Abstract: A method for identifying compounds that alter higher order chromatin dependent chromosome stability is based on determining the compounds' ability to modify a methyltransferase with Suv39h-like methyltransferase activity. The identified compounds are useful in therapy, in particular the therapy of human cancer and for contraception.

Abstract: An agglutination assay method for quantitatively determination of an analyte in a liquid sample using particles bearing an anti-analyte. A non-fluid substance which retains the particles while suppressing the diffusion of the particles therein is used as a medium which is to be a place where the agglutination of the particles takes place. Upon analysis, a solation agent is added to the non-fluid substance medium to increase the fluidity of the non-fluid substance, thereby the particles bearing the anti-analyte can diffuse in the medium to cause the agglutination with the analyte. Preferably, the solation agent is added to the non-fluid medium together with the sample. The non-fluid substance medium containing the particle-labeled anti-analyte can be stored with a higher stability in the dry state. A dry analysis element for enabling such analysis method is also provided.

Abstract: The present invention relates to the field of compounds which are substrates or inhibitors of proteolytic enzymes and to apparatus and methods for identifying substrates or inhibitors for proteolytic enzymes. We have devised a combinatorial method for the rapid indentification of binding motifs which will greatly expedite the synthesis of inhibitors of a variety of proteolytic enzymes such as aspartyl proteases, serine proteases, metallo proteases and cysteinyl proteases.

Abstract: Electrochemiluminescent-labels and enzyme substrates, which preferably are conjugated, are used in immunoassays and electrochemiluminescence is generated catalytically. In conventional electrochemiluminescence immunoassays, an anti-analyte antibody molecule can give rise to typically 6-8 electrochemiluminescence-active ruthenium atoms, while in the present invention, each enzyme-labeled anti-analyte molecule can give rise to thousands of electrochemiluminescence-active ruthenium atoms per second. An exemplary immunoassay is based on a catalytic process employing &bgr;-lactamase-conjugated anti-analytes which enzymatically hydrolyze electrochemiluminescent-labeled substrates, making them strongly electrochemiluminescent. The electrochemiluminescence signal generated by each anti-analyte molecule (i.e., each analyte molecule) is much greater than with the conventional method. Accordingly, greater sensitivity can be gained in the measurement of low concentrations of a given immunoassay analyte.

Abstract: A method for the multiplexed diagnostic and genetic analysis of enzymes, DNA fragments, antibodies, and other biomolecules comprises the steps of constructing an appropriately labeled beadset, exposing the beadset to a clinical sample, and analyzing the combined sample/beadset by flow cytometry. Flow cytometric measurements are used to classify, in real-time, beads within an exposed beadset and textual explanations, based on the accumulated data obtained during real-time analysis, are generated for the user. The inventive technology enables the simultaneous, and automated, detection and interpretation of multiple biomolecules or DNA sequences in real-time while also reducing the cost of performing diagnostic and genetic assays.

Abstract: An immunoassay kit for the quantification of degradation products of carboxy-terminal telopeptides of type I collagen in a human serum sample, including an antibody that is characterized by binding to at least one peptide derived from the carboxy-terminal telopeptide domain of type I collagen and isolatable from a urine sample of a patient with active Patet's disease.

Abstract: The present invention provides a method of assaying an enzyme-mediated coupling reaction between a first and a second reactant. The method includes contacting the first reactant with the second reactant in the presence of the enzyme. The second reactant includes a thiol derivative to yield a first product including a thiol derivative. The thiol derivative is then detected in the first product.

Abstract: The invention relates to methods and compositions of WW-domains as phosphoserine and phosphothreonine binding modules. The WW-domain containing polypeptides of the invention can be used, for example, to regulate cell growth; to treat neurodegenerative diseases; to screen for substances that modulated interactions between WW-domain containing polypeptides and phosphorylated ligands; as drug targeting vehicles; to direct protein degradation; and in the treatment of certain diseases or conditions characterized by aberrant WW-domain containing polypeptides or their ligands.

Abstract: The invention is directed to purified and isolated novel DAKAR (death associated kinase containing ankyrin repeat) polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides and the uses of the above.

Abstract: The invention relates to novel compounds comprising a ubiquitination recognition element and a protein binding element. The invention also relates to the use of said compounds for modulating the level and/or activity of a target protein. The compounds are useful for the treatment of disease such as infections, inflammatory conditions, cancer and genetic diseases. The compounds are also useful as insecticides and herbicides.

