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1. A safety device for breaking glass, provided with a housing (2) built up from at least two housing parts and a head (4), the head (4) being provided with a relatively hard end (14), characterized in that at least a part of the housing (2) is provided with a fluorescent outer surface. 2. A safety device according to claim 1, wherein the housing (2) is manufactured from plastic which is of fluorescent design. 3. A safety device according to claim 2, wherein the plastic is fluorescent. 4. A safety device according to claim 1, wherein at least a part of the housing (2) is provided with a fluorescent print (30). 5. A safety device according to claim 4, wherein at least a part of the fluorescent print (30) has been provided with the aid of in-mold-labeling technique. 6. A safety device according to claim 1, wherein the entire housing (2) on the outside is of fluorescent design. 7. A safety device according to claim 1, wherein the housing comprises two parts (2), wherein each of the parts (2) is provided at the outside with a fluorescent surface. 8. A safety device according to claim 1, wherein at least a part of the fluorescent surface has been obtained by injection or printing with the aid of paint or ink after formation of the respective parts (2) of the housing. 9. A method for manufacturing a safety device (1), wherein at least two housing parts (2) are injection-molded, provided with at least a part of an outside surface with an in-mold label (20) which is of fluorescent design, which housing parts (2) are assembled for forming the housing of the safety device (1), wherein between at least a part of the parts of the housing (2) a head (4) is included extending at least partly outside the housing and being provided with at least one relatively hard end (14). 10. A safety device according to claim 7, wherein the parts are mirror symmetrical. |
Methods |
The molecules of formula (I) are useful in treating diabetes, obesity, hypercholesterolaemia, hyperlipidaemia, cancer, inflammation or other conditions in which modulation of lipid or eicosanoid status or functions may be desirable. Formula (I): Z1-X-Z2 wherein a) Z1 represents CO2H or a derivative thereof; b) Z2 represents F, H, —CO2H or a derivative thereof; and c) X represents fluorinated alkylene; or a solvate thereof, for example a perfluorinated fatty acid or derivative thereof. |
1. A method of treatment of a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin, comprising administering to the patient an effective amount of a compound of formula I, Z1-X-Z2 I wherein Z1 represents —CO2H or a derivative thereof; Z2 represents F, H, —CO2H or a derivative thereof; and X represents fluorinated alkylene; or a solvate thereof. 2. A method of treatment of a patient in need of an antitumour agent or an antiinflammatory agent, or in need of modulation in lipid or eicosanoid status, comprising administering to the patient an effective amount of a compound of formula I as defined in claim 1. 3. A method of treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart-disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition, comprising administering to the patient an effective amount of a compound of formula I as defined in claim 1. 4. A method of treatment of a patient in need of modulation of PPAR (for example PPARα) activity, comprising administering to the patient an effective amount of a compound of formula I as defined in claim 1. 5. A method of treatment of a patient in need of modulation of lipid or eicosanoid status or function, comprising administering to the patient an effective amount of a compound of formula I as defined in claim 1. 6. Use of a compound of formula I as defined in claim 1 in the manufacture of a medicament for treating a patient in need of modulation of PPAR (for example PPARα) activity. 7. The method of claim 4 wherein the patient is in need of an increase in PPAR activity and the compound is a PPAR agonist. 8. The method of claim 7 wherein the PPAR is PPARα or PPARγ. 9. The use of a compound of formula I as defined in claim 1 in the manufacture of a medicament for the treatment of a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 10. The method of claim 1 wherein the patient is in need of reduction of body mass or prevention of increase in body mass, and/or in need of reduction of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 11. The use of a compound of formula I as defined in claim 1 in the manufacture of a medicament for the treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition. 12. The use of a compound of formula I in the manufacture of a medicament for the treatment of a patient in need an antitumour agent or an antiinflammatory agent or of modulation of lipid or eicosanoid status or function, or of modulation of a lipid metabolising or binding entity activity. 13. The method of treatment of claim 1 wherein the compound is or comprises a perfluorinated fatty acid or derivative thereof. 14. The method of treatment of claim 1 wherein the compound is or comprises a fluorinated carboxylic acid or perfluorinated carboxylic acid or pharmaceutically acceptable salt, ester or halide thereof. 15. The method of claim 13 wherein the compound is perfluorooctanoic acid (PFOA) or a pharmaceutically acceptable salt, ester or halide thereof, for example ammonium perfluorooctanoate (APFO). 16. The method of claim 1 wherein the patient is human. 17. A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound in which (1) a mammal is exposed to a compound of formula I as defined in claim 1 or derivative thereof (2) the plasma insulin, glucose, cholesterol, triglyceride and/or leptin level of the mammal is measured, and/or bodyweight of the mammal is measured, and/or lipid or eicosanoid status or function of the mammal is measured. 18. The method of claim 17 comprising the step of selecting a compound on exposure to which the plasma insulin, glucose, cholesterol, triglyceride and/or leptin level of the mammal is changed or reduced, and/or bodyweight or bodyweight increase of the mammal is changed or reduced. 19. A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound in which (1) a compound of formula I as defined in claim 1 or derivative thereof is exposed to a PPAR polypeptide (2) the binding of the compound to the PPAR polypeptide is measured or the change in the activity of the PPAR polypeptide is measured. 20. A screening method for identifyg a drug-like compound or lead compound for the development of a drug-like compound in which (1) a compound of formula I as defined in claim 1 or derivative thereof is exposed to a lipid metabolising or binding entity, for example cycloxygenase (for example cyclooxygenase I or cyclooxygenase II) or phospholipase A (for example phospholipase A2) (2) the binding of the compound to the lipid metabolising or binding entity is measured or the change in the activity of the lipid metabolising or binding entity is measured. 21. A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound in which (1) a cell is exposed to a compound of formula I as defined herein (for example a perfluorinated fatty acid) or derivative thereof (2) the phenotype (for example differentiation) and/or eicosanoid biosynthesis of the cell is measured. 22. The method of claim 21 further comprising the step of selecting a compound on exposure to which the phenotype, for example differentiation, of the cell is changed, and/or eicosanoid biosynthesis of the cell is changed, preferably reduced. 23. A compound identifiable or identified by a screening method according to claim 17. 24. A compound identified or identifiable by a screening method of according to claim 17 for use in medicine. 25. The use of a compound identified or identifiable by a screening method according to claim 17 in the manufacture of a medicament for the treatment of a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 26. Use of a compound identified or identifiable by a screening method according to claim 17 in the manufacture of a medicament for the treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition. 27. The use of a compound identified or identifiable by a screening method according to claim 17 in the manufacture of a medicament for treating a patient in need of modulation of PPAR (for example PPARα) activity, or in need of an antitumour agent or an anninflammatory agent, or in need of modulation of lipid or eicosanoid status or function, or in need of modulation of lipid metabolising or binding entity activity. 28. The use of claim 27 wherein the patient is in need of an increase in PPAR activity and the compound is a PPAR (for example a PPARα) agonist. 29. A method of treatment of a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin, comprising administering to the patient an effective amount of a compound identified or identifiable by the screening method of claim 17. 30. A method of treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition, comprising administering to the patient an effective amount of a compound identified or identifiable by the screening method of claim 17. 31. A method of treatment of a patient in need of modulation of PPAR (for example PPARα) activity, or in need of an antitumour agent or an antiinflammatory agent, or in need of modulation of lipid or eicosanoid status or function, or of a lipid metabolising or binding entity activity, comprising administering to the patient an effective amount of a compound identified or identifiable by the screening method of claim 17. 32. A compound identified or identifiable by the screening method of claim 17 for use in the manufacture of a composition for use as a food supplement or a food additive. 33. A food product comprising a foodstuff and a compound of formula I as defined in claim 1 or a compound identified or identifiable by the screening method of claim 17, wherein the food is not laboratory rodent feed. 34. A kit of parts of screening system comprising (1) a library of compounds each of formula I as herein defined or a derivative thereof, and (2) a PPAR polypeptide or polynucleotide encoding a PPAR polypeptide, and/or a test mammal. 35. A kit of parts of screening system comprising (1) a library of compounds each of formula I as herein defined or a derivative thereof and (2) a lipid metabolising or binding entity (for example COXI or COXII or phospholipase A2 or lipoxygenase) or polynucleotide encoding a lipid metabolising or binding entity. 36. (canceled) |
Catalysts |
A tethered ligand comprising the reaction product of an organofunctional silica and a ligand containing a functional group capable of reaction with said organofunctional silica, wherein the organofunctional silica is prepared from an alkyl silicate and an organofunctional silane is described. A supported catalyst is also described comprising additionally a source of catalytically-active metal. Methods for preparing the tethered ligand and supported catalyst are provided and uses of the supported catalyst for performing asymmetric reactions are claimed. The catalysts are readily separable from the reaction mixtures and may be re-used if desired. |
1. A tethered ligand comprising the reaction product of a meso-porous organofunctional silica having an average pore width, as measured by BET porosimetry, of between 20 and 500 Angstroms and a ligand containing a functional group capable of reaction with said organofunctional silica, wherein the organofunctional silica is prepared from an alkyl silicate and an organofunctional silence. 2. A tethered ligand according to claim 1, wherein the alkyl silicate has the general formula Si(OR)4 in which each R may be the same or different and is an alkyl group or substituted alkyl group having between 1 and 4 carbon atoms. 3. A tethered ligand according to claim 1, wherein the organofunctional silane has the general formula (Y)aSi((Z)X)b in which; Y is a halogen or alkoxy group having 1 to 3 carbon atoms; Z is an alkyl, aryl or alkyl-aryl group, which optionally contains at least one heteroatom selected from oxygen, nitrogen, phosphorus or sulphur; X is a functional group selected from halide, hydroxyl, carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide, vinyl, nitrile, mercapto, amine, imine,. amide and imide; a=3 or 2, b=1 or 2 and a+b=4. 4. A tethered ligand according to claim 1, wherein the organofunctional silane is prepared by reaction of an organofunctional silane with a linker molecule that contains a functional group that is capable of reacting with the organofunctional silane and a functional group capable of reacting with a functional group-containing ligand, said linker molecule selected from the group comprising C1-C10 alkyl, alkoxy, alkyl-aryl, aryl, phenoxy or anilide compounds containing functional groups selected from halide, hydroxyl, carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide, vinyl, nitrile, mercapto, isocyanate, amine, imine, amide and imide. 5. A tethered ligand according to claim 1, wherein more than one organofunctional silane is used. 6. A tethered ligand according to claim 1, wherein the organofunctional silica is prepared from an alkyl silicate and an organofunctional silane and a silane not having a functional group capable of reaction with a functional group-containing ligand. 7. A tethered ligand according to claim 1, wherein the functional group on the organofunctional silica is changed by chemical conversion before reaction of the organofunctional silica with the functional group-containing ligand. 8. A tethered ligand according to claim 1, wherein the organofunctional silica is reacted with a linker molecule that contains a functional group that is capable of reacting with the organofunctional silica and a functional group capable of reacting with a functional group-containing ligand. 9. A tethered ligand according to claim 1, wherein the ligand containing a functional group is a chiral or non-chiral mono-, bi-, tri- or tetra-dentate ligand having a reactive group capable of reacting with the organofunctional silica. 10. A tethered ligand according to claim 9, wherein the ligand containing a functional group is a racemic or non-racemic mixture or single enantiomer of a β-diketonate, β-ketoester, alkanolamine, Schiff base, aminoacid, peptide, phosphite, phosphate, alkyl- or aryl-phosphine, diamine, crown-ether and bis-oxazoline, each having a reactive group selected from the group consisting of halide, hydroxyl, carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide, vinyl, nitrile, mercapto, amine, imine, amide and imide. 11. A method for the preparation of a tethered ligand comprising the steps of; a) forming an organofunctional silica by the reaction of an alkyl silicate, an organofunctional silane and water, optionally in the presence of a template compound, b) removing the template compound if present, and c) reacting said organofunctional silica with a ligand containing a functional group capable of reaction with said organofunctional silica. 12. A method according to claim 11, wherein the functional group present on the organofunctional silica formed in step (a) is changed by a chemical conversion before reaction of the organofunctional silica with the functional group-containing ligand. 13. A method according to claim 11, wherein the organofunctional silica formed in step (a) is reacted with a linker molecule that contains a functional group that is capable of reacting with the organofunctional silica and a functional group capable of reaction with a function group-containing ligand. 14. A method according to claim 11, wherein the molecular ratio of alkyl silicate to organofunctional silane is 1:1 to 99:1. 15. A supported catalyst comprising the reaction product of a tethered ligand as claimed in claim 1 and a source of catalytically-active metal. 16. A catalyst according to claim 15, wherein the catalytically-active metal is selected from the group comprising Sc, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re, Fe, Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Al, Ge, Sb and Sn. 17. A catalyst according to claim 15, wherein the source of catalytically-active metal is an organic complex of the metal or metal salt. 18. A method for the preparation of a supported catalyst comprising the steps of; a) forming an organofunctional silica by reaction of an alkyl silicate, an organofunctional silane and water, optionally in the presence of a template compound, b) removing the template compound if present. c) reacting said organofunctional silica with a ligand containing a functional group capable of reaction with said organofunctional silica to produce a tethered ligand and d) carrying out a chemical reaction between a metal compound and said tethered ligand. 19. The use of a supported catalyst according to claim 15 for hydrogenation reactions, dihydroxylation reactions, hydrolysis reactions, metathesis reactions, carbon-carbon bond formation reactions, hydroamination reactions, epoxidations, aziridinations, cycloadditions, hetero-Diels-Alder reactions, hetero-ene reactions, Claisen rearrangements, carbonyl reductions, sigmatropic rearrangements, additions of nucleophiles to π-bonds, addition of nucleophiles to carbonyl groups and ring-opening reactions. 20. The use of a supported catalyst according to claim 19 for hydrogenation reactions, hydrolysis reactions and carbon-carbon bond formation reactions. 21. The use of a supported catalyst according to claim 19, wherein the catalyst is separated from the reaction mixture, and re-used in subsequent reactions. 22. The use of a supported catalyst according to claim 20, wherein the catalyst is separated from the reaction mixture, and re-used in subsequent reactions. 23. The use of a supported catalyst according to claim 21, wherein the catalyst is separated from the reaction mixture, and re-used in subsequent reactions. |
