Abstract: The present invention is directed to a cryoprotective system that comprises an aqueous solution containing polymeric nano- and micro-particles that exhibit a reversible temperature-dependent volume change. It is also directed to a method for providing cryoprotection to an organism or parts of an organism by pumping the cryoprotective system into the vasculature of the organism prior to exposing the organism to a lower, preferably below 0° C., temperature.

Abstract: The invention is generally related to methods of treating autoimmune diseases, including both antibody-mediated and cell-mediated disorders.

Abstract: The invention relates to methods and devices for detecting a cell-cell interaction between a first living cell and a second living cell. The method comprises (a) providing a flow passage defined at least in part by a substrate having a first living cell, or tissue section containing living cells, immobilized on a surface thereof, (b) introducing a second living cell by controlled delivery of a carrier fluid containing the second living cell in contiguous laminar flow through the flow passage, thereby effecting contact or proximity between the first living cell and the second living cell, and (c) detecting a cell-cell interaction, if present, as a result of the contact or proximity between the first living cell and the second living cell. Devices for carrying out the method and for providing a cell-cell interaction are provided as well.

Abstract: Biochemical libraries are screened for transdominant intracellularly bioactive agents by expressing a molecular library of randomized nucleic acids as a plurality of corresponding expression products in a plurality of cells, each of the nucleic acids comprising a different nucleotide sequence, detecting a cell of the plurality of cells exhibiting a changed physiology in response to the presence in the cell of a transdominant expression product of the corresponding expressio products; and isolating the cell and/or transdominant expression product.

Abstract: Disclosed is a method for modulating an immune response by modulating signaling via PD-1. The immune response may be downregulated by increasing signaling via PD-1, or may be upregulated by decreasing signaling via PD-1. Agents which are useful for stimulating signaling via PD-1 to downregulate an immune response include an activating antibody that recognizes PD-1, a form of B7-4 that binds to an inhibitory receptor, and a small molecule that binds to PD-1. Agents which are useful for inhibiting signaling via PD-1 to upregulate an immune response include a blocking antibody that recognizes PD-1, a non-activating form of B7-4, an antibody that recognizes B7-4, and a soluble form of PD-1. Also disclosed is a method for modulating the interaction of B7-4 with an inhibitory receptor on an immune cell. The method comprises contacting an antigen presenting cell which expresses B7-4 with an agent such as a form of B7-4, a form of PD-1, or an agent that modulates the interaction of B7-4 and PD-1.

Abstract: An adsorbent for removing hepatitis C virus which has the ability to adsorb HCV particles, particularly immune-complex HCV particles, from a patient's body blood safely and with high efficiency and high selectivity for enhancing the efficacy of interferon therapy, an HCV adsorption apparatus including said adsorbent, and a adsorbing method for removing HCV are provided.

Abstract: This invention provides: agents determined to be capable of specifically inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell, but not a T cell-tropic isolate of HIV-1 to a CD4+ cell; and agents determined to be capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+ cell, but not a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell. This invention also provides: agents capable of specifically inhibiting the fusion of a macrophage tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1; and agents capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 with a CD4+ cell susceptible to infection by a T cell-tropic isolate of HIV-1. The agents include but are not limited to antibodies.

Abstract: The isolation and characterization of multiple viruses from a sample is provided.

Abstract: The present invention provides a method for identifying a binding molecule having selective affinity for a ligand. The method consists of selectively immobilizing a diverse population of binding molecules to a solid support, simultaneously contacting the diverse population immobilized on the solid support with two or more ligands and determining at least one binding molecule which selectively binds to one or more of the ligands. The invention additionally provides a method for identifying an antibody having selective affinity for a tumor antigen. The method consists of selectively immobilizing a diverse population of antibodies to a solid support, simultaneously contacting the diverse population immobilized on the solid support with two or more tumor antigens and determining at least one antibody which selectively binds to one or more of the tumor antigens. The invention also provides an isolated binding polypeptide selective for a tumor antigen.

