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 plasmid vectors may also contain bidirectional, rho-independent transcriptional terminators flanking the multiple cloning site, which allows for greater insert stability, and thus, greater genomic representation. Each vector may vary in its selection marker region, mobilization function, and promoter used to express insert sequences. These vectors are of use in the screening of highly representational genomic libraries in a broad variety of Gram negative species.

The invention provides arrays of glycans for detecting entities that bind to glycans. In some embodiments, the arrays can be used to detect disease, blood types, antibodies, bacterial or viral infection, cancer, and the like. The invention also provides methods and kits for such detection. In another embodiment, the invention provides methods of preventing or treating disease in a mammal by administering to the mammal a composition that includes at least glycan.

The invention relates to a method of identifying N-terminal proBNP in a sample with at least two antibodies that detect different epitopes of the N-terminal proBNP. The method is used to differentiate or classify samples of healthy individuals and samples of patients of NYHA classes I to IV. The invention further relates to recombinant N-terminal proBNP, its use as standard in a method of identifying N-terminal proBNP, to antibodies that detect recombinant N-terminal proBNP and to their production.

Described are methods for producing libraries of cells expressing at least two separate single polypeptide chain binding proteins, in which the binding proteins have different target epitopes. Such libraries are made by integration of the nucleic acid sequences encoding the polypeptide chains into the genome of the host cell, and selecting for cells that have successfully integrated these nucleic acids. The selected cells are preferably subjected to a cloning step. Mixtures of binding proteins are produced without having to individually produce each of the components of the mixture. A library of cells wherein essentially each cell encodes at least two single polypeptide chain binding proteins having different target epitopes is also herewith provided, as well as methods for producing a composition comprising at least two separate single polypeptide chain binding proteins having different target epitopes.

This invention provides novel liposome-based articles of manufacture and microarrays and methods of making and using them (1) to detect the presence of one or more agents in a sample, (2) to determine the amount of one or more agents in a sample, and (3) to determine whether a subject is afflicted with a disorder. This invention also provides kits which comprise the instant microarrays.

Data acquisition and cataloging are used to classify polypeptides into a reference index or database. The database can be used to identify previously unidentified samples. New polypeptides are characterized and added to the database.

Post-translational O-sulfonation of a serine or threonine residue of proteins is detected, optionally comparatively, wherein the detected O-sulfonation is detected under a first physiological condition, and is compared with a control O-sulfonation detected under a second physiological condition, and a difference between the detected and control O-sulfonations indicates a difference between the first and second physiological conditions. Predetermined changes in physiological conditions are used to infer specific changes in O-sulfonation. Proteins are modified by introducing a predetermined change in O-sulfonation at a serine or threonine residue of the protein, and optionally, detecting a resultant change in O-sulfonation. These methods include introducing or increasing O-sulfonation, eliminating or reducing O-sulfonation; and derivatizing or substituting O-sulfonation.

The invention provides for methods for producing water-soluble iron oxide nanoparticles comprising encapsulating the nanoparticles in phospholipids micelles. Also provided are methods for conjugating the inventive nanoparticles via functionalized phospholipids to a target molecule, such as an antibody. The invention further provides methods for using the nanoparticle-antibody conjugate of the invention as a contrast agent to image specific cells or proteins in a subject using fluorescent and magnetic imaging techniques.

The invention provides methods of monitoring the production of a target polypeptide by generating surface enhanced laser desorption/ionization mass spectral profiles of samples taken from multiple cell culture batches or of samples taken at different times from a given batch. The invention additionally provides methods for monitoring the purification of a target polypeptide from a mixture by generating surface enhanced laser desorption/ionization mass spectral profiles of samples taken at various times during a purification process. In addition, the invention relates to methods of identifying conditions that can be used in increasing the scale of a given purification process.

The invention relates to a kit for prenatal testing comprising a size-based separation module which enriches a first cell type from a maternal blood sample found in vivo in a pregnant female at a concentration of less than 1% of all blood cells, and a set of instructions for analyzing said one or more enriched cells to make a prenatal diagnosis. In some embodiments, the size-based separation module can comprise a plurality of obstacles to selectively direct the one or more cells of the first cell type in a first direction away from one or more cells of a second cell type.

Methods for identifying potential therapeutic agents involve determining the affinity and/or efficacy of a test compound for an adensoine receptor at a relatively high pH and at a relatively low pH. Compounds with greater affinity and/or efficacy at the low pH are identified as potential therapeutic agents, in particular for the treatment of pain or inflammation.

The present invention relates to a phosphorylated form of mammalian glyoxalase I. The present invention relates further to the use of phosphorylated mammalian glyoxalase I to modulate MG-modification of proteins (AGE formation) and consequent cell death, especially upon stress such as oxidative stress, or upon TNF treatment.

A device having an air sampler, an electrospray apparatus, and a fluorescence excitation and detection system. The air sampler is capable of moving air suspected of containing a biological or chemical aerosol particle into a chamber. The electrospray apparatus is capable of spraying a charged solution into the chamber to coat the aerosol particles with a coating. The solution has a fluorescent-labeled biological or chemical marker capable of specific binding to the aerosol particle. The fluorescence system is capable of detecting fluorescence of the fluorescent label in the coating. A method of detecting the aerosol particle by: moving air suspected of containing the aerosol particle into a chamber; spraying the charged solution into the chamber with an electrospray apparatus, such that a coating of the solution is formed around the particle; exciting the fluorescent label; and detecting fluorescence of the fluorescent label.

A bio-analysis chip which is convenient in use and can promptly detect microbes with high accuracy. The bio-analysis chip comprises a collection member for collecting microbes in the atmosphere with the microbes adhering to the collection member, and a substrate in the form of a thin plate on which the collection member is mounted. The substrate has a collection member receiving section in which the collection member is placed, and a plurality of reagent reservoirs in which reagents for treating and analyzing the microbes are stored. The plurality of reagent reservoirs are connected to the collection member receiving section.

The present invention relates to compounds which are suitable for coupling to pharmaceuticals, in particular biopharmaceuticals, and to conjugates composed of the compounds and biomolecules or pharmaceutical active compounds. The compounds according to the invention can be readily formed by means of multicomponent reactions. The invention also relates to the use of the conjugates as an improved formulation of pharmaceuticals, and to their preparation. The invention furthermore provides a laboratory kit for the in-vitro preparation of conjugates which are composed of the compounds according to the invention and pharmaceuticals as well as biotechnological substances, in particular biopharmaceuticals, pharmaceutical active compounds, synthetic molecules or surfaces.

The present invention relates to a method for generating a network of direct and indirect interaction partners of a disease-related (poly)peptide comprising the steps of (a) contacting a selection of (poly)peptides suspected to contain one or several of said direct or indirect interaction partners with said disease-related (poly)peptides and optionally with known direct or indirect interaction partners of said disease-related (poly)peptide under conditions that allow the interaction between interaction partners to occur; (b) detecting (poly)peptides that interact with said disease-related (poly)peptide or with said known direct or indirect interaction partners of said disease-related (poly)peptide; (c) contacting (poly)peptides detected in step (b) with a selection of (poly)peptides suspected to contain one or several (poly)peptides interacting with said (poly)peptides detected in step (b) under conditions that allow the interaction between interaction partners to occur; (d) detecting proteins that interact with said (poly)peptides detected in step (b); (e) contacting said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide, said (poly)peptides detected in steps (b) and (d) and a selection of proteins suspected to contain one or several (poly)peptides interacting with any of the afore mentioned (poly)peptides under conditions that allow the interaction between interaction partners to occur; (f) detecting (poly)peptides that interact with said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide or with said (poly)peptides identified in step (b) or (d); and (g) generating a (poly)peptide-(poly)peptide interaction network of said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide and said (poly)peptides identified in steps (b), (d) and (f). Moreover, the present invention relates to a protein complex comprising at least two proteins and to methods for identifying compounds interfering with an interaction of said proteins. Finally, the present invention relates to a pharmaceutical composition and to the use of compounds identified by the present invention for the preparation of a pharmaceutical composition for the treatment of Huntington's disease.

The present invention provides methods of detecting nucleic acid polymerase activity and methods of detecting compounds that modulate nucleic acid polymerase activity.

This invention is related to a method for detecting toxic and non-toxic cyanobacteria. The method comprises that nucleic acid from a biological sample is brought into contact with an oligonucleotide designed to be specific for the mcy gene, in particular mcyE and/or mcyD, and with an oligonucleotide designed to be specific for 16SrDNA, and the presence or absence of toxic cyanobacteria is detected by a suitable molecular biology method. The invention is related also to oligonucleotides used in the method.

Methods for identifying potential therapeutic agents, such as anti-tumor agents, based on their modulation of the expression of specified genes, especially genes mapping to specific chromosomal regions, are disclosed. Also described are methods for diagnosing cancerous, or potentially cancerous, conditions as a result of the expression, or patterns of expression, of such genes, including detecting changes in levels of gene copy number and/or level of amplification of the said gene, or sets of genes, to detect and/or diagnose the cancer. Methods for detecting or determining functionally related genes, as well as methods for treating cancer based on targeting expression products of such genes, determining genes involved in the cancerous process and the success and/or response rates and survival statistics for cancer patients on treatment are encompassed by the invention. Also encompassed are methods involving determining the modulated expression of the genes in these regions of interest (ROIs) as pharmacodynamic/pharmacogenetic /surrogate markers and/or for patient profiling prior to accrual for clinical trials/treatments based on the identification of these genes as validated gene/drug targets in various cancer tissue types.

Human MARK genes are identified as modulators of the PTEN pathway, and thus are therapeutic targets for disorders associated with defective PTEN function. Methods for identifying modulators of PTEN, comprising screening for agents that

The disclosure provides methods of examining the binding of proteins to DNA across a genome (e.g., the entire genome or a portion thereof, such as one or more chromosomes or a chromosome regions). In particular, the disclosure relates to a method of identifying a regulatory region (e.g., a protein or enhancer region) of genomic DNA to which a protein of interest binds. In one aspect, the disclosure looks at tissue related regulation. In another aspect, the disclosure looks at developmental related regulation. In yet another aspect, the disclosure looks at regulation of expression in a particular disease state or disorder.

The invention provides a methods and materials for detecting an activity of a glycopeptide antibiotic (such as a vancomycin-type antibiotic), in a sample, the method comprising the steps of: (a) providing a microorganism in which a first endogenous gene encoding peptidyltransferase activity is inactivated, which activity is necessary for growth of the microorganism, and which activity can be complemented by a second, different, peptidyltransferase, which second peptidyltransferase is inducible in the microorganism by the presence of the antibiotic, (b) contacting the sample with the microorganism, (c) observing the microorganism for growth, wherein growth of the microorganism is correlated with the presence of the antibiotic. Unlike systems of the prior art, the system does not rely on the expression of a heterologous reporter gene in order to detect antibiotic activity, but instead utilizes a "drug dependent" microorganism that can only grow in the presence of antibiotics that act an inducers of the relevant genes.

We describe a method for the identification of genes which show regulated expression in response to carbon source utilisation, typically genes associated with the initiation and/or promotion of cell transformation from a non-cancerous to a cancerous phenotype, typically of cells found in the colon; the use of these genes in diagnostic assays and as targets for the development of chemotherapeutic drugs and agents identified by said assay

This disclosure describes isolated or purified deoxyribonucleotide (DNA) sequences, useful for the development of antibacterial agents, which contain the coding sequences of bacterial pathogenesis genes or essential genes, which are expressed in vivo. It further describes isolated or purified DNA sequences which are portions of such bacterial genes, which are useful as probes to identify the presence of the corresponding gene or the presence of a bacteria containing that gene. Also described are hypersensitive mutant cells containing a mutant gene corresponding to any of the identified sequences and methods of screening for antibacterial agents using such hypersensitive cells. In addition it describes methods of treating bacterial infections by administering an antibacterial agent active against one of the identified targets, as well as pharmaceutical compositions effective in such treatments.

Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.

The inventors set out to identify a set of genes for use as prognostic markers for breast tumours which correlate with the Nottingham Prognostic Index (NPI). Initially they were unable to identify a single set of genes whose expression correlates with the NPI. However after segregating the dataset into molecular subcategories (estrogen receptor positive, estrogen receptor negative, and ErbB2 positive) they identified a set of 62 genes which are differentially expressed in tumours of different prognoses. Methods and apparatus for determining prognosis are provided. Also provided are methods of determining the response of tumours to chemotherapy involving comparing the expression levels of the predictive gene set before and after treatment.

This invention provides nanometer-sized fluorescent magnetic particles and processes of making them. The nanoparticle has a core particle comprising a magnetic material and a fluorescent material, and the particle size is less than about 1 micrometer. The nanoparticles can be coated with an inorganic or organic layer and can be surface-modified. The nanoparticles can be used in many biological assays.

The present invention relates generally to a method of diagnosing, predicting and/or monitoring the development or progress of an inflammatory response in a mammal. More particularly, the present invention relates to a method of diagnosing, predicting and/or monitoring the development or progress of an inflammatory response by analysing one or both of activin or follistatin expression levels either in a subject mammal or in a biological sample derived from said mammal. The present invention further provides a method for predicting, diagnosing and/or monitoring conditions associated with or characterised by the onset of inflammatory response. Also provided are diagnostic agents useful for detecting activin and/or follistatin expression levels.

The invention relates to the utilization of a substance for diagnostic determination of sgk1 (serum and glucocorticoid dependent kinase 1) and to the utilization of an active agent in order to influence sgk1 for therapeutic treatment of diseases associated with disordered activity of the tissue factor and to a diagnostic kit related thereto.

A digested phagocyte prepared by contacting in vitro a phagocyte with a foreign microorganism and isolating the phagocyte so contacted; a process for producing the same; and a process and a kit in which these are utilized are disclosed. An experimental model, which enables in vitro evaluation of a phagocytotic function of phagocytes, is provided.

A process for preparing a composition comprising dried microorganisms, comprising culturing one or more species of a microorganism; admixing the cultured microorganism with one or more carriers; treating the microorganism with pulsed electromagnetic fields; incubating the culture:carrier mixture for at least about 6 hours; drying the microorganism with one or more carriers; and treating the microoragnisms; wherein the microorganisms in the composition have significantly enhanced survival rate and/or shelf-life.

Disclosed are methods and kits for identifying a virus in a sample, which may include a coronavirus capable of causing Severe Acute Respiratory Syndrome ("SARS") or SARS-like symptoms. The virus may be a SARS-Associated Coronavirus ("SARS-CoV"). Typically, the methods may include reacting a mixture that includes, in addition to nucleic acid isolated from the sample, at least one oligonucleotide capable of specifically hybridizing to SARS-CoV nucleic acid where the oligonucleotide includes at least one non-natural base. In addition, the mixture may include control nucleic acid.

A method for producing improved results for applications of any kind which directly or indirectly utilizes gene expression assay results.

The invention relates to a method for diagnosing an animal for a condition by obtaining a fluid sample from the animal, enriching a first analyte having a concentration of less than 1.times.10.sup.-3 analytes/.mu.L from said sample by a factor of at least 10,000 fold; and analyzing one or more enriched first analytes to determine a condition in said animal. Enrichment is preferably performed using one or more size-based separation modules.

A method of identifying an antiviral agent effective against viruses, which utilize -1 programmed ribosomal frameshifting is provided. The method includes providing cells harboring a -1 frame plasmid including a translation start site followed by a -1 ribosomal frameshifting signal followed by a reporter gene which is in a -1 frame relative to the translation start site. The method further includes contacting the cells with a test agent; and measuring the activity of the reporter gene in the presence of the test agent, wherein the reporter gene activity is dependent on -1 ribosomal frameshifting.