Abstract: In an automated analyzer containing a spectrophotometer for determining color changes in a urine sample the urine is admixed with a basic indicator effecting the first color change and an acidic indicator effecting a second color change, a surfactant and water. The spectrophotometer determines and prints whether a first or second color change has occurred.

Abstract: The present invention relates to methods and compositions for the direct detection of membrane conformational changes through the detection of color changes in biopolymeric materials. In particular, the present invention allows for the direct colorimetric detection of membrane modifying reactions and analytes responsible for such modifications and for the screening of reaction inhibitors.

Abstract: The invention relates to novel compounds comprising a ubiquitination recognition element and a protein binding element. The invention also relates to the use of said compounds for modulating the level and/or activity of a target protein. The compounds are useful for the treatment of disease such as infections, inflammatory conditions, cancer and genetic diseases. The compounds are also useful as insecticides and herbicides.

Abstract: The present invention relates to novel Death Domain Containing Receptor-4 (DR4) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR4 proteins. DR4 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR4 activity.

Abstract: In accordance with the present invention, there are provided substantially pure glycosidases obtainable from the genus Chryseobacterium. In particular, there is provided a substantially pure exo &agr;-N-Acetylgalactosaminidase from Chryseobacterium meningosepticum. A method of cloning this enzyme and producing a recombinant form of the enzyme is also provided by the present invention.

Abstract: A test piece for use in biological analyses includes a plurality of different known specific binding substances disposed in predetermined positions on a substrate. The specific binding substances are disposed on a plurality of surfaces provided by the substrate and arranged in the direction of thickness of the substrate.

Abstract: Chemiluminescent endogenous enzyme assays which provide for the rapid, simple, and sensitive quantitation of cells directly in microwell cultures by the measurement of endogenous enzyme activity. These endogenous enzyme assays provide homogeneous chemiluminescent formats for measuring cell proliferation, growth inhibition, cell adhesion, cell migration, and cell number quantitation and normalization. Methods and kits employing such assays are also provided.

Abstract: The invention features screening methods which can be used to identify agents, known as vasoprotective agents, which inhibit vascular smooth muscle cell activation and/or proliferation or enhance vascular endothelial cell activation and/or proliferation or activate estrogen responsive genes in vascular cells. Preferred vasoprotective agents are relatively vasospecific, i.e., their effect on one or more types of vascular cells is more pronounced than their effect on other cell types. Treatment with such vasospecific agents will generally be associated with fewer undesirable side-effects than treatment with estrogen. The methods of the invention are screening assays in which candidate agents are examined to identify vasoprotective agents. One type of screening assay involves examining the effect of a candidate agent on cell proliferation and/or cell activation. Another type of screening assay involves examining the effect of a candidate agent on the expression of a gene which is responsive to estrogen.

Abstract: The invention concerns a device and a method for carrying out fluorescence immunoassays, wherein from at least one light source light is directed onto a surface at one end of a light waveguide and with the light coupled into the light waveguide by evanescent field excitation at the surface of the light waveguide fluorescence of at least one labelling substance bound to a chemical or biochemical partner of a general receptor-ligand system is excited. The solution according to the invention is here to provide a possible way of carrying out fluorescence immunoassays with high accuracy of measurement at low cost and within a short time. To achieve this object, the fluorescent light is decoupled from the light waveguide and directed via an optical system onto an optical detector with which the intensity of the fluorescent light is measured.

Abstract: This invention provides novel assays for measuring the metabolic side-effects of antiretroviral protease inhibitors on the Glut4 glucose transporter. The invention also provides improved methods for developing antiretroviral protease drugs, particularly those used to fight HIV infection. The invention further provides novel models of insulin-resistant glucose transport disease states.

Abstract: The invention relates to an isolated nucleic acid molecule encoding a caspase-14 polypeptide or functional fragment thereof, a vector that contains the nucleic acid molecule and a host cell that contains the vector. The invention also relates to an isolated gene encoding caspase-14, as well as functional fragments thereof. The gene or nucleic acid molecule can include single or double stranded nucleic acids corresponding to coding or non-coding strands of the caspase-14 nucleotide sequence. Isolated caspase-14 polypeptides or functional fragments thereof are also provided, as are antibodies that specifically bind thereto. In addition, the invention relates to methods of identifying compounds that modulate caspase-14 activity.

Abstract: Provided are methods for detecting membrane derived apoptotic activity. In one embodiment, the present invention provides methods for identifying membrane derived caspase activity. In other embodiments, drug discovery methods are provided for screening compounds that inhibit or enhance membrane derived caspase activity. In the various embodiments, heavy membrane fractions are utilized for the screening methodologies described herein.

