Abstract: The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumor progression in cells involved in human tumors such as melanomas, breast, gastrointestinal, lung, and bone tumors, various types of skin cancers, and other neoplastic conditions such as leukemias and lymphomas. Genes are identified that are differentially expressed in benign (e.g., non-malignant) tumor cells relative to malignant tumor cells exhibiting a high metastatic potential. Genes are also identified via the ability of their gene products to interact with gene products involved in the progression to, and/or aggressiveness of, neoplastic tumor disease states. The genes and gene products identified can be used diagnostically or for therapeutic intervention.

Abstract: Genomic or cDNA, or fragments and mixtures thereof, can be screened by generation of subsets and then subjecting the subsets to mismatch scanning procedures. Alternatively, DNA fragments can be generated by cutting with a restriction endonuclease that generates variable overhangs. For either of the above methods, Y-shaped adapters having a region of non-complementary single-stranded DNA at the end can be used. Heterohybrid DNA, containing one DNA strand derived from each of two different samples, or homohybrids, containing DNA strands from the same sample, can be selected. Adapters attached to the ends of the fragments are designed to allow the selective isolation of homohybrid or heterohybrid DNA.

Abstract: Provided are purified and isolated VEGF-C polypeptides capable of binding to at least one of KDR receptor tyrosine kinase (VEGFR-2) and Flt4 receptor tyrosine kinase (VEGFR-3); analogs of such peptides that have VEGF-C-like or VEGF-like biological activities or that are VEGF or VEGF-C inhibitors; polynucleotides encoding the polypeptides; vectors and host cells that embody the polynucleotides; pharmaceutical compositions and diagnostic reagents comprising the polypeptides; and methods of making and using the polypeptides.

Abstract: The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

Abstract: Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T½ kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.

Abstract: A method of detecting binding interactions and target molecules, such as proteins, protein fragments, recombinant proteins, recombinant protein fragments, extracellular matrix proteins, ligands, carbohydrates, steroids, hormones, drugs, drug candidates, immunoglobulins and receptors of eukaryotic, prokaryotic or viral origin, by mediated electrochemistry using labels that react with transition metal mediator complexes in a detectable catalytic redox reaction. These labels are attached directly to binders, target molecules, surrogate target molecules, or to affinity ligands capable of binding to the target or to surrogate target molecules capable of competing with the target for binding to another binder. The labels can be naturally present (endogenous) in the binder, target or affinity ligand, or constructed by the covalent attachment of the label to the binder, target, affinity ligand or surrogate target (exogenous).

Abstract: The present invention relates to cloning vectors, cloning methods and cloning kits. More particularly, the present invention relates to a cloning vector comprising a nucleic acid sequence encoding a polypeptide which when expressed is lethal for a bacterial host cell and at least one cloning site wherein the insertion of a foreign nucleic acid insert in the cloning site causes a disruption of the expression of the lethal polypeptide.

Abstract: Provided are mutant DNA polymerases having at least one mutation which exhibit substantially reduced polymerase activity at 25° C. when compared to the same DNA polymerases without the at least one mutation and which exhibit normal or near-normal polymerase activity at optimum temperatures when compared to the same DNA polymerases without the at least one mutation. Also provided are amino acid sequences and nucleic acid sequences encoding such DNA polymerases, and vector plasmids and host cells suitable for the expression of these sequences. Also described herein are improved methods for performing polymerase chain reaction (PCR) amplification and other genetic manipulations and analyses using the mutant DNA polymerases of the invention.

Abstract: The cellular effects of potentially therapeutic compounds are characterized in mammalian cells and yeast. In the latter case the effects can be characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays.

Abstract: Disclosed are a method which can simultaneously analyze a plurality of analytes and can realize the determination of the base sequence of a large quantity of gene information in a short time, and an apparatus for the method. The method comprises the steps of: preparing four samples, for each of a plurality of nucleic acid analytes, containing analyte nucleic acid-derived oligonucleotide fragments with the end bases having been base-specifically fragmented; labeling the oligonucleotide fragments with a different label for each of the analyte nucleic acids; and subjecting the four samples to an analytical method which can distinguish oligonucleotide fragments based on a difference in length of one base, thereby determining the base sequence of the target nucleic acids.

Abstract: The present invention makes available assays and reagents for identifying agents which can be used to modulate at least one proliferation, differentiation and cell death by apoptosis.