This invention provides isolated nucleic acid and amino acid sequences of gastrointestinal endocrine cell specific G-protein coupled receptors, methods of detecting such receptors, and methods of screening for ligands of such receptors. Furthermore, this invention demonstrates that SrC-1 enteroendocrine cells express multiple bitter taste receptors as well as a-subunits of G proteins that mediate taste signal transduction and respond to bitter taste compounds initiating changes in intracellular calcium concentration. Given that at present there are no cultured cell model system to determine the functional effects of taste receptor-mediated signaling, our findings identify STC-1 cells as a cell model for studying taste-mediated signal transduction.

Hybrid glycosylated products such as polyketides and peptides are produced by transforming a host cell with (a) a gene cassette for synthesising an activated sugar and (b) nucleic acid encoding a glycosyltransferase (GT). The cell also produces or is supplied with an aglycone template. At least some of the components (sugar, aglycone, GT, sugar synthesis genes, cells) are mutually heterologous.

A sensor chip that includes: a fluorescence quenching surface; a nucleic acid probe that contains first and second ends with the first end bound to the fluorescence quenching surface, a first region, and a second region complementary to the first region, the nucleic acid probe having, under appropriate conditions, either a hairpin conformation with the first and second regions hybridized together or a non-haipin conformation; and a first fluorophore bound to the second end of the first nucleic acid molecule. When the first nucleic acid molecule is in the hairpin conformation, the fluorescence quenching surface substantially quenches fluorescent emissions by the first fluorophore; and when the first nucleic acid molecule is in the non-hairpin conformation, fluorescent emissions by the fluorophore are substantially free of quenching by the fluorescence quenching surface. Various nucleic acid probes, methods of making the sensor chip, biological sensor devices that contain the sensor chip, and their methods of use are also disclosed.

Detects the presence of binding between a sample biopolymer and a probe biopolymer and the amount of binding, without modifying the sample biopolymer in any way. The present invention provides a reagent for biopolymer detection comprising semiconductor nanoparticles on which a functional group having a positive or negative charge is exposed, and a method for biopolymer detection which detects the presence of binding between a sample biopolymer and a probe biopolymer and the amount of binding by electrostatically binding a semiconductor nanoparticle on which a functional group having a positive or negative charge is exposed to a negative or positive charge of the sample biopolymer.

The present disclosure provides efficient and reproducible methods for individually synthesizing oligomers in a parallel manner (e.g., oligonucleotides) on a solid support to produce pools of oligomers. Pools of oligonucleotides can be used for a variety of genomic and proteomic applications, including synthesis of genes or long DNA of any arbitrary sequence, PCR template amplification, and to generate primers for multiplexing PCR or transcription. Rapid availability of these oligonucleotide products will greatly accelerate the processes of de novo protein design, vaccine development, production of short RNA fragments, such as siRNA, oligonucleotide-based drug screening, and SNP sample preparation.

A method for determining the susceptibility of a subject to infection, which method comprises: (i) providing a sample from said subject; (ii) detecting any LL-37 present in said sample; (iii) optionally comparing the level of LL-37 in said sample to a control sample; and (iv) determining the susceptibility of said subject to infection, wherein no LL-37 or a low level of LL-37 indicates that said subject is susceptible to infection.

Disclosure of a method for the detection and quantitation of polynucleotide sequences in a sample of biological or non-biological material through target poly nucleotide sequence amplification by polymerase chain reaction using chemically labeled oligonucleotide amplification primers and formation of an entity between the amplified polynucleotide sequence and chemically labeled polynucleotide having a sequence complementary to the target polynucleotide sequence for determining the identity and/or presence and/or quantitation of the target poly nucleotide sequences. The chemical label covalently attached to the oligonucleotide amplification primer and polynucleotide or oligonucleotide comprise molecular energy transfer labels (donor and acceptor). It is again a very sensitive, rapid and reliable method with better sensitivity, specificity and reliability for the detection of polynucleotide sequence. It also greatly reduces the possibility of amplification product carry-over contamination and adaptable for many formats of nucleic acids amplifications and real time measurements.

The present invention is based on the discovery of genetic polymorphisms that are associated with vascular diseases, particularly stroke. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

The invention provides a human prostaglandin E2 EP1 which is associated with the cardiovascular diseases, respiratory diseases, hematological diseases, urological diseases, gastrointestinal diseases, endocrinological diseases and metabolic diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, respiratory diseases, hematological diseases, urological diseases, gastrointestinal diseases, endocrinological diseases an and metabolic diseases. The invention also features compounds which hind to and/or activate or inhibit the activity of prostaglandin E2 EP1 as well as pharmaceutical compositions comprising such compounds.

Multiple transcripts from the same gene maybe differentially regulated. Finding such differential regulation under distinct physiological conditions implicates the gene in the generation or response to the physiological condition. Transcripts have been identified from five genes which appear to be differentially regulated in lung cancer and normal cells. We have also identified a set of transcripts from a gene which are differentially regulated in squamous cell lung cancer from lung adenocarcinoma. The technique employed to identify these differentially regulated transcripts can be applied to other physiological conditions and samples to identify other differentially regulated transcripts.

Microtubules are excellent candidates for the fabrication of nanostructures, including nanowires. A method for controlled nucleation and growth of microtubules on substrates (e.g., gold on a silicon wafer) is provided. The substrate is functionalized with a nucleating agent for microtubule growth. The method can be employed to generate nanoscale structures on substrates or between substrates by additional attachment of MT capture agents which function to capture the ends of growing MT to form connecting MT structures. The method can be used to form 2- and 3-D structures on or between substrates and can function to establish interconnects between nanoscale devices or molecular electronic devices and electrodes. A specific method for metallization of biological macromolecules and structures in provides which can be beneficially applied to metallized the MT formed by the growth and capture method. The metallization method is biologically benign and is particularly useful for copper metallization of MTs.

Methods and apparatus are provided for detection of microorganisms in a sample. Methods and apparatus of the invention are based on the specificity that phage, for example bacteriophage, have for target microorganisms, for example bacterium. Typically, phage adsorption to target microorganisms act as signal, or a signal target, for the presence of the target microorganism. Typically, the phage are labeled with a detectable signal. Apparatus of the invention are directed toward concentrating the phage adsorbed microorganisms at a predetermined site for flag dependent observation.

The present invention relates to novel sequences for use in diagnosis and treatment of lymphoma and leukemia. In addition, the present invention describes the use of novel compositions for use in screening methods.

The present invention provides novel Secreted Epithelial Colon Stromal-1 (Secs-1) polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, selective binding agents, and methods for producing Secs-1 polypeptides. The invention further provides methods for the treatment, diagnosis, amelioration, or prevention of diseases associated with Secs-1 polypeptides.

A method of: submitting reference sequences to a taxonomic database to produce taxonomic results; and reporting a taxonomic identification based on the taxonomic results. The reference sequences are the output of genetic database queries that return a score for each reference sequence. A method for processing a biological sequence obtained from an assay by: converting base calls located in a predetermined list of positions within the biological sequence to N; and determining the ratio of single nucleotide polymorphisms in the biological sequence relative to a reference sequence. Each entry in the predetermined list of positions represents the capability of a substance hybridizing to a microarray used to generate the biological sequence. The substance is not the nucleic acid of a target pathogen.

The invention provides isolated nucleic acids molecules, designated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 and 49933 nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 gene has been introduced or disrupted. The invention still further provides isolated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 proteins, fusion proteins, antigenic peptides and anti-25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

The present methods and apparatus concern nucleic acid sequencing by incorporation of nucleotides into nucleic acid strands. The incorporation of nucleotides is detected by changes in the mass and/or surface stress of the structure. In some embodiments of the invention, the structure comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide is distinguishably labeled with a bulky group and each incorporated nucleotide is identified by the changes in mass and/or surface stress of the structure upon incorporation of the nucleotide. In alternative embodiments of the invention only one type of nucleotide is exposed at a time to the nucleic acids. Changes in the properties of the structure may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure, and/or position sensitive photodetection.

The present invention provides a novel DNA microarray chip that can be used for simultaneous testing of transcriptional responses to cutaneous stressors in the context of neuro-endocrine-immune functions of the skin. The transcriptional responses to ultraviolet radiation in epidermal keratinocytes were tested using such microarray chip containing more than 700 neuro-endocrine-immune related genes. The gene expression pattern was non-random and time dependent; it included increased expression of genes involved in water and salt balance, prostaglandin synthesis, keratinocyte differentiation as well as genes coding for stress effectors, cytokines and metalloproteinases. In contrast, expression was decreased for genes coding for growth factors and their receptors, and for elements of extracellular matrix. This stochastic pattern suggests that transcriptional responses are coordinated and aimed at preservation of epidermal barrier function, prevention of early carcinogenic events and remodeling of extracellular matrix.

This invention provides methods for treating a subject afflicted with a proliferative disorder comprising administering to the subject a therapeutically effective amount of an agent which inhibits the expression of p46 Shc and/or p52 Shc, inhibits the activity of p46 Shc and/or p52 Shc in the subject, or increases the level of phosphorylated p66 Shc in the subject. This invention also provides methods for determining whether an agent inhibits the phosphorylation of p46 Shc or p52 Shc; inhibits the dephosphorylation of p66 Shc comprising; or an agent inhibits the binding of a Shc A protein with a protein to which the Shc A protein must bind in a cell in order to carry out its proliferative function. This invention also provides articles of manufacture for use in treating a proliferative disorder in a subject.

The invention relates to the use of particles comprising binding ligands and electron transfer moieties (ETMs). Upon binding of a target analyte, a particle and a reporter composition are associated and transported to an electrode surface. The ETMs are then detected, allowing the presence or absence of the target analyte to be determined.

The present invention relates to methods and compositions for identifying covalent joining or modification of proteins. In particular, the present invention relates to covalent fluorescence complementation assays for the detection of modified (e.g., ubiquitinated proteins). The present invention further relates to the use of such fluorescence complementation assays in drug screening and research applications.

Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

A novel gene 282P1G3 and its encoded protein, and variants thereof, are described wherein 282P1G3 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 282P1G3 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 282P1G3 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 282P1G3 can be used in active or passive immunization.

The present invention relates in general to the detection of antibiotic resistance genes in Enterococci. The present invention discloses a micro-array for the detection of the presence of bacteria of the genus Enterococcus and antibiotic resistance genes in said organism, a method for the detection of said genes and a kit. This micro-array concept offers the rapid sensitive and specific identification of antibiotic resistance profiles.

The invention relates to a method of identifying fetal abnormality from a maternal blood sample by capturing an image of a fetal nucleated red blood cell obtained from the maternal blood sample; inputting probe intensities for a plurality of nucleic acid probes that bind fetal nucleic acids of interest; analyzing the probe intensities; and generating a diagnostic output according to results of the analysis. In some embodiments, the probes are specific to a chromosome.

Fusion proteins comprising a single strand DNA binding protein and a nucleic acid polymerase (e.g. DNA polymerase or reverse transcriptase). These high fidelity proteins are suitable for use in nucleic acid amplification methods, including the polymerase chain reaction (PCR).

Genes, SNP markers and haplotypes of susceptibility or predisposition to T2D and subdiagnosis of T2D are disclosed. Methods for diagnosis, prediction of clinical course and efficacy of treatments for T2D using polymorphisms in the T2D risk genes are also disclosed. The genes, gene products and agents of the invention are also useful for monitoring the effectiveness of prevention and treatment of T2D. Kits are also provided for the diagnosis, selecting treatment and assessing prognosis of T2D.

Described herein are genes whose expression are up-regulated or down-regulated in prostate cancer. Also described are such genes whose expression is further up-regulated or down-regulated in drug-resistant prostate cancer cells. Related methods and compositions that can be used for diagnosis and treatment of prostate cancer are disclosed. Also described herein are methods that can be used to identify modulators of prostate cancer.

The present invention provides compositions and methods for aiding in the diagnosis, monitoring and prognosis of SLE in a subject and for identifying potential therapeutic agents to treat and/or ameliorate the symptoms associated with SLE. Accordingly, embodiments of the invention are directed to methods of identifying the gene expression profile of a suitable sample by screening for the presence of a differentially expressed SLE-associated gene isolated from a sample containing or suspected of containing a cell that can differentially express an SLE-associated gene.

Described herein are approaches to the measurement of gene expression for chosen genes in a biological sample. The methods permit the quantitation of target nucleic acids, e.g., DNAs or RNAs in a nucleic acid sample, both singly and in a multiplex format that permits the determination of levels (e.g., expression levels or copy numbers) for two or more target nucleic acids in a single reaction.

Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.

MAGI polypeptides, polynucleotides, antibodies, and methods for producing the same by recombinant techniques are disclosed. Also disclosed are methods for utilizing MAGI polypeptides and polynucleotides in diagnostic assays.

The present invention regards predicting a response to a therapy using RNA expression profiling. In particular, a resistance to a chemotherapy, such as tamoxifen, is predicted by comparing expressed genes in a patient on the therapy to a patient sensitive to the chemotherapy. In further embodiments, there is an RNA expression profile indicative of tamoxifen resistance in an individual. In additional embodiments, the RNA expression profile comprises DUSP6 EBP50, and/or RhoGDIa.

The present invention relates to business methods in which screening services and diagnostics for the condition of a fetus are provided. Fetal abnormalities, include chromosomal and other genetic ies, are detected through the analysis of fetal cells obtained from maternal blood samples.

The present invention relates to methods for detecting and concentrating minute amounts of biohazard analytes, including but not limited to bacteria, protozoa, viral pathogens, and toxins, in environmental and other samples. These analytes can be substantially enriched by the methods of the invention, and further, a second analyte can be removed from the sample.

Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R54 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.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R64 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.

A novel gene (designated 101P3A11 or PHOR-1) and its encoded protein, and variants thereof, are described wherein 101P3A11 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 101P3A11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 101P3A11 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 101P3A11 can be used in active or passive immunization.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R64 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.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R75 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.

A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

The present invention describes a transgenic mouse susceptible to neuromuscular disease. The present invention also includes methods for treatment of neuromuscular diseases by interfering with activity between androgen and androgen receptors exclusively in the muscle fibers.

The present invention relates to the discovery of a specific human taste receptor in the T2R taste receptor family, hT2R51 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.

A method of producing botulinum toxin C-terminal receptor binding domain (HCR) is disclosed. The one embodiment, the method comprises the steps of (a) preparing E. coli transformed with an expression vector comprising DNA encoding HCR protein, (b) inducing expression of the HCR protein at a reduced temperature in a culture media, and (c) purifying the HCR protein via extraction, wherein the extraction comprises a clarification by centrifugation and a filtration, wherein the purified HCR protein is at least 10 mg/L of culture medium.

Apparatus and methods for seeding an implantable medical device, such as a vascular prosthesis, with cells, such as endothelial cells, are described. The invention supports techniques for seeding a luminal surface of the device with axial centrifugation. Cells are introduced in suspension into the lumen of the device. The introduction of the cells may occur after a blood centrifugation product, such as platelet-poor plasma, is applied to the luminal surface. After the cells are introduced, the device is then subjected to centrifugation around a longitudinal axis defined by the lumen. Axial centrifugation causes the cells to concentrate toward and adhere to the luminal surface. Shortly after axial centrifugation, the seeded device can be presented for implantation in a patient. The implantable medical device may be inserted into a protective sleeve prior to seeding the device with cells, and the sleeve may or may not be removed prior to implantation.

Site-specific Listeria integration vectors and methods for their use are provided. The subject vectors include a bacteriophage integrase gene and a bacteriophage attachment site, where in many embodiments the bacteriophage that is the source of these elements is a listeriophage. In certain embodiments, the subject vectors further include a multiple cloning site, where the multiple cloning site may further include a polypeptide coding sequence, e.g., for a heterologous antigen. The subject vectors and methods find use in a variety of different applications, including the study of Listeria species and the preparation of Listeria vaccines.

