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<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the purpose(s) of this invention, as embodied and broadly described herein, this invention, in one aspect, relates to immunoreactive peptides. In another aspect, it relates to compositions or vaccines comprising the peptides, including polypeptides and proteins. The synthetic peptides of the invention are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) GAS serotypes and which are immunoreactive. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. The invention is also a composition or a vaccine comprised of these synthetic serotype-specific peptides of 20-25 amino acids in length from GAS M proteins. The peptides can be used, for example, individually, in a mixture, or in a polypeptide or protein. Examples of ways the polypeptide or protein can be created include fusing or linking the peptides to each other, synthesizing the polypeptide or protein based on the peptide sequences, and linking or fusing the peptides to a backbone. Also, a liposome may be prepared with the peptides conjugated to it or integrated within it. The compositions or vaccines may further comprise additional components, including but not limited to, carriers, vehicles (e.g., encapsulated, liposomes), and other immune-stimulatory molecules (e.g., adjuvants, other vaccines). Additionally, a DNA vaccine comprising DNA encoding the peptides or compositions of the present invention is disclosed. The invention may also be isolated antibodies which are elicited in response to the peptides, compositions or vaccines. In further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines. The invention still further relates to kits for using the peptides or antibodies, which can, for example, be used for diagnostic purposes. Additional aspects of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The aspects of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. |
Method for producing an electronic component, especially a memory chip |
A method for producing an electronic component, especially a memory chip, using a laser-induced correction to equalize an integrated circuit by means of at least one laser via in a layer at least partially covering the circuit. The component comprises a rewiring of the contact pads. The inventive method comprises the following steps: each laser via is closed by means of a separate covering layer which is to be applied locally; a rewiring extending between the local covering layers is created; the local covering layers are removed; and the laser-induced correction is carried out by means of the open laser vias. |
1. A method for producing an electronic component, in particular a memory chip, with a laser-indexed correction for the adjustment of an integrated circuit by means of one or more laser vias introduced into a layer that at least partially covers the circuit, the component having a rewiring of the contact pads, comprising the following steps: closing off of each laser via by means of a separate cover layer that is to be applied locally, production of a rewiring running between the local cover layers, removal of the local cover layers, carrying out of the laser-induced correction by means of the opened laser vias. 2. The method as claimed in claim 1, characterized in that the laser vias are covered again by means of a covering layer after laser adjustment has been effected. 3. The method as claimed in claim 1, characterized in that a cover layer that can be decomposed chemically, thermally or by irradiation, in particular by UV irradiation, is used as the cover layer. 4. A method for producing an electronic component, in particular a memory chip, with a laser-indexed correction for the adjustment of an integrated circuit by means of one or more laser vias introduced into a covering layer that at least partially covers the circuit, the component having a rewiring of the contact pads, comprising the following steps: closing off of each laser via by means of a separate thin cover layer that is to be applied locally, production of a rewiring running between the local cover layers, and carrying out of the laser-induced correction by means of the closed laser vias. 5. The method as claimed in claim 4, characterized in that a reinforcing cover layer is applied to the thin cover layer after the correction. 6. The method as claimed in claim 4, characterized in that the if appropriate first cover layer has a thickness of ≦1 μm. 7. The method as claimed in claim 4, characterized in that the if appropriate first cover layer is resistant to a subsequent etching step that is effected in particular for the purpose of producing the rewiring. 8. A method for producing an electronic component, in particular a memory chip, with a laser-indexed correction for the adjustment of an integrated circuit by means of one or more laser vias introduced into a covering layer that at least partially covers the circuit, the component having a rewiring of the contact pads, comprising the following steps: closing off or coating of the individual laser fuse lines by means of a thin passivation layer comprising silicon nitride, silicon oxynitride, silicon oxide or other suitable materials, application of a covering layer, generally a polyimide layer, to the entire wafer, opening of the laser vias and of the contact pads, production of a rewiring running between the laser vias, and carrying out of the laser-induced correction at the passivated laser fuse lines through the opened laser vias. 9. The method as claimed in claim 8, characterized in that the laser vias are covered again by means of a covering layer after laser adjustment has been effected. 10. The method as claimed in claim 8, characterized in that the passivation layer on the laser fuse lines has a thickness of ≦0.5 μm. 11. The method as claimed in claim 8, characterized in that the passivation layer on the laser fuse lines is resistant to a subsequent etching step that is effected in particular for the purpose of producing the rewiring. 12. A method for producing an electronic component, in particular a memory chip, with a laser-indexed correction for the adjustment of an integrated circuit by means of one or more laser vias introduced into a covering layer that at least partially covers the circuit, the component having a rewiring of the contact pads, comprising the following steps: coating of the individual laser fuse lines by means of a thin passivation layer comprising silicon nitride, silicon oxynitride, silicon oxide or other suitable materials, application of a covering layer, generally a polyimide layer, to the entire wafer, opening of the contact pads, production of a rewiring running between the laser vias, and opening of the laser vias, carrying out of the laser-induced correction at the passivated laser fuse lines through the opened laser vias. 13. The method as claimed in claim 12, characterized in that the laser vias are covered again by means of a covering layer after laser adjustment has been effected. 14. The method as claimed in claim 12, characterized in that the passivation layer on the laser fuse lines has a thickness of between zero and 0.5 μm. 15. The method as claimed in claim 12, characterized in that the component is tested before the carrying out of the laser-induced correction and the laser fuse lines and/or a burn-in is carried out. 16. The method as claimed in claim 1 claims, characterized in that the first and/or the reinforcing cover layer and/or the covering layer are printed on. 17. The method as claimed in claim 16, characterized in that the respective layer are printed on in a mask or screen printing method. 18. The method as claimed in claim 1, characterized in that a polymer layer is used as the cover layer and/or as the covering layer. 19. The method as claimed in claim 1, characterized in that the component is tested before the removal of the cover layers that locally cover the laser vias or before the carrying out of the laser-induced correction through the closed laser vias or passivated laser fuse lines and/or a burn-in is carried out. 20. (canceled) |
Method for cracking open and separating an egg and a device for use thereof |
The invention relates to a method for cracking open an egg using a device for cracking open and separating an egg, comprising, (a) placing an egg into a predetermined position in said device; (b) gripping said egg (by said device); (c) penetrating the shell of said egg in a predetermined manner; (d) opening the shell of said egg so as to release the contents therein. The invention also discloses a device for cracking open an egg. |
1. A method for cracking open an egg using a device for cracking open and separating an egg, comprising, (One) placing an egg into a predetermined position in said device; (Two) gripping said egg (by said device); (Three) penetrating the shell of said egg in a predetermined manner; (Four) opening the shell of said egg so as to release the contents therein; 2. A method according to claim 1, further comprising the step of separating the yolk of the egg from the white of the egg. 3. A method according to claim 1, wherein penetrating the shell of the egg is accomplished by two piercing members positioned adjacent to one another. 4. A method according to claim 3, wherein opening of the shell occurs when said piercing members are moved away from one another. 5. A device for cracking open an egg comprising an upper handle and a lower handle for grasping and operating said device, holding means for holding an egg to be cracked in a predetermined position, and gripping, penetrating, and opening mechanism coupled to said handles and said holding means, for gripping said egg, for penetrating the shell of said egg, and for opening said shell so as to release the inner contents of the egg, wherein said gripping, penetrating, and opening mechanism comprises; (One) a first arm and second arm, wherein said arms are movable between a first position wherein said arms are substantially parallel to one another and a second position wherein said arms are angled with respect to one another; (Two) moving means for moving said first and second movable arms from said first position to said second position, wherein said moving means are actuated by the pushing together of the handles by a user; (Three) a first piercing member and second piercing member protruding from said first and second movable arms, respectively, said first and second piercing members being positioned adjacent to another when said arms are in said first position, and said piercing members moving apart from one another when said arms are moved to said second position; wherein said piercing members are positioned at a location directly below said holding means such that when an egg is positioned inside said holding means, said egg will be gripped, penetrated, and opened as said handles are pushed together. 6. A device according to claim 5, wherein the holding means comprises a first ring and a second ring, wherein said first and second rings are attached, at their lower ends, to said first and second movable arms, respectively. 7. A device according to claim 5, further comprising a protruding element positioned at the proximal end of said lower handle for facilitating gripping of the egg by the device. 8. A device according to claim 5, further comprising a cup positioned below said holding means for receiving the yolk of an egg following opening of said egg. |
<SOH> BACKGROUND OF THE INVENTION <EOH>It is sometimes difficult and messy to crack open and egg, and, moreover, to separate the yolk of the egg from the white. Various egg-separating devices are known in the art that facilitate performance of this task including, U.S. Pat. No. 4,068,573 to Romero, U.S. Pat. No. 4,665,813 to Maisonneuve, and U.S. Pat. No. 5,083,508 to Banks et al. None of the egg-crackers currently available satisfactorily perform the job of cracking open and separating an egg. A device for cracking open an egg should make said task easier to perform, not harder. Instead, many devices cause the yolk to break, are messy, and are awkward for the user to handle. The present invention relates to a device for cracking open an egg that is both simple to use and reliable. The device of the present invention employs a three-stage process, comprising gripping the egg, cracking the shell of the egg, and separating the shell of the egg so that the contents inside fall into a receiving vessel. The receiving vessel may be any container employed by the user to receive the contents of the egg. Alternatively, the device has a removable cup adapted in size and shape for receiving the yolk of the egg while the white falls to a receiving vessel positioned underneath the device. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a method for cracking open and egg to obtain the contents therein and for separating the egg yolk from the white (if desired) and to a device for use in carrying out said method. The device is adapted for cracking open an egg in three simple steps, leading to mess-free, and convenient opening of an egg without pieces of the shell remaining in the white or the yolk and without breakage of the yolk. The device is suitable for eggs of all different sizes. It will become evident from the description provided that the present invention provides an egg-cracking device far superior to those already known in the art both in its simplicity of use and in its efficiency. The present invention relates to a method for cracking open an egg using a device for cracking open and separating an egg, comprising, (One) placing an egg into a predetermined position in said device; (Two) gripping said egg (by said device); (Three) penetrating the shell of said egg in a predetermined manner; (Four) opening the shell of said egg so as to release the contents therein; According to preferred embodiments of the present invention, the method further comprises the step of separating the yolk of the egg from the white of the egg. Furthermore according to preferred embodiments of the present invention, the step of penetrating the shell of the egg is accomplished by two piercing members positioned adjacent to one another. Moreover according to preferred embodiments of the present invention, the step of opening of the shell occurs when said piercing members are moved away from one another. The present invention also relates to a device for cracking open an egg comprising an upper handle and a lower handle for grasping and operating the device, holding means for holding an egg to be cracked in a predetermined position, and gripping, penetrating, and opening mechanism coupled to the handles and the holding means, for gripping said egg, for penetrating the shell of said egg, and for opening said shell so as to release the inner contents of the egg. The gripping, penetrating, and opening mechanism comprises; (One) a first arm and second arm, wherein the arms are movable between a first position wherein the said arms are substantially parallel to one another and a second position wherein the arms are angled with respect to one another; (Two) moving means for moving the first and second movable arms from the first position to the second position, wherein the moving means are actuated by the pushing together of the handles by a user; (Three) a first piercing member and second piercing member protruding from the first and second movable arms, respectively, the first and second piercing members being positioned adjacent to another when the arms are in the first position, and the piercing members moving apart from one another when the arms are moved to the second position; The piercing members are positioned at a location directly below the holding means such that when an egg is positioned inside said holding means, the egg will be gripped, penetrated, and opened as the handles are pushed together. According to preferred embodiments of the present invention, the holding means comprises a first ring and a second ring. The first and second rings are attached, at their lower ends, to the first and second movable arms, respectively. Moreover according to preferred embodiments of the present invention, the device further comprises a protruding element positioned at the proximal end of the lower handle for facilitating gripping of the egg by the device. Additionally according to preferred embodiments of the present invention, the device further comprises a cup positioned below the holding means for receiving the yolk of an egg following opening of the egg. |
Method of optimising content presented to a user within a communication network |
A method of optimising content presented to a user within a communications network, wherein the user (32) establishes a session (6) with the communications network (31) and generates one or more session events (7-19) during that session, the method including the step of: at least once during that session comparing (70-82) the past performance as a traffic stream of multiple sources of content that could be presented to a user to predetermine traffic performance criteria, to enable content (39) to be presented to the user from a content source meeting the predetermined traffic performance criteria. |
