Abstract: The invention provides monoclonal antibodies that selectively bind to ectodermally- and endodermally-derived stem cells and methods for the diagnosis of a neoplasm in a subject by contacting a tissue sample from the subject with the antibodies. Also disclosed are methods for isolating such stem cells from a heterogeneous cell population by contacting the population with antibodies which selectively bind to stem cells.

Abstract: The invention provides neuropeptide ligands, G protein-coupled receptors and methods of screening for modulators of receptor activity. Identified modulators, including neuropeptide ligand mimetics, are useful as biostatic and biocidal agents of varying scope, ranging from lethal activity restricted to particular invertebrate parasites to broad spectrum invertebrate parasiticides active on a wide range of invertebrates, including helminths and insects.

Abstract: An assay method for detecting the response or activation of cells, including lymphocytes, and a method for detecting immunological sensitization in a subject, which involves the introduction of cell-activating substance which causes an enzyme of the cells to become available for reaction, and the measurement of the enzymatic reaction using a substrate which generates a detectable product, and a kit for performing such assays.

Abstract: This invention concerns an immunoassay for quantitative determination of the amount of the complex (PSA-A2M) between prostate specific antigen (PSA) and &agr;2-macroglobulin (A2M) in a sample. The assay comprises the steps of removing immunoreactive PSA from the sample, treating the PSA-A2M complex in the remaining supernatant so as to make the PSA thereof immunoreactive, determining the immunoreactive PSA derived from the PSA-A2M complex by exposing it to an antibody which binds immunoreactive PSA, and detecting the PSA. The invention also concerns a method for differentiating patients with cancer of the prostate (PCa) from patients with benign prostatic hyperplasia (BPH) or healthy male subjects without PCa, wherein the individual's body fluid concentration of PSA has been determined as free PSA and as total PSA.

Abstract: The invention pertains to an immunoassay, and a kit for said assay, in which at least one monoclonal antibody or polyclonal antibody specifically binds to an epitope corresponding to amino acids 145 to 234 of human chromogranin A.

Abstract: Mutant ob receptors have been made which a) lack a functional first CK-F3 domain; b) lack a functional second CK-F3 domain or c) lack a functional intracellular domain. These receptors may be used in various assays, such as a transactivation assay to identify novel ligands.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: This invention relates to glutamine:fructose-6-phosphate amidotransferase, or its partial peptide or a salt thereof; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein; a pharmaceutical composition comprising the protein, its partial peptide or a salt thereof; and an antibody against the protein or its partial peptide. The protein, its partial peptide or a salt thereof, and the DNA are useful for a prophylactic or therapeutic agent for hypoglycemia. The antibody can be used in the assay of the protein, its partial peptide or a salt thereof. The protein, its partial peptide or a salt thereof is useful as a reagent for the screening for candidate medical compounds.

Abstract: The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: Enzyme assays are performed in microfluidic devices including, e.g., in-line labeling, separation, and detection of assay products. In-line labeling allows assays, e.g., protease assays, to be performed in a continuous flow microfluidic format. Also included are microfluidic devices and integrated systems for performing in-line labeling in continuous flow enzyme assays.

Abstract: Cytochrome P-450 assay methods and kits for the methods are provided employing a cytochrome P-450 enzyme, substrates characterized by having an oxidizable methylene group oxidized to an aldehyde and a fluorescent hydrazine. A fluorescent hydrazine is added to the reaction mixture and the resulting hydrazone analyzed by capillary electrophoresis. The method finds use in evaluating compounds for enzyme modulating activity.

