Abstract: Disclosed herein are apparatuses and methods for conducting multiple simultaneous micro-volume chemical and biochemical reactions in an array format. In one embodiment, the format comprises an array of microholes in a substrate. Besides serving as an ordered array of sample chambers allowing the performance of multiple parallel reactions, the arrays can be used for reagent storage and transfer, library display, reagent synthesis, assembly of multiple identical reactions, dilution and desalting. Use of the arrays facilitates optical analysis of reactions, and allows optical analysis to be conducted in real time. Included within the invention are kits comprising a microhole apparatus and a reaction component of the method(s) to be carried out in the apparatus.

Abstract: The present invention describes the use of molecular expression profiles in the primary screening of compounds for pharmacological activity. In some embodiments, the methods of the invention comprise characterizing a profile of expression levels of a number of distinct biological molecules for two distinct sample types (A and B) that differ by some relevant parameter, in order to characterize the difference between the two types in terms of expression profile. Following this, one of the types (B) is treated with an analyte of unknown activity relative to the parameter by which the sample types differ. The expression profile of treated B is then measured and compared with the expression profiles of A and untreated B to ascertain whether the analyte has induced a shift in the profile of B to more closely or more distantly resemble the profile of A in some meaningful way.

Abstract: The present invention provides an array of polymers and methods of forming arrays of polymers by providing a substrate having a first layer including one or more dielectric coatings on a solid support and a second layer including a plurality of polymers disposed on the first layer. The invention also provides methods for forming an array of polymers on a substrate using light-directed synthesis by providing a substrate having a first layer including one or more dielectric coatings on a solid support; derivatizing the first layer by contacting the first layer with a silanation reagent, and a second layer disposed on said first layer wherein the second layer includes functional groups protected with a photolabile protecting group.

Abstract: The present invention relates a process of quality examining for microarray of biological material. More particularly, the present invention is directed to a process of quality examining for microarray of biological material, which comprises 1) a step for mixing probe and a compound which emits light or heat and does not react with said probe, 2) a step for microarraying the mixture obtained in step 1) on a substrate, and 3) a step for measuring light or heat emitted by the scanning of each spots of the microarray mixture.

Abstract: A method for detecting methylated nucleotides within a nucleic acid sample is provided. The method includes the steps of splitting a nucleic acid sample into separate reaction vessels; contacting nucleic acid in one reaction vessel with bisulfite; amplifying the nucleic acid in each reaction vessel; cleaving the nucleic acids in each reaction vessel to produce fragments thereof; and obtaining a mass spectrum of the resulting fragments from one reaction vessel and another mass spectrum of the resulting fragments from another reaction vessel.

Abstract: The SOST gene gives rise to sclerostin, a protein that leads to apoptosis of bone progenitor cells. The invention provides antagonists to the sclerostin protein, and methods for identifying new sclerostin antagonists. The invention also provides molecules that can depress expression of the SOST gene, as well as methods for identifying such molecules. Such molecules and antagonists are useful for increasing bone mineralization in mammals, for example, in the treatment of osteoporosis.

Abstract: The invention provides a method useful for detection of genetic disorders. The method comprises determining the sequence of alleles of a locus of interest, and quantitating a ratio for the alleles at the locus of interest, wherein the ratio indicates the presence or absence of a chromosomal abnormality. The present invention also provides a non-invasive method for the detection of chromosomal abnormalities in a fetus. The invention is especially useful as a non-invasive method for determining the sequence of fetal DNA. The invention further provides methods of isolation of free DNA from a sample.

Abstract: The present invention relates to methods for detecting, quantifying and high throughput screening of donor-products and the catalytic activities generating the donor-products in group-transfer reactions. The invention further provides immunoassays, antibodies and kits that may be used to practice the methods of the invention.

Abstract: A novel gene defining a novel enzyme in the UDP-D-galactose: beta-N-acetylglucosamine/beta-N-acetylgalactosamine beta 1,3galactosyltransferase family, termed beta3Gal-T5, with unique enzymatic properties is disclosed. The enzymatic activity of beta3Gal-T5 is shown to be distinct from that of previously identified enzymes of this gene family. The invention discloses isolated DNA molecules and DNA constructs encoding beta3Gal-T5 and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting beta3Gal-T5 activity, as well as cloning and expression vectors including such DNA, cells transfected with the vectors, and recombinant methods for providing beta3Gal-T5. The enzyme beta3Gal-T5 and beta3Gal-T5-active derivatives thereof are disclosed, in particular soluble derivatives comprising the catalytically active domain of beta3Gal-T5.

