Abstract: The present invention relates to a method of detecting a DNA sequence by means of a DNA:DNA hybrid in real time using fluorescence. The present invention eliminates the need to use radioactive probes to detect the DNA and eliminates the delay needed for autoradiographic exposure of the X-ray to the radioactive label.

Abstract: The DNA sequence spanning the fragile X site on the X human chromosome has been obtained in purified and isolated form. As fragile X is associated with mental retardation, the availability of a DNA which spans this locus permits diagnosis and treatment of the related mental disorders.

Abstract: A method of determining the relative number of nucleic acid sequences in test cells which provides for a high resolution during comparative genomic hybridization by keeping all components separate from each other and selecting target nucleic acids which have a high resolution capability for determining genomic imbalances in the test cells and which facilitate a screening of the test cells for over- or under-expression of individual genes.

Abstract: The present invention is directed to a method for detection, characterization and isolation of nucleic acids encoding proteins of a desired property, such as a particular cellular localization. The invention further provides for rapid expression of such proteins or glycoproteins in mammalian cells and for facilitated purification of the novel secreted proteins or glycoproteins. Further, the invention provides for radioactive labelling of the novel proteins or glycoproteins, for rapid identification of sites of binding including animals and for rapid production of infective viral vectors for use in gene transfer.

Abstract: The present invention discloses a self-contained miniature DNA biosensor designed to detect specific molecular targets, particularly suitable for detection of nucleic acids. For example, hybridized DNA may be detected without external monitoring or signal transmission. The miniaturized biosensor is a biochip comprising multiple biological sensing elements such as DNA probes, excitation microlasers, a sampling waveguide equipped with optical detectors (fluorescence and Raman), integrated electrooptics, and a biotelemetric radio frequency signal generator. The novel integrated circuit biochip microsystem (ICBM) is suitable for gene analysis and will allow rapid, large-scale, and cost-effective production of gene biochips.

Abstract: This invention provides vectors comprising isolated polynucleotides comprising a member selected from the group consisting of: (a) a polynucleotide encoding MAB-21 protein; (b) a polynucleotide capable of hybridizing to and which is at least 60% identical to the polynucleotide of (a); and (c) a polynucleotide fragment of the polynucleotide of (a) or (b). This invention further provides host-vectors system for the expression of MAB-21 protein and protein products of mab-21 homologs. This invention further provides MAB-21 protein and protein products of mab-21 homologs. This invention also provides antibodies capable of specifically binding to the MAB-21 protein or protein products of mab-21 homologs. Finally, this invention also provides methods for identifying various suppressor, enhancer and modifier genes of the mab-21 and its homologs.

Abstract: The present invention provides methods for assessing cardiovascular status in an individual, which comprise determining the sequence at one or more polymorphic positions within the human genes encoding angiotensin converting enzyme (ACE), angiotensinogen (AGT), and/or type 1 angiotensin II receptor (AT1). The invention also provides isolated nucleic acids encoding ACE, AGT, and AT1 polymorphisms, nucleic acid probes that hybridize to polymorphic positions, kits for the prediction of cardiovascular status, and nucleic acid and peptide targets for use in identifying candidate cardiovascular drugs.

Abstract: The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Abstract: A method for diagnosing or screening for bovine &agr;-mannosidosis comprises detecting in nucleic acid samples from cattle the presence or absence of &agr;-mannosidosis-causing mutations in the gene encoding bovine lysosomal &agr;-mannosidase (LAMAN). A method of detecting &agr;-mannosidosis-causing mutations in cattle comprises detecting the presence or absence of base transitions in the gene encoding bovine LAMAN which are associated with the disease.

Abstract: A process is described for denaturing native double-stranded nucleic acid material into its individual strands in an electrochemical cell. The process disclosed is an electrical treatment of the nucleic acid with a voltage applied to the nucleic acid material by an electrode. The process may also employ a promoter compound such as methyl viologen to speed denaturation. The process may be used in the detection of nucleic acid by hybridizing with a labelled probe or in the amplification of DNA by a polymerase chain reaction or ligase chain reaction. A process is described for annealing complementary strands of nucleic acid by application of an electrical voltage.