Compositions and methods to prevent metastasis from primary malignancies |
We have now discovered a new method for treating carcinoembriyonic antigen (CEA) associated cancers. This involves blocking a protein expressed by the hnRNP M4 gene (preferably the human hnRNP M4 gene). We identified and isolated a liver-derived recombinant cDNA clone, termed heterogeneous nuclear RNA binding protein M4 (hnRNP M4) SEQ ID NO: 1, from rat macrophages Kupffer cells (KC) that encodes a novel protein interacting with CEA molecules and is 91% homologous with the deletion mutant of the human hnRNP M4 gene (# U32577). The novel protein is, hereinafter, considered as one protein population with the human homologue and referred to herein as hnRNP M4 CEA receptor, or hnRNP M4. |
1. A method of preventing tumor metastasis comprising administering to a host having a primary tumor a compound that inhibits binding of CEA to a hnRNP M4 receptor. 2. The method of claim 1, wherein the compound is an antibody. 3. The method of claim 1, wherein the compound is an antisense DNA. 4. The method of claim 1, wherein the compound is a soluble receptor. 5. An isolated DNA segment encoding a protein comprising the amino acids of SEQ ID NO: 2. 6. A DNA segment encoding an hnRNP M4 receptor having the amino acid of SEQ ID NO: 2. 7. An isolated DNA segment encoding a human hnRNP M4 receptor. 8. A protein encoded by the DNA of claim 5, 6 or 7. 9. An antibody directed to the protein of claim 8. 10. An isolated DNA segment comprising the nucleotide sequence of SEQ ID NO: 1, or the complement thereof. 11. A host cell containing the DNA of claim 5, 6 or 7. 12. A bioassay for detecting hnRNP M4 mRNA in a biological sample comprising the steps of: i) contacting said biological sample with a DNA segment according to claims 5, 6 or 7 under conditions such that a DNA:RNA hybrid molecule containing said DNA segment and complementary RNA can be formed; and ii) determining the amount of said DNA segment present in said hybrid molecule. 13. A bioassay for testing potential analogs of ligands of hnRNP M4 receptors for the ability to affect an activity mediated by said hnRNP M4 receptors, comprising the steps of: i) contacting a molecule suspected of being a ligand with hnRNP M4 receptors produced by a cell according to claim 11; and ii) determining the amount of a biological activity mediated by said hnRNP M4 receptors in said cells. 14. An assay for detecting an hnRNP M4 in a biological sample comprising the steps of: i) contacting said sample with an antibody according to claim 9, under conditions such that specific complexes of said antibody and an antigen can be formed; and ii) determining the amount of said antibody present as said complexes. 15. A method for targeting a therapeutic drug to cells having high levels of hnRNP M4 receptors, comprising the steps of: i) conjugating an antibody according to claim 9, or an active fragment thereof, to said drug; and ii) administering the resulting conjugate to an individual with cells having high levels of hnRNP M4 receptors in an effective amount and by an effective route such that said antibody is able to bind to said receptors on said cells. 16. Use of antibody of claim 9, or an active fragment thereof, conjugated to a therapeutic drug to target said therapeutic drug to cells having high levels of hnRNP M4 receptors. |
<SOH> BACKGROUND <EOH>1. Field of the Invention The present invention relates to carcinoembryonic antigen (CEA) molecules generally and metastasis of malignant cells. More specifically, the present invention relates to a method for treating CEA-associated cancers. 2. Background of the Invention The liver is a common site for metastasis from various forms of primary malignancies. Both experimental and clinical results reveal that the presence of CEA enhances liver metastasis from colorectal carcinoma cells (1, 2). Increased amount of CEA in the serum correlates with the development of metastatic recurrence after the surgical removal of the primary tumor. In malignant conditions, the reported incidence of elevated serum CEA level ranges from 9% in testicular, ovary, lung, pancreatic and thyroid carcinomas to more than 50% in the metastatic colorectal carcinomas. CEA is an FDA approved tumor marker in the management of metastatic colon and breast cancers (3). It has been previously shown that CEA production of human colorectal cancer cell lines directly correlates with the metastatic potential (4, 5). Poorly metastatic colon cancer cell lines become highly metastatic when transfected with the cDNA coding for CEA (6). As a member of the immunoglobulin supergene family, CEA is involved in the intercellular recognition and may facilitate attachment of colorectal carcinoma cells to sites of metastasis. In an experimental metastasis model of colorectal carcinoma in athymic nude mice, systemic injection of CEA enhanced experimental liver metastasis and implantation in liver by weakly metastatic tumor cells (7). The mechanism by which CEA causes enhancement of metastasis is largely unknown. We have shown earlier that CEA is rapidly cleared from the circulation of experimental animals, accumulates in the liver and is endocytosed in vitro by KC (8). This uptake is independent of carbohydrates and is mediated by an 80 kD protein (9). The structure and the sequence of this protein is unknown. We have further shown that CEA is recognized by this binding protein through a five amino acid sequence, Pro-Glu-Leu-Pro-Lys (PELPK), located at the hinge region (amino-acids 108-112) between the N-terminal and the first immunoglobulin loop domain in the CEA sequence (10), and that the CEA binding to Kupffer cells initiates series of signaling events that lead to the tyrosine phosphorylation (23) and induction of IL-1α, IL-6, IL-10 and TNF-α cytokines (24). Molecular modeling studies have suggested that this region is exposed on the surface of the molecule (P. A. Bates, personal communication). In order to successfully treat a multitude of malignant conditions, it is necessary to prevent the development of metastasis from cancerous cells after the treatment or removal of the primary malignancy. Therefore, there is a need to elucidate the mechanism by which CEA initiates series of signaling events that lead to metastasis from cancerous cells to healthy tissues, e.g., liver. |
<SOH> SUMMARY OF THE INVENTION <EOH>We have now discovered a new method for treating carcinoembryonic antigen (CEA) associated cancers. This involves blocking a protein expressed by the hnRNP M4 gene (preferably the human hnRNP M4 gene). We identified and isolated a liver-derived recombinant cDNA clone, termed heterogeneous nuclear RNA binding protein M4 (hnRNP M4) SEQ ID NO: 1, from rat macrophages Kupffer cells (KC) that encodes a novel protein interacting with CEA molecules and is 91% homologous with the deletion mutant of the human hnRNP M4 gene (# U32577). The novel protein is, hereinafter, considered as one protein population with the human homologue and referred to herein as hnRNP M4 CEA receptor, or hnRNP M4. We have surprisingly discovered that this gene product is the receptor for CEA. For example, transfection of rat hnRNP M4 cDNA into mouse macrophage cell line p388D1 resulted in CEA binding. To isolate the novel CEA receptor we used two approaches: screening of a KC cDNA library with the specific antibody and the yeast 2-hybrid system for the protein interaction using as a bait N-terminal part of the CEA encoding the binding sequence. Both techniques resulted in the isolation of a deletion mutant (amino acids 158-197) of the rat and human hnRNP M4 proteins. Thus, the new rodent clone is the rat homologue of the human hnRNP M4 (# U32577). The full-length cDNA is a 2351 bp complete ORF with the polyadenylation signal AATAAA (SEQ ID NO: 3) and a termination polyA tail. The mRNA shows ubiquitous tissue expression as a 2.4 kb transcript. The deduced amino acid sequence comprised a 78-kD membrane protein with 3 putative RNA-binding domains, arginine-methionine-glutamine rich C-terminus and 3 potential membrane spanning regions. Computer assisted evaluation of the hnRNP M4 sequence revealed a motif for tyrosine phosphorylation (KVGEVTY, SEQ ID NO: 4), 7 potential protein kinase C phosphorylation sites, 11 casein kinase 11 phosphorylation sites, two glucosaminoglycan attachment sites and 15 N-myristoylation sites. When hnRNP M4 protein is expressed in pGEX3T-4 vector system in E. coli it binds 125 I labeled CEA in a Ca 2+ -dependent fashion. These data provide an evidence for a new function of hnRNP M4 protein as a CEA binding protein. To further study the interaction between the peptide sequence PELPK (SEQ ID NO: 5) and rat Kupffer cells, the CEA binding protein was purified using a combination of gel filtration, preparative polyacrylamide gel electrophoresis and affinity chromatography on CEA sepharose (11). A polyclonal antibody to the rat 80-kD protein was produced in mice that blocks both CEA and PELPK-albumin uptake by isolated rat Kupffer cells and shows a high degree of specificity for the rat 80-kDa protein by FACS analysis and Western blotting (11). The present invention further provides DNA segments encoding the hnRNP M4 receptor proteins. The present invention also provides an isolated DNA encoding a protein comprising the amino acids as set forth in SEQ ID NO: 2, as well as an isolated protein comprising the amino acids as set forth in SEQ ID NO: 2. Antibodies directed to amino acids of SEQ ID NO: 2, or a protein comprising amino acids of SEQ ID NO: 2 are also included. A DNA segment comprising the nucleotides as set forth in SEQ ID NO: 1 is further provided. The present invention further provides assays for expression of the RNA and protein products of the DNA of the present invention to enable determining whether abnormal expression of such DNA is involved with a particular disease, e.g., cancer. The present invention also provides antibodies, either polyclonal or monoclonal, specific to a unique portion of the receptor protein; a method for detecting the presence of a receptor ligand that is capable of either activating or down-regulating, i.e., modulating, the receptor protein; a method of screening potential ligand analogs for their ability to modulate the receptor protein; and procedures for targeting a therapeutic drug to cells having a high level of the receptor protein. The present invention also provides binding assays that permit the ready screening for molecules that affect the binding of the receptor and its ligands. The present invention further provides use of the receptor for intracellular or extracellular targets to affect binding. Intracellular targeting can be accomplished through the use of intracellularly expressed antibodies referred to as intrabodies. Extracellular targeting can be accomplished through the use of receptor specific antibodies. Additionally, the soluble form of the receptor can be used as a receptor decoy or aptamer to inhibit binding. The present invention also provides use of antisense technology to affect binding of the CEA receptor and its ligands by designing an antisense nucleic acid molecule which is complementary to a nucleic acid molecule encoding the CEA receptor. The present invention also provides an assay to determine the presence or absence of the receptors that can be used as a diagnostic or prognostic tool to identify the presence or stage of differentiation of tissue, e.g., tumor tissue. Finally, a nucleic acid of the invention could be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. RNA-mediated interference (RNAi) may also be used. |
Method for producing gene libraries |
The presented invention refers to a method for the creation of gene libraries wherein a defined number of adjacent nucleotides is exchanged and gene libraries are produced which code for protein variants having more manifold amino acid exchanges and a more homogenous distribution of mutations than can be obtained using conventional methods. DNA-strands are incorporated at random positions into a gene of interest. Then parts of the donor strands and parts of the gene sequence that is flanking these strands are removed, however, a defined number (e.g. 3) of nucleotides that originate from the donor strand remain in the gene at the place of a defined number (e.g. 3) of nucleotides of the original gene having been removed from it. Combined with a selection step after the incorporation of the donor strand into the gene it can be ensured that the nucleotides to be exchanged/introduced are in a specific reading frame. When the nucleotides of the donor strand that remain in the genes are degenerate, gene libraries can be produced with variants that have any codon at any position. |
1-44. (canceled) 45. A method for producing sequence variation in DNA, which comprises the steps of: a) incorporation of a transposon (DONOR) into said DNA (GEN) at different random positions and b) specific removal of DONOR from GEN and specific removal of a defined number of adjacent nucleotides of GEN from GEN, such that at exactly the position of these removed nucleotides within the sequence of GEN a defined number of nucleotides remain that originate from DONOR and which can be completely degenerate. 46. A method according to claim 45, wherein step 1 (b) occurs by several cycles of the following steps (a) to (d), followed by the steps (e) to (g): a) restriction digestion of GEN and at least parts of DONOR containing DNA using a restriction endonuclease of type IIs b) by demand, treatment of the DNA-ends with enzymes that make the DNA-ends blunt and/or isolation of the GEN containing part of the restricted DNA c) intramolecular ligation of the free DNA ends of the GEN containing part of the restricted DNA by which a circular strand of DNA is formed, which such receives a new recognition site for a restriction enzyme of type IIs and d) by demand isolation and/or amplification of this circular DNA-strand e) restriction digestion using at least one restriction enzyme of type IIs of the products obtained from the last cycle in step (c) or, when necessary of the amplified and/or isolated products from the last cycle in step (d) f) treatment of the DNA-ends with enzymes that make DNA-ends blunt and/or isolation of the GEN containing part of the restricted DNA g) intramolecular ligation of the free DNA-ends of the GEN containing part of the restricted DNA by which a circular DNA strand (cGEN') is formed, which has the original sequence of GEN with the exception of few nucleotides of GEN that were replaced by degenerate nucleotides from DONOR. 47. A repertoire of sequence variants of DNA that has been produced using a method according to claim 45. 48. A kit for creating sequence variation in DNA based on a method according to claim 45. 49. A method for producing sequence variation in DNA, comprising the steps: a) introduction of a double strand breakage in said DNA (GEN), b) ligation of a DNA Strand (DONOR) to both DNA-ends of GEN, formed by the double strand breakage of GEN, producing a ligation product (LP), c) removal of the major part of DONOR from LP apart from few nucleotides that can be degenerate and removal of a small part of GEN from LP d) intramolecular ligation of the free DNA-ends of the remaining part of LP such that a circular DNA strand (cGEN') is formed, which has the original sequence of GEN with the exception of few nucleotides of GEN that were replaced by degenerate nucleotides from DONOR. 50. A repertoire of sequence variants of DNA that has been produced using a method according to claim 49. 51. A kit for creating sequence variation in DNA based on a method according to claim 49. 52. A repertoire of sequence variants of DNA that has been produced using a method according to claim 2. 53. A kit for creating sequence variation in DNA based on a method according to claim 2. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Enzymes are increasingly applied in the biotechnological and chemical industry, as well as in the medical diagnostics and therapie 1 . They help to improve existing processes and make new applications possible. Therefore, there is an increasing demand of enzymes with new or improved properties. The improvement/optimization of enzymes by rational or computerized methods, however, has been mostly without success 2 . Directed evolution of proteins, on the contrary, has been quite successful in optimizing properties of enzymes 3 . Directed evolution consists of two steps. Firstly, a gene library is created by varying one or more DNA sequences encoding the according enzyme and secondly, using selection or screening methods, those variants of the genes are isolated that encode enzymes variants with the desired, optimized properties. The advantage of this approach is that it does not require any information on the structure of the enzyme in question, its dynamics or its interactions with different substrates. Therefore, methods of directed evolution are increasingly accepted and applied by many biotech companies worldwide 1,4 . Success and failure of directed evolution above all depend on the quality of the libraries and the efficiency of the selection or screening method. The quality of a library is determined by the available sequence variation and depends mostly on the method used to create the sequence variation. Nowadays mainly two approaches are used to create sequence variation: in-vitro DNA-recombination 5-7 and random mutagenesis 8-10 . In-vitro DNA-recombination is based on a small repertoire of DNA sequences that are similar but not identical to each other. The differences (mutations) between these sequences can originate from natural evolution (family shuffling) 11 or could have been introduced by a combination of random mutagenesis and selection 5 . They therefore represent a pre-selection and in general improve or at least are neutral to the properties of the enzyme encoded by the DNA sequence. In the in-vitro DNA-recombination a repertoire of DNA sequences is produced, the variants of which contain new combinations of the mutations that were present in the original repertoire. The advantage of this approach is that a high number of positions in a gene are varied at once and that mostly advantageous mutations are recombined. The disadvantage of this approach is that variation is confined to sequence positions that show variation in the original repertoire and additionally to the types of mutations present at these positions. Random mutagenesis, on the contrary, provides access to completely new mutations. It has the advantage that all positions of a gene can contain every possible variation. Random mutagenesis, therefore, is not limited to mutations that are already present somewhere. Nowadays there are two techniques that are almost exclusively used for introducing random mutations into genes: error prone PCR 8 and site specific (cassette-) mutagenesis using degenerated oligonucleotides 9 . Error Prone PCR The by far most dominant method of the site-nonspecific random mutagenesis is to use error prone PCR. Here the gene to be mutated is amplified by PCR using a thermostable polymerase (usually Taq-polymerase) that introduces wrong nucleotides in a rate that depends on the conditions of the PCR einbaut 12 . A common variant of this method applies Manganese(II)-Ions 8 or nucleotide analoga 13 to adjust the error rate to suitable levels. Error prone PCR is inexpensive and simple, but it has the following drastic disadvantages: 1.) Due to the construction of the genetic code—three nucleotides encode one amino acid, each amino acid is encoded by up to six different codons—a single nucleotide exchange can only lead to 9 new codons (three new nucleotides on three positions in the codons) which on average give rise to only 6 different amino acids. Many amino acid exchanges can only be achieved when two or even all three nucleotide in a codon are exchanged. For example, a codon for Isoleucine (ATT, ATA, ATC) can only be gained by two exchanges when starting from the codon CAA (Glutamine) or even three exchanges when starting from the codon CAG (also Glutamine). There are examples from applications of mutagenesis for enzyme improvement where the exchange of all three nucleotides of a codon was indeed necessary to achieve the required properties of the enzyme 14, 15 . A repertoire of variants of a protein that contains all single amino acid mutations (each amino acid is represented on each position of the protein) has to be very large when it is produced by single nucleotide exchanges (e.g. error prone PCR). An average protein of 300 amino acid length has exactly 300×19=5700 variants that differ to each other by exactly one amino acid. A repertoire of variants of the same protein, which was produced by on average three nucleotide exchanges contains (900×3)ˆ3=2×10 10 different variants. Repertoires of such sizes can only be handled by few selection methods 16 . Error prone PCR, therefore, can not be used to obtain complete high quality repertoires. 2.) Error prone PCR does not exchange all nucleotides alike. Transversions and transitions occur with different rates 17 so that some mutations occur more frequently than others do. This effect leads to a further diminishing of the effective size of a repertoire produced by error prone PCR. 3.) The high redundancy of the codons—several codons encode the same amino acid—leads to the phenomenon that on average 23% of all nucleotide exchanges result in synonymous mutations in which the mutated codon encodes the same amino acid as the original one. Such mutations might lead to desired changes in the expression rate of proteins 18 , important intrinsic properties of the a protein, like for example the enzymatic activity or stability, however, are unchanged. The effect of this phenomenon is that the effective size of a repertoire is diminished. 4.) On average 4% of all nucleotide exchanges introduce new stop codons. By choosing a high mutation rate to achieve a maximum number of amino acid exchanges, many stop codons can be introduced which leads to shortened gene products. A repertoire produced with an average mutation rate of three exchanges per gene (in theory necessary to place at least all amino acids on one position) has already more than 10% prematurely terminated gene products [1−(1−0.04)ˆ3]=0.115. 5.) The introduction of mutations is mostly a stochastic process in which the number of mutations per gene in each single variant in one repertoire follows a Poisson distribution. Depending on the average mutation rate a significant part of the repertoire can have no mutation at all while others contain a very high number of mutations. The result is a further diminishment of the effective size of the repertoire. 6.) The introduction of non-natural amino acids in the biosynthesis of proteins can be achieved by using modified components of the complex biochemical apparatus for protein translation together with new codons that consist of four instead of three bases 19 . To generate protein variants that contain such non-natural amino acids at random positions complete codons, meaning three consecutive nucleotides have to be exchanged against four nucleotides. This is effectively impossible. Site Directed Random Mutagenesis An alternative for error prone PCR is to exchange several nucleotides at once at several defined positions in a gene by using degenerated oligonucleotides and PCR. When all three nucleotides of one codon are varied freely, any natural amino acid can be encoded at the position of this codon within the repertoire 20 . However, a repertoire obtained such a way is distributed rather unevenly. For example, Arginine and Serine are represented 6 times as often as Methionine or Tryptophane. Additionally, the introduction of stop codons can be problematic. The degree of degeneracy of the oligonucleotides can be adjusted by using combinations or mixtures of certain nucleotides at different positions and such that some of these problems are circumvented. So, for example, DNA sequence repertoires can be obtained that encode only a specific part of all amino acids or that encode all amino acids with the same frequency 21,22 . In theory a better alternative for nucleotide mixtures in the chemical synthesis of DNA strands is the usage of nucleotide triplets, entire codons so to say, instead of single nucleotides 23-27 . Unfortunately the different tri-nucleotides all show a different efficiency of the chemical coupling during DNA synthesis, leading again to unevenly distributed repertoires 27 . And even in the case that all these problems can be overcome, site directed random mutagenesis, as its name implies, is always limited to pre-selected, defined sites in a gene. All presented limitations of the currently applied methodologies for random mutagenesis clearly show, how important and advantageous it was, to have a method that could: 1.) exchange complete codons (independent on the number of nucleotides within a codon) instead of single nucleotides randomly along the entire strand of DNA, and 2.) introduce a defined number of mutations (i.e. codon mutations) per each strand of DNA. The invention presented here exactly describes such a method. Repertoires of gene variants prepared by the invented method have a better quality than repertoires that were prepared by conventional methods of error prone PCR. They contain a higher number of different variants while having the same number of repertoire members. When coupled to a selection or screening variants that encode proteins with new and desired properties can be isolated more efficiently from these repertoires. These proteins, for example, can be applied as enzymes in the biotechnological industry, in medical diagnostics or therapy. The above features and many other advantages of the invention will be become better understood by reference to the following detailed description when taking in conjunction with the accompanying drawings. |
Control of priority and instruction rates on a multithreaded processor |
A method and apparatus for controlling issue rate of instructions for an instruction thread to be executed by a processor is provided. The rate at which instructions are to be executed for an instruction thread are stored (46) and requests are issued (44) to cause instructions to execute in response to the stored rate. The rate at which instruction requests are issued is reduced in response to instruction executions and is increased in the absence of instruction executions. In a multi-threaded processor, instruction rate is controlled by storing the average rate at which each thread should execute instructions (48). A value representative of the number of instructions available and not yet issued is monitored and is decreased in response to instruction executions (42). Execution of instructions is prevented on a thread if the number of instructions available but not yet issued falls below a defined value. A ranking order is assigned to a plurality of instructions threads for execution on a multi-threaded processor. A plurality of metrics related to the threads and required for establishment of the rank order are provided. Each metric is assigned to a set of bits and these are assembled in a composite metric being assigned to the most significant bits and the least important metric being assigned to the least significant bits. A ranking order is then assigned to the composite metrics in dependence on their values. |
1. A method for issue rate control of instructions for an instruction thread to be executed by a processor comprising the steps of: storing the rate at which instructions are to be executed for an instruction thread; issuing requests to cause instructions to execute in response to the stored rate; reducing the rate at which instruction requests are issued in response to instruction executions; increasing the rate at which instructions are to be executed in the absence of instruction executions. 2. A method according to claim 1 including the step of accumulating a difference value between an intended rate of execution and the actual rate of execution of instructions; and and wherein the step of issuing requests to cause instructions to execute is dependent on the deficit between the actual rate and intended rate of execution. 3. A method according to claim 2 including the step of stopping the executio of instructions in response to an accumulated excuses. 4. A method according to claim 1 in which the processor is a multithreaded processor which handles a plurality of instructions threads. 5. A method according to claim 4 including the step of assigning a priority to each thread and executing instructions on each thread in dependence on the priority of each thread. 6. A method according to claim 5 in which the step of assigning a priority to the threads comprises: providing a plurality of metrics required for the establishment of rank order for each thread; assigning each metric to a set of bits; and assembling the sets of bits in a composite metric for each thread with the most important metric being assigned to the most significant bits and the least important metric being assigned to the least significant bits of the composite metric. 7. A method according to claim 5 including the step of monitoring a real time deadline for execution of the thread and adjusting the priority of the thread in dependence on the time left to expiry of the deadline. 8. Apparatus for issue rate control of instructions for an instruction thread to be executed by a processor comprising: means for storing the rate at which instructions are to be executed for an instruction thread; means for issuing requests to cause instructions to execute in response to the stored rate; means for reducing the rate at which requests are issued in response to executions; and means for increasing the rate at which instructions are to be executed in the absence of instruction executions. 9. Apparatus according to claim 8 including: means for accumulating a difference in value between an intended rate of execution and the actual rate of execution; wherein the means for issuing requests to cause instructions to execute is dependent on to the deficit between the actual and intended rate of execution. 10. Apparatus according to claim 8 including means to stop execution in response to an accumulated excess between the actual and intended rate of execution. 11. Apparatus according to claim 8 in which the processor is a multithreaded processor which handles a plurality of instruction threads. 12. Apparatus according to claim 11 including means to assign a priority to each thread and wherein the means for issuing requests does so in dependence on the priority of each thread. 13. Apparatus according to claim 12 in which the means for assigning a priority to a thread comprises; means for providing a plurality of metrics required for establishment of rank order for each thread; means for assigning each metric to a set of bits; and means for assembling the sets of bits in a composite metric for each thread with the most important metric being assigned to the most significant bits and the least significant metric being assigned to the least significant bits of the composite metric 14. Apparatus according to claim 12 including means to monitor a real time deadline for execution of the thread and means for adjusting the priority of the thread in dependence on the time left to expiry of the deadline. 15. A method for assigning a ranking order to a plurality of instruction threads to be executed on a multi-threaded processor, comprising the steps of: providing a plurality of metrics required for the establishment of rank order for each thread; assigning each metric to a set of bits; assembling the sets of bits in a composite metric with the most important metric being assigned to the most significant bits of the composite metric and the least important metric being assigned to the least significant bits of the composite metric; and assigning a ranking order to the composite metrics in dependence on their values. 16. A method according to claim 15 in which the step of assigning a ranking order to the composite metrics comprises the steps of: comparing a pair of composite metrics and swapping their order if the lower positioned composite metric has a greater or equal value than the higher positioned composite metric. 17. A method according to claim 16 in which the step of comparing a pair of composite metric proceeds from the lowest ranked pair to the highest ranked pair of composite metrics. 18. A method according to claim 17 in which the process returns to the lowest ranked pair after comparison of the highest ranked pair. 19. Apparatus for assigning a ranking order to a plurality of instruction threads to be executed on a multi-threaded processor comprising: means for providing a plurality of metrics required for establishment of rank order for a thread; means for assigning each metric to a set of bits; means for assembling the sets of bits in a composite metric with the most important metric being assigned to the most significant bits and the least important metric being assigned to the least significant bits; and assigning a ranking order to the composite metrics in dependence on their values. 20. Apparatus according to claim 19 in which the means for assigning a ranking order to the composite metric comprises: means to compare a pair of composite metrics; and means to swap the ranking order of the pair of composite metrics if the lower positioned composite metric has a greater of equal value than the higher positioned composite metric. 21. Apparatus according to claim 20 in which the means to compare composite metrics proceeds from the lowest ranked pair to the highest ranked pair. 22. Apparatus according to claim 21 in which the comparison means returns to the lowest ranked pair after comparison of the highest ranked pair. 23. A method for controlling the instruction issue rate of threads executing on a multithreaded processor comprising the steps of: storing the average rate at which each thread should execute instructions; monitoring a value representative of the number of instructions not yet issued for a thread, increasing the value in dependence on the stored average rate for each thread; and decreasing the value in response to instruction executions. 24. A method according to claim 23 including the step of accumulating the value representative of the number of instructions not yet issued for a thread; 25. A method according to claim 24 including the step of setting a maximum value on the number of instructions that can be accumulated for a thread. 26. A method according to claim 24 in which a thread which builds up an accumulation of instructions not yet issued may be allocated a burst of execution time in which the instructions execute at the higher rate, the burst being bounded by the accumulated value. 27. Apparatus for controlling the instruction issue rate of threads executing on a multithreaded processor comprising: means for storing the average rate at which each thread should execute instructions; means for monitoring a value representative of the number of instructions available but not yet issued for a thread; means for increasing the value in dependence on the stored average rate for each thread; means for decreasing the value in response to instruction executions on a thread; and means for preventing execution of instructions on a thread if the number of instructions available but not yet issued falls below a defined value. 28. Apparatus according to claim 27 including means for accumulating the average instruction issue rate into the value representative of the number of instructions available but no yet issued for a thread. 29. Apparatus according to claim 28 including means for setting a maximum value on the number of instructions available but not yet issued for a thread. 30. Apparatus according to claim 28 in which a thread which builds up an accumulation of instructions not yet issued may be allocated a burst of execution time in which instructions execute at a rate higher than the average rate, the burst being bounded by the accumulated value. 31-36. (Cancelled) |