Abstract: The present inventors have discovered that homocitrate synthase is essential for fungal pathogenicity. Specifically, the inhibition of homocitrate synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, homocitrate synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit homocitrate synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Abstract: A rapid method for detecting spoilage of a food sample, particularly a fish sample, by detecting and enumerating sulfide-producing bacteria (SPB). A growth medium containing iron and sulfur is combined with the food sample forming an incubation mixture which is incubated for a period of time. A plurality of fluorescence measurements are taken during an incubation period of about 4 hours to 17 hours at 30° C. SPB are determined to be present in the sample if the fluorescence measurement initially increases and then decreases to form a fluorescence maximum (peak). The time to detection of the fluorescence peak can be used with a correlation schedule to enumerate the SPB in the food sample. A visual test can also be used to identify color changes in the incubation mixture to provide a semi-quantitative enumeration of SPB effective in about 4 hours to 17 hours at 30° C.

Abstract: An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins of catalyzing an oxidation step in the biological pathway, for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of: the conversion of cholesterol to pregnenolone; the conversion of pregnenolone to progesterone; the conversion of progesterone to 17&agr;-hydroxyprogesterone; the conversion of 17&agr;-hydroxyprogesterone to cortexolone; the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in that host.

Abstract: Novel fusions of a GPI signal domain and a polypeptide heterologous to the GPI signal domain donor polypeptide are provided for industrial use. Therapeutic administration of the GPI-linked product of the fusions enables the targeting of biological activity to cell membrane surfaces.

Abstract: Methods are disclosed for refolding proteins of the TGF-&bgr; family of proteins. The methods employ as refolding agents one or more compounds which are acid substituted aminocyclohexanes.

Abstract: The present invention provides the genomic sequences of a library of purified nucleic acid molecules, or their complements, comprising the genome of Moraxella catarrhalis. The invention also provides the identification of open reading frames contained within the nucleic acid molecules of the library. The present invention further provides for the use of the nucleic acid molecules, their complements or fragments, and proteins or portions thereof for identifying ligands and useful diagnostic and therapeutic compositions. In addition the invention provides for vectors, host cells and methods for producing M. catarrhalis proteins or portions thereof.

Abstract: There is disclosed an expression vector utilizing an internal polyadenylation signal. The internal polyadenylation signal is inserted between a DNA encoding a protein of interest and a DNA encoding a selectable marker, and allows a single promoter to generate both monocistronic messages and dicistronic messages. Similar, multicistronic vectors can also be prepared. Also disclosed are methods of using the expression vector utilizing an internal polyadenylation signal, host cells transfected therewith, stable pools of cells transfected with an expression vector utilizing an internal polyadenylation signal, and clones of such transfected cells.

Abstract: Disclosed are methods for improving the solubility of a protein of interest produced recombinantly by expressing the protein of interest as a fusion protein with Uracil DNA glycosylase inhibitor (UGI).

Abstract: The invention concerns the use of Escherichia coli (E. coli) strains whereof the gene coding for the Rnase E comprises a mutation such that the enzyme produced when said mutated gene is expressed no longer has a degrading activity on mRNA, said mutation more significantly not affecting the growth of E. coli strains, for implementing a method for producing specific exogenous recombinant polypeptides.

Abstract: Using nucleic acids encoding mutant SEA and SEB exotoxins from Staphylococcus aureus, compositions and methods for use in inducing an immune response which is protective against staphylococcal aureus intoxication in subjects is described.

Abstract: The present invention relates to a method and apparatus for performing a large number of reactions using array assembly. In particular, the present invention features a method and apparatus for performing a large number of chemical and biological reactions by bringing two arrays into close apposition and allowing reactants on the surfaces of two arrays to come into contact. The present invention is exemplified by performing a large number of polynucleotide amplification reactions using array assembly. In addition, the present invention features a method and apparatus for coupling the amplification of polynucleotides and the detection of sequence variations, expression levels, and functions thereof.

Abstract: The present invention relates to genes for detecting the genus Pectinatus frisingensis or Pectinatus cerevisiiphilus of the genus Pectinatus, which is known as beer-spoilage bacteria, and a method for detecting the bacteria by using the genes. The present invention provides gene sequences of spacer regions between 16S rRNA genes and 23S rRNA genes specific for the genus Pectinatus relating to beer-spoilage and a method for quickly and sensitively detecting the bacteria by using the sequences.