Abstract: The invention provides chimeric flavivirus vectors including foreign peptides inserted into the envelope proteins of the vectors and methods of using these vectors.

Abstract: Multiple epitope fusion proteins and immunoassays using the same are disclosed. The multiple epitope fusion proteins are encompassed by the general structural formula (A)x-(B)y-Cz which represents a linear amino acid sequence, wherein B is an amino acid sequence of an epitope or cluster of epitopes and each B contains at least five and not more than 1,000 amino acids, y is an integer of 2 or more, A and C are each independently an amino acid sequence of an epitope or cluster of epitopes not adjacent to B in nature and x and z are each independently an integer of 0 or more wherein at least one of x and z is 1 or more.

Abstract: A technique is described for determining the effectiveness of medical therapy and dosage formulations by analyzing dot spectrograms representative of quantized hybridization activity in biological samples, such as DNA, RNA or other protein biomolecular array samples, taken at different sampling times from a patient undergoing the treatment. The technique directly lends itself to disease progression analysis based on markers such as viral load. In accordance with the technique, a viral diffusion curve associated with a therapy of interest is generated and each dot spectrogram is then mapped to the viral diffusion curve using fractal filtering to yield a filtered viral diffusion curve for each sample. A degree of convergence between the filtered viral diffusion curves is determined.

Abstract: The invention is directed to methods for identifying agents that affect mitochondrial functions and cell death. Such agents are useful for treating diseases associated with mitochondrial dysfunction and to methods of identifying a risk or presence of such diseases. In particular, the invention relates to the loss of mitochondrial membrane potential (&Dgr;&PSgr;m) during mitochondrial permeability transition (MPT) and further provides a measurable rate loss function, changes in which are useful, inter alia, for detecting agents that affect one or more mitochondrial functions, for detecting mitochondrial diseases and for studying molecular components of mitochondria that regulate MPT.

Abstract: Devices and methods for conducting binding reactions are described. The devices comprise first and second surfaces with channels extending between them. Specific binding reagents are immobilized in discrete groups of the channels. Sample passing through the channels reacts with the binding reagents. Binding of the sample component to the binding reagent in different groups of channels is detected providing information about sample composition. The devices provide increased surface area and accelerated reactions kinetics compared with flat surfaces.

Abstract: This invention concerns a reagent composition comprising at least two different terminators of a nucleic acid template-dependent, primer extension reaction. This invention also concerns a method for determining the identity of a nucleotide base at a specific position in a nucleic acid of interest. This invention further concerns a method for determining the presence or absence of a particular nucleotide sequence in a sample of nucleic acids. This invention further concerns a method for identifying different alleles in a sample containing nucleic acids. This invention further concerns a method for determining the genotype of an organism at one or more particular genetic loci.

Abstract: This invention concerns a reagent composition comprising at least two different terminators of a nucleic acid template-dependent, primer extension reaction. This invention also concerns a method for determining the identity of a nucleotide base at a specific position in a nucleic acid of interest. This invention further concerns a method for determining the presence or absence of a particular nucleotide sequence in a sample of nucleic acids. This invention further concerns a method for identifying different alleles in a sample containing nucleic acids. This invention further concerns a method for determining the genotype of an organism at one or more particular genetic loci.

Abstract: Methods are provided for selective nucleic acid sequence detection in primer extension reactions of high specificity. These methods are useful for detecting small amounts of mutant nucleic acid in a heterogeneous biological sample. These methods are particularly useful for identifying individuals with gene mutations indicative of early colorectal cancer.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: The present invention is based at least in part on the discovery of the genomic structure of the human SR-BI gene and on the identification of polymorphic regions within the gene. Accordingly, the invention provides nucleic acids having a nucleotide sequence of an allelic variant of an SR-BI gene and nucleic acids having an SR-BI intronic sequence. The invention also provides methods for identifying specific alleles of polymorphic regions of an SR-BI gene, methods for determining whether a subject has or is at risk of developing a disease which is associated with a specific allele of a polymorphic region of an SR-BI gene, and kits for performing such methods.

