern. 70. The apparatus of claim 69 further comprising: e) a memory for storing: i) said digital signature; and ii) said embedding pattern. 71. The apparatus of claim 69 wherein said video encoder is a transform-based video encoder. 72. The apparatus of claim 71 wherein said transform-based video encoder is a block-based video encoder. 73. The apparatus of claim 72 wherein said block-based video encoder is a DCT-based video encoder. 74. The apparatus of claim 73 wherein said DCT-based video encoder is selected from the group consisting of: an H.261 video encoder, an H.263 video encoder, an H.263+ video encoder, an H.263L video encoder, an MPEG1 video encoder, an MPEG2 video encoder, and an MPEG4 video encoder. 75. The apparatus of claim 74 wherein: a) said signature-embedding unit receives an input from a quantizer module of said video encoder and outputs a signal to: i) said inverse quantizer module of said video encoder; ii) said embedding-pattern-generation unit; and iii) an entropy coding module of said video encoder; b) said embedding-pattern-generation unit outputs said embedding pattern to an input of said memory for storing said embedding pattern; c) said digital-signature-generation unit receives: i) an output of said entropy coding module of said video encoder; and ii) a secret key; and outputs said digital signature to another input of said memory for storing said digital signature; and d) said memory for storing outputs said embedding pattern and said digital signature to respective inputs of said signature embedding unit. 76. An apparatus for authenticating and verifying respective embedded digital signatures in an input sequence of digital frames comprising: a) a video decoder for decompressing and decoding the input sequence, thereby providing a decompressed and decoded sequence; b) a stream-signature generation unit for calculating a digital signature for each frame of said decompressed and decoded sequence; c) an embedding pattern generating unit for generating a respective embedding pattern for each frame of said decompressed and decoded sequence to point to a location, in said each frame, of the respective embedded digital signature; d) a frame signature extracting unit for extracting the respective embedded digital signature from each frame of said decompressed and decoded signature in accordance with said respective embedding pattern; and e) an authenticity-verification unit for determining an authenticity and veracity of said decompressed and decoded sequence. 77. The apparatus of claim 76 further comprising: f) at least one memory for: (i) storing said calculated digital signature; (ii) storing said extracted embedded digital signature; and (iii) storing said generated embedding pattern. 78. The apparatus of claim 76 wherein said video decoder is a transform-based augmented video decoder. 79. The apparatus of claim 78 wherein said transform-based augmented video decoder is a block-based augmented video decoder. 80. The apparatus of claim 79 wherein said block-based augmented video decoder is a DCT-based augmented video decoder. 81. The apparatus of claim 80 wherein said DCT-based augmented video decoder is selected from the group consisting of: an H.261 augmented video decoder, an H.263 augmented video decoder, an H.263+ augmented video decoder, an H.263L augmented video decoder, an MPEG1 augmented video decoder, an MPEG2 augmented video decoder, and an MPEG4 augmented video decoder. 82. The apparatus of claim 81 wherein: a) said frame signature extraction unit receives an input from an entropy decoding module of said video decoder and outputs a signal to an inverse quantizer module of said video decoder; b) said embedding pattern generation unit receives an input from said entropy decoding module of said video decoder and outputs said generated embedding pattern to said memory for storing said generated embedding pattern; c) said memory for storing said generated embedding pattern outputs said generated embedding pattern to said frame signature extraction unit; d) said stream signature generation unit receives: i) a same input as said entropy decoding module; and ii) a secret key; and outputs said calculated digital signature to said memory for storing said calculated digital signature; e) said memory for storing said calculated digital outputs said calculated digital signature to said authenticity-verification unit; and f) said authenticity-verification unit also receives a said extracted embedded digital signature from said frame-signature extraction unit and outputs an authenticity decision. |
<SOH> FIELD AND BACKGROUND OF THE INVENTION <EOH>The present invention relates to digital video and, more particularly, to a means of incorporating therein and extracting hidden information for authenticity verification. The widespread use of digital media for recording information has brought with it a need to be able to the authenticity of such records. It is well known that digital media are more susceptible to alteration and manipulation than any previously known medium. Verification is particularly needed in courts of law, where such records may be tendered as evidence. A mechanism is therefore required to authenticate and verify information and to detect fabrication of, or tampering with evidence. Media tampering refers to any manipulation of media that modifies its content, e.g. image blurring or cropping, and frame eliminating or reordering. The present invention is concerned with recorded video from a variety of systems, such as security CCTV. An example of such a system is the NICE-Vision® video recording system (NICE Systems Ltd., Ra'anana, Israel), which performs compression of analog video channels and digitally saves the compressed data (in accordance with the H.263+ standard) on disks that can be accessed and played back, as required. |
<SOH> SUMMARY <EOH>As seen above, various attempts have been made to embed signatures into digital video. There is thus a widely recognized need for, and it would be highly advantageous to have, a means of verifying the authenticity and integrity of digital media. |
System for cellular storage and genetic information retrieval |
A system for storage of cellular material and retrieval of genetic information comprises a cell bank comprising a plurality of cell storage units for storage of cellular material from individual depositors. Cryo-preservation of the material is contemplated. Genetic information obtained from the cellular material is complied in a digital information which can be accessed such as for medical, pharmaceutical, and biological research, diagnosis, and treatment. Fees generated in connection with retrieval of the genetic information will permit cost-effective storage of cellular material. When a decrease in storage costs and storage fees leads to an increase in the number of depositions of cellular material, the significance and the value of the genetic information available in the data base will increase. |
1. A system for cellular material storage and genetic information retrieval, comprising: a cell bank comprising a plurality of cell storage units for storage of cellular material; a digital information unit for digitally storing genetic information obtained from the cellular material stored in said cell storage units; and data retrieval means interfaced with said digital information unit for retrieving selected genetic information. 2. A system for cellular storage and genetic information retrieval in accordance with claim 1, wherein: said cell bank provides cryo-preservation of cellular material storage in said cell storage units. 3. A system for cellular storage and genetic information retrieval in accordance with claim 1, wherein: said digital information unit comprises a digital computer. 4. A system for cellular storage and genetic information retrieval in accordance with claim 1, wherein: said data retrieval means is operatively interconnected with telephone or Internet access. 5. A system for cellular storage and genetic information retrieval in accordance with claim 1, wherein: said digital information unit anonymously digitally stores said genetic information. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Cell banking is a service industry in which live cells are stored for later use. This type of storage of cellular material has been practiced for a number of years, as exemplified by the storage of bovine sperm cells for artificial insemination of cows, which has been practiced for several decades. Presently, many types of cells, from fungi to human cells, are stored for varying periods of time, till the use of the cells is required, such as for research, production of bio-active molecules, diagnosis, or medical treatment. A well-known method for long-term storage of cells, while maintaining their viability, is cryo-preservation. Such preservation is effected by freezing and cooling the cells, along a prescribed path, to a temperature on the order of −196° C., in the presence of compounds which render the cells resistant to frost damage. After such a procedure, maintaining the cells at such a low temperature prevents deterioration of the cellular material. With the technical advances that are being made in biomedical research and tissue engineering, it is being recognized that many possibilities may exist for use of human stem cells for various replacement therapies. These developments have led to a growing demand for facilities where stem cells of individuals can be isolated, cryo-preserved, and stored for later (autologous) use. By way of example, the desirability of storing the cord blood stem cells of newborns, is becoming increasingly recognized, with a rapidly increasing number of deposits of such stem cells in private cell banks. Because of the rapid progress in biomedical sciences, an increasing number of applications are being found for use of cellular material in medical treatments. Moreover, it is expected that the potential of “tissue engineering” in the future may lead to the “re-growth” of organs from stem cells. This would address the growing shortage in donor material for transplants, and could potentially result in large savings in healthcare costs. It is believed that such developments will create an increased demand for storage facilities for cells or tissue, either for relatively short periods of time such as for the depositor's benefit, or for longer time periods so as to benefit the depositors, other individuals (such as family members), selected groups in society, and society as a whole, by use of the material for medical treatment and/or research. It has been recognized that private cell banking can be a potentially profitable business, with the recognition that virtually anyone could be a potential client of such services in view of the potential benefits that could be derived. However, it is recognized that the relatively high fees and expenses associated with private cell banking substantially prevents a relatively high percentage of market penetration, particularly in less affluent societies. In accordance with the present invention, it is recognized that cell banking market penetration could be significantly enhanced if fees and expenses associated therewith could be moderated, thus enhancing overall, global market penetration. Of course, the ability of a cell banking facility to control and moderate expenses facilitates competition with other like storage facilities. |
