Abstract: Methods and reagents are provided for determining endocytosis, using a cell expressing an externally polypeptide labeled cell membrane receptor, and as a reagent an antibody to said label conjugated to a fragment of an enzyme fragment complementation pair. Compounds are tested for their effect on endocytosis by complexing the reagent with said cells, adding the test compound at any time in relation to the complexing, allowing any endocytosis to occur, proteolytically degrading external enzyme fragment, adding protease inhibitor and the complementary member of the enzyme fragment complementation pair and substrate. The product provides a detectable signal related to the amount of endocytosis that occurred. The method is readily automated as all steps can occur in a single vessel without separations and washings.

Abstract: The invention relates to defined peptides and the quantitative determination thereof in body fluids of patients suffering from progredient chronic dementia, in relation to the concentration of said peptides in a control group. The inventive peptides come from a protein precursor having the corresponding gene, are processed in a specific manner, and are optionally post-translationally modified, especially phosphorylized. An increase in the concentrations of these peptides or the corresponding non-processed protein indicates progredient chronic dementia. Progredient chronic dementia is detected by identifying the peptides and/or the protein individually or in combinations. The invention also relates to the use of said peptides for controlling the course of progredient chronic dementia and for the prognosis of progredient chronic dementia, especially for complementing or replacing mini-mental scores, and for developing therapeutic agents to combat progredient chronic dementia such as Alzheimer's disease.

Abstract: The present invention relates to compositions and methods for cancer therapies and diagnostics, including but not limited to, cancer markers. In particular, the present invention provides tumor antigens associated with specific cancers and diagnostic assays for the detection of such antigens and associated autoantibodies as indicative of the presence of specific cancers. The present invention further provides cancer immunotherapy utilizing the tumor antigens of the present invention.

Abstract: The invention relates to the use of a fluorescent protein chosen in particular from autofluorescent proteins, for the detection of the non-covalent interactions between a target protein labeled with the fluorescent protein and one of its ligands labeled with a label consisting: either of a molecule which is capable of absorbing the light emitted by the fluorescent protein, or of a fluorescent substance, this detection taking place by fluorescence energy transfer: between the fluorescent protein and the above-mentioned fluorescent substance, the fluorescent substance being such that either it is excitable at the emission wavelength of the fluorescent protein, or it emits at the excitation wavelength of the fluorescent protein, or between the fluorescent protein and the above-mentioned molecule which is capable of absorbing the light emitted by the fluorescent protein.

Abstract: The present invention provides a simple and sensitive aqueous method for determining cholesterol in remnant-like particles in a biological sample without the separation of components of the sample. The method comprises contacting the sample with (i) cholesterol esterase, (ii) cholesterol oxidase or cholesterol dehydrogenase, and (iii) phospholipase with a surfactant that inhibits cholesterol oxidase or cholesterol dehydrogenase in lipoproteins other than remnant-like particles in the presence of oxygen or an oxidized coenzyme. Formed hydrogen peroxide or reduced coenzyme is measured and correlated to a quantitative determination of cholesterol in remnant-like particles.

Abstract: Platelet contractile force (PCF) is used as a surrogate marker of thrombin generation. PCF generation occurs concomitant with the burst of prothrombin fragment F 1+2 release. The time between assay start and PCF onset is identified as the thrombin generation time (TGT), and is used in assessing risk of bleeding, in diagnosing various disorders, and in monitoring the effects of pharmaceutical and other treatments. TGT is prolonged in clotting factor deficiencies and in the presence of direct and indirect thrombin inhibitors. TGT shortens to normal with clotting factor replacement and shortens with administration of rVIIa. TGT is short in thrombophilic states such as coronary artery disease, diabetes and thromboangiitis obliterans and prolongs toward normal with oral and intravenous anticoagulants.

Abstract: Compositions and methods are provided for the treatment of diseases associated with mitogen activated protein kinase cascades. In particular, the mitogen-activated protein kinase p38-2, and polypeptide variants thereof that stimulate phosphorylation and activation of substrates such as ATF2, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the p38-2 kinase cascade. Such polypeptides and agents may also be used for the treatment of diseases associated with mitogen-activated protein kinase cascades.

Abstract: A method for determining the level of kinase activity or phosphatase activity in a sample without the use of antibodies or radioactive labels is disclosed. The method employs a fluorescently-labeled phosphorylatable reporter peptide that is capable of being cleaved by a protease only when the peptide is in an unphosphorylated state. A change in fluorescence characteristics is an indication that the peptide is cleaved and, therefore, in an unphosphorylated state. Thus, the level of protease cleavage, as measured by the fluorescence change, provides a direct measure of phosphatase activity whereas the level of kinase activity is inversely proportion to the level of protease cleavage. The method is particularly well suited to high throughput screening, for example, for screening compounds which modulate kinase or phosphatase activity.