Abstract: Methods and kits for classifying patients having diffuse large B-cell lymphoma (DLBCL) based upon expression of a plurality of genes are disclosed. Real-time quantitative RT-PCR can be used to measure expression values. Correlating expression values of the plurality of genes in a tumor sample from the patient to reference expression values obtained from DLBCL patients can stratify patients in the classification groups. The methods and kits can be used to predict overall patient survival.

Abstract: 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.

Abstract: The present invention relates to the NIPA-1 proteins and nucleic acids encoding the NIPA-1 proteins. The present invention further provides assays for the detection of NIPA-1 polymorphisms and mutations associated with disease states, as well as methods of screening for ligands and modulators of NIPA-1 proteins.

Abstract: A novel biosensor comprises at least one fluorophore and at least two quenchers, and is capable of selectively and specifically detecting the presence of an ion in the presence of other ions.

Abstract: Novel DNA sequence determination method and DNA sequencer system providing a sequencing speed 103 to 104 times faster than the current DNA sequencing speed (105 bases per day with a lane at maximum) of the existing DNA sequencer based on electrophoresis. The method includes the step of discriminating base-specific labels of heavy elements using a magnified image of elongated single-chain DNA or RNA produced by a transmission electron microscope (TEM). The DNA sequencer system uses this method. The invention provides a DNA sequencing speed that is higher than the existing speed by 3 or 4 orders of magnitude.

Abstract: The present invention relates to a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligase detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.

Abstract: A peptide or protein microassay method and apparatus in which a wide variety of chromogenic or fluorogenic peptide or protein substrates of interest are individually suspended or dissolved in a hydrophilic carrier, with aliquots of each substrate being deposited in an array or microarray of reaction loci, or “dots.” Each dot, therefore, provides an individual reaction vessel containing the peptide or protein of interest, to which a biological sample may be applied for assay purposes. The sample is applied to the array or microarray of dots by one of a variety of focused sample application techniques, including aerosolizing or misting of the sample, or target application of the sample, onto each dot without creating fluid channels between the dots which would cause cross-contamination.

Abstract: Mammastatin has an approximate molecular weight of 44 kDa in its inactive, non-phosphorylated form. Normal mammary cells express functional phosphorylated forms having approximate molecular weights of 53 kDa and 49 kDa. Metastatic mammary cells either do not express Mammastatin at all, or do not express the 53 kDa or 49 kDa, phosphorylated forms. Mammary cancer cells are inhibited in their growth by the administration of phosphorylated Mammastatin.

Abstract: A highly sensitive assay is disclosed which combines immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis to detect, enumerate and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood and has a greater sensitivity than conventional PCR or immunohistochemistry by 1-2 orders of magnitude. In addition, the assay facilitates the biological characterization and staging of carcinoma cells.

Abstract: A method for removing contaminant DNA in a sample containing a physiologically active protein, which comprises the following steps: 1) converting the sample containing a physiologically active protein into a neutral aqueous solution of low conductivity; and 2) removing the resulting particles.

Abstract: The present invention relates to compositions and methods for cancer diagnostics, including but not limited to, cancer markers. In particular, the present invention provides gene expression profiles associated with prostate cancers. The present invention also provides novel markers useful for the diagnosis, characterization, and treatment of prostate cancers. In particular, the present invention provides methods and compositions for the detection of ?-methylacyl-CoA racemase (AMACR) in the urine as a marker for prostate cancer detection.

Abstract: The present invention relates to a G-protein coupled receptor and a novel ligand therefor. The invention provides screeing assays for the identification of candidate compounds which modulate the activity of the G-protein coupled receptor, as well as assays useful for the diagnosis and treatment of a disease or disorder related to the dysregulation of G-protein coupled receptor signaling.