Abstract: Compositions, formulae, devices and methods for the detection of target microorganisms, such as by visual immunoprecipitate assay, enzyme linked immunoassay, chemiluminescence, immunoblotting, or similar detection technology, wherein detection requires the discrimination among closely related genera, species and strains of antigenically related microorganisms based on immunological reactivity of a highly conserved antigen epitopes with a reagent system comprised of an antibody linked to a detecting reagent. The invention permits a detectable event to occur by exposing inaccessible but highly conserved and specific antigen epitopes to the detecting reagent. Exposure of such antigen epitopes without inactivating microbial metabolism allows for specific detection.

Abstract: This invention relates to methods for detecting the deficiency of magnesium tightly bound to cellular membranes, i.e. magnesium binding defect, which deficiency is associated with certain abnormal physiological states e.g., salt-sensitive essential hypertension or Type 2 diabetes mellitus.

Abstract: A method for selectively determining a fungal biomass by detection of a fungal enzymatic activity that is present in substantially all fungal species, such as enzymes involved in chitin metabolism (chitinase, chitin synthase, chitosanase, N-acetyl-glucosaminidase and &bgr;-N-acetylhexosamidase). The invention can be used for detecting a fungal biomass in environmental samples, food products, plant material, building materials, industrial fungal cultures or sample from a human being or animal including blood samples. In particular, 4-methylumbelliferyl-N-acetyl-&bgr;-D-glucosaminide is used as substrate for &bgr;-N-acetylhexosamidase (EC 3.2.1.52). This enzyme activity correlates with the amount of fungal biomass present in a sample.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity and means are shown for slowing the loss of telomeric repeats in aging cells.

Abstract: The invention provides a human ubiquitin-like conjugating protein (UBCLE) and polynucleotides which identify and encode UBCLE. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of UBCLE.

Abstract: 4-(4-hydroxystyryl) pyridine-containing compounds are disclosed as substrates for use in assays. Also, a method for detecting or quantitating an analyte is provided which includes reacting an enzyme with a 4-(4-hydroxystyryl) pyridine-containing compound to form a reactive intermediate wherein the reactive intermediate deposits covalently on a surface by binding to a receptor, wherein deposited reactive intermediates either directly or indirectly through a label generate a signal which can be detected or quantitated.

Abstract: The present invention relates to novel methods for detecting and evaluating bladder cancer. The methods of the present invention are based on the discovery that normalized amounts of hyaluronic acid (HA) and hyaluronidase (HAase) are diagnostic markers for the detection of bladder cancer, evaluation of its grade, monitoring of the efficacy of its treatment, and tumor recurrence.

Abstract: Substantially pure glycosidases capable for cleaving selected glycosidic bonds have been described including glycosidases isolated from Xanthomonas and recombinant glycosidases. Substrate specificity of isolated enzymes have been identified for GlcNac&bgr;1-X, Gal&agr;1-3R, Gal&agr;1-6R, Gal&bgr;1-3R, Fuc&agr;1-2R, Fuc&agr;1-3R, Fuc&agr;1-4R, Man&agr;1-2R, Man&agr;1-3R, Man&agr;1-6R, Man&bgr;1-4R, Xyl&bgr;1-2R, Glc&bgr;1-4R, and Gal&bgr;1-4R providing improved capability for selectively cleaving a glycosidic linkage in a carbohydrate substrate and for forming modified carbohydrates.

Abstract: The present invention relates to methods of tyramide coating live cells for flow cytometry, using catalyzed reporter deposition and serial amplification staining. A catalyzed reporter deposition or an analyte dependent enzyme activation system is described for detecting and/or quantitating an analyte of interest on the surface of a cell by flow cytometry. Also described is a method for serial amplification staining by tyramide coating cells which possess an analyte of interest or a solid phase to which an analyte is bound.

Abstract: A reagent is described for incorporating phosphorylation sites into compounds, particularly into proteins and peptides. The reagent has the structure A—B—C wherein A is a moiety that is specifically reactive with a reactive side chain in the compound, B is a linking moiety, and C is a peptide sequence that contains a kinase substrate.