Abstract: Described herein are methods which identify candidate agents as binding to a protein or as a modulator of the binding characteristics or biological activity of a protein. Generally, the methods involve the use of ADP or phosphate. The assays can be used in a high throughput system to obviate the cumbersome steps of using gels or radioactive materials.

Abstract: The present invention relates to new genes encoding for the production of novel nox enzyme proteins involved in generation of reactive oxygen intermediates that affect cell division. The present invention also provides vectors containing these genes, cells transfected with these vectors, antibodies raised against these novel proteins, kits for detection, localization and measurement of these genes and proteins, and methods to determine the activity of drugs to affect the activity of the proteins of the present invention.

Abstract: The present invention relates to new genes encoding for the production of novel nox enzyme proteins involved in generation of reactive oxygen intermediates that affect cell division. The present invention also provides vectors containing these genes, cells transfected with these vectors, antibodies raised against these novel proteins, kits for detection, localization and measurement of these genes and proteins, and methods to determine the activity of drugs to affect the activity of the proteins of the present invention.

Abstract: The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encode Rhipicephalus sanguineus glutamate gated chloride channels. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encoding R. sanguineus glutamate gated chloride channels, substantially purified forms of associated R. sanguineus glutamate gated chloride channels and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associated Rhipicephalus sanguineus glutamate gated chloride channels, which will be useful as insecticides.

Abstract: Described is a novel process for the production of at least one protein of interest by secretion of the protein of interest from a pro- or eukaryotic host cell in a compartment system, which host cell is stably expressing a secretion system and capable of heterologous secretion of the protein of interest and which compartment system has at least a first and a second compartment and wherein the host cell is located in the first compartment and wherein the first and second compartment are separated from each other by a barrier, wherein the barrier is permeable for the secreted protein of interest, but not permeable for the host cell.

Abstract: The present invention provides novel polynucleotides encoding BGS-19 polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying the novel BGS-19 polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: DNAs encoding the mammalian histamine H4 receptors have been cloned and characterized. These recombinant molecules are capable of expressing biologically active histamine H4 receptor protein. The cDNA's have been expressed in recombinant host cells that produce active recombinant protein. The pharmacology of known histamine ligands is demonstrated. The recombinant protein may be purified from the recombinant host cells. In addition, recombinant host cells are utilized to establish methods to identify modulators of the receptor activity, and receptor modulators are identified.

Abstract: The invention comprises a method of screening compound(s) that inhibit the interaction between IGF-1R and IIP-10.

Abstract: Fusion protein including a fusion part and a protein of interest, the combination of the two proteins leading to the fusion protein being secreted into a supernatant of a bacterial host with the protein of interest being present in its correct three-dimensional structure. Nucleic acid including a sequence coding for a fusion protein, the sequence including: —F—Asm—Rn—Y—, where F is a nucleic acid sequence coding for an amino acid sequence which allows secretion of a protein encoded by Y into a fermentation medium, As is a chemical bond or a nucleic acid sequence comprising a codon, m is an integer from 0–10, R is a chemical bond or an arginine codon, n is 0 or 1, and Y is a nucleic acid sequence coding for a protein of interest. Processes therefor.

Abstract: According to the present invention, by using a microorganism having the ability to produce the L-amino acid which carries the avtA gene encoding alanine-valine transaminase (transaminase C) and whose alanine-valine transaminase activity is enhanced compared with its parent strain, it is possible to reduce the production of by-product amino acids which disturb purification in L-amino acid production by fermentation, and an industrially advantageous process for producing an L-amino acid can be provided.

Abstract: The invention relates to an isolated polynucleotide comprising a polynucleotide sequence chosen from the group consisting of a) polynucleotide which is identical to the extent of at least 70% to a polynucleotide which codes for a polypeptide which comprises the amino acid sequence of SEQ ID No. 2, b) polynucleotide which codes for a polypeptide which comprises an amino acid sequence which is identical to the extent of at least 70% to the amino acid sequence of SEQ ID No. 2, c) polynucleotide which is complementary to the polynucleotides of a) or b), and d) polynucleotide comprising at least 15 successive nucleotides of the polynucleotide sequence of a), b) or c), and a process for the fermentative preparation of L-amino acids using coryneform bacteria in which at least the mikE17 gene is present in attenuated form, and the use of polynucleotides which comprise the sequences according to the invention as hybridization probes.

