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The instant invention describes a novel reaction that includes spontaneous racemization of an azalactone via enol tautomerization. This racemization results in improved yield and ee over other reactions previously described.

Processes for the production of a product by the enzymatic treatment of a soluble or particulate substrate with a particulate, immobilized enzyme, by treating a process liquor containing the substrate in a bioreactor to produce a slurry of effluent immobilized enzyme and the product in an effluent liquor. The slurry is subject to a non-immobilized enzyme damaging shear inducing effective separation process to provide effluent immobilized enzyme, and effluent liquor containing the product; and reusing the effluent immobilized enzyme in the enzymatic treatment. The process provides for the reclamation and reuse of the immobilized enzyme even when a further particulate solid is present in the effluent/product stream.

The invention provides methods for producing products comprising improved host cells genetically engineered to have uncoupled productive and catabolic pathways. In particular, the present invention provides host cells having a modification in nucleic acid encoding an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a modification of nucleic acid encoding an enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such improved host cells are used for the production of products, such as, ascorbic acid intermediates. Methods for making and using the improved host cells are provided. Nucleic acid and amino acid sequences for glucokinase and gluconokinase are provided.

Isolated nucleic acid molecules, designated SRT nucleic acid molecules, which encode novel SRT proteins from Corynebacterium glutamicum are described. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing SRT nucleic acid molecules, and host cells into which the expression vectors have been introduced. The invention still further provides isolated SRT proteins, mutated SRT proteins, fusion proteins, antigenic peptides and methods for the improvement of production of a desired compound from C. glutamicum based on genetic engineering of SRT genes in this organism.

The present invention relates to a novel composition useful for inhibiting White Spot Syndrome Virus (WSSV) infection of crustacean animals, particularly those of the genera Penaeus sp. More specifically, the novel composition comprises a polypeptide whose amino acid sequence corresponds to at least a portion of Vp28, a surface protein of WSSV, or an antibody that specifically binds the polypeptide. The polynucleotide sequences encoding the Vp28 polypeptides of the present invention are also disclosed. Further disclosed are methods for using the novel compositions to inhibit WSSV infection in crustacean animals.

Isolated nucleic acid molecules, designated MR nucleic acid molecules, which encode novel MR proteins from Corynebacterium glutamicum are described. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing MR nucleic acid molecules, and host cells into which the expression vectors have been introduced. The invention still further provides isolated MR proteins, mutated MR proteins, fusion proteins, antigenic peptides and methods for the improvement of production of a desired compound from C. glutamicum based on genetic engineering of MR genes in this organism.

The present invention provides a method for inhibiting growth of a cancer cell, particularly a renal cell carcinoma, by contacting the cell with a composition composed of an HIG2 siRNA or HIG2 antibody. Methods of diagnosing renal cell cancer are also provided within the present invention.

This invention is directed generally to methods of controlling the odor of a biological material, and more particularly to methods comprising providing the biological material with an Fe(III)-reducing bacteria and a source of Fe(III). This invention also is directed generally to compositions and kits for controlling the odor of a biological material.

This invention relates generally to the field of PCR. In particular, the invention provides methods, compositions and kits for optimizing multiplex PCR primers using, inter alia, a plurality of 5' and 3' specific primers and a 5' and a 3' universal primer at various ratios.

Methods are provided for treating a vaccine containing infectious particles which may be viral, bacterial, and/or cellular in nature. Preferred methods include the steps of adding an effective, non-toxic amount of an endogenous photosensitizer to the fluid and exposing the fluid to photoradiation sufficient to inactivate the infectious particles but not enough to damage the antigenic characteristics of the infectious particles.

An apparatus for brewing compost tea from an aqueous compost mixture using only air bubbles as a means to circulate the mixture during fermentation. The mixture is held in a tank having a continuous sidewall and a conical bottom section with a central discharge opening. A plurality of equidistant conduits extend from the tank discharge opening to discharge nozzles having discharge ends at or just above the water level in the tank. A compressed air supply is joined by air lines to air diffusers in each of the conduits. During use, air is discharged from the diffusers to continually circulate the aqueous compost mixture upwardly in said conduits from the tank discharge opening to the discharge nozzles. The microorganisms grow rapidly in the aerated water, resulting in a rich compost tea. Due to the conical tank bottom and angled nozzles, the water swirls in the tank, creating a vortex.

