Abstract: The invention provides new processes for preparing polyglutamic acid-therapeutic agent conjugates for clinical development and pharmaceutical use, and polyglutamic acid-therapeutic agent conjugates prepared by these processes.

Abstract: The invention provides polyglutamic acid-therapeutic agent conjugates and methods for their preparation and use.

Abstract: Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g.

Abstract: The invention provides polyglutamic acid-therapeutic agent conjugates and methods for their preparation and use.

Abstract: A method is provided for preparing a highly purified lysozyme dimer product which comprises dimerizing the lysozyme monomer with a suberimidate coupling reagent in a buffer solution adjusted to pH 10, stopping the dimerization at a given point by lowering the pH to 7 via addition of HCl or other suitable acid solution, and purifying the dimeric lysozyme by a series of elution steps carried out using ion exchange resin column chromatography. Monomeric lysozyme remaining undimerized by the initial dimerization step is recycled into the process in order to increase yield. The present system is advantageous in that large amounts of purified lysozyme dimer can be prepared efficiently and relatively inexpensively, and the lysozyme dimer so produced is useful in treating viral and/or bacterial diseases without causing the cytotoxic effects associated with the lysozyme monomer.

Abstract: In an arrangement for producing a vacuum in a motor vehicle system including an internal combustion engine with an air intake system, a vacuum-operated power brake system for braking the vehicle and a fuel vapor adsorption system for collecting fuel vapors, a vacuum pump is provided which has a suction side in communication selectively with the vacuum operated power brake system and the fuel vapor adsorption system and a discharge side in communication with the air intake system of the internal combustion engine.

Abstract: The ultrasound imaging system and method of the present invention defines the gray-scale value and other parameters for each of a plurality of image elements in an output volume by determining all of the image information in the scanning planes that is contained within a defined portion of the output volume (which contains the image element) and thereafter simultaneously analyzing the selected image information. These steps are repeated for each of the image elements in the output volume.

Abstract: The present invention relates to a positively charged virosome for efficient delivery of genetic material to resting or proliferating mammalian cells in vitro and in vivo. The virosome membrane contains cationic and/or polycationic lipids, at least one viral fusion peptide and preferably at least one cell-specific marker, advantageously selected from the group consisting of monoclonal antibodies, antibody fragments F(ab′)2 and Fab′, cytokines, and growth factors, for a selective detection and binding of target cells. The invention further relates to a method for the manufacture of the novel virosomes and to applications thereof, particularly for the manufacture of pharmaceutical compositions to treat cancer or leukemia.

Abstract: A system and method for compiling source code comprising natural language declarations, natural language method calls, and natural language control structures into computer-executable object code is disclosed. The system and method allow the compilation of source code containing both natural language and computer language into computer-executable object code. The system and method use a component database, containing components and associated natural language instructions, to select one or more components having an instruction declaration associated with the natural language instruction. A solution manager is used to resolve ambiguities inherent in the use of natural language instructions in the source code.

Abstract: Disclosed are therapeutic compounds having the formula:(R)j-(core moiety),including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.

Abstract: Disclosed are enantiomers diastereomers, salts, solvates, hydrates and mixtures thereof, of formula I: ##STR1## The core moiety is non-cyclic or at least one five- to seven-membered ring, n is an integer from about 4 to about 16, R.sub.1 and R.sub.2 are hydrogen, halogen or C.sub.1-12 alkyl or alkenyl, and (CH.sub.2).sub.n may be substituted by a hydroxyl, halogen, oxygen, a (C.sub.1-4) alkyl group or a dimethylamino group. The compounds and pharmaceutical composition thereof are useful in methods for treating an individual having a disease or treatment-induced toxicity, mediated by second messenger activity.

Abstract: Compounds and pharmaceutical compositions, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, have the formula:CORE MOIETY--(R).sub.jIn these compounds, j is an integer from one to three; the core moiety is a cyclic core, the cyclic core being non-cyclic or at least one five- to seven-member non-heterocyclic ring or heterocycle; and R is selected from the group consisting of amine, hydrogen, halogen, hydroxyl, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic group or formula I. At least one R having formula I: ##STR1## In formula I, n is an integer from four to twenty; and each R.sub.1 or R.sub.2 is independently hydrogen, substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or cyclic or heterocyclic group.

Abstract: Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:CORE MOIETY --(R).sub.jwherein j is an integer from one to three. The core moiety is non-cyclic or cyclic (carbocyclic or heterocyclic). R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, carbocyclic or heterocyclic groups and at least one R has the formula I: ##STR1## wherein: one or two p are the integer one, otherwise p is two; and n is an integer from three to twenty; R.sub.1 is selected from the group consisting of substituted and unsubstituted CH.sub.2 ; NR.sub.3, R.sub.3 being hydrogen, substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or C.sub.(1-20) hydroxyalkyl, or carbocyclic or heterocyclic group; O; --CHR.sub.4 O--, R.sub.4 being substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl, C.sub.(1-20) hydroxyalkyl, or R.sub.