Abstract: A method of identifying embryonic or fetal red blood cells in a sample containiing maternal blood cells and embryonic or fetal red blood cells or both, the method comprising determining which cell or cells contain or express an adult liver component. A method of isolating embryonic or fetal red blood cells from a sample containing maternal blood cells and embryonic or fetal red blood cells or both, the method comprising isolating the cells which contain or express an adult liver component. A method of determining a fetal abnormality the method comprising identifying or isolating embryonic or fetal cells according to the above methods and analysing said embryonic or early fetal cells for said abnormality. Use of a means for determining whether a cell contains or expresses an adult liver component for identifying or isolating an embryonic or fetal red blood cell.

Abstract: The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins (“CCR-proteins”). As described herein, this family of proteins is characterized by four ankyrin repeats and the ability to bind to a cyclin dependent kinase (CDK). The family includes a polypeptide having an apparent molecular weight of 16 kDa, and a polypeptide having an apparent molecular weight of approximately 15 kDa, each of which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth. Thus, similar to the role of p21 to the p53 checkpoint, the subject CCR-proteins may function coordinately with the cell-cycle regulatory protein, retinoblastoma (RB).

Abstract: The invention relates to an intact cell assay for direct quantitation of protein tyrosine phosphatase (PTP) activity using the baculovirus expression system. A PTP expressed in transformed host insect cells is processed and localized in their predicted subcellular compartments. Assays are performed on the PTP expressing host cells challenged with a substrate such as, p-nitrophenyl phosphate. This substrate is hydrolysed to p-nitrophenol by expressed phosphatase activity. Emergence of p-nitrophenol is determined spectrophotometrically and is a measure of PTP activity. Further, the assay and transformed host cells of this invention are particularly useful in a screening method for selecting potential inhibitors to PTPs. Basically, transformed host cells are pre-incubated with or without inhibitors and the assay conducted as described. This invention relates to an intact cell assay with a direct readout of PTP activity that is useful in a cell-based screening method for selecting inhibitors of PTPs.

Abstract: The invention concerns a method and reagent for the determination of lipase in the presence of a colour substrate and at least one N-substituted carboxylic acid amide derivative or a compound of the general formula (I) or (Ia) in which R1 and R2 independently of one another represent hydrogen or a saturated or unsaturated, substituted or unsubstituted hydrocarbon residue with 2 to 24 carbon atoms, Z denotes a saturated or unsaturated, substituted, cyclic or straight-chained hydrocarbon residue with 1 to 10 carbon atoms, X represents an atom or a group of atoms with positive charge and n is a number from 1 to 3. Tetra-sodium-N-(1,2-dicarboxylethyl)-N-alkylsulfosuccinamide or a mixture containing such a compound has proven to be particularly advantageous for the elimination of unspecific reactions in the determination of lipase in a biological sample.

Abstract: The gp4l and Dda helicases were found to significantly enhance the dissociation rate of streptavidin from biotin-labeled oligonucleotides in an ATP dependent reaction, demonstrating that these enzymes are capable of imparting a significant force on a molecule blocking their path. The present invention describes an assay for studying enzymatic activity of a helicase using the rate of dissociation of streptavidin from biotinylated oligonucleotides.

Abstract: The present invention relates to a method for isolating cloned papillomavirus E1 protein from a eukaryotic expression system having demonstrable and reproducible viral helicase activity and preparation containing essentially pure E1 protein. The invention further relates to the use of this novel E1 protein preparation in a screening assay for identifying antiviral agents. More particularly a high throughput assay to screen for agents capable of inhibiting HPV DNA replication. The assay is based on measuring the effect of antiviral agents on the activity of the E1 protein and more specifically on its helicase activity.

Abstract: An antibody reacting specifically with human LECT2. This antibody is produced by hybridoma clones G2A5D7 (Accession No. FERM P-15638), A1G1C6 (Accession No. FERM P-15639), 5C5 (Accession No. FERM P-15640), H12D10D6 (Accession No. FERM P-15641), etc. Human LECT2 can be assayed by reacting human LECT2 successively with an immobilized antibody which has been formed by binding the above-mentioned antibody to an insoluble support and a labeled antibody which has been formed by labeling another antibody reacting with human LECT2 with a labeling agent, and then determining the amount of label in the reaction product.

Abstract: The invention relates to novel compounds comprising a ubiquitination recognition element and a protein binding element. The invention also relates to the use of said compounds for modulating the level and/or activity of a target protein. The compounds are useful for the treatment of disease such as infections, inflammatory conditions, cancer and genetic diseases. The compounds are also useful as insecticides and herbicides.