Abstract: This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes. The invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies.

Abstract: An iterative and regenerative method for sequencing DNA is described. This method sequences DNA in discrete intervals starting at one end of a double stranded DNA segment. This method overcomes problems inherent in other sequencing methods, including the need for gel resolution of DNA fragments and the generation of artifacts caused by single-stranded DNA secondary structures. A particular advantage of this invention is that it can create offset collections of DNA segments and sequence the segments in parallel to provide continuous sequence information over long intervals. This method is also suitable for automation and multiplex automation to sequence large sets of segments.

Abstract: A method for rapidly determining the species and/or strain of an organism by genotyping is presented. The method extends the use of indexing linkers to a method of genotyping. The genome of an unknown organism is digested by a restriction endonuclease which cleaves at a site different from the recognition site of the enzyme thereby producing DNA fragments and producing staggered ends. A subset of these fragments is ligated to linkers with staggered ends, with only those DNA fragments with staggered ends which are complementary to the staggered ends of the linkers being ligated to the linkers. DNA fragments with linkers at each end are then amplified. The number and sizes of amplified DNA fragments are then compared to a database containing the expected number and sizes of fragments from known organisms. A match between the assay data and the database is determinative of the species or strain of the unknown organism.

Abstract: The invention provides a method for reducing stutter in the amplification of a microsatellite comprising the steps of providing a sample comprising a microsatellite having a G+C content of 50% or less; contacting the sample with at least one enzyme having nucleic acid polymerase activity; and incubating the sample with the enzyme for a sufficient amount of time and under conditions sufficient to amplify the microsatellite; wherein the incubation is performed in the presence of an amount of betaine, sorbitol or mixtures thereof, effective to reduce stutter relative to the amount of stutter observed in the absence of betaine and/or sorbitol. The invention also provides compositions containing betaine and/or sorbitol, kits for amplifying microsatellites having a G+C content of 50% or less, and methods of using all of the foregoing.

Abstract: The present invention provides methods and compositions for interaction trap assays for detecting protein-protein, protein-DNA, or protein-RNA interactions. The methods and compositions of the invention may also be used to identify agents which may agonize or antagonize a protein-protein, protein-DNA, or protein-RNA interaction. In certain embodiments, the interaction trap system of the invention is useful for screening libraries with greater than 107 members. In other embodiments, the interaction trap system of the invention is used in conjunction with flow cytometry. The invention further provides a means for simultaneously screening a target protein or nucleic acid sequence for the ability to interact with two or more test proteins or nucleic acids.

Abstract: An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

Abstract: A rapid fluorescence polarization immunoassay (FPIA) for accurate quantification of any protein carrying an N-terminal polypeptide affinity tag especially a polyhistidine affinity tag (HisTag).

Abstract: A method of diagnosing exposure to a toxic agent comprising the steps of detecting the amount of protein/gene expression present in a sample of mammalian tissue or mammalian body fluids that has not been exposed to a toxic agent. Then the amount of protein/gene expression present in a sample of mammalian tissue or mammalian body fluids that has been exposed to the toxic agent is detected. A determination of the difference in the detected amount of protein/gene expression between the exposed and unexposed samples is made. A comparison of the difference to a library of expected protein/gene expression for predetermined toxic agents is made. Finally, an evaluation is made whether the difference indicates the exposure to a particular toxic agent. A treatment method for administering a therapeutic agent which inhibits the mechanistic pathways necessary to maintain the progression of lethal shock is also disclosed.

Abstract: The invention relates to adaptor molecules and kits and arrays comprising adaptor molecules. The invention also relates to methods of making and using adaptor molecules.