Abstract: A method of preparing the sugar 1,5-D-anhydrofructose is described. The method comprises treating an &agr;-1,4-glucan with an &agr;-1,4-glucan lyase wherein the enzyme is used in substantially pure form. In a preferred embodiment, if the glucan contains links other than and in addition to the &agr;-1,4-links, the &agr;-1,4-glucan lyase is used in conjunction with a suitable reagent that can break the other links.

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) and b) and d) polynucleotide comprising at least 15 successive nucleotides of the polynucleotide sequence of a), b) or c), and processes for the fermentative preparation of L-amino acid with amplification of the zwa1 gene in the coryneform bacteria employed.

Abstract: The present invention provides compositions comprising thermostable DNA polymerases derived from hyperthermophilic eubacteria. In particular, the present invention comprises thermostable DNA polymerases from the hyperthermophilic eubacterial species Thermoactinomyces vulgaris. The present invention also provides methods for utilizing naturally-occurring and non-naturally-occurring forms of T. vulgaris DNA polymerase in sequencing, reverse transcription, and amplification reactions.

Abstract: Enzymes produced by mutating the genes for a number of subtilisin proteases and expressing the mutated genes in suitable hosts are presented. The enzymes exhibit improved wash performance in comparison to their wild type parent enzymes. The enzymes are well-suited for use in detergent compositions.

Abstract: The present invention relates to the use, in humans, of inactivated parapoxviruses for the prophylaxis and treatment of diseases which are accompanied by an increased deposition of collagen, with it being possible for both internal organs, such as the liver, and the skin and its appended structures, to be affected. The invention relates, in particular, to liver fibrosis and/or liver cirrhosis consequent upon virus hepatitis, or to ethanol-induced liver diseases and to cystic fibrosis.

Abstract: The invention relates to methods of sterilizing biologically active products, particularly therapeutic or prophylactic products and the compositions obtained thereby. The methods include obtaining a dried sample containing an amount of trehalose sufficient to render heat stability to the product and exposing the dried sample to heating conditions at a temperature and for a duration sufficient to substantially inactivate viruses, especially non-lipid encapsulated viruses. The drying methods include both ambient drying conditions and lyophilization. The heating conditions include any known in the art and cover a wide range of temperatures and heating times. The compositions obtained contain stable products and do not contain measurable infectious virus, particularly parvovirus.

Abstract: The growth of the bacterium, Burkholderia cepacia (ex Pseudomonas cepacia) CIP 1-2052 is substantially increased when it is supplied with tert-butanol (TBA) or tert-amyl alcohol (TAA) as the sole source of carbon and energy in the presence of at least one cobalt salt, at a concentration of 0.01 to 4 mg/l of medium. The bacterium is degraded to CO2 in the presence of oxygen. The inoculom produced by the process and the degradation process for these alcohols are useful for water treatment applications.

Abstract: A 10 kb gene cluster has been isolated from Rhodococcus ruber SC1 comprising genes encoding enzymes useful for the synthesis of dodecanoic diacid from cyclododecanone and other cyclic intermediates. The six specific open reading frames have been identified that are associated with dodecanoic diacid biosynthesis. In addition to the expected substrates the enzymes of the instant invention have moderate specificity for C11-C15 compounds.

Abstract: A growth support scaffold for cells and tissue is formed of naturally derived connective or skeletal tissue which has been treated for elimination of cellular and cytosolic elements, and modified by cross-linking with hyaluronic acid, proteoglycans, glycosaminoglycans, chondroitin sulfates, heparan sulfates, heparins or dextran sulfates. The scaffold may contain cell adhesive molecules and growth factors, and can be formulated as a malleable prosthesis. A tissue maintenance system is provided containing a chamber having a constant atmosphere which may contain the scaffold impregnated with cells, a medium-containing reservoir, a pump which can be computer controlled for circulating the medium between the chamber and reservoir and may change direction of medium flow every 1 to 3 minutes, and a pressure generator, which can be the pump, for producing rhythmic pulses of pressure such as between 0.5 to 30 atm and frequency of 5-300 per minute.