Abstract: Nucleotide triphosphate probes containing a fluorophore attached to the &ggr;-phosphate and a quencher moiety sufficiently proximal to the fluorophore moiety for use in pyrophosphate detection assays are disclosed. These probes exhibit distinguishable fluorescence characteristics when the fluorophore is attached to the nucleotide through the &ggr;-phosphate and when it is unattached to the nucleotide. The present invention also provides kits and integrated systems for practicing the assays described herein.

Abstract: Disclosed herein are cloning vectors which include: (a) a cloning site which permits the cloning of a nucleic acid in defined orientation; (b) at least one cleavage site adjacent to the cloning site, the cleavage site being rarely-occurring in nucleic acids; and (c) a long region which is located on the side of the cloning site opposite to the cleavage site (b), wherein the long region and the region between the cloning site and the cleavage site (b) contain neither the cloning site nor at least two frequently-occurring cleavage sites.

Abstract: Methods of performing fast polymerase mediated reactions are provided. These reactions can be used in an inefficient fashion in the cycles of the polymerase mediated reactions to produce product at a much faster rate than conventional polymerase mediated reaction methods. Integrated systems for performing these methods are also provided.

Abstract: Pharmaceutical compositions having a cholesterol-lowering effect which comprises as the active ingredient a compound having a PPAR (peroxisome proliferator-activated receptor)&dgr; activating effect or a PPAR&dgr;- and PPAR&ggr;-activating effect or a pharmaceutically acceptable salt thereof; pharmaceutical compositions wherein the cholesterol-lowering effect is an LDL-cholesterol-lowering effect; and a method for identifying a compound having a cholesterol-lowering effect characterized by measuring the PPAR&dgr;-activating effect or the PPAR&dgr;- and PPAR&ggr;-activating effect thereof. Means for Solution: It is found out that a compound exerting an excellent cholesterol-lowering effect on higher animals such as humans and ape has an effect of activating PPAR&dgr; or PPAR&dgr; and PPAR&ggr;.

Abstract: The present invention features inhibitors of target-independent amplification and the use of such inhibitors for enhancing an amplification protocol. The inhibitors are believed to enhance an amplification protocol by inhibiting the ability of one or more nucleic acid polymerases to use nucleic acid in a polymerase reaction in the absence of target nucleic acid.

Abstract: The present invention is directed to novel methodology whereby different populations of the tuberculosis bacterial pathogen, Mycobacterium tuberculosis, or related Mycobacteria, can be genetically classified in relation to other isolates. Sites in the genome of Mycobacterium, which define previously unrecognized points of variability, are disclosed. The existence of this variability is of use to the clinician in order to consistently determine the identity of isolates of Mycobacterium responsible for individual cases of disease or disease outbreaks, thus suggesting appropriate choices for treatment protocols.

Abstract: Processes are disclosed using the depolymerization of a nucleic acid hybrid to qualitatively and quantitatively analyze for the presence of predetermined nucleic acid target sequences using a multiplex assay format. Applications of those processes include the detection of single nucleotide polymorphisms, identification of single base changes, speciation, genotyping, medical marker diagnostics, and the like.

Abstract: A method for removing a target DNA fragment having a predetermined base-pair length from a mixture of DNA fragments comprises the following steps. A mixture of DNA fragments which may contain the target DNA fragments is applied to a separation column containing media having a nonpolar, nonporous surface, the mixture of DNA fragments being in a first solvent mixture containing a counterion and a DNA binding concentration of driving solvent in a cosolvent. The target DNA fragments are separated from the media by contacting it with a second solvent solution containing a counterion and a concentration of driving solvent in cosolvent which has been predetermined to remove DNA fragments having the target DNA fragment base pair length from the media. The target DNA fragments can be collected and optionally amplified. When the method is being applied to collect a putative fragment, if present, no DNA fragments having the base pair length of the target DNA could be present in the mixture.

Abstract: The present invention provides a method and a kit for the purpose of diagnosing a disease or determining the predisposition for a disease by measuring abnormalities in imprinting of a gene or population of genes. The disease that can be diagnosed by the present invention is selected from any disease that is mediated by, or is associated with, a particular gene or combination of genes that are subject to imprinting. According the present invention, the imprinting can be abnormally on or can be abnormally off. In those cases where the particular gene that is being examined is normally imprinted, but in the disease state is abnormally not imprinted, the present invention is designed to detect the “loss of imprinting” (hereinafter “LOI”) thereby indicating that the disease may be present.