Abstract: The present invention provides nucleoside derivatives which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside derivatives of the present invention.

Abstract: The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Abstract: The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Abstract: A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3′-end of the oligo, i.e. 3′-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

Abstract: A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3'-end of the oligo, i.e. 3'-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

Abstract: The present invention provides rapid accurate sensitive assays specific for the detection of at least one a single stranded oligonucleotide produced by the action of an enzyme on a substrate. The assays are useful to detect the presence in a sample of an enzyme which acts on an oligonucleotide substrate to generate a single stranded oligonucleotide product and to detect inhibitors of such an enzyme.

Abstract: A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3'-end of the oligo, i.e. 3'-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

Abstract: The claimed invention is drawn to RNA molecules with catalytic activity comprising at least one modified nucleoside having a modifier group replacing the hydroxy group at the 2'-position of the ribose sugar where the modifier group is an halo, amino, mono- or disubstituted amino, or an azido group, and methods of use in vivo.

Abstract: The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2'-position of the fibose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino, and disubstituted andno groups, a process for the preparation of modified KNA molecules and the use of modified KNA molecules as therapeutic agents and biocatalysts.

Abstract: The claimed invention is drawn to RNA molecules with catalytic activity comprising at least one modified nucleoside having a modifier group replacing the hydroxy group at the 2'-position of the ribose sugar where the modifier group is an halo, amino, mono- or disubstituted amino, or an azido group.

Abstract: An assay for the influenza virus endonuclease has been developed which involves DNA polymerase-catalyzed extension of the viral endonuclease cleavage product using labeled nucleotides and a DNA template containing a 3' region complementary to the product joined to a 5' region consisting of repeated residues. The DNA polymerase coupled assay does not involve gel electrophoretic separation and is amenable to high volume screening of potential inhibitors. Another key feature of the assay is that it is sensitive enough to detect 200 attomoles of product.

Abstract: A sheet bending brake comprises a frame having a fixed jaw and a movable jaw. The fixed jaw defines a clamping surface and the movable jaw has a clamping surface movable between workpiece clamping and non-clamping positions relative to the clamping surface on the fixed jaw. A bending member is hingedly connected to the fixed jaw. A handle is pivoted to the frame. A plurality of axially extensible links are provided. Each link is pivoted at one end to the handle and at the other end to the movable jaw such that in one position of the handle, the links move the movable jaw out of clamping position, and in another position of the handle, the movable jaw is in clamping position. Each link includes an upper block connected to the frame, a shaft extending from the upper block and rotatable therein and threaded into a lower block pivoted to the movable jaw. The shaft has a socket connection in the upper end thereof accessible through an opening in the upper block.

Abstract: An engine cooling system including a filter connected in a radiator overflow system so that engine coolant flowing from the radiator to an overflow reservoir under the influence of pressure in the radiator will flow through the filter, whereas fluid flowing from the overflow reservoir to the radiator under the influence of atmospheric pressure when the pressure in the radiator drops will draw filtered engine coolant from the reservoir.

Abstract: A shingle ridge cap cutter utilized for cutting uniform sections from roof shingles comprising a frame along which a shingle is guided to a manually operated cutter that comprises spaced blades that are moved to sever a section of the shingle. The cutter blades are provided in spaced-apart, non parallel relationship so that a combined rectangular and trapezoidal-shaped ridge cap is made by single movement of the cutter with the roof shingle positioned so that the cutter blades are aligned with the slots along one edge of the shingle. Provision is made for operation to prevent injury to the hands of the worker.

Abstract: An engine cooling system including a filter connected in a radiator overflow system so that fluid flowing from the radiator to an overflow reservoir under the influence of pressure in the radiator will flow around the filter, whereas fluid flowing from the overflow reservoir to the radiator under the influence of atmospheric pressure when the pressure in the radiator drops will pass slowly through the filter.

Abstract: A hydrophilic-surfaced metallic foil capable of providing a lithographic printing plate upon imaging by the silver salt diffusion transfer process, the foil being treated with an aqueous solution of a water soluble Group IV-B hexavalent metal fluoride compound prior to imaging, and the lithographic plate so produced.