Abstract: The invention provides an isolated gene encoding Mch4 or an isolated gene encoding Mch5 as well as functional fragments thereof. Also provided are isolated nucleic acid sequences encoding Mch4 or Mch5 or functional fragment thereof The gene or nucleic acid sequences can be single or double stranded nucleic acids corresponding to coding or non-coding strands of the Mch4 or Mch5 nucleotide sequences. Also provided are genes and nucleic acids encoding functional fragments such as the FADD-like domains Mch4A, Mch4B, Mch5A and Mch5B. Isolated Mch4 or Mch5 polypeptides or functional fragments thereof including the FADD-like domains Mch4A, Mch4B, Mch5A and Mch5B are also provided.

Abstract: The invention features a monoclonal antibodies specific for human type I alveolar cells or for human type II alveolar cells. The invention also features methods of detecting lung injury in a subject using these monoclonal antibodies.

Abstract: The present invention relates to an assay for the detection of modified nucleoside levels in a patient. Detection of the modified nucleoside levels in a patient having a disease such as cancer allows for the progression of the disease to be followed and therapeutic regimens to be altered. Such an assay is particularly useful in following the response of cancer patients to chemotherapeutic treatment.

Abstract: The invention provides an isolated gene encoding Mch6 as well as functional fragments thereof. Also provided are isolated nucleic acid sequences encoding Mch6 or functional fragments thereof. The gene or nucleic acid sequences can be single or double stranded nucleic acids corresponding to coding or non-coding strands of the Mch6 nucleotide sequences. The invention further provides an isolated Mch6 polypeptide and isolated large and small subunits of the Mch6 polypeptide, including functional fragments thereof.

Abstract: Methods to detect prion or PrP-Sc protein as an indication of transmissible spongiform encephalopathies (TSEs) are described. In one aspect, the invention is directed to monoclonal antibodies that specifically bind a conserved epitope of prion proteins and use of the antibodies in immunoassays to detect PrP-Sc, in fixed or unfixed tissue, as an indication of the presence of TSE infection. In another aspect, the invention is directed to a monoclonal antibody cocktail having the monoclonal antibody in combination with a second monoclonal antibody which specifically binds to a second conserved epitope of prion proteins. One or both monoclonal antibodies of the cocktail can recognize epitopes found in all mammalian species in which a natural TSE has been reported and in a number of closely related species.

Abstract: There is disclosed a cancer malignancy diagnostic assay comprising obtaining a sample of a body fluid or tissue, performing a sequence identity assay to look for the presence of iPFK-2 specific sequences; an anticancer pharmaceutical composition comprising a specific antisense oligonucleotide to the inventive isolated iPFK-2 sequence and a pharmaceutically acceptable oligonucleotide carrier; and a method for finding therapeutically active anti-cancer compounds comprising screening compounds for activity to inhibit iPFK-2, preferably kinase activity.

Abstract: The invention relates to novel methods and compositions for the detection of analytes using the nuclear reorganization energy, &lgr;, of an electron transfer process.

Abstract: Heterogenous and homogenous assays are provided for the detection of protease inhibitory activity in a sample or target compound, taking advantage of the chemiluminescent characteristics of 1,2-dioxetanes. In the heterogenous assay, a peptide bearing a cleavage site for the protease of interest is provided with a first member of a first ligand binding pair at one end, and a first member of a second ligand binding pair at the other end. The other member of the first ligand binding pair is attached to a surface, which binds the peptide, or protease substrate, to the surface. The peptide substrate is combined with the protease and target compound or sample. Substrate cleavage, if not inhibited, is allowed to occur, and any unbound cleaved fragments are removed. An enzyme complexed with the second member of the second ligand binding pair is added, and allowed to bind to any of the (uncleaved) first member of the second ligand binding pair remaining.

Abstract: An assay for the detection of growth hormone secretagogue receptors and growth hormone secretagogue related receptors is described. As these receptors are a member of the G protein coupled receptors, a subunit of the G protein must be present in order for expression to be detected. A similar assay is described where the presence of growth hormone secretagogues are detected.

Abstract: An analytical system for rapid detection and identification of different analytes directly from a test sample by mixing test material with a germinogenic source and enzyme-free spores, allowing the mixture to stand for a time to allow analyte-induced spore germination and subsequent de novo synthesis of an enzyme capable of producing a germinant in the presence of the germinogenic source and detecting the presence of a germination-derived product. The germinant which is formed promotes further spore germination with concomitant additional de novo enzyme synthesis which results in a propagating cascade of analyte-independent germination after which a germination-derived product can be easily detected. The technique is particularly efficient to conduct thousands of parallel assays in an array of microscopic wells.