Abstract: This invention pertains to agonists that activate nuclear receptors. These agonists include an extension that contacts a region of the nuclear receptor outside the native ligand binding pocket. Methods for producing, identifying and designing such agonists are included along with nuclear receptor agonist complexes and libraries of agonists.

Abstract: This invention pertains to the discovery that nerve growth factor (NGF) is capable of preventing further demyelination of nervous tissue in pathologies characterized by the demyelination of nervous tissue (e.g. multiple sclerosis). In one embodiment, this invention provides a method for inhibiting demyelination in a subject having an inflammatory disease of a nervous tissue. The method involves administering an effective amount of NGF, an NGF analogue, or an active fragment of NGF where the effective amount is sufficient to downregulate the production of interferon ? by T cells infiltrating the central nervous system and/or to upregulate IL-10 production by glial cells.

Abstract: This invention provides novel peptides for the treatment of atherosclerosis.

Abstract: This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. In certain embodiments, the peptide comprises an amino acid sequence that ranges in length from about 10 up to about 30 amino acids, that comprises at least one class A amphipathic helix, that bears at least one protecting group, that protects a phospholipid against oxidation by an oxidizing agent; and that is not the D-18A peptide. The peptides are highly stable and readily administered via an oral route.

Abstract: This invention provides nucleic acid sequences and characterization of the gene cluster responsible for the biosynthesis of the enediyne C-1027 (produced by Streptomyces globisporus). The pathway comprises a nonriobsomal peptide synthetase (NRPS). Methods are provided for the biosynthesis of enediynes, enediyne analogs and other biological molecules.

Abstract: Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread.

Abstract: A behavioral monitoring system useful for the analysis of complex behaviors in a number of animal species. The monitoring systems of this invention allow continuous monitoring of feeding, drinking and movement of animals with high temporal and spatial resolution. In certain embodiments, the system comprises an enclosure comprising: an animal position indicator; a food consumption indicator; and a fluid consumption indicator, where the system reports behavioral data at a temporal resolution of 20 seconds or lower.

Abstract: This invention provides a new design and fabrication for a three-dimensional crossbar architecture embedding a sub-micron or nanometer sized hole (called a molehole) in each cross-region. Each molehole is an electrochemical cell consisting of two or more sectional surfaces separated by a non-conductor (e.g. a dialectric layer and solid electrolyte). When used in electrochemical molecular memory device (EMMD), the architecture provides unique features such as a nano-scale electroactive surface, no interaction between memory elements, and easier miniaturization and integration.

Abstract: Oligonucleotide sequences encoding gp120 polypeptides from breakthrough isolates of vaccine trials using MN-rgp120 and the encoded gp120 polypeptides are provided. Use of the gp120 polypeptides from one or more of the isolates in a subunit vaccine, usually together with MN-rgp120, can provide protection against HIV strains that are sufficiently different from the vaccine strain (e.g.; MN-rgp120) that the vaccine does not confer protection against those strains. Antibodies induced by the polypeptides are also provided.

Abstract: This invention provides novel high density memory devices that are electrically addressable permitting effective reading and writing, that provide a high memory density (e.g., 1015 bits/cm3), that provide a high degree of fault tolerance, and that are amenable to efficient chemical synthesis and chip fabrication. The devices are intrinsically latchable, defect tolerant, and support destructive or non-destructive read cycles. In a preferred embodiment, the device comprises a fixed electrode electrically coupled to a storage medium having a multiplicity of different and distinguishable oxidation states wherein data is stored in said oxidation states by the addition or withdrawal of one or more electrons from said storage medium via the electrically coupled electrode.

Abstract: The present invention relates to cDNA sequences from a region of amplification on chromosome 20 associated with disease. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases. The sequences can also be used for treatment of diseases.