Intraocular lens |
An intraocular lens system to be implanted in the posterior chamber of an eye, the system comprises a lens having an optical axis and at least two haptics extending from the circumference of the lens. The two haptics each includes one or more teeth located on their periphery. |
1. An intraocular lens system to be implanted in the posterior chamber of an eye, the system comprising a lens having an optical axis and at least two haptics extending from the circumference of the lens, said two haptics each including one or more teeth located on their periphery. 2. An intraocular lens system according to claim 1, wherein said teeth are capable of penetrating the ciliary sulcus of the scleral wall of the eye, to anchor the lens in place. 3. An intraocular lens system according to claim 2, wherein at least one of said teeth is oriented to form an acute angle with the circumference of the haptic, so as to allow smooth rotation of the intraocular lens system in one direction relative to the optical axis and to enable penetration of the teeth into the ciliary sulcus when rotated in the other direction. 4. An intraocular lens system according to claim 1, wherein at least one of said teeth has a harpoon-shaped outer surface. 5. An intraocular lens system according to claim 1, wherein at least one of said teeth has a smooth outer surface. 6. An intraocular lens system according to claim 1, wherein at least one of said teeth has a jagged outer surface. 7. An intraocular lens system according to claim 1, wherein said lens and said haptics are produced as one body. 8. And intraocular lens system according to claim 1, wherein said haptics are produced as separate bodies, attachable to said lens. 9. An intraocular lens system according to claim 1, wherein said haptics and said teeth are produced as one body. 10. An intraocular lens system according to claim 1, wherein at least one of said teeth is produced as a separate body, attachable to at least one of said haptics. 11. An intraocular lens system according to claim 10, wherein said haptics are produced with teeth engaging means. 12. An intraocular lens system according to claim 10, wherein at least one of said teeth is made of a biodegradable material. 13. An intraocular lens system according to claim 10, wherein at least one of said teeth is made of a magnetic material. 14. An intraocular lens system according to claim 1, further including longitudinal positioning holes to facilitate the manipulation of the haptics and the lens. 15. An intraocular lens system according to claim 1, further including positioning holes at the haptic base and tip as to facilitate the manipulation of the haptics and the lens. 16. An intraocular lens system according to claim 1, further including a rigid tool to support the lens system for directing it into its operative position. 17. An intraocular lens system according to claim 16, wherein said tool is adapted to accommodate said lens system and to keep it secure by limiting its movement thereon. 18. An intraocular lens system according to claim 17, wherein said tool has an operative end, which is soft and flexible to avoid damaging the ciliary sulcus. 19. An intraocular lens system according to claim 1, further including a protective, possibly removable sleeve to be placed on at least one of said haptics for depressing said teeth thereon. 20. Haptic to be attached to an intraocular lens in a lens system defined in claim 1. 21. An intraocular lens system to be implanted in an eye, comprising a lens having an optical axis and at least two haptics extending from the periphery of the lens, said two haptics each being formed with teeth engaging means to enable the attachment thereto of one or more teeth. 22. An intraocular lens system according to claim 21, adapted to be implanted in the posterior chamber of an eye, wherein said engaging means is so located on the haptics as to enable the teeth, when attached thereto, to penetrate the ciliary sulcus of the scleral wall of the eye, to anchor the lens in place. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Cataract is clouding of the natural lens of the eye or of its surrounding transparent membrane, which obstructs the passage of light causing various degrees of blindness. To correct this condition, a surgical procedure is known to be performed in which the opaque natural lens, or cataract, is extracted and replaced by an artificial intraocular lens. The natural lens, located behind the iris in the posterior chamber in front of the vitreous cavity of the eye, is composed of a capsular bag containing gelatinous material. If this bag, called the posterior capsule, is left intact during a cataract extraction procedure, it may serve as a stable support site for implanting an intraocular lens. However, in the course of surgery, the posterior capsule may be inadvertently damaged or removed along with the cataract, in which case it would no longer be able to provide a support base to keep the intraocular lens from floating back into the vitreous cavity. In his case, it is known to implant the lens in the anterior chamber in front of the iris, or in the posterior chamber behind the iris, wherein the iris serves as a carrier for the lens in both instances. In the latter case, it has also been known to fix the intraocular lens in place behind the iris by suturing it to the ciliary sulcus. In both of the above cases, to maintain the intraocular lens properly centered, it is normally equipped with extensions, called haptics, which may have positioning holes to facilitate the centering of the lens. U.S. Pat. No. 4,750,904 discloses a method of implanting an intraocular lens in the posterior chamber by tying the haptics to the iris and using small, radially disposed loops formed on the lens to serve as suture sites for securing the implanted lens directly to the iris. |
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, there is provided a novel solution for the self-fixation of an intraocular lens system in the posterior chamber of an eye. The lens system comprises a lens having an optical axis and at least two extending haptics attached to the circumference of the lens. These two haptics each have one or more teeth located on their periphery, which are particularly capable of penetrating the ciliary sulcus of the scleral wall of the eye, thereby anchoring the lens in place. The teeth may be oriented to form an acute angle with the circumference of the haptic, thereby allowing free rotation of the haptic in one direction relative to the optical axis and allowing penetration of the teeth into the ciliary sulcus, when rotated in the other direction. The teeth may be harpoon-shaped, smooth or jagged in order to further facilitate their penetration or grasping of the ciliary sulcus. The present invention provides for a secure self-attachment of the intraocular lens in the posterior chamber independently of the posterior capsule and without involving the iris. |
Method for secure storing of personal data and for consulting same, chip card, terminal and server used to carry out said method |
A method for the secure storing of personal data and for consulting same is carried out in a terminal that is connected to a chip card reader and fitted with a man-machine interface. A browser executing on the terminal conducts a dialogue with a remote server by way of a communication network. Pages of data are viewed on a display device of the interface. Personal data is input by a user in response to the pages displayed, and the data is stored locally for consultation and remotely on the server for saving. |
1. A method for the secure storage of personal data and for consultation, comprising the following steps: using a terminal connected to a chip-card reader and provided with a man-machine interface comprising a display and data input means, using a browser capable of dialoguing with a remote server through a communication network, from the said terminal, displaying pages of data with the said display means, inputting personal data of a user in response to the pages displayed and storing them locally for consultation and remotely on the server for saving. 2. A storage method according to claim 1, wherein the data pages are supplied by the server. 3. A storage method according to claim 1, wherein the data pages are supplied during a communication and entry. 4. A storage method according to claim 1, wherein the data entry is carried out on line. 5. A storage method according to claim 1, wherein the personal data are recorded locally on a chip card connected to said reader and a copy is saved on the server. 6. A storage method according to claim 3, wherein the saving of the copy remotely is carried out substantially simultaneously with the recording locally. 7. A storage method according to claim 1, wherein the personal data are encrypted by a card connected to said reader before being saved. 8. A storage method according to claim 7, wherein the personal data are encrypted by means of an enciphering algorithm using one or more keys saved in the card. 9. A storage method according to claim 8, wherein the enciphering key or keys are also saved by an entrusted entity. 10. A storage method according to claim 1, wherein the browser comprises the functions of a browser of the type defined by the S@T standard (SIM Alliance Toolbox). 11. A storage method according to claim 10, wherein pages supplied by the server are pages of the type defined by the S@TML language. 12. A chip card comprising a processing unit and one or more program memories comprising programs including the operating system of the card, and further including a browser program capable of dialoguing with a distant server through a terminal connected to a chip card reader, provided with a man-machine interface, and wherein the browser permits the entry of personal data by a user of the terminal on pages of data and their storage locally in the card for consultation and remotely on the server. 13. A chip card according to claim 12, wherein said card is a SIM card. 14. A chip card according to claim 12, wherein the browser comprises the functions of a browser of the type defined by the S@T (SIM Alliance Toolbox) standard. 15. A communication terminal for implementing the method according to claim 1, said terminal being provided with a man-machine interface comprising display and inputting means able to establish communication through a network with a remote server, and including a browser able to display personal data entry pages and to store data entered both locally at the terminal and remotely on the server. 16. A terminal according to claim 15, wherein the terminal is a mobile telephone. 17. A terminal according to claim 15, wherein the terminal is of the microcomputer type, and a chip card is inserted in the terminal by a user at each use. 18. A server for implementing the method according to claim 1, comprising an application able to supply to a distant browser, via a communication terminal, pages which can be interpreted and/or executed by the browser, the pages comprising at least requests for the input of personal information and requests for the local storage of this information, requests to return this information to the server, said application executing a step of storing information received. |
Method for producing freshly catched seafood |
A process for the production of ready-to-prepare portions of freshly caught fish such as cod, saithe, salmon, trout etc., comprising the steps of: catch and quality control; 2) gutting and filleting; 3) deep-freezing; 3) acceptance at processing facility and quality control; 4) defrosting; 5) portioning and placing in transport or retail packaging; 6) cooling/freezing; and 8) packing, wherein a) the deep-freezing in step 3) is carried out as an “interleave” freezing of the individual fillets with interleaving to about −20° C.; b) the defrosting in step 5) is carried out in a brine solution containing 0.5-5% NaCl and 0.5-10% commercially available 60% K-Lac; c) the cooling/freezing in step 7) is carried out as a shell-freezing with CO2 saturation and cooling with CO2 in CO2 cabinets to as close to the freezing point of the product as possible, adjusted according to the intended distance of transport; d) packing in an open system where air is replaced by a mixture of N2+CO2 as a transport and packaging atmosphere. |
1. A process for the production of ready-to-prepare portions of freshly caught fish such as cod, saithe, salmon, trout, etc., comprising the steps of: 1) catch and quality control; 2) gutting and filleting; 3) deep-freezing; 3) acceptance at processing facility and quality control; 4) defrosting; 5) portioning and placing in transport or retail packaging; 6) cooling/freezing; and 8) packing, characterised in that a) the deep freezing in step 3) is carried out as an “interleave” freezing of the individual fillets with interleaving to about −20° C.; b) the defrosting in step 5) is carried out in a brine solution containing 0.5-5% NaCl and 0.5-10% commercially available 60% K-Lac; c) the cooling/freezing in step 7) is carried out as a shell-freezing with CO2 saturation and cooling with CO2 in CO2 cabinets to as close to the freezing point of the product as possible, adjusted according to the intended distance of transport; d) packing in an open system where air is replaced by a mixture of N2+CO2 as a transport and packaging atmosphere. 2. A process according to claim 1, characterised in that the defrosting in step 5) is carried out in a brine solution comprising 2% NaCl and 5% commercially available 60% K-Lac. |
Novel substituted imidazotriazinones |
The invention relates to novel substituted imidazotriazinones, to a method for their production and to the use thereof for producing medicaments, in particular to improve perception, powers of concentration, learning capacity and/or memory retentiveness. |