Abstract: A novel, highly polymorphic DNA marker based on the pentanucleotide repeat (CCTTT/GGAAA)n has been identified in the human inducible nitric oxide synthase (iNOS) gene. Twelve different alleles, having between 7 and 18 repeats, have been identified. The repeat is highly polymorphic in the human population and so lends itself to use as a microsatellite marker with uses in, for example, forensic medicine, population studies, family linkage studies and disease diagnosis.

Abstract: The invention provides a method of sequencing a nucleic acid in a reaction mixture comprising first and second nucleic acid target sequences. The target sequences may be present on the same or different nucleic acid molecules. First and second labelled sequencing primers are provided that are hybridizable, respectively, to the first and second nucleic acid target sequences. The second sequencing primer being at least as long as the total length of the first sequencing primer plus the length of the first target sequence. Each of the sequencing primer extension products beginning with the second sequencing primer will be longer than the primer extension products in the pool beginning with the first sequencing primer. Once the sequencing reactions have been completed, the lengths of the primer extension products in the pool may be detected by known methods, such as by gel electrophoresis.

Abstract: The present invention provides a human tumor suppressor (HKALL) and polynucleotides which identify and encode HKAL,. The invention also provides expression vectors and host cells, agonists, antibodies, or antagonists. The invention provides methods for treating diseases associated with expression of HKALL.

Abstract: The invention provides human myosin heavy chain-like proteins (MHCP) and polynucleotides which identify and encode MHCP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating disorders associated with expression of MHCP.

Abstract: Disclosed herein are methods for linking a protein or other biomolecule containing a carboxylic acid moiety to a PNA or DNA probe molecule. The methods disclosed herein involve activating the carboxylic acid moiety with an activating agent and reacting the activated carboxylic acid moiety with a PNA or DNA probe having an arylamine or aminooxyacetyl moiety. Conjugates produced by these methods are also disclosed.

Abstract: Amplification primers and methods for specific amplification and detection of a Yersinia enterocolitica target are disclosed. The primer-target binding sequences are useful for amplification and detection of Y. enterocolitica target in a variety of amplification and detection reactions.

Abstract: An article suitable for use as a biosensor includes a molecule of a formula X—R—Ch adhered to a surface of the article as part of a self-assembled monolayer. X is a functionality that adheres to the surface, R is a spacer moiety, and Ch is a chelating agent. A metal ion can be coordinated by the chelating agent, and a polyamino acid-tagged biological binding partner of a target biological molecule coordinated to the metal ion. A method of the invention involves bringing the article into contact with a medium containing or suspected of containing the target biological molecule and allowing the biological molecule to biologically bind to the binding partner. The article is useful particularly as a surface plasmon resonance chip.

Abstract: The present invention provides a computer method and apparatus for detecting mutations in DNA fragments. Specifically, percent acetonitrile and threshold temperature, for use in the denaturing high performance liquid chromatography method of separating DNA fragments, are determined. In a preferred embodiment, the present invention serves as a preprocessor to the DHPLC system described in the cited art.

Abstract: The present invention relates to genes in Saccharomyces cerevisiae which are essential for germination and proliferation of S. cerevisiae and using the identified genes or their encoded proteins as targets for highly specific antifungal agents, insecticides, herbicides and anti-proliferation drugs. The present invention provides antisense molecules and ribozymes comprising sequences complementary to the sequences of mRNAs of essential genes that function to inhibit the essential genes. The present invention also provides neutralizing antibodies to proteins encoded by essential genes that bind to and inactivate the essential gene products. The present invention further provides pharmaceutical compositions for treating fungal and proliferative diseases, as well as methods of treatment of fungal and proliferative diseases.

Abstract: The chromosomal location of Fusarium head blight (FHB) resistance genes in wheat and the discovery of molecular markers for detecting the presence of these genes is herein described. The markers are generated via PCR or similar amplification reaction using primers identified herein. As a result, seed material can be assayed, thereby eliminating the time and cost involved in assaying adult plants for FHB resistance. Furthermore, the markers allow for gene pyramiding of the multiple, independent resistance genes into complex genetic backgrounds. In addition, the markers can be assayed in parallel. Finally, the markers are cost effective, highly reliable and accurate, and require just a few hours for testing.