1. A method of optimising content presented to a user within a communications network, wherein the user establishes a session with the communications network and generates one or more session events during that session, the method including the step of: at least once during that session comparing past performance as a traffic stream of multiple sources of content that could be presented to a user to predetermine traffic performance criteria, to enable content to be presented to the user from a content source meeting the predetermined traffic performance criteria. 2. The method according to claim 1, wherein the past performance as a traffic stream source of each content source is determined by deriving a traffic performance index for each content source. 3. The method according to claim 2, wherein content is presented to a user from the content source having an optimal traffic performance index value. 4. The method according to claim 3, wherein the traffic performance index is derived from one or more key performance indicators representative of user behaviour with each of the multiple sources of content. 5. The method according to claim 4, wherein the key performance indicators are derived from predetermined session metrics related to historical session events. 6. The method according to claim 1, wherein optimisation takes place before the user requests access to content from one of the multiple sources of content. 7. The method according to claim 1, wherein the optimisation takes place during a user request for access for content from one of multiple sources of content. 8. The method according to claim 7, wherein a user requests access to content from a predetermined content category, and optimisation is applied to multiple sources of content meeting that predetermined content category. 9. The method according to claim 8, wherein content from a content source within the predetermined content category having an optimal traffic performance index value is displayed to the user. 10. The method according to claim 1, wherein optimisation takes place after the user requests access to content from one of the multiple sources of content. 11. The method according to claim 10, wherein a user requests access to content from one of the multiple sources of content, and in addition to the requested content, optimised advertising content is then provided to the user. 12. The method according to claim 1, wherein the past performance as a traffic stream source of the multiple sources of content is determined by: (a) one or more users each establishing a session with related content source within the communications network, (b) each user generating one or more session events during that session, (c) determining a session event key for selected session events, (d) deriving one or more predetermined session metrics related to session events generated during each session, (e) recording the session metrics against one or more of the session event keys, (f) processing the recorded session metrics to derive one or more key performance indicators representative of user behaviour in relation to each content source, and (g) deriving a traffic performance index for each content source from the key performance indicators for that content source. 13. The method according to claim 12, wherein the session events include at least one of: (a) an impression event whenever content is accessed by a user from one of the content sources, (b) a results event whenever a quantifiable result is achieved, and, (c) an advertising event whenever advertising content is presented to a user. 14. The method according to claim 13, wherein a session event key is determined for at least each impression event. 15. The method according to claim 12, wherein the recorded session metrics characterise the number of events generated in sessions in which each impression event occurred. 16. The method according to claim 15, wherein the recorded session metrics further characterise the number of sessions during which each impression event occurred. 17. The method according to claim 12, wherein one or more session event keys are determined for identifying the time at which the session event occurred. 18. The method according to claim 12, wherein the session metrics further characterise the total number of at least one of impression events, long held sessions and session length. 19. The method according to claim 12, wherein a session event key is determined for each results event. 20. The method according to claim 12, wherein the session metrics further characterise the nature, cost and/or revenue of each results event. 21. The method according to claim 20, wherein the session metrics further characterise the total number of transactions. 22. The method according to claim 12, wherein a session event key is generated for each advertising event. 23. The method according to claim 22, wherein the session event key characterises the identity of the advertising source. 24. The method according to claim 12, wherein the session metrics characterise the number of banner impressions, clicks and/or unique clicks from banner impressions. 25. The method according to claim 12, wherein the key performance indicators are derived by selecting and sorting the session metrics according to one or more session event keys. 26. The method according to claim 25, wherein the key performance indicators include at least one of a click through ratio, click to conversion ratio, session to conversion rate, average number of sites per session or like indicator characterising the relationship between impression events, results events and advertising events. 27. The method according to claim 1, wherein data capture is initiated by a client associated with each user or by a server hosting content accessed by or presented to each user. 28. The method according to claim 27, the method further including the steps of: capturing raw user activity data in a log file, and transmitting the log file to a central server within the communications network. 29. The method according to claim 28, wherein the log file is batched or transmitted in real time to the central server. 30. The method according to claim 29, the method further including the step: storing the recorded session metrics in a data storage device associated with the central server. 31. The method according to claim 30, wherein the data storage device includes one or more data tables of session event keys and corresponding predetermined session metrics. 32. A central measurement server including a processing unit and associated memory device for storing program instructions to cause the central measurement server to carry out a method according to claim 1. 33. A computer program including program instructions for use with a central measurement server, the central server including a processing unit and associated memory device for storing the program instructions, wherein the program instructions causes the central measurement server to carry out a method according to claim 1. |
Facile diagnosis and monitoring of pneumocystis carinii infection |
Significantly low circulating, S-adenosylmethionine levels were found to be diagnostic for human Pneumocystis carinii infection, and rise in levels towards normal correlated with successful treatment. Diagnosis of P. carinii injection and monitoring of progress of treatment based thereon are described. |
1. A method for identifying the presence of a Pneumocystis carinii infection in a human comprising the steps of a) obtaining a blood sample from said human; b) measuring the level of S-adenosylmethionine in said blood sample; and c) correlating a S-adenosylmethionine level below that of an uninfected standard level as indicating the presence of a Pneumocystis carinii infection in said human. 2. The method of claim 1 wherein said human is infected with HIV, has AIDS, has cancer, is immunosuppressed, or is otherwise susceptible to infection by Pneumocystis carinii. 3. The method of claim 2 wherein said blood sample is plasma. 4. The method of claim 1 wherein said level below that of an uninfected standard level is a level below two standard deviations of the mean value of asymptomatic HIV-infected individuals. 5. A method for monitoring changes over time in the level of infection of Pneumocystis carinii in a human comprising the steps of a) obtaining a series of sequential blood samples over time from said human; b) measuring the level of S-adenosylmethionine in said blood samples; and c) correlating an increase, decrease or no change in the level of S adenosylmethionine in said blood samples over time with a decrease, increase, or no change, respectively, in the level of infection of Pneumocystis carinii infection in said human. 6. The method of claim 5 wherein said human is infected with HIV, has AIDS, has cancer, is immunosuppressed, or is otherwise susceptible to infection by Pneumocystis carinii. 7. The method of claim 5 wherein said blood sample is plasma. 8. The method of claim 5 wherein said human is undergoing treatment for said Pneumocystis carinii infection. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Pneumocystis carinii is a fungus that causes P. carinii pneumonia (PCP) in people with AIDS, patients undergoing cancer chemotherapy, and others with conditions causing severe immunosuppression. Although the frequency of PCP in HIV-infected persons has decreased dramatically over the fast 8 years, due first to widespread prophylaxis against PCP and more recently to the reduced immunosuppression brought on by improved anti-HIV therapy, PCP remains common in AIDS patients. A large portion of all HIV infections are in Africa yet PCP there was considered rare. However, a recent South African survey reports that PCP is the most common opportunistic infection associated with AIDS in that country—for persons of African as well as European origin (Mahomed et al., 1999 , East Afr Med J. 76:80-4). An entirely new risk for PCP was identified by a study of autopsy specimens in the UK and Chile. After eliminating all cases of HIV infection, analysis of the data suggested that PCP plays a role in a significant number of cases of sudden infant death syndrome (Vargas et al., 1999 , Clin Infect Dis. 29:1489-93). Treatment for PCP is less than ideal with frequent severe side effects from the two most effective drugs, pentamidine and the combination of trimethoprim and sulfamethoxazole (cotrimoxazole, TMIP-SMZ) (Wilkin, A., and Feinberg, J. (1999) Am. Fam. Physician 60, 1699-1708, 1713-1714). The mortality rate also remains high (21.5%) (Azoulay, E., Parrot, A., Flahault, A., Cesari, D., Lecomte, I., Roux, P., Saidi, F., Fartoukh, M., Bernaudin, J. F., Cadranel. J., and Mayaud, C. (1999) Am. J. Respir. Crit. Care Med. 160, 493-499). Diagnostic methods for PCP are less than ideal. Although bronchoscopy with bronchioalveolar lavage is 95% sensitive, it is expensive, invasive and requires skilled personnel. Induced sputum, an alternative method of diagnosis, is noninvasive but is often much less sensitive (80%). Moreover, the ability to assess treatment effectiveness by means other than clinical improvement is lacking other than by the aforementioned diagnostic methods. S-Adenosyl-L-methionine (interchangeably referred to herein as S-adenosylmethionine, AdoMet, or SAM) plays a pivotal role in the physiology of all cells, both as methyl donor in myriad of biological and biochemical events and as a precursor of polyamines. About 95% of AdoMet is used for transmethylation reactions in which the N-methyl group of the methionine moiety is transferred to large molecules such as proteins, complex lipids, and DNA or to small molecules to form lecithin, regenerate methionine, etc. (Cohen, S. (1998) A Guide to Polyamines , Oxford University Press, Oxford). The remaining 2-5% of AdoMet is decarboxylated to become the aminopropyl donor for synthesis of the essential polyamines spermidine and spermine (Newman, E. B., Budman, L. I., Chan, E. C., Greene, R. C., Lin. R. T., Woldringh, C. L., and D'Ari, R. (1998) J. Bacteriol. 180, 3614-3619). Transmethylation reactions result in the formation of S-adenosylhomocysteine which is then hydrolyzed by S-adenosylhomocysteine hydrolase to form adenosine and homocysteine. Decarboxylation of AdoMet is catalyzed by S-adenosylmethionine decarboxylase producing decarboxylated AdoMet, an intermediate committed to polyamine biosynthesis. Decarboxylated AdoMet donates an aminopropyl group to putrescine to form spermidine or to spermidine to form spermine. The end product of the aminopropyl transfer reactions is methylthioadenosine which is cleaved by a specific phosphorylase, the products being recycled in various ways to methionine and purines, respectively. A comprehensive review of polyamine metabolism and function has: been published (Cohen, ibid.). It is towards a facile means for both diagnosing P. carinii infection in humans and monitoring the effectiveness of treatment of the infection that the present invention is directed. The citation of any reference herein should not be deemed as an admission that such reference is available as prior art to the instant invention. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is generally directed to the diagnosis and to the monitoring of the progress of infection and treatment of Pneumocystis carinii in a human by measuring the level of S-adenosylmethionine (AdoMet) in the blood, and basing the diagnosis on a standard level of uninfected individuals, or for monitoring changes over time on the individual's previous values. Infection of humans by P. carinii is associated with a significantly decreased level of S-adenosylmethionine in circulation; successful treatment of human P. carinii infection results in an increase and normalization in such levels. In one embodiment, a method for identifying the presence of a Pneumocystis carinii infection in a human is provided by carrying out at least the steps of a) obtaining a blood sample from the human; b) measuring the level of S-adenosylmethionine in the blood sample; and c) correlating a S-adenosylmethionine level below that of an uninfected standard level as indicating the presence of a Pneumocystis carinii infection in the human. By way of non-limiting example, the human may be infected with HIV, have AIDS, have cancer, may be immunosuppressed, or may be otherwise susceptible to infection by Pneumocystis carinii . In a preferred embodiment, the blood sample is a plasma sample or a serum sample; most preferred is plasma. In another embodiment of the invention, a method for monitoring changes over time in the level of infection of Pneumocystis carinii in a human is provided by carrying out at least the steps of a) obtaining a series of sequential blood samples over time from the human; b) measuring the level of S-adenosylmethionine in the blood samples; and c) correlating an increase, decrease or no change in the level of S-adenosylmethionine in the blood samples over time with a decrease, increase, or no change, respectively, in the level of infection of Pneumocystis carinii infection in the human. At least two samples are necessary for monitoring changes in levels over time, but many samples may be taken and evaluated over the course of treatment and afterwards. In a non-limiting example, the human may be infected with HIV, may have AIDS, may have cancer, may be immunosuppressed, or may be otherwise susceptible to infection by Pneumocystis carinii . In a preferred embodiment, the blood samples are plasma or serum; most preferably it is plasma. The human may be undergoing treatment for the Pneumocystis carinii infection. These and other aspects of the present invention will be better appreciated by reference to the following drawings and Detailed Description. |
Thermal insulation containing supplemental infrared radiation absorbing material |
A thermal insulation product includes an infrared radiation absorbing and scattering material dispersed on fibers forming a porous structure. The infrared absorbing and scattering material can include borate compounds, carbonate compounds, and alumina compounds. |