Abstract: A method of inactivating viruses comprises contacting the virus with a virucidally effective amount of a composition consisting essentially of a C1 to C3 monohydroxy alcohol or a C2 to C4 diol and a sufficient amount of an acid to adjust the pH of the composition to below 4.6. Topical administration of the composition is preferred and is effective in treating lesions associated infections by viruses such as herpes simplex. Nasal deliverable forms are effective in treating symptoms due to viruses that cause the common cold. Pharmaceutical compositions for use in the present method are provided.

Abstract: Disclosed are improved pharmaceutical formulations comprising dehydroepiandrosterone (DHEA), enriched in selected polymorphic forms, for therapeutic applications. In one embodiment, the formulation comprises, in solid form, DHEA, at least 85% of which is present as a single polymorph selected from the form I polymorph or the form II polymorph, and at least one pharmaceutical excipient. Methods for making and using such compositions are also disclosed.

Abstract: The invention provides antibodies specific for HIV env, including monoclonal antibodies and related hybridomas. The antibodies block CD4/g120 binding and reduce reverse transcriptase activity in vitro.

Abstract: This invention provides novel high density memory devices (FIG. 3) that are electrically addressable permitting effective reading and writing, that provide a high memory density (102), that provide a high degree of fault tolerance, and that are amenable to efficient chemical synthesis and chip fabrication. The devices arc intrinsically latchable, defect tolerant, and support destructive or non-destructive read cycles. In a preferred embodiment, the device comprises a fixed electrode electrically coupled to a storage medium having a multiplicity of different and distinguishable oxidation states wherein data is stored in said oxidation states by the addition or withdrawal of one or more electrons from said storage medium via the electrically coupled electrode.

Abstract: This invention identifies a novel family of bilin reductases. Designated herein HY bilin reductases, the enzymes of this invention are useful in a wide variety of contexts including but not limited to the conversion of biliverdins to phytobilins and the assembly of holophytochromes or phytofluors.

Abstract: The invention provides methods and devices for detecting the presence of one or more target analytes in a sample employing a channel having affixed therein one or more binding partners for each target analyte. Assays are carried out by transporting the sample through the channel to each successive binding partner so that target analyte present in said sample binds to the corresponding binding partner. The sample is then transported beyond the binding partner(s), followed by detection of any target analyte bound to each binding partner. In one embodiment, binding efficiency is increased by the use of segmented transport, wherein a first bolus or bubble of a fluid that is immiscible with the sample precedes the sample during transport and a second bolus or bubble of a fluid that is immiscible with the sample follows the sample. Many configurations are possible for the device of the invention.

Abstract: This invention provides detailed sequence analysis and characterization of the gene cluster responsible for the synthesis of bleomycin in Streptomyces verticillus. The bleomycin gene cluster provides the first hybrid polyketide synthase/nonribosomal peptide synthetase pathway and elucidation of the various modules and enzymatic domains characterizing the pathway provides convenient synthetic routes for bleomycins, bleomycin analogs, and various other polyketides.

Abstract: This invention provides approaches to improve the signal to noise ratio (S/N) in electrochemical measurements (e.g. amperometry, voltammetry, etc.). In particular, a method is described wherein the faradaic current is temporally dissociated from the charging current associated with reading the charge of a redox-active species (e.g. a self-assembled monolayer (SAM)). This method, designated herein as open circuit potential amperometry (OCPA), quantitatively reads the charge of the redox species bound to (electrically coupled to) an electrode surface, while discriminating against both charging current(s) and amperometric signal(s) that arise, e.g. from diffusion-based species in solution.

Abstract: The present invention provides for novel reagents whose fluorescence changes upon cleavage or a change in conformation of a backbone. The reagents comprise a backbone (e.g. nucleic acid, polypeptide, etc.) joining two fluorophores of the same species whereby the fluorophores form an H-dimer resulting in quenching of the fluorescence of the fluorophores. When the backbone is cleaved or changes conformation, the fluorophores are separated, no longer forming an H-type dimer, and are de-quenched thereby providing a detectable signal. The use of a single fluorophore rather than an “acceptor-donor” fluoresecence resonance energy transfer system offers synthesis and performance advantages.