<SOH> SUMMARY Of The INVENTION <EOH>The present invention contemplates a system for cellular material storage, i.e., cell banking, and genetic information retrieval, whereby fees generated in connection with the storage of retrieved information facilitates cost-effective cell storage. By this system, it is contemplated that increasingly large numbers of cell samples may be efficiently and cost-effectively stored, with the genetic information obtained from the cellular material creating a highly valuable data base from which information can be retrieved for medical, pharmaceutical, and biological research, diagnosis, and treatment. The system embodying the principles of the present invention comprises a cell bank comprising a plurality of cell storage units for storage of cellular material. Typically, such cell storage is effected by cryo-preservation, but it is within the purview of the present invention that alternative storage techniques can be employed. The present system further includes a digital information unit for digitally storing genetic information obtained from the cellular material stored in the cell storage units. The digital information unit preferably comprises at least one digital computer having sufficient digital storage capacity for storage of the potentially vast amounts of genetic information obtained from the stored cellular material. The present system further comprises an arrangement for digital data retrieval interfaced with the digital information unit for retrieving selected genetic information stored in the digital information unit The data retrieval arrangement may be integrated with the digital computer. Remote access of the digital information via the telephone, the Internet, or by like means, enhances the value of the stored digital information by permitting rapid and convenient access of the information on a global basis. The present invention contemplates that the expenses associated with stored cellular material can be recouped through subscription or like fees paid by users who access the stored genetic information. Because such genetic information is potentially quite valuable, such as for research, diagnosis, and treatment, payment for such potentially unique information will be highly cost-effective in comparison to previously-known techniques. As a consequence, expenses associated with cell storage can be increasingly covered by fees paid for data retrieval thus desirably increasing the use of such cell storage, which in turn enhances the depth, and resultant value, of the genetic information data base. Other features and advantages of the present invention will become readily apparent from the following detailed description, the accompanying drawing, and the appended claims. |
Method for a first semiconductor device to determine if it is coupled to a second semiconductor device |
A method for a first semiconductor device (1) coupled to a non-floating bus (3) to determine whether a second semiconductor device (2) is also coupled to the non-floating bus (3). The first semiconductor device (1) sends a control signal for the second semiconductor device (2) to the non-floating bus (3), and the first semiconductor device waits for a response signal from the non-floating bus (3). The first semiconductor device (1) determines that the second semiconductor device (2) is coupled to the non-floating bus (3) if a response signal is received, and determines that the second semiconductor device (2) is not connected to the non-floating bus (3) if a response signal is not received. |
1. A method for a first semiconductor device coupled to a non-floating bus to determine whither a second semiconductor device is also coupled to the non-floating bus, the method comprising the first semiconductor device sending a control signal for the second semiconductor device to the non-floating bus, and the first semiconductor device waiting for a response signal from the non-floating bus, the first semiconductor device determining that the second semiconductor device is coupled to the non-floating bus if a response signal is received and determining that the second semiconductor device is not connected to th non-floating bus if a response signal is not received. 2. A method according to claim 1, wherein if the first semiconductor device does not receive a response signal, the first semiconductor device resends the control signal pattern for the second semiconductor device to the non-floating bus after a time interval. 3. A method according to claim 2, wherein the time interval is a predetermined time interval. 4. A method according to claim 2, wherein the first semiconductor device resends the control signal a predetermined number of times and if no response signal is received after the control signal has been sent the predetermined number of times, the first semiconductor device determines that the second semiconductor device is not coupled to the non-floating bus. 5. A method according to claim 1, wherein the control signal comprises a control pattern for the second semiconductor device. 6. A method according to claim 1, wherein the first semiconductor device waits for a predetermined response signal. 7. A method according to claim 1, wherein the first semiconductor device is a master chip. 8. A method according to claim 1, wherein the second semiconductor device is a slave chip. 9. A method according to claim 1, wherein the non-floating bus is a non-floating serial bus. 10. A method according to claim 9 wherein the non-floating serial bus is an IIC serial bus. |
Process for size classifying ammonium sulfate crystals which are present in a suspension |
The invention relates to a process for size classifying ammonium sulfate crystals using a screen, said process comprising feeding a feed suspension to the screen, said feed suspension comprising said ammonium sulfate crystals in an ammonium sulfate solution, size classifying the ammonium sulfate crystals, and keeping both sides of the screen immersed in liquid during said size classifying. |
1. Process for size classifying ammonium sulfate crystals using a screen, said process comprising: feeding a feed suspension to the screen, said feed suspension comprising said ammonium sulfate crystals in an ammonium sulfate solution, size classifying the ammonium sulfate crystals, and keeping both sides of the screen immersed in liquid during said size classifying. 2. Process according to claim 1, wherein the process comprises withdrawing a permeate suspension from the screen, said permeate suspension comprising ammonium sulfate crystals and ammonium sulfate solution which have been transported through the openings of the screen, and withdrawing a product suspension from the screen, said product suspension comprising ammonium sulfate crystals and ammonium sulfate solution which have not been transported through the openings of the screen. 3. Process according to claim 2, wherein a screening apparatus is used, said screening apparatus comprising a first chamber, a second chamber and the screen, the screen forming a partition between the first chamber and the second chamber, and wherein the process comprises: introducing the feed suspension into the first chamber, withdrawing the permeate suspension from the second chamber, and withdrawing the product suspension from the first chamber. 4. Process according to claim 1, wherein the process comprises controlling the flow rate of the feed suspension entering the first chamber, the flow rate of the permeate suspension exiting the second chamber and/or the flow rate of the product suspension exiting the first chamber, such as to keep both sides of the screen immersed in liquid. 5. Process according to claim 1, wherein the feed suspension which is fed to the screen comprises less than 25 vol. % ammonium sulfate crystals. 6. Process according to claim 2, wherein the product suspension which is withdrawn from the screen comprises less than 50 vol. % ammonium sulfate crystals. 7. Process according to claim 1, wherein transport of the suspension at the side of the screen to which the feed suspension is fed, takes place in a direction essentially parallel to the screen. 8. Process according to claim 7, wherein transport of the suspension at the side of the screen to which the feed suspension is fed, takes place at a rate of at least 0.01 m/s in a direction parallel to the screen. 9. Process according to claim 1, wherein the process comprises wiping off ammonium sulfate crystals from the screen with mechanical means. 10. Process according to claim 9, wherein a screening apparatus is used, said screening apparatus comprising a first chamber, a second chamber and the screen, the screen forming a partition between the first chamber and the second chamber, and wherein the mechanical means are inside the first chamber. 11. Process according to claim 10, wherein at least part of the wall of the first chamber forms a cylinder, said cylindrical part of the wall including at least part of the screen, wherein the mechanical means are inside the first chamber and wherein said mechanical means can be rotated around an axis parallel to the length axis of the cylinder. 12. Process according to claim 1, wherein the feed suspension comprises fine crystals to which the openings of the screen are permeable, and coarse crystals to which the openings of the screen are not permeable, and wherein the process comprises at least partially separating said fine crystals from said coarse crystals. 13. Process according to claim 1, wherein contact of the openings of the screen with air is prevented. |
<SOH> BRIEF DESCRIPTION OF THE DRAWING <EOH>FIG. 1 is a schematic diagram of a preferred embodiment of the process according to the invention. detailed-description description="Detailed Description" end="lead"? |
Thiazolidinediones alone or in combination with other therapeutic agents for inhibiting or reducing tumour growth |
Use of thiazolidinedione derivatives for the preparation of medicaments for inhibiting or reducing tumour growth or metastases, alone or in combination with an RXR agonist or well-known antitumour agent. |