1. A thermal insulation product comprising fibers; and an infrared absorbing and scattering material dispersed on the fibers, wherein the infrared absorbing and scattering material comprises at least one compound selected from the group consisting of carbonate compounds, borate compounds, and alumina compounds; and the product further comprises a porous structure. 2. The product according to claim 1, wherein at least a portion of the infrared absorbing and scattering material is dispersed on fibers inside the thermal insulation product. 3. The product according to claim 1, wherein the porous structure is nonwoven. 4. The product according to claim 1, wherein the fibers are inorganic. 5. The product according to claim 1, wherein the fibers comprise a glass. 6. The product according to claim 1, wherein the product comprises the infrared absorbing and scattering material in an amount of from 1 to 40% by weight. 7. The product according to claim 1, wherein the infrared absorbing and scattering material comprises a carbonate compound selected from the group consisting of calcium carbonate, dolomite and magnesite. 8. The product according to claim 1, wherein the infrared absorbing and scattering material comprises a borate compound selected from the group consisting of borax and colemanite. 9. The product according to claim 1, wherein the infrared absorbing and scattering material comprises hydrated alumina. 10. The product according to claim 1, further comprising a binder selected from the group consisting of thermosetting polymers, thermoplastic polymers, and inorganic compounds. 11. The product according to claim 1, wherein the infrared absorbing and scattering material absorbs infrared radiation having a wavelength in a range of 4 to 40 μm. 12. The product according to claim 11, wherein the infrared absorbing and scattering material absorbs infrared radiation having a wavelength in a range of 6 to 8 μm. 13. Use of an infrared absorbing and scattering material comprising at least one compound selected from the group consisting of carbonate compounds, borate compounds, and alumina compounds to improve the thermal resistance of a thermal insulation product comprising fibers, the infrared absorbing and scattering material being dispersed on the fibers, wherein the product further comprises a porous structure. 14. Use of an infrared absorbing and scattering material comprising at least one compound selected from the group consisting of carbonate compounds and alumina compounds to improve the thermal resistance at a temperature of 300° C. or more of a thermal insulation product comprising fibers, the infrared absorbing and scattering material being dispersed on the fibers, wherein the product further comprises a porous structure. 15. Use of an infrared absorbing and scattering material comprising at least one compound selected from the group consisting of carbonate compounds and alumina compounds to improve the thermal resistance at a temperature of 400° C. or more of a thermal insulation product comprising fibers, the infrared absorbing and scattering material being dispersed on the fibers, wherein the product further comprises a porous structure. 16. A method of forming a thermal insulation product, the method comprising dispersing on fibers an infrared absorbing and scattering material comprising at least one compound selected from the group consisting of carbonate compounds, borate compounds, and alumina compounds; and forming the fibers into a porous structure. 17. The method according to claim 16, wherein the infrared absorbing and scattering material comprises calcium carbonate. 18. The method according to claim 16, wherein the dispersing comprises soaking or spraying the fibers with a liquid mixture containing the infrared absorbing and scattering material. 19. The method according to claim 18, wherein the infrared absorbing and scattering material is suspended in the liquid mixture. 20. The method according to claim 16, wherein the infrared absorbing and scattering material is dispersed on the fibers after the fibers are formed into the porous structure. 21. The method according to claim 16, wherein the dispersing comprises mixing the infrared absorbing and scattering material and the fibers. 22. The method according to claim 16, wherein the dispersing comprises mixing the infrared absorbing and scattering material and the fibers; heating the infrared absorbing and scattering material; and binding the fibers together with the infrared absorbing and scattering material. 23. The method according to claim 16, wherein the mixing comprises sucking or blowing a dry powder of the infrared absorbing and scattering material into the porous structure. 24. The method according to claim 16, wherein the dispersing comprises mixing the infrared absorbing and scattering material, the fibers, and a binder. 25. The method according to claim 16, wherein the dispersing comprises mixing the infrared absorbing and scattering material and the fibers with a binder; heating the binder; and binding the fibers and the infrared absorbing and scattering material together with the binder. 26. The method according to claim 25, wherein the mixing comprises sucking or blowing the binder and a dry powder of the infrared absorbing and scattering material into the porous structure. 27. The method according to claim 16, wherein the porous structure is nonwoven. 28. The method according to claim 16, wherein the fibers are inorganic. 29. The method according to claim 16, wherein the fibers comprise a glass. 30. The method according to claim 16, wherein the infrared absorbing and scattering material comprises a compound selected from the group consisting of carbonate compounds and alumina compounds. 31. The method according to claim 16, further comprising forming the porous structure into a pipe section comprising the infrared absorbing and scattering material and the fibers. 32. The method according to claim 31, wherein the infrared absorbing and scattering material is dispersed on the fibers before the porous structure is formed into the pipe section. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention relates to thermal insulation. More specifically, this invention relates to thermal insulation containing infrared radiation (“IR”) absorbing and scattering material, which reduces radiative heat transfer through the thermal insulation. 2. Description of Related Art Heat passes between two surfaces having different temperatures by three mechanisms: convection, conduction and radiation. These heat transfer mechanisms are combined in a quantitative measure of heat transfer known as “apparent thermal conductivity.” Insertion of glass fiber thermal insulation in the gap between two surfaces reduces convection as a heat transport mechanism because the insulation slows or stops the circulation of air. Heat transfer by conduction through the glass fiber of the insulation is also minimal. However, many glass compositions used in glass fiber insulation products are transparent in portions of the infrared spectrum. Thus, even when the gap between surfaces has been filled with glass fiber thermal insulation, radiation remains as a significant heat transfer mechanism. Typically, radiation can account for 10 to 40% of the heat transferred between surfaces at room (e.g., 24° C.) temperature. Fiber to fiber radiative heat transfer is due to absorption, emission and scattering. The amount of radiative heat transfer between fibers due to emission and absorption is dependent on the difference in fiber temperatures, with each fiber temperature taken to the fourth power. To reduce radiative heat loss through thermal insulation, a number of approaches have been considered. U.S. Pat. No. 2,134,340 discloses that multiple reflections of infrared radiation from a powder of an infrared transparent salt, such as calcium fluoride, added to glass fiber insulation can prevent the infrared radiation from penetrating any substantial distance into the insulation. U.S. Pat. No. 5,633,077 discloses that an insulating material combining certain chiral polymers with fibers can block the passage of infrared radiation through the insulating material. U.S. Pat. No. 5,932,449 discloses that glass fiber compositions displaying decreased far infrared radiation transmission may be produced from soda-lime borosilicate glasses having a high boron oxide content and a low concentration of alkaline earth metal oxides. There remains a need for a cost effective thermal insulation product that can reduce radiative heat loss. |
<SOH> SUMMARY OF THE INVENTION <EOH>A thermal insulation product is provided in which an IR absorbing and scattering material is dispersed on fibers arranged in a porous structure. The IR absorbing and scattering material can be applied to the fibers before or after the fibers are formed into the porous structure. The IR absorbing and scattering material substantially reduces the radiative heat loss through the thermal insulation. Inclusion of the IR absorbing and scattering material improves the effective wavelength range over which the porous structure absorbs infrared radiation and improves its overall extinction efficiency. The IR absorbing and scattering material is about as effective as glass fiber in reducing radiative heat loss through a porous fiber structure, but can be much less expensive than glass fiber. Hence, the IR absorbing and scattering material can provide a cost-effective means of improving thermal insulation. |
Dihydroimidazo[5,1-a]sg(b)-carboline derivatives, method for preparing same and use thereof as medicine |
The invention concerns dihydroimi-dazo[5,1-a]-β-carboline compounds of general formula (1), wherein in particular, R1, R2, R2, Ra, R6 and K7, identical or different, independently of one another, represent a hydrogen, halogen atom, an alkyl, hydroxy, alkoxy, trihalogenoalkyl, alkylamino, dialkylamino, aryl, arylalkyl, carboxy, alkylcarbonyloxy, acyl, aryloxy or arylalkoxy group; R3 represents a hydrogen atom, an alkyl or arylalkoxy group; and their isomers as well as their addition salts to a pharmaceutically acceptable acid. The inventive compounds arm for use as medicine, in particular as hypnotic. |
1. Compounds of dihydroimidazo[5,1-a]-β-carboline with general formula (I): in which: R1, R2, R3 and R4, which may be identical or different, independently represent a hydrogen atom, a halogen atom, a linear or branched (C1-C6) alkyl group, a hydroxyl group, a linear or branched (C1-C6) alkoxy group, a linear or branched trihalogeno (C1-C6) alkyl group, a linear or branched trihalogeno (C1-C6) alkoxy group, a nitro group, a cyano group, an amino group, a linear or branched (C1-C6) alkylamino group, a linear or branched di (C1-C6) alkylamino group, an aryl group, a linear or branched aryl (C1-C6) alkyl group, a carboxyl group, a linear or branched (C1-C6) alkylcarbonyloxy group, a linear or branched (C1-C6) acyl group, an aryloxy group or a linear or branched aryl (C1-C6) alkoxy group; R5 represents a hydrogen atom, a linear or branched (C1-C6) alkyl group or a linear or branched aryl (C1-C6) alkyl group; and R6 and R7, which may be identical or different, independently represent a hydrogen atom, a halogen atom, a linear or branched (C1-C6) alkyl group, a hydroxyl group, a linear or branched (C1-C6) alkoxy group, a linear or branched trihalogeno (C1-C6) alkyl group, a linear or branched trihalogeno (C1-C6) alkoxy group, a cyano group, an amino group, a linear or branched (C1-C6) alkylamino group, a linear or branched di (C1-C6) alkylamino group, an aryl group, a linear or branched aryl (C1-C6) alkyl group, a carboxyl group, a linear or branched (C1-C6) alkylcarbonyloxy group, a linear or branched (C1-C6) acyl group, an aryloxy group, or a linear or branched aryl (C1-C6) alkoxy group; with the exception, however, of compounds with general formula I in which R1 to R6 represent a hydrogen atom and R7 represents a CH3 group or a phenyl group; their isomers and their addition salts with a pharmaceutically acceptable acid. 2. The compounds as claimed in claim 1, wherein: R1, R3 and R4 represent a hydrogen atom; R6 and R7 independently represent hydrogen, a linear or branched (C1-C6) alkyl group or an aryl group, in particular a phenyl group; and R5 represents a hydrogen atom, or a linear or branched (C1-C6) alkyl group. 3. The compounds as claimed in claim 1, wherein: R2 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6) alkyl group, a hydroxyl group or a linear or branched (C1-C6) alkoxy group. 4. The compounds as claimed in claim 1, which are selected from the following compounds: 3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-3-methyl-1-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 1-ethyl-8-methoxy-3-methyl-5,6-dihydroimidazo[5, 1-a]-β-carboline; 8-methoxy-3-isopropyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-11-methyl-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-hydroxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-hydroxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3-methyl-11-ethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3,8,11-trimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 11-ethyl-3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-bromo-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-bromo-11-ethyl-3-methyl-5,6-dihydroimidazo[5, 1-a]-β-carboline methane sulfonate. 5. A method for preparing compounds with formula (I) as claimed in claim 1, wherein a compound with formula (II): in which R1, R2, R3, R4 and R5 have the meanings given in formula (I), is reacted under peptide coupling synthesis conditions with a compound with formula (III): in which R6 and R7 are as defined in formula (I), to produce a compound with formula (IV): in which R1, R2, R3, R4, R5, R6 and R7 have the meanings defined above, the compound with formula (IV) being treated in the presence of phosphorous oxychloride in a solvent such as toluene to produce compounds with formula (I) in which R1, R2, R3, R4, R5, R6 and R7 are as defined above, the compounds with general formula (I) being transformed if appropriate into their addition salts with a pharmaceutically acceptable acid. 6. Pharmaceutical compositions comprising, as the active principle, at least one compound with formula (I) or one of its addition salts with a pharmaceutically acceptable acid as claimed in claim 1, in combination with one or more nontoxic and pharmaceutically acceptable excipients or inert vehicles. 7. A method for treatment comprising administering an effective amount of a compound as claimed in claim 1 to a patient in need of such treatment. 8. A method for treating a patient with a hypnotic drug comprising administering an effective amount of a compound as claimed in claim 1 to a patient in need of such treatment. |
Inductive voltage generator |
A voltage generator (1) for conversion of non-electrical primary energy (PE) to a voltage signal (USIG, USIG′) by means of induction. The voltage generator (1) has at least one mechanical energy store (2) for holding the primary energy (PE), and which has at least one changeover point (P). At least one induction system (3) is provided which can be coupled to the mechanical energy store (2), with the mechanical energy store (2) carrying out a movement on reaching the at least one changeover point (P) by means of which movement a voltage signal (USIG, USIG′) can be induced in the induction system (3). |
1. A voltage generator (1) for conversion of non-electrical primary energy (PE) to a voltage signal (USIG, USIG′) by means of induction, characterized in that the voltage generator (1) has at least one mechanical energy store (2) for holding the primary energy (PE), and which has at least one changeover point (P), at least one induction system (3) which can be coupled to the mechanical energy store (2), with the mechanical energy store (2) carrying out a movement on reaching the at least one changeover point (P) by means of which movement a voltage signal (USIG, USIG′) can be induced in the induction system (3). 2. The voltage generator (1) as claimed in claim 1, in which the mechanical energy store (2) contains a spring (6) to which a magnet, in particular a permanent magnet (7) is attached. 3. The voltage generator (1) as claimed in claim 2, in which the induction system (3) has an induction coil (8) with a ferromagnetic core (9), in which the magnet can be placed on the ferroelectric core. 4. A switch, in particular for mechanical operation, having a voltage generator (1) as claimed in claim 1. 5. A sensor system, having a voltage generator (1) as claimed in claim 1, and having at least one sensor (5). 6. A method for inductive voltage generation, in which primary energy (PE) is stored in a mechanical energy store (2) until at least one changeover point (P) is reached, the mechanical energy store (2) is moved on reaching the changeover point (P) such that a voltage signal (USIG, USIG′) is generated in an induction system (3) which is coupled to the mechanical energy store (2). 7. The method as claimed in claim 6, in which the primary energy (PE) is stored in the mechanical energy store (2) by expansion or deformation of said mechanical energy store (2). 8. The method as claimed in claim 6, in which, on reaching the changeover point (P), a magnet, in particular a permanent magnet (7), is moved such that an induction voltage (USIG, USIG′) is generated by means of a change in a magnetic flux (Φ) in the area of an induction coil (8). |
Pipes for steam power-plant |
A turbine for use in electricity generation is provided with pipework for gas or vapor entering or leaving the turbine. The pipework includes a rigid section the centerline of which curves in three dimensions. |
1. A turbine for use in electricity generation, including pipework for gas or vapor entering or leaving the turbine, wherein the pipework comprises at least one substantially rigid pipe, having at least one section with a centerline curving in three dimensions. 2. A turbine as claimed in claim 1, wherein said turbine is a steam turbine, and said pipework is positioned between a boiler and the turbine. 3. A turbine as claimed in claim 1, wherein said turbine is a steam turbine, and said pipework is positioned between the exit of the turbine and a condenser. 4. Pipework for use with a turbine as claimed in claim 1. |