A petri dish that includes a cell trapping portion having a plurality of suction holes. A cell-contained liquid is placed in the petri dish and the cell-contained liquid is sucked from the suction holes, which are smaller that the cells, from below the petri dish to trap the cells in the suction holes. The petri dish includes a liquid retaining portion having a space of a capacity that allows sucked-liquid, which is liquid sucked through the suction holes and that do not contain cells, to be retained therein, and configured so that an interface between the sucked-liquid in the space and gas being positioned at a lower level than a surface level of the cell-contained liquid in the petri dish.

An apparatus for producing a tissue array, having at least one receiver block (1) and at least one donor block (2) that comprises tissue (3) to be investigated, is described. The donor block (2) comprises tissue (3) to be investigated, a first hollow needle (4) for creating a cavity in the receiver block (1), and a second hollow needle (5) for removing a sample from the tissue (3) and introducing the sample (3) into the cavity of the receiver block (1), being provided. For positioning of the first and/or the second hollow needle (4; 5) above the receiver block (1) and/or the donor block (2), a positioning array (11) having predefined markings, as well as a movably mounted lever, are provided for transferring the position of the markings onto a corresponding position on the donor block (2) and/or onto a corresponding position on the receiver block (1).

A biochemical reaction cassette comprises a housing member, a reaction chamber arranged in the housing member and having a bottom section and a ceiling facing the bottom section, an injection port arranged at the ceiling of the reaction chamber, a discharge port arranged at the ceiling of the reaction chamber and a probe carrier arranged at the bottom section of the reaction chamber, the ceiling having an inclination with the highest part located at the discharge port in the vertical direction.

Vaccines against prion disease eliciting a humoral immune response when administered mucosally are described. The vaccines comprise a prion protein, a prion protein fragment, or a non-amyloidogenic prion protein homolog and an adjuvant suitable for inducing a humoral immune response after mucosal administration. Suitable adjuvants include cholera toxin subunit B, heat-labile enterotoxin and aluminum hydroxide. Alternatively, the vaccine comprises a vector encoding a prion protein, fragment, or homolog in an attenuated Salmonella host. The vaccines can be used to prevent or treat prion disease in humans and other mammals.

Lentivector constructs for expression of recombinant proteins, polypeptides or fragments thereof and methods of making the same are described. The lentivectors typically have a self-processing cleavage sequence between a first and second protein or polypeptide coding sequence allowing for expression of a functional protein or polypeptide under operative control of a single promoter and may further include an additional proteolytic cleavage sequence which provides a means to remove the self-processing cleavage sequence from the expressed protein or polypeptide. The vector constructs find utility in methods relating to enhanced production of biologically active proteins, such as immunoglobulins or fragments thereof in vitro and in vivo.

The present invention relates to a binding motif and methods of regulating cell function which methods target a single amino acid residue preferably a Tyr in a binding motif equivalent to a motif of the common beta chain (.beta.c) of the GM-CSF/IL-3/IL-5 receptor. Preferably, the cell functions affect cell survival and proliferation in cells. The methods can be used for treatments of conditions relating to cell survival and proliferation and can be used to expand progenitor cells, for instance, for transplantation purposes.

The nucleic acid sequence of the POMC enhancer is disclosed herein. Sequences from the human, rat, rabbit, hamster, mouse, and cow POMC enhancer are disclosed. Hybrid transgenes, comprising a POMC transcriptional control element operably linked to a nucleic acid sequence encoding a marker are also enclosed. In addition, transgenic mice carrying a hybrid transgene including a POMC control element operably linked to a marker are disclosed herein.

Disclosed herein are methods and compositions for modulation of gene expression, with single-gene specificity, in a human-sized genome.