Abstract: Methods and apparatus for sorting microstructures, such as macromolecules, viruses, cells, and minute particles, in a fluid using microlithographic sorting array that is reversibly sealed by a cover. A silicone elastomer cover is used in one embodiment. In another, silicon microstructures are used to case elastomeric replicas of obstacle arrays, the tops of which reversibly seal against a flat surface. The reversible seal allows access to fractionated microstructures within the structure for further analysis.

Abstract: In a preferred embodiment, a method of performing a reagent protocol using polymerase chain reaction, including: indexing patterns of reagent wells on a continuous basis through at least one step of reagent addition to the reagent wells; and then indexing the patterns of reagent wells on a continuous basis through a plurality of individual heat transfer stations, whereby at each of the individual heat transfer stations, the patterns of reagent wells are subjected to a unique temperature change to cause one amplification step, with the plurality of individual heat transfer stations providing total amplification required for the protocol.

Abstract: An elongate canister having a generally rectangular cross-section sized to house a plurality of antibiotic susceptibility test arrays stacked one atop another and maintained secure within an environmentally controlled inventory chamber in a random access microbiological analyzer.

Abstract: Arrays of flowable or fixed particle sets are used in microfluidic systems for performing assays and modifying hydrodynamic flow. Also provided are assays utilizing flowable or fixed particle sets within a microfluidic system, as well as kits, apparatus and integrated systems comprising arrays and array members.

Abstract: Apparatus and methods are provided for performing cell growth and cell based assays in a liquid medium. The apparatus comprises a base plate supporting a plurality of micro-channel elements, each micro-channel element comprising a cell growth chamber, an inlet channel for supplying liquid sample thereto and an outlet channel for removal of liquid sample therefrom, a cover plate positioned over the base plate to define the chambers and connecting channels, the cover plate being supplied with holes to provide access to the channels. Means are incorporated in the cell growth chambers, for cell attachment and cell growth. In particular, the invention provides a rotatable disc microfabricated for performing cell growth and cell based assays. The apparatus and method can be used for the growth of cells and the detection and measurement of a variety of biochemical processes and products using non-invasive techniques, that is techniques which do not compromise the integrity or viability of cells.

Abstract: An apparatus for cultivating tissue cells or microorganisms in suspension, in a manner which ensures formation of an axially symmetric vortex motion of liquid with an axial countercurrent flow in the cell suspension without stagnant zones at various locations. The apparatus has guide elements that stabilize the position of an annular partition with respect to the surface of the suspension, including first blades and second blades. The first blades are attached to the upper surface of the partition with the help of the first struts. The second blades are attached to the lower surface of the partition with the help of the second struts. Each of the first blades and the second blades is provided with a clamping device of “screw-nut” or collet type for varying the angle of attack with respect to the incoming flow of gas and liquid and for securing to the respective strut on the upper surface of the annular partition and at the lower surface of it.

Abstract: The method for the holding in flotation of a substance such as a tissue part in a bioreactor (61) is characterized in that the substance (73) is acted upon with a fluid; and in that the flow of the fluid acts counter to gravity in such a manner that the substance (73) is held in flotation. The bioreactor (61) with a container (62) for a substance (73) which is to be acted upon with fluid comprises a first flow chamber (66a) to which a flowing fluid can be supplied, with the first flow chamber (66a) being designed in such a manner that the fluid which flows upwardly therein has a lower speed with increasing height.

Abstract: The invention discloses an apparatus and a method for UV oxidation and microbiological decomposition of organic waste air. The invention provides an integrated system consisting of UV oxidation as a pretreatment process and biofiltration and biotrickling filtration, in which the organic pollutant residuals are decomposed with microorganisms.