Agents for reducing atmospheric oxidising pollutants |
A method of reducing atmospheric oxidising pollutants comprises contacting an atmospheric oxidising pollutant, such as ozone, with a precious metal-free reducing agent, wherein the reducing agent comprises at least one transition clement and/or one or more compounds including at least one transition element wherein the standard electrode potential of the redox reaction including the transition element and an ionic species of the transition element or between the ionic species of the transition element present in the or each compound and a further ionic species of the transition element is less than +1.0 volt. Illustrative reducing agents include a mixture of, optionally reduced, copper (II) oxide and zinc oxide on an alumina support, copper (II) oxide per se, and iron oxide on a mixed alumina/ceria support or a mixture of any two or more thereof. |
1. A method of reducing atmospheric oxidising pollutants, which method comprises contacting an atmospheric oxidising pollutant with a precious metal-free reducing agent, which reducing agent comprising a mixture of copper (II) oxide and zinc oxide carried on a support. 2. A method according to claim 1, wherein the support is a high surface area oxide selected from the group consisting of alumina, ceria, silica, titania, zirconia and mixed oxides of any two or more thereof. 3. A method according to claim 1, wherein the reducing agent is Cu/ZnO//Al2O3. 4. A method according to claim 1, wherein the atmospheric oxidising pollutant is selected from the group consisting of O3, NO2, N2O4 and SO3. 5. An apparatus for reducing atmospheric oxidising pollutants, which apparatus comprises an atmosphere contacting surface; a composition including a precious metal-free reducing agent supported on the surface, wherein the reducing agent is a mixture of copper (II) oxide and zinc oxide carried on a support; and means for causing movement of the surface relative to the atmosphere, whereby atmospheric oxidising pollutants contacting the supported reducing agent are reduced. 6. Apparatus according to claim 5, wherein the support is a high surface area oxide selected from the group consisting of alumina, ceria, silica, titania, zirconia and mixed oxides of any two or more thereof. 7. Apparatus according to claim 5, wherein reducing agent is in the reduced form. 8. Apparatus according to claim 7, wherein the reducing agent is Cu/ZnO//Al2O3. 9. Apparatus according to claim 5, wherein the atmosphere-contacting surface comprises aluminium or an aluminium alloy. 10. Apparatus according to claim 5, wherein the composition further includes a thermosetting polymeric binder, a thermoplastic polymeric binder or a mixture of a thermosetting polymeric binder and a thermoplastic polymeric binder. 11. Apparatus according to claim 10, wherein the binder is a water-soluble binder. 12. Apparatus according to claim 11, wherein the water-soluble binder is a cellulosic binder. 13. Apparatus according to claim 12, wherein the cellulosic binder is selected from the group consisting of an ether cellulosic binder, an ester cellulosic binder and a semi-synthetic cellulosic binder. 14. Apparatus according to claim 11, wherein the water-soluble binder is a vinyl or acrylic binder. 15. Apparatus according to claim 5, wherein the means for causing movement of the surface relative to the atmosphere is a power plant. 16. Apparatus according to claim 15, wherein the power plant is an engine fuelled by gasoline, diesel, liquid petroleum gas, natural gas, methanol, ethanol, methane or a mixture of any two or more thereof. 17. Apparatus according to claim 5, wherein the apparatus comprises a heat exchanger. 18. Apparatus according to claim 17, wherein the heat exchanger is a radiator and/or a condenser. 19. A vehicle including an apparatus according to claim 5. 20. A vehicle according to claim 19, wherein the apparatus comprises a radiator housed in an engine compartment of the vehicle. 21. Apparatus according to claim 5, wherein the composition further includes a latex binder. 22. Apparatus according to claim 12, wherein the cellulosic binder is a hydroxypropyl- or methylcellulose binder. 23. Apparatus according to claim 11, wherein the water soluble binder is polyvinyl alcohol or ammonium polymethacrylate. 24. Apparatus according to claim 15, wherein the power plant is an electric cell, a solar cell or a hydrocarbon or hydrogen-powered fuel cell. |
Method for developing a translator and a corresponding system |
The invention relates to a method for developing a translator and a corresponding system, which translator is intended to translate the code of an input language into that of a target language. In the method, a descriptive language (V) is used to depict on a semantic level two source languages that are independent of each other, that is, the said input language (X) and a target language (Y) and conversion instructions are prepared using this descriptive language. The corresponding system includes the translator and accessory files, which convert the input language first of all into the semantic descriptive language (VX), which is converted to the target language converted to the descriptive language (VY), from which the target language code is finally generated. In this way, the conversion instruction is as small as possible. |
1. A method for developing a translator, which translator is intended to convert input-language code into target-language code, and in which method a descriptive language (v) is used to formally depict two source languages that are independent of each other, that is, the said input language (x) and the target language (y), each source language including formal master terms (Xi, Yj) and in each master term there being one or several occurrences with possible parameters in these, and in which a program framework is formed for the translator, as well as a group of files, which are linked together and translated for the selected operating system, characterized in that the said file are formed in the following stages: the grammars of both source languages (X and Y) are stored in a selected format in files, in such a way that all the occurrences of the master terms of both languages are itemized (stages 1 and 1′), descriptive language versions (VX and VY) of both source languages (X and Y) are formed in a database, in which descriptive language each occurrence of a term (VXi, VYj) is stated semantically, with the aid of the selected descriptive language term (Vk) and the defined terms of the source language, (stages 2 and 2′), the accessory files VX(a-e) and VY(a-e), such as for example, a) glossary and scanner terms b) datatypes c) parsing logic d) generating code e) format clauses required for the translator are formed from the descriptive language versions (VX) and (VY) of the input and target languages (VX) and (VY) and from the stored grammars of the source languages (X and Y) (stages 3 and 3′), the interactive connection of each converted input-language term VXi to the selected target-language term VYn is carried out, comprising in steps of (stages 4 and 5): the connection of the master terms to each other the matching of the occurrences to each other, and the conversion instruction (VX[ ]VY) of each converted input-language term (VXi) is stored in a file. 2. A method according to claim 1, characterized in that: the input language's parsing logic (VX(c)) and the necessary generating code (VY(d)) of the target language and the conversion instructions (VX[ ]VY) and the necessary format clauses (VY(e)) of the target language, are stored in a database or similar for the translator, so that the translator can form, with the aid of the parsing logic (VX(c)) and the code of the input language to be translated, a parsing tree (stage 9) including the code in descriptive language form and convert the code with the aid of the conversion instructions (VX[ ]VY) into descriptive language form (stage 10) and generate and format the descriptive language code into target-language code (stage 11), with the aid of target-language generation and format clauses (VY(d,e)). 3. A method according to claims 1, characterized in that, in the interactive connection, an inference engine is used, which exploits one or more of the following criteria: the linking of previously connected occurrences is proposed, the linking of occurrences/parameters having the same name, on the basis of descriptive language terms is proposed, the linking of parameters on the basis of order is proposed. 4. A method according to any of claims 1, characterized in that the interactive connection is carried out using a graphical interface including at least selection windows for the terms being proposed, for the conversion instructions being formed, as well as at least one pop-up menu window for the selection list, and in which in each selection window each component acts as a link to the corresponding selection list that appears. 5. A method according to any of claims 1, characterized in that the PROLOG language is used as the descriptive language and/or the source language of the translator. 6. A system for translating a computer program from a first source language, i.e. the input language (X), to a second source language, i.e. the target language (Y), which system includes an input file (7) including several lines of code containing the input-language computer program, a translator (X>Y) connected to the input file (7), which translator reads the input file and generates a translated version of the computer program, and in which the translator includes conversion instructions (VX[ ]VY, 41) relating to each input-language term, a translated file (12) connected to the translator (X>Y), for receiving the translated version of the computer program thus generate, an operation library, containing routines to be called by the translator (X>Y), characterized in that the system also includes: a first accessory file (VX(c), 31c) containing the input-language parsing logic for the selected semantic descriptive language (V), a second accessory file (P(Y(d,e), 42), containing the source-language generating and format clauses; in which case the translator (X>Y) is arranged: to convert the computer program's lines of code first of all into descriptive language form, using the parsing logic of the first accessory file VX(c), (stage 9); and then to convert them in descriptive language form, using the said conversion instruction (VX[ ]VY, 41), (stage 10) and to generate and format the descriptive language code into formal target-language code (stage 11), using the target-language generating code (VY(d), 42) and format clauses (VY(e), 42). 7. A system according to claim 6, characterized in that the target language (Y) is a selected-form documentation format for the automatic documentation of the input-language (X) program. 8. A system according to claim 7, characterized in that the selected-form documentation is a program variable list. 9. A system according to claim 7, characterized in that the selected-form documentation of the input-language (X) program is a cross-reference table. 10. A system according to claim 7, characterized in that the target language (Y) is a selected-form documentation of the input-language (X) program is a data-flow diagram. |
User interface systems |
A user interface system for allowing users to initiate events comprises: a plurality of markers each having a marker identity; a plurality of portable readers each having a reader identity and arranged to read said marker identities from adjacent markers, and at least one base station arranged to communicate with said readers in a wireless manner, wherein at least one reader is provided with actuation means which when actuated by a user causes the reader identity of the reader and the marker identity of an adjacent marker to be transmitted by the reader to said base station, so as to cause, for at least one of said markers, said base station to initiate, directly or indirectly, an action which is at least partly determined by the reader identity of said reader. |
1-25. (cancelled) 26. A user interface system for allowing users to initiate events, the system comprising: a plurality of markers each having a marker identity; a plurality of portable readers each having a reader identity and arranged to read said marker identities from adjacent markers, and at least one base station arranged to communicate with said readers in a wireless manner, wherein at least one reader is provided with actuation means which when actuated by a user causes the reader identity of the reader and the marker identity of an adjacent marker to be transmitted by the reader to said base station, so as to cause, for at least one of said markers, said base station to initiate, directly or indirectly, an action which is at least partly determined by the reader identity of said reader. 27. A system as claimed in claim 26, wherein said action is also determined by the identity of said adjacent marker. 28. A system as claimed in claim 26, wherein at least some of said readers are associated with different users, in order to allow said action to be customized for different users. 29. A system as claimed in claim 26, wherein at least one reader provided with said actuation means is also provided with reading means for reading the identity of an adjacent marker, and said reading means is arranged to operate in a low power mode until actuation of said actuation means, and to switch to an operational mode following actuation of said actuation means. 30. A system as claimed in claim 29, wherein said reading means returns to said low power state after reading the identity of an adjacent marker. 31. A system as claimed in claim 30, wherein said reading means returns to said low power state before transmission of said identity of an adjacent marker and the reader identity to a base station. 32. A system as claimed in claim 26, wherein some or all of said portable readers are provided without any screen for displaying information to the user. 33. A system as claimed in claim 26, wherein some or all of said portable readers have a maximum dimension which is not greater than 4, 6 or 8 cm. 34. A system as claimed in claim 26, wherein said action takes place in the vicinity of said adjacent marker. 35. A system as claimed in claim 26, wherein said action is carried out by a device which is not part of, and not physically connected to, said reader. 36. A system as claimed in claim 26, wherein said base station is arranged to transmit to at least one reader a confirmation that the marker and reader identities have been received. 37. A system as claimed in claim 36, wherein said confirmation includes information relating to said action. 38. A system as claimed in claim 36, wherein at least one reader is arranged to provide a perceivable indication of said confirmation to the user. 39. A system as claimed in claim 36, wherein said at least one reader remains connected to said base station, in a networking sense, only until said confirmation has been received, or shortly thereafter. 40. A system as claimed in claim 26, wherein when actuated by a user the transmission from at least some readers also includes a sequence number, which is incremented or decremented for each transmission. 41. A system as claimed in claim 40, wherein said sequence number is also included in a confirmation transmitted from the base station to the reader that the marker and reader identities have been received. 42. A system as claimed in claim 26, wherein transmissions between at least some readers and base stations include a checksum. 43. A system as claimed in claim 26, which further comprises a monitoring system to which the or each base station is connected, and which contains a database of actions corresponding to each pair of reader and marker identities. 44. A system as claimed in claim 43, wherein the monitoring system is a CORBA object running on a computer connected to the internet. 45. A system as claimed in claim 26, wherein actuation of a reader adjacent to two markers within a predetermined period of time causes one or more actions which result in an association being formed between two hardware devices associated with said two markers respectively. 46. A system as claimed claim 26, wherein actuation of a first reader adjacent a given marker prevents the successful actuation of a further reader adjacent the same marker for a predetermined period of time, or until a particular event has occurred. 47. A system as claimed in claim 46, wherein said particular event is a subsequent actuation of said first reader adjacent said given marker. 48. A system as claimed in claim 26, wherein the or each base station records the time of each reader transmission. 49. A system as claimed in claim 26, wherein transmissions between at least some readers and base stations are encrypted. 50. A system as claimed in claim 26, wherein at least one reader is provided with a miniaturized antenna in the form of a wound inductor, so that the range of the reader is about 1 cm or less. |