1. Compounds of the general formula (I), in which R1 denotes phenyl which can be substituted up to three times identically or differently by radicals selected from the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy, halogen, cyano, —NHCOR8, —NHSO2R9, —SO2NR10R11, —SO2R12, and —NR13R14, in which R8, R10, R11, R13 and R14 independently of one another are hydrogen or (C1-C4)-alkyl, and R9 and R12 independently of one another are (C1-C4)-alkyl, or R10 and R11 together with the adjacent nitrogen atom form an azetidin-1-yl, pyrrol-1-yl, piperid-1-yl, azepin-1-yl, 4-methyl-piperazin-1-yl or morpholin-1-yl radical, or R13 and R14 together with the adjacent nitrogen atom form an azetidin-1-yl, pyrrol-1-yl, piperid-1-yl, azepin-1-yl, 4-methyl-piperazin-1-yl or morpholin-1-yl radical, R2 and R3 independently of one another denote hydrogen or fluorine, R4 denotes (C1-C4)-alkyl, R5 denotes (C1-C3)-alkyl, R6 denotes hydrogen or methyl, R7 denotes (C1-C10)-alkyl, (C2-C10)-alkenyl or (C2-C10)-alkinyl, and L denotes carbonyl or hydroxymethanediyl, and their physiologically tolerable salts, hydrates and/or solvates. 2. Compounds according to claim 1, where R1 denotes phenyl, whose meta and/or para positions are substituted up to three times identically or differently by radicals selected from the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy and —SO2NR10R11, and R10 and R11 have the meaning indicated in claim 1. 3. Compounds according to claim 1 or 2, where R7 denotes (C4-C7)-alkyl or (C4-C7)-alkenyl. 4. Compounds according to claim 1, where R1 denotes phenyl whose meta and/or para positions are substituted up to three times identically or differently by radicals selected from the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy and —SO2NR10R11, in which R10 and R11 independently of one another are hydrogen or (C1-C4)-alkyl, R2 and R3 denote hydrogen, R4 denotes methyl or ethyl, R5 denotes methyl, R6 denotes hydrogen or methyl, L denotes carbonyl or hydroxymethanediyl, and R7 denotes n-butyl, n-pentyl, n-hexyl or n-pent-4-en-1-yl. 5. Process for the preparation of compounds of the general formula (I) according to claim 1, where [A] a compound of the general formula (IIa), in which R1, R2, R3, R4, R5, R6 and R7 have the meaning indicated in claim 1, is reacted under suitable condensation conditions to give a compound of the general formula (Ia), in which R1, R2, R3, R4, R5, R6 and R7 have the meaning indicated in claim 1, and then, if appropriate, [B] is reduced under suitable conditions to give a compound of the general formula (Ib) in which R1, R2, R3, R4, R5, R6 and R7 have the meaning indicated in claim 1. 6. Compounds of the general formula (II), in which R1, R2, R3, R4, R5, R6, R7 and L have the meaning indicated in claim 1, and their salts. 7. Compounds according to one of claims 1 to 4 for the treatment and/or prophylaxis of illnesses. 8. Medicaments comprising a compound according to one of claims 1 to 4. 9. Compounds according to one of claims 1 to 4 for improving perception, concentration power, learning power and/or memory power. 10. Compounds according to one of claims 1 to 4 for the treatment and/or prophylaxis of disorders of perception, concentration power, learning power and/or memory power. 11. Use of compounds according to one of claims 1 to 4 for the production of a medicament for improving perception, concentration power, learning power and/or memory power. 12. Use of compounds according to one of claims 1 to 4 for the production of a medicament for the treatment and/or prophylaxis of disorders of perception, concentration power, learning power and/or memory power. 13. Use according to claim 12, the disorder being a result of dementia. 14. Use of compounds according to one of claims 1 to 4 for the production of a medicament for the treatment and/or prophylaxis of dementia. |
Pyrazole derivative, intermediate therefor, processes for producing these, and herbicide containing these as active ingredient |
The present invention provides a pyrazole derivative of the general formula (1), which has an excellent efficacy as an active component for a herbicide, an intermediate for the production thereof, processes for the production thereof, and a herbicide containing the derivative as an active ingredient. |
1. A pyrazole derivative of the general formula (1), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, R3 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, R4 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms or an optionally substituted phenyl group, or, R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which they bond, R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, and Y is an oxygen atom or a sulfur atom. 2. A pyrazole derivative of the general formula (2), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group. 3. A process for the preparation of a pyrazole derivative of claim 2 which comprises reacting a 3-hydroxypyrazole derivative of the general formula (3), and a compound of the general formula (4), R5-Z (4) wherein Z is a leaving group, in the presence of a base. 4. The process of claim 3, wherein R5 in the general formula (4) is a phenyl group or a pyridyl group substituted with an electron-withdrawing group such as a halogen atom, a haloalkyl group, a cyano group or a nitro group. 5. A process for the preparation of a pyrazole derivative of the general formula (2b), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, and R5a is a hydrogen atom, an optionally substituted phenyl group or an optionally substituted pyridyl group and R2a is a halogen atom, which comprises halogenating a pyrazole derivative of the general formula (2a), 6. A process for the preparation of a pyrazole derivative of the general formula (1a) in the present invention, wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R5a is a hydrogen atom, an optionally substituted phenyl group or an optionally substituted pyridyl group and R2a is a halogen atom, Y is an oxygen atom or a sulfur atom, and R3a is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, which comprises reacting a pyrazole derivative of the general formula (2c), and isocyanate or isothiocyanates of the general formula (5), R3a—NCY (5) optionally in the presence of a base. 7. A process for the preparation of a pyrazole derivative of the general formula (1b), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R3a is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, and which comprises reacting a 3-hydroxypyrazole derivative of the general formula (3a), and a compound of the general formula (4), R5-Z (4) wherein Z is a leaving group, in the presence of a base. 8. A process for the preparation of a pyrazole derivative of the general formula (1c), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R3a is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, and Y is an oxygen atom or a sulfur atom, R4a is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms or an optionally substituted alkynyl group having 3 to 6 carbon atoms, which comprises reacting the thus-obtained pyrazole derivative of the general formula (1b), and a compound of the general formula (6), R4a-Z (6) wherein Z is a leaving group, in the presence of a base. 9. A process for the preparation of a pyrazole-1-carboxamide derivative of the general formula (1d), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, and each of R3b and R4b is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms or an optionally substituted phenyl group, or R3b and R4b may form a heterocyclic ring together with a nitrogen atom to which they bond, which comprises reacting a pyrazole derivative of the general formula (2), and carbamic acid chlorides of the general formula (7), in the presence of a base. 10. A pyrazole derivative of the general formula (2d), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group. 11. A process for the preparation of a pyrazole derivative of claim 10, which comprises reacting a pyrazole derivative of the general formula (2), with phosgene or a material equivalent to phosgene. 12. A process for the preparation of a pyrazole-1-carboxamide derivative of the general formula (1e), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, R4 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms or an optionally substituted phenyl group, or, R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which they bond, R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, R3c is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, or R3c and R4 may form a heterocyclic ring together with a nitrogen atom to which they bond, which comprises reacting a pyrazole derivative of the general formula (2d) as an intermediate in production, with amines of the general formula (8) optionally in the presence of a base. 13. A process for the preparation of a pyrazole derivative of the general formula (1g), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R3 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, R4 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms or an optionally substituted phenyl group, or, R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which they bond, R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, Y is an oxygen atom or a sulfur atom, and and R2b is a halogen atom, which comprises halogenating a pyrazole derivative of the general formula (1f), 14. A process for the preparation of a pyrazole-1-carboxamide derivative of the general formula (1i), wherein R1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms or an optionally substituted phenyl group, R2 is a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 6 carbon atoms, R3 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms, an optionally substituted phenyl group, an optionally substituted alkyloxy group having 1 to 6 carbon atoms, an optionally substituted cycloalkyloxy group having 3 to 8 carbon atoms, an optionally substituted aralkyloxy group having 7 to 11 carbon atoms, an optionally substituted alkenyloxy group having 3 to 6 carbon atoms, an optionally substituted alkynyloxy group having 3 to 6 carbon atoms or an optionally substituted phenyloxy group, R4 is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted aralkyl group having 7 to 11 carbon atoms, an optionally substituted alkenyl group having 3 to 6 carbon atoms, an optionally substituted alkynyl group having 3 to 6 carbon atoms or an optionally substituted phenyl group, or, R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which they bond, and R5 is an optionally substituted phenyl group or an optionally substituted pyridyl group, which comprises oxidizing a pyrazole-1-carbothioamide derivative of the general formula (1h), 15. A herbicide containing, as an active ingredient, a pyrazole derivative of claim 1 |
<SOH> TECHNICAL BACKGROUND <EOH>Conventionally, there are known a number of pyrazole derivatives having pesticidal activity such as herbicidal activity or insecticidal activity. However, nothing has been reported on any pyrazole derivative having a substituted oxy group at the 3-position of a pyrazole ring and a substituted carbamoyl group or a substituted thiocarbamoyl group on a nitrogen atom at the 1-position as shown in the following general formula (1) in the present invention, nor is there any report on biological activities thereof. As pyrazole derivatives structurally similar to the pyrazole derivative (1) of the present invention, there are known pyrazole derivatives described in WO97/24332 (EP876351, JP2000/502686, U.S. Pat. No. 6,075,149) and EP256667 (JP63/044571, U.S. Pat. No. 5,374,644). However, these pyrazole derivatives are completely different from the pyrazole derivative (1) of the present invention in that they have an alkyl group on a nitrogen atom of their pyrazole ring. Further, it is described that the pyrazole derivatives described in the above WO97/24332 and EP256667 have pesticidal activity against fungi and harmful insects, but these Publications describe nothing concerning any other biological activity. |
Composite structures of membranes that are selectively permeable to hydrogen and combustible gas processors using same |
The invention relates to a composite structure consisting of a relatively long filtration bar comprising, from the outside, an ultra-thin layer (26) that is selectively permeable to hydrogen and made from palladium or silver alloy. Said layer is disposed on a permeable, rigid, refractory substrate consisting of a more or less solid body (30) that is covered with an intermediary thin layer (28) having a relatively smooth surface. The body (30) and the intermediary layer (28) are made respectively by sintering with fine and ultra-fine Inconel grains. A rigid metallic axial structure (32) is embedded in the body (30). Veinlets (31), which are made in the body (30) through the destruction of thermo-destructible wires during sintering, increase the permeability of the substrate. The invention is particularly applicable to hydrogen-producing combustible gas processors. |
1. Improved composite membrane structure selectively permeable to hydrogen (10-24-40) constituted by a continuous filtering film (12-26-42) measuring several microns thick and made of palladium or a palladium-based alloy deposited on a rigid porous refractory substrate (1-30-46) connected to a pipe (20-34-52) for collecting the extracted hydrogen, characterised in that: said substrate is a permeable sintered metallic body (16-30-46) provided with good mechanical resistance or open pores measuring between several microns and about ten microns; a thin metallic film (14-28-44) known as the intermediate film with a thickness of between twenty and fifty microns and containing open pores smaller than one micron is deposited on the body of the substrate; the body of the substrate and the intermediate film are made of a metal or alloy having within the range of use temperatures and pressures of the structure, heat expansion coefficients in the presence of hydrogen which are both compatible with those of palladium; the material constituting the intermediate film has within said range a satisfactory chemical stability with regard to the filtering film and the body of the substrate. 2. Membrane structure selectively permeable to hydrogen according to claim 1, characterised in that the heat expansion coefficient of the materials constituting the body of the substrate and the intermediate film is lower than or at the most slightly greater than that of the material constituting the filtering film. 3. Membrane structure selectively permeable to hydrogen according to claim 2, characterised in that: the ultra-thin filtering film (12-26-42) is made of a palladium-based alloy including silver and/or nickel; the sintered body (16-30-46) of said substrate is embodied from a relatively fine powder with appropriate size grading formed from a nickel-based super-alloy including chromium and iron and in particular from an Inconel 600 powder; the intermediate film (14-28-44) is embodied from an ultra-fine powder with suitable size grading of nickel or a super-alloy similar to the one used for the body of the substrate; the filtering film is fixed by microwelds to the tops of the surface grains of the intermediate film. 4. Membrane structure selectively permeable to hydrogen according to one of the preceding claims, characterised in that the body (16-34-46) of said substrate comprises small veins (17-31-47) adapted to improve its permeability. 5. Membrane structure selectively permeable to hydrogen according to one of the preceding claims, characterised in that said substrate (16-30) is a cylindrical rod (10-24) provided at one extremity with a collar (20-34) for evacuating the extracted hydrogen and, if appropriate, equipped with a vector gas feed collar (22-36) at the other extremity. 6. Membrane structure according to claim 5, characterised in that said cylindrical rod (24a-b-c) is relatively long and comprises a rigid axial metallic reinforcement (32a-b-c) adapted to give it good mechanical resistance. 7. Membrane structure selectively permeable to hydrogen, characterised in that it is in the form of a grid, preferably square and relatively large, constituted by a relatively large number of rods according to claim 6, said rods being placed a small distance from one another and mounted fixed on two hollow transversal beams (71-73) respectively allocated to the collection of the extracted hydrogen and vector gas feeding. 8. Membrane structure according to claim 7, characterised in that said relatively long rod (24c) is of the glove-finger type with vector gas injection, its axial reinforcement (32c) is hollow and allocated to said injection and opens into a cavity (38) provided in a cupel (40) welded to said other extremity. 9. Membrane structure selectively permeable to hydrogen according to one of claims 1 to 4, characterised in that said substrate, which includes a porous body (46) and an intermediate film (44), is a sealed plate fitted in a metallic border (48a-b) provided with an orifice connected to a pipe (52a-b) for evacuating the extracted hydrogen and, if appropriate, to another orifice opposite the first connected to a vector gas feeding pipe (50a-b). 10. Membrane structure according to claim 9, characterised in that said plate has relatively large dimensions, said substrate being provided with a rigid metallic internal reinforcement (49) adapted to give it good mechanical resistance. 11. Combustible gas processor (54-65-91) in which a cold plasma reaction chamber (58-66-92) fed in suitable conditions by a conditioning cell (88) supplying a primary mixture of said gas, water vapour and air provides a secondary mixture formed of hydrogen and carbon dioxide and carbon monoxide, characterised in that: said chamber (58-66-92) comprises several membrane structures selectively permeable to hydrogen (64-68-94) according to one of claims 1 to 10 and connected to a common hydrogen collector (76), said structures having a given shape and dimensions; placed close to these structures is/are one or several electrodes provided with a nonconducting refractory sheath (60-62, 68a-b, 96a-b) having a high dielectric coefficient and an adapted shape and dimensions enabling them to effectively cooperate with said structures so as to constitute a unit intended to produce in response to an appropriate electric power source (84) barrier electric discharges generating said cold plasma in the spaces separating the electrodes-and structures. 