Abstract: The present invention provides two new microorganism strains of Saccharothrix, designated as YS-44442 and YS-45494, a process of producing pravastatin using the strains, and an improved process for isolation of (HMG)-CoA reductase inhibitors.

Abstract: A process for producing rhamnolipids involving culturing Pseudomonas chlororaphis strain NRRL B-30761 in a first aqueous culture medium containing about 0.3% NH4H2PO4, about 0.2% K2HPO4, about 0.2% carbon source, about 0.5 mg/L FeSO4, and about 0.1% MgSO4 for about 24–about 48 hours at about 25°–about 30° C. with orbital shaking, and then culturing Pseudomonas chlororaphis strain NRRL B-30761 in a static second aqueous culture medium containing per liter about 2% carbon source, about 0.7 g KH2PO4, about 0.9 g Na2HPO4, about 2 g NaNO3, about 0.4 g MgSO4.7H2O, and about 0.1 g CaCl2.2H2O for at least about 72 hours at about 20°–about 23° C., wherein the first and second aqueous culture medium contains only one source of carbon.

Abstract: Several novel PHA polymer compositions produced using biological systems include monomers such as 3-hydroxybutyrate, 3-hydroxypropionate, 2-hydroxybutyrate, 3-hydroxyvalerate, 4-hydroxybutyrate, 4-hydroxyvalerate and 5-hydroxyvalerate. These PHA compositions can readily be extended to incorporate additional monomers including, for example, 3-hydroxyhexanoate, 4-hydroxyhexanoate, 6-hydroxyhexanoate or other longer chain 3-hydroxyacids containing seven or more carbons. This can be accomplished by taking natural PHA producers and mutating through chemical or transposon mutagenesis to delete or inactivate genes encoding undesirable activities. Alternatively, the strains can be genetically engineered to express only those enzymes required for the production of the desired polymer composition. Methods for genetically engineering PHA producing microbes are widely known in the art (Huisman and Madison, 1998, Microbiology and Molecular Biology Reviews, 63: 21–53).

Abstract: A stabilized liquid preparation of a protease which activates blood coagulation Factor VII or of its proenzyme is herein described. The preparation also contains one or more compounds selected from the group consisting of ornithine, diaminopimelic acid, agmatine, creatine, guanidinoacetic acid, acetylornithine, citrulline, arginoinosuccinic acid, tranexamic acid and epsilon-aminocaproic acid or their salts and has a pH of 2–8.

Abstract: A composition combining an extracellular matrix-degrading protease and a growth factor related to epithelial cell functions together without inactivation or degradation of the growth factor by the protease. Preferably, the protease is plasmin/plasminogen or a related one, and the growth factor is KGF or a related one. The combination associates two independent, but synergistic functions essential to the re-epithelialization process or healing process, i.e, stimulating epithelial cell proliferation/differentiation and facilitating its migration by clearing the extracellular matrix components. The combination may be constructed in various ways and can be used to treat wounds or any other disease conditions involving cells of epithelial origin or any other cell types that the growth factor may affect.

Abstract: Described herein is a novel three domain gene from Schizochytrium, denoted carotene synthase, that encodes a protein with three different enzymatic activities: phytoene dehydrogenase (PD), phytoene synthase (PS), and lycopene cyclase (LC). Also described is the isolated gene encoding the carotene synthase, homologues thereof, the enzyme encoded by such gene, biologically active portions and homologues thereof, recombinant nucleic acid molecules, microorganisms and plants that have been genetically modified to increase or decrease the action of such gene, and methods of producing carotenoids and derivatives thereof or methods of producing microorganisms and lipid products lacking pigmentation using the knowledge of the carotene synthase described herein.

Abstract: An isolated enone reductase characterized by a molecular mass of 61300+/?5000 Da; NADPH and NADPH as co-factor; a temperature optimum of 55–60° C. at pH 7.4; a pH optimum of 4.5–8.5 and substrate specificity on ?,?-unsatured ketones; a process for producing it from a microorganism and a process for producing levodione from ketoisophorone using such reductase.

Abstract: This invention provides (R)-2-octanol dehydrogenase that catalyzes oxidation-reduction reaction using NAD+ (NADH) as a coenzyme and the genes that encodes them. The enzymes of this invention can be obtained from microorganisms such as the genera Pichia, Candida, and Ogataea, and so on. It is possible to produce alcohols, in particular, alcohols such as (S)-4-halo-3-hydroxybutyric acid esters and (R)-propoxybenzene derivatives by reducing ketones with this (R)-2-octanol dehydrogenase. Moreover, the (R)-2-octanol dehydrogenase of this invention is excellent in activity and stereoselectivity.