Microprocessors with improved power efficiency |
A microprocessor is arranged to process instructions at least some of which contain at least one immediate value which forms an operand of the function, wherein said immediate value is represented in a format which achieves a greater power efficiency than two's complement when said instructions are processed. |
1-13. (cancelled) 14. A microprocessor arranged to process instructions at least some of which contain at least one immediate value which forms an operand of the function, said immediate value being represented in a format which achieves a greater power efficiency than two's complement when said instructions are processed. 15. A microprocessor as claimed in claim 14, wherein said format is standard sign magnitude format. 16. A microprocessor as claimed in claim 14, wherein said format is a Gray code. 17. A microprocessor as claimed in claim 14, wherein said format is a variant sign magnitude format in which: (a) non-negative values (including zero) are represented by a sign bit of 0 and a binary representation of the value (b) negative values are represented by a sign bit of 1 and a binary representation of one less than the magnitude of the value. 18. A microprocessor as claimed in claim 17, which further comprises at least one arithmetic and logic unit (ALU) having an input arranged to receive either one of said immediate values or an alternative value from elsewhere. 19. A microprocessor as claimed in claim 18, which further comprises a multiplexor having a first input adapted to receive said one of said immediate values and a second input adapted to receive said alternative value. 20. A microprocessor as claimed in claim 19, wherein said ALU is arranged to perform at least addition and subtraction, and wherein a conversion circuit, for converting values from said variant sign-magnitude format to two's complement, is merged with said ALU in such a way that the merged circuit operates with an overhead of one AND gate and one exclusive-or gate. 21. A microprocessor as claimed in claim 20, wherein said multiplexor is connected to said ALU by a circuit substantially the same as that shown in FIG. 10. 22. A microprocessor as claimed in claim 14 wherein some or all bits of said immediate values are inverted or permuted. 23. A processing system comprising a microprocessor, a memory, and a data bus connecting, and arranged to pass data between, the microprocessor and the memory, said data being represented in a variant sign-magnitude format in which: (a) non-negative values (including zero) are represented by a sign bit of 0 and a binary representation of the value (b) negative values are represented by a sign bit of 1 and a binary representation of one less than the magnitude of the value. 24. A processing system as claimed in claim 23, wherein some or all bits in said data are inverted or permuted. 25. A processing system as claimed in claim 23, wherein said microprocessor processes said data in two's complement format, and wherein a conversion circuit is provided for converting said data from said variant sign-magnitude format to two's complement, and vice-versa. 26. A processing system as claimed in claim 23, wherein said microprocessor is arranged to process instructions at least some of which contain at least one immediate value which forms an operand of the function, said immediate value being represented in a format which achieves a greater power efficiency than two's complement when said instructions are processed. |
Urine collection device |
A urine collection device (50) comprises a collection means (55) to collect urine voided, advantageously midstream, by the user. The device (50) has an outlet means (51) integral with the collection means (55) to direct urine out of the collection means (55). Both the collection means (55) and the outlet means (51) are operable moveable from a flat storage configuration and an expanded in-use configuration. The device (50) also includes one or more resilient means (53) which are so biased to cause the device (50) to move from the storage to the expanded configuration. The resilient means (53) can include an elastic band or resilient strips (14) located on either or both of the collection (55) and outlet means (51). Tabs or gloves can be included as part of the device (50) in order to reduce the risk of the user's hands becoming contaminated by urine. |
1. A urine collection device comprising: a collection means to collect urine voided by a user; an outlet means, integral with the collection means, to direct the urine out of the collection means; the collection means and outlet means being operably moveable between a storage configuration and an expanded in-use configuration, the device including one or more resilient means, so biased to cause the device to move from the storage to the expanded configuration. 2. A urine collection device according to claim 1, wherein the device is symmetric at least along a central longitudinal plane. 3. A device according to claim 1, wherein the device is flat when in its storage configuration. 4. A urine collection device according to claim 1, wherein the or each resilient means comprises one or more resilient strips located on one or both of the collection means and the outlet means. 5. A urine collection device according to claim 1, wherein the resilient means includes an elastic band amounted on the collection means. 6. A urine collection device according to claims 1, wherein the device is formed substantially wholly of a self-supporting resilient material 7. A urine collection device according to claim 6, wherein the self-supporting resilient material is a semi-rigid plastics material. 8. A urine collection device according to claim 6, wherein the resilient material is biodegradable. 9. A urine collection device according to claims 1, wherein the collection means is funnel shaped to collect and channel urine to the outlet means. 10. A urine collection device according to claims 1, which includes one or more tabs for positioning the device in-use so as to reduce the risk of a user or individual handling the device coming into direct contact with the urine. 11. A urine collection device according to claims 1, further comprising a glove portion to cover the user's hand during use. 12. A urine collection device according to claims 1, wherein the device includes diagnostic strips on the surfaces of the device which, in use, come into contact with urine. 13. A urine collection device according to claims 1, wherein the outlet means includes an adhesive strip to hold the device in contact with a sample tube. 14. A urine collection device according to claim 1, wherein the outlet means is a spout. 15. A urine collection device according to claim 14, wherein the spout has, in-use, a square or rectangular cross-section. 16. A urine collection device according to claims 1, further comprising a sample tube, removably attached to the outlet means. 17. A urine collection device according to claims 1, further comprising an overflow means to direct excess urine out of the device and preventing the overflow of urine from the device. 18. A urine collection device according to claims 1, wherein the device is supplied in a flat folded configuration and held in such configuration by packaging material. 19. (Cancelled) 20. A diagnostic device comprising: a collection means to collect urine voided by a user; one or more diagnostic strips on the surface of the device which, in-use, come into contact with urine; the collection means being operably moveable between a storage configuration and an expanded in-use configuration, the device including one or more resilient means, so biased to cause the device to move from the storage to the expanded configuration. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Urine sampling is an important diagnostic method for detecting a wide range of conditions and illnesses. Analysis of the presence and concentration of chemicals in a urine specimen can, for example, show if a person is pregnant, diabetic, has a kidney dysfunction, has a urinary tract infection etc. Normally, the specimen is produced by the patient directly into a suitable sterile tube which can then be taken away for analysis. Tubes which are normally used however, have only a narrow neck opening through which to pass the specimen into the tube and to deliver the specimen accurately, without mess, can present difficulties. The difficulties are particularly acute where the patient is female, due to the problem of correctly locating the tube to receive the sample. A number of devices have been devised to assist people in delivering a urine specimen. Patent publication No's EP 009980 and GB 1497777 disclose two such devices, but these are relatively complex as they are particularly concerned with a collection of an aseptic sample. The present invention seeks to alleviate the problems of the above disclosed devices, and to provide an easy to use, disposable device to direct urine voided by a female into a sample tube. |
<SOH> SUMMARY OF THE INVENTION <EOH>According to the invention there is provided a urine collection device comprising: a collection means to collect urine voided by the user; an outlet, integral with the collection means, to direct the urine out of the collection means; the collection means and outlet being operably moveable between a storage configuration and an expanded in-use configuration, the device including one or more resilient means, so biased to cause the device to move from the storage to the expanded configuration. The device is thus removed from storage, the resilient means expanding the device directly into a useable configuration with the minimum of inconvenience to the user. The device can be used to collect voided urine, advantageously mid-stream, and direct the urine into a sample tube. The sample tube typically has an opening, of industry standard size, through which the urine must pass. The device is preferably symmetric in at least the longitudinal plane, to enable the device to be used correctly in more than one orientation and so reduce the possibilities of incorrect use. Preferably, the device is flat when in its storage configuration. This allows a large number of devices to be stored in a relatively small volume. The resilient means preferably comprises one or more strips, formed from a resilient material, located on the collection means and/or the outlet means. The strips provide the necessary force to move the collection means from its storage configuration to its in-use configuration with minimum of space uptake and weight. Optionally, the resilient means is an elastic band mounted on the collection means, the elastic band being under tension when the device is in the flat configuration, the tension being releasable to cause the device to open to its in-use configuration. Alternatively, the device can be formed from a material having resilient properties, such as a semi-rigid plastics material or a biodegradable paper. The collection means is conveniently a funnel to collect and channel urine to the outlet means. The device preferably includes one or more tabs by which the device for positioning the device so as to reduce the chance of the user accidentally getting urine on their hands. The device can also include a glove portion to cover the user's hand during use, again preventing contamination. Diagnostic strips can also be included on the surfaces of the device which, in use, come into contact with the urine. The strips can provide information on, for example, the presence of sugar or protein in the urine and so aid diagnosis. The outlet optionally includes a retention means to hold the device in contact with a sample tube. The outlet means overflow outlet advantageously has a square cross-section to facilitate storage of the device in a flat configuration. Preferably, the outlet a spout which projects from the body of the collection means. The retention means hinders a sample tube from falling away from the device during use. Advantageously, the retention means comprises a washer to engage a sample tube and provide a seal to prevent running onto the collection means. Optionally, an adhesive is included to retain a sample tube in position. The device conveniently includes a further outlet means to direct excess urine out of the device, into for example a toilet, and preventing the overflow of urine from the device onto the user or the floor. The device is conveniently supplied in a carrier, to minimise damage to and contamination of the device before use and maintain the device in an aseptic condition. A removable securing tab is preferably included to secure the device in a flat configuration until the device is required. The device optionally includes a sample tube, removably attached to the outlet means. |
Dental restorative materials |
The present invention relates to a composition for dental restoration including a dental restorative material and an effective amount of a casein phosphopeptide(CPP)-amorphous calcium phosphate (ACP) complex or casein phosphopeptide(CPP)-amorphous calcium fluoride phosphate (ACFP) complex. |
1. A composition for dental restoration including a dental restorative material and an effective amount of a casein phosphopeptide(CPP)-amorphous calcium phosphate (ACP) complex or casein phosphopeptide(CPP)-amorphous calcium fluoride phosphate (ACFP) complex. 2. A composition according to claim 1, wherein the CPP includes the amino acid sequence -Ser(P)-Ser(P)-Ser(P)-. 3. A composition according to either claim 1 or 2, wherein the ACP is formed under alkaline conditions. 4. A composition according to any one of claims 1 to 3, wherein the ACP is of the formula Ca3(PO4)2.xH2O, where x≧1. 5. A composition according to claim 1, wherein the ACFP is formed under alkaline conditions. 6. A composition according to either claim 1 or 5, wherein the ACFP is of the formula Ca2F(PO4).xH2O, where x≧1. 7. A composition according to claim 6, wherein the ACFP also contains ACP, wherein ACP and ACFP are in the ratio of n:1, where n is an integer ≧1. 8. A composition according to any one of claims 1 to 7, wherein the dental restorative material is dental cement. 9. A composition according to claim 8, wherein the dental cement is a glass ionomer cement. 10. A composition according to any one of claims 1 to 9, wherein the effective amount of the CPP-ACP complex or CPP-ACFP complex is 0.01 to 80% by weight. 11. A composition according to claim 10 wherein the effective amount is 0.5 to 10% by weight. 12. A composition according to claim 11 wherein the effective amount is 1 to 5% by weight 13. A composition according to any one of claims 1 to 12, having a pH from 2 to 10. 14. A composition according to claim 13, wherein the pH is from 5 and 9. 15. A composition according to claim 14, wherein the pH is from 7 and 9. 16. A method of manufacture of a composition according to any one of claims 1 to 15, wherein the method includes the addition of ACP or ACFP, and CPP to the dental restorative material. 17. A method of manufacture of a composition according to any one of claims 1 to 15, wherein the method includes the addition of CPP-ACP complex or CPP-ACFP complex to the dental restorative material. 18. Use of a composition according to any one of claims 1 to 15, or manufactured by the method according to either claim 16 or 17, for the preparation of a medicament intended for the treatment and/or prevention of dental caries in animals. 19. Use according to claim 18 wherein the animal is human. 20. A method of treatment and/or prevention of dental caries in animals including providing the composition according to any one of claims 1 to 15, or manufactured by the method according to either claim 16 or 17, and applying to teeth in an animal in need of treatment and/or prevention. 21. A method according to claim 20, wherein the animal is human. 22. A kit of parts including (a) dental restorative material and (b) CPP-ACP complex and/or CPP-ACFP complex, together with instructions for their use for the preparation of a composition according to any one of claims 1 to 16. 23. A kit of parts including (a) dental restorative material, (b) casein phosphopeptides (c) calcium ions and (d) phosphate ions, together with instructions for their use for the preparation of a composition according to any one of claims 1 to 15. 24. A kit of parts according to claim 23, further including flouride ions. 25. A composition according to claim 1, substantially as described herein with reference to either example. 26. A method of manufacture according to claim 16, substantially as described herein with reference to either example. 27. Use according to claim 18, substantially as described herein with reference to either example. 28. A method of treatment and/or prevention of dental caries according to claim 20, substantially as described herein with reference to either example. 29. A kit of parts according to any one of claims 22 to 24, substantially as described herein with reference to either example. |