12. Combustible gas processor according to claim 11, characterised in that in the reaction chamber (65-92) each unit formed by an insulated electrode (78a-c or 96a-b) associated with a filtering structure (68a-b or 94) is followed by a unit formed by an insulated electrode (78b-d) and a basket (80a-b or 98a-b) containing catalyst granules for high temperature “water-gas shift” reaction. 13. Gas processor of the type including a reaction chamber provided with a chemical catalyst specific to the reaction concerned, characterised in that membrane structures selectively permeable to hydrogen according to one of claims 1 to 10 are placed close to said catalyst. 14. Combustible gas processor according to claim 11 or 12, characterised in that: the filtering structures (68a-b-c-d) and the insulated electrodes (78a-b-c-d) have the shape of long pencils (24a-b) assembled in grids of given dimensions, in particular square; said grids are constituted by a relatively large number of pencils almost touching fixed to two projecting beams (71-73) which are either neutral gas injection and hydrogen evacuation pipes for the filtering structures (68) or electric insulated linking conductors (79a-b) for the insulated electrodes (78), said beams (71-73) being adapted to be mounted secured to a frame installed in the reaction chamber. 15. Hydrogen purification device (100), characterised in that it includes: a filtering chamber (102) constituted by a refractory casing (106) lagged by a nonconducting coating (144) containing one or several membranes (1081 . . . n) selectively permeable to hydrogen, said device being of the type defined by one of claims 1 to 10, said membranes being connected to two common pipes (110-122) respectively allocated to vector gas feeding and collection of the extracted hydrogen; heating (118-120-126), temperature adjustment (140-142-138) and compression (130) means adapted to provide the flow of hydrogen to be purified with a temperature and pressure respectively situated inside pressure and temperature ranges corresponding to the best possible functioning of the membranes (108). 16. Hydrogen purification device according to claim 15, characterised in that: said heating means include a boiler (116) and a burner (118) associated with high thermic conduction heating pipes (120) passing through the boiler (116); the boiler (116) is fed with excess pressure by the hydrogen to be purified and communicates with the filtering chamber (102) via a perforated wall (122); the burner (118) is fed by the residual hydrogen evacuated downstream of the filtering chamber (102) by a collecting pipe (136) and by the compressed air provided by a compressor (138) whose flow is dependent on a regulation device (142) controlled by a signal delivered by a thermo couple (140) placed in the filtering chamber (102); the chimney (126) of the burner (118) has a ring-shaped section, surrounds the filtering chamber (102) and is lagged by the nonconducting coating (144). |
Isocyanate composition and its use in the preparation of expanded polyurethane with improved physico-mechanical properties |
Isocyanate compositions with isocyanate functionality between 2.2 and 2.9 which include: a) 20 to 80% by weight of the reaction product of methylene diphenyl isocyanate (MDI) with an ethylene oxide (EO)/propylene oxide (PO) polyether polyol of functionality 2 to 8, an average molecular weight of 200 to 6000, and an ethylene oxide content of 20 to 90% having a free NCO group content of 26 to 33% by weight; and 20 to 80% by weight of an MDI polymer. |
1. An isocyanate composition having an isocyanate functionality of 2.2 to 2.9 which comprises: a) 20 to 80% by weight of the reaction product of methylene diphenyl isocyanate (MDI) with at least one polyether polyol comprising ethylene oxide (EO) and propylene oxide (PO) with a functionality of 2 to 8, an average molecular weight of 200 to 6000 and an ethylene oxide content of 20 to 90% by weight and in which said reaction product has a free NCO group content of 26 to 33% by weight; and b) 10 to 80% by weight of a polymeric methylene diphenyl isocyanate having a general formula (I): where Φ represents a phenyl group and n is a whole number greater than or equal to 1. 2. An isocyanate composition according to claim 1 which comprises 30 to 70% by weight of component a) wherein the at least one polyether polyol has an average molecular weight of 400 to 6000 and 10 to 70% by weight of component b) and 5 to 30% by weight of modified methylene diphenyl isocyanate uretonimine. 3. An isocyanate composition according to claim 1 in which the at least one polyether polyol comprises a mixture comprising a first polyether polyol having an average molecular weight of 1000 to 6000 and a second polyether polyol having an average molecular weight of less than 1000, wherein the first and second polyols, independently comprise ethylene oxide and propylene oxide with a functionality of 2 to 8, and an ethylene oxide content of 20 to 90% by weight and the second polyether polyol is present at a concentration of less than 50% by weight relative to the first polyol. 4. An isocyanate composition according to claim 1 in which the methylene diphenyl isocyanate comprises a mixture of the 4,4′ and 2,4′ MDI isomers, in which the 2,4′ isomer concentration is from 20% to 30% based on the total amount of MDI. 5. An isocyanate composition according to claim 1 in which the at least one polyether polyol comprises a polyether diol. 6. An isocyanate composition according to claim 5 in which the polyether diol has an ethylene oxide content of 50 to 75% or 80% and especially 70 to 80%. 7. An isocyanate composition according to claim 1 in which component a) comprises the reaction product of MDI comprising 20 to 30% of the 2,4′-MDI isomer and a polyether diol polyether diol having an ethylene oxide content of 70 to 80% in which the reaction product has a free NCO group content of 29 to 33%. 8. An isocyanate composition according to claim 1 in which the methylene diphenyl isocyanate and the polymeric methylene diphenyl isocyanate are both reacted with the at least one polyether polyol. 9. A process for the preparation of a flexible expanded polyurethane which comprises reacting together: i) an isocyanate composition having an isocyanate functionality of 2.2 to 2.9 which comprises: a) 20 to 80% by weight of the reaction product of methylene diphenyl isocyanate (MDI) with at least one polyether polyol comprising ethylene oxide (EO) and propylene oxide (PO) with a functionality of 2 to 8, an average molecular weight of 200 to 6000 and an ethylene oxide content of 20 to 90% by weight in which said reaction product has a free NCO group content of 26 to 33%; and b) 20 to 80% by weight of a polymeric methylene diphenyl isocyanate having a general formula (I): where Φ represents a phenyl group and n is a whole number greater than or equal to 1; and ii) a polyol component comprising at least one polyol, with a functionality of 2 to 8 and an equivalent weight of 200 to 2000 and water. 10. A process according to claim 9 in which the isocyanate composition is as defined in claim 1. 11. A process according to claim 9 in which the isocyanate composition comprises a reaction product of MDI with 20 to 30% of the 2,4′-MDI isomer and a polyether diol having an ethylene oxide content of 70 to 80% in which the reaction product has a free NCO group content of 29 to 33%. 12. A process according to claim 9 in which, in i), the methylene diphenyl isocyanate and the polymeric methylene diphenyl isocyanate are both reacted with the at least one polyether polyol. 13. A process according to claim 12 in which at least one polyol and the polyol to be reacted with the isocyanate composition are the same and optionally the MDI and polymeric MDI are reacted with the polyether polyol to produce the expanded polyurethane in a single step. 14. A process according to claim 9 in which the water is between 3 and 6 parts by weight to 100 parts of the polyol component. 15. Use of an isocyanate composition according to claim 1 in the preparation of an expanded polyurethane having a density up to 50 Kg/m3, a bearing capacity greater than 40 N, according to ISO 2439-97, a % thickness loss of less than 5% and a % compression resistance loss of less than 16% when tested under Peugeot Test Method D42.1047-84. |
Optical pickup apparatus |
An optical pickup apparatus for detecting a symmetric S-shaped signal to obtain a focus-error signal by an SSD method for stability in operation is provided. In an optical pickup apparatus for irradiating laser light onto an optical recording medium and for directing the light reflected from at least the optical recording medium to a light-receiving device section through a diffraction element to detect a focus-error signal by a spot size detection method using diffracted light caused by the diffraction element, the position of the light-receiving device section is set to the position offset closer to the diffraction element from the focal position of the 0 order light passing through the diffraction element. |
1. An optical pickup apparatus which irradiates laser light onto an optical recording medium and directs light reflected from at least the optical recording medium to a light-receiving device section through a diffraction element and detects a focus-error signal by a spot size detection method using diffracted light caused by the diffraction element, wherein the position of the light-receiving device section is set to a position offset closer to the diffraction element from a focal position of 0 order light passing through the diffraction element. 2. An optical pickup apparatus according to claim 1, wherein the position of the light-receiving device section is offset closer to the diffraction element from the focal position of the 0 order light passing through the diffraction element as long as the following relation is substantially satisfied: (NA[+1]/NA[−1])<(D2/D1)≦(NA[+1]/NA[−1])2 where NA[+1] indicates a numerical aperture of +1 order light diffracted by the diffraction element; NA[−1] indicates a numerical aperture of −1 order light diffracted by the diffraction element; D1 indicates a distance from a focal position of the +1 order light diffracted by the diffraction element to the light-receiving device section; and D2 indicates a distance from a focal position of the −1 order light diffracted by the diffraction element to the light-receiving device section. 3. An optical pickup apparatus according to claim 1, wherein the position of the light-receiving device section is offset closer to the diffraction element from the focal position of the 0 order light passing through the diffraction element so that the following relation is substantially satisfied: (D2/D1)=(NA[+1]/NA[−1])2 where NA[+1] indicates a numerical aperture of +1 order light diffracted by the diffraction element; NA[−1] indicates a numerical aperture of −1 order light diffracted by the diffraction element; D1 indicates a distance from a focal position of the +1 order light diffracted by the diffraction element to the light-receiving device section; and D2 indicates a distance from a focal position of the −1 order light diffracted by the diffraction element to the light-receiving device section. 4. An optical pickup apparatus according to claim 1, wherein the light-receiving device section includes a light-receiving device corresponding to +1 order light diffracted by the diffraction element, and a light-receiving device corresponding to −1 order light diffracted by the diffraction element, each light receiving device being divided into three or five light-receiving regions, and a width of a center light-receiving region of the light-receiving device corresponding to the +1 order diffracted light is different in size from a width of a center light-receiving region of the light-receiving device corresponding to the −1 order diffracted light in order so as to compensate for a deviation between a focal position on the optical recording medium and a position of the an origin of the focus-error signal. 5. An optical pickup apparatus according to claim 4, wherein a ratio of the width (s1) of the center light-receiving region of the light-receiving device corresponding to the +1 order diffracted light to the width (s2) of the center light-receiving region of the light-receiving device corresponding to the −1 order diffracted light is substantially set as follows: s1:s2=(D1/NA[−1]):(D2/NA[+1]) where NA[+1] indicates a numerical aperture of the +1 order light diffracted by the diffraction element; NA[−1] indicates a numerical aperture of the −1 order light diffracted by the diffraction element; D1 indicates a distance from a focal position of the +1 order light diffracted by the diffraction element to the light-receiving device section; and D2 indicates a distance from a focal position of the −1 order light diffracted by the diffraction element to the light-receiving device section. 6. An optical pickup apparatus according to claim 4, wherein a ratio of the width (s1) of the center light-receiving region of the light-receiving device corresponding to the +1 order diffracted light to the width (s2) of the center light-receiving region of the light-receiving device corresponding to the −1 order diffracted light is substantially set as follows: s1:s2=NA[−1]:NA[+1] where NA[+1] indicates a numerical aperture of the +1 order light diffracted by the diffraction element; and NA[−1] indicates a numerical aperture of the −1 order light diffracted by the diffraction element. |
<SOH> BACKGROUND ART <EOH>Optical pickup apparatuses for detecting a focus-error signal by a spot size detection method (SSD method) using diffracted light caused by a diffraction element are known. Such an optical pickup apparatus is described with reference to FIGS. 6 through 8 . FIG. 6 illustrates an example structure of an optical pickup apparatus for detecting a focus-error signal by an SSD method. A laser beam emitted from a laser light source 21 such as a laser diode reaches an objective lens 23 through a beam splitter 22 , and is irradiated via the objective lens 23 onto an information recording surface of an optical recording medium 10 such as an optical disc. The light reflected from the optical recording medium 10 returns to the beam splitter 22 through the objective lens 23 , the optical path thereof being refracted by the beam splitter 22 , and is directed to a diffraction element 24 . The reflected light is divided by the diffraction element 24 into the 0 order light passing therethrough, and +1 order light (diffracted light) and −1 order light (diffracted light) diffracted by the diffraction element 24 . The 0 order light, the +1 order light, and the −1 order light reach a light-receiving device section 25 . In the light-receiving device section 25 , for example, light-receiving patterns shown in FIG. 8 are formed. A light-receiving device 31 has a light-receiving region E corresponding to the 0 order light. A light-receiving device 32 has three divided light-receiving regions A, S 1 , and B, and corresponds to the +1 order light. A light-receiving device 33 also has three divided light-receiving regions C, S 2 , and D, and corresponds to the −1 order light. Each of the light-receiving regions E, A, S 1 , B, C, S 2 , and D of the light-receiving devices 31 , 32 , and 33 outputs an electrical signal having a current level corresponding to the light intensity of the incident light. The electrical signal output from each of the light-receiving devices 31 , 32 , and 33 is supplied to a matrix amp (not shown) for processing, such as current-to-voltage conversion, amplification, and matrix calculation, thereby generating a required signal. That is, a playback signal, focus-error signal, tracking error signal, etc., corresponding to the information recorded in the optical recording medium 10 are generated. The objective lens 23 is held by a two-axis mechanism (not shown) having a focus coil and a tracking coil so as to be displaceable in the near-and-apart direction with respect to the optical recording medium 10 (focusing direction) and in the direction transverse to the track orientation of the optical recording medium (tracking direction). A focus drive signal is generated by a servo circuit (not shown) based on the focus-error signal to drive the focus coil of the two-axis mechanism, so that the objective lens 23 is driven in the focusing direction so as to be focused with respect to the optical recording medium 10 . A tracking drive signal is further generated by the servo circuit based on the tracking error signal to drive the tracking coil of the two-axis mechanism, so that the objective lens 23 is driven in the tracking direction so as to track with