Abstract: The invention provides novel polynucleotides and polypeptides encoded by such polynucleotides and mutants or variants thereof that correspond to a novel human stem cell growth factor-like protein. These polynucleotides comprise nucleic acid sequences isolated from cDNA libraries from human testis cells (Hyseq clone identification numbers 2880984 and 2881695), from human fetal skin (Hyseq clone identification number 15375176), adult spleen (Hyseq clone identification number 14856094), and human endothelial cells (Hyseq clone identification numbers 13804756, 13687487, 13804756). Other aspects of the invention include vectors containing processes for producing novel human stem cell growth factor-like polypeptides, and antibodies specific for such polypeptides.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The present invention provides a novel method for ligation of oligonucleotides containing 5′-phosphorothioates on complementary templates by the action of DNA ligases. This reaction is readily applied to the synthesis of a single stranded circular DNA containing a phosphorothioate linkage at the site of ligation junction. The efficiency of 5′-phosphorothioate directed ligation reaction by ATP dependent DNA ligase reaction is similar to conventional 5′-phosphate ligation. The utility of enzymatic ligation in probing specific sequences of DNA is also described. The present invention also provides a novel non-enzymatic ligation of 5′-phosphorothioates that has been applied to the synthesis of single strand phosphorothioate and phosphate circular DNA.

Abstract: Assay methods are provided for detection or quantitation of any of several proteins which are specifically produced in the endometrium in association with hyperplasia, adenocarcinoma or the proliferative phase of the endometrium. The relevant proteins have been identified by 2D gel electrophoresis with subsequent sequence identification by mass spectroscopic finger printing of tryptic digests.

Abstract: The present invention relates to compositions and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for forming a nucleic acid cleavage structure on dendrimers and cleaving the nucleic acid cleavage structure in a site-specific manner. For example, in some embodiments, a 5′ nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

Abstract: The invention provides methods, PCR primers, sequence determination oligonucleotides, and kits for predicting a human's capacity to metabolize a substrate of the CYP2D6 enzyme using genetic analysis.

Abstract: Methods of producing ligand arrays, e.g., polypeptide and nucleic acid arrays, as well as the arrays produced thereby, methods for use of the arrays and kits that include the same, are provided. In the subject methods, a substrate having a surface displaying olefinic functional groups, e.g., olefin groups having a single site of unsaturation, are modified such that the olefinic functional groups are converted to ligand reactive functional groups. The resultant substrate is then contacted with ligands, e.g., via deposition of each different ligand onto a different region of the surface, resulting in covalent attachment of the contacted ligand to the surface via reaction with the ligand reactive functional groups. Ligand arrays produced via the subject methods demonstrate a number of desirable properties, e.g., nucleic acid arrays produced by the subject methods provide high signal intensity with low background in nucleic acid hybridization assays, etc.

Abstract: The present invention is directed to the production of a sample microarray for use in detecting one or more target biopolymers in the sample. The sample microarray of this invention is formed by distributing equivalent amounts of a single sample at discrete, spatially defined locations on a substrate. Each site in the microarray, thus, has the same composition of target biopolymers. The microarray is then interrogated by one or more probes specific for one or more the target biopolymers.

Abstract: Novel methods for drug discovery including identification of targets and identification of the functions of targets are disclosed. The methods provide for rapid identification and high throughput screening of targets for developing therapeutics to treat disease conditions.

Abstract: A microarray containing microspheres is provided. A substrate defines an arrayed pattern of test sites, and one or more microspheres are retained in proximity to each test site by an attachment point disposed on the test site. Each microsphere retained at a particular test site has a common ligand on its surface, which binds a particular analyte. Preferably, different ligands are used at each of the test sites, allowing for the detection of multiple analytes. A method of fabricating a microarray according to the present invention is also provided.

Abstract: An in-vivo cellular logic device includes a substrate and a structure for providing a stimulus to a plurality of discrete portions of the substrate. At least one whole cell is disposed on the substrate, the cell having at least one transcriptional unit, the transcriptional unit comprising a gene and a promoter. Upon application of a stimulus to the promoter, a gene product is expressed. A detector is provided to detect the presence of the gene product, the gene product preferably conferring a bioluminescent output. The cell can be genetically engineered. A method for processing data includes the steps of providing at least one genetically engineered cell, the genetically engineered cell having at least one transcriptional unit. The transcriptional unit includes a gene and a promoter, wherein application of a stimulus to the promoter results in the expression of a gene product.

