Abstract: Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly (lactic acid) (PLA), poly (glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.

Abstract: The invention is directed to 1-methyl-benzo[1,2,4]thiadiazine 1-oxide derivatives and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

Abstract: This invention provides a method of modifying a cellular response in a mammal. The method comprises administering to the mammal an effective amount of biodegradable nanoparticles, each of said nanoparticles comprising an active agent, a biodegradable polymer, and a bone targeting agent administering to a mammal an effective amount of a composition comprising a compound absorbed in a biodegradable nanoparticle which is attached to a bone targeting agent. The invention also provides a method for modifying a cellular response in a mammalian cell comprising contacting the mammalian cell with biodegradable nanoparticles. The invention further provides a method of delivering an exogenous substance to a mammal. The method comprises administering to the mammal a composition comprising the exogenous substance absorbed into a biodegradable nanoparticle, wherein the biodegradable nanoparticle is covalently attached to a bone targeting agent.

Abstract: Methods for the formation of sulfurized oligonucleotides are provided. The methods allow for the formation of phosphorothioate linkages in the oligonucleotides or derivatives, without the need for complex solvent mixtures and repeated washing or solvent changes. Oligonucleotides having from about 8, and up to about 50, nucleotides can be sulfurized according to the methods of the invention with higher yields than have been previously reported.

Abstract: An improved liquid handling machine capable of regulating the temperature of assay compounds in the automated preparation of culture trays for biological assays is disclosed. The machine includes a horizontally movable table positioned beneath a vertically movable head. The table is divided into a plurality of stations holding mixing trays, culture trays and reservoirs of liquid assay compound. The head holds a plurality of pipettes which aspirate and expel liquid to transfer and mix the assay compounds between the reservoir, the mixing trays and the culture trays upon coordinated movement of the head and the table as controlled by a microprocessor. Each station on the table has independent heating, cooling and temperature sensing elements for regulating the temperature of the liquid held in a tray or reservoir at the station.

Abstract: The invention provides in vitro and cell-based assays for parkin activity, in which parkin-mediated ubiquitination of the S5a subunit of the 26S proteasome is measured, or ubiquitination of troponin 1. The assays may be used to screen for agents that modulate parkin protein ligase activity.

Abstract: This invention provides methods, novel formulations and kits to reduce the toxicity of anticancer drugs. Disclosed are therapeutics and treatment methods employing anticancer drags that exhibit a known toxicity, including, for example, adriamycin, campthothecin, and the like, chemically linked to a phosphonoformic acid partial ester resulting in a novel formulation that significantly decreases drug-related toxicity, enhances synergy with other chemotherapeutic drugs and provides increased efficacy against drug-resistant cancers.

Abstract: The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection.

Abstract: The present invention provides novel quinolinone derivatives which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder, and depression.

Abstract: Provided are methods for determining the activity of proteins that modulate the acetylation state of a protein substrate. The methods may be used for determining both acetyltransferase activity and deacetylase activity. The methods involve fluorescence polarization measurements for determining the acetylation state of a substrate peptide. The methods may also be used to identify compounds that modulate the activity of a protein having acetyltransferase or deacetylase activity. Also provided are substrates for acetyltransferase or deacetylase enzymes for use in association with a fluorescence polarization assay.

Abstract: A composition for transdermal administration resulting from an admixture includes: a therapeutically effective amount of a drug that includes a parent drug and a prodrug; and and a pharmaceutically acceptable carrier, wherein the parent drug and prodrug are individually present in an amount sufficient for a pharmacological effect. In a preferred embodiment, the admixture includes: a therapeutically effective amount of a pharmaceutically active agent that includes a corresponding steroid and a steroid derivative; and a carrier for the pharmaceutically active agent. The steroid and the corresponding steroid derivative are present in a weight ratio of 10:1 to 1:10 steroid: corresponding steroid derivative. In a preferred embodiment ratio is 6:1 to 1:6. In a preferred embodiment, the corresponding steroid derivative is a steroid ester. In another preferred embodiment, the carrier is a polymer that includes a pressure-sensitive adhesive.

Abstract: Disclosed is an active, isolated ?-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (APP and APPsw) are also disclosed. These compositions are useful for use in methods of selecting compounds that modulate ?-secretase. Inhibitors of ?-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract: Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where G, J, L, M, x, y, W, V, R2, R3, R4, R5, R6, R7, R8, R8a, R9, R9a, R10, R10a, R11 and R11a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

Abstract: The invention relates to a novel group of phenylpiperazines having interesting pharmacological properties such as a high affinity for the dopamine D2 receptor and/or the serotonin reuptake site, and the ability to treat conditions related to disturbances in the dopaminergic and/or the serotonergic systems such as anxiety disorders, depression, Parkinson's disease, and schizophrenia. The invention relates to a group of novel phenylpiperazine derivatives of the formula (I): wherein: X is a group of formula 1, 2, 3, 4, 5, 6, or 7 as defined in the text, m has the value 2 to 6; n has the value 0-2; R5 and R6 are independently H or alkyl (1-3C); or R5+R6 represent a group —(CH2)—p wherein p has the value 3-5, and R7 is alkyl (1-3C), alkoxy (1-3C), halogen or cyano; or R6+R7 (R7 at position 7 of the indole group) represent a group —(CH2)q wherein q has the value 2-4, and salts thereof.

Abstract: Compositions and methods for the inducible expression of genes in eukaryotic cells. Expression of a nucleotide sequence of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a legends-binding domain. When the cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale production of a desired product in eukaryotic cells.

Abstract: The present invention relates to methods of treating ischemia-related conditions by administering to a patient in need of such methods certain thiosemicarbazone compounds. Preferred embodiments of the present invention relates to methods of treating specific ischemia-related conditions, including but not limited to Alzheimer's disease, Parkinson's disease, Coronary artery bypass graft surgery, Global cerebral ischemia due to cardiac arrest, focal cerebral infarction, cerebral hemorrhage, hemorrhage infarction, hypertensive hemorrhage. hemorrhage due to rupture of intracranial vascular abnormalities, subarachnoid hemorrhage due to rupture of intracranial arterial aneurysms, hypertensive encephalopathy, carotid stenosis or occlusion leading to cerebral ischemia, cardiogenic thromboembolism, spinal stroke and spinal cord injury, diseases of cerebral blood vessels: e.g., atherosclerosis, vasculitis, Macular degeneration, myocardial infarction, cardiac ischemia and superaventicular tachyarrhytmia.

Abstract: The present invention relates generally to the field of anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. More particularly, the invention relates to a family of compounds having both a biaryl moiety and at least one heterocylic moiety that are useful as such agents.

Abstract: Novel hydroxamic acid containing amino acid derivatives are provided that are useful for treatment of inflammation, inflammatory and immunological diseases; lowering blood glucose, serum insulin, free fatty acids, cholesterol and triglyceride levels; and for treatment or prophylaxis of metabolic disorders.

Abstract: The present invention is macrocycles of the formula (X): for treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme for the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: The 3?-L-valine ester of ?-D-2?-C-methyl-ribofuranosyl cytidine provides superior results against flaviviruses and pestiviruses, including hepatitis C virus. Based on this discovery, compounds, compositions, methods and uses are provided for the treatment of flaviviridae, including HCV, that include the administration of an effective amount of val-mCyd or its salt, ester, prodrug or derivative, optionally in a pharmaceutically acceptable carrier. In an alternative embodiment, val-mCyd is used to treat any virus that replicates through an RNA-dependent RNA polymerase.