Abstract: The present invention provides nucleotide and amino acid sequences that identify and encode a novel pancreas-derived serpin (PDS) expressed in human pancreas. The present invention also provides for antisense molecules to the nucleotide sequences which encode PDS, expression vectors for the production of purified PDS, antibodies capable of binding specifically to PDS, hybridization probes or oligonucleotides for the detection of PDS-encoding nucleotide sequences, genetically engineered host cells for the expression of PDS, diagnostic tests based on PDS-encoding nucleic acid molecules and a pharmaceutical composition containing PDS capable of binding specifically to a serine protease.

Abstract: The present invention is directed to a method of analyzing at least two analytes at the same time using at least two fluorescent detecting entities. More particularly, the present invention relates to the use of fluorescently labeled hybridization probes to identify the genotypes of a nucleic acid sample at more than one locus by measuring fluorescence throughout a range of temperatures and correcting for temperature-dependent spectral overlap of the fluorescent probes.

Abstract: The invention provides genetic suppressor elements that confer the transformed phenotype of malignant mammalian cells upon untransformed cells, methods for identifying and obtaining such elements, methods for isolating and identifying genes corresponding to such elements, and methods of using such elements. The invention also provides genes corresponding to the GSEs of the invention.

Abstract: Disclosed is a method for quantitatively identifying polymers in an aqueous system using immunoassay techniques, wherein at least a portion of the polymers contain a detectable terminus. This is particularly useful in water treatment systems. Also disclosed are new hybridoma cell lines which express MAbs which specifically recognize such a detectable terminus.

Abstract: A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling tube. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to present only on cancer cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to present only on hematologic progenitor cells.

Abstract: The lymphocyte ativation gene (LAG-3) is a member of the immunoglobulin superfamily that is selectively transcribed in human activated T and NK cells. Surface LAG-3 expression correlated with IFN-&ggr; but not IL-4, production in antigen-stimulated T-cells and it was up-regulated by IL-12 and is preferentially associated with CD4+ T-cells producing Th1-type cytokines. The presence of LAG-3 on the surface of Th1 lymphocytes is used as a marker to detect and identify Th1 lymphocytes and differentiate them from Th2 lymphocytes. Monoclonal antibodies to LAG-3 are used in methods of detecting and isolating Th1 cells as well as methods of diagnosing Th1-mediated disease. The present invention also relates to methods of treating infectious diseases, cancer, and disorders assocated with Th1/Th2 imbalance.

Abstract: Isolated receptors for IL-17, DNA's encoding such receptors, pharmaceutical compositions made therefrom, detection assays and methods of inhibiting binding of the receports are disclosed. The isolated receptors can be used to regulate an immune response.

Abstract: Methods for detecting human factor VIII or factor VIII-like polypeptides in and isolating it from solutions such as blood or conditioned media are disclosed, together with reagents suitable for the purpose comprising binding moieties that recognize human factor VIII and/or a factor VIII-like polypeptide and form a binding complex therewith. Preferred polypeptide binding moieties are particularly disclosed.

Abstract: This invention provides novel assays for topoisomerase activity and for identifying topoisomerase inhibitors. The assays include both solid-phase and liquid-phase methods that are amenable to high throughput screening methods. The assays of the invention are readily adaptable to numerous types of topoisomerase, and are capable of identifying novel classes of topoisomerase activity modulators.

Abstract: The present invention relates to compositions of retinoids plus immunotoxins. More particularly this invention relates to the use of retinoids to potentiate the activity of immunotoxins for treatment of mammalian diseases.

Abstract: Linear substituted oligoalkyleneimine molecules and libraries of molecules are disclosed, as are their methods of synthesis and use in acceptor binding assays. Each molecule or chain of a library contains the same number of 2 to about 10 substituted alkyleneimine repeating units, whose substituents are reduced amino acid side chains bonded to the repeating units at a position alpha to the nitrogen atom, and the member chains of a library are present in equimolar amounts. The chains of a library contain one or more predetermined reduced amino acid side chain-substituted repeating units at one or more predetermined positions of the substituted oligoalkyleneimine chain. The library contains equimolar amounts of at least six different reduced amino acid side chain-substituted repeating units at one or more of the same predetermined positions of the substituted oligoalkyleneimine chain. Particularly preferred linear substituted oligoalkyleneimine molecules and libraries are linear substituted oligoethyleneimines.