The present invention relates to a method for long-term culturing of avian spermatogonial stem cells, which comprises the steps of: (a) preparing an avian testis; (b) isolating a population of testicular cells from said avian testis; and (c) culturing said avian spermatogonial stem cells in said population of testicular cells on a feeder cell layer in a medium containing a cell growth factor, a population of avian spermatogonial stem cells and a method for producing transgenic aves.

A method for promoting or stimulating growth of tissue (22) comprising providing an element (23) which is adapted to receive blood, locating the element (23) in contact with the tissue (23) with at least one portion of the element (23) extending away from an external surface of the tissue (22), and conditioning the element (23) by introducing blood into said at least one portion whereby, when located in contact with the tissue, the conditioned element (23) is arranged to stimulate or promote growth of tissue in (27) and from (28) the at least one portion.

With the object of providing a liposome having cellular and nuclear entry ability, to achieve this object, a liposome is provided having on its surface a peptide comprising multiple consecutive arginine residues, and specifically a liposome is provided wherein the peptide is modified with a hydrophobic group or hydrophobic compound and the hydrophobic group or hydrophobic compound is inserted into a lipid bilayer so that the peptide is exposed on the surface of the bilayer.

A process for producing a starch comprises treating a feed starch that comprises amylopectin with glucanotransferase to produce a chain-extended starch, and treating the chain-extended starch with a debranching enzyme to produce a starch product that comprises amylose fragments. At least about 38% by weight of the amylose fragments have a degree of polymerization (DP) of at least about 35.

The present invention provides a new method for extracting Homoharringtonine (HHT) by culture cells or culture plant tissues. Also, disclosed are methods of obtaining HHT from semi-synthesis and biosynthesis. The present invention disclosed that HHT combined with some botanical drugs could induce cancer cells to resemble normal cells. To add some botanical drugs combined with HHT can significantly increase anticancer effects of HHT. These drugs include Matrine (MAT), Guanzhongsu (GU), Maidongsu (MU), and Indirubin (IND). The experimental data showed that above drugs have strong synergisms effects for treating leukemia and other cancer cells and more safe.

Described are methods and systems for identifying a secondary metabolite synthesized by a target gene cluster within a microorganism. A putative or confirmed function is attributed to a gene within the gene cluster, and an extract from the microorganism is obtained which is suspected to contain the secondary metabolite synthesized by the gene cluster. The extract is then assessed for chemical, physical or biological properties, and the metabolite is identified and optionally isolated. Further, the invention provides a knowledge repository in which gene cluster information is linked to secondary metabolite production data. The invention further relates to a graphical user interface for accessing the knowledge repository, and a memory for storing data, having a data structure that is stored in the memory.

The present invention provides systems useful for the enrichment of analytes, for example, cells of selected types, including but not limited to blood cells, stem cells, and pathogens, in samples. The invention also provides methods for analyzing the condition of a patient based on characteristics identified through analysis of the analytes in case and control samples.

A breast milk detection device includes a plurality of test strips slidably and removably coupled to a test housing. Each test strip is connected to an absorbent section so that a breast milk sample deposited thereon is communicated to the test strips. Each test strip includes an analyte-specific moiety for identifying the presence of a predetermined contaminant when contacted by the breast milk sample. The housing includes apertures so that a portion of the test strip may be viewed by a user and the result of the chemical reaction may be analyzed. Indicia indicative of the contaminant being tested for and a legend for interpreting the test results are imprinted upon a top surface of the housing. The breast milk detection device is useful for a nursing mother to determine if her breast milk is safe for the baby.

A novel inbred maize line designated PH7GD and seed, plants and plant parts thereof. Methods for producing a maize plant that comprise crossing inbred maize line PH7GD with another maize plant. Methods for producing a maize plant containing in its genetic material one or more traits introgressed into PH7GD through backcross conversion and/or transformation, and to the maize seed, plant and plant part produced thereby. Hybrid maize seed, plant or plant part produced by crossing the inbred line PH7GD or an introgressed trait conversion of PH7GD with another maize line. Inbred maize lines derived from inbred maize line PH7GD, methods for producing other inbred maize lines derived from inbred maize line PH7GD and the inbred maize lines and their parts derived by the use of those methods.

A cotton cultivar, designated DPX 08Q818F, is disclosed. The invention relates to the seeds of cotton cultivar DPX 08Q818F, to the plants of cotton DPX 08Q818F and to methods for producing a cotton plant produced by crossing the cultivar DPX 08Q818F with itself or another cotton variety. The invention further relates to hybrid cotton seeds and plants produced by crossing the cultivar DPX 08Q818F with another cotton cultivar.

A method is disclosed for demonstrating the efficacy of a topically applied active ingredient, which method includes topically applying a composition containing an active ingredient to an area of skin, applying an absorbent material to the area of skin to extract at least a portion of the active ingredient from the skin, thereby incorporating the portion of active ingredient with the absorbent material in a releasable manner, removing the absorbent material from the skin, extracting the active ingredient from the absorbent material, combining the extracted active ingredient with cellular growth media, incubating the cellular growth media with cultured cells for a period of time to produce a biomarker, and measuring the biomarker to indicate efficacy of the active ingredient.

The present invention relates to a method for preparing nonlamellar bioresorbable microparticles to which protein substances are bonded, characterized in that it comprises the steps of: (i) preparing said microparticles from at least one bioresorbable polymer without stabilizer and without surfactant, and (ii) bonding said protein substances to the microparticles obtained in step (i) without surfactant. It further relates to the bioresorbable microparticles thus obtained and use thereof in diagnosis and therapy.

A method of screening for agents that stimulate the innate immune system in mammals employs markers that respond to Toll-like receptor binding. Agents identified in the assay boost both innate and adaptive immune responses, when administered alone or in combination with vaccines.

The present invention relates to a method for detecting an analyte in a sample, wherein the sample to be analyzed is applied to a chromatographic carrier. After separating from an interfering substance which may be present in the sample, the analyte of interest is detected on the carrier by means of an immunological assay. Further, a test strip for carrying out the method of the invention is provided. The invention further relates to a method for reducing interference in a method for detecting an analyte on a chromatographic carrier.

The present invention relates to isolated polypeptides having antimicrobial activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

We describe transgenic cells comprising nucleic acid molecules that comprise nucleic acid sequences which encode enzymes involved in the biosynthesis of n-3 fatty acids.

Isolated polynucleotides and polypeptides encoded thereby are described, together with the use of those products for making transgenic plants.

The present invention is directed to a promoter, designated EPSP. The present invention is also directed to DNA molecules including the EPSP promoter, such as a DNA construct containing the promoter operably linked to one or more genes or antisense DNA. The invention is further directed to transformed plant tissue including the DNA molecule and to transformed plants and seeds thereof. The promoter is useful for driving gene or antisense expression for the purpose of imparting agronomically useful traits such as, but not limited to, increase in yield, disease resistance, insect resistance, herbicide tolerance, drought tolerance and salt tolerance in plants.

A method for obtaining improved fertility restorer lines for male sterile crop plants and a DNA construct for use in said method are disclosed. The invention relates to the simultaneous use of two different gene sequences encoding the same protein product, one being the naturally occurring wild type sequence and the other sequence being generated by modification of the wild type sequence for expression in crop plants by using codon degeneracy to avoid homology between the two sequences at the DNA and mRNA levels, each of the said sequences being placed under independent transcriptional control of different overlapping plant tissue-specific regulatory elements in the same DNA construct.

Methods and compositions for expressing a polynucleotide of interest are provided. Compositions comprise an enhancer domain set forth in SEQ ID NO: 1, 10, 15, or 16 and active variants and fragments thereof. Further provided are DNA constructs comprising at least one transcriptional enhancer sequence comprising the nucleotide sequence set forth in SEQ ID NO:1, 10, 15, or 16 or an active variant or fragment thereof, operably linked to a heterologous promoter. Such chimeric transcription regulatory regions can be operably linked any polynucleotide of interest. Further provided are cells, plants, plant parts, and germplasm comprising the DNA construct. Methods of using the chimeric transcriptional regulatory region are also provided. In specific embodiments, methods of expressing a polynucleotide of interest, including for example, sequences that confer tolerance to herbicides, and methods to select a cell having the DNA construct are provided.

The present invention relates to a system for controlling the development of fungi during a phytopathogenic attack which enables the plant to express a construct for inhibiting the expression of a gene essential to the development or to the pathogenicity of the fungus.

Methods for preparing cell lines that contain artificial chromosomes, methods for preparation of artificial chromosomes, methods for purification of artificial chromosomes, methods for targeted insertion of heterologous DNA into artificial chromosomes, methods for amplification of nucleic acids and methods for delivery of the chromosomes to selected cells and tissues are provided. Also provided are cell lines for use in the methods, and cell lines and chromosomes produced by the methods. Methods for use of the artificial chromosomes are also provided.

Disclosed are Bacillus thuringiensis strains comprising novel crystal proteins which exhibit insecticidal activity against lepidopteran insects. Also disclosed are novel B. thuringiensis genes and their encoded crystal proteins, as well as methods of making and using transgenic cells comprising the novel nucleic acid sequences of the invention.

The invention relates to plant transcription factor polypeptides, polynucleotides that encode them, homologs from a variety of plant species, and methods of using the polynucleotides and polypeptides to produce transgenic plants having advantageous properties compared to a reference plant. Sequence information related to these polynucleotides and polypeptides can also be used in bioinformatic search methods and is also disclosed.

Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.

The present invention concerns methods and compositions for improving viability and transgene expression in transfected cells. In one embodiment, the present invention provides a method for increasing the viability of a transfected cell, the method comprising: transfecting a cell with a nucleic acid sequence; and contacting the transfected cell with a nuclease in a manner effective to enhance the viability of the transfected cell.

The present invention relates to a method of introducing nucleic acids into cells by electroporation, comprising the step (A) of loading nucleic acids to the surface of an electrode; the step (B) of adhering cells on the obtained nucleic acid-loaded electrode surface; and the step (C) of applying electric pulses to the adhering cells. According to this method, not only efficient introduction of a gene into cells but also gene introduction at desirable timing and at desirable sites can be performed without damaging the adhering cells.

The present invention relates to isolated and/or purified rat apoptosis-specific eucaryotic initiation Factor-5A (eIF-5A) and deoxyhypusine synthase (DHS) nucleic acids and polypeptides. The present invention also relates to methods of modulating apoptosis using apoptosis-specific eIF-5A and DHS, and antisense oligonucleotides and expression vectors of apoptosis-specific eIF-5A and DHS useful in such methods.

Disclosed is a method for treating biological material via electrical current, in which the biological material is added to a small volume of a buffer solution having relative high ionic strength. A strong electrical field is generated in the buffer solution by a high voltage pulse having a preset duration. The biological material is added to at most 50 .mu.l of a buffer solution with an ionic strength of at least 100 mmol/l. By at least one voltage pulse having a preset duration of at least 10 .mu.s, an electrical field with a field strength of at least 1 kV/cm is generated in the buffer solution. The voltage pulse is hereby interrupted at least once for a duration of at least 100 .mu.s and is then again continued.

The present invention provides a method of treating an ocular disease in a subject. In a first step, a nucleic acid is introduced into cells or a tissue. The nucleic acid is introduced by electron avalanche transfection. With this technique, a high electric field induces a vapor bubble and plasma discharge between an electrode and the surrounding medium. The formation of a vapor bubble generates mechanical stress. Plasma discharge through the ionized vapor in the bubble enables connectivity between the electrode and the surrounding medium, so that mechanical stress and electric field are applied simultaneously, which results in permeabilization of the cells or tissue. This permeabilization in turn allows the nucleic acid to enter the cell or tissue. Cells or tissue containing the nucleic acid are then transplanted into an ocular region of the subject.

The invention relates to chiral separation chromatographic and electrophoretic techniques. The aim of said invention is to obtain chiral stationary and mobile phases comprising an oligonucleotide which is specifically selected by a SELEX method against an enantiomer to be separated as a special-purpose chiral selector. Methods for separating enantiomers by the chiral stationary and mobile phases are also disclosed.

The present disclosure relates to processes and methods for producing a hydrophobic zone boundary that surrounds a hydrophilic porous material layer mounted on a substrate, the hydrophilic porous material layer containing tortuous channels and pores such that the fluid contained within one hydrophilic layer region does not cross the hydrophobic zone boundary and the articles formed thereby and, more particularly, to processes and methods for producing a hydrophobic zone boundary that separates adjacent regions of a hydrophilic porous material layer mounted on a substrate, the hydrophilic porous material layer containing tortuous channels and pores mounted on a substrate such that a uniform hydrophobic zone boundary layer in the z-direction is formed in the hydrophilic porous material or the removal of the hydrophilic porous material layer from the substrate to form a hydrophilic porous material zone on the substrate, the so formed hydrophilic porous material zone having a predetermined geometric shape such that the combination produced thereby is useful in microarray applications and other applications. Products of the processes and methods are also disclosed.

Compositions and methods for regulating genes of interest are provided. The compositions comprise sense-antisense double stranded nucleic acid molecules, which have homology to a target nucleic acid sequence in a cell. The compositions and methods are useful for the treatment of disease and for preventing the proliferation of neoplastic cells.

The methods and compositions of the present invention find use in modulating myeloid cell development, particularly differentiation and proliferation. The compositions of the invention include isolated transgenic cells, transgenic tissue, transgenic animals, and transgenic mice. The methods allow generation of myeloid cell lines suitable for tissue culture. Further the invention provides methods of modulating immune disorders, particularly myeloid disorders, more particularly leukemias.

The present invention relates to compositions and method for the modulation of Wnt pathway signaling. The Wnt signaling pathway is instrumental in the regulation of cell proliferation, differentiation and morphogenesis.

The present invention relates to compositions and methods for culturing stem cells, such that neuronal differentiation can be achieved.

The present invention relates to a method for isolating progenitor cells from a human body, inclusive of all cells with stem cell-like characteristics, in particular pluripotent or multipotent progenitor cells, wherein such cells are directly or indirectly derived from human mammary secretion, be it colostrum, mature milk, or dry period secretion from males or females, of said human body during at least one of the following periods: non-pregnant period, pregnant period, lactating period, involuting period. The present invention furthermore relates to preferred uses of such isolated cells.

An improved method for preparing a cell culture is disclosed. The method includes culturing a multicellular tissue explant in the presence of growth medium that is substantially free of enzymes capable of digesting the explant and, subsequently, removing the explant at a predetermined time.

The present invention relates to a purified population of fibroblast-like macrophage (f-macrophage, f-M.PHI.) and methods using the same. The f-M.PHI. can be expanded in vitro and differentiated into several lineages, including insulin-expressing cells, endothelial cells, and neuronal cells. The f-M.PHI. described herein have been generated from human umbilical cord blood (CB f-M.PHI.) and have characteristics similar to f-M.PHI. derived from peripheral blood. Thrombopoietin (TPO), at low dosage, significantly stimulates the proliferation of CB f-M.PHI., wherein the TPO-expanded CB f-M.PHI. retain their pluripotent differentiation potential.

Antibodies that bind to polypeptides and peptides comprising the sequence of zalpha11 Ligand as shown in SEQ ID NO: 2 are described. The antibodies may bind the full length sequence of 162 amino acid residues or a fragment thereof, including a mature polypeptide of 131 amino acid residues and smaller polypeptide and peptide sequences. The antibodies may include antibodies that are polyclonal, monoclonal, murine, humanized or neutralizing. Methods for producing the antibodies are also described.

A carrier for nucleic acid molecule delivery formed from a saccharified copolymer comprising repeating unit (A) having a cationic group, saccharified repeating unit (B). There is further provided a carrier for nucleic acid molecule delivery formed from a saccharified copolymer comprising, in addition to the repeating units (A) and (B), repeating unit (C) having a hydrophobic substituent.