The present invention provides a chaperonin-target protein complex and a method of producing the same, and a method of stabilizing the target protein, a method of immobilizing the target protein, a method of analyzing the structure of the target protein, a sustained-release formulation, and a method of producing an antibody against the target protein. The chaperonin-target protein complex in the present invention includes a fusion protein having a chaperonin subunit and an affinity tag linked to the chaperonin subunit via a peptide bond and a target protein for which the affinity tag shows a specific affinity, wherein the target protein is bound to the affinity tag by means of the specific affinity, thereby forming a chaperonin ring structure consisting of a plurality of chaperonin subunits. The chaperonin-target protein in the present invention stabilizes the target protein and surely immobilize on a carrier without causing any change in its stereostructure.

Polynucleotides and polypeptides which participate in influenza virus infection of cells and nucleic acid molecules, which include a polynucleotide sequence capable of specifically binding the polypeptides of the present invention. Also provided are methods of using such nucleic acid molecules, polynucleotides and antibodies directed thereagainst for diagnosing, treating and preventing influenza virus infection.

The present invention provides a method and compositions for synthesizing an oligopeptide or polypeptide by convergent assembly of a plurality of pairs of oligopeptides in chemical ligation reactions. An important aspect of the present invention is an oligopeptide having a C-terminal disulfide-protected carboxythioester group that can be deprotected to spontaneously generate a free C-terminal thioester moiety. This allows a single precursor to participate in a succession of chemical ligation reactions, thereby making the convergent synthesis approach possible. The present invention is useful in methods for chemical synthesis of oligopeptides, polypeptides and proteins, and improves the efficiency of native chemical ligation reactions, particularly where four or more peptide fragments are used to assemble an oligopeptide, polypeptide or protein product.

The invention also provides a process for preparing a composition comprising: preparing a mixture of polypeptides, wherein each polypeptide in the mixture (a) is a copolymer of the amino acids L-alanine, L-glutamic acid, L-tyrosine and L-lysine, and (b) may be present in the form of a pharmaceutically acceptable salt; and wherein in the mixture 13% to 38% of the polypeptides have a diethylamide group instead of a carboxyl group present at one end thereof; determining the average molecular weight of the polypeptides in the mixture by size exclusion chromatography on a gel permeation chromatography column calibrated using a plurality of copolymers of defined sequence and molecular weight; and including in the composition only those polypeptide mixtures determined to have an average molecular weight between 13,500 and 18,500 Daltons, wherein each of the copolymers is a polypeptide consisting of L-alanine, L-glutamic acid, L-tyrosine and L-lysine with a defined molecular weight between 12,000 and 30,000 Daltons, and a process for making same.

The invention provides Sp35 polypeptides and fusion proteins thereof, Sp35 antibodies and antigen-binding fragments thereof and nucleic acids encoding the same. The invention also provides compositions comprising, and methods for making and using, such Sp35 antibodies, antigen-binding fragments thereof, Sp35 polypeptides and fusion proteins thereof.

A vector of the present invention has DNA encoding a protein or a product having the same effect as the protein, the protein containing an amino acid sequence from amino acid numbers 47 to 802 in SEQ. ID. NO:2. Expression of the DNA gives human chondroitin synthase. By using human chondroitin synthase, it is possible to produce a saccharide chain having a repeating disaccharide unit of chondroitin. The DNA or part thereof may be used as a probe for hybridization for the human chondroitin synthase.

Homogeneous preparations of IL-28A, IL-28B, and IL-29 have been produced by mutating one or more of the cysteine residues in the polynucleotide sequences encoding the mature proteins. The cysteine mutant proteins can be shown to either bind to their cognate receptor or exhibit biological activity. One type of biological activity that is shown is an antiviral activity.

This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to develop epitope-based vaccines directed towards HBV. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use in the prevention and treatment of HBV infection.

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

The present invention provides an adsorbent, adsorption unit, and an adsorption method which make it possible to selectively adsorb an immunoglobulin and/or an immune complex present in a body fluid (for example, blood, plasma, etc.) efficiently without pretreating the body fluid. By immobilizing a compound having binding activity for an immunoglobulin and/or an immune complex on a water-insoluble carrier, an adsorbent having remarkably excellent adsorption capacity may be obtained.

The invention provides isolated polypeptide and nucleic acid sequences derived from Streptococcus pneumoniae that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from bacterial infection.