1. A method of inhibiting or reducing tumor growth or metastases comprising administering, to a patient in need thereof, a therapeutically effective amount of a compound of formula I wherein A is CH═CH or S; R is selected from naphthalenyl, thienyl or phenyl which could be mono- or disubstituted with C1-C3 alkyl, CF3, C1-C3 alkoxy, F, Cl, Br or OH; R1 is selected from H or C1-C6 alkyl; X is selected from S, O or NR′2 where R′ refers to H or C1-C6 alkyl; Y is CH or N; n is an integer from 1-3, or the enantiomers thereof, the diastereomers, racemates and mixtures as well as salts of these compounds with pharmaceutically acceptable acids and bases. 2. (canceled) 3. (canceled) 4. (canceled) 5. (canceled) 6. (canceled) 7. (canceled) 8. (canceled) 9. The method according to claim 1, wherein the compound is selected from the group consisting of 5-{4-[2-(5-Methyl-2-phenyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-(thien-2-yl)oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-phenyloxazol-4-yl)-ethoxy]-naphth-1-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Fluorophenyl)-5-methyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Chlorophenyl)-5-methyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-(4-trifluoromethylphenyl)-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Hydroxyphenyl)-5-methyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; and 5-{4-[2-(5-Methyl-2-(thien-2-yl)-oxazol-4-yl)-ethoxy]-naphthalen-1-ylmethyl}-thiazolidine-2,4-dione. 10. The method according to claim 1, further comprising administering, to a patient in need thereof, a therapeutically effective amount of an RXR agonist. 11. The method according to claim 10, wherein the RXR agonist is 9-cis-retinoic acid. 12. The method according to claim 1, further comprising administering, to a patient in need thereof, a therapeutically effective amount of an anti-tumour agent. 13. The method according to claim 12, wherein the antitumour agent is selected from the group consisting of cisplatin, carboplatin, cyclophosphamide, docetaxel, paclitaxel, bleomycin, 5-fluorouracil, 5′-deoxy-5-fluoro-N-pentyloxycarbonyl-cytidine, doxorubicine and tamoxifen. 14. A pharmaceutical composition comprising a compound of formula I wherein A is CH═CH or S; R is selected from naphthalenyl, thienyl or phenyl which could be mono- or disubstituted with C1-C3 alkyl, CF3, C1-C3 alkoxy, F, Cl, Br or OH; R1 is selected from H or C1-C6 alkyl; X is selected from S, O or NR′2 where R′ refers to H or C1-C6 alkyl; Y is CH or N; n is an integer from 1-3, or the enantiomers thereof, the diastereomers, racemates and mixtures as well as salts of these compounds with pharmaceutically acceptable acids and bases; and a pharmaceutically acceptable carrier. 15. The pharmaceutical composition according to claim 14, wherein the compound is selected from the group consisting of 5-{4-[2-(5-Methyl-2-phenyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-(thien-2-yl)oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-phenyloxazol-4-yl)-ethoxy]-naphth-1-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Fluorophenyl)-5-methyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Chlorophenyl)-5-methyloxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(5-Methyl-2-(4-trifluoromethylphenyl)-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; 5-{4-[2-(2-(4-Hydroxyphenyl)-5-methyloxazol-4-yl )-ethoxy]-benzo[b]thiophen-7-ylmethyl}-thiazolidine-2,4-dione; and 5-{4-[2-(5-Methyl-2-(thien-2-yl)-oxazol-4-yl)-ethoxy]-naphthalen-1-ylmethyl}-thiazolidine-2,4-dione. 16. The pharmaceutical composition according to claim 14, further comprising administering, to a patient in need thereof, a therapeutically effective amount of an RXR agonist. 17. The pharmaceutical composition according to claim 16, wherein the RXR agonist is 9-cis-retinoic acid. 18. The pharmaceutical composition according to claim 16, wherein the ratio of the amount compound and RXR agonist to the amount pharmaceutical carrier is a ratio of 100:1 to 1:100. 19. The pharmaceutical composition according to claim 14, further comprising administering, to a patient in need thereof, a therapeutically effective amount of an anti-tumour agent. 20. The pharmaceutical composition according to claim 19, wherein the antitumour agent is selected from the group consisting of cisplatin, carboplatin, cyclophosphamide, docetaxel, paclitaxel, bleomycin, 5-fluorouracil, 5′-deoxy-5-fluoro-N-pentyloxycarbonyl-cytidine, doxorubicine and tamoxifen. 21. The pharmaceutical composition according to claim 19, wherein the ratio of the amount compound and anti-tumour agent to the amount pharmaceutical carrier is a ratio of 100:1 to 1:100. 22. The pharmaceutical composition according to claim 14, wherein wherein the ratio of compound to pharmaceutical carrier is a ratio of 100:1 to 1:100. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The peroxisome proliferator-activated receptors (PPARs) belong to the steroid receptor superfamily and, as such, are ligand activated transcription factors and exist in different subtypes and isoforms (see, for example, Pershadsingh, H. A., Exp. Opin. Invest. Drugs 8 (1999) 1859-1872; Willson, T. M., et al., J. Med. Chem. 43 (2000) 527-550; Kersten, S., et al., Nature 405 (2000) 421-424; Rami, H. K., and Smith, S. A., Exp. Opin. Ther. Patents 10 (2000) 623-634 and references cited therein). Three subtypes of PPARs (PPAR alpha, PPAR gamma and PPAR delta) have been identified and cloned from mouse and human. PPAR gamma, existing in three isoforms (termed PPAR gamma 1, PPAR gamma 2 and PPAR gamma 3), is the most extensively studied and is considered to be of clinical importance. The antidiabetic activity of different natural and synthetic ligands is correlated with the activation of this receptor. Thiazolidinediones are a class of compounds that selectively activate PPAR gamma and thus serve as oral insulin-sensitizing agents that lower the blood lipid and blood glucose levels. Exemplary thiazolidinediones are troglitazone, pioglitazone, ciglitazone, rosiglitazone, englitazone, BM 13.1258, BM 15.2054 and derivatives thereof. The PPAR gamma activity of BM 13.1258 and BM 15.2054 has already been reported by Fürnsinn, C., et al. (Br. J. Pharmacol. 128 (1999) 1141-1148) which is incorporated by reference. Apart from the recognised importance of PPAR gamma agonists in the area of metabolic diseases the discovery of PPAR gamma-dependent modulation of the cell cycle has led to a substantial number of different approaches for the treatment of proliferative diseases utilising compounds that bind to and thereby activate PPAR gamma. In addition to adipose tissue, PPAR gamma is reported to be highly expressed in several cancer cell lines including liposarcoma (Iijima, K., et al., Biochem. Biophys. Res. Commun. 247 (1998) 353-356), breast cancer (Mueller, E., et al., Molecular Cell (1998) 465-470; Elstner, E., et al., Proc. Nat. Acad. Sci. USA 95 (1998) 8806-8811), prostate cancer (Kubota, T., et al., Cancer Res. 58 (1998) 3344-3352) and colon cancer (Sarraf, P., et al., Nat. Med. 4 (1998) 1046-1052). Additionally, troglitazone as a specific PPAR gamma agonist from the thiazolidinedione class is known to inhibit the growth of human cancer cells in vitro and in vivo which is disclosed in some patent applications (WO 98/25598, WO 00/18234, WO 00/30628) and described in a number of papers. In addition, thiazolidinediones including troglitazone have been shown to induce terminal differentiation in human liposarcoma cells (Tontonoz, P., et al., Proc. Nat. Acad. Sci. USA 94 (1997) 237-241). The differentiation of malignant cells represents an ideal concept for treating cancer as opposed to a cell death mediated mechanism. The PPARs belong to type II steroid receptors that are functionally distinct from the classical steroid receptors and do not bind to their respective binding site to form a homodimer. PPAR gamma heterodimerizes with at least one other member of the steroid receptor family, the retinoid acid receptors, namely RXR alpha (Kliewer, S. A., et al., Nature 358 (1992) 771-774; Tontonoz, P., et al., Mol. Cell. Biol. 15 (1995) 351). The combination of specific PPAR gamma ligands and RXR alpha ligands activates both receptors, leads to an additive stimulation of differentiation and results in a synergistic inhibition of the cancer cell growth (Tontonoz, P., et al., Proc. Nat. Acad. Sci. USA 94 (1997) 237-241; Elstner, E., et al., Proc. Nat. Acad. Sci. USA 95 (1998) 8806-8811). detailed-description description="Detailed Description" end="lead"? |
Method |
The present invention provides an improved method of separation of alleles in a sample (sample alleles), involving the use of a reference allele and further comprising the use of double stranded sample alleles and/or the use of said reference allele in a double stranded form wherein one of the strands of the double stranded alleles present has been labelled so as to allow specific digestion of one of the strands. In preferred embodiments the label is a 5′-phosphorylated group and the digestion is carried out using λ-exonuclease. Use of this method in genotyping and/or diagnosis and kits for use in such methods of allele separation and genotyping are also included. |
1. A method of separation of alleles in a sample, comprising the use of a modified reference allele, wherein said modified reference allele comprises one or more modifications such that heteroduplexes formed between said reference allele and a sample allele present in the sample are resistant to digestion with one or more endonuclease enzymes which digest homoduplexes or heteroduplexes of said sample alleles. 2. The method of claim 1, wherein said modified reference allele is single-stranded. 3. The method of claim 1, wherein either or both of said sample allele and reference allele is in double stranded form and is rendered single stranded by specific digestion of one of the strands of said allele. 4. The method of claim 3, wherein said strand which is digested is labeled to permit said digestion. 5. A method of separation of sample alleles in a sample, comprising the use of a reference allele and further comprising the use of either or both of a double stranded sample allele and said reference allele in a double stranded form, wherein one of the strands of the double stranded allele present is labeled so as to allow specific digestion of one of the strands. 6. The method of claim 5, wherein said reference allele is modified to comprise one or more modifications such that heteroduplexes formed between said reference allele and a sample allele present in the sample are resistant to digestion with one or more endonuclease enzymes which digest homoduplexes or heteroduplexes of said sample alleles. 7. The method of claim 1, wherein said endonuclease enzymes also digest homoduplexes of said reference alleles. 8. The method of claim 1, wherein said endonuclease enzymes are restriction enzymes. 9. The method of claim 3, wherein said specific digestion is achieved by use of an enzyme. 10. The method of claim 9, wherein said enzyme is λ-exonuclease and said strand which is specifically digested is 5′-phosphorylated. 11. The method of claim 3, wherein both the sample and reference alleles are provided in a double stranded form, and either the sense or the antisense strand of the sample alleles is labeled with a 5′-phosphorylated group and the opposing strand of the double stranded reference allele is labeled with a 5′-phosphorylated group. 12. The method of claim 3, wherein only one of the sample and reference alleles is supplied in a double stranded form and one of the strands is phosphorylated at the 5′ end. 13. The method of claim 3, wherein said reference allele is single-stranded and said sample allele is double-stranded. 