The device incorporates a structurally stable membrane (4, 4', 34, 35) that incorporates a surface (15) to be bonded to a tissue to be regenerated, specifically a vital bone (2, 22, 38, 39). Means (9, 5, 6, 25, 36) are additionally provided whereby the membrane (4, 4', 24, 35) is movable for the regeneration with a certain pulling force and speed. According to the invention the membrane (4, 4', 24, 35) has, on its surface facing the tissue or bone, means (16) for the biological anchoring and adhesion for tissue or bone cells. These means (16) for the biological anchoring of tissue cells are specifically bone cells, protein molecules and/or osteoblasts (17), as well as indentations (45, 46, 48) and surface peaks (50) of the membrane.

The invention concerns a novel sample tube and a method of manufacturing a such a sample tube. According to the method an oversized mould cavity is formed with an opposing pair of mould members of an injection moulding machine, the mould members being movable relative to each other and between which mould members the sample tube is formed. A volume of resin exceeding the prescribed volume of the sample tube is injected into the cavity and force is applied to said mould members in order to reduce the volume of said mould cavity for displacing molten polymer in the cavity and for compressing the polymer to form said sample tube. By means of the invention, sample tubes and vessels having ultra thin walls can be manufactured.

Methods are disclosed that provide for the preservation of living human and other cells at room temperature or higher temperatures which can be applied to research, medical and defense applications. These methods represent a significant improvement relative to currently used methods that employ preservation at cryogenic temperatures. Using these methods, living human and other cells can be stored at room temperature or higher, and subsequently be recovered as living cells capable of dividing and exhibiting other well recognized properties of living cells.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. In particular, the invention describes a gene known in the art, alternatively, as ST2, T1 and Fit-1, and referred to herein as the 103 gene. The 103 gene is disclosed herein to be differentially expressed in TH2 cells and not in TH1 cells. Further, the 103 gene product is demonstrated herein to be an important modulator of TH2 and TH2-like immune response both in vitro and in vivo. Thus, the 103 gene, its gene products and antibodies that specifically bind thereto can be used diagnostically or as targets for therapeutic intervention in the treatment of a variety of immune disorders. In this regard, the invention provides methods for the identification and therapeutic use of compounds for treatments of immune disorders, especially TH cell subpopulation-related disorders and including TH2 and TH2-like disorders (i.e., disorders associated with a TH2 or TH2-like mediated immune response) such as atopic conditions (e.g., allergy and asthma). Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders and for monitoring the efficacy of compounds used in clinical trials.

Organisms, compositions, and methods for at least partially reducing the formation of a biofilm and/or at least partially removing a biofilm are provided. The organisms, compositions, and methods may be used on biotic and abiotic surfaces.

The present invention provides therapeutic formulations for hematopoietic diseases comprising as effective ingredient, synoviolin which is reported to be isolated as a synovial cell protein and its gene, and therapeutic methods and such comprising the step of administering the protein or polynucleotide. The present invention also provides as models of hematopoietic diseases, animals whose synoviolin is homozygously deficient and cells derived from such animals; and additionally provides methods that use these models in the screening of therapeutic agents for hematopoietic diseases.

The present invention includes fully human, neutralizing, monoclonal antibodies against human Insulin-like Growth Factor Receptor-I (IGFR1). The antibodies are useful for treating or preventing cancer in a subject. Also included are methods of using and producing the antibodies of the invention.

Compositions are provided that comprise antibody against membrane proteins such as chemokine receptors. In particular, monoclonal human antibodies against human CXCR4 are provided that are capable of inhibiting HIV infection and chemotaxis in human breast cancer cells. The antibodies can be used as prophylactics or therapeutics to prevent and treat HIV infection and cancer, for screening drugs, and for diagnosing diseases or conditions associated with interactions with chemokine receptors.

A syringe control device includes a linear reciprocating mechanism and a syringe mechanism. The linear reciprocating mechanism has a power drive including an electric control unit and an actuation rod driven by the power drive to act a linear reciprocating motion. The actuation rod has a first contact portion provided with two electrically conductive contacts electrically connected to the electric control unit. The syringe mechanism has a syringe unit including a second contact portion made of electrically conductive material and corresponding to the first contact portion of the actuation rod. When the first contact portion of the actuation rod contacts the second contact portion during the linear reciprocating motion, a signal will be sent to the electric control unit for controlling the displacement of the actuation rod so as to further control the syringe amount of the syringe unit.

The present invention relates generally to the generation and characterization of neutralizing anti-IFN-.alpha. monoclonal antibodies with broad reactivity against various IFN-.alpha. subtypes. The invention further relates to the use of such anti-IFN-.alpha. antibodies in the diagnosis and treatment of disorders associated with increased expression of IFN-.alpha., in particular, autoimmune disorders such as insulin-dependent diabetes mellitus (IDDM) and systemic lupus erythematosus (SLE).

The present invention provides methods and compositions for supplementing or replacing a damaged organ. The damaged organ to be supplemented or replaced in accordance with the present invention include, for example, kidney, heart, liver, spleen, pancreas, bladder, ureter and urethra. In one embodiment, the tissue-engineered construct of the invention has has at least the following characteristics: (a) differentiated cells on a three-dimensional biocompatible scaffold, wherein the differentiated cells originated from transferred pluripotent cells; and (b) at least one physiological function of the organ.

There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human CD22. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a modified CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by cells expressing CD22.

The invention provides methods of screening for modulators of microbial PA-I lectin/adhesin activity, including modulators of PA-I expression, as well as the modulators so identified, pharmaceutical compositions and kits containing such modulators. These modulators include soluble and membrane-bound bacterial signaling compounds produced by cells of a host containing a microbial pathogen. Methods for preventing and treating cell disorders, such as epithelial cell disorders including gut-derived sepsis, a burn injury, neonatal necrotizing enterocolitis, infection associated with severe neutropenia, toxic colitis, inflammatory bowel disease, irritable bowel syndrome and other GI infectious diseases, enteropathy, transplant rejection, pouchitis, pig belly or pig-bel, Pseudomonas-mediated ophthalmologic infection, Pseudomonas-mediated otologic infection and Pseudomonas-mediated cutaneous infection, using the modulators are contemplated, as are methods for ameliorating a symptom associated with such a disorder.

The present invention provides novel pseudotyped retroviral vectors that can transduce human and other cells. Vectors are provided that are packaged efficiently in packaging cells and cell lines to generate high titer recombinant virus stocks expressing novel envelope glycoproteins. The present invention further relates to compositions for gene therapy.

The present invention provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

The present invention relates to canine and feline proteins. In particular, the present invention discloses feline interleukin-18, feline caspase-1, feline interleukin-12 single chain and canine interleukin-12 single chain proteins. The present invention also includes feline interleukin-18, feline caspase-1, feline interleukin-12 single chain and canine interleukin-12 single chain nucleic acid molecules encoding such proteins, antibodies raised against such proteins and/or inhibitors of such proteins or nucleic acid molecules. The present invention also includes therapeutic compositions comprising such nucleic acid molecules, proteins, antibodies and/or inhibitors, as well as their use to evaluate and regulate an immune response in an animal.

The invention provides a family of antibodies that specifically bind the human cell surface glycosphingolipid GD2. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies may be coupled to a therapeutic agent and used in the treatment of cancer.

The present invention relates to a transcriptional regulatory sequence with enhanced tumor-specificity and strength and a recombinant vector comprising the transcriptional regulatory sequence. More particularly, the present invention relates to a transcriptional regulatory sequence comprising a human telomere reverse transcriptase (hTERT) promoter linked to a nucleotide sequence that comprises one or more c-Myc binding sites and/or one or more Sp1 binding sites, and a recombinant vector comprising a certain gene that is operably linked to the above transcriptional regulatory sequence.

The present invention describes DNA vaccines that encode for and direct the coincident expression of an antigen and an ADP-ribosyltransferase toxin that is devoid of ADPribosyltransferase activity and methods for vaccinating animals with the same. The DNA vaccines are useful for vaccinating against viral, bacterial and parasitic pathogens.

The present invention describes a method of identifying inducible genetic regulatory sequences that can control the transcription of specific gene transcripts. Methods of using inducible genetic regulatory sequences are also discussed. In particular, the genetic regulatory sequences of the present invention can modulate the transcription of a nucleic acid transcript in vivo.

The present invention discloses the identification of a human obesity susceptibility gene, which can be used for the diagnosis, prevention and treatment of obesity and related disorders, as well as for the screening of therapeutically active drugs. The invention more specifically discloses that the MAP3K11 gene on chromosome 11 and certain alleles thereof are related to susceptibility to obesity and represent novel targets for therapeutic intervention. The present invention relates to particular mutations in the MAP3K11 gene and expression products, as well as to diagnostic tools and kits based on these mutations. The invention can be used in the diagnosis of predisposition to, detection, prevention and/or treatment of coronary heart disease and metabolic disorders, including hypoalphalipoproteinemia, familial combined hyperlipidemia, insulin resistant syndrome X or multiple metabolic disorder, coronary artery disease, diabetes and dyslipidemic hypertension.

Immunomodulating agents comprising at least one Fc receptor ligand and at least one immunosuppressive factor are provided as are methods for their manufacture and use. The immunomodulating agents may be in the form of polypeptides or chimeric antibodies and preferably incorporate an immunosuppressive factor comprising a T cell receptor agonist or antagonist. The compounds and compositions of the invention may be used to selectively suppress the immune system to treat symptoms associated with immune disorders such as allergies, transplanted tissue rejection and autoimmune disorders including autoimmune diabetes, rheumatoid arthritis and multiple sclerosis.

The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from Streptococcus pneumoniae. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention further provides monoclonal antibodies which selectively bind PsaA. In addition peptides are provide that immunospecifically bind to the monoclonal antibodies of the invention, and that are immunogenic against Streptococcus pneumoniae infection. Also provided are vaccines comprising such immunogenic polypeptides, and methods of conferring protective immunity against Streptococcus pneumoniae infection by administering therapeutic compositions comprising the munogenic peptides of the invention. Also provided are methods of detecting the presence of Streptococcus pneumoniae in a sample using antibodies or antigens, and methods of preventing and treating Streptococcus pneumoniae infection in a subject. In addition a method of identifying the sequence of a peptide potentially capable of eliciting protective immunity against a pathogenic microorganism is provided.

The present invention is directed to a sperm flagellar energy carrier, SFEC, antibodies specific for the SFEC and the use of the SFEC protein to identify antagonists of SFEC activity. SFEC is believed to be essential for sperm motility, is localized to a specific region of the sperm, and thus antagonists of SFEC activity are anticipated to have utility as contraceptive agents.

The present invention relates to methods for the killing of infectious bacteria by modulating the extra-cellular concentration of bacterial cell signalling molecules. This has the effect of inducing rapid cell death (autolysis) in the majority of bacter cells, and preventing virulence or restoring a benign state in surviving cells. These receptors have applications for the treatment of individuals with susceptibility to infection, the treatment of patients with existing infections, in disease management, and in related applications where the host for infection is an animal or plant. The compositions described herein are particularly relevant to Pseudomonas aeruginosa infection, for example in the treatment of pulmonary infection in cystic fibrosis patients, and represent a unique bactericidal medication that does not directly target the bacteria.

The invention provides a human KLK2 which is associated with the hematological disorders, cancer, cardiovascular diseases, inflammatory diseases, neurological disorders, reproduction disorders and urological disorders. The invention also provides assays for the identification of compounds useful in the treatment or prevention of hematological disorders, cancer, cardiovascular diseases, inflammatory diseases, neurological disorders, reproduction disorders and urological disorders. The invention also features compounds which bind to and/or activate or inhibit the activity of KLK2 as well as pharmaceutical compositions comprising such compounds.

The present invention is directed to an antibody or derivative thereof of human origin for inhibiting platelet aggregation, characterized in that it is effective by substantially exclusive binding to the activated state of platelet integrin receptor GPIIb/IIIa.

Silicatein is an enzyme of silicate-forming organisms used for the synthesis of their silicate scaffold. The present invention relates to the use of highly-expressed and highly active recombinant silicatein, silicatein isolated from natural sources after gene induction as well as silicatein-fusion proteins for the synthesis of amorphous silicon dioxide (silicic acids and silicates), siloxanes as well as modification of these compounds and their technical use.

Anti-polyubiquitin monoclonal antibodies, and methods for using the antibodies, are provided.

The present invention discloses the identification of a human autism susceptibility gene, which can be used for the diagnosis, prevention and treatment of autism and related disorders, as well as for the screening of therapeutically active drugs. The invention more specifically discloses that the PITX1 gene on chromosome 5 and certain alleles thereof are related to susceptibility to autism and represent novel targets for therapeutic intervention. The present invention relates to particular mutations in the PITX1 gene and expression products, as well as to diagnostic tools and kits based on these mutations. The invention can be used in the diagnosis of pervasive developmental disorder, mental retardation, anxiety, depression, attention deficit hyperactivity disorders, speech delay, epilepsy, metabolic disorder, immune disorder, bipolar disease and other psychiatric and neurological diseases.

The present invention relates to blocking, inhibiting, reduceing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, as well as methods of using the same in inflammation.

A human anti-IL-23p19 antibody, including isolated nucleic acids that encode at least one anti-IL-23p19 antibody, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

The present invention provides a cell marker that is characterized by binding to a GCTM-5 antibody of active fragment. The cell marker identifies a unique sub-population of stem cells that show characteristics of hepatic or pancreatic stem cells or hepatic or pancreatic progenitor cells. More specifically the marker is an early liver marker, which could prove a useful tool for the isolation and identification of liver and pancreatic progenitors for both diseased adult liver and differentiating human embryonic stem cells.

The present invention provides a screening method that enables the development of a pharmaceutical of a new mechanism of action allowing the regulation of the formation of elastic fibers, and various means necessary for the method. More specifically, the present invention provides a polypeptide obtained by cleaving DANCE and a polynucleotide that encodes the same; a method of cleaving DANCE; an antibody against a polypeptide obtained by cleaving DANCE; a method of measuring the amount of DANCE cleaved and a kit therefor; a DANCE mutant and a polynucleotide that encodes the same; various DANCE complexes and methods of preparing the same; a screening method for a substance capable of regulating the activity of DANCE or a DANCE-specific protease, and the substance obtained thereby; a regulator of the formation of elastic fibers; and a kit comprising at least DANCE and a polynucleotide that encodes the same, and the like.

Use of a novel vaccine antigen applied in a preventive or therapeutic way against diseases in general, being such disease of bacterial, viral, cancer related, or other origin. The technical objective that this invention pursues is the development of formulations with the ability to increase the protective spectrum of existing vaccines and hence expanding it against different pathogens.In order to achieve this goal the NMB1125 protein was isolated and identified as a component of outer membrane preparations of Neisseria meningitidis capable of inducing bactericidal activity. Additionally, the gene codifying for NMB1125 protein was cloned and expressed, and the said polypeptide was purified and its immunogenicity evaluated in animal models. The sequence data from homologous genes showed, due to the high degree of conservation, its high value as a target antigen of a cross-reactive response when it is presented by different routes. Resultant formulations of this invention are of use in the pharmaceutical industry as vaccine formulations for human use.

The present invention provides polypeptides that contain one or more PDZ domains and are useful in the detection of pathogens. The polypeptides of the invention are also useful in the diagnosis, treatment, and prevention of diseases. Also provided are methods of preparing polypeptides of the invention.

The present invention provides a reporter system comprising a reporter gene encoding a reporter protein that is secretable from cells in which it produced or expressed either in vitro or in vivo and excretable in a body fluid from whole animals comprising such systems. The reporter system is useful for the detection of gene activation events or biochemical changes related to, or that occur, as a result of altered metabolic or disease status or toxicological stress in toxicological screening.

