Abstract: This invention provides methods of inhibiting calcification of a soft tissue (e.g., an artery, a heart valve, an atherosclerotic plaque, a cancer, a kidney, a prostate, skin, muscle, cartilage, viscera, and heart muscle) in a mammal. These methods involve inhibiting osteoclastic bone resorption in said mammal (e.g., a mammal diagnosed as having or at risk for a pathology characterized by calcification of a soft tissue). The inhibition is preferably by administration of a bisphosphonate to the mammal in a concentration sufficient to inhibit bone resorption without inhibiting bone mineralization. The methods of this invention can also be used to mitigate a symptom of atherosclerosis in a mammal. Such methods involve inhibiting osteoclastic bone resorption in the mammal.

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: This invention provides methods of selecting antibodies that are internalized into target cells. The methods generally involve contacting target cells with one or more members of an antibody phage display library. The members of the phage display library are also contacted with cells of a subtractive cell line. The target cells are then washed to remove the subtractive cell line cells and members of the phage display library that are non-specifically bound or weakly bound to the target cells. The target cells are cultured under conditions where members of the phage display library can be internalized if bound to an internalizing marker and internalized members of the phage display library are then identified.

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. The storage medium typically comprises a storage molecule that is a triple-decker sandwich heterodimer. Such dimers can provide 8 or more oxidation states and permit the storage of at least 3 bits per molecule.

Abstract: This invention pertains to the discovery of a class of reagents that effectively form intramolecular disulfide bonds in peptides. Intermolecular disulfide linkage formation is low or essentially non-existent. In addition, preferred reagents of this invention are relatively mild and do not oxidize “vulnerable” residues in the subject peptide(s). In addition the reagents and reaction products are safe and essentially non-toxic. One particularly preferred reagent is [Pt(en)2Cl2]2+ where en is ethylenediamine.

Abstract: This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route.

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: This invention provides novel assays that are prognostic and/or diagnostic for atherosclerosis or risk of atherosclerosis. It was discovered that high density lipoprotein (HDL) or components thereof can prevent the oxidation of lipids (e.g. lipids present in LDLs) and can also repair (reduce) already oxidized lipids and thereby reduce the inflammatory response associated with and characteristic of atherosclerotic plaque formation. Moreover it was a discovery of this invention that individuals vary in the ability of their HDL to afford such protection. Thus an assay of HDL protective and/or repair activity provides a highly effective assay for risk of atherosclerosis and its associated pathologies and such assays are provided herein.

Abstract: This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column.

Abstract: The present invention involves the discovery that synthetic thyroid hormones can be used as compositions to reduce intraocular pressure in vivo. Methods of screening synthetic thyroid hormones for effect on intraocular pressure, aqueous pressure, hydraulic conductivity, hyaluronic acid secretion, and extracellular matrix assembly are provided. Methods of treating glaucoma and treating excess intraocular pressure with synthetic thyroid hormones and compositions therefore are also provided.

Abstract: This invention provides novel chimeric molecules that specifically binds a tumor cell bearing a c-erbB-2. The chimeric molecules comprise an effector molecule attached to a C6 antibody that specifically binds to c-erbB-2. The chimeric molecules can specifically target and deliver effector molecules to cells overexpressing c-erb-B2.

Abstract: This invention pertains to the discovery that L-arginine and type V phosphodiesterases act synergistically to inhibit vasospasm and/or to induce vasodilation. Methods are provided using combinations of L-arginine and type V phosphodiesterase inhibitors in the treatment of cardiac pathologies and/or the treatment of erectile dysfunction.

Abstract: This invention pertains to the discovery that inhibition of phosphatidylinositol 3-kinase (PI3K) in human fetal undifferentiated cells induces morphological and functional endocrine differentiation. This is associated with an increase in mRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion response to secretagogues. Blockade of PI3K also increases the proportion of pluripotent precursor cells coexpressing multiple hormones and the total number of terminally differentiated cells originating from these precursor cells.

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: A generic signaling assay method comprising an affinity matrix for the detection of low molecular weight compositions is provided. A test sample is mixed with a pre-determined amount of a substance conjugated to at least two molecules of the target analyte. When the test sample containing the multiple-analyte conjugated substance is passed over the immunoaffinity column, the antibodies can bind competitively to two species: free analyte and multiple-analyte conjugated substance. The column is then exposed to a second tagged antibody. Upon elution, high label activity is seen in a clean sample. Conversely, only a small amount of the label activity is detected in the eluant of a test sample that is highly contaminated with the free analyte.

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 comprising a storage molecule comprising a first subunit and a second subunit wherein the first and second subunits are tightly coupled such that oxidation of the first subunit alters the oxidation potential(s) of the second subunit rendering the oxidation potential(s) of the second unit different and distinguishable from the oxidation potentials of the first subunit.

Abstract: A flow-through microchannel (e.g. capillary) biosensor is described for the for the detection of multiple, different analytes (e.g. nucleic acids, proteins, sugars, etc.) targets in a sample by binding them to “complementary” binding partners (e.g. complementary nucleic acids, ligands, antibodies, etc.). The binding partners are immobilized in different sections of a microchannel (e.g. a fused silica capillary). After fabrication of the biosensor, a sample is flushed through the capillary, and any target analyte(s) contained within the sample are bound to the immobilized binding partner(s) on the microchannel wall forming bound complexes. Finally, the bound complexes are simultaneously denatured along the entire length of the capillary and flushed out past a detector poised downstream, and the analyte concentration is measured (e.g., using sinusoidal voltammetry).

Abstract: The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

Abstract: This invention provides a novel intracellular recycling free cholesterol pathway whose activity is required for cell division. The pathway provides the cholesterol needed for cell division prior to separation of daughter cells (mitosis). The new pathway offers several targets from pharmaceutical intervention, either via small molecules (such as sterol analogs) or by molecular engineering (preventing the cell from accumulating cholesterol by promoting free cholesterol efflux by transfection of caveolin cDNA).

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 comprising one or more thiol-derivatized porphyrins. The storage medium has a multiplicity of different and distinguishable oxidation states and data is stored in said oxidation states by the addition or withdrawal of one or more electrons from the storage medium via the electrically coupled electrode(s).