The invention provides isolated polypeptide and nucleic acid sequences derived from Streptococcus pneumoniae that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from bacterial infection.

A fluorescence detection apparatus for analyzing samples located in a plurality of wells in a thermal cycler and methods of use are provided. In one embodiment, the apparatus includes a support structure attachable to the thermal cycler and a detection module movably mountable on the support structure. The detection module includes one or more channels, each having an excitation light generator and an emission light detector both disposed within the detection module. When the support structure is attached to the thermal cycler and the detection module is mounted on the support structure, the detection module is movable so as to be positioned in optical communication with different ones of the plurality of wells. The detection module is removable from the support structure to allow easy replacement.

A selective targeting method is disclosed which comprises contacting a peptide library with an anti-target to allow the peptides to bind; separating non-binding peptides from the anti-target bound peptides, contacting the non-binding anti-target peptides with a target allowing the unbound peptides to bind with the target to form a target-bound peptide complex; separating the target-bound peptide complex from peptides which do not bind to the target, and identifying the target-bound peptides. In one embodiment the target is skin or hair. In another embodiment the anti-target is hair when the target is skin, and the anti-target is skin when the target is hair.

In a nucleic acid isolation method for a solid biological sample, since two or more kinds of instruments are used for biological sample disruption and nucleic acid isolation, the operations are complicated, thereby increasing the operating labor, prolonging the operation time, and deteriorating the property of a nucleic acid associated with the prolonged operation time. A sample stuck to the instrument for disruption during the sample disruption operation is not brought to the subsequent nucleic acid isolation operation, thereby causing a problem of reducing the nucleic acid isolation efficiency. In the present nucleic acid isolation method, a step of disrupting a biological sample and a step of isolating a nucleic acid released from the disrupted sample are conducted with one instrument. The nucleic acid isolation efficiency can be improved without losing a sample stuck to an instrument for sample disruption, and the operability can be improved by simplifying the operations.

There is provided an identification technique that can consistently maintain a set of information specifying a specimen through all the processes from the amplification process to the detection process of a specific sequence. A base sequence incorporating as a set of decodable information an individual code imparted to the specimen is disposed in an amplifiable region to form an identifier; the identifier is amplified together with the specimen and the presence of the identifier in the amplification product is detected; thus, the individual code of the specimen in the amplification product can be recognized, which specimen the amplification product is derived from can be easily identified, and whether or not the amplification has been carried out satisfactorily can also be simultaneously tested.

The present invention relates generally to molecules such as peptides, polypeptides and proteins which interact immunologically with T lymphocytes in subjects having latex allergy and genetic sequences encoding same. These molecules are preferentially immunointeractive with T cells in subjects having a Hev b 5 allergy. The present invention also extends to antibodies, preferably monoclonal antibodies, directed to latex allergens and in particular to Hev b 5, and to the B cell epitopes recognised therein. The molecules of the present invention are useful in the development of diagnostic, therapeutic and prophylactic agents for conditions characterised by an aberrant, inappropriate or otherwise unwanted immune response to Hev b 5 or derivative or homologue thereof.

The present invention provides a class of Conformationally Assisted Probes comprising (a) a nucleic acid moiety; (b) an energy donor moiety; (c) an energy acceptor moiety; and (d) one or more stabilizing moieties.

Methods, kits, and compositions for detecting the methylation status of various genes are useful in various diagnostic applications involving suspected proliferative disorders such as prostate cancer.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R63 that responds to particular bitter compounds The present invention further relates to the use of this receptor in assays for identifying ligands that modulate the activation of this taste receptor. These compounds may be used as additives and/or removed from foods, beverages and medicinals in order to modify (block) T2R-associated bitter taste. A preferred embodiment is the use of the identified compounds as additives in foods, beverages and medicinals for blocking bitter taste.

Chlorinated ethylene-decomposition bacteria is detected by performing PCR using nucleic acid comprising 18.about.25 nucleotides that preferentially hybridizes to the 16S rRNA or rDNA of chlorinated ethylene-decomposing bacteria and has any of base sequences of SEQ ID No. 1.about.15, a base sequence that has at least 90% homology with any of these base sequences, or a base sequence complementary to any of these base sequences as the primer and the nucleic acid in a sample as the template. The DNA fragment that has been synthesized is detected. Chlorinated ethylene or ethane is decomposed by introducing the chlorinated ethylene-decomposing bacteria detected by this method to contaminated soil or underground water.