Proteins that bind to matrix metalloproteinase 14 and methods of using such proteins are described.

Manipulation of the EphB6 receptor and its active Eph partners allow for regulation of T cell responses, including TCR signalling, T cell proliferation, and induction of T cell death. Methods of modulating EphB6 are described as well as various therapeutic applications.

SVCT2 is consistently expressed at high levels in brain microvessel endothelial cells. Disclosed herein are assays for determining whether a test material/molecule is a substrate for, and/or is actively transported by, the SVCT2 transporter, and therefore a candidate substrate for crossing the blood brain barrier. The assays are useful in screening for therapeutic, cytotoxic or imaging compounds used in the treatment or diagnosis of neurological diseases.

Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease EOS. The deduced amino acid sequence, and it alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease EOS mRNA is expressed in platelets and leukocytes and more specifically eosinophils. Although this protease is abundantly expressed in ovary, retina and stomach, where it may perform important functions, its expression in platelets and certain cells of the immune system suggests that it may play roles in thrombosis and in the immune process. Enzymatically active protease EOS is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators

The present disclosure describes a tissue system with conjunctival cells, including conjunctival stem cells. The conjunctival tissue system is derived from isolated tissue comprising conjunctival cells, and is suitable for restoring ocular surface impairments, particularly those that result from damaged or diseased conjunctiva. The tissue system is generated using a simple single medium culture scheme, and a support material, such as human amniotic membrane. The conjunctival tissue system generate is suitable for transplantation to treat the ocular surface of an eye of a subject that is damaged or diseased.

There is disclosed a topical composition having substantially undifferentiated plant seed cells and, preferably, a pharmaceutically or cosmetically acceptable vehicle. There is also a method for topically applying the composition. There are also methods for delivering a consistent level of an active to skin, nail, lips and/or hair and for enhancing the therapeutic efficacy of a topical composition having substantially undifferentiated plant seed cells.

Bioimplants and methods of making the bioimplants are provided. The bioimplants comprise biological tissues having conjugated thereto adjunct molecules. The biological tissues are sterilized with a chemical sterilizing agent, such as a water soluble carbodiimide. The processes of making the bioimplants include a process in which an adjunct molecule is conjugated to a biological tissue during the sterilization process.

Methods of evaluating patients by assessing expression of B7-H4 in the vasculature are described.

The present invention provides a novel drug/agent for the prevention and/or treatment of Alzheimer's disease based on a different Alzheimer's disease onset mechanism from the amyloid hypothesis, and a method of screening for it.

The present invention is directed to the use of a compound stimulating deubiquitinating activity in a cell for the manufacture of a medicament for enhancing the expression of integral membrane proteins on the cell surface. Especially, the invention is directed to the use of such compound for the manufacture of a medicament for the treatment of a disease of condition selected from the group consisting of cystic fibrosis, diabetes insipidus, hypercholesterinaemia and long QT-syndrome-2.

A novel pea cultivar, designated FP2280, is disclosed. The invention relates to the seeds of pea cultivar FP2280, to the plants of pea line FP2280 and to methods for producing a pea plant by crossing the cultivar FP2280 with itself or another pea line. The invention further relates to methods for producing a pea plant containing in its genetic material one or more transgenes and to the transgenic plants produced by that method and to methods for producing other pea lines derived from the cultivar FP2280.

A novel pea cultivar, designated FP2282, is disclosed. The invention relates to the seeds of pea cultivar FP2282, to the plants of pea line FP2282 and to methods for producing a pea plant by crossing the cultivar FP2282 with itself or another pea line. The invention further relates to methods for producing a pea plant containing in its genetic material one or more transgenes and to the transgenic plants produced by that method and to methods for producing other pea lines derived from the cultivar FP2282.

The present invention provides compositions and methods for regulating expression of isolated nucleotide sequences in a plant. The compositions are novel nucleic acid sequences for callus-tissue and seed embryo-preferred regulatory sequences. Methods for expressing an isolated nucleotide sequence in a plant or callus tissue using the regulatory sequences are also provided. The methods comprise transforming a plant cell to contain an isolated nucleotide sequence operably linked to the regulatory sequences of the present invention and regenerating a stably transformed plant or callus tissue from the transformed plant cell.

A DNA isolation method by removal of constituents, interfering with a subsequent PCR is disclosed. According to an embodiment of the method, all substances and method steps are fully integrated into a closed unit (cartridge) for single use, which allows entry of a DNA-containing sample and DNA-binding substrates are used for isolating the released DNA. In particular, when the method is applied to DNA isolation from whole blood by disruption of white blood cells, the reagents, required for carrying out the cell disruption and other reactions, are stored in a form which is stable at room temperature. For disrupting the white blood cells and for DNA isolation, a dry stored lysis reagent is dissolved in an aqueous solution and brought into contact with the white blood cells. The corresponding assembly includes a unit, for housing DNA-containing biological containers and/or reagents, whereby at least one microchannel is provided to contain reagents, whereby the reagent is present in the microchannel as a dry mixture with a negligible vapour pressure, which forms a stable substance at room temperature.

A lettuce cultivar, designated 50-0401001-B, is disclosed. The invention relates to the seeds of lettuce cultivar 50-0401001-B, to the plants of lettuce cultivar 50-0401001-B and to methods for producing a lettuce plant by crossing the cultivar 50-0401001-B with itself or another lettuce cultivar. The invention further relates to methods for producing a lettuce plant containing in its genetic material one or more transgenes and to the transgenic lettuce plants and plant parts produced by those methods. This invention also relates to lettuce cultivars or breeding cultivars and plant parts derived from lettuce cultivar 50-0401001-B, to methods for producing other lettuce cultivars, lines or plant parts derived from lettuce cultivar 50-0401001-B and to the lettuce plants, varieties, and their parts derived from the use of those methods. The invention further relates to hybrid lettuce seeds, plants, and plant parts produced by crossing cultivar 50-0401001-B with another lettuce cultivar.

The present invention is related to the identification of cancer stem cells using the MMTV-Wnt-1 transgenic mouse model. These cancer stem cells have a gene expression signature that allows them to be distinguished from their non-tumorigenic counterparts. Moreover, the gene expression pattern can also predict survival in a diverse group of solid tumors.

The present invention is in the field of plant biochemistry. More specifically the invention relates to nucleic acid sequences from plant cells, in particular, nucleic acid sequences from maize and soybean plants associated with the cytokinin pathway. The invention encompasses nucleic acid molecules that encode proteins and fragments of proteins. In addition, the invention also encompasses proteins and fragments of proteins so encoded and antibodies capable of binding these proteins or fragments. The invention also relates to methods of using the nucleic acid molecules, proteins and fragments of proteins and antibodies, for example for genome mapping, gene identification and analysis, plant breeding, preparation of constructs for use in plant gene expression and transgenic plants.

The invention provides methods of identifying herbicidal auxins. The invention further provides auxin-herbicide-resistant plants and genes conferring auxin-herbicide resistance. This invention also provides a method of identifying other proteins that bind picolinate auxins from additional plant species. The invention further provides a method to identify the molecular binding site for picolinate auxins. The invention also includes the use of the picolinate herbicidal auxin target site proteins, and methods of discovering new compounds with herbicidal or plant growth regulatory activity. The invention also includes methods for producing plants that are resistant to picolinate herbicidal auxins. Specific examples of novel proteins associated with herbicide binding include AFB5, AFB4, and SGT1b.

A cotton cultivar, designated DP 121 RF, is disclosed. The invention relates to the seeds of cotton cultivar DP 121 RF, to the plants of cotton DP 121 RF and to methods for producing a cotton plant produced by crossing the cultivar DP 121 RF with itself or another cotton variety. The invention further relates to hybrid cotton seeds and plants produced by crossing the cultivar DP 121 RF with another cotton cultivar.

Disclosed are plants that have been genetically modified to express a PKS-like system for the production of PUFAs (a PUFA PKS system), wherein oils produced by the plant contain at least one PUFA produced by the PUFA PKS system and are free of the mixed shorter-chain and less unsaturated PUFAs that are fatty acid products produced by the modification of products of the FAS system in standard fatty acid pathways. Also disclosed are the oil seeds, oils, and products comprising such oils produced by this system, as well as methods for producing such plants.

A nucleic acid sequence is provided which encodes a gibberellin 2-oxidase gene which catalyses the 2.beta.-oxidation of a gibberellin molecule to introduce a hydroxyl group at C-2 and further catalyses the oxidation of the hydroxyl group introduced at C-2 to yield the ketone derivative. Such sequences can find application in the preparation of transgenic plants with altered levels of gibberellin 2-oxidase.

Disclosed is a viral vector, whose transcripts induce gene inactivation in plants, comprising a cDNA sequence reverse transcribed from RNA of Cymbidium mosaic virus. In addition, the invention provides a method to inactivate plant genes, which comprises the steps of: (a) providing a viral vector comprising a cDNA sequence reverse transcribed from RNA of Cymbidium mosaic virus; (b) constructing a recombinant plasmid containing a homologous gene fragment of the plant and the viral vector; (c) preparing transcripts of the plasmid through in vitro transcription; (d) infecting the plant with said transcripts; and (e) forming siRNA from said transcripts to inactivate the homologous gene. The viral vectors and the method provided in the present invention can ensure the studies of the function of plant genes in a short period, and can be applied in screening plants with properties of commercial values and changing the plant characteristics.

A cotton cultivar, designated PM 3225 B2RF, is disclosed. The invention relates to the seeds of cotton cultivar PM 3225 B2RF, to the plants of cotton PM 3225 B2RF and to methods for producing a cotton plant produced by crossing the cultivar PM 3225 B2RF with itself or another cotton variety. The invention further relates to hybrid cotton seeds and plants produced by crossing the cultivar PM 3225 B2RF with another cotton cultivar.

A cotton cultivar, designated 06W650F, is disclosed. The invention relates to the seeds of cotton cultivar 06W650F, to the plants of cotton 06W650F and to methods for producing a cotton plant produced by crossing the cultivar 06W650F with itself or another cotton variety. The invention further relates to hybrid cotton seeds and plants produced by crossing the cultivar 06W650F with another cotton cultivar.

Surprisingly, the present inventors have discovered that expression of TAT-046 protein in human patients is associated with cancer, and that the overexpressed protein is present in plasma membrane fractions. Thus, the present inventors have discovered that TAT-046 is associated with abnormal development and growth, and may be useful as a target for the identification of anti-cancer compounds, including antibodies for use in immunotherapy. Accordingly, the present invention provides methods for the identification of compounds that inhibit TAT-046 expression or activity, comprising: contacting a candidate compound with a TAT-046 and detecting the presence or absence of binding between said compound and said TAT-046, or detecting a change in TAT-046 expression or activity. Methods are also included for the identification of compounds that modulate TAT-046 expression or activity, comprising: administering a compound to a cell or cell population, and detecting a change in TAT-046 expression or activity. The methods of the invention are useful for the identification of anti-cancer compounds.

Methods for treating neurological diseases and for testing Caloric Restriction (CR) mimetics or CR mimetic candidates. In one exemplary method, a CR mimetic candidate is administered to a transgenic animal and the effects of the administering are determined; the transgenic animal includes an added gene from another type of animal or a modified gene which is designed to produce a disease or ailment of the another type of animal, and the method seeks to determine whether the CR mimetic candidate improves the disease or ailment. Methods relating to neurological disease and other methods relating to CR mimetic testing are also described.

The present invention relates to a method for regulating the expression of a target gene in a prokaryotic cell and a horrigent suitable for conducting the method.

Disclosed is a HPV-16 peptide antigen, and the antigen comprises a peptide sequence of SEQ ID No: 1. The peptide antigen of the invention is able to bind with MHC class I antigen on the cell and be presented on the cell surface. It can be recognized by cytotoxic T lymphocytes (CTLs), therefore induces CTL responses for cytolysis to control the replication and expression of the HPV-16.

The present invention broadly relates to the synergistic attenuation of vesicular stomatitis virus (VSV). More particularly, the invention relates to the identification of combined mutation classes which synergistically attenuate the pathogenicity of VSV vectors in mammals and immunogenic compositions thereof.

An isolated, altered fibronectin-binding protein (Fnb) of S. aureus having at least one mutation in an amino acid selected from residues corresponding to Gln103, Gln105, Lys157, Lys503, Lys620, Lys702, Lys762, Gln783 and Gln830 of FnbA of S. aureus strain ATCC49525 is described. Replacement of these reactive residues within the fibronectin-binding protein renders this protein less capable than wild-type Fnb of covalently cross-linking with fibronectin and fibrin. The altered fibronectin-binding protein effectively interferes with adhesion of S. aureus to fibronectin and fibrin, and therefore, an immunogenic composition comprising such altered Fnb exhibits improved immunogenic properties and is safer to use.

The present invention relates to a human papillomavirus (HPV) vaccine that comprises peptides from host cell proteins and more particularly, a vaccine that is directed against cancers that are associated with HPV infections, such as cervical cancer, head and neck cancer and skin cancers. The peptides comprise fragments of host cell proteins that have been targeted for degradation by HPV proteins, such as E6 and E7 and are presented on the surface of HPV infected cells in relatively large amounts. These peptides can be recognised by CTL and elicit an immune response, and are therefore ideal tumour-specific markers. The invention also relates to novel peptide: peptide complexes such as peptide/HLA complexes and their use in a tumour-specific vaccine.

This invention relates to the relationship between infection with adipogenic adenoviruses, such as adenovirus-36 (Ad-36) and the etiologies of obesity and obesity-related cancers and other diseases. Additionally, the invention relates to assaying a subject for Ad-36 status and using Ad-36 status as a marker for the presence of cancer, to predict the future risk of developing cancers, such as breast or prostate cancer, and/or to predict the aggressiveness and prognosis of these cancers.

Sequences encoding two immunoreactive glycoproteins were cloned from Ehrlichia canis (p153 gene) and Ehrlichia chaffeensis (p156 gene). These two glycoproteins are species-specific immunoreactive orthologs that are useful as subunit vaccines and for serologic and molecular diagnostics for E. canis and E. chaffeensis.

The invention relates to a test kit based on a dry-chemical determination method and to the method for the rapid determination of the content of yeast-available nitrogen components in must and wine. By means of the method according to the invention, nitrogen is determined in the form of ammonium. It is possible here to determine on the one hand free ammonium and on the other hand ammonium which has previously been liberated from arginine.

A method is provided for evaluating drug compounds based on their binding properties to human serum albumin wherein structural information at particular albumin binding regions is entered into a computer database and assessed with regard to particular contacting binding residues located in accordance with the invention. The information obtained through the computer database is thus useful in assessing and predicting drug interactions at albumin binding sites. Further, protein fragments including one or more albumin binding sites are provided which can be used in methods of assessing and designing drugs.

It is intended to provide a peroxisome proliferator-activated receptor (PPAR) activator, which is free from the problem of side effects, can be taken over a long term and has no characteristics taste. .beta.-cryptoxantine is employed as a PPAR activator. .beta.-cryptoxantine, which is contained in a large amount in the pulp of citrus fruits (in particular, mandarin-type citrus fruits) such as satsuma oranges, for example, has been consumed for many years. Thus, it is free from any problem in safety and has a low calorie content. Therefore, it can be taken over a long term. Because of being tasteless and odorless, moreover, .beta.-cryptoxantine would not damage the unique taste when added to a food. Therefore, it can be added to foods and taken.

A sustained release delivery system and composition of materials for slowly releasing an additive to a fermentation fluid over a sustained period of time of up to 96 hours is described. The product of the present invention includes a complement of additives and a sustained release mechanism to allow a single addition of components that yield release profiles consistent with multiple additions in juice, fermented beverages, other foodstuffs, and biofuels production.