14. The method of claim 1, wherein said reference allele comprises a modification which induces a mismatch between a sample and reference allele. 15. The method of claim 14, wherein at least 1% of the total number of bases in the reference allele are modified to form the modified reference allele. 16. The method of claim 1, wherein in said modified reference allele, a restriction site for at least one restriction enzyme has been removed or inactivated, and introduced at a different location. 17. The method of claim 1, wherein said duplex molecules and digested molecules are separated using separation means which physically separate molecules on the basis of one or more of size, conformation, hydrophobicity and charge. 18. The method of claim 17, wherein said separation means is selected from the group consisting of polyacrylamide gel electrophoresis (PAGE), denaturing high performance liquid chromatography (DHPLC), capillary electrophoresis and mass spectrometry. 19. The method of claim 1, wherein the sample strand of a heteroduplex formed between said sample and reference alleles is amplified following separation of said heteroduplex. 20. The method of claim 19, wherein said reference allele is further modified at a site corresponding to a primer binding site in a sample allele so as to prevent or disrupt binding of a sample amplification primer for said sample allele to said reference allele. 21. The method of claim 19 wherein a competitor primer is used to suppress amplification of the reference strand. 22. A method of genotyping the alleles present in a biological sample, comprising subjecting said sample to the method of allele separation of claim 1, separating the heteroduplexes formed between sample and reference alleles in a separation medium and identifying the alleles present, wherein the alleles present are identified by the migration pattern of the separated heteroduplexes in or on the separation medium, by direct sequencing of the sample alleles in the separated heteroduplexes, or by both the migration pattern of the separated heteroduplexes and direct sequencing of the sample alleles in the separated heteroduplexes. 23. The method of claim 22, wherein the method of genotyping the alleles present in a biological sample is used in HLA typing, determination of polymorphisms involved in metabolism of pharmaceuticals, determination of mutations in disease loci, determination of mutations in cancers, or determination of viral variants in chronic viral diseases. 24. A method of diagnosis of disease in a subject, or the susceptibility of a subject to a disease, comprising subjecting a nucleic acid sample of said subject to the method of allele separation of claim 1, and carrying out genomic typing to determine whether at least one particular mutation is present. 25. The method of claim 22, wherein the migration of the heteroduplexes in the separation medium is monitored or detected by ethidium bromide staining, detection of fluorescently-labeled alleles or by detecting elution position of column peaks. 26. A modified reference allele which has been modified to delete or inactivate at least one endonuclease site which is present in a corresponding sample allele, and to re-introduce said endonuclease site at a different location, which is not present in said sample allele. 27. A method for preparing a modified reference allele, said method comprising the steps of (i) selecting a sample allele, (ii) identifying one or more endonuclease enzymes which cleave all known sample alleles at least once, (iii) deleting or inactivating these endonuclease sites, and (iv) introducing one or more alternative sites for the same enzyme into the allele, thereby forming a modified reference allele. 28. The modified reference allele of claim 27, further comprising a modification at a site corresponding to a primer binding site in said sample allele so as to prevent or disrupt binding of a sample amplification primer for said sample allele to said reference allele. 29. The modified reference allele of claim 26, wherein said modified reference allele is an HLA allele. 30. The modified reference allele of claim 29, wherein said modified reference allele is a nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO. 1, or a fragment thereof comprising a functionally active sequence, or a sequence which is degenerate, substantially homologous with, or which hybridizes with the sequence of SEQ ID NO. 1 or with the sequence complementary thereto, or a fragment thereof encoding a functionally active product. 31. A kit for use in allele separation or typing comprising the modified reference allele of claim 26, and one or more further components selected from the group consisting of sample primers to amplify the particular sample alleles concerned, reference primers to amplify the modified reference allele, a restriction enzyme, and an exonuclease. 32. A method of separation of alleles in a sample, wherein the alleles are separated by denaturing high-performance liquid chromatography (DHPLC), comprising the use of a modified reference allele which forms heteroduplexes with sample alleles contained within the sample and which contains a plurality of additional modifications such that improved separation of alleles is obtained. 33. The method of claim 32, wherein said reference allele comprises a modification which induces a mismatch between a sample and reference allele. 34. The method of claim 33, wherein at least 1% of the total number of bases in the reference allele are modified to form the modified reference allele. 35. The method of claim 32, wherein the difference in retention time on said DHPLC between different homo- and heteroduplexes is at least one minute. 36. The method of claim 32, wherein the elution profile of said DHPLC is used to genotype unknown samples independently of sequence analysis by comparison with known sample profiles. 37. The method of claim 6, wherein said endonuclease enzymes also digest homoduplexes of said reference alleles. 38. The method of claim 6, wherein said endonuclease enzymes are restriction enzymes. 39. The method of claim 5, wherein said specific digestion is achieved by use of an enzyme. 40. The method of claim 39, wherein said enzyme is λ-exonuclease and said strand which is specifically digested is 5′-phosphorylated. 41. The method of claim 5, wherein both the sample and reference alleles are provided in a double stranded form, and either the sense or the antisense strand of the sample alleles is labeled with a 5′-phosphorylated group and the opposing strand of the double stranded reference allele is labeled with a 5′-phosphorylated group. 42. The method of claim 5, wherein only one of the sample and reference alleles is supplied in a double stranded form and one of the strands is phosphorylated at the 5′ end. 43. The method of claim 5, wherein said reference allele is single-stranded and said sample allele is double-stranded. 44. The method of claim 5, wherein said reference allele comprises a modification which induces a mismatch between a sample and reference allele. 45. The method of claim 44, wherein at least 1% of the total number of bases in the reference allele are modified to form the modified reference allele. 46. The method of claim 6, wherein in said modified reference allele, a restriction site for at least one restriction enzyme has been removed or inactivated, and introduced at a different location. 47. The method of claim 5, wherein said duplex molecules and digested molecules are separated using separation means which physically separate molecules on the basis of one or more of size, conformation, hydrophobicity and charge. 48. The method of claim 47, wherein said separation means is selected from the group consisting of polyacrylamide gel electrophoresis (PAGE), denaturing high performance liquid chromatography (DHPLC), capillary electrophoresis and mass spectrometry. 49. The method of claim 5, wherein the sample strand of a heteroduplex formed between said sample and reference alleles is amplified following separation of said heteroduplex. 50. The method of claim 49, wherein said reference allele is further modified at a site corresponding to a primer binding site in a sample allele so as to prevent or disrupt binding of a sample amplification primer for said sample allele to said reference allele. 51. The method of claim 49, wherein a competitor primer is used to suppress amplification of the reference strand. 52. A method of genotyping the alleles present in a biological sample, comprising subjecting said sample to the method of allele separation of claim 5, separating the heteroduplexes formed between sample and reference alleles in a separation medium and identifying the alleles present, wherein the alleles present are identified by the migration pattern of the separated heteroduplexes in or on the separation medium, by direct sequencing of the sample alleles in the separated heteroduplexes, or by both the migration pattern of the separated heteroduplexes and direct sequencing of the sample alleles in the separated heteroduplexes. 53. The method of claim 52, wherein the method of genotyping the alleles present in a biological sample is used in HLA typing, determination of polymorphisms involved in metabolism of pharmaceuticals, determination of mutations in disease loci, determination of mutations in cancers, or determination of viral variants in chronic viral diseases. 54. A method of diagnosis of disease in a subject, or the susceptibility of a subject to a disease, comprising subjecting a nucleic acid sample of said subject to the method of allele separation of claim 5, and carrying out genomic typing to determine whether at least one particular mutation is present. 55. The method of claim 52, wherein the migration of the heteroduplexes in the separation medium is monitored or detected by ethidium bromide staining, detection of fluorescently-labeled alleles or by detecting elution position of column peaks. |
Fatty alcohols and fatty acid esters useful for treatment of inflammation |
Immunomodulators selected from: (a) a saturated or cis-unsaturated C10-C20 fatty alcohol or an ester thereof with a C1-C6 alkanoic acid; (b) a monoester of a C2-C8 alkanediol or of Glycerol with a saturated or cis-unsaturated C10-C20 fatty acid; and (c) a diester of glycerol with a saturated or cis-unsaturated C10-C20 fatty acid, are useful for treatment of inflammation, particularly immunologically-mediated inflammation such as it occurs in autoimmune diseases. |
