Abstract: The invention provides a compound of compound of formula (I): or a salt thereof, wherein R1, n, L, and X have any of the values described herein, as well as compositions and lipid nanoparticles comprising a compound of formula I, and their use for delivering therapeutic agents such as siRNA and mRNA.

Abstract: A surgical instrument, has an end effector that includes an ultrasonic blade, and a clamp arm that moves relative to the ultrasonic blade from an opened position toward an intermediate position and a closed position. The clamp arm is offset from the ultrasonic blade to define a predetermined gap in the intermediate position between the opened position and the closed position. A clamp arm actuator connects to the clamp arm and moves from an opened configuration to a closed configuration to direct the clamp arm from the opened position toward the intermediate position and the closed position. A spacer connects with the clamp arm to inhibit movement of the clamp arm from the intermediate position toward the closed position for maintaining the predetermined gap between the clamp arm and the ultrasonic blade.

Abstract: The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: Certain embodiments of the invention provide lipids useful for preparing lipid nanoparticles for delivering therapeutic agents to, e.g., hepatic stellate cells.

Abstract: Certain embodiments of the invention provide lipids useful for preparing lipid nanoparticles for delivering therapeutic agents to, e.g., hepatic stellate cells.

Abstract: The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: Provided herein are certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to treat certain diseases, such as liver fibrosis, e.g., in the setting of NASH or ASH.

Abstract: Provided herein are certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. He conjugates are useful to treat certain diseases, such as acromegaly.

Abstract: The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: Certain embodiments of the invention provide a cationic lipid of formula (I): wherein R1, R2, R3 and R4 are defined as described herein, as well as methods of making these lipids. Certain embodiments of the invention also provide nucleic acid-lipid particles comprising a cationic lipid of formula (I), methods of making the lipid particles, and methods of delivering and/or administering the lipid particles.

Abstract: The invention provides conjugates that comprise a bivalent targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates, compositions comprising the bidentate targeting ligands and the conjugates, as well as methods for targeting therapeutic nucleic acids with the bidentate conjugates. The conjugates are useful to target therapeutic nucleic acids.

Abstract: The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.

Abstract: The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: A surfactant component and a composition comprising the same are provided. The surfactant component comprises a first surfactant, a second surfactant, and water. The first surfactant comprises an alcohol alkoxylate having a high degree of alkoxylation of greater than 30 to 150. The first surfactant is present in an amount of from 1% to 50% by weight based on the total weight of the surfactant component. The second surfactant is present in an amount of at least 5% by weight based on the total weight of the surfactant component. Water is present in an amount of from 20% to 90% by weight based on the total weight of the surfactant component. The second surfactant enables higher concentrations of the first surfactant in water to be achieved without gelling than what has been accomplished to date.

Abstract: A surfactant component and a composition comprising the same are provided. The surfactant component comprises a first surfactant, a second surfactant, and water. The first surfactant comprises an alcohol alkoxylate having a high degree of alkoxylation of greater than 30 to 150. The first surfactant is present in an amount of from 1% to 50% by weight based on the total weight of the surfactant component. The second surfactant is present in an amount of at least 5% by weight based on the total weight of the surfactant component. Water is present in an amount of from 20% to 90% by weight based on the total weight of the surfactant component. The second surfactant enables higher concentrations of the first surfactant in water to be achieved without gelling than what has been accomplished to date.

Abstract: A cleaning composition comprises a first surfactant and a second surfactant. The first surfactant is of the general formula R1—O-(A)mH, wherein R1 is an aliphatic hydrocarbon having from 10 to 16 carbon atoms, A is an alkyleneoxy group, and subscript m is a positive number. The second surfactant is of the general formula R2—O—(B)nH, wherein R2 is an aliphatic hydrocarbon having from 12 to 15 carbon atoms, B is an alkyleneoxy group, and subscript n is a positive number. The cleaning composition has an average degree of alkoxylation of from about 3 to about 8 moles and an excess of the first surfactant relative to said second surfactant. The cleaning composition can further comprise a third surfactant in addition to the first and second surfactants. If employed, the third surfactant typically can comprise a linear alkyl sulfonate (LAS) and/or an alkyl ether sulfate (AES).

Abstract: A cleaning composition comprises a first surfactant and a second surfactant. The first surfactant is of the general formula R1-O-(A)mH, wherein R1 is an aliphatic hydrocarbon having from 10 to 16 carbon atoms, A is an alkyleneoxy group, and subscript m is a positive number. The second surfactant is of the general formula R2 -O-(B)nH, wherein R2 is an aliphatic hydrocarbon having from 12 to 15 carbon atoms, B is an alkyleneoxy group, and subscript n is a positive number. The cleaning composition has an average degree of alkoxylation of from about 3 to about 8 moles and an excess of the first surfactant relative to said second surfactant. The cleaning composition can further comprise a third surfactant in addition to the first and second surfactants. If employed, the third surfactant typically can comprise a linear alkyl sulfonate (LAS) and/or an alkyl ether sulfate (AES).

Abstract: Hard surface cleaning formulations include an associative thickener and a blend of at least two nonionic surfactants selected from the group consisting of ethoxylated alcohols and ethoxylated fatty acids. The formulations exhibit an advantageously high foam volume of at least about 150 cc when a 100 ml aqueous solution containing about 0.1 wt. % of the formulation is agitated at 2,500 rpm for a cumulative agitation period of about 1200 seconds. The formulations also exhibit satisfactory foam stability sufficient to clean at least about 25 plates (ASTM D4009-92). Preferably, the associative thickener is the reaction product of a C6 or greater epoxide compound with a polyoxyalkylene polyol. The ethoxylated alcohols and ethoxylated fatty acids each most preferably contain C8 to C18 carbon chains which are ethoxylated with between about 3 to about 20 moles of ethylene oxide.

Abstract: Cleaning formulations and methods are provided by which solid deposition is inhibited on hydrophobic hard surfaces typically encountered in bathroom and outdoor environments without detrimentally affecting the appearance of such surfaces. The formulations most preferably include an aqueous mixture of an organically solvated nonionic copolymer, a polyacrylic acid homopolymer and a nonionic surfactant. Optionally, a hydrotrope may also be present in the formulation. Most preferably, the formulations of this invention have a pH between about 4.0 to about 7.0, most preferably around neutral (i.e., about 7.0).