The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a "polymersome." The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

The present invention relates to novel sequences for use in detection, diagnosis and treatment of cancers, especially lymphomas. The invention provides cancer-associated (CA) polynucleotide sequences whose expression is associated with cancer. The present invention provides CA polypeptides associated with cancer that are present on the cell surface and present novel therapeutic targets against cancer. The present invention further provides diagnostic compositions and methods for the detection of cancer. The present invention provides monoclonal and polyclonal antibodies specific for the CA polypeptides. The present invention also provides diagnostic tools and therapeutic compositions and methods for screening, prevention and treatment of cancer.

A procedure is described for conjugating the hydrazone derivatives of doxorubicin having a maleimide terminal group to lactosaminated human albumin (L-HAS). The procedure is based on the use of trialkylphosphines to reduce the disulfide bonds of the protein and make its SH groups available for the formation of the thioether bond. In comparison with the conjugation obtained by using thiol reducing agents, such as dithiothreitol, this has the advantage that even when it is performed under very simple conditions, specifically without using an inert atmosphere, in the absence of oxygen, and without preliminary purification of the "reduced" L-HAS, it does not bring about the formation of a precipitate in the reaction means. In comparison with conjugation to L-HAS thiolated by using iminothiolane, the novel procedure has the advantage of greater simplicity and of not introducing exogenous molecules into the L-HAS in order to make the SH groups available.

Modified, furin resistant human TSLP polypeptides and polynucleotides encoding the modified human TSLP polypeptides are provided. Pharmaceutical compositions, B and T cell activation agents, assays and methods of use are also described.

A polypeptide having an RNase III activity with which the length of a dsRNA degradation product can be easily controlled depending on reaction conditions and, in preparing a dsRNA having a length allowing it to serve as an siRNA in RNA interference, a low-molecular weight product having little RNA interferring effect is scarcely formed; a method of degrading a dsRNA with the use of the above polypeptide; and a composition and a kit for the above method.

Methods and compositions detect and quantify viable Legionella and other heterotrophic aerobic bacteria. Dip-slides that include an absorbent medium, growth promoting, and growth selective substances are useful in rapid detection and quantification of microcolonies of Legionella. Most probable number method of detection and quantification of Legionella are disclosed.

Disclosed is a medium for the detection and/or identification of a Candida yeast, the medium comprising: a chromogen; carbohydrate in the range 1-5 gms/litre; and an alcohol; the medium being such that growth of the Candida yeast under appropriate conditions results in hydrolysis of the chromogen to generate a chromophore of a derived colour which is a different colour from that generated by hydrolysis of the chromogen in a standard medium.

Disclosed are methods of identifying subjects with Diabetes or a pre-diabetic condition, methods of identifying subjects at risk for developing Diabetes or a pre-diabetic condition, methods of differentially diagnosing diseases associated with Diabetes or a pre-diabetic condition from other diseases or within sub-classifications of Diabetes, methods of evaluating the risk of progression to Diabetes or a pre-diabetic condition in patients, methods of evaluating the effectiveness of treatments in subjects with Diabetes or a pre-diabetic condition, and methods of selecting therapies for treating Diabetes or a pre-diabetic condition, using biomarkers.

The invention provides a method for measuring binding of a test compound to a G-Protein Coupled Receptor (GPCR). The invention also provides a method for identifying and measuring the effect that an agent has upon modulating the binding of a test compound to a G-Protein Coupled Receptor.

The present invention provides a process for producing a dipeptide other than D-alanyl-D-alanine and D-alanyl-D-serine using, as an enzyme source, a culture of a microorganism having the ability to produce a protein having D-alanine-D-alanine ligase activity or a treated matter of the culture, and a process for producing a dipeptide comprising D-amino acid using, as enzyme sources, a culture of a microorganism having the ability to produce the D-amino acid or a treated matter of the culture and a culture of a microorganism having the ability to produce a protein having D-alanine-D-alanine ligase activity or a treated matter of the culture.

The invention relates to methods for the fermentative production of sulfur-containing fine chemicals, in particular L-methionine, by using bacteria which express a nucleotide sequence coding for a methionine synthase (meta) gene.

Compositions and methods for biomass conversion are provided. Compositions comprise novel enzyme mixtures that can be used directly on lignocellulose substrate. Methods involve converting lignocellulosic biomass to free sugars and small oligosaccharides with enzymes that break down lignocellulose. Novel combinations of enzymes are provided that provide a synergistic release of sugars from plant biomass. Also provided are methods to identify enzymes, strains producing enzymes, or genes that encode enzymes capable of degrading lignocellulosic material to generate sugars.

There is provided a new strain, i.e. the alternaria alternata var. monosporus ST-026R CGMCC No. 0899, and its use in the production of paclitaxel. The invention also provides a method for the production of paclitaxel by using the strain CGMCC No. 0899.

A non-reducing saccharide-forming enzyme and a trehalose-releasing enzyme, which have an optimum temperature in a medium temperature range, i.e., a temperature of over 40 or 45.degree. C. but below 60.degree. C.; and an optimum pH in an acid pH range, i.e., a pH of less than 7. The two-types of enzymes can be obtained in a desired amount, for example, by culturing in a nutrient culture medium microorganisms capable of producing the enzymes or by recombinant DNA technology.

Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, as well as polynucleotides encoding same. Fusion proteins comprising cleavage half-domains are used in pairs, to reconstitute a functional cleavage domain. In these fusion proteins, the zinc finger domain can be N-terminal to the cleavage half-domain, or the cleavage half-domain can be N-terminal to the zinc finger domain. The availability of fusion endonucleases having these different polarities allows targeting (and thereby binding) of zinc finger endonucleases either to opposite strands of the DNA target or to the same strand of the DNA target, thereby increasing the number of possible sequences which can be targeted and cleaved by the fusion proteins.

The invention provides an isolated nucleic acid encoding a water-soluble polypeptide fragment of human tryptophanyl-tRNA synthetase, which is useful for the inhibition of angiogenesis. The nucleic acid comprises a polynucleotide of SEQ ID NO: 6, a polynucleotide hybridizable to SEQ ID NO: 6, a polynucleotide that encodes the polypeptide of SEQ ID NO: 7, a polynucleotide that encodes a polypeptide of SEQ ID NO: 12, a polynucleotide that encodes a polypeptide epitope of SEQ ID NO: 7, or a polynucleotide that is hybridizable to a polynucleotide that encodes a polypeptide epitope of SEQ ID NO: 7. Vectors and recombinant cells comprising the nucleic acid are also provided.

A polypeptide, called Tir (for translocated intimin receptor, which is secreted by attaching and effacing pathogens, such as the enteropathogenic (EPEC) and enterohemorrhagic (EHEC) E. coli. These bacterial pathogens inserts their own receptors into mammalian cell surfaces, to which the bacterial pathogen then adheres to trigger additional host signaling events and actin nucleation. Diagnosis of disease caused by pathogenic E. coli can be performed by the use of antibodies which bind to Tir to detect the protein or the use of nucleic acid probes for detection of nucleic acids encoding Tir polypeptide. Isolated nucleic acid sequences encoding Tir polypeptide, Tir peptides, a recombinant method for producing recombinant Tir, antibodies which bind to Tir, and a kit for the detection of Tir-producing E. coli are provided. A method of immunizing a host with Tir to induce a protective immune response to Tir or a second polypeptide of interest is also provided. A method for screening for compounds which interfere with the binding of bacterial pathogens to their receptors is further provided.

The present invention provides a composition which includes a sclareol or a derivative thereof, wherein the sclareol or a derivative thereof is bound by a glycoprotein matrix. The composition of the invention provides improved potency, stability and bioactivity characteristics of sclareol, or its derivatives.

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 invention provides an in vitro method for observing an effect of a test agent on a murine tumour model. The model consists a three-dimensional array of murine fibroblasts in a collagen gel which mimics a connective tissue substrate, on or in which are grown benign or malignant murine tumour cells. The model mimics the interactions between the tumour and the underlying tissue substrate, which in turn influence the effect which potential therapeutic or oncogenic agents have on the tumour tissue. Thus the models of the invention provide more physiologically relevant data than monolayer cultures or other available issue models about the effects a particular test agent will have on tumour tissue in vivo. Preferred embodiments provide a model of epithelial tissue and tumours derived therefrom.

The invention provides polypeptides comprising inhibitor of apoptosis protein (IAP) family members, such as BmIAP initially derived from Bombyx mori BmN cells, and nucleic acids encoding them, and methods for making and using these compositions, including their use for inhibiting apoptosis.

Methods, compositions and kits are disclosed directed at haptens, immunogens and immnoassays for buprenorphine (BUP) and nor buprenorphine (norBUP). The method comprises providing in combination in a medium (i) a sample suspected of containing buprenorphine (BUP) or norbuprenorphine (norBUP) and (ii) an antibody raised against an immunogen of buprenorphine (BUP) or norbuprenorphine (norBUP). The medium is examined for the presence of a complex comprising a labeled hapten of buprenorphine (BUP) or norbuprenorphine (norBUP) where the presence of such as complex indicates the presence of the compound in the sample.

Systems, methods, apparatus, and computer programming useful in identifying proteins, peptides, carbohydrates, and other biomolecules, or for a validation of an identification of proteins, peptides, carbohydrates, and other biomolecules, is described. In particular, the invention provides systems, methods, apparatus, and programming useful for identifying proteins and other precursor biomolecules using expression patterns associated with peptides or other biomolecule fragments expressed from analyte samples, and data representing such expression patterns, and for determining and improving confidence levels associated with identification of precursor biomolecules using such methods, through the correlation of expression patterns for fragments associated with precursor biomolecules.

The present invention relates to the diagnosis of colorectal cancer. It discloses the use of protein proteasome subunit alpha 3 (PSA3) in the diagnosis of colorectal cancer. It relates to a method for diagnosis of colorectal cancer from a liquid sample, derived from an individual by measuring PSA3 in said sample. Measurement of PSA3 can, e.g., be used in the early detection or diagnosis of colorectal cancer.

The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell, and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.

The Present invention relates to biological test methods using micro trays for determining red blood cell antigens and corresponding antibodies of the serum or plasma from individuals using cell aggregation analysis method. This invention also relates to kits for determining red blood cell typing, wherein the kits including mixture monoclonal antibodies, can recognize red blood group's specific antigens. The kits can also have specific red blood cells or cell membrane to determine the corresponding antibodies in the serum. The cell aggregation information may be readable by microscope that may be connected with computer for storage and future analysis. The cell aggregation method in the micro tray can be used for red blood cell antigen determination, antibody recognition and cross match for transfusion with minimal amount of antibody or samples.

In this application is described the production of recombinant, chimeric, humanized antibodies specific for both BoNt/A and BoNT/B. The humanized antibodies were converted from a mouse anti-BoNT/A/B Fab fragment into a whole human IgG1 antibody. The antibodies are useful in assays for detecting human exposure to BoNT/A and BoNT/B.

The invention provides methods of diagnosing Graves' disease (GD), Rheumatoid Arthritis (RA) and other autoimmune diseases in an individual by detecting a disproportionately large fraction of peripheral blood T cells express IGF-1R (CD3.sup.+ IGF-R.sup.+) compared to normal control samples. In a further embodiment, the invention provides methods of diagnosing, prognosing, staging, and/or monitoring GD, RA and other autoimmune diseases. Or a predisposition thereto in an individual by detecting a disproportionately large fraction of CD3.sup.+ IGF-1R.sup.+ T cells that express CD45RO.sup.+ compared to normal control samples. In a further embodiment, the invention provides a method of diagnosing, prognosing, staging, and/or monitoring GD, RA and other autoimmune diseases or a predisposition thereto in an individual by detecting an increased CD45RO.sup.+/RA.sup.+ ratio in peripheral blood T cells compared to normal control samples. In addition to peripheral blood T cells, the methods of the invention also can be practiced with test samples comprising T cells harvested from affected orbital tissues. Embodiments directed to the prognosis, staging, and/or monitoring of GD, RA and other autoimmune diseases or a predisposition thereto also are provided, along with diagnostic kits for practicing the various embodiments of the invention.

The present invention relates to genes whose expression is correlated to the prevalence of coronary artery disease. In particular, the invention relates to methods of prognosis, diagnosis and methods of monitoring coronary artery disease based on the measurement of gene expression. In addition, the present invention relates to methods of screening compounds for use in treatment of coronary artery disease as well as kits and arrays for use in identifying coronary artery disease.

Disclosed herein are compositions and methods involving identifying MMP-26 in a subject with cancer.

The present invention provides a novel genetically modified Escherichia coil JM109 bearing accession number PTA 1579, containing the gene coding for poly-beta-hydroxybutyrate synthesis and a method of using this bacterium to produce poly-beta-hydroxybutyrate to the extent of 60% or more of the cell weight.

The present invention relates to methods of determining the immunogenic potential of a test product by comparing the immunogenic profile or fingerprint of the test product to the immunogenic profile or fingerprint of a reference product.

This invention provides novel human LXR.alpha. variant polypeptides and nucleic acids encoding such polypeptides. This invention also provides the therapeutic, diagnostic, and research utilities as well as the production of such polynucleotides and polypeptides. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

The presently disclosed subject matter provides vectors that encode small interfering RNAs (siRNAs) designed to down regulate the expression of hypoxia-inducible genes in a cell. Also provided are compositions and host cells based upon the vectors, as well as methods of using the vectors. The presently disclosed subject matter further provides a method of inhibiting tumor growth infecting cells in a tumor with an adenovirus vector that encodes an siRNA directed against the hypoxia-inducible factor 1.alpha. (HIF-1.alpha.) gene.

The invention relates to compositions comprising cell culture medium conditioned by cells grown in three-dimensional culture. The cells used to condition the medium may be genetically modified to alter the concentration of growth factors and antioxidants in the medium. The conditioned cell medium (conditioned medium) may be used for at least one of cosmetic applications, cosmeceutical applications, and pharmaceutical applications, among other things. The invention also relates to proteins comprising a heterologous sequence that enhances cell penetration. The invention also relates to cells comprising DNA encoding such proteins. Methods for preparing the inventive compounds are also provided.

A premesenchymal stem cell differentiated from a pluripotent stem cell in vitro which is positive for Sox1, and a method for the preparation of the same.

Self-assembling fusion proteins and nucleic acids encoding the same are provided. The subject fusion proteins include a first dimer forming oligomerization domain and a second tetramer forming oligomerization domain rigidly linked to each other. Also provided are regular structures made up of a plurality of self-assembled fusion proteins of the subject invention, and methods for producing the same. The subject fusion proteins find use in the preparation of self-assembled nanostructures, e.g., two-dimensional layers and three-dimensional networks, which structures find use in a variety of different applications.

The invention relates to a method for the expansion and differentiation of haematopoietic stem cells into enucleated erythrocytes, in two steps: a first step in a culture medium, where cell proliferation and erythroid differentiation are induced in the presence of growth factors, and a second step modeling a reconstitution of the microenvironment, substantially without erythropoietin (EPO). Optionally, the method of culture may comprise an intermediate step, with haematopoietic growth factors.

A main object of the present invention is to provide a cell culture patterning substrate and a method for manufacturing the same, which can be used to culture the cells on the substrate in an intended shape. To achieve the object, the present invention provides a cell culture patterning substrate comprising: a base material provided with a convex portion; and a cell culture region, which is a region for culturing a cell, formed on a surface of the base material, wherein the cell culture region is partitioned with the convex portion of the base material provided with the convex portion.

The invention features methods for increasing cell death. The invention also features compounds used to increase cell death. The invention further features methods for identifying compounds that increase cell death.

Embodiments of the present invention provide methods and compositions for microorganisms having increased alcohol tolerance. In certain embodiments, methods for using such microorganisms, and methods for identifying gene or genetic regions responsible for increased alcohol tolerance are contemplated.