Abstract: The present invention relates to agonist-independent methods of screening for compounds that alter GPCR desensitization. Included in the present invention are cell lines containing GRKs, in which GPCRs are desensitized in the absence of agonist; the GRKs may be modified. The present invention relates to methods to determine if a GPCR is expressed at the plasma membrane, and if the GPCR has an affinity for arrestin. Modified GPCRs which have increased arrestin affinity are included in the present invention. These modified GPCRs are useful in methods to screen for compounds that alter desensitization, including both the agonist-independent methods and agonist-dependent methods described herein.

Abstract: A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter.

Abstract: Elevated blood levels of the chemokine CXCL10 polypeptide are associated with respiratory illnesses (e.g. SARS, influenza and community-acquired pneumonia) and are useful in diagnosis of patients. Methods are provided for diagnosis and treatment of patients suffering from respiratory illnesses. Methods are provided for identifying inhibitors of the CXCL10:CXCR3 axis, for use in treating patients suffering from respiratory illnesses.

Abstract: This invention relates to an improved procedure for the multiparameter analysis of leukocyte subpopulations from peripheral blood, bone marrow or any body fluid containing blood nucleated cells, including the quantification of each subpopulation in terms of cells per microliter. The method uses a cocktail of at least four monoclonal antibodies labelled each with a different fluorescent tag, the measurement of at least two light scatter and four fluorescence emissions related parameters and at least one population of fluorescent beads to differentiate and enumerate between and among the different leukocyte subpopulations in the peripheral blood, the bone marrow or other body fluid.

Abstract: The invention provides methods for quantifying enzymatic activity of an enzyme with a known substrate. The methods employ SELDI-TOF mass spectrometry, and are suitable, in particular, for assaying aspects of the renin-angiotensin system. The methods may be utilized to assess and/or monitor biological conditions associated with the renin-angiotensin system prior to the manifestation of known physiological and biomarkers for such conditions. The methods are suitable for analysis of pharmacological effectors of the renin-angiotensin system, and are particularly suitable for automation and high-throughput screening assay design.

Abstract: The invention relates to a novel method for enzymatic polymerization which includes (1) obtaining a reaction mixture including a monomer, a template, and an enzyme; and (2) incubating the reaction mixture for a time and under conditions sufficient for the monomer to align along the template and polymerize to form a polymer-template complex. The template can be a micelle, a borate-containing electrolyte, or lignin sulfonate. Such a complex possesses exceptional electrical and optical stability, water solubility, and processibility, and can be used in applications such as light-weight energy storage devices (e.g., rechargeable batteries), electrolytic capacitors, anti-static and anti-corrosive coatings for smart windows, and biological sensors.

Abstract: A method for constructing stable bioactive fusion proteins of the difficult to express tum or necrosis factor superfamily (TNFSF), and particularly members CD40L (CD 154) and RANKL/TRANCE, with collectins, particularly pulmonary surfactant protein D (SPD) is described. Single trimers of these proteins lack the full stimulatory efficacy of the natural membrane forms of these proteins in many cases. The multimeric nature of these soluble fusion proteins enables them to engage multiple receptors on the responding cells, thereby, mimicking the effects of the membrane forms of these ligands. For CD40L-SPD, the resulting protein stimulates B cells, macrophages, and dendritic cells, indicating its potential usefulness as a vaccine adjuvant. The large size of these fusion proteins makes them less likely to diffuse into the circulation, thereby limiting their potential systemic toxicity.

Abstract: The present invention generally relates to methods of modifying the glycosylation structures of recombinant proteins expressed in fungi or other lower eukaryotes, to more closely resemble the glycosylation of proteins from higher mammals, in particular humans. The present invention also relates to novel enzymes and, nucleic acids encoding them and, hosts engineered to express the enzymes, methods for producing modified glycoproteins in hosts and modified glycoproteins so produced.

Abstract: This invention relates to an isolated nucleic acid fragment encoding a sugar transport protein. The invention also relates to the construction of a chimeric gene encoding all or a portion of the sugar transport protein, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the sugar transport protein in a transformed host cell.

Abstract: Using the proteins of the present invention, DNAs encoding the proteins, and antibodies recognizing the proteins, detection methods for diseases relating to the novel insulin-like growth factor binding proteins of the present invention, as well as diagnostic agents, preventive agents, and therapeutic agents for diseases relating to the proteins of the present invention can be provided.

Abstract: There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human chemokine beta-11 (Ck beta-11) polypeptide and a human leukocyte adhesion inhibitor-1 (LAI-1) polypeptide (previously termed chemokine ?1 (CK?1 or CKa-1), a well as Ck beta-11 and/or LAI-1 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same.