Abstract: Methods for chemically transforming compounds using a mutated enzyme are provided, and more particularly a method for the production of an amino acid from a target 2-ketoacid, the production of an amine from a target ketone and the production of an alcohol from a target ketone. The methods comprise creating a mutated enzyme that catalyzes the reductive amination or transamination of the target 2-ketoacid or ketone or the reduction of the ketone and providing the mutated enzyme in a reaction mixture comprising the target 2-ketoacid or ketone under conditions sufficient to permit the formation of the desired amino acid, amine or alcohol to thereby produce the amino acid, amine or alcohol.

Abstract: The invention provides pth polypeptides and polynucleotides encoding pth polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing pth polypeptides to screen for antibacterial compounds.

Abstract: The invention concerns a method for the recombinant production or expression of eukaryotic alkaline phosphatase mutants in yeast cells wherein the specifically introduced mutations result in a reduction of the specific AP activity by at least a factor 1:100. The invention also concerns a method for inserting corresponding nucleic acid sequences into a vector for expression in methylotrophic yeast strains and it concerns corresponding vectors and host strains.

Abstract: The present invention is directed to human analogs of murine hematopoetic-specific, cytokine-inducible deubiquinating proteases (“DUBs”) clustered on chromosomes 4 and 8 and their respective regulatory regions. The nucleotides or proteins encoded thereby my be used in assays to identify inhibitors of human DUBs.

Abstract: The present invention provides nucleic acid and corresponding amino acid sequences of two isoforms of cold adapted trypsin-like activity protein, insolated from antarctic marine origin, preferably from antarctic krill (Euphausia superba) that can be used in a variety of industrial contexts and commercial purposes including laundry detergents, food processing, drugs and skin care products. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using the cold adapted trypsin-like protein.

Abstract: New genes containing a DNA sequence coding for hydroxynitrile lyase, which genes can be prepared via a primer combination based on the DNA sequence of the 5?-region of the mdl genes from the Prunus serotina and from Prunus amygdalus and/or a primer 2 based on the 3?-region of the DNA sequences of one of the hydroxynitrile lyase isoenzymes from Prunus serotina or from Prunus amygdalus, subsequent amplification with a DNA polymerase using a DNA from organisms, containing genes coding for hydroxynitrile lyase, as templates and cloning, and also recombinant proteins which can be prepared in suitable host cells by heterologous expression of the DNA sequence of said HNL genes, and proteins and fusion proteins derived therefrom and use of said proteins for preparing (R)- or (S)-cyanohydrins.

Abstract: Methods and compositions are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The invention also provides optical devices useful as narrow band filters.

Abstract: The increased use of nucleotide sequence data mining techniques has amplified the demand for efficient methods of producing recombinant proteins in prokaryotic cells. A strategy is provided for enhancing the synthesis of recombinant amino acid sequences by improving translation from expression cassettes in vitro before producing recombinant hosts.

Abstract: Liquid or frozen compositions containing adenoviral-particles, comprising a buffer solution capable of maintaining the pH of the medium at slightly alkaline values, supplemented with glycerol and without addition of divalent metal cations or of alkali metal cations.

Abstract: This invention pertains to BIV constructs encompassing BIV combination vectors, BIV vectors and BIV packaging vectors and particularly the invention pertains to a three vector system comprising: a) a BIV vector construct including a DNA segment from a BIV genome, a packaging sequence to package RNA into virions; a promoter operably linked to the DNA segment; and a transgene operably linked to a second promoter; b) a BIV packaging vector construct comprising a BIV DNA sequence fragment comprising at least a gag gene or pol gene of BIV; a promoter operably linked to the BIV DNA fragment; and a polyadenylation sequence located downstream of the BIV DNA fragment; and c) an expression vector construct comprising a gene encoding a viral surface protein. Also provided is a method for transferring a gene of interest into a mammalian cell.

Abstract: The subject invention comprises culture methods for transdifferentiation of non-pancreatic stem cells to the pancreatic differentiation pathway. It also concerns the endocrine hormones that can be produced by such cultures, and the use of the transdifferentiated cells in the treatment of pancreatic diseases.

Abstract: A method for the simultaneous determination of cell proliferation inhibition activity and cell toxicity (induction of cell death) of a substance using a proliferating mammalian cell sample as a test system.

Abstract: The present invention relates to novel immortalized pre-osteoblast cell lines derived from the periost and capable of differentiate to osteoblasts. In particular, the present invention pertains to the use of such cell lines in assays for detecting substances controlling the differentiation of pre-osteoblasts to osteoblasts and for detecting substances enabling improved bone formation, maintenance of bone mass, bone repair and for preventing the onset of osteoporosis.