<SOH> BACKGROUND <EOH>Dental caries is initlated by the demineralisation of hard tissue of the teeth by organic acids produced from fermentation of dietary sugar by dental plaque odontopathogenic bacteria. Dental caries is still a major public health problem and restored tooth surfaces can be susceptible to further dental caries around the margins of the restoration. Casein phosphopeptide-amorphous calcium phosphate complexes (CPP-ACP) and CPP-stabillsed amorphous calcium fluoride phosphate complexes (CPP-ACFP) in solution have been shown to prevent enamel deminerallsation and promote remineralisation of enamel subsurface lesions in animal and human in situ caries models [Reynolds 1997 patent application. PCT/AU98/001 60]. The active CPP have been specified in the U.S. Pat. No. 5,015,628 and include peptides Bos α e1 -casein X-5P (f59-79) [1], Bos β-casein X-4P (f1-25) [2], Bos α e2 -casein X-4P (f46-70) [3] and Bos α e2 casein X-4P (f1-21) [4] as follows: [1] Gln 59 -Met-Glu-Ala-Glu-Ser(P)-Ile-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ile-Val-Pro-Asn-Ser(P)-Val-Glu-Gin-Lys 79 , α e1 (59-79) [2] Arg 1 -Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile-Val-Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ser-Ile-Thr-Arg 25 , β(1-25) [3] Asn 46 -Ala-Asn-Glu-Glu-Glu-Tyr-Ser-Ile-Gly-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ser(P)-Ala-Glu-Val-Ala-Thr-Glu-Glu-Val-Lys 70 , α e2 (46-70) [4] Lys 1 -Asn-Thr-Met-Glu-His-Val-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ser-Ile-Ser(P)-Gin-Glu-Thr-Tyr-Lys 21 , α e2 (1-21) These peptides stabilise novel forms of very soluble amorphous calcium phosphate and amorphous calcium fluoride phosphate [Reynolds 1997 patent application, PCT/AU98/00160]. Glass ionomer cements (GICs) are water-based, tooth coloured and chemically adhesive materials used in dentistry as bases and restorations. Microleakage around restorations remains a significant problem, which can lead to caries of the underlying tooth tissues (Bergenholtz et al., 1982; Davis et al., 1993; Pachuta and Melers, 1995). However, GICs are ion-releasing materials and the incorporation and slow release of fluoride ions from the cement provides a significant anticariogenic property (Forss, 1993; Williams et al., 1999) Although H would be expected that inclusion of CPP-ACP into a GIC would result in the incorporation of the calcium ions into the GIC matrix making them unavailable, surprisingly, we have discovered that incorporation of CPP-ACP into a standard, commercially-available GIC resulted in a GIC with unexpected superior properties in terms of microtensile bond strength. Comprehensive strength and ion-release. In fact, surprisingly the GIC containing CPP-ACP was able to significantly remineralize the underfying dentine whereas the standard GIC could not. These results form the basis of this invention which is novel dental restorative materials containing CPP-ACP or CPP-ACFP with superior physiochemical and anticariogenic properties. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a composition for dental restoration including a dental restorative material and an effective amount of a casein phosphopeptide(CPP)-amorphous calcium phosphate (ACP) complex or casein phosphopeptide(CPP)-amorphous calcium fluoride phosphate (ACFP) complex. According to one aspect of the invention, there is provided a composition for dental restoration, including a dental restorative material to which has been added amorphous calcium phosphate (ACP) or amorphous calcium fluoride phosphate (ACFP) stabilized by phosphopeptides containing the amino acid sequence -Ser(P)-Ser(P)-Ser(P)-. Preferably, the ACP and ACFP are formed under alkaline conditions. The amorphous calcium phosphate is preferably of the approximate formula Ca 3 (PO 4 ) 2 .xH 2 O where x≧1, ie there are one or more H 2 O per Ca 3 (PO 4 ) 2 . The calcium phosphate derivative may be a calcium fluoride phosphate of approximate formula Ca 2 F(PO 4 ).xH 2 O where x≧1 providing amorphous calcium fluoride phosphate (ACFP). More preferably the calcium phosphate derivative may be a mixture of ACP and ACFP in the ratio n:1, where n is an integer≧1, eg 1:1 giving Ca 5 (PO 4 ) 3 or 2.1 giving Ca 8 F(PO 4 ) 5 . It is expected that the exact ratios described above, and the proportions of components in the amorphous calcium phosphate, will be different in the final composition due, for example, to interactions between components. The phosphopeptide may be from any source; it may be obtained by tryptic digestion of casein or other phospho-acid rich proteins or by chemical or recombinant synthesis, provided that it comprises the core sequence -Ser(P)-Ser(P)-Ser(P)-. The sequence flanking this core sequence may be any sequence. However, those flanking sequences in α e1 (59-79) [1], β(1-25) [2], α e2 (48-70) [3] and α e2 (1-21) [4] are preferred. The flanking sequences may optionally be modified by deletion, addition or conservative substitution of one or more residues. The amino acid composition and sequence of the flanking region are not critical as long as the conformation of the peptide is maintained and that all phosphoryl and caboxyl groups interacting with calcium ions are maintained as the preferred flanking regions appear to contribute to the structural action of the motif. The base of the dental restorative material can be a glass ionomer cement, a composite material or any other restorative material which is compatible. It is preferred that the amount of CPP-ACP complex or CPP-ACFP complex included in the dental restorative material is 0.01-80% by weight, preferably 0.5-10% and more preferably 1-5% by weight. The dental restorative material of this invention which contains the above mentioned agents may be prepared and used in various forms applicable to dental practice. The dental restorative material according to this invention may further include other ions, eg. antibacterial ions Zn 2+ , Ag + , etc or other additional ingredients depending on the type and form of a particular dental restorative material. It is preferable that the pH of the CPP-ACP complex or CPP-ACFP complex be between 2-10, more preferably 5-9 and even more preferably 7-9. It is preferable that the pH of the dental restorative material containing the CPP-ACP complex or ACFP complex be between 2-10, more preferably 5-9 and even more preferably 7-9. The invention is also directed to a method of manufacture of a restorative composition. Preferably, the method includes the addition of ACP and/or ACFP, stabillsed by phosphopeptides as stated above, to a base dental restorative material. The invention also relates to use of a restorative composition as stated above for the treatment and/or prevention of dental caries. The invention also provides a method of treatment and/or prevention of dental caries in animals including providing the composition according to the invention or manufactured according to the invention and applying to teeth in an animal in need of treatment and/or prevention. The invention also relates to a kit of parts including (a) dental restorative material and (b) CPP-ACP complex or CPP-ACFP complex together with instructions for their use for the preparation of a composition for dental restoration. The invention also relates to a kit of parts including (a) dental restorative material (b) casein phosphopeptide (c) calcium ions and (d) phosphate ions, and optionally flouride ions, together with instructions for their use for the preparation of a composition for dental restoration. It will be clearly understood that, although this specification refers specifically to applications in humans, the invention is also useful for veterinary purposes. Thus in all aspects the invention is useful for domestic animals such as cattle, sheep, horses and poultry, for companion animals such as cats and dogs; and for zoo animals. |
Electromagnetic brake cooling structure of phase variable device in car engine |
An electromagnetic-brake cooling structure of a phase-variable device having an electromagnetic brake means (40) and varying the phase of a camshaft, wherein engine oil in an oil sump (74) on the radial inner side of a clutch case (60) led to the relative sliding surfaces of a friction material (66) and a rotary drum (44) through a notch (61) provided in the clutch case (60) at the front edge part of the inner peripheral wall of the clutch case (60), a notch (61b) for leading oil to the front edge part of the clutch case outer peripheral wall (60b), the oil on the relative sliding surfaces of the friction material (66) and the rotary drum (44) is discharged positively to the outside, and the circulation of the cooling oil is activated to increase the cooling effect of the sliding surface of the friction material (66). |
1. An electromagnetic-brake cooling structure of a phase varying apparatus for use with an automobile engine, said phase varying apparatus including: an annular sprocket to which the driving power of the crank shaft of said engine is transmitted; a camshaft coaxial with, and slidable relative to, said annular sprocket, said camshaft constituting a valve mechanism; a rotational drum rotatably supported by said camshaft; and an electromagnetic brake means mounted at an axial position facing said rotational drum for applying a retarding force onto said rotational drum such that said retarding force causes a delay in rotational motion of said rotational drum to vary the phase of said camshaft relative to said sprocket, said electromagnetic brake means including: an annular clutch case pinned not to rotate about its axis and having a U-shaped cross section with its open end facing a disc-shaped surface of said rotational drum; an electromagnetic coil housed in said clutch case; a plate for holding a friction member (friction member holding plate) fixed inside the opening of said clutch case; and a generally flat friction member bonded to said friction member holding plate and having a surface slightly projecting from the leading edges of the inner and outer circular walls of said clutch case; an oil sump formed in a radially small section of said clutch case, said oil sump communicating with an oil passage of said camshaft and with the radially inner porions of the sliding sections of said clutch case and rotational drum; oil lead-in notches formed in the leading edge of the inner circular wall of said clutch case to lead engine oil from said oil sump to the sliding surfaces of said friction member and rotational drum via said oil lead-in notches, wherein oil lead-out notches are formed in the leading edge of the outer wall of said clutch case to outwardly lead said engine oil from said sliding surfaces of said friction member and rotational drum to the outside of said of the clutch case. 2. The electromagnetic-brake cooling structure according to claim 1, wherein oil lead-out holes are provided in the disc surface of said rotational drum at positions facing said friction member so that the oil staying in said sliding sections of the friction member and the rotational drum is led out through said oil lead-out holes. 3. The electromagnetic-brake cooling structure according to claim 2, wherein said oil lead-out holes are formed near the outer circumferential wall of the clutch case. 4. The electromagnetic-brake cooling structure according to claim 2, wherein said clutch case is provided with a multiplicity of oil lead-in notches and oil lead-out notches, and said rotational drum is provided with a multiplicity of oil lead-out holes, said notches and holes formed at multiple circumferential positions. 5. The electromagnetic-brake cooling structure according to claim 1, wherein said friction member has an annular face adapted to abut against the base plate of said rotational drum, and is provided on said face with oil grooves that communicate with said oil lead-out notches. 6. The electromagnetic-brake cooling structure according to claim 1, further comprising annular gaps formed between the inner and outer circular walls of said clutch case and the inner and outer peripheries of said friction member. 7. The electromagnetic-brake cooling structure according to claim 1, wherein said friction member is made of a non-woven fabric of carbon fiber and/or aramid fiber impregnated with a heat-hardening resin, in the form of a porous member containing at least 80 volume percent of all the pores having pore diameters in the range of 5-100 μm. |
<SOH> BACKGROUND OF THE INVENTION <EOH>This type of phase varying apparatus is disclosed in, for example, Japanese Patent Early Publication H4-272411. This apparatus has a movable plate 3 mounted between a drive member (sprocket) 1 , to which driving power of a crank shaft of the engine is transmitted, and a camshaft 2 of a valve mechanism, the apparatus configured to vary the relative phase of the drive member 1 and camshaft 2 by axially moving the movable plate 3 , as shown in FIG. 11 . That is, by means an electromagnetic brake means 4 that is pinned not to rotate, a retarding or braking force is acted on a rotational drum 5 rotatably supported by the camshaft 2 to thereby delaying the rotational drum 5 relative to the drive member 1 , which in turn causes an axial movement of the movable plate 3 to rotate the camshaft 2 relative to the drive member 1 , resulting in a change in phase between the drive member 1 and camshaft 2 . The apparatus is installed inside the engine room of the engine so that it operas in engine oil atmosphere. The electromagnetic brake means 4 is constituted an annular housing 4 b having a U-shaped cross section for housing an electromagnetic coil 4 a , a root member 4 c for closing an opening of the housing 4 b , and a friction member 4 d bonded to the root member 4 c . This apparatus has a drawback in that when the sliding surfaces of the friction member 4 d of the housing 4 b and the rotational drum 5 are heated to a high temperature due to friction between them, the surface of the friction member 4 d which is generally made of a porous material is clogged with deposits of antioxidant, friction modifier, reactants of additives such as detergent dispersant, and insoluble compositions dispersed in the engine oil, thereby losing frictional torque generated between the friction member 4 d and the rotational drum 5 . Hence, in order to cool and suppress heating of the sliding surfaces of the friction member 4 d of the housing 4 b and the rotational drum 5 , the apparatus is provided with an oil passage 6 a , a cross hole 6 b , a cavity 6 c , and a cross hole 6 d in the camshaft 2 , an annular cavity 6 e formed between the camshaft 2 and the housing 4 b , and a notch 6 f formed on the leading edge of the peripheral wall of the housing 4 b to supply the engine oil to the sliding surfaces of the friction member 4 d and the rotational drum 5 . Thus, the conventional electromagnetic-brake cooling structure is passably satisfactory in cooling the sliding surface of the friction member. However, in order to suppress the heating of the sliding surface of the friction member at even higher temperatures, a further innovated efficient cooling measure is necessary. Thus, the inventor of the present invention has fully examined conventional cooling structures in which the engine oil supplied between the friction member 4 d and the rotational drum 5 is merely scattered outwardly by a centrifugal force, and has reached a concept of new cooling structure, in which oil lead-out grooves (or notches) are formed in the leading edge of the outer peripheral wall of the housing 4 b to outwardly drain the oil staying between the sliding surfaces of the friction member 4 d and the rotational drum 5 , so that the amount of oil lead to the sliding sections of the friction member 4 d and the rotational drum 5 is increased and circulation of the engine oil is enhanced to thereby cool the sliding surfaces. In fact, it is found in numerous experiments that this inventive structure is effective. In view of the prior art problems and the inventor's finding as mentioned above, it is an object of the invention to provide a cooling structure effective in suppressing heating of the sliding surfaces of the friction member and the rotational drum of an electromagnetic-brake of a phase-varying apparatus for use with an automobile engine, the cooling structure adapted to enhance the circulation of engine oil to cool the sliding surfaces. |