A bacterial protein which converts 2-methyl citrate to 2-methyl isocitrate is a previously unknown target for antibacterial agents. The protein of this activity is associated with mucoid bacteria and inhibitors of production or activity of this protein in combination with propionic acid mitigate the virulence of these bacteria.

Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states in cells having Wnt receptors.

An antimicrobial formulation containing biologically stabilized silver nano particles stabilized by a `green` biological route with an average size 1-100 nm in a carrier in which the concentration is 1 to 6 ppm.

The invention relates to a method for coating a support plate for carrying out functional tests on biological cells, to a support plate for carrying out functional tests on biological cells and to the use of corresponding support plates for carrying out functional tests on biological cells.

An apparatus 20 for the separation of a subpopulation of cells from an intact organ or other biological material is provided. The apparatus 20 includes: (1) a digestion chamber 24 that integrates the primary digestion process, (2) a measuring cylinder 26, (3) a cell collection chamber 28, (4) a heat exchanger 30 for raising and lowering temperatures in the digestion chamber 24 to activate or inactivate enzymes, (5) sensors 112, 114, 116, 118, 120, 122 to complete a closed feedback loop for allowing optimization of the digestion process, and (6) mock cells which mimic the cells to be harvested and which are used to fully optimize the process without unnecessary destruction of harvested cells. The manipulation of the digestion process may be manual or may be automated under computer control.

A system for generating viral vectors carrying two distinct expression cassettes is provided. The system utilizes a unique polyvalent transfer vector that permits efficient detection and selection of inserted expression cassettes.

The invention provides polypeptides, nucleic acid sequences, bacterial strains, methods and kits for producing exogenous protein. More specifically, the invention provides RNase E polypeptides that posses impaired mRNA degrading activity and efficient rRNA and tRNA processing activity. These polypeptides may be utilized for producing exogenous protein.

Methods of producing properly folded recombinant .alpha.1-antitrypsin (AAT) polypeptide are provided. Denatured recombinant AAT polypeptide is refolded by first solubilizing the polypeptide with a chaotroph at high pH, followed by refolding in the presence of reduced concentrations of chaotroph and in the presence of PEG, glycerol or sucrose, or a detergent while the pH is slowly reduced and is generally maintained.

It is an object to provide an antibody chip and a light source measuring apparatus which are excellent in a reproducibility and a workability of a measurement and can easily be utilized. A light source measuring apparatus (1) includes, as a main structure, a concentration measuring device (2), an antibody chip (3) and a cell washing device (4). The concentration measuring device (2) serves to measure a concentration of an antigen in a specimen solution taken by the antibody chip (3) The cell washing device (4) has solution injecting means constituted by an injecting pump (44), an injecting tube (45), a first solution vessel (46), a second solution vessel (47) and a solution selecting valve (48) and solution discharging means constituted by a plurality of discharging pumps (51), a discharging tube (52), an intake end (52a) and the like. In a state in which a container cover (8) is opened, an inner part of a cell (39) of the antibody chip (3) having an antibody fixing layer formed on a main surface of a substrate (37) on a chip carrier (7) is washed to stabilize the antibody fixing layer without the solution remaining in the cell.

The present invention is based on the realization that the bonds between a target molecule, or a target molecule attached to a particle, and a surface, can be ruptured by mechanically oscillating the surface at increasing amplitude, leading to detachment of the target molecule or particle from the surface. The required acceleration, and hence force, will depend on a variety of factors, including the mass of the molecule or particle, the nature of the bond to the surface and the geometric shape or size of the target molecule or particle. The present invention may therefore be used to separate or to size different target molecules, or to detect their presence.

Novel quinoline inhibitors of retroviral integrase, particularly HIV-1 integrase. The quinoline inhibitors are oxoquinolines that can be used for preventing or treating AIDS or HIV infection in a subject.

A process for treating ammonia containing wastewater includes bringing an ammonia-treating material and ammonia containing wastewater into contact with each other to remove ammonia in the wastewater continuously as nitrogen gas, the ammonia-treating material including a long carrier and complex bacterial sludge attached and immobilized on the biomass carrier, the carrier including a net, a nonwoven fabric or a woven fabric of fibers or filaments, the carrier being attached to a support, the complex bacterial sludge containing bacterial sludge including autotrophic anammox bacteria and bacterial sludge including autotrophic ammonia-oxidizing bacteria, the ammonia containing wastewater containing dissolved oxygen at a concentration of not less than 0.5 mg/l. The process for treating ammonia containing wastewater uses the treating material in which the bacterial sludge are attached and immobilized, and nitritation and anammox reaction can take place efficiently and economically even when the wastewater contains dissolved oxygen at a high concentration.

In one embodiment the present invention provides a blood analyte meter that is user-friendly and easy to use. In accordance with an embodiment of the present invention an analyte measurement device, for use with a test strip for determining the amount of an analyte in a sample, displays a hierarchy of information or options to a user. The hierarchy of information or options may include, among other information or options, subroutines that are performable by the processor of the device, stored data related to past tests performed by the user, and alarm features of the device. A user scrolls through and selects individual options or pieces of information by rotating and translating a rotatable user interface around and along an axis of rotation.

The present invention relates to methods and apparatuses involving biocompatible structures for tissue engineering and organ replacement and, more specifically, to methods and apparatuses involving biocompatible structures formed by three-dimensional fabrication for tissue engineering and organ replacement. In some embodiments, the biocompatible structures are scaffolds for cells that can be used as tissue engineering templates and/or as artificial organs. The structures may be three-dimensional and can mimic the shapes and dimensions of tissues and/or organs, including the microarchitecture and porosities of the tissues and organs. In some cases, a structure formed by three-dimensional fabrication comprises a wall defining a cavity and a plurality of pores in at least a portion of the wall. The pores may permeate the wall and enable exchange of a component (e.g., a molecule and/or a cell) between a portion interior to the cavity and a portion exterior to the cavity. For instance, pores may allow delivery of molecules, cell migration, and/or generation of connective tissue between the structure and its host environment. Structures of the invention can be implanted into a mammal, or alternatively and/or additionally, can be used ex vivo as bioartificial assist devices.

An apparatus and method that may be used for collecting target cells or tissue and preparing a cell block are disclosed.

A method is described for treating a biomaterial waste stream to remove pollutants and to generate a product. The method comprises the steps of injecting the biomaterial waste stream into a waste fermentation system, contacting the biomaterial waste stream with a microorganism, and subjecting the biomaterial waste stream to conditions conducive to aerobic fermentation of the biomaterial waste stream. The microorganism can be artificially flocculated, and the microorganism is the product generated from the method.

The invention disclosure is a method of bioremediation of wastewater, particularly groundwater, by utilizing coupled anaerobic and aerobic biological treatment, more specifically, methanogenic (strictly anaerobic) and methanotrophic (strictly aerobic) microbial populations, in combination with a supply of in-situ generated water-dissolved oxygen and hydrogen. Water electrolysis is used to produce water-dissolved oxygen and hydrogen. The immediate advantage of using H.sub.2 from the electrolysis, is to provide electron donors to methanogens to reductively dechlorinate the chloroaliphatics, and to reduce the water carbonates and generate methane which is used as energy and carbon source for the methanotrophic bacteria. Oxygen is used as electron acceptor by the aerobic bacteria, including the methanotrophs. The addition of an organic carbon source can be minimized or even eliminated, so as to diminish the competition between methanotrophic bacteria and heterotrophic bacteria for oxygen.

A method for the degradation of methyl-tertiary-butyl-ether (MTBE) and tertiary-butanol (TBA) using a mixture of Pseudomonas putida is described. The method enables almost complete remediation of MTBE and TBA in situ in contaminated water and/or soil.

This invention relates, in part, to newly identified polynucleotides, polypeptides, variants and derivatives thereof; processes for making the polynucleotides and the polypeptides, and their variants and derivatives; and uses of the polynucleotides, polypeptides, variants and derivatives. The invention also relates to compositions of orthogonal aminoacyl-tRNA synthetases, and pairs of orthogonal aminoacyl-tRNA synthetases, and orthogonal tRNAs that incorporate fluorinated amino acids into proteins in response to selector codons. The present invention also includes translation biochemistry methods for site-specific incorporation of fluorinated amino acids, for example, .sup.18F- or .sup.19F-labelled amino acids, into proteins or peptides. Such amino acids may be used as an NMR probe for characterizing protein structure, dynamics, and reactivity or for radionuclide imaging (e.g., PET). Fluorinated amino acids may also be used to stabilize proteins or peptides.

Methods and compositions for determining the suitability of a lung for transplantation are described.

The invention provides a method for generating and selecting drug-sensitizing antisense DNA fragments. In one embodiment, the method includes identifying a gene of interest using knowledge of bacterial physiology, biochemistry, genetics, genomics, and other means. The method includes PCR amplification of a gene of interest using genomic DNA as a template; fragmentation of the DNA by sonication or other means; selecting DNA fragments no longer than 400 base pairs; ligating the DNA fragments into a suitable expression plasmid with a selectable marker; transforming the plasmids containing the DNA fragments into the organism from which the gene of interest originated; and selecting clones from transformed cells that show a phenotypic difference of the clone grown in the presence of the inducer relative to the phenotype in the absence of inducer.

A method, and apparatus and computer program products for executing the method. The method includes obtaining a set of multiple images of a target feature location on an array of multiple features, each image of the set representing the target feature location following deposition of a corresponding sub-set of multiple droplets for that feature. An overlay composite may be generated from the image set. The overlay composite may be used as a quality control tool, or in interrogating the array or processing results of the interrogation.

This invention provides compounds, methods, immunoassays, and kits relating to active, metabolically sensitive ("met-sensitive") moieties of anti-HIV therapeutics, such as HIV protease inhibitors (PI), HIV nucleoside reverse transcriptase inhibitors (NRTI) and HIV entry inhibitors (EII).

Gene probes for specific regions of chromosomes 1, 3, 9, 10 and 17 are now shown to be useful in the diagnosis and prognosis of smoking related cancers such as non-small cell lung cancer (NSCLC). For example, these probes can be used with fluorescence in situ hybridization (FISH), and used to stratify smokers into high and low risk groups, to determine susceptibility to the development of smoking related cancers, to predict cancer progression and treatment efficacy, and to rule out other diseases.

The present invention provides for a method for identifying patients that are suitably treated by a therapy, such as a therapy involving administration of a fluoropyrimidine drug and/or a platinum drug. The method includes determining the expression level of at least one gene selected from a phospholipase 2 (PLA2) gene, a thymidine phosphorylase (TP) gene, and a glutathione S-transferase P1 (GSTP-1) gene in suitable sample isolated from the patient. Overexpression of the gene or genes identifies the patient as not being suitable for the therapy.

The invention provides compositions and methods useful for identifying, verifying or authenticating any type of sample, whether the sample, is biological or non-biological.

This invention relates to a multiplex PCR assay capable of screening or detecting the relevant microbial organism specific to Mycobacterium tuberculosis, Toxoplasma gondii, pathogenically important fungii and cytomegalo virus (CMV) in a sample, comprising a reaction mixture of a combination of 4 sets of primers, one of said primer for detection of Mycobacterium tuberculosis, a second of said primer for detection of Toxoplasma gondii, a third primer for the detection of pathogenically important fungi and a fourth primer for the detection of CMV, said primers being compatible to each other.

A method and apparatus for searching a gene sequence. The gene sequence search method includes receiving the gene sequence from a user, generating extended sequences including the received gene sequence, partial sequences included in the gene sequence and an inverse sequence complementary to the gene sequence, storing the gene sequence, the extended sequences, the partial sequences, the inverse sequence and input-related record information in a database, integrated-searching the gene sequence using a gene sequence search server, estimating a gene sequence search ranking for a predetermined period using the database and outputting an integrated and searched result of the gene sequence and a gene sequence search ranking result to the user.

The present invention provides compositions, kits and methods for rapid identification and quantification of bacteria by molecular mass and base composition analysis.

The methods of the invention allow extremely high throughput screening of chemicals against a large number of pharmacologically relevant targets. All of the pharmacologically relevant targets are expressed in cells, which are then screened against a fluorescently-tagged combinatorial library. Binding of the small molecules to the cells is then detected by fluorescence activated cell sorting or imaging.

The present invention provides novel methods for characterizing organisms by identifying the presence, absence, size or sequence polymorphism of intronic regions. The method involves selecting intronic regions from nuclear or organellar gene sequences that are useful for differentiating between and among taxonomic groupings of organisms. Such intronic regions can be analyzed directly or after amplification in a primer extension reaction. The amplification product is then analyzed by, for example, size fractionation, nucleotide sequencing or (RFLP). Intronic regions that contain an open reading frame encoding all or a portion of a protein can be used to generate antibodies to detect the presence or absence of the protein, which indicates the presence or absence of the intronic region. Methods of detecting an organism in a sample by detecting the presence or absence of one or more intronic regions also are provided using nucleic acid based or immunological based approaches. Kits are provided for practicing the methods of the invention.

Methods for fragmenting and labeling DNA in a single reaction volume and incubation step using a uracil DNA glycosylase, an apurinic/apyrimidinic endonuclease, and a terminal transferase are disclosed. In a preferred embodiment the UDG, AP and TdT activities are first mixed together to form an enzyme mixture and then the enzyme mixture is mixed with the uracil containing DNA. The fragmentation and labeling reactions thus take place simultaneously as part of the same reaction. The methods may be used in a variety of applications where fragmenting and end-labeling single or double stranded DNA is desired.

The present invention provides methods and kits for the rapid exponential amplification of nucleic acid molecules using a padlock probe. The present invention improves upon the existing methods for amplifying padlock probes by eliminating or delaying the appearance of artifact products that cause false positive results, and also increase the sensitivity and speed of the assay. Further provided are nucleic acid amplification primers containing non-informative base analogs.

Disclosed are methods of identifying microRNA motifs or microRNA precursors for a target gene or a set of target genes. Also disclosed are related computer-readable media

Methods are disclosed for identifying one or more proteins or polypeptides comprised by a sample. The methods comprise determining binding of each polypeptide with respect to each binding pool of a plurality of binding pools, wherein each binding pool comprises one or more probes which bind a structure comprised by a protein or polypeptide. In some aspects, polypeptides can be denatured and separated into individual polypeptide strands and immobilized on a solid support prior to determining binding of the binding pools. A protein, polypeptide or polypeptide strand can be identified by searching, in at least one database, for a protein or polypeptide sequence comprising binding pool targets either identical to or most similar to the binding pool targets comprised by the protein, polypeptide or polypeptide strand to be identified. Kits for identifying proteins, polypeptides and polypeptide strands are also disclosed.

A method and apparatus for detection whereby live bacteria among microbes as an antigen can be detected rapidly in a short period of time through specifically labeling of live bacteria within a test subject antigen and whereby testing assurance can be ensured. The method and apparatus are characterized in that labeled antigen (14) is formed by action, on a test subject antigen such as Escherichia coli, of labeled substance (13) zymolyzable by live bacteria (target bacteria (12)) within the test subject antigen, and the resultant labeled antigen (14) is trapped on an immobilization phase having, immobilized thereon, a specific binding antibody capable of specifically binding to the test subject antigen.

Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise, for example, administering to a mammal in need thereof a compound of formula (I): where x, y, J, K, L, M, W, V, R.sup.2, R.sup.3, R.sup.5, R.sup.5a, R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8 and R.sup.8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

Disclosed herein are antibodies that bind with high specificity to soluble oligomers of amyloid .beta. (Abeta) and methods of employing those antibodies. The antibodies are able to distinguish between Alzheimer's Disease (AD) and control human brain extracts. The antibodies identify endogenous Abeta oligomers in AD brain slices and also bind to Abeta oligomers on cultured hippocampal cells. The antibodies neutralize endogenous Abeta oligomers and Abeta oligomers produced in solution.