1-40. (canceled) 41. A method for the treatment of inflammation, particularly immunologically-mediated inflammation, which comprises administering to a patient in need an effective amount of an immunomodulator selected from: (a) a saturated or cis-unsaturated C10-C20 fatty alcohol or an ester thereof with a C1-C6 alkanoic acid; (b) a monoester of a C2-C8 alkanediol or of glycerol with a saturated or cis-unsaturated C10-C20 fatty acid; and (c) a diester of glycerol with a saturated or cis-unsaturated C10-C20 fatty acid. 42. A method according to claim 41, wherein said immunomodulator is a saturated C10-C12 fatty alcohol. 43. The method according to claim 42, wherein said saturated C10-C20 fatty alcohol is selected from decyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol and stearyl alcohol. 44. The method according to claim 41, wherein said immunomodulator is a cis-unsaturated C16-C18 fatty alcohol. 45. The method according to claim 44, wherein the cis-unsaturated C16-C18 fatty alcohol is selected from oleyl alcohol, linoleyl alcohol, y-linolenyl alcohol and linolenyl alcohol. 46. The method according to claim 41, wherein the immunomodulator is an ester of a saturated or cis-unsaturated C10-C20 fatty alcohol with a C2-C6 alkanoic acid. 47. The method according to claim 41, wherein said immunomodulator is a monoester of a saturated or cis-unsaturated C10-C20 fatty acid with a C2-C8 alkanediol. 48. The method according to claim 47, wherein said alkanediol is selected from 1,2-ethylene glycol, 1,3-propanediol and 1,4-butanediol. 49. The method according to claim 41, wherein said immunomodulator is a monoester of glycerol with a saturated or cis-unsaturated C10-C20 fatty acid. 50. The method according to claim 41, wherein said immunomodulator is a diester of glycerol with a saturated or cis-unsaturated C10-C20 fatty acid. 51. The method according to claim 41, wherein said fatty acid is a saturated C10-C20 fatty acid. 52. The method according to claim 51, wherein said saturated C10-C20 fatty acid is selected from capric acid, lauric acid, myristic acid, palmitic acid, stearic acid and arachidic acid. 53. The method according to claim 41, wherein said fatty acid is a cis-unsaturated C10-C20 fatty acid. 54. The method according to claim 53, wherein said cis-unsaturated Cio-C2o fatty acid is selected from palmitoleic acid, oleic acid, cis-vaccenic acid, linoleic acid, y-linolenic acid, linolenic acid, and arachidonic acid. 55. The method according to claim 54, wherein said immunomodulator is glyceryl monooleate. 56. The method according to claim 54, wherein said immunomodulator is glyceryl dioleate. 57. A method according to claim 41 for the treatment of immunologically-mediated inflammatory disorders selected from an autoimmune disease, severe allergies, asthma, graft rejection or for the treatment of chronic degenerative diseases such as Alzheimer's disease, and in neuroprotection, organ regeneration, chronic ulcers of the skin, and schizophrenia. 58. The method according to claim 57, wherein said autoimmune disease is multiple sclerosis or a human arthritic condition. 59. The method according to claim 58, wherein said human arthritic condition is selected from rheumatoid arthritis, reactive arthritis with Reiter's syndrome, ankylosing spondylitis and other inflammations of the joints mediated by the immune system. 60. The method according to claim 57, wherein said immunologically-mediated inflammatory disorder is myasthenia gravis, Guillain Barre syndrome, and other inflammatory diseases of the nervous system; psoriasis, pemphigus vulgaris and other diseases of the skin; systemic lupus erythematosus, glomerulonephritis and other diseases affecting the kidneys; atherosclerosis and other inflammations of the blood vessels, autoimmune hepatitis, inflammatory bowel diseases, pancreatitis, and other conditions of the gastrointestinal system; type 1 diabetes mellitus, thyroiditis, and other diseases of the endocrine system. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Inflammation is commonly divided into three phases: acute inflammation, the immune response and chronic inflammation. Acute inflammation is the initial response to tissue injury and is mediated by the release of histamine, serotonin, bradykinin, prostaglandins and leukotrienes. The immune response, usually preceded by the acute inflammation phase, occurs when immunologically competent cells are activated in response to foreign organisms or antigenic substances liberated during the acute or chronic inflammatory response. The outcome of the immune response for the host may be beneficial, as when it causes invading organisms to be phagocytosed or neutralized. However, the outcome may be deleterious if it leads to chronic inflammation without resolution of the underlying injurious process as it occurs in rheumatoid arthritis. The treatment of patients with inflammation envisages the relief of pain, which is the presenting symptom and the major continuing complaint of the patient, as well as the slowing or arrest of the tissue-damaging process. Anti-inflammatory agents are usually classified as steroidal or glucocorticoids and nonsteroidal anti-inflammatory agents (NSAIDs). The glucocorticoids are powerful anti-inflammatory agents but the high toxicity associated with chronic corticosteroid therapy inhibits their use except in certain acute inflammatory conditions. Therefore, the nonsteroidal anti-inflammatory drugs have assumed a major role in the treatment of chronic conditions such as rheumatoid arthritis. Among the nonsteroidal anti-inflammatory agents are included derivatives of aminoarylcarboxylic acids, arylacetic acids, arylbutyric acids, arylcarboxylic acids, arylpropionic acids, pyrazole, pyrazolone, salicylic acid and some other derivatives of different chemical structure, including specific anti-arthritic/anti-rheumatic agents. Some fatty alcohols and esters of fatty acids have been described as solvents or emulsifiers for use in pharmaceutical compositions. For example, cetyl alcohol may be used in pharmaceutical compositions as emulsifying and stiffening agent (The Merck Index, pp. 347-8, # 2037), oleyl alcohol may be used as a carrier for medicaments (The Merck Index, p. 1222, # 6900), and alkyl esters of oleic acid may be used as solvents for medicaments (The Merck Index, p. 6899, # 6898). A mixture of higher aliphatic primary alcohols, primarily isolated from beeswax, was described as having moderate anti-inflammatory activity. The composition of such a mixture was not disclosed (Rodriguez et al., 1998). Feeding laboratory animals with fish oil rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), was described to reduce acute and chronic inflammatory responses, to improve survival to endotoxin and in models of autoimmunity and to prolong the survival of grafted organs, and it was therefore suggested that fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation (Calder, 1998). A pharmaceutical preparation comprising eicosapentaenoic acid and/or stearidonic acid for treatment of schizophrenia is described in WO 98/16216 and U.S. Pat. No. 6,331,568. Modified polyunsaturated fatty acids and derivatives thereof have been proposed for pharmaceutical uses. WO 99/27924 and U.S. Pat. No. 6,280,755 describe anti-inflammatory fatty acids uninterrupted by a methylene group for use in topical pharmaceutical and cosmetic compositions. WO 97/38688 and U.S. Pat. No. 6,262,119 describe polyunsaturated fatty acids having 1 or 2 substitutions selected from oxa and thia in position beta or gamma to the acyl group, for treating or ameliorating symptoms of T-cell mediated disease. WO 99/58122 and U.S. Pat. No. 6,365,628 describe saturated fatty acids in which one or more methylene groups are substituted by O, S, SO, SO 2 , or Se and alkyl esters thereof, for treatment or prevention of diabetes. U.S. Pat. No. 5,019,383 describes synthetic vaccines comprising a peptide residue coupled to one or more alkyl or alkenyl groups of at least 12 carbon atoms or other lipophilic substance, wherein said alkyl or alkenyl group may be a fatty acid residue coupled to one or more functional groups of a polyfunctional group which is bound to the N-terminal amino group and/or C-terminal carboxy group of the peptide residue. There is no description in the literature that isolated fatty alcohols or esters thereof with alkanoic acids may be used themselves as medicaments, and specifically not that they may be involved in immunomodulation of inflammation. |
<SOH> SUMMARY OF THE INVENTION <EOH>It has now been surprisingly found, in accordance with the present invention, that certain long-chain fatty alcohols, esters thereof with C 1 -C 6 alkanoic acids, or certain esters of long-chain fatty acids with alkanediols or glycerol can suppress inflammation in experimental adjuvant arthritis (AA) and experimental autoimmune encephalomyelitis (EAE) models in rats and can prevent graft rejection in mice. The present invention thus relates to pharmaceutical compositions for the treatment of inflammation, particularly immunologically-mediated inflammation, comprising as active ingredient an immunomodulator selected from: (a) a saturated or cis-unsaturated C 10 -C 20 fatty alcohol or an ester thereof with a C 1 -C 6 alkanoic acid; (b) a monoester of a C 2 -C 8 alkanediol or of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid; and (c) a diester of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid. In another embodiment, the invention relates to the use of an immunomodulator selected from: (a) a saturated or cis-unsaturated C 10 -C 20 fatty alcohol or an ester thereof with a C 1 -C 6 alkanoic acid; (b) a monoester of a C 2 -C 8 alkanediol or of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid; and (c) a diester of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid, for the preparation of a pharmaceutical composition for the treatment of inflammation, in particular immunologically-mediated inflammation. In still another embodiment, the invention relates to a method for the treatment of inflammatory disorders, in particular immunologically-mediated inflammation, which comprises administering to an individual in need thereof an effective amount of an agent selected from an immunomodulator selected from: (a) a saturated or cis-unsaturated C 10 -C 20 fatty alcohol or an ester thereof with a C 1 -C 6 alkanoic acid; (b) a monoester of a C 2 -C 8 alkanediol or of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid; and (c) a diester of glycerol with a saturated or cis-unsaturated C 10 -C 20 fatty acid. |
Fuel-injection valve for internal combustion engines |
An injection valve member for closing or opening injection orifices of a valve seat element is integrated, in a longitudinally displaceable manner, into a central housing bore of a fuel-injection valve. The valve seat element is fixed to the housing and the part of the element that includes the injection orifices and the seat projects out of the housing. Elements for determining the rotational position of the valve seat element in relation to the housing are provided on the exterior of the part. The fuel injection valve requires simple production and assembly engineering and permits a slimline injector configuration for both large and small internal combustion engines. |