<SOH> SUMMARY OR THE INVENTION <EOH>To attain the objects described above, there is provided a structure for cooling an electromagnetic brake (referred to as electromagnetic-brake cooling structure) of a phase varying apparatus for use with an automobile engine, as defined in claim 1 , the phase varying apparatus including: an annular sprocket to which the driving power of the crank shaft of the engine is transmitted; a camshaft constituting a valve mechanism, the camshaft coaxial with, and slidable relative to, the annular sprocket; a rotational drum rotatably supported by the camshaft; and an electromagnetic brake means, mounted at an axial position to face the rotational drum, for applying a retarding force onto the rotational drum such that the retarding force causes a delay in rotational motion of the rotational drum to vary the phase of the camshaft relative to the sprocket, the electromagnetic brake means including: an annular clutch case pinned not to rotate about its axis and having a U-shaped cross section with its open end facing a disc-shaped surface of the rotational drum; an electromagnetic coil housed in the clutch case; a plate for holding a friction member (hereinafter referred to as friction member holding plate) fixed inside the opening of the clutch case; and a generally flat friction member bonded to the friction member holding plate and having a surface slightly projecting from the leading edges of the inner and outer circular walls of the clutch case, wherein an oil sump is formed inside the clutch case, the oil sump communicating with the oil passage of the camshaft and with the inner peripheries of the sliding sections of the clutch case and rotational drum; oil lead-in notches are formed in the leading edge of the inner peripheral wall of the clutch case to introduce thereinto engine oil; the engine oil is lead from the oil sump to the sliding surfaces of the friction member and rotational drum via the oil lead-in notches, and wherein oil lead-out notches are formed in the leading edge of the outer circular wall of the clutch case to outwardly lead the engine oil from the sliding surfaces of the friction member and rotational drum to the outside of the of the clutch case. A structure for delaying the rotational motion of the rotational drum behind the sprocket by a retarding force of an electromagnetic brake means for causing an intermediate member to shift in the axial direction so that the phase of the camshaft is varied relative to the sprocket, can be attained by an inventive arrangement in which an intermediate member 30 threadedly engaged with a rotational drum 44 and undergoes internal and external helical spline engagement with both a sprocket (external cylinder 10 ) and a camshaft (inner cylinder 20 ). (FUNCTION) In this arrangement, the sprocket to which the driving power of the engine is transmitted by a crank shaft is adapted to rotate integrally with, and in synchronism with, a camshaft that functions as a valve mechanism, in such a way that when a retarding force is acted on the rotational drum by the electromagnetic brake means, the drum is delayed in rotation behind the sprocket, resulting in a change in phase of the camshaft with respect to the sprocket. Engine oil is introduced to the sliding sections of the friction member and the rotational drum via an oil passage formed in the camshaft, an oil sump provided formed in a radially small section of the clutch case, and the oil lead-in notches formed in the leading edge of the inner peripheral wall of the clutch case in order to cool the sliding surfaces of the friction member and the rotational drum. It should be noted that the engine oil is supplied to and drained from the sliding surfaces of the friction member and the rotational drum at a higher flow rate via the oil lead-out notches formed in the leading edge of the outer circular wall of the clutch case to enhance the drainage of the oil from the sliding sections to the outside of the clutch case, which facilitates cooling of the sliding surfaces. That is to say, the amount of oil introduced into the sliding sections is increased by the amount led out of the sliding sections, resulting in enhanced circulation of the engine oil through the sliding sections and corresponding cooling effect on the friction member and the rotational drum. In another aspect of the invention as defined in claim 2 , there is provided an electromagnetic-brake cooling structure of a phase varying apparatus for use in an automobile engine, wherein oil lead-out holes are provided in the disc surface of the rotational drum at positions facing the friction member so that the oil staying in the sliding sections of the friction member and the rotational drum is led out through the oil lead-out holes. (FUNCTION) In this arrangement, the oil staying in the sliding sections is also led out therefrom to the outside through the oil lead-out hole, thereby increasing the amount of oil that circulates through the sliding sections. In an electromagnetic-brake cooling structure of a phase varying apparatus for use in an automobile engine as defined in claim 3 , the oil lead-out holes are formed near the outer circular wall of the clutch case. (FUNCTION) In this arrangement, the amount of oil led out from the sliding sections of the friction member and the rotational drum through the oil lead-out holes is further increased, thereby further increasing the amount of oil led to the sliding sections and enhancing the circulation of the oil. The closer is the old lead-out notch to the oil lead-in notches, the less flow resistance (resulting in energy loss) the flow of oil suffers. Hence, a larger flow rate of oil passing through the oil lead-out holes is obtained. This ensures provision of higher flow rate and circulation rate of fresh engine oil through the sliding surfaces of the friction member. In an electromagnetic-brake cooling structure of a phase varying apparatus for use in an automobile engine as defined in claim 4 , the clutch case is provided with a multiplicity of oil lead-in notches and oil lead-out notches, and the rotational drum is provided with a multiplicity of oil lead-out holes, the notches and holes formed in the multiple circumferential positions. (FUNCTION) The amount of engine oil led into and out of the sliding sections of the friction member and the rotational drum is multiply increased by the increment in number of the oil lead-in notches, oil lead-out notches, and the oil lead-out holes, which in turn enhances the circulation of the engine oil through the sliding sections of the friction member and the rotational drum, and hence the cooling of the sliding surfaces of the friction member and the rotational drum. In an electromagnetic-brake cooling structure of a phase varying apparatus for use in an automobile engine as defined in claim 5 , the friction member has an annular face adapted to abut against the base plate of the rotatable drum, and is provided on the face with oil grooves that communicate with the oil lead-out notches. (FUNCTION) The engine oil introduced to the sliding sections of the friction member and the rotational drum smoothly flows into the oil grooves and into the oil lead-out notches, resulting in an increased flow rate, thereby uniformly cooling the entire surface of the friction member and enhancing the circulation of the oil. In addition, since the oil can easily circulate via the oil grooves on the surface of the friction member, transition from fluid lubrication to boundary lubrication can be easily attained, which enhances frictional torque acting on the surfaces of the friction member and the rotational drum, thereby increasing the retarding force acting on the rotational drum when the electromagnetic brake means is energized. In an electromagnetic-brake cooling structure for use in an automobile engine as defined in claim 6 , there are provided annular gaps formed between the inner and outer circular walls of the clutch case and the inner and outer peripheries of the friction member. (FUNCTION) The engine oil introduced through the oil lead-in notches passed through the gaps (or oil passages) between the inner peripheral wall and the friction member, and spreads over the entire circumferential area of the friction member. The oil staying in the sliding sections of the friction member and the rotational drum smoothly flows through the gaps (oil passage) between the outer circular wall of the clutch case and the friction member and led out from the oil lead-out notches. In an electromagnetic-brake cooling structure for use in an automobile engine as defined in claim 7 , the friction member is made of a non-woven fabric of carbon fiber and/or aramid fiber impregnated with a heat-hardening resin, in the form of a porous member containing at least 80 volume percent of all the pores having pore diameters in the range of 5-100 μm. (FUNCTION) Since the porous member thus formed has more than 80 volume percent of all pores being in the range from 5 to 100 μm in pore size, it is less likely to be clogged, thereby creating a large frictional (retarding) torque acting on the disc surface of the rotational drum. In addition, the friction member has good abrasion resistance and hence excellent durability. |
Fractionation of protein containing mixtures |
Thus, a primary aspect of the present invention relates to a method for the fractionation of a protein-containing mixture wherein the protein-containing mixture is selected from the group consisting of milk, milk derived products, milk derived raw materials, vegetable derived products, vegetable derived extracts, fruit derived products, fruit derived extracts, fish derived products, and fish derived extracts, said method comprising the steps of: a) optionally adjusting the pH of the mixture; b) applying said mixture to an adsorption column comprising an adsorbent, said adsorbent comprises a particle with at least one high density non-porous core, surrounded by a porous material, the adsorbent having a particle density of at least 1.5 g/ml and a mean particle size of at most 150 μm; c) optionally washing the column; d) eluting at least one protein from the adsorbent. |
1. A method for the fractionation of a protein-containing mixture wherein the protein-containing mixture is selected from the group consisting of milk, milk derived products, milk derived raw materials, vegetable derived products, vegetable derived extracts, fruit derived products, fruit derived extracts, fish derived products, and fish derived extracts, said method comprising the steps of: a) optionally adjusting the pH of the mixture; b) applying said mixture to an adsorption column comprising an adsorbent, said adsorbent comprise particles with at least one high density non-porous core, surrounded by a porous material, the adsorbent having a particle density of at least 1.5 g/ml and a mean particle size of at most 150 μm; c) optionally washing the column; d) eluting at least one protein from the adsorbent. 2. A method according to claim 1, wherein the applying of said mixture is performed at a flow-rate of at least 3 cm/min. 3. A method according to claim 2, wherein the applying of said mixture is performed at a flow-rate of about 5-50 cm/min. 4. A method according to claim 1, wherein the high density non-porous core has a density of at least 4 g/ml. 5. A method according to claim 1, wherein the high density non-porous core has a density in the range of about 4-25 g/ml. 6. A method according to claim 1, wherein the adsorbent has a particle density of at least 1.8 g/ml. 7. A method according to claim 1, wherein the adsorbent has a mean particle size of at most 120 μm. 8. A method according to claim 1, wherein the adsorbent has a mean particle size in the range of 40 to 150 μm. 9. A method according to claim 1, wherein the non-porous core constitute of at the most 50% of the total volume of the adsorbent particle. 10. A method according to claim 1, wherein the adsorption column is selected from the group consisting of expanded bed adsorption column, a packed bed adsorption column or a combination thereof. 11. A method according to claim 1, wherein the adsorbent present in the column relative to the protein-containing mixture to be loaded on to the column are provided at a ratio of at least 1:1000 measured on a volume/volume basis 12. A method according to claim 1, wherein eluting is performed with an eluant selected from the group consisting of dilute base, dilute acid, and water. 13. A method according to claim 12, wherein the diluted bases is selected from the group comprising sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide. 14. A method according to claim 1, wherein the elution of the bound substances from the adsorbent provides a final salt concentration in the eluate less than 50 mM salt. 15. A method according to claim 1, wherein the porous material comprises a polymeric base matrix. 16. A method according to the claim 15, wherein the polymeric base material is a polysaccharide. 17. A method according to claim 1, wherein the adsorbent comprises a ligand with affinity to proteins. 18. A method according to claim 17, wherein the ligand concentration of the adsorbent is at least 30 mM. 19. A method according to claim 1, wherein the adsorbent has a binding capacity of at least 10 g/L of BSA according to test Method A. 20. A method according to claim 1, wherein at least one protein to be isolated is selected from the group consisting of lactoperoxidase, lactoferrin, bovine serum albumin, β-lactoglobulin, immunoglobulin, α-lactalbumin and glycomacropeptide. 21. A method according to claim 19, wherein at least one isolated protein mixture comprises at least 70% w/w of a single protein. 22. A method according to claim 1, wherein the purity of the protein to be isolated measured in the eluate is at least 65%. 23. A method according to claim 1, wherein the protein-containing mixture comprises at least 2 proteins and said fractionation of the at least 2 proteins is performed using an expanded adsorbent bed or packed adsorbent bed or combinations thereof. 24. A method according to claim 23, wherein the method comprises at least 2 adsorbents each placed in a modular unit. 25. A method according to claim 24, wherein the fractionation of the proteins from the adsorbents comprises the steps of: i) optionally adjusting the pH in the protein-containing mixture; ii) optionally equilibrating the adsorbent; ii) applying the protein-containing mixture to the adsorbents; iii) optionally washing with a liquid; iv) eluting the adsorbed proteins with one or more eluents selected from the group consisting of dilute acid, dilute base and water; vi) isolating at least one protein mixture comprising a single protein or various proteins. 26. A method according to claim 24, wherein two or more modular units are connected in series. 27. A method according to claim 1, wherein a plug flow is established in the adsorbent by providing a layer of inert glass beads positioned in the stirring zone. 28. A method according to claim 1, wherein the particle size is less than 120 μm and the particle density is at least 1.6 g/ml. 29. A method according to claim 1, wherein the particle size is less than 90 μm and the particle density is at least 1.8 g/ml. 30. A method according to claim 1, wherein the particle size is less than 75 μm and the particle density is at least 2.0 g/ml. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Milk is one of the most thoroughly researched foods in history. Countless scientific papers document milk's composition and describe the biological functionalities in this complex bio-resource. Proteins, peptides, enzymes and other biomolecular substances constitute a major and very important fraction in milk and are believed responsible for many of the specific functionalities passed on from a mother to her new-born in addition to basic nutrients. During the past two decades, there has been significant focus on utilisation of bovine whey proteins. Today, several bovine Whey Protein Concentrates (WPC) and bovine Whey Protein Isolates (WPI) are standard products obtained through various membrane filtration techniques as well as ion exchange adsorption procedures. Further utilisation of the bovine whey in terms of fractionation of the proteins into individual protein fractions, such as β-lactoglobulin, α-lactalbumin, immunoglobulins, lactoperoxidase, and lactoferrin, is made possible through chromatographic packed bed separation techniques. Protein products from chromatographic separation technologies are generally characterised by their low- to non-fat content and are useful for a broad range of applications e.g. within food, feed, functional foods, and health care products. Since the first market introductions of WPC and WPI products and more recently the first purified single protein products (e.g. lactoferrin and lactoperoxidase) there has evolved an ever increasing demand for even more sophisticated and still more efficient and cost effective productions methods. Among the various industrial chromatographic separation techniques developed in recent years, Expanded Bed Adsorption (EBA) has been successfully introduced to the certain fields of biotechnology industry. EBA is a type of fluidised bed adsorption wherein the level of back-mixing is kept at a minimum. Compared with other chromatographic separation technologies, EBA offer a significant advantage because it can be used directly with non-clarified feed. During EBA, the adsorbent bed is allowed to expand inside the column when a flow of liquid is applied (see FIG. 1 ). Expansion/fluidisation of the bed is often effected in a column having provided at each of its ends a net structure covering the cross-sectional area of the column, or some other perforated devices, which will not generate turbulence in the flow. See, for instance, WO-A-9218237 (Amersham Pharmacia Biotech AB, Sweden). The same effect has also been observed in a system utilising a stirred inlet flow WO-A-9200799, (UpFront Chromatography A/S). In addition, other distributors are likely to be feasible. In the expanded bed state, the distance between the adsorbent particles result in a free passage of particulate impurities in the feed stream. By contrast, traditional packed beds work as depth filters that can clog, resulting in increased back-pressure unless the feed is thoroughly clarified. Since no significant pressure builds up in an EBA column, it is possible to apply EBA without the limitations in size and flow rate normally associated with packed-bed columns. An EBA process is characterised by very limited back-mixing of the liquid inside the column as opposed to the well know turbulent fluidised beds typically employed for chemical reactions. Back-mixing in a bed is often measured as axial dispersion (“vessel dispersion number”), see Levenspiel, “Chemical Reaction Engineering” 2nd Edition, John Wiley & Sons (1972). The adsorbent media employed in an EBA process must have a higher density than the feed stock in order to produce acceptable flow rates during operation. If the density is too low, the media will be lost in the column effluent. Generally, EBA adsorbent particles may either be designed to be impermeable to the fluid, in which case the available surface area per unit volume is small; or particles may be designed to be permeable to the fluid, in which case the material chosen has to have the correct density per se. Unfortunately, the most interesting materials for many applications, e.g. materials such as natural and synthetic polysaccharides like agar, alginates, carrageenans, agarose, dextran, modified starches, and celluloses; synthetic organic polymers and copolymers typically based on acrylic monomers used for chromatographic purification of proteins in packed bed columns are not of suitable density per se. Therefore, these materials are not readily applied in EBA. However, certain types of organic polymers and certain types of silica based materials may be produced to provide carrier particles of suitable density, but such carriers may not at the same time be suitable adsorbents, e.g. for protein purification procedures, where such materials may provide low permeability, non-specific interactions and denature bound proteins. Further, for such polymers, it may be difficult and expensive to design derivatisation schemes for affinity chromatography media. In addition, certain types of permeable silica particles have been used for EBA. However, the properties of these materials are far from optimal. Thus, the materials are unstable at pH above 7, fragile to shear forces, and provide non-specific interactions. In addition solid silicate materials have a maximal density of approx. 