The present invention provides a screening method for a compound which is highly safe and has a prophylactic or therapeutic effect on diabetes, and a highly safe pharmaceutical composition for the prophylaxis or treatment of diabetes. Specifically, a drug for the prophylaxis or treatment of diabetes, which contains, as an active ingredient, a compound having PPAR.gamma. activation activity and PTP inhibitory activity, and a method of screening for the drug are provided.

The present invention discloses compositions and methods for enabling the longterm storage and/or use of colloid particles without substantial degradation of their performance, for example, by chemical or physical degradation, by particle aggregation, changes in pH and/or relative humidity, changes in salt concentration, and/or by a decrease in the binding activity or other detrimental change in biological, chemical, or physical properties of the colloid particles. In one aspect of the invention, the colloid particles are treated with an aggregation-preventing entity, for example, by immobilizing the entity relative to the colloid particle. In one embodiment, the aggregation-preventing entity forms at least a part of, and/or is immobilized relative to, a self-assembled monolayer ("SAM") immobilized to the colloid particle. The aggregation-preventing entity may be added to non-aggregated or aggregated particles, for example to prevent aggregation and/or to reduce the degree of aggregation. In some embodiments of the invention, the colloid particles are essentially free of surfactants and/or other non immobilized aggregation-preventing entities. The colloid particles and/or solutions thereof may be stored before use without substantial degradation or aggregation over long periods of time in a dried state and/or at low temperatures. After storage, certain colloid particles provided by the invention can remain substantially non-aggregated. Various colloid particles of the invention may be used in many techniques, for example, in gels or other assay systems. In some cases, the colloid particles have a high degree of specificity and/or activity, which is due, at least in part, to their ability to remain in a substantially non-aggregated and detergent-free state during storage and/or use.

A method and apparatus of interrogating an addressable array unit, which includes a substrate, a light reflecting layer on a front side of the substrate, and a plurality of features on a front side of the array. The method may include, for each of multiple features, illuminating the feature simultaneously with reflected and non-reflected interrogating light. A light emitted from respective features is detected. Either or both, constructive interference of interrogating light at the features, or constructive interference of light emitted from the features, can be obtained to allow lowering of light power from the source, enhanced signal, or reduced noise, or combinations of the foregoing. High depth discrimination may also be obtained without the need for a confocal detection system with conventional pinhole.

The present invention provides compositions and methods for the regulation of cytokine signaling through the Tumor Necrosis Factor (TNF) pathway. Specifically, the invention provides a novel gene, polypeptide and related compositions and methods for the regulation of ectodomain shedding. In preferred embodiments, methods and compositions for the regulation of TNF Type-1 Receptor ectodomain shedding are provided. The present invention finds use in therapeutics, diagnostics, and drug screening applications.

Methods and compositions for diagnosing, detecting and treating a pancreatic disease associated with differential expression of E-cadherin in comparison to healthy cells. Also provided are antagonists or agonists of E-cadherin, and methods for screening agents that modulate the E-cadherin level or activity in vivo or in vitro.

With an insulated gate field effect transistor in which deoxyribonucleic acid (DNA) probes are immobilized on a gold electrode, extension reaction on the gold electrode is performed with DNA polymerase to directly measure an increased amount of a phosphate group caused by the extension reaction, that is, negative charge, by means of a current change between a source and a drain of the insulated gate field effect transistor. Thus, presence/absence of hybridization of target DNAs with the DNA probes, and presence/absence of the extension reaction are detected. Optimum immobilization density of the DNA probes on the gold electrode is set at 4.times.10.sup.12 molecules/cm.sup.2. To reduce surface potential fluctuation caused by external variation (influences of foreign substances), which is a problem when using the gold electrode in a solution, a high-frequency voltage equal to or above 1 kHz is applied between the gold electrode and a reference electrode by a power source.

