Abstract: The present invention provides a fast and efficient method for determining the three-dimensional conformation of a protein. The steps of the method of the invention include: 1) formation of physical distance constraints, e.g., forming intramolecular chemical crosslinks of known size between residues of a protein; 2) enriching the number of the molecules that have intramolecular chemical crosslinks in the reaction pool, e.g., using size separation to remove proteins with intermolecular bonds; 3) exposing the enriched reaction pool to a protease that cuts the protein at specific sites to produce peptide fragments; 4) measuring the size of the peptide fragments to determine linkage sites with a certain spatial relationship in the protein; and 5)interpreting the data produced to determine spatial geometry and protein structure based on the deduced spatial relationship of the linkage sites.

Abstract: Provided are peptidomimetic protein-binding arrays, their manufacture, use, and application. The protein-binding array elements of the invention include a peptidomimetic segment linked to a solid support via a stable anchor. The invention contemplates peptidomimetic array element library synthesis, distribution, and spotting of array elements onto solid planar substrates, labeling of complex protein mixtures, and the analysis of differential protein binding to the array. The invention also enables the enrichment or purification, and subsequent sequencing or structural analysis of proteins that are identified as differential by the array screen. Kits including proteomic microarrays in accordance with the present invention are also provided.

Abstract: Provided are protein microarrays, their manufacture, use, and application. Protein microarrays in accordance with the present invention are useful in a variety preoteomic analyses. Various protein arrays in accordance with the present invention may immobilize large arrays of proteins that may be useful for studying protein-protein interactions to improve understanding of disease processes, facilitating drug discovery, or for identifying potential antigens for vaccine development. The protein array elements of the invention are native or modified proteins (e.g., antibodies or fusion proteins). The protein array elements may be attached directly to a organic functionalized mirrored substrate by a binding reaction between functional groups on the substrate (e.g., amine) and protein (e.g., activated carboxylic acid). Techniques for chemical blocking of the arrays are also provided.

Abstract: Novel peptides that are capable of binding to uPAR and inhibiting the binding of an integrin and vitronectin are described. Also provided are nucleic acid sequences encoding the novel peptides. Methods for screening for small molecules, other peptides, or peptoids that mimic the antagonistic function of the peptides of the invention are described. The invention has applications in design of therapeutics for treating disorders characterized by upregulation of uPA and uPAR, and cancer and chronic inflammation, cell migration or uPAR: integrin binding interactions, and diagnostical applications to such disorders.

Abstract: The present invention relates to the use of fluorogenic or chromogenic dyes as reporter molecules for detecting cell entry by a specific molecule.

Abstract: Provided are affinity support materials having intermediate binding affinity for biological samples. Among the materials provided by the present invention are hydrophilic solid supports composed of hydrophilic ligands coupled to hydrophilic matrixes which are compatible with biological samples, for example, a cell line, a biological fluid such as blood, or a tissue cell lysate. The ligands may include affinity property groups and hydrophilic groups pendent from a backbone, and be configured to at least partially resolve components of a biological sample. Affinity supports in accordance with the present invention may be used in a variety of techniques and apparatuses to achieve improved separations of complex biological samples and thereby enhance the results of biological sample component fractionations, enrichments, purifications, expression product determinations and comparisons, and other biological sample processing techniques.

Abstract: Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Abstract: Provided are methods, apparatuses and systems for balancing the load of data transmissions through a port aggregation. The methods and apparatuses of the present invention allocate port assignments based on load, that is, the amount of data being forwarded through each port in the group. The load balancing of the present invention is preferably dynamic, that is, packets from a given stream may be forwarded on different ports depending upon each port's current utilization. When a new port is selected to transmit a particular packet stream, it is done so that the packets cannot be forwarded out of order. This is preferably accomplished by ensuring passage of a period of time sufficient to allow all packets of a given stream to be forwarded by a port before a different port is allocated to transmit packets of the same stream. The invention may be used in a variety of different network environments and speeds, including 10Base-T, 100Base-T, and Gigabit Ethernet, and other network environments.

Abstract: Methods and systems for verifying the volume of a reagent dispensed into an affinity assay vessel are described. In one embodiment, a method is for verifying the volume of a reagent dispensed into an affinity assay vessel described in which a fluid sample is deposited into a vessel that includes a reaction chamber and a volume determination reference point. The reaction chamber further includes a test strip. According to one embodiment, the dispensed fluid is agitated to promote contact between the fluid and a test strip disposed within the reaction chamber. The relative positions of the volume determination reference point and an edge of the meniscus of the dispensed fluid are then determined such that the meniscus of the dispensed fluid is not penetrated. The volume of the dispensed fluid is determined from these relative positions.

Abstract: Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.