This invention provides novel assays for the detection of dysfunctional HDL. The assays are good diagnostics and/or prognostics for atherosclerosis or other pathologies characterized by an inflammatory response. In certain embodiments the methods involve measurements of heme-related HDL-associated proteins (e.g., haptoglobin, hemopexin, etc.), and/or measurements of the relative distribution of HDL-associated proteins between HDL and the non-lipoprotein fractions of plasma/serum, and/or measurements of the ability of pro-inflammatory HDL to consume nitric oxide, and/or measurement of the ability of HDL to inhibit LDL aggregation.

The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying optimum probe attachment sites. Biosensors are provided having functional molecules that can locate and bind to specific biomolecules within living cells. Biosensors can detect chemical and physiological changes in those biomolecules as living cells are moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, an environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound. New fluorophores whose fluorescence responds to environmental changes are also provided that have improved detection and attachment properties, and that can be used in living cells, or in vitro.

The present invention provides methods for detecting a predisposition for stroke in individuals by correlating allelic variants of the phosphodiesterase 4D (PDE4D) gene and hypertension status. The invention further contemplates kits and computer program products for detecting PDE4D polymorphisms indicative of a predisposition for stroke correlated with an individual's hypertension status.

A polypeptide that contains an amino acid sequence present in human leptin blocks the inhibitory effect of human C-Reactive Protein on human leptin. Accordingly, such a polypeptide is implicated in an approach to treating or preventing conditions associated with the impact of CRP on leptin.

The present invention relates to materials and procedures for evaluating patients suffering from cardiovascular conditions, particularly acute coronary syndromes. In particular, an assay configured to measure the level of soluble FLT-1 in a patient sample, alone or in combination with one or more other markers, provides diagnostic and/or prognostic information. While applicable to diseases and conditions in which inflammation is generally manifested, the methods and compositions described herein are particularly applicable to acute coronary syndromes, including conditions selected from the group consisting of stable angina, unstable angina, non-ST-elevation non-Q wave myocardial infarction, ST-elevation non-Q wave MI, and transmural (Q-wave) MI.

The invention relates to method for the diagnosis of Alzheimer's disease or the early stages thereof or a predisposition to said disease. Said method is based on quantitative determination of a mitogenically expressible surface marker, in particular CD69, and peripherally accessible cells, e.g. skin cells or lymphocytes, (a) prior to and (b) after mitogenic stimulation. A specific stimulation index a:b is an indication of Alzheimer's disease or early stages thereof or of a predisposition to said disease. The invention also relates to kits which are suitable for carrying out the inventive method of diagnosis.

The disclosure relates to methods of detecting cancer and evaluating risk of cancer. The disclosure also relates to methods of predicting patient response to chemotherapy. The disclosure further relates to the use of a single nucleotide polymorphism in the human AFAP gene for the preparation of a diagnostic compounds for detection of cancer, evaluation of risk of cancer, and prediction of response to chemotherapy.

The present invention provides methods and, accordingly, in vitro systems for generating stable and soluble oligomers of amyloid proteins, under physiological pH and temperature; and hence, a system for identifying and validating drugs that have the potential to prevent formation of soluble oligomers of amyloid proteins, to disaggregate soluble oligomers of amyloid proteins already formed and possibly disaggregate downstream larger insoluble aggregates of amyloid proteins.

Disclosed is a method of determining interferon responsiveness in a patient suffering from multiple sclerosis. The method comprises determining an amount of a XAF-1 gene expression level in a blood sample, which is obtained from the patient undergoing interferon therapy. The amount of the XAF-1 gene expression level in the blood sample is then correlated with the responsiveness of the patient to the interferon.

End Labelled Free Solution Electrophoresis (ELFSE) provides a means of separating polymer molecules such as ssDNA according to their size, via free solution electrophoresis, thus eliminating the need for polymer separation via gels or polymer matrices. Here, end labels are provided that optimize branching architecture to increase hydrodynamic drag of the end label, and improve separation of polymer molecules by ELFSE.

A method for determination of CK19 mRNA is provided characterized in that a part of CK19 mRNA is amplified using a first primer hybridizing to a region located on a first exon of the CK19 gene and a second primer hybridizing to a region located on a second exon of the CK19 gene locating downstream of the first exon. The amplificate is than detected using two kinds of probes.

The present invention provides methods, libraries and computer program products for selecting siRNA that reduce off-target effects and methods for gene silencing using these siRNAs. By comparing nucleotide sequences at positions 2-7 or 2-8 of the sense and/or antisense regions of candidate siRNAs to the 3' UTR region of mRNAs, one can select siRNAs that have reduced off-target effects.

The invention provides nucleic acid monomers with a 2'-modification that are useful for the incorporation of dyes or blocking groups. The monomers can be incorporated on the 3'-end of a dual labeled probe to inhibit PCR polymerase extension during PCR. The polymerase is inhibited from extending the probe at the 3'-hydroxyl group when the monomer is present; there is no need to add a chemical moiety to the 3'-hydroxyl or remove the 3'-hydroxyl. The monomers can also be incorporated internally or at the 5'-end of the oligonucleotide. A detectable label, such as a fluorescent or quenching dye, can be incorporated on the 2'-position of such monomers.

A method of detecting a target nucleic acid sequence comprising providing a stem-and-loop structured nucleic acid for measurement wherein the nucleic acid comprises complementary sequence portions located at both terminals and a target sequence portion therebetween as well as a double-stranded portion formed by hybridization of the complementary sequence portions located at both terminals and a remaining looped single-stranded portion, providing a probe nucleic acid having a sequence complementary to the target sequence portion wherein one end of the probe nucleic acid being immobilized to a solid substrate surface, reacting the nucleic acid for measurement with the probe nucleic acid to specifically hybridize the target sequence portion of the nucleic acid for measurement to the probe nucleic acid, and detecting presence or absence of the nucleic acid for measurement hybridized to the probe nucleic acid.

This document provides methods and materials related to treating trinucleotide repeat conditions. For example, methods and materials for treating a trinucleotide repeat condition as well as methods and materials for identifying OGG1 polypeptide inhibitors that can be used to treat a trinucleotide repeat condition are provided.

The present invention relates, in general, to Syk kinase and, in particular, to a method of inhibiting Syk kinase expression using small interfering RNA (siRNA).

A therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein. The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro; or made in recombinant cultures of microorganisms and isolated therefrom, or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell. In methods of treatment of prophylaxis of virus infections, other pathogenic infections or certain cancers, these compositions are administered in amounts effective to reduce or inhibit the function of the target polynucleotide sequence, which can be of pathognic origin or produced in response to a tumor or other cancer, among other sources.

A cosmetic composition contains an aqueous complex nutritive base comprising a plurality of amino acids, at least one vitamin, a plurality of assimilable organic components, and at least one inorganic salt. The cosmetic composition does not contain a biological extract of animal or cellular origin, or a living nourishing substrate. A cosmetic method comprises contacting human skin with the cosmetic composition.

Methods and compositions for reducing, preventing or reversing organ damage and/or enhancing organ preservation by administration of a peroxisome-proliferator activated receptor-alpha (PPAR.alpha.) agonist to the organ.

This invention relates to a hollow-nanoparticle-based biosensing tool, which comprises proteins capable of forming nanoparticles through the incorporation of a lipid bilayer and specific biorecognition molecules bound thereto and a biosensing method using such tool.

The present invention relates especially to a process for the localized distribution of drops of a liquid of interest on an active surface. The process comprises the following steps an introduction of liquid of interest into a box containing the said active surface, and an extraction of liquid of interest from the said box, the said active surface and also the other surfaces inside the box being substantially non-wetting with respect to the liquid of interest, with the exception of several uptake areas localized on the said active surface, which are each suitable for taking up a drop of liquid of interest. The uptake areas may surround working areas. The present invention also relates to processes for the electrochemical and optical detection of at least one analyte in a liquid of interest, and to an electropolymerization process.

The present invention provides a nerve cell differentiation inducing drug containing a Synoviolin expression inhibitor which is a useful drug for treatments of neural disorders, particularly Alzheimer's disease, Parkinson's disease, peripheral nerve disorders or spinal injury. As Synoviolin expression inhibitors, there are siRNA against gene coding Synoviolin (SEQ ID No. 1 or 2), or shRNA, a decoy nucleic acid that inhibits the promoter activity by binding to the transcription factor of the promoter of the Synoviolin gene or antisense oligonucleotide against gene coding the Synoviolin. The nerve cell differentiation inducing drug of the present invention is used for the treatment of neural disorders including Alzheimer's disease, Parkinson's disease, peripheral nerve disorders or spinal injury.

The invention relates to small interfering RNA specific to sub-units .alpha., .alpha. and .beta. of the kinase protein CK2, and to the applications of the same, especially for treating cancer and viral illnesses.

The present invention relates to a novel bidentate motif that is composed of two adjacent residues of tyrosine and serine which have been found to be involved in the binding of crucial cytoplasmic proteins which are involved in cell signalling pathways. In some cases, the cytoplasmic proteins are ubiquitous proteins involved in cell signalling pathways that may include mitogenesis, transformation and survival. The bidentate motif may have a sequence alignment TABLE-US-00001 (SEQ ID NO: 71) N-X-X-Y- (X) .sub.1-13-[R/K/H/Q]-[X/.PSI.] .sub.2-3-S/T-X-P; (SEQ ID NO: 72) Y- (X) .sub.1-16-[R/K/H/Q]-[X/.PSI.] .sub.2-3-S/T-X-P; or (SEQ ID NO: 73) N-X-X-Y-[X].sub.1-30-[R/K/Q/H]-[X].sub.1-4-[S/T]-X-pwherein X is any residue, Y is tyrosine, S/T is serine or threonine and .PSI. is a hydrophobic residue or an equivalent thereof. Preferably the residues are Tyr577 and Ser585 of the common .beta.c of the GM-CSF/IL-5/IL-3 receptor.

Disclosed herein is a method for detecting DNA using a nanopore including treating the surface of a nanopore formed in a solid substrate with a substance carrying positive charges; introducing a DNA-containing sample into the surface-treated nanopore; and detecting electrical signals generated during translocation of the sample through the nanopore. Also disclosed herein is device for detecting DNA using a nanopore including a solid substrate including a nanopore, treated with a substance which carries positive charges to change a surface property of the nanopore so that the nanopore surface carries positive charges; an electrode applying voltage to the nanopore of the solid substrate; and a measurement unit measuring an electrical signal generated during translocation of a DNA-containing sample through the nanopore.

High affinity, chemically modified triplex-forming oligonucleotides (TFOs) and methods for use thereof are disclosed. TFOs are defined as triplex-forming oligonucleotides which bind as third strands to duplex DNA in a sequence specific manner. Triplex-forming oligonucleotides may be comprised of any possible combination of nucleotides and modified nucleotides. Modified nucleotides may contain chemical modifications of the heterocyclic base, sugar moiety or phosphate moiety. A high affinity oligonucleotide (K.sub.d.ltoreq.2.times.10.sup.-8) which forms a triple strand with a specific DNA segment of a target gene DNA is generated. It is preferable that the K.sub.d for the high affinity oligonucleotide is below 2.times.10.sup.-10. The nucleotide binds or hybridizes to a target sequence within a target gene or target region of a chromosome, forming a triplex region. The binding of the oligonucleotide to the target region stimulates mutations within or adjacent to the target region using cellular DNA synthesis, recombination, and repair mechanisms. The mutation generated activates, inactivates, or alters the activity and function of the target gene.

Novel polypeptides and polynucleotides encoding same are provided. Also provided methods and phamaceutical compositions which can be used to treat various disorders such as cancer and retinopathies, using the polypeptides and polynucleotides of the present invention.

Disclosed herein are compositions and methods for and involving selectively targeting tumor lymphatics.

Black bear parathyroid hormone (PTH) and functional fragments thereof are provided. Also provided are methods of using black bear PTH and functional fragments for increasing cAMP in a bone-forming cell; reducing apoptosis in a bone-forming cell; decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell; increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell; enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a subject; also provided are antibodies directed against black bear parathyroid hormone (PTH) and functional fragments thereof.

The present invention relates to an optical detection cell for micro-fluidics. The detection cell provides a first layer, a detection cell layer contacting the first layer, a third layer contacting the detection cell layer and a detection channel defined through the detection cell to serve as a light path for receiving light for detecting a molecule Methods of detecting molecules and making the detection cell are also disclosed

The present invention relates generally to a novel chymotrypsin that exhibits resistance to a plant serine proteinase inhibitor. More particularly, the present invention provides a chymotrypsin which is up-regulated in the gut of Helicoverpa armigera and Helicoverpa punctigera insect larvae when fed the serine proteinase inhibitors of Nicotiana alata. The novel chymotrypsin represents, therefore, a target for the identification of antagonists including inhibitors which are proposed to be useful in the control of Helicoverpa spp. populations that have become resistant to serine proteinase inhibitors produced in plants. The antagonists of the chymotrypsin may be topically applied to the plants or, when in proteinaceous form, may be produced by genetic means in plant cells. The antagonists may act at the level of gene expression or protein activity.

The invention features methods and compositions for use in a screening assay to identify agents having antiviral activity against a DNA virus by assessing the effect of a candidate agent upon alternative splicing of MxA, or by assessing the effect of a candidate agent on production of a variant form of MxA protein. The invention also provides methods for enhancing resistance of cells to infection by a DNA virus by providing for elevated MxA and/or by providing for reduced production of variant MxA protein.

Systems and methods for increasing protoporphyrin IX accumulation in a target cell population using aminolevulinate synthase variants. Aminolevulinic acid-mediated photodynamic therapy is a promising approach to treating dysplasic disorders such as cancer and atherosclerosis, but is limited by the lack of a means to deliver optimal quantities of aminolevulinic acid selectively to the target cells, and thereby ensure the best therapeutic response. The disclosed invention provides a means for enhancing the natural production of aminolevulinic acid selectively within target cells to levels predetermined to give an optimal therapeutic response, and is expected to lead to increased efficacy of treatment, possibly broadening the scope of diseases treatable by photodynamic therapy considerably. The disclosed invention is also amenable to patient specific therapy, meaning that a patient's target cells could be used to screen for the aminolevulinic acid delivery system most appropriate for the patient's needs.

This invention provides superactive analogs of FSH demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type FSH. In particular, the analogs of the invention demonstrate at least a ten fold increase in potency or at least a ten percent increase in maximal efficacy as compared to wild type protein. The analogs are particularly useful for treating subjects showing low FSH receptor expression or poor FSH receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

The present invention relates to a method for detecting the presence of water born pathogens and indicator microorganism including bacteria from water sample by selecting the target gene carried in template DNA by amplifying the target DNA using specific primers with biotinylated tag consist of all or a substantial part of 5'-CTGATCGAATGGCTGCCAGGCTCC-3' and 5'-CAACCAGACGATAGTTATCACGCA-3' and taq DNA polymerase to get desired biotinylated tagged probe followed by hybridization of biotinylated tagged probe with target gene in template DNA followed by enzyme coupled reaction.

The present invention discloses methods and compositions for detecting novel mutations in the .alpha. chain of the hexosaminidase gene. These methods facilitate rapid screening for Tay-Sachs disease carriers, especially in the Ashkenazi Jewish population. The novel mutations include the single nucleotide substitutions 638A>C and 181C>T.

A system for reliably and reproducibly exposing the contents of a biological cell to an analysis instrument comprising a sample handling unit that includes a first substrate with first substrate face and a second substrate with second substrate face. The first substrate face and the second substrate face are opposed. The biological cell is positioned between the first substrate face and the second substrate face. A framework with a mechanism for applying a range of pressures to the first substrate face and the second substrate face reliably and reproducibly exposes the contents of the biological cell to the analysis instrument.