The present teachings provide novel methods, compositions, and kits for analyzing mature micro RNAs (miRNAs). By taking advantage of the observation that most mature miRNAs in cells are tightly associated with RISCs, the present teachings provide approaches for studying mature miRNAs without the complications of additional nucleic acids. For example, in some embodiments the present teachings provide a method of purifying mature miRNAs comprising heating a sample to form a lysate, and, degrading the additional nucleic acids. The resulting mixture lacks the additional nucleic acids, and contains mature miRNAs associated with RISCs. Liberating the mature miRNAs from RISCs, for example by a protease, a detergent, and/or heat, can result in a pure collection of mature miRNAs.

The present invention provides methods, compositions, and kits useful for reducing pain in a subject by inhibiting Epac, PLC.epsilon., and/or PLD. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that reduce pain. Methods of the invention can involve assaying test agent binding to Epac, PLC.epsilon., or PLD. Alternatively, test agents can be screened for their ability to alter the level of Epac, PLC.epsilon., or PLD polypeptides, polynucleotides, or action.

The present invention encompasses methods and compositions useful in diagnosing and treating hepatic disorders, especially those characterized by inflammation. The method comprises administration of an agent which prevents the interaction of MAdCAM with a MAdCAM binding partner or ligand. These compositions are useful in treating diseases or disorders involving .alpha.4.beta.7/MAdCAM blockade, as well as inhibiting a primary event in the inflammatory response such as blocking interactions between intercellular adhesion molecules and their ligands. Disorders treatable using the methods disclosed herein include infections, especially viral infections, iatrogenic disorders, cholestatic disorders, hereditary disorders, sarcoidosis, organ transplant, and the like. The diagnostic methods of the invention can be employed to detect the presence of a disorder or to monitor the course of therapy used to treat the disorder.

The invention concerns sensitive methods to measure mRNA levels in biopsied tumor tissues, including archived paraffin-embedded biopsy material. Th invention also concerns breast cancer gene sets important in the diagnosis and treatment of breast cancer, and methods for assigning the most optimal treatment options to breast cancer patient based upon knowledge derived from gene expression studies.

In labeling a cell, and separating and collecting the cell according to a degree of the labeling using a cell separator, effects on the cell is minimized and the use of the collected cell is facilitated, thereby, when labeling a cell, the cell is labeled in the state where interaction of each cell is retained. In the labeling, a specific labeling material present on a surface of a target cell is taken in the cell via a transporter, and the cell is dispersed one by one to separate the same with a cell separator. Immediately after the separation, the cell is put in a solution not containing the specific labeling substance to remove the specific labeling substance taken in the cell. This series of steps is continuously conducted with a cell separation chip.

Provided herein are methods for determining if a subject will benefit from A.sub.2B receptor antagonist therapy.

Disclosed herein is a process for stripping oligonucleotide target from a microarray to allow reuse of the microarray. The process comprises providing a microarray having probe oligonucleotides attached thereto and target oligonucleotides hybridized to the probe oligonucleotides. The microarray is then incubated with a formulation comprising an organic solvent and an organic base. The target oligonucleotides are substantially removed from the microarray by the formulation. Alternatively, prior to or after incubation of the microarray with the formulation, the microarray may be contacted to an aqueous solution of a base to improve the efficiency of removal of the target oligonucleotides.

The present invention relates to a method of producing a composite particle of a nanoparticle and a liposome in which a substance to be introduced has been encapsulated, characterized in that a hollow nanoparticle containing a hepatitis B virus protein or a modification thereof is fused to the liposome in which the substance to be introduced has been encapsulated.

The present invention is based on the discovery of methods and combinations of probes to chromosomal regions that are gained or lost or imbalanced in melanoma that provide highly specific and sensitive assays for the detection of melanoma cells.

Methods of injury assessment in an individual include the steps of determining a pattern of expression exhibited by blood cells obtained from an individual and comparing the pattern of expression exhibited by the obtained blood cells to an injury database to assess the injury.

Isolated nucleic acid molecules, designated MCP nucleic acid molecules, which encode novel MCP proteins from Corynebacterium glutamicum are described. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing MCP nucleic acid molecules, and host cells into which the expression vectors have been introduced. The invention still further provides isolated MCP proteins, mutated MCP proteins, fusion proteins, antigenic peptides and methods for the improvement of production of a desired compound from C. glutamicum based on genetic engineering of MCP genes in this organism.