Abstract: The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, illustratively, but not limited to, fed-batch cell cultures. The methods comprise feeding the cells with D-galactose, preferably with feed medium containing D-galactose, preferably daily, to sustain a sialylation effective level of D-galactose in the culture for its duration, thus increasing sialylation of the produced proteins. The methods can also comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. The cell culture processes of the invention involving two or more temperature shifts sustain a high cell viability, and can allow for an extended protein production phase. The methods can also comprise the delayed addition of polyanionic compound at a time after innoculation.

Abstract: A biosynthetic method for producing glucosamine and N-acetylglucosamine is disclosed. Such a method includes the fermentation of a genetically modified microorganism to produce glucosamine and/or N-acetylglucosamine. Also disclosed are genetically modified microorganisms that are useful for producing glucosamine and N-acetylglucosamine. In addition, methods of recovering N-acetylglucosamine that has been produced by a fermentation process, including methods that result in N-acetylglucosamine of high purity, are described. Also disclosed is a method to produce glucosamine from N-acetylglucosamine.

Abstract: The present invention relates to an in vitro method for diagnosing or detecting a predisposition to a condition at least partially characterised by inappropriate fibrosis or scarring (e.g. Dupuytren's Disease). The method comprises examining the ZF9 gene, and regulatory elements thereof, derived from a subject of interest to detect the presence of a genetic poylmorphism or mutation in said gene which is linked with the condition.

Abstract: A melting curve analysis is performed for a nucleic acid containing a mutation in a nucleotide sequence resulting in a mutation replacing serine at position 20 in an amino acid sequence of the pancreatic islet amyloid polypeptide with glycine (IAPP S20G), by using a nucleic acid probe of which end is labeled with a fluorescent dye, and in which fluorescence of the fluorescent dye decreases upon hybridization, wherein the nucleic acid probe has a nucleotide sequence complementary to a nucleotide sequence ending at the nucleotide number 247 in the nucleotide sequence of SEQ ID NO: 1 and having a length of 13 to 30 nucleotides, and the 5? end of the probe is labeled with the fluorescent dye, and measuring fluorescence of the fluorescent dye, and the mutation is detected on the basis of the result of the melting curve analysis.

Abstract: The present invention is directed to bacteriophage therapy, using methods which enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects. The HDS normally reduces the number of bacteriophage in an animal, which decreases the efficiency of the bacteriophage in killing the host bacteria present during an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes by physico-chemical alteration of the bacteriophage surface proteins, so that the altered bacteriophage remain active in the body for longer periods of time than the unmodified bacteriophage.

Abstract: A series of methods that utilize the incremental truncation of nucleic acids are described to create a plurality of modified nucleic acids and hybrid polypeptides. A plurality of substantially all possible single base-pair deletions of a given nucleic acid sequence is created. A method of making shuffled incremental truncated nucleic acids, which is independent of nucleic acid sequence homology, is also described. These methods can be used in protein engineering, protein folding, protein evolution, and the chemical synthesis of novel hybrid proteins and polypeptides.

Abstract: The invention relates to a process for the preparation of L-amino acids, in particular L-threonine, in which the following steps are carried out: a) fermentation of microorganisms of the Enterobacteriaceae family which produce the desired L-amino acid and in which at least one or more of the genes chosen from the group consisting of sucC and sucD, or nucleotide sequences which code for these, is or are enhanced, in particular over-expressed, b) concentration of the desired L-amino acid in the medium or in the cells of the bacteria, and c) isolation of the desired L-amino acid.

Abstract: Novel polynucleotides derived from microorganisms belonging to coryneform bacteria and fragments thereof, polypeptides encoded by the polynucleotides and fragments thereof, polynucleotide arrays comprising the polynucleotides and fragments thereof, recording media in which the nucleotide sequences of the polynucleotide and fragments thereof have been recorded which are readable in a computer, and use of them.

Abstract: By this invention, nucleic acid sequences encoding for fatty acyl-CoA:fatty alcohol acyltransferase (wax synthase) are provided, wherein said wax synthase is active in the formation of a wax ester from fatty alcohol and fatty acyl-CoA substrates. Of special interest are nucleic acid sequences obtainable from a jojoba embryo wax synthase having an apparent molecular mass of approximately 33 kD. Also considered are amino acid and nucleic acid sequences obtainable from wax synthase proteins and the use of such sequences to provide transgenic host cells capable of producing wax esters.