Abstract: The invention features assays for the identification of compounds useful for the modulation of body weight. Such compounds are useful for the treatment of obesity and cachexia. The methods of the invention involve cell-free and cell-based assays that identify compounds which bind to and/or activate or inhibit the activity of GPR10, a G protein-coupled receptor, followed by an in vivo assay of the effect of the compound on feeding behavior, body weight, or metabolic rate. The invention also features compounds which bind to and/or activate or inhibit the activity of GPR10 as well as pharmaceutical compositions comprising such compounds. In addition, the invention includes nucleic acid molecules comprising a nucleotide sequence encoding all or a portion of murine GPR10, polypeptides comprising all or a portion of murine GPR10, antibodies directed against murine GPR10, and animals harboring a murine GPR10 transgene (e.g., mice overexpressing murine GPR10).

Abstract: A method for determining the immunocompetence of a mammal is described. Bodily fluid having T cell receptor complexes from a mammal is provided. Expression of a first component and a second component of the T cell receptor complexes is evaluated. An abnormal ratio of the number of cells expressing the first component as compared to the number of cells expressing the second component indicates altered immunocompetence in the mammal.

Abstract: Measurements of elevated levels of riboflavin carrier protein (RCP) can be used to detect breast, liver, ovarian, and endometrial cancers. Stains for riboflavin carrier protein can be used to visualize malignancies in tissue specimens. The new technique is particularly well-suited for the early detection of breast cancer. With a radioimmunoassay for RCP, we have observed that serum RCP levels were significantly elevated in women with breast cancer as compared to control subjects. A serum RCP level ≧1.0 ng/ml was highly predictive of the presence of breast cancer (other than in pregnant females).

Abstract: There is described a method for the chemical modification of antibodies and/or antigens in order to minimise sample interference in immunoassays, an immunoassay method in which chemically modified antibodies and/or antigens are employed, the use of chemically modified antibodies and/or antigens in an immunoassay and a kit for assaying biological specimens which comprises the chemically modified antibodies and/or antigens.

Abstract: Disclosed are methods and sensors for detecting the presence or concentration of an analyte in a sample, preferably a sugar such as glucose, which preferably utilizes a labeled engineered protein, or fragment thereof, that is capable of binding the analyte to be detected.

Abstract: The present invention is relates to a method for purifying a &ggr;-carboxylase from Conus snails and to a method for assaying the activity of this &ggr;-glutamyl carboxylase.

Abstract: The process according to the present invention allows expression and isolation of polypeptides with the proteolytic activity of HCV NS3 protease in a pure, catalytically active form, and in amounts that are sufficient for discovery of NS3 protease inhibitors and for determination of the three-dimensional structure of the NS3 protease. A further subject of the present invention is a procedure that defines the chemical and physical conditions necessary for completion of the proteolytic activity of the above polypeptides. The invention further comprises new compositions of matter (expression vectors) containing nucleotide sequences capable of expressing the above mentioned polypeptides in culture cells. Finally, new compounds of matter are defined, suitable to measure the above proteolytic activity, and useful to develop NS3 protease inhibitors and therefore therapeutic agents for use against HCV. The figure shows the kinetic parameters of HCV NS3 protease using the S3 depsipeptide substrate (SEQ ID NO:45).

Abstract: The present invention provides an assay for detecting and quantifying protease that is sensitive, rapid, and capable of screening numerous samples of small volume. Also provided by the present invention is a method for diagnosing disorders associated with connective tissue destruction in a subject by detecting and quantifying a particular protease in a biological sample. Further provided by the present invention is a method of detecting inhibitors of the activity of a protease by detecting primary amines that are exposed by the enzymatic degradation of a protease substrate.

Abstract: A method and apparatus for ascertaining and measuring the quality of milk by analyzing reflected or absorbed colors or both with which the milk is irradiated. The milk is thus irradiated with three colors of light in wavelengths of red, green and blue and the intensity and color of the light reflected by the milk or absorbed thereby, or both, is measured. The light sources are periodically switched off whereby the receiving sensors measure the same red, green and blue wavelengths due to background sources to the extent that they are reflected or absorbed or both by the milk. This data is then compared with data with the light sources switched on to produce the net data which is relevant to the milk as it is being received from the animal being milked.