Abstract: A new class of xanthine compounds, variously substituted at the 1, 3, 7 and 8 positions, is characterized by an ability to modulate the activity of key enzymes involved in drug metabolism. These compounds generally are useful in affecting drug metabolism and, particularly, in extending the circulating half-life of compounds that are metabolized via P-450-mediated pathways.

Abstract: A pulley which can be driven by the output element of the engine in a motor vehicle to transmit torque to one or more endless belts or chains has a rotary input member, a rotary output member and a damper which yieldably opposes rotation of the input and output members relative to each other about a common axis and is at least partially confined in an annular chamber defined by at least one of the input and output members. The chamber can further receive a friction bearing which operates between the input and output members, as well as a vibration absorbing device. Such device can have a mass which is adjacent a flange of one of the input and output members and one or more energy storing elements acting in the circumferential direction of the pulley.

Abstract: Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:CORE MOIETY --(R).sub.jwherein j is an integer from one to three. The core moiety is non-cyclic or cyclic (carbocyclic or heterocyclic). R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C(.sub.1-10) alkyl, C(.sub.2-10) alkenyl, carbocyclic or heterocyclic groups and at least one R has the formula I: ##STR1## wherein: one or two p are the integer one, otherwise p is two; and n is an integer from three to twenty; R.sub.1 is selected from the group consisting of substituted and unsubstituted CH.sub.2 ; NR.sub.3, R.sub.3 being hydrogen, substituted or unsubstituted C(.sub.1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or C.sub.(1-20) hydroxyalkyl, or carbocyclic or heterocyclic group; O; --CHR.sub.4 O--, R.sub.4 being substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl, C.sub.(1-20) hydroxyalkyl, or R.sub.

Abstract: The phospholipid bilayer contains at least one pharmaceutically active drug and comprises cell-specific markers on the membrane which have at least 90% biological activity when measured according to Luescher & Glueck, Antiviral Research 14, 39-50. In the membrane, the cholesterol content is preferably less than 2% by weight, the detergent content preferably less than 1 ppb. The vesicle diameter preferably is about 80 nm. the phospholipid in the membrane may comprise 70 to 95% by weight of phosphatidylcholine and preferably 10 to 20% by weight of phosphatidylethanolamine; preferably 6-8% by weight of a crosslinker, preferably of a sulfosuccinimidyl derivate, and at least one cell-specific fusion peptide are linked to the membrane. The vesicles are used for the preparation of pharmaceuticals against AIDS and carcinomas.

Abstract: Therapeutic compounds, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, having a formula: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, halo, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic groups, wherein the substituents of substituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl are other than halo; n is an integer from one to sixteen; R.sub.1, R.sub.2, and R.sub.3 are independently selected from the group consisting of a halo; haloacetoxy; hydrogen; hydroxy; oxo; --N.dbd.C.dbd.S; --N.dbd.C.dbd.O; --0--C.tbd.N; --C.tbd.N; --N.dbd.N.dbd.N; and --C--(R.sub.5).sub.3, R.sub.5 being independently a halo or hydrogen, at least one R.sub.5 being halo, at least one of R.sub.1, R.sub.2, and R.sub.3 being halo, cyano, isocyano, isothiocyano, azide or haloacetoxy group; R.sub.4 is hydrogen, C.sub.(1-6) alkyl, C.sub.(1-6) alkenyl, cyclo C.sub.

Abstract: A method is provided for preparing a highly purified lysozyme dimer product which comprises dimerizing the lysozyme monomer with a suberimidate coupling reagent in a buffer solution adjusted to pH 10, stopping the dimerization at a given point by lowering the pH to 7 via addition of HCl or other suitable acid solution, and purifying the dimeric lysozyme by a series of elution steps carried out using ion exchange resin column chromatography. Monomeric lysozyme remaining undimerized by the initial dimerization step is recycled into the process in order to increase yield. The present system is advantageous in that large amounts of purified lysozyme dimer can be prepared efficiently and relatively inexpensively, and the lysozyme dimer so produced is useful in treating viral and/or bacterial diseases without causing the cytotoxic effects associated with the lysozyme monomer.

Abstract: Compounds and pharmaceutical compositions thereof comprise the formula:(R)j- (core moiety),including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, wherein J is an integer from one to three, the core moiety is non-cyclic or comprises at least one, five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, alkyl (C.sub.1-6) or alkenyl (C