The present invention discloses a method that can be used to identify one DNA sequence or one specific group of DNA sequences from a complex biological sample. Diverse molecular biology methods require the use of short DNA sequences, called oligonucleotides, that are artificially synthesized from a description of their composing bases. The disclosed method allows the design of oligonucleotides useful for said molecular biology procedures, like probe design procedures, and is characterized by the construction of a database of reference sequences, the selection of a subset of sequences belonging to target organisms, the selection of candidate oligonucleotides from such sequences, the depuration of these candidate oligonucleotides according to hybridization specificity and thermodynamic stability criteria, and the sorting of such oligonucleotides according to their taxonomic specificity. In a second aspect, a method is disclosed to design oligonucleotides pairs or primers, which are required in certain molecular biology techniques, like polymerase chain reaction (PCR) techniques. This method is similar to the first aspect of the invention, but thermodynamically compatible oligonucleotides pairs or primers that hybridize to the same sequence at a distance which is within a given range are evaluated.

Described herein are genes whose expression are up-regulated or down-regulated in specific cancers. Related methods and compositions that can be used for diagnosis and treatment of those cancers are disclosed. Also described herein are methods that can be used to identify modulators of selected cancers.

A system and method for conducting high-throughput interactions between test compositions and analytes, comprising one or more test compositions, and a plurality of independent micromatrices, wherein each said micromatrix encapsulates at least one said test composition; and said micromatrices are made of a material that is permeable to an analyte.

Magnets and magnetic particle-labeled reagents are used to capture and/or release magnetic particle-tagged entities for immunohematology diagnostic testing purposes, especially tests performed in blood banking. The magnetic tagged entities may be tagged antibodies, tagged blood cells, tagged universal binding partners, especially tagged lectins and tagged Coombs reagent, and other binding agents such as biotin-avidin, Protein A or G, ligands and their receptors and the like. Separation of unbound material from bound material is effected through the use of one or both the magnetic field effect on the magnetic labeled reactants and the density gradients of layers of an assay construct. Constructs such as chromatographic strip lateral flow format, and liquid phase reactions in suitable vessels with end point determinations that do not require centrifugation to detect reacted entities. Readable labels such as enzymes, fluorophors, chemiluminescent materials, radioactive isotopes, and other labels may be attached to Coombs reagent to provide a readable product of the Coombs reagent with any antibody participating in the assay.

This invention provides methods for the diagnosis of cancer by identifying novel glycans that are diagnostic of cancerous cells or tumors in an human or animal subject, and methods for identifying markers of disease states in humans and/or animals using mass spectrometry on partially purified glycan-containing samples.

The invention relates to one or more size-based separation modules adapted to increase a concentration of a first analyte in a sample by at least 10,000 fold, wherein said first analyte has an initial concentration in said sample of less than 1.times.10.sup.-3 analytes/.mu.L, and an analyzer for analyzing said first analytes in an enriched medium.

A system for the detection of ligands comprising at least one receptor and an amplification mechanism coupled to the receptor wherein an amplified signal is produced as a result of receptor binding a ligand. Examples of suitable amplification mechanisms include antibody-embedded liquid crystalline materials; use of alpha-2-macroglobulin to encage an enzyme, whereby the enzyme is separated from its substrate by an receptor; and a receptor engineered to inhibit the active of site of an enzyme only in the absence of a ligand. Also provided are methods for the automatic detection of ligands.

The present invention relates to oligonucleotides useful for determining the presence of Chlamydophila pneumoniae in a test sample. The oligonucleotides of the present invention may be incorporated into detection probes, capture probes and amplification oligonucleotides, and used in various combinations thereof.