Abstract: The invention is directed to novel methods of stabilizing blood compositions for use in the quality control of analytical techniques. The novel method comprises removing leucocytes from a blood composition to yield a depleted blood composition, stabilizing the leucocytes by treatment with an effective amount of a stabilizing agent comprising an aged transition metal solution, and then adding the resultant stabilized leucocytes to the depleted blood composition or a second blood component composition.

Abstract: The invention is directed to novel stabilized blood compositions and methods of stabilizing blood compositions for use in the quality control of analytical techniques. The novel blood compositions comprise leucocytes and an effective amount of an aged transition metal solution. The novel method comprises removing leucocytes from a blood composition to yield a depleted blood composition, stabilizing the leucocytes by treatment with an effective amount of a stabilizing agent comprising an aged transition metal solution, and then, adding the resultant stabilized leucocytes to the depleted blood composition or a second blood component composition.

Abstract: The DNA encoding the cell surface receptor for thrombin has been cloned and sequenced. The availability of this DNA permits the recombinant production of thrombin receptor which can be produced at cell surfaces and is useful in assay systems both for the detection of thrombin and for the evaluation of candidate thrombin agonists and antagonists. Further, the elucidation of the structure of the thrombin receptor permits the design of agonist and antagonist compounds which are useful diagnostically and therapeutically. The availability of the thrombin receptor also permits production of antibodies specifically immunoreactive with the receptor per se or with specific regions thereof which are also useful diagnostically or therapeutically.

Abstract: The invention relates to genetic manipulations of eukaryotic organisms, with recombinant DNA comprising RNA virus derived sequences for protecting such organisms against RNA viruses or enabling inducible or tissue-specific production of foreign proteins/peptides or RNAs. One embodiment of the recombinant DNA according to the invention comprises recombinant DNA, comprising two, 12-1250 base pair long, inverted repeat nucleotide sequences with therebetween at least one nucleotide sequence which is derived from RNA virus which for its replication is dependent upon a viral RNA/RNA polymerase, said RNA virus derived sequence comprising at least cis elements for replication but no gene that codes for viral RNA/RNA polymerase and no gene that codes for viral coat protein. The invention also relates to eukaryotic or prokaryotic cells or organisms which incorporate the recombinant DNA according to the invention.

Abstract: The invention provides three human vesicle membrane protein-like proteins (VMP) and polynucleotides which identify and encode VMP. The invention also provides expression vectors, host cells, agonists, antibodies, and antagonists. The invention also provides methods for treating and preventing disorders associated with expression of VMP.

Abstract: SBSEMVL polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilising SBSEMVL polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: The present invention provides a yeast cell comprising a nucleic acid functionally encoding a eukaryotic (e.g., mammalian) protein homologue of a subunit (Sec11p, Spc1p, Spc2p and/or Spc3p) of the yeast signal peptidase complex. The yeast cell of this invention can be, for example, of the genus Saccharomyces, Schizosaccharomyces, Pichia, Hansenula, Kluyveromyces and/or Yarrowia. Furthermore, the yeast cell can lack one or more functional subunits (Sec11p, Spc1p, Spc2p and/or Spc3p) of the yeast signal peptidase complex. The present invention further provides a method for producing a protein heterologous to a yeast cell comprising expressing, in the yeast cell of this invention, a nucleic acid functionally encoding the heterologous protein under conditions which permit the expression of the nucleic acid as a precursor protein having a signal peptide and processing of the precursor protein to a signal peptide-cleaved form of the protein.

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

Abstract: An artificial operon comprising genes encoding each of a trigger factor, GroEL and GroES, an expression plasmid carrying the operon, an expression plasmid carrying a gene encoding the trigger factor, a cotransformant harboring an expression vector for a foreign protein and any one of the expression plasmids, and a method for producing a foreign protein comprising expressing a foreign protein by the use of the cotransformant, which are capable of expressing a foreign protein in a solubilized form and in a state of having a correct conformation.

Abstract: Production of Bordetella pertactin antigens by expression in the methyltrophic yeast, Pichia; expression vectors containing DNA encoding the antigens and Pichia transformants containing the one of more copies of the DNA encoding a pertactin antigen.