Abstract: The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3?-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3?-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: A method and system for electrically wounding and/or monitoring cell activity in vitro. The invention comprises methods and systems for wounding and/or monitoring cells that place a cell culture on a well that has an exposed electrode. The cell culture can then be wounded and/or monitored using the electrode.

Abstract: The present invention discloses a biosensor for quantitatively analyzing a bio-material and a manufacturing method thereof. The biosensor has an exposed conductive region of a few-nanometer scale distributed on an insulated metallic substrate in a desired pattern or randomly. The quantitative analysis of protein can be carried out by means of simplified procedures, without the necessity of rinsing out a signal-producing material, which is non-specifically bonded to the materials to be analyzed. The biosensor utilizes only the size of the molecules, and thus can be universally used for the analysis of bio-materials. A selective and separate analysis can be realized in which interference caused by other materials is significantly reduced.

Abstract: Provided are methods of removing bisulfite material from a composition that contains a bisulfite material and an enzyme. The method includes contacting the composition with a compound containing at least one aldehyde functional group to form an aldehyde-bisulfite complex, whereby the aldehyde-bisulfite complex may be separated from the composition.

Abstract: The present invention relates to methods for stimulating root growth and/or enhancing the formation of lateral or adventitious roots and/or altering root geotropism comprising expression of a plant cytokinin oxidase or comprising expression of another protein that reduces the level of active cytokinins in plants or plant parts. The invention also relates to novel plant cytokinin oxidase proteins, nucleic acid sequences encoding cytokinin oxidase proteins as well as to vectors, host cells, transgenic cells and plants comprising said sequences. The invention also relates to the use of said sequences for improving root-related characteristics including increasing yield and/or enhancing early vigor and/or modifying root/shoot ratio and/or improving resistance to lodging and/or increasing drought tolerance and/or promoting in vitro propagation of explants and/or modifying cell fate and/or plant development and/or plant morphology and/or plant biochemistry and/or plant physiology.

Abstract: The present invention is to provide a novel phosphodiesterase and a gene thereof, specifically, Type 11 phosphodiesterase (PDE11) and a gene thereof, more specifically, a phosphodiesterase selected from (A) a protein having an amino acid sequenced shown by SEQ.ID.NO: 2, SEQ.ID.NO: 4, SEQ.ID.NO: 6 or SEQ.ID.NO: 39, and (B) a protein having an amino acid sequence shown by SEQ.ID.NO: 2, SEQ.ID.NO: 4, SEQ.ID.NO: 6 or SEQ.ID.NO: 39 in which one or several amino acids are deleted, substituted or added, and having an activity of hydrolyzing a cyclic nucleotide, and a gene thereof, and a method of characterizing, identifying and selecting a phosphodiesterase inhibitor by using the same.

Abstract: Novel calcium-independent phospholipases A2; genes encoding the same; an antibody against them; an inherent promoter or a regulator gene which comprises a base sequence occurring in intron and inducing site-specific expression in response to an external stimulus; a method of expressing a target protein in response to an external stimulus; and an organism having this gene transferred thereinto. Novel calcium-independent phospholipases A2 having an amino acid sequence represented by SEQ ID NO: 1, 3 or 5 or an amino acid sequence derived from such an amino acid sequence by the substitution, deletion or addition of one or more amino acids; a gene having a base sequence occurring in an intron and being capable of initiating RNA transcription due to an external stimulus such as a stimulus with kainic acid or an electrical stimulus; a method of regulating expression by using the gene; and an organism having the gene transferred thereinto.

Abstract: The present invention relates to the co-expression and production of a heterologous alpha amylase and an endogenous glucoamylase in an Aspergillus strain and enzyme compositions including the same.

Abstract: The present invention provides novel protein variants that exhibit reduced immunogenic responses, as compared to the parental proteins. The present invention further provides DNA molecules that encode novel variants, host cells comprising DNA encoding novel variants, as well as methods for making proteins less allergenic. In addition, the present invention provides various compositions that comprise these proteins that are less immunogenic than the wild-type proteins.