Abstract: A system includes a clip having a pair of clip arms, proximal ends of the clip arms received within a channel of a capsule to be moved between an open configuration and a closed configuration. A proximal end of the capsule including a plurality of connecting elements extending proximally therefrom. Each of the connecting elements including a hook along a proximal portion thereof. An applicator includes an elongated flexible member and a control member extending therethrough, the control member configured to be connected to the clip arms to move the clip assembly between the open and closed configurations, the elongated flexible member including a bushing including a first ramped portion and a necked portion extending proximally from the first ramped portion, a proximal end of the first ramped portion including a lip configured to engage the hook when the connecting elements are crimped thereover.

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3?-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5?-terminal, a 3?-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5?-terminal, a 3?-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.

Abstract: The invention features a hybridized polynucleotide construct including a passenger strand, a guide strand loadable into a RISC complex, and one or more auxiliary moieties. At least one of the auxiliary moieties is non-bioreversibly linked to an internucleoside phosphate or phosphorothioate in the passenger strand. The invention further features methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell. The methods typically involve contacting the cell with the hybridized polynucleotide construct.

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3?-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5?-terminal, a 3?-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5?-terminal, a 3?-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.

Abstract: Compounds of Formula I, wherein R1—R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are also described.

Abstract: The present invention provides a 2-amino-5-cycloalkyl-hydantoin compound of formula I The present invention also provides methods and compositions for the inhibition of ?-secretase (BACE) and the treatment of ?-amyloid deposits and neurofibrillary tangles.

Abstract: The present invention provides an azolylacylquanidine compound of formula I The present invention also provides methods for the use thereof to inhibit ?-secretase (BACE) and treat ?-amyloid deposits and neurofibrillary tangles.

Abstract: A bracket is disclosed for use in open bottom type cabinets, such as file cabinets, which enables caster assemblies and the like to be secured thereto. The bracket is configured to be secured in the corners of an open bottom cabinet. In accordance with the present invention, the bracket provides stiffening of the cabinet as well as a secure surface for securing caster assemblies thereto. The brackets are simply mounted to the corners of the cabinet utilizing, for example, a pair of fasteners.

Abstract: Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof.

Abstract: A modulator has an FET output driver for applying repetitive pulses to an inductive load. A predriver comprises a resistor and capacitor in parallel across the FET source and gate for shaping the control voltage. A constant current source, turned on and off by an input signal, couples the shaping circuit to ground. The resistor and capacitor values determine the rate of control voltage change which is the same for turn-on and turn-off, to control the driver current slew rate for minimizing RFI emissions.