Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: Provided are compounds capable of covalently binding to a protein tyrosine phosphatase (PTP). The compounds comprise Formula A: Also provided are compositions comprising one of the above compounds covalently bound to a member of the PTP superfamily, methods of labeling a PTP using the compounds, methods of isolating a PTP from a mixture of proteins using the compounds, methods of evaluating whether a substance is an inhibitor of a PTP using the compounds, methods of evaluating the specificity of an inhibitor of a PTP using the compounds, methods of identifying a PTP involved in a disease in a mammal using the compounds, and methods of diagnosing a disease in a mammal using the compounds.

Abstract: This invention provides methods of using Rhenium radioisotopes to detect and treat tumors that express a Na+/I? symporter. The invention also provides compositions and methods of making compositions comprising Rhenium radioisotopes for detection and treatment of tumors that express a Na+/I? symporter.

Abstract: Methods for reducing peripheral blood glucose levels, food intake, glucose production, gluconeogenesis, triglyceride levels, and low density lipoprotein (VLDL) levels in mammals are provided. Also provided are methods of increasing glucose production and food intake in mammals. Further provided are methods of treating a disorder selected from the group consisting of obesity, type 2 diabetes, type 1 diabetes, hyperglycemia, insulin resistance, glucose intolerance, leptin resistance, metabolic syndrome, heart failure, ischemia, coronary heart disease, familial lipoprotein lipase deficiency, hypopituitarism, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, atherosclerosis, hypercholesterolemia, hypertension, and any combination of the foregoing. The methods involve manipulations of amino acid presence or metabolism in the hypothalamus of the mammal.

Abstract: Methods of reducing food intake and glucose production in a mammal, or restoring hepatic autoregulation are provided. The methods involve increasing long-chain fatty acyl-Co-A (LC-CoA) levels in the hypothalamus, or stimulating efferent fibers in the hepatic branch of the vagus nerve. Also provided are methods of increasing food intake and glucose production in a mammal. The methods involve decreasing long-chain fatty acyl-Co-A (LC-CoA) levels in the hypothalamus of the mammal.

Abstract: Provided are RNA oligonucleotides having an aptamer flanked by two self-cleaving ribozymes. Vectors encoding the oligonucleotides, and cells transfected with these vectors are also provided. Additionally, methods of inhibiting replication of a virus in a cell, methods of treating an organism with an aptamer, methods of determining whether a test aptamer is effective in inhibiting the function of a target of the aptamer in a cell, and methods of expressing an RNA aptamer in a cell are provided.

Abstract: The present invention provides oxygenated hemoglobins in powdered form and methods of preparing a powdered form of a protein, such as hemoglobin, which comprise (a) mixing a solution of the protein with inulin, and optimally with a reducing sugar such as glucose or tagatose, and (b) drying the mixture. Also provided are blood substitutes formed from reconstituted powdered hemoglobins, and methods of treatment using the blood substitutes.

Abstract: Provided are compounds that bind to SH3 domains. Also provided are combinatorial libraries for discovering such compounds. Methods of identifying a compound that binds to an SH3 domain are also provided. Methods of inhibiting an activity of a protein comprising an SH3 domain are additionally provided. Additionally provided are methods of inhibiting the activity of a protein comprising an SH3 domain and methods of treating a mammal having a deleterious condition that is mediated by a protein comprising an SH3 domain. The use of a compound that binds to the SH3 domain of a protein kinase in the manufacture of a medicament for the treatment of a deleterious condition in a mammal that is dependent on a protein kinase for induction or severity are also provided.

Abstract: This invention provides methods for treating infections in a subject which comprise administering to the subject an amount of a radiolabeled antibody effective to treat the infection, wherein the antibody specifically binds to the agent causing the infection. The invention also provides compositions and methods of making compositions comprising radiolabeled antibodies for the treatment of infections.