Abstract: Promoters capable of efficiently expressing a gene of interest in plants include (1) either a DNA containing SEQ ID No:1 or SEQ ID No:7, or a biological functional equivalent DNA containing SEQ ID No:1 or SEQ ID No:7 that have modifications in their respective nucleotide sequence provided that each retains more than 90% identity to the nucleotide sequence of any region containing at least 250 bp within SEQ ID No:1 or SEQ ID No:7, respectively. Terminators capable of efficiently expressing a gene of interest in plants include either a DNA containing SEQ ID No:2, or a biological functional equivalent DNA containing a SEQ ID No:2 that has a modified nucleotide sequence provided that it retains more than 90% identity to the nucleotide sequence of any region containing at least 250 bp within SEQ ID No:2.

Abstract: A ?-alanine NMTase was isolated from Lumonium latifolium. The purified enzyme catalyzes the N-methylation of ?-alanine betaine, has an isoelectric point of about 5.15 and an apparent molecular weight of about 43 kilodaltons. A full-length cDNA encoding the NMTase was cloned by screening a L. latifolium cDNA library and was sequenced. Expression of the cDNA in transgenic, non-L. latifolium plants resulted in modulation of resistance to stress in the plants.

Abstract: DNA constructs and other compositions and methods for controlling gene expression in eukaryotic cells and organisms are derived from bacterial quorum sensing systems. One or more cis elements from the luxI promoter (“lux box”) or a functionally similar sequence are incorporated in a eukaryotic promoter. A receptor protein from the LuxR family of transcriptional regulators, upon binding an acylated homoserine lactone (AHL) compound, interacts with the lux box, modulating the activity of the promoter.

Abstract: The invention concerns the field of molecular biology and more particularly that of mutagenesis. It concerns a method of high-rate directed mutagenesis, that is the formation of numerous directed mutants in reduced time and with reduced number of steps. Said method is therefore referred to as massive mutagenesis.

Abstract: A solid heparin tablet composition has a melting point of 25° C. or higher and is a continuous lipid component containing one or more polar lipids, one or more non-polar lipids, optionally one or several of water and mono- to trivalent alcohol in an amount of up to 15% by weight of the composition, and native heparin or fractionated heparin. Also described is a corresponding tablet, processes for production of the composition and the tablet, and a method of preventing or treating conditions amenable to preventive or therapeutic treatment by administration of the tablet.

Abstract: The present invention relates to an arrangement, in particular for the parallel testing of a plurality of building blocks of a material library for performance characteristics, in which the arrangement has a block containing at least one reaction module and at least two heating/cooling modules.

Abstract: A method is described for the early detection of stroke which uses a reagent which includes a fluorescently modified fatty acid binding protein. A fluorescence difference is noted between the bound and unbound condition. Elevated levels of unbound free fatty acids from blood are used as indicators of stroke.

Abstract: To provide a hardness measurement reagent unaffected by an M alkalinity in hardness measurement. A hardness measurement reagent as a one-solution type reagent includes a dye chosen from Eriochrome Black T (EBT) and Calmagite, triethanolamine, a glycol compound, and a pH buffer, in which the pH buffer includes a combination of amines selected from primary amines and secondary amines and a salt of a weak base.

Abstract: Systems and methods for establishing and/or maintaining the accuracy of a multivariate calibration model designed for quantitative optical spectroscopic measurement of attributes or analytes in bodily tissues, bodily fluids or other biological samples, which are particularly useful when the spectral absorbance of the attribute or analyte is small relative to the background. The present invention provides an optically similar reference sample to reduce the effect of instrument or environment variation on the measurement capability of the model. The optically similar reference can be a gel composition having scattering particles suspended therein. The reference gel can be directly applied to a spectroscopic instrument sampler, or can be in a container specifically designed for optimal coupling to a spectroscopic instrument.

Abstract: Derivatives and conjugates of indinavir for generation of antibodies and labeled conjugates for use for detection of indinavir in biological samples. The derivatives are synthesized out of the indane ring hydroxyl group or the pyridine ring nitrogen of indinavir. Also disclosed is synthesis of a major metabolite of indinavir (M6) in a single step from indinavir using palladium catalyst and hydrogen gas. Indinavir M6 has been extended to synthesize various analogs of indinavir with suitable functional groups. These derivatives are useful in the development of indinavir immunogens, antibodies, and labeled conjugates in the development of indinavir immunoassays.