Abstract: The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of ?-secretase (BACE) polypeptide. Polypeptides used herein are derived from human BACE which is also known by the synonyms “mamapsin 2”, “human ?-site APP-cleaving enzyme, and Asp2”. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Abstract: Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

Abstract: A method of treating, preventing or ameliorating one or more symptoms associated with hepatitis C virus (HCV) in a patient in whom either the HCV is of Genotype 1 and/or the patient was previously treated with interferon and the previous interferon therapy was ineffective to treat the one or more symptoms associated with HCV, comprising administering to such a patient an effective amount of at least one compound of formulae I-XXVI of which the following structural formula is exemplary or a pharmaceutically acceptable salt, solvate or ester thereof. Optional combined administration of said at least one compound with an interferon or pegylated interferon and/or ribaviron is also contemplated.

Abstract: A heat tunnel for applying heated air to articles enclosed in shrink-wrap film includes at least one air supply unit; a conveyor; and a heat shroud spaced from the conveyor. Tha air supply unit includes a source of heated air, a fan, a heated air plenum, air ducts, and a return air plenum. Multiple air supply units can be provided along the conveyor to create a heat tunnel of desired length.

Abstract: A method of treating, preventing or ameliorating one or more symptoms of hepatitis C, or inhibiting cathepsin activity, in a subject is provided, in which at least one compound (e.g., a HCV protease inhibitor) is administered in one or more discrete dosages over a twenty-four hour time interval in an asymmetric pattern as to dosage amount and/or timing of dosage, wherein the at least one compound is selected from the group consisting of compounds of Formulae I-XXVI, described herein. Methods of modulating the activity of hepatitis C virus protease in a subject are also provided. Asymmetric dosing as to amount of dose and/or timing of dose permits adjustment of dosing to accommodate variations in drug metabolism and/or viral activity caused by viral cell division or a patient's circadian rhythms, thus delivering the maximum amount of dose at the time or times it is most effective.

Abstract: Methods are provided for using at least one novel hepatitis C (“HCV”) protease inhibitor in combination with at least one antiviral and/or immunomodulatory agent, which is different from the at least one HCV protease inhibitor, for treating a wide variety of diseases or disorders associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) and reducing HCV viral load in a subject in a reduced treatment period. With the present invention, a hepatitis C viral load is reduced in a subject to a concentration of less than 6×10?5 HCV virions per milliliter of plasma in a time period of less than or equal to about 24 weeks. With the present invention, a hepatitis C viral production is suppressed with an effectiveness in a range of 0.7 to 0.997.

Abstract: Controlled-release dosage formulations including at least one compound of Formulae I to XXVI herein and a controlled-release carrier and methods of treatment using the same are provided.

Abstract: Methods for preventing, ameliorating or treating one or more symptoms of Hepatitis C virus (HCV), modulating HCV protease activity and/or inhibiting cathepsin activity in a subject, wherein the methods comprise administering to a subject in need of such treatment a dosage formulation containing at least one compound of Formulae I-XXVI herein, wherein the dosage formulation is capable of maintaining an average Cmin plasma concentration of the compound at or above 10 ng/ml.

Abstract: The present invention provides methods of inhibiting cathepsin activity in a subject in need thereof comprising administering to said subject an effective amount of at least one compound of various formulae (e.g., formula I-XXVI) disclosed herein. The present invention also provides methods of treatment of various diseases utilizing the foregoing compounds.

Abstract: The present invention provides methods for treating infections, in a host, by viruses belonging to the Flaviviridae family, such as HCV, comprising administering an Ara-C homologue to the host.

Abstract: Disclosed are medicaments containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) a pharmaceutically active agent for simultaneous, sequential or separate administration in the treatment of a viral infection and/or other disease states and the symptoms associated therewith.

Abstract: The present invention is directed to certain diaryl amide compounds as NS3-Serine protease inhibitors of hepatitis C virus.

Abstract: An apparatus for perforating or slitting heat shrink film. The apparatus consists of a rotating perforating wheel having a number of sharpened teeth, with dull portions between the teeth. The apparatus may also include a slitter for slitting the film.

Abstract: A heat tunnel for applying heated air to articles enclosed in shrink-wrap film. The heat tunnel includes at least one air supply unit, the air supply unit further having a source of heated air, a fan, a heated air plenum, air ducts, and a return air plenum; a conveyor chain; and a heat shroud spaced from the conveyor chain. Multiple air supply units can be provided along the conveyor to create a heat tunnel of desired length.

Abstract: This invention provides a sensitive method for detecting RNA-dependent polymerase activity and for characterizing inhibitors of these enzymes, particularly NS5B of HCV and RT of HIV. The invention further provides methods wherein the elongation of RNA is measured in real time through the continuous detection of light generated from a reaction cascade involving a coupled enzyme system based on firefly luciferase.

Abstract: This invention relates to the treatment of viral infections in animals, particularly mammals. The treatment comprises the administration of a pharmaceutical composition comprising combinations of antiviral compounds useful for treating viral infections. The anti-viral compounds are combined in such a manner as to reduce the detrimental side effects of treatment and to enhance the efficacy. In a particular embodiment, the invention provides a method for treating a viral infection in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a combination of ribavirin in association with (S)-N-3-[3-(3-methoxy-4-oxazol-5-yl-phenyl)ureido]-benzylcarbamic acid tetrahydrofuran-3-yl-ester and pegylated interferon-alpha-2b.

Abstract: Covalent HCV NS4A-NS3 complexes comprising the central hydrophobic domain of native HCV NS4A peptide, a linker, and the HCV NS3 serine protease domain, wherein the hydrophobic domain of native HCV NS4A peptide is tethered by the linker to the amino terminus of the HCV NS3 protease domain.

Abstract: The invention relates to a leg assembly for an offshore structure, such as a self-elevating jack-up rig. The leg assembly has a pair of parallel leg chords divided into a plurality of sections by transverse bracing members. A unit of angular bracing members is secured within each such section. The unit has four angular members defining a rhombus, with each angular bracing member attached to a transverse bracing member and an adjacent leg chord. The braces are connected at four points to each other. The leg assembly is free from obstructing, drag-increasing auxiliary braces.

Abstract: The present invention is directed to certain diaryl amide compounds as NS3-Serine protease inhibitors of hepatitis C virus.

Abstract: The invention relates to a semi-submersible vessel designed to operate in harsh environment. The vessel has a twin-hull pontoon structure that supports four corner caissons extending vertically from the pontoons above an operational draft of the vessel. A pair of slender parallel horizontal braces connects each pair of opposing caissons, the braces extending in a general plane perpendicular to longitudinal axes of the pontoons. One of the pair of braces is secured between the forward columns and another of the pair of braces is secured between the aft columns. The braces reduce spreading and torque-induced forces acting on the columns, while not substantially increasing water plane area of the vessel. Each brace has an internal “redundancy” feature, being divided into two independent watertight compartments to continue providing buoyancy to the structure if one of the compartments is breached.