2.5 g/mL. The density of the adsorbent media may be controlled by an inert, high-density core incorporated in the polymer phase (composite media, conglomerates see e.g. WO-A-9200799). High-density core materials are typically chosen from high density materials such as glass, quartz or heavy metals either in the form of an alloy such as stainless steel or an oxide (e.g. zirconium oxide) or some other metal salt (e.g. tungsten carbide). The core material may also comprise metal spheres (e.g. tantalum). The core material of the particles may vary in size and shape. Typical sizes are within 5-80 micrometers. In EBA, as a result of the optimisation of the characteristics of the adsorbent media (size distribution), plug-flow conditions with very little back-mixing is obtained inside the column. The plug-flow behaviour is crucial in order to obtain an efficient adsorption. Today, several important bio-pharmaceuticals are being produced using the EBA technology. However, no commercial processes for milk and whey fractionation are based on EBA so far. This is in great part due to the large scale of the process required for milk and whey fractionation, typically involving extremely high volumes of raw material to be treated per day (e.g. several m 3 /hour) which requires extremely high efficiency and productivity of the EBA system. Current processes are not capable, in practice, to achieve the level of performance for these and certain other raw materials. A major supplier of EBA adsorbents and EBA columns is UpFront Chromatography A/S, Denmark. These products are supplied under the trademark FastLine (see e.g.WO 92/00799, UpFront Chromatography A/S, Denmark), which discloses a large number of fillers and polymeric materials that can be combined to produce composite beads, conglomerates) intended for adsorption in EBA. Amersham Pharmacia Biotech AB, Sweden markets StreamLine which utilise porous beads of agarose with quartz particles as filler material (WO-A-9218237, Pharmacia Biotech AB). Another supplier is Bioprocessing Ltd. (Durham, England) whose porous glass beads (Prosep0) can be used for chromatography on expanded beds (Beyzavi et al, Genetic Engineering News, Mar. 1, 1994 17). WO 97/17132 (Amersham Pharmacia Biotech) discloses a population of beads having a density >1 g/cm 3 and comprising a polymer base matrix in which a particulate filler is incorporated. The beads are characterized in that the filler particles have a density >3 g/cm 3 and in that the density and/or size of the beads are distributed within predetermined density and size ranges. Particularly important filler particles are those which have rounded shapes, for instance spheres, ellipsoids or aggregates/agglomerates thereof. The bead population is particularly usable in adsorption processes in fluidized beds, with preference to stable expanded beds. WO 00/57982 discloses a particulate material having a density of at least 2.5 g/mL, where the particles of the particulate material have an average diameter of 5-75 μm, and the particles of the particulate material are essentially constructed of a polymeric base matrix, e.g. a polysaccharide such as agarose, and a non-porous core material, e.g. steel and titanium, said core material having a density of at least 3.0 g/mL, said polymeric base matrix including pendant groups which are positively charged at pH 4.0 or which are affinity ligands for a bio-molecule. Possible pendant groups include polyethyleneimine (PEI), diethylaminoethyl (DEAE) and quaternary aminoethyl (QAE). The materials are useful in expanded bed or fluidised bed chromatography processes, in particular for purification of bio-macromolecules such as plasmid DNA, chromosomal DNA, RNA, viral DNA, bacteria and viruses. WO-A-8603136 (Graves and Burns; University Patents Inc) discloses beads containing magnetic filler particles and their use in fluidized beds stabilized by an externally applied magnetic field. See also Burns et al., Biotechnol. Bioengin. 27 (1985) 137-145. WO-A1-9833572 (Amersham Pharmacia Biotech) discloses a method for adsorption of a substance from a liquid sample on a fluidized bead or stirred suspension, in which the beads used comprise a base matrix and exhibit a structure having affinity to the substance, characterized in that the structure is covalently bound to the base matrix via an extender. Populations of beads in which the beads contain a filler incorporated in a base matrix and an extender are also described. In chromatography on packed beds it has earlier been suggested to use porous beads, the pores of which wholly or partly have been filled with hydrophilic gels carrying affinity ligands, such as ion exchange groups. One example is Macrosob-K which is macroporous kieselguhr which has been filled with agarose which in turn has been derivatized to exhibit DEAE or CM ion exchange groups (Macrosorb-KAX.DEAE and Macrosorb KAX.CM, respectively (GB-A-1,586,364, Miles). This latter type of materials have also been applied in fluidized bed chromatography (Bite et al., In: Verrall et al., Separations for Biotechnology (1987), Ellis Horwood LTD, Chapter 13, 193-199). U.S. Pat. No. 4,976,865 (Sanchez, et al, CNRS) teaches fluidised beds and the use of segmented columns to mimic the multi-step adsorption taking place in packed as well as stabilised expanded beds for isolation of whey compounds. The beads used in the experimental part are silica particles (Spherosil, density=1.4 g/mL, mean particle size=225 μm) that have been coated. The linear flow rate implemented in the experimental part is 1.3×10 −3 m/s, which is equal to 468 cm/hour). The experimental parts discloses the use of this type of fluidized bed adsorption for separation of biological macromolecules from whey. There is no disclosure of any flow rates and/or binding capacities obtainable with adsorbents having a lower than 225 μm mean particle size. Immunoglobulins—or antibodies—constitute a very important class of proteins which are present in various body fluids of mammals, birds and fish functioning as protective agents of the animal against substances, bacteria and virus challenging the animal. Immunoglobulins are typically present in animal blood, milk, and saliva as well as other body fluids and secretions. All the above mentioned applications of immunoglobulins requires some sort of isolation of the antibody from the crude raw material, but each kind of application has its own very varying demands with respect to the final purity and allowable cost of the antibody product. Generally, there exists a very broad range of different methods available for isolation of immunoglobulins giving a very broad range of final purities, yields and cost of the product. Traditional methods for isolation of immunoglobulins are based on selective reversible precipitation of the protein fraction comprising the immunoglobulins while leaving other groups of proteins in solution. Typical precipitation agents being ethanol, polyethylene glycol, lyotropic (anti-chaotropic) salts such as ammonium sulfate and potassium phosphate, and caprylic acid. Typically, these precipitation methods are giving very impure products while at the same time being time consuming and laborious. Furthermore, the addition of the precipitating agent to the raw material makes it difficult to use the supernatant for other purposes and creates a disposal problem. This is particularly relevant in relation to the large scale purification of immunoglobulins from for instance, whey. Ion exchange chromatography is another well known method of protein fractionation frequently used for isolation of immunoglobulins. However, this method is not generally applicable because of the restraints in ionic strength and pH necessary to ensure efficient binding of the antibody together with the varying isoelectric points of different immunoglobulins. Protein A and Protein G affinity chromatography are very popular and widespread methods for isolation and purification of immunoglobulins, particularly for isolation of monoclonal antibodies, mainly due to the ease of use and the high purity obtained. Although being popular it is however recognised that Protein A and Protein G poses several problems to the user among which are: very high cost, variable binding efficiency of different monoclonal antibodies (particularly mouse IgG 1 ), leakage of Protein A/Protein G into the product, and low stability of the matrix in typical cleaning solutions, e.g. 1 M sodium hydroxide. Each of these drawbacks have its specific consequence in the individual application, ranging from insignificant to very serious and prohibitive consequences. Hydrophobic chromatography is also a method widely described for isolation of immunoglobulins, e.g. in “Application Note 210, BioProcess Media” published by Pharmacia LKB Biotechnology, 1991. In this publication, a state of the art product “Phenyl Sepharose High Performance” is described for the purpose of purifying monoclonal antibodies from cell culture supernatants. As with other hydrophobic matrices employed so far it is necessary to add lyotropic salts to the raw material to make the immunoglobulin bind efficiently. The bound antibody is released from the matrix by lowering the concentration of lyotropic salt in a continuous or stepwise gradient. It is recommended to combine the hydrophobic chromatography with a further step if highly pure product is the object. The disadvantage of this procedure is the necessity to add lyotropic salt to the raw material as this gives a disposal problem and thereby increased cost to the large scale user. The addition of lyotropic salts to the raw materials would in many instances be prohibitive in large scale applications as the salt would prevent any economically feasible use of the immunoglobulin depleted raw material in combination with the problem of disposing several thousand litres of waste. Thiophilic adsorption chromatography was introduced by J. Porath in 1985 (J. Porath et al; FEBS Letters, vol.185, p.306, 1985) as a new chromatographic adsorption principle for isolation of immunoglobulins. Porath describes the technology wherein divinyl sulfone-activated agarose in combination with various ligands comprising a free mercapto-group demonstrate specific binding of immunoglobulins in the presence of 0.5 M potassium sulfate, i.e. a lyotropic salt. It was postulated that the sulfone group, from the vinyl sulfone spacer, and the resulting thio-ether in the ligand was a structural necessity to obtain the described specificity and capacity for binding of antibodies. It was, however, later shown that the thio-ether could be replaced by nitrogen or oxygen if the ligand further comprised an aromatic radical (K. L. Knudsen et al, Analytical Biochemistry, vol 201, p.170, 1992). Although the matrices described for thiophilic chromatography generally show good performance, they also have a major disadvantage in that it is needed to add lyotropic salts to the raw material to ensure efficient binding of the immunoglobulin, which is a problem for the reasons discussed above. Other thiophilic ligands coupled to epoxy activated agarose have been disclosed in (I. Porath et.al., Makromol. Chem., Makromol. Symp., vol. 17, p.359, 1988) and (A. Schwarz et.al., Journal of Chromatography B, vol. 664, pp. 83-88, 1995), e.g. 2-mercaptopyridine, 2-mercaptopyrimidine, and 2-mercaptothiazoline. However, all these affinity matrices still have inadequate affinity constants to ensure an efficient binding of the antibody without added lyotropic salts. To avoid the above mentioned problems and disadvantages the investigators of the present invention have developed a method for large scale fractionation, purification and isolation of at least one protein from a protein-containing mixture. This method is applicable for industrial use, it can handle very large volumes of a protein-containing mixture, it is fast and it provides a highly purified protein. The investigators of the present invention also found that it was possible to carry out the fractionation, purification and isolation of proteins without the use of lyotropic salts. |
<SOH> SUMMARY OF THE INVENTION <EOH>Accordingly a general aspect of the present invention relates to a method of fractionating large volumes of protein-containing solutions using adsorbent which, despite having a small particle diameter and a very high density, exhibit a high binding capacity for the desired protein. One object of the present invention is to provide a process for industrial-scale fractionation of proteins from raw materials using EBA methodology by selection of EBA adsorbents. As stated, this object is achieved at least in part by providing an EBA process utilising a specific adsorbent selected according to its particle diameter and particle density. This allows an EBA process for operating efficiently at linear flow rates above at least 200 cm/hour. Thus, a primary aspect of the present invention relates to a method for the fractionation of a protein-containing mixture wherein the protein-containing mixture is selected from the group consisting of milk, milk derived products, milk derived raw materials, vegetable derived products, vegetable derived extracts, fruit derived products, fruit derived extracts, fish derived products, and fish derived extracts, said method comprising the steps of: a) optionally adjusting the pH of the mixture; b) applying said mixture to an adsorption column comprising an adsorbent, said adsorbent comprises a particle with at least one high density non-porous core, surrounded by a porous material, the adsorbent having a particle density of at least 1.5 g/ml and a mean particle size of at most 150 μm; c) optionally washing the column; d) eluting at least one protein from the adsorbent. |
Method of modulating the activity of calcium channels in cardiac cells and reagents therefor |
The present invention relates generally to novel peptides that are capable of modulating the activity of calcium channels in cardiac cells. More specifically, the present invention provides a method of modulating the activity of a cardiac calcium channel comprising contacting a cardiac ryanodine receptor (RyR2) with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide sufficient to modulate the activity of said RyR2, and determining the activity of said calcium channel. The inventive method is useful for the treatment of a range of disorders and diseases associated with cardiac dysfunction, particularly those diseases and disorders involving reduced cardiac output and/or aberrant excitation-contraction coupling, calcium overload, or calcium leakage, in cardiac cells. |
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