1-21. (canceled) 22. A fuel injection valve for intermittent fuel injection into a combustion space of an internal combustion engine, comprising: a) a housing; b) a valve seat element including a seat provided with injection orifices; c) means for fastening the valve seat element to the housing, the valve seat element projecting with a part having the seat out of the housing; d) an injection valve member arranged longitudinally adjustably in the housing and configured to cooperate with the seat; e) a control device for controlling adjusting movement of the injection valve member; f) a central housing bore that runs in a direction of a longitudinal axis of the housing and in which the injection valve member runs and that is connected to a fuel high pressure connection and to the seat for the injection valve member; and g) that part of the valve seat element that has the seat and projects out of the housing is provided on its outside with means for defining a rotary position of the valve seat element with respect to the housing during fastening of said valve seat element to the housing. 23. The fuel injection valve as claimed in claim 22, wherein the means for defining the rotary position of the valve seat element with respect to the housing is formed by a positioning face, centering countersink, or visually readable marking formed on an outside of the part projecting out of the housing. 24. The fuel injection valve as claimed in claim 22, wherein the injection valve member is closely guided with a part slideably in a bore, said bore extending as far as the seat provided with the injection orifices, of the valve seat element, this part slideably in the bore being provided on its circumference with ground-down faces, by which the central bore is connected to the seat. 25. The fuel injection valve as claimed in claim 22, wherein the means for fastening the valve seat element to the housing comprises a union nut configured to be screwed onto the housing, and a metallic washer is provided with lapped end faces arranged between an upper face of the valve seat element and a lower face of the housing. 26. The fuel injection valve as claimed in claim 24, wherein the valve seat element is inserted sealingly by a press fit into a part of the central housing bore and is supported axially on a step face, that part of the injection valve member which is provided with ground-down faces being closely guided slideably in a region of the bore located outside the housing, and, in the press fit region, the injection valve member being stepped in diameter with respect to the part provided with ground-down faces. 27. The fuel injection valve as claimed in claim 22, wherein the injection valve member is closely guided slideably, with a part provided with ground-down faces, in a guide bore of the housing or of a lower housing part, and the valve seat element has a short design, as seen in a longitudinal direction of the fuel injection valve, and is welded together with the lower housing part such that the longitudinal axis of the valve seat element is arranged coaxially to an axis of the guide bore. 28. The fuel injection valve as claimed in claim 27, further comprising means for centering the valve seat element with respect to the housing or to the guide bore. 29. The fuel injection valve as claimed in claim 27, wherein the valve seat element is inserted with part of its outer face from below into the guide bore and is welded into the guide bore, the guide bore being sealed off by at least one of a weld seam and a thin-walled valve seat element part pressed sealingly against the wall of the guide bore by the fuel system pressure prevailing in the guide bore. 30. The fuel injection valve as claimed in claim 28, wherein the valve seat element is welded to the housing on an end face and has a bore that extends as far as the seat provided with the injection orifices and that is connected to the central housing bore by the guide bore, the means for centering the valve seat element with respect to the guide bore being formed by a sleeve-shaped thin-walled valve seat element part projecting into the guide bore from below, this part projecting into the guide bore configured to be pressed sealingly against a wall of the guide bore by fuel system pressure prevailing in the bore. 31. The fuel injection valve as claimed in claim 28, wherein the valve seat element is welded sealingly on an end face to the housing and has a bore that extends as far as the seat provided with the injection orifices and that is connected to the central housing bore by the guide bore, the means for centering the valve seat element with respect to the guide bore being formed by a sleeve-shaped valve seat element part projecting from below into a recess coaxial to the guide bore. 32. The fuel injection valve as claimed in claim 28, wherein the valve seat element is welded on an end face to the housing and has a bore that extends as far as the seat provided with the injection orifices and that is connected to the central housing bore by the guide bore, the means for centering the valve seat element with respect to the guide bore being formed by a centering sleeve that projects, at a first end, into the guide bore and, at a second end, into the valve seat element bore and that is configured to be pressed sealingly against walls of the two bores by the fuel system pressure. 33. A method for mounting a valve seat element having a seat provided with injection orifices in a defined rotary position on a housing of a fuel injection valve configured for intermittent fuel injection into a combustion space of an internal combustion engine, comprising: detecting a position of at least one of the injection orifices by a sensor; and positioning the valve seat element into the defined rotary position as a function of a signal from the sensor and mounting the valve seat element on the housing. 34. A fuel injection valve for intermittent fuel injection into a combustion space of an internal combustion engine, comprising: a) a housing with a central housing bore running in a longitudinal direction and connected to a fuel high pressure connection; b) an injection valve member arranged longitudinally adjustably in the housing bore and that cooperates with a valve seat and by which a connection between the housing bore and a space leading to injection orifices can be made and broken; c) a control device for controlling adjusting movement of the injection valve member; d) wherein the injection valve member is closely guided with a part slideably in a guide bore forming a lower part of the housing bore; and e) wherein the injection orifices are manufactured in a nozzle body welded to the housing. 35. The fuel injection valve as claimed in claim 34, wherein the nozzle body is inserted into the guide bore from below and is welded on its circumference together with the guide bore, a part which forms the valve seat being arranged in the guide bore above the nozzle body and being pressed against the nozzle body by the fuel system pressure prevailing in the guide bore, and with a thin-walled sealing-off lip against a wall of the guide bore. 36. The fuel injection valve as claimed in claim 34, wherein the nozzle body is welded together with the housing on an end face, and the valve seat is formed by a conically narrowing part of the central housing bore, said part being adjacent to the guide bore. 37. A fuel injection valve for intermittent fuel injection into a combustion space of an internal combustion engine, comprising: a) a housing; b) a valve seat element including a seat; c) the valve seat element connected to the housing by a union nut configured to be screwed onto the housing, such that said valve seat element projects with a part having the seat out of the housing; d) an injection valve member arranged longitudinally adjustably in the housing and cooperating with the seat; e) a control device for controlling adjusting movement of the injection valve member; f) a central housing bore that runs in a direction of a longitudinal axis of the housing and in which the injection valve member runs and which is connected to a fuel high pressure connection and to the seat; g) the injection valve member is closely guided with a part slideably in a bore of the valve seat element, said bore extending as far as the seat; and h) a metallic washer arranged between an end face of the valve seat element and a lower face of the housing. 38. The fuel injection valve as claimed in claim 37, wherein a thickness of the washer is selected such that the injection valve member executes a predetermined maximum stroke during opening and closing of the valve. 39. A fuel injection valve for intermittent fuel injection into a combustion space of an internal combustion engine, comprising: a) a housing with a central housing bore running in a longitudinal direction and connected to a fuel high pressure connection; b) a valve seat element including a seat; c) an injection valve member arranged longitudinally adjustably in the housing bore and cooperating with the seat; d) a control device for controlling adjusting movement of the injection valve member; e) the valve seat element is inserted sealingly with a press fit into a part of the central housing bore and is supported axially on a step face, a part of the valve seat element that has the seat projecting out of the housing; f) the injection valve member is closely guided with a part slideably in a bore of the valve seat element, said bore extending as far as the seat; g) that part of the injection valve member which is closely guided slideably in the bore of the valve seat element has on its circumference ground-down faces, by which the central housing bore is connected to the seat; h) that part of the injection valve member that is closely guided slideably in the bore of the valve seat element is located in a region of the valve seat element that projects out of the housing; and i) the injection valve member is stepped in diameter in the press fit region of the valve seat element. 40. A method for fastening a valve seat element with a central bore and a valve seat to a housing, provided with a central housing bore, of a fuel injection valve, the valve seat being provided for cooperation with an injection valve member arranged longitudinally adjustably in the housing bore, the method comprising: placing the valve seat element onto a countertool corresponding in its shape to it and pressing with a pressure force onto the countertool by a positioning tool that corresponds in its form essentially to its injection valve member and that is guided in a guide bore of the housing, said guide bore being provided for the injection valve member and forming part of the central housing bore; pressing end faces of the valve seat element and of the housing against one another with a lower force; a welding operation, simultaneously at two opposite points, in a region of end faces on a circumference of the parts to be connected together. 41. The method as claimed in claim 40, wherein a radial gap for a welding bead is provided in the region of the end faces between the positioning tool and the parts to be connected. 42. The method as claimed in claim 40, wherein, with the end faces lying in one plane, the positioning tool is stepped in diameter in the region of the end faces and in the region lying below them and extending as far as the valve seat, and the countertool, together with the valve seat element, can be adjusted in a transverse direction prior to the welding together and can thus be aligned radially with respect to the positioning tool. |