Presence of free insulin receptor .alpha.-subunit in blood was discovered. Furthermore, methods for measuring the insulin receptor .alpha.-subunit was provided, the method comprising the steps of contacting the insulin receptor .alpha.-subunit in a blood sample with an antibody recognizing the insulin receptor .alpha.-subunit, and detecting the binding between the two. Measurement of the free insulin receptor .alpha.-subunit in the blood is useful for evaluating risk factors for diabetes. In addition, the measurement methods of the present invention showed that concentrations of the free insulin receptor .alpha.-subunit in the blood of diabetes or cancer patients are significantly high. Free insulin receptor .alpha.-subunit in blood is useful as a marker for diabetes or cancer.

Biomarkers may be used in the treatment of cancer, and as an aid in clinical decision making regarding which anti-cancer therapy to use in a particular patient. Described herein are methods of assessing whether a subject with a solid tumor is suitable for treatment with a dual EGFR/erbB2 tyrosine kinase inhibitor, by assessing the relative localization of pERK or pAKT in tumor cells, and/or assessing pre-treatment tumor cell levels of ErbB2.

An enzymatic process for preparing ethers is disclosed which includes reacting one or more alcohols with an ether in the presence of at least one enzyme.

A method to increase carotenoid production in carotenogenic microbial host cells is provided by down-regulating or disrupting glycogen synthesis. Disruption of glycogen synthase activity in a carotenogenic microbial host cell significantly increased carotenoid production. Carotenogenic microorganisms are also provided that have been optimized for the production of carotenoid compounds through the down-regulation and/or disruption of glycogen synthase activity.

A method and apparatus for electrically measuring an adverse effect of toxic substances on prokaryotic cells includes measuring a whole intracellular change caused by the presence of toxic substances as a change in an electric signal of cell membranes of the prokaryotic cells. According to the present invention, it is possible to electrically measure the presence of toxicity and the extent of the adverse effect very easily and within a rapid period of time and also to measure the adverse effect of toxic substances regardless of their type. Thus, the method and apparatus of the present invention have wide applicability and can be easily applied to a lab-on-a-chip.

Compositions, methods, and kits for detecting and monitoring kinase, phosphatase and protein post-translational modification activity are described. The compositions typically include a peptide, a detectable moiety, and a protease cleavage site. Modification of a peptide by a kinase, phosphatase or other protein post-translational modification alters the proteolytic sensitivity of the peptide, resulting in a change of a detectable property of the composition. Panel assays for determining substrates or modulators of kinase, phosphatase or other protein post-translational modification activity are also described.

The present invention provides a chemiluminescence enhancer treated to retain favorable dispersibility of fine solid carriers and stably exert a chemiluminescence enhancing action. The invention provides a chemiluminescence enhancer used for signal detection in a solid phase immunoassay using antigen or/and antibody immobilized onto fine solid carriers dispersible in a liquid medium, consisting of a water soluble macromolecular quaternary ammonium salt, a quaternary sulfonium salt or a quaternary phosphonium salt in order to enhance emission of light caused by an enzymatic reaction of a chemiluminescent substrate having dioxetane, wherein the chemiluminescence enhancer is given an aggregation inhibition treatment of the fine solid carriers by the treatment with an oxidizing agent or a reducing agent, and a chemiluminescence method and a kit using the chemiluminescence enhancer.

Improved colony forming cell (CFC) assays are described. The improved assay comprises modifications to the standard CFC assay that enable analysis of temporal, real-time changes in antigen expression during colony development without need to fixate or destroy the culture. The improved assay is applicable to hematopoietic CFC assays as well as to CFC assays for other cells, such as neural cells and mammary cells. In one embodiment, the invention comprises adding a detection reagent, most likely a fluorescently labeled antibody, that is specific for antigens (most likely a cell-surface antigen) expressed on progenitors or on specific mature cell types to a culture at the start or during culture. The invention also comprises modifications to the culture medium and cell preparations used in standard CFC assays to selectively promote the development of one colony type while preventing or suppressing the development of other colony types.

This invention provides a methods of detecting a bleeding disorder in mammals where the bleeding disorder is characterized by normal fibrinogen binding to ADP-activated platelets, but decreased fibrinogen binding to thrombin-activates platelets.

The present invention concerns methods and compositions for the construction of a series of stable vectors for genomic library construction useful in Gram negative species. In certain embodiments, the vectors contain the pBBR1 replicon, capable of to stable replication in a broad range of Gram negative species. In various embodiments, the