Abstract: For the brain, a variety of automated non-iterative shimming methods using phase evolution derived B0 maps have been reported. These methods assume that there is only a single chemical species contributing to the image. Although true in the brain, lipid contributions from skin, bone marrow and structural fat, may approach or exceed the concentration of water in other organs. In these instances, standard B0 mapping methods cannot be used due to contributions arising from the lipids. To overcome these limitations the present invention discloses a multi-point B0 mapping method combined with Dixon imaging to provide fully automated shimming of the human calf.

Abstract: The invention provides methods and compositions tor treating and preventing a skin rash secondary to anti-epidermal growth factor receptor (BGKR) therapy, where the method comprises applying a vitamin K analog or a phosphatase inhibitor to the skin.

Abstract: The invention provides methods and compositions for treating and preventing a skin rash secondary to anti-epidermal growth factor receptor (EGFR) therapy, where the method comprises applying a vitamin K analog or a phosphatase inhibitor to the skin.

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5?-methylthioadenosine phosphorylases (MTAP), 5?-methylthioadenosine mucliosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Abstract: The present invention is directed to pegylated red blood cells comprising a polyethylene glycol (PEG) attached to a thiolated amino group on a membrane protein, and to compositions comprising the pegylated red blood cells. The invention also provides methods of preparing pegylated red blood cells comprising reacting red blood cells with a compound that produces a thiolated amino group on a red blood cell membrane protein, and reacting the thiolated red blood cell with a PEG. The invention further provides methods of treatment using pegylated red blood cells.

Abstract: The present invention provides a method for identifying a peptide which binds to an anti-double stranded DNA antibody. The present invention also provides a class of peptides identified by the method of the present invention which bind to anti-double stranded DNA antibodies and compositions containing these peptides. The present invention also provides methods for the diagnosis and treatment of systemic lupus erythematosus utilizing the peptides of the present invention.

Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: The invention provides methods of regulating smooth muscle tone in a subject, comprising the introduction, into smooth muscle cells of the subject, of a DNA sequence encoding a potassium channel protein involved in the regulation of smooth muscle tone, and expression of the DNA sequence in a sufficient number of smooth muscle cells of the subject to regulate smooth muscle tone in the subject. The invention provides methods of gene transfer for treating erectile dysfunction, bladder dysfunction, and other smooth muscle disorders.

Abstract: The present invention provides a hemoglobin molecule (Hb) having six ± one PEG chains, wherein two of said PEG chains are bound to Cys-93 (?) of Hb, and the remaining PEG chains are bound to thiol groups introduced on ?-NH2 of Hb. The present invention also provides a process for preparing a modified hemoglobin molecule (Hb), comprising the steps of: (a) reacting Hb with 8-15 fold excess of iminothiolane to form thiolated Hb; and (b) reacting the thiolated Hb with 16-30 fold excess of PEG functionalized with a maleimide moiety, to form the modified Hb.

Abstract: This invention provides methods of using of the sizes and levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles, the -641 allele of the promoter of the gene encoding apolipoprotein C-3 (APOC-3), the 405 allele of the gene encoding cholesteryl ester transfer protein (CETP), and plasma levels of insulin-like growth factor-1 (IGF-1), adiponectin, CETP and APOC-3, for determining and increasing an individual's likelihood of longevity and of retaining cognitive function during aging, and for determining and decreasing an individual's likelihood of developing a cardiovascular-, metabolic- or age-related disease.

Abstract: Methods for treating a demyelinating condition in a subject in need of treatment are provided. In some aspects the methods encompass administering to the subject an amount of a Ca2+-channel blocker effective to treat the demyelinating condition. In other aspects, the methods encompass administering to the subject an amount of a glutamate inhibitor effective to treat the demyelinating condition. In additional aspects, the methods encompass administering to the subject a Ca2+-channel blocker in combination with a glutamate inhibitor, in amounts effective to treat the demyelinating condition. In still other aspects, the methods encompass administering to the subject a Ca2+-channel blocker in combination with a hypertensive agent, in amounts effective to treat the demyelinating condition. Also provided are pharmaceutical compositions having a Ca2+-channel blocker, a glutamate inhibitor, and a pharmaceutically-acceptable carrier.