Device for transmitting optical waves with inclined coupling surfaces |
The invention concerns an integrated-structure device for transmitting optical waves comprising a plurality of optical microguides (11), a plurality of notches (12) with coupling surfaces through which respectively emerge said optical microguides; optical fibers whereof the end parts are respectively arranged and fixed in said notches so as to optically couple the end surfaces of said optical fibers and said coupling surfaces of said optical microguides; said coupling surfaces (7) of said notches (4) extend perpendicular to said integrating planes and are slanting relative to the longitudinal direction of the end part (5) of the optical fiber (6) and/or of said optical micro-guide (3) and are aligned; said end surfaces (8) of said optical fibers (6) extend parallel to said coupling surfaces (7) of said notches (4) and are aligned. |
1. An optical wave transmission device of integrated structure, comprising: a multiplicity of optical microguides that lie in an integration plane, the end parts of which are located beside one another and are of approximately parallel directions; a multiplicity of notches that have coupling faces through which the respective said end parts of said optical microguides emerge and that lie perpendicular to said integration planes; and optical fibers, the end parts of which are respectively placed and fixed in said notches and lie parallel to the integration planes of said structure so as to optically couple the end faces of these optical fibers to the aforementioned coupling faces of said optical microguides; wherein said coupling faces of said notches lie perpendicular to said integration planes and are oblique to the longitudinal direction of the end part of the optical fiber and/or of said optical microguide and are aligned; and wherein said end faces of said optical fibers lie parallel to said coupling faces of said notches and are aligned. 2. The device as claimed in claim 1, wherein the longitudinal directions of the end parts of the optical fibers coincide approximately with the longitudinal directions of said end parts of said optical microguides. 3. The device as claimed in claim 1, wherein said optical fibers are assembled or grouped together in the form of a sheet. 4. The device as claimed in claim 2, wherein said optical fibers are assembled or grouped together in the form of a sheet. |
Pesticidal preparations comprising copolymers |
The present invention relates to aqueous concentrates and solid formulations of pesticide preparations comprising copolymers which may be obtained by copolymerization of a) glycerol, b) at least one dicarboxylic acid, and c) at least one monocarboxylic acid of the formula (I) R1—COOH (I) Where R1 is (C5-C29)-alkyl; (C7-C29)-alkenyl; phenyl or naphthyl. The copolymer of the present invention increases the biological activity of the pesticide or herbicide. |
1. A pesticide preparation comprising at least one pesticide and at least one copolymer obtained by copolymerization of a) glycerol, b) at least one dicarboxylic acid, and c) at least one monocarboxylic acid of the formula (I) R1—COOH (I) where R1 is (C5-C29)-alkyl; (C7-C29)-alkenyl; phenyl or naphthyl, wherein the copolymers comprise 19.9 to 99% by weight of component a), 0.1 to 30% by weight of component b) and 0.9 to 80% by weight of component c). 2. The pesticide preparation as claimed in claim 1, wherein the dicarboxylic acid b) is oxalic acid; a dicarboxylic acid according to formula (II) HOOC—R2—COOH (II) and/or a dicarboxylic acid according to formula (III) wherein R2 is a (C1-C40)-alkylene bridge or a (C2-C20)-alkenylene bridge and R is one or more radicals selected from the group consisting of H, (C1-C20)-alkyl, (C2-C20)-alkenyl, phenyl, benzyl, halogen, —NO2, (C1-C6)-alkoxy, —CHO, —CO((C1-C6)-alkyl), and mixtures thereof. 3. The pesticide preparation as claimed in claim 1, wherein the dicarboxylic acid b) is selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, fumaric acid, malic acid, phthalic acid, isophthalic acid, terephthalic acid, and mixtures thereof. 4. The pesticide preparation as claimed in claim 1, wherein the dicarboxylic acid b) is selected from the group consisting of phthalic acid, isophthalic acid, terephthalic acid, and mixtures thereof. 5. The pesticide preparation of claim 1, wherein the monocarboxylic acid c) is a fatty acid or a mixture of fatty acids. 6. The pesticide preparation of claim 1, wherein the monocarboxylic acid c) is selected from the group consisting of coconut acid, tallow fatty acid, and mixtures thereof. 7. The pesticide preparation of claim 1, wherein the dicarboxylic acid b) is phthalic acid and the monocarboxylic acid c) is coconut fatty acid. 8. The pesticide preparation of claim 1, wherein the copolymer comprises 1 to 10% by weight of component b). 9. The pesticide preparation of claim 1, wherein the copolymers have an OH number of from 400 to 1000 mg of KOH/g. 10. The pesticide preparation of claim 1, wherein the copolymer comprises a viscosity at 60° C. in the range of 1500 mPas to 35000 mPas. 11. The pesticide preparation of claim 1, wherein during the copolymerization, firstly the glycerol component a) is polymerized to a polyglycerol, and then the polyglycerol and a mixture of the dicarboxylic acid component b) and the monocarboxylic acid component c) are copolymerized. 12. The pesticide preparation of claim 1, wherein the glycerol component a) is firstly polymerized to polyglycerol, then the dicarboxylic acid component b) is copolymerized and then the monocarboxylic acid component c) is copolymerized. 13. The pesticide preparation of claim 1, wherein the glycerol component a) is firstly polymerized to polyglycerol, then the monocarboxylic acid component c) is copolymerized and then the dicarboxylic acid component b) is copolymerized. 14. The pesticide preparation of claim 1, wherein the pesticide is selected from the group consisting of herbicides, insecticides, fungicides, bactericides, molluscicdes, nematicides, rodenticides, and mixtures thereof. 15. The pesticide preparation of claim 1, wherein the pesticide is an herbicide herbicides. 16. The pesticide preparation of claim 15, wherein the herbicide is selected from the group consisting of glyphosate, glyphosate salts glyphosate derivatives, and mixtures thereof. 17. The pesticide preparation of claim 1, which is in a form selected from the group consisting of a “tank-mix”, “ready to use composition”, concentrate, powder, pellet, tablet, and granulate. 18. A method for increasing the bioactivity of at least one pesticide, said method comprising adding to the pesticide at least one copolymer obtained by copolymerization of a) glycerol. b) at least one dicarboxylic acid, and c) at least one monocarboxylic acid of the formula (I) R1—COOH (I) where R1 is (C5-C29)-alkyl: (C7-C29)-alkenyl; phenyl or naphthyl, wherein the copolymers comprise 19.9 to 99% by weight of component a), 0.1 to 30% by weight of component b) and 0.9 to 80% by weight of component c). 19. The pesticide preparation as claimed in claim 1, wherein the dicarboxylic acid b) is phthalic acid. 20. The pesticide preparation of claim 1, wherein the monocarboxylic acid c) is coconut acid. 21. The pesticide preparation as claimed in claim 1, wherein the pesticide preparation is in the form of a concentrate formulation having from 5 to 60% by weight of the pesticide and from 3 to 50% by weight of the copolymer. 22. The pesticide preparation of claim 21 wherein the concentrate formulation has a weight ratio of copolymer to pesticide of from 1:20 to 1:1. 23. The pesticide preparation of claim 21 wherein the concentrate formulation is a phase stable aqueous concentrate. |
Appliance having a clock set to universal time |
A appliance (100) having a receiver (324) capable of receiving and a decoder (314) capable of decoding a time signal (400) into a time value. A clock (308) in the appliance (100) is updated or set with the received time value and an indicator (104) is activated to notify consumers that time synchronization to a time signal has occurred. The decoder (314) from the decoded time signal (400) is able to identify leap years and changes to and from daylight savings time. |
1. A method of reporting time in an appliance comprising the steps of: receiving a radio signal having an encoded time signal at a receiver located in the appliance; decoding the encoded time signal into at least one time value; setting a clock with the at least one time value, wherein the clock is in communication with the receiver; and activating an indicator when the clock is set with the at least one time value. 2. The method of claim 1, where the step of receiving further comprises the step of activating the receiver at predetermined intervals. 3. The method of claim 1, where the step of decoding further comprises the steps of identifying the beginning of a WWVB time packet in the encoded time signal, and extracting at least one time value from the WWVB time packet. 4. The method of claim 1, where the step of decoding further comprises the steps of identifying the beginning of a DCF-77 time packet in the encoded time signal and, extracting at least one time value from the DCF-77 time packet. 5. The method of claim 1, where the step of decoding further comprises the step of identifying a minute change. 6. The method of claim 5, where the step of identifying further includes the step of identifying a peak of a double frame in a WWVB signal. 7. The method of claim 1, where the step of decoding further comprises the steps of identifying a leap year indicator in the at least one time value, and adjusting the clock with the at least one time value in response to the leap year indicator. 8. The method of claim 1, where the step of setting further includes the step of updating the clock at a predetermined interval. 9. The method of claim 8, wherein the predetermined interval is one minute. 10. The method of claim 1, where the step of activating further comprises the step of activating a human perceptible indicator. 11. The method of claim 10, where the step of activating further comprises the step of activating a visual indicator. 12. The method of claim 11, wherein the visual indicator is a light indicator. 13. The method of claim 11, wherein the visual indicator is a mechanical indicator. 14. The method of claim 1, wherein the step of activating further comprises the step of activating an audio indicator. 15. The method of claim 1, including the step of deactivating the indicator when the setting step does not occur within a predetermined period of time, wherein the predetermined period of time is starts when the indicator is activated. 16. The method of claim 1, including the step of activating a safety timer when the appliance is activated. 17. The method of claim 16, where the step of activating a safety timer further comprises the step of identifying a predetermined future time, and adjusting the predetermined future time for a time change. 