respect to the optical recording medium 10 . In the SSD method, the focus-error signal is generated according to the spot size of the diffracted light. In the focused state shown in FIG. 8 ( a ), the spot size of the +1 order light incident on the light-receiving device 32 is equivalent to the spot size of the −1 order light incident on the light-receiving device 33 . On the other hand, in the defocused state where the objective lens 23 is too close to or too far from the optical recording medium 10 , as shown in FIGS. 8 ( b ) and 8 ( c ), the spot size of the +1 order light incident on the light-receiving device 32 is different from the spot size of the −1 order light incident on the light-receiving device 33 . Accordingly, by comparing the spot sizes on the light-receiving devices 32 and 33 , the focus-error signal can be generated. More specifically, the focus-error signal is generated by, in the subsequent matrix amp, calculating (A+B+S 2 )−(C+D+S 1 ) on the outputs of the light-receiving regions A, S 1 , B, C, S 2 , and D. In general, when the objective lens 23 moves from the position most distant from the optical recording medium 10 to the position closest thereto, as known in the art, in the focus-error signal, a so-called S-shaped curve shown in FIG. 7 is observed in the vicinity of the focused position. A substantially linear region from peak P 1 to peak P 2 in the curve corresponds to a so-called in-focus region. In basic operation, when the objective lens 23 is positioned within the in-focus region, a focus servo controls the position of the objective lens 23 to be brought to the position of the origin of the S-shaped curve (i.e., the position where focus error=0) based on the focus-error signal. As shown in FIG. 7 , it is assumed herein that the distance of the in-focus region of the S-shaped signal is indicated by d. In other words, “d” is defined as the displacement distance of the optical recording medium (the distance by which the optical recording medium changes with respect to the position of the objective lens) when the S-shaped signal varies from the peak P 1 to the peak P 2 . Furthermore, one-side in-focus regions d 1 and d 2 of the S-shaped curve with respect to the origin of the S-shaped curve are defined as the displacement distances of the optical recording medium when the S-shaped signal goes from the origin of the S-shaped curve to the peaks P 1 and P 2 of the S-shaped curve, respectively. Then, the following equation holds true: in-line-formulae description="In-line Formulae" end="lead"? d=d 1 +d 2 Formula (1) in-line-formulae description="In-line Formulae" end="tail"? The origin of the S-shaped curve coincides with the focal position on the optical recording medium. This relationship is established, in the standard SSD method, when the diffracted light (the +1 order light and the −1 order light) diffracted by the diffraction element 24 has the same spot diameter r, as shown in FIG. 8 ( a ), resulting in substantial coincidence with the focal position of the 0 order light (strictly speaking, however, it is shifted towards the diffraction element 24 by L·cos θ, where θ denotes the angle of diffraction and L denotes the distance between the diffraction element 24 and the light-receiving device section 25 ). It is assumed herein that the NA (numerical aperture) of the objective lens 23 is indicated by NA[L]. It is further assumed that the NA of the 0 order light in the light focused at the light-receiving device section 25 which passes through the diffraction element 24 is indicated by NA[0]. It is still further assumed that the NAs of the +1 order light and the −1 order light diffracted by the diffraction element 24 are indicated by NA[+1]′ and NA[−1]′, respectively. It is also assumed that the NAs are so small that the following approximation applies: NA=sin θ=tan θ=θ. Then, the following relationship is obtained: in-line-formulae description="In-line Formulae" end="lead"? NA[−1]′<NA[+1]′ Formula (2) in-line-formulae description="In-line Formulae" end="tail"? Thus, the following relationship holds true: in-line-formulae description="In-line Formulae" end="lead"? NA[− 1 ]′+NA[+ 1]′=2 ·NA[L] Formula (3) in-line-formulae description="In-line Formulae" end="tail"? As shown in FIG. 6 , the distances from the position of the light-receiving device section 25 (the focal position of the 0 order light) to the focal positions of the diffracted light (the +1 order light and the −1 order light) diffracted by the diffraction element 24 are indicated by D11 and D12, respectively. Then, the above-noted one-side in-focus regions d 1 and d 2 of the S-shaped curve can be approximated as follows: in-line-formulae description="In-line Formulae" end="lead"? d 1={(½)· D 11·( NA[+ 1]′) 2 }/( NA[L ]) 2 Formula (4) in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? d 2={(½)· D 12·( NA[− 1]′) 2 }/( NA[L ]) 2 Formula (5) in-line-formulae description="In-line Formulae" end="tail"? Since the spot diameters r of the diffracted light on the light-receiving devices 32 and 33 on the origin of the S-shaped curve are the same, the following equation is obtained: r / 2 = D11 · NA [ + 1 ] ′ = D12 · NA [ - 1 ] ′ Formula ( 6 ) Therefore, the following relationship holds true from Formula (6): in-line-formulae description="In-line Formulae" end="lead"? D 11 /D 12 =NA[− 1 ]′/NA[+ 1]′ Formula (7) in-line-formulae description="In-line Formulae" end="tail"? If NA[0]=NA[+1]′=NA[−1]′ can be approximated, D11 is equal to D12, and the following equation is obtained from Formulas (4) and (5): in-line-formulae description="In-line Formulae" end="lead"? d 1 /d 2=1 Formula (8) in-line-formulae description="In-line Formulae" end="tail"? Thus, the following relationship is obtained between the diffracted light (the +1 order light and the −1 order light) and the 0 order light: in-line-formulae description="In-line Formulae" end="lead"? NA[+ 1 ]′=L /( L−D 11)· NA[ 0] Formula (9) in-line-formulae description="In-line Formulae" end="tail"? in-line-formulae description="In-line Formulae" end="lead"? NA[− 1 ]′=L /( L+D 12)· NA[ 0] Formula (10) in-line-formulae description="In-line Formulae" end="tail"? If the distance L between the diffraction element 24 and the light-receiving device section 25 is sufficiently large, or if the distances D11 and D12 are sufficiently small, Formula (8) holds true. If the above-noted approximation does not apply, however, the relationship NA[0]=NA[+1]′=NA[−1]′ does not hold true, and Formula (11) rather than Formula (8) is obtained: d1 / d2 = ( NA [ + 1 ] ′ ) 2 / ( NA [ - 1 ] ′ ) 2 · ( D11 / D12 ) = NA [ + 1 ] ′ / NA [ - 1 ] ′ Formula ( 11 ) In this case, an asymmetric in-focus region of the S-shaped curve is exhibited. That is, the in-focus region shown in FIG. 7 is exhibited. An asymmetric S-shaped curve means instability in gain of a focus servo signal or an asymmetric focus margin, and is disadvantageous in view of the stability in recording to and playback from an optical recording medium. In a device supporting a high-density recording medium, the objective lens 23 has a high NA. In order to accomplish the same in-focus region d of the S-shaped curve as that described above, as is understood from Formulas 4 and 5, the focal change distance D11 (D12) with respect to the diffraction element 24 must increase as the numerical aperture (NA[L]) of the objective lens 23 increases. This further results in a greater amount of change in the NA of the diffracted light diffracted by the diffraction element 24 than that of the 0 order light, as is given by Formulas 9 and 10. In an optical pickup apparatus which includes the objective lens 23 having a high NA, therefore, a more asymmetric in-focus region of the S-shaped curve is exhibited. Furthermore, desirably, the distance L from the diffraction element 24 to the light-receiving device section 25 should be reduced in order to reduce the size of the optical pickup apparatus. However, as is understood from Formulas 9 and 10, as the distance L from the diffraction element 24 to the light-receiving device section 25 becomes shorter, the amount of change in the NA of the diffracted light diffracted by the diffraction element 24 becomes greater than that of the 0 order light. Thus, this case also results in a more asymmetric in-focus region of the S-shaped curve. As described above, an optical pickup apparatus which obtains a focus-error signal by the SSD method using a diffraction element has a problem of such an asymmetric in-focus region of the S-shaped curve. A noticeably asymmetric in-focus region of the S-shaped curve is exhibited, resulting in a large problem, particularly in an optical pickup apparatus which includes the objective lens 23 having a high NA and in which the distance L from the diffraction element 24 to the light-receiving device section 25 is small, that is, a compact optical pickup apparatus used for high-density optical recording media. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a diagram illustrating the structure of an optical pickup apparatus according to an embodiment of the present invention. FIG. 2 is a diagram illustrating a focus-error signal obtained by the optical pickup apparatus of the embodiment. FIG. 3 is a diagram illustrating a light-receiving device in a light-receiving device section of the optical pickup apparatus of the embodiment. FIG. 4 is a diagram illustrating a modification of the light-receiving device section of the embodiment. FIG. 5 is a diagram illustrating a modification of the light-receiving device section of the embodiment. FIG. 6 is a diagram illustrating the structure of an optical pickup apparatus of the related art. FIG. 7 is a diagram illustrating a focus-error signal obtained by the optical pickup apparatus of the related art. FIG. 8 is a diagram illustrating a light-receiving device in a light-receiving device section of the optical pickup apparatus of the related art. detailed-description description="Detailed Description" end="lead"? |
Blaster lights used for signalling and/or marking purposes |
Blister lights are used for signaling and/or marking purposes. The blister lights include a housing which is embedded in a traffic area, e.g. a street, an airport runway for taking off and for landing, or the like. It further includes a housing cover by which the housing embedded in the traffic area can be closed on its upper side, the cover being detachably connected to the housing and including at least one light outlet. It additionally includes an illuminating element which is arranged in the housing and by which the light can radiate through the light outlet of the housing cover. In order to enable the illuminating element to have higher current densities and thus to enable the blister lights to have a higher light output capacity, a thermoconducting bridge is formed between illuminating element and the housing cover. By this, the thermal energy produced by the illuminating element can be conducted to the housing cover From these, the thermal energy is guided to the traffic area via the housing which is embedded therein. |
1. A blister light, for at least one of signaling and marking purposes, comprising: a housing, embeddable in a traffic area; a housing cover, by which the housing is closable at its upper side, the cover being detachably connected to the housing and including at least one light exit opening; and a luminous device, arranged in the housing, adapted to emit light through the light exit opening in the housing cover; and a thermoconducting bridge, formed between the luminous device and the housing cover, adapted to conduct thermal energy produced by the luminous device to the housing cover. 2. The blister light as claimed in claim 1, wherein the luminous device includes at least one power LED. 3. The blister light as claimed in claim 1, wherein the luminous device includes at most six power LEDs per light exit opening. 4. The blister light as claimed in claim 2, wherein a collimator element is assigned to the at least one power LED. 5. The blister light as claimed in claim 2, wherein the at least one power LED is seated with its carrier plate on a base plate fitted on at least one cover inner part connected to an underside of the housing cover, and forms, with said cover inner part, the thermoconducting bridge to the housing, cover. 6. The blister light as claimed in claim 5, wherein the base plate is connected to the underside of the housing cover via two cover inner parts, arranged on both sides of the carrier plate. 7. The blister light as claimed in claim 6, wherein the two cover inner parts are arranged on the end sections of the base plate. 8. The blister light as claimed in claim 5, wherein each cover inner part bears against the base plate in two dimensions on one side, and against the underside of the housing cover in two dimensions on the other side. 9. The blister light as claimed in claim 5, wherein the mutually assigned bearing surfaces on the side of the cover inner part and of the base plate, and the mutually assigned bearing surfaces on the side of the cover inner part and of the cover, are formed in a metallically smooth fashion. 10. The blister light as claimed in claim 1, wherein the mutually assigned bearing surfaces, on the side of the cover and of the housing, are formed in a metallically smooth fashion. 11. The blister light as claimed in claim 5, wherein the base plate is formed from a material having a high coefficient of thermal conductivity. 12. The blister light as claimed in claim 5, wherein the carrier plate of the power LED is formed from a material having a high coefficient of thermal conductivity. 13. The blister light as claimed in claim 5, wherein at least one cover inner part is formed from a material having a high coefficient of thermal conductivity. 14. The blister light as claimed in claim 3, wherein a collimator element is assigned to at least one power LED. 15. The blister light as claimed in claim 3, wherein at least one power LED is seated with its carrier plate on a base plate fitted on at least one cover inner part connected to an underside of the housing cover, and forms, with said cover inner part, the thermoconducting bridge to the housing, cover. 16. The blister light as claimed in claim 4, wherein the at least one power LED is seated with its carrier plate on a base plate fitted on at least one cover inner part connected to an underside of the housing cover, and forms, with said cover inner part, the thermoconducting bridge to the housing, cover. 17. The blister light as claimed in claim 15, wherein the base plate is connected to the underside of the housing cover via two cover inner parts, arranged on both sides of the carrier plate. 18. The blister light as claimed in claim 16, wherein the base plate is connected to the underside of the housing cover via two cover inner parts, arranged on both sides of the carrier plate. 19. The blister light as claimed in claim 6, wherein each cover inner part bears against the base plate in two dimensions on one side, and against the underside of the housing cover in two dimensions on the other side. 20. The blister light as claimed in claim 7, wherein each cover inner part bears against the base plate in two dimensions on one side, and against the underside of the housing cover in two dimensions on the other side. 21. The blister light as claimed in claim 6, wherein the mutually assigned bearing surfaces on the side of the cover inner part and of the base plate, and the mutually assigned bearing surfaces on the side of the cover inner part and of the cover, are formed in a metallically smooth fashion. 22. The blister light as claimed in claim 7, wherein the mutually assigned bearing surfaces on the side of the cover inner part and of the base plate, and the mutually assigned bearing surfaces on the side of the cover inner part and of the cover, are formed in a metallically smooth fashion. 23. The blister light as claimed in claim 2, wherein the mutually assigned bearing surfaces, on the side of the cover and of the housing, are formed in a metallically smooth fashion. 24. The blister light as claimed in claim 3, wherein the mutually assigned bearing surfaces, on the side of the cover and of the housing, are formed in a metallically smooth fashion. 25. The blister light as claimed in claim 5, wherein the base plate is formed from a metal. 26. The blister light as claimed in claim 5, wherein the carrier plate of the power LED is formed from a metal. 27. The blister light as claimed in claim 1, wherein the traffic area includes at least one of a road, an airport taxiway, and an airport runway. 28. The blister light as claimed in claim 1, wherein the thermal energy is dissipatable to the traffic area via the housing, upon the housing being embedded in the traffic area. 29. A blister light, comprising: a housing, embeddable in a traffic area; a housing cover, detachably connected to the housing and including at least one opening; luminous means, arranged in the housing, for emitting light through an opening in the housing cover; and thermoconducting means, between the luminous means and the housing cover, for conducting thermal energy produced by the luminous means to the housing cover. 30. The blister light as claimed in claim 29, wherein the thermal energy is dissipatable to the traffic area via the housing, upon the housing being embedded in the traffic area. 31. The blister light as claimed in claim 29, wherein the luminous means includes at least one power LED. 32. The blister light as claimed in claim 29, wherein the luminous means includes at most six power LEDs per light exit opening. |