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

Abstract: A method is provided for classifying or typing a prokaryote to a class or a type. The method is effected by characterizing at least one polymorphic simple sequence repeat locus in a genome of the prokaryote and, based on a characterization of the polymorphic simple sequence repeat, classifying or typing the prokaryote to a class or a type. Compounds and articles of manufacture are provided for effecting the method.

Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: A plasmid has been isolated from Rhodococcus erythropolis strain AN12 comprising a unique replication protein. The replication protein may be used in a variety of cloning and expression vectors and particularly in shuttle vectors for the expression of heterologous genes in Rhodococcus sp.

Abstract: The present invention discloses a process using one, not two, labels to perform parallel analysis of multiple samples for their differential gene expression profiles. This process is achieved by using a platform technology, which integrates current DNA micro array and current high throughput screening technology. The invention defines a process that may use a single label to carry out parallel comparison of multiple gene expression samples. The process takes advantage of high density DNA micro array technology and high throughput automation equipment to perform high throughput gene expression analysis, but uses only a single label. Such labeling and analysis reduces variations found in dual fluorescent dye labeling and converts the current manual sample handling to automated sample processing. Thus, the invention enables the transformation of the current DNA micro array technology into a high throughput screening tool.

Abstract: A method of identifying transcription factors comprising providing cells with a nucleic acid sequence at least comprising a sequence CACCT (SEQ ID NO: ______ ) as bait for the screening of a library encoding potential transcription factors and performing a specificity test to isolate said factors. Preferably, the bait comprises twice the CACCT (SEQ ID NO: ______ ) sequence, more particularly the bait comprises one of the sequences CACCT-N-CACCT(SEQ ID NO: ______ ), CACCT-N-AGGTG(SEQ ID NO: ______ ), AGGTG-N-CACCT(SEQ ID NO: ______ ), or AGGTG-N-AGGTG (SEQ ID NO: ______ ) wherein N is a spacer sequence. The transcription factors identified using the methods of the invention include separated clusters of zinc fingers, such as, for example, a two-handed zinc finger transcription factor. Also, at least one such zinc finger transcription factor, denominated as SIP1, induces tumor metastasis by down regulation of the expression of E-cadherin.

Abstract: The present invention relates to technologies for assessing a subject's susceptibility to development of a cardiovascular disorder. The invention further relates to methods for selecting therapeutics which will be optimally effective for treating patients suffering from a cardiovascular disorder. The invention also includes methods, compositions and kits useful for determining a patients cholesteryl ester transfer protein (CETP) genotype.

Abstract: Nucleic acid sequences that identify a gene product associated with Glioblastoma Multiforme are disclosed. Nucleic acid probes for mRNA transcripts whose expression is associated with glioblast transformation and methods for using these probes in identifying patients at risk for progression into a malignant phenotype are also disclosed.

Abstract: The invention provides compositions and novel cDNAs that co-express with cell differentiation gene transcripts induced by retinoic acid. The invention also provides expression vectors, host cells, proteins encoded by the cDNAs and antibodies which specifically bind the proteins. The invention also provides methods for the diagnosis, prognosis and treatment of and disorders associated with cell and tissue development and differentiation.

Abstract: Cancer-testis (CT) antigens have been identified by screening public databases for transcripts that are expressed in tumor tissues and a limited set of normal tissues, or by screening for genes that are expressed in cancer and testis tissues (but not other normal tissues). The invention relates to nucleic acids and encoded polypeptides which are CT antigens expressed in patients afflicted with cancer. The invention provides, inter alia, isolated nucleic acid molecules, expression vectors containing those molecules and host cells transfected with those molecules. The invention also provides isolated proteins and peptides, antibodies to those proteins and peptides and cytotoxic T lymphocytes which recognize the proteins and peptides. Fragments of the foregoing including functional fragments and variants also are provided. Kits containing the foregoing molecules additionally are provided.