18. A method of reporting time in an appliance comprising the steps of: receiving a radio signal having an encoded time signal at a receiver located in the appliance; detecting a synchronization pattern in the radio signal; decoding the encoded time signal into at least one time value; and setting a clock with the at least one time value, wherein the clock is in communication with the receiver. 19. The method of claim 18, where the step of receiving further comprises the step of activating the receiver at predetermined intervals. 20. The method of claim 18, where the step of decoding further comprises the steps of identifying the beginning of a WWVB time packet in the encoded time signal, and extracting at least one time value from the WWVB time packet. 21. The method of claim 18, where the step of decoding further comprises the steps of identifying the beginning of a DCF-77 time packet in the encoded time signal and, extracting at least one time value from the DCF-77 time packet. 22. The method of claim 18, where the step of detecting further comprises the step of identifying a minute change. 23. The method of claim 22, where the step of identifying further includes the step of identifying a peak of a double frame. 24. The method of claim 18, where the step of decoding further comprises the steps of identifying a leap year indicator in the at least one time value, and adjusting the clock with the at least one time value in response to the leap year indicator. 25. The method of claim 18, where the step of setting further includes the step of updating the clock at a predetermined interval. 26. The method of claim 25, wherein the predetermined interval is one minute. 27. The method of claim 18, further including, the step of activating an indicator when the clock is set with the at least one time value. 28. The method of claim 27, where the step of activating further comprises the step of activating a human perceptible indicator. 29. The method of claim 28, wherein the human perceptible indicator is a light indicator. 30. The method of claim 28, wherein the human perceptible indicator is a mechanical indicator. 31. The method of claim 27, wherein the indicator is an audio indicator. 32. The method of claim 27, including the step of deactivating the indicator when the setting step does not occur within a predetermined period of time, wherein the predetermined period of time is starts when the indicator is activated. 33. The method of claim 18, including the step of activating a safety timer when the appliance is activated. 34. The method of claim 33, where the step of activating a safety timer further comprises the step of identifying a predetermined future time, and adjusting the predetermined future time for a time change. 35. A method of reporting time in an appliance comprising the steps of: receiving a time value from an external device directly coupled to the appliance; setting a clock to with the time value; uncoupling from the external device; and powering the clock from a secondary power source. 36. The method of claim 36, wherein the time value is associated with a GPS signal. 37. The method of claim 36, wherein the time value is associated with a WWVB time signal. 38. The method of claim 36, wherein the time value is associated with a network time signal. 39. An apparatus that reports time, comprising: a receiver able to receive a radio signal having an encoded time signal; a decoder coupled by a signal path to the receiver that decodes the encoded time signal into at least one time value; a clock; a controller coupled by at least one other signal path to the clock and the decoder, wherein the controller updates the clock with the at least one time value from the decoder. 40. The apparatus of claim 40, wherein the receiver is activates at predetermined time to receive the encoded time signal. 41. The apparatus of claim 40, wherein the decoder identifies a WWVB time packet in the encoded time signal and a plurality of frames located within the WWVB time packet. 42. The apparatus of claim 40, wherein the decoder identifies a DCF-77 time packet in the encoded time signal and a plurality of frames located within the DCF-77 time packet. 43. The apparatus of claim 40, wherein the decoder identifies a minute change. 44. The apparatus of claim 44, wherein the decoder locating a peak of a double frame in a WWB signal identifies the minute change. 45. The apparatus of claim 40, wherein a plurality of flags represent a time change are detected in the encoded time signal when decoded by the decoder and the controller processing the flag from the decoder resulting in the clock being updated in accordance with the flag. 46. The apparatus of claim 40, further comprising an indicator electrically coupled to the controller that is activated upon the clock being updated with the at least one time value. 47. The apparatus of claim 47, wherein the indicator is a mechanical indicator. 48. The apparatus of claim 47, wherein the indicator is audio indicator. 49. The apparatus of claim 47, wherein the indicator is a visual indicator. 50. The apparatus of claim 47, wherein the visual indicator is deactivated when at least one time value is not received within a predetermined period of time. 51. The apparatus of claim 40, wherein the controller sets a safety timer by determining a predetermined future time and generates a safety timer signal upon the clock matching the predetermined future time. 52. The apparatus of claim 52, wherein controller adjusts the predetermined future time in response to the decoder detecting at least one flag from the plurality of flags that represents the time change. 53. A time setting system, comprising: a server having a receiver for reception of a time signal that results in a time value; an appliance with a input/output port coupled to a controller and a clock, in physical contact with the server, wherein the controller updates the clock with the time value upon receipt at the appliance of the time value. 54. The system of claim 36, wherein the time value is associated with a GPS signal. 55. The system of claim 36, wherein the time value is associated with a WWVB time signal. 56. The system of claim 36, wherein the time value is associated with a network time signal. 57. The system of claim 54, wherein the clock is powered by a secondary power supply located in the appliance after receipt of the time value. 58. A signal bearing media having machine readable instructions for adjusting image lighting on a preparatory image, comprising: a first set of machine readable instructions for receiving a radio signal having an encoded time signal at a receiver; a second set of machine readable instructions for decoding the encoded time signal into at least one time value; a third set of machine readable instructions for setting a clock with the at least one time value; and a fourth set of machine readable instructions for activating an indicator when the clock is set with the at least one time value. 59. The signal bearing media of claim 59, wherein the second set of instructions further comprise, instructions for identifying the beginning of a WWVB time packet in the encoded time signal, and another set of instructions for extracting at least one time value from the WWVB time packet. 60. The signal bearing media of claim 60, wherein the instructions for identifying the beginning of a WWVB time packet, further include instructions for identifying a peak of a double frame in the encoded time signal. 61. A signal bearing media having machine readable instructions for adjusting image lighting on a preparatory image, comprising: a first set of machine readable instructions for receiving a radio signal having an encoded time signal at a receiver; a second set of machine readable instructions for decoding the encoded time signal into at least one time value; and a third set of machine readable instructions for setting a clock with the at least one time value. 62. The signal bearing media of claim 59, wherein the second set of instructions further comprise, instructions for identifying the beginning of a WWVB time packet in the encoded time signal, and another set of instructions for extracting at least one time value from the WWVB time packet. 63. The signal bearing media of claim 60, wherein the instructions for identifying the beginning of a WWVB time packet, further include instructions for identifying a peak of a double frame in the encoded time signal. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Technical Field This invention relates generally to clocks and more particularly to an appliance having a clock set to Coordinated Universal Time (UTC). 2. Related Art Consumers often have numerous appliances that have clocks for displaying time. In order to synchronize the time between the clocks in different appliances, the consumer is required to set each clock individual. Furthermore, when power outages or time changes occur, a consumer again has to reset the clocks. A common method for an appliance having a clock to maintain time during a power outage requires a second power source to be present in the appliance. But, the clock still must be initially set by the consumer and adjusted for time changes from or to “Daylight Saving Time.” Further, it is not uncommon for clocks to contain calendars for displaying date information that must be adjusted for leap years. Since the accuracy of a clock is often directly proportional to the cost, the clocks found in appliances will have time drift resulting in larger and larger inaccuracies over an increasing period of time. Therefore, there is a need to provide an approach for maintaining and adjusting the time of stand alone clocks and clocks that are integrated with appliances while using common quality parts to correct time drift, changes from/to “Daylight Saving Time”, and leap years. |
<SOH> SUMMARY <EOH>Broadly conceptualized, a clock integrated with an appliance or standing alone is connected to a receiver that receives a timing signal that can be locked on to and decoded with minimal decoding of the timing signal. A human perceptible indicator is activated upon the synchronization with the time signal and the human perceptible indicator stays on for a predetermined period after synchronization. Furthermore, a predictive process can be used to compensate for noise contained in the received timing signal. The initial time is set in the factory and automatically adjusts to time changes, thus limiting the consumer interaction to selecting the time zone for the displayed time. Other systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims. |
Pharmaceutical products, preparation and uses thereof |
A pharmaceutical product comprising at least one therapeutic agent, whereby a unit dose of said therapeutic agent as provided by said pharmaceutical product can be administered to a patient during the passage of said therapeutic agent through the gastrointestinal tract of the patient, wherein said therapeutic agent is characterised as having an aqueous solubility of not greater than about 1 in 30 to 1 in 100, weight/volume, when measured at a temperature in the range of 15 to 25° C. |
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