<SOH> BACKGROUND OF THE INVENTION <EOH>In known blister lights, in which use is also made as luminous device of, inter alia, LEDs (light-emitting diodes), the quantity of heat produced during operation of the luminous device is usually transferred by convection into a gas, which is often air. In some known blister lights, the luminous device is assigned a heat sink starting from which the quantity of heat produced during operation of the luminous device is given off to the gas or air by convection. Because of the limited spatial conditions prevailing in blister lights, even blister lights equipped with a heat sink with low heat transfer resistance have a total heat transfer resistance of usually more than 30 K/W power loss. In the use, known from the prior art, of LEDs mounted on PC plates, a heat transfer resistance of more than 150 K/W results between the barrier layer of the LEDs and the PC plate. In some automotive applications, a heat transfer resistance of the order of approximately 70 K/W is achieved. These high heat transfer resistances, which accompany maximum temperatures of the barrier layers that are usually of the order of magnitude of a little above 120° C., limit the current density possible and/or permissible during operation of the blister light. They thus produce, in a corresponding way, a limitation of the light-emitting power of the LEDs that can be achieved per unit of area of the barrier layer. In the case of freely arranged lighting devices, for example traffic lights or the like, this limitation of the emitting power per unit of area is compensated by an increase in the area used for the emission of light and in the number of the light-emitting diodes. This enlargement of the light-emitting area is not practicable for blister lights, since blister lights are embedded in the traffic area. Further, since the emitting area of a blister light that is available in total for the emission of light is limited by the projection of the blister light above the surface of the traffic area, it is necessary for this projection to be as small as possible owing to a multiplicity of technically and mechanically conditioned requirements placed on the blister light. |
<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of an embodiment of the invention to provide a blister light, in the case of which the light-emitting power can be increased without increasing the light-emitting area, without exceeding permissible barrier surface temperatures of the luminous device or reducing the service life of the luminous device. An object may be achieved according to an embodiment of the invention, by virtue of the fact that formed between the luminous device and the housing cover of the blister light is a thermoconducting bridge. By this bridge, thermal energy produced by the luminous device can be conducted to the housing cover. Starting from this, the thermal energy can be dissipated to the traffic area via the housing embedded in the traffic area. Owing to this configuration of the blister light with a thermoconducting bridge connecting the luminous device to the housing cover or the housing, it is possible to optimize the light output power by using a higher current density in the luminous device. This occurs since the thermal energy occurring can be given off to the traffic area by creating a thermal dissipation path with a low heat transfer resistance, such that the temperatures at the barrier layers of the luminous device remain in the permissible range, and the service life of the luminous means is not reduced. The capacitance of the traffic area for absorbing thermal energy is virtually unlimited, the traffic area having, moreover, a very large surface for emitting heat. According to an embodiment of the invention, the traffic area is used like a heat sink of unlimited absorptive capacity by virtue of the fact that the barrier layer of the luminous device is connected to the traffic area via the outlined heat dissipation path with a low heat transfer resistance. The heat dissipation from the luminous device, by convection that is substantially less effective by comparison with the outlined heat dissipation path to the traffic area, takes place in the case of the blister light according to an embodiment of the invention only at a negligible order of magnitude. Owing to the electric current densities prevailing in the case of the inventive configuration of the blister light, it is particularly expedient when power LEDs, also termed high-intensity LEDs, are used as luminous device. The most varied requirements placed on blister lights can be fulfilled by way of such power LEDs, without particular further measures. There is a need, moreover, only for a comparatively limited number of power LEDs. These emit through a transparent emission window that is implemented by the light exit opening present in the housing cover. Owing to the high emitting power of the unit of area of the emitting area that can be realized by means of power LEDs, the requirements placed on blister lights with regard to the emitting power can be fulfilled without the projection of the blister light above the surface of the traffic area being more than 13 mm, smaller projections also being possible. The required light-emitting powers can be realized in many instances even with a single power LED provided as a luminous device. It is expedient to provide at most six power LEDs per light exit opening as the luminous device. In order to optimize still further the light output or the light-emitting power of the blister light according to an embodiment of the invention, it is expedient when a collimator element is assigned to the at least one power LED. This collimator element can be used in order to emit the optical radiation directly through the emitting window; alternatively, the light emission can be performed by means of the collimator element after a preceding reflection on a beam-shaping or beam-deflecting mirror. The respectively desired optical radiation distribution can be achieved by the use of collimators, lenses, prisms, deffractors and/or mirrors. The thermoconducting bridge between the luminous device and the housing cover can be realized in a less complicated way in technical design terms when the at least one power LED is seated with its carrier plate on a base plate that is fitted on at least one cover inner part connected to the underside of the housing cover, and forms with the cover inner part the thermoconducting bridge to the housing cover and thus to the housing. The thermoconducting bridge is advantageously formed by the base plate and two cover inner parts which are arranged on both sides of the carrier plate and can be connected to the underside of the housing cover. The two cover inner parts can be arranged on the end sections of the base plate, in which case it is advantageous that each cover inner part bears against the base plate in two dimensions on one side, and against the underside of the housing cover in two dimensions on the other side. In order to simplify the dissipation of the thermal energy from the at least one power LED to the traffic area, it is expedient when the mutually assigned bearing surfaces on the side of the cover inner part and of the base plate as well as the mutually assigned bearing surfaces on the side of the cover inner part and of the cover are formed in a metallically smooth fashion, so that the heat transfer resistance is as low as possible there. Of course, the mutually assigned bearing surfaces on the side of the cover and of the housing should correspondingly also be formed in a metallically smooth fashion. Materials with a high coefficient of thermal conductivity, for example metals, apply in particular as material for the base plate on which the power LED is seated with its carrier plate, for the carrier plate and the cover inner parts. The thermal energy produced by way of the power LED can be transferred to the traffic area, which serves as a virtually unlimited heat sink, by way of the previously outlined thermoconducting bridge of the blister light according to an embodiment of the invention. The total heat transfer resistance of the barrier layer of the power LED for the base plate is at most approximately 11 K/W; a heat transfer resistance which is less than 1.5 K/W must for this purpose be added for the heat dissipation path from the base plate to the traffic area. Although the maximum light output power is reached at a current of 350 to 1000 mA in the case of the use of power LEDs as the luminous device, the thermal energy produced in the event of the current densities resulting therefrom can be dissipated immediately in the case of the blister light according to an embodiment of the invention. |
Solarization stable borosilicate glass and uses thereof |
The invention relates to a borosilicate glass consisting of 0.01 0.05 wt. % Fe2O3 and 0.05 0.8 wt. % TiO2, which is highly resistant to solarization and which is especially suitable for use as backlight bulbs. |
1. A borosilicate glass of a composition (in weight-% and on an oxide base) of SiO2 70-80 B2O3 13-18 Al2O3 0.5-4 Li2O 0-1 Na2O 2-5 K2O 1-3 MgO 0-1 CaO 0-1 BaO 0-1 Fe2O3 0.01-0.05 TiO2 0.05-08 2. The borosilicate glass in accordance with claim 1, characterized by a composition (in weight-% on and on an oxide base) of SiO2 70-80 B2O3 13-18 Al2O3 0.5-<2 Na2O 2-5 K2O >1-3 MgO 0-1 CaO 0-1 BaO 0-1 Fe2O3 0.01-0.05 TiO2 0.05-08 3. The borosilicate glass in accordance with claim 1, characterized in that it contains at least 0.2 weight-%, preferably at least 0.2 weight-%, of TiO2. 4. The borosilicate glass in accordance with at least one of claim 1, characterized in that it additionally contains (in weight-% on and on an oxide base) ZrO2 0-1 SnO2 0-0.5 MnO2 0-0.1 Sb2O3 0-0.5 5. The borosilicate glass in accordance with at least one of claim 1, characterized in that, except for unavoidable impurities, it is free of As2O3 and PbO. 6. The borosilicate glass in accordance with at least one of claim 1, with a transmission drop at lambda=300 nm of less than 5% following the HOK-4 irradiation for 15 hours of a glass sample of 0.2 mm thickness. 7. The borosilicate glass in accordance with at least one of claim 1, with a transmission temperature Tg<520° C., with a thermal expansion coefficient α20/300 between 3.7×10−6/K and 4.2×10−6/K, a transmission tau at lambda ≦260 nm of ≦30% (with 0.2 mm sample thickness). 8. The borosilicate glass in accordance with at least one of claim 1, with a transmission temperature Tg<520° C., with a thermal expansion coefficient α20/300 between 3.7×10−6/K and 4.2×10−6/K, a transmission tau at lambda ≦260 nm of ≦0.7% (with 0.2 mm sample thickness). 9. Use of the glass in accordance with at least one of claim 1 8 for producing fluorescent tubes for the background illumination of displays. 10. Use of the glass in accordance with at least one of claim 1 8 for producing fluorescent tubes for brake lights of vehicles. 11. Use of the glass in accordance with at least one of claim 1 for producing flash tubes. 12. Use of the glass in accordance with at least one of claim 1 for producing gas discharge lamps. |
Method and device for determining a temperature variable |
A device and method for determining a temperature variable, in particular a temperature variable that characterizes the condition of an exhaust-gas treatment system of a combustion engine, are described. The temperature is specified on the basis of variables that characterize the mass flow in the exhaust-gas treatment system, and/or of a second temperature variable that characterizes the temperature upstream from the exhaust-gas treatment system. |
1-5. (canceled) 6. A method for determining at least one of a first temperature of an exhaust-gas treatment system of a combustion engine and a second temperature of an exhaust temperature downstream from the exhaust-gas treatment system, comprising: providing a first variable that characterizes an exhaust gas mass flow in the exhaust-gas treatment system; providing a second variable corresponding to a third temperature that characterizes an exhaust temperature upstream from the exhaust-gas treatment system; measuring the first temperature and the second temperature by a temperature sensor; calculating a difference between the first temperature and the second temperature; comparing at least one of the first temperature and the second temperature with a threshold value; and recognizing an error when the threshold value is exceeded. 7. The method as recited in claim 6, further comprising: determining the first variable on the basis of at least one of an air variable that characterizes a quantity of air fed to the combustion engine and a fuel variable that characterizes a mass of a fuel fed to the combustion engine. 8. The method as recited in claim 6, wherein: the first temperature and the second temperature are used in a dynamic condition of the combustion engine to control/regulate the exhaust-gas treatment system. 9. The method as recited in claim 6, wherein: the method is provided for calculating the first temperature of a particle filter contained in the exhaust-gas treatment system. 10. The method as recited in claim 6, further comprising: measuring the second temperature by another temperature sensor. |
<SOH> BACKGROUND INFORMATION <EOH>To control and/or monitor exhaust-gas treatment systems, exact knowledge of the condition, especially of the flow condition, is necessary. This condition is determined in particular by the temperature in the exhaust-gas treatment system. However, this temperature is only accurately detectable with very great effort and expense. |
<SOH> SUMMARY OF THE INVENTION <EOH>Because the temperature variable is specified on the basis of other variables that characterize the condition of the combustion engine and/or of the exhaust-gas treatment system, such as the mass flow in the exhaust-gas treatment system and a second variable that characterizes the temperature upstream from the exhaust-gas treatment system, an exact determination of the mean temperature of the particle filter and/or of the exhaust downstream from the particle filter is possible. The procedural method according to the present invention is not limited here to particle filters; it is usable with all exhaust-gas treatment systems. This also applies especially to all types of catalytic converters. Determination of the temperature variable according to the present invention makes this variable available more quickly. Rapid recognition of the condition of the particle filter is therefore possible. In particular, the degree of loading of the particle filter, or a defect in the particle filter, is recognizable significantly more quickly. Because of the earlier recognition of the condition, more precise control, regulation and/or monitoring of the exhaust-gas treatment system is possible. It is especially advantageous when the variable that characterizes the mass flow in the exhaust-gas treatment system is determined on the basis of an air variable that characterizes the quantity of air fed to the combustion engine, and/or a fuel variable which characterizes the mass of fuel fed to the combustion engine. That allows this variable to be determined very simply and precisely, without need of an additional sensor. The air variable is usually available in the control unit, since it is also used for controlling the combustion engine, especially the quantity of fuel injected and/or the quantity of air. This variable is usually measured using a sensor in the intake line of the combustion engine. The fuel variable is also a variable that is present in the control unit. For example, a variable derived from the desired moment and/or a variable derived from the actuating signal of a quantity-determining actuator may be used here. Preferably, the method is used to determine the temperature of the exhaust-gas treatment system and/or the temperature of the gases downstream from the exhaust-gas treatment system. The method according to the present invention is preferably suitable for exhaust-gas treatment systems that include at least one particle filter. At the same time, additional systems that treat the exhaust gas may be present, in addition to the particle filter. It is especially advantageous when the temperatures determined are used only in certain conditions, for example in dynamic conditions, to control and/or regulate the exhaust-gas treatment system. It is also advantageous when the temperature determined is used for error monitoring. Preferably, there may be provision for the measured values of the temperature to be compared with the calculated values, and for errors to be recognized on the basis of this comparison. |
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