Abstract: The present invention provides, among other things, supports upon which one or more species can be adsorbed, captured, or immobilized for biochemical procedures. In various embodiments, the supports include a plurality of deformable petal-like members that provide binding sites for biochemical species. The invention provides an apparatus and method for the ready insertion of the petal-like members into respective wells of a multi-well microplate (e.g., a standard-format 96- or 384-well plate).

Abstract: A device for culturing microorganisms and its use are described. The claimed device comprises a substrate having a top side, a pedestal mounted on the top side of the substrate and comprising a non-absorbent culture surface, a flexible cover sheet attached to the substrate and comprising a bottom surface, the cover sheet being configured to cover the culture surface, and a culture medium deposited on one or more surfaces selected from: the culture surface, and the cover sheet bottom surface. An aqueous sample is spread and contained by the claimed device without additional equipment or manipulation by the end user.

Abstract: The invention concerns a device for lysis (1) of micro-organism to release at least one intracellular biological constituent, comprising a container (2) wherein are present a biological sample, in liquid medium, containing the micro-organism to be lyzed, and a material in the form of particles, relatively hard and inert with respect to the sample. The invention also concerns a grinding method. The material in the form of particles comprises at least two types of grinding means into different dimensions: at least large dimension magnetic means (3) automatically controlled by a magnetic field; and at least small dimension means (4) actuated by the large dimension grinding means (3). The invention is useful for separating biological constituents.

Abstract: Nucleic acid, including DNA, immunization is used to generate a protective immune response in a host, including humans, to a serine-threonine kinase (STK) of a strain of Chlamydia. A non-replicating vector, including a plasmid vector, contains a nucleotide sequence encoding a STK or a fragment of the STK that generates antibodies that specifically react with STK and a promoter sequence operatively coupled co the first nucleotide sequence for expression of the STK in the host. The non-replicating vector may be formulated with a pharmaceutically-acceptable carrier for in vivo administration to the host.

Abstract: An avian infectious recombinant herpesvirus is prepared by inserting a foreign gene, in particular a heterologous antigen gene, into an insertion site in an untranslated genetic region in the genome. A chicken vaccine comprising such a recombinant virus is also provided.

Abstract: An isolated nucleic acid molecule encodes the genomic sequence encoding a human 3′-5′ exonuclease. A human exonuclease independent of DNA polymerase is produced in host cells from recombinant vectors. Methods of use include inhibition of exonuclease activity to increase incorporation of nucleotide analogs into DNA in rapidly dividing cells.

Abstract: Gel-based medium compositions and a method of use thereof in normothermic, hypothermic or cryopreservative storage and transport of cell samples are described. These gel-based compositions contain a cell maintenance and preservation medium together with a gelling agent. Such gel-based medium compositions protect various cell samples, such as animal or plant organs, tissues and cells, from the mechanical, physiological and biochemical stresses inherently associated with liquid preservation techniques.

Abstract: The present invention provides methods of modulating the shedding of L-selectin in cells or tissues using an inhibitor of TACE expression or activity. Antisense oligonucleotides targeted to nucleic acids encoding TACE are preferred forms of TACE inhibitors. These methods are believed to be useful both therapeutically and diagnostically and as research tools. The present invention further comprises methods of treating conditions associated with altered L-selectin shedding or altered L-selectin levels.

Abstract: A monolayer sheet structure is prepared containing a confluent monolayer of primary hepatocytes cultured on a substrate in sheet form. The monolayer sheet structure is formed by treating the hepatocytes in the monolayer formation stage with a protein-phosphorylation inhibitor having an indolo [2,3-a] carbazole structure, such as staurosporine, or other similar structure.

Abstract: The invention disclosed herein provides a purified polynucleotide, wherein the polynucleotide comprises a nucleic acid encoding a plant DFD kinase polypeptide, methods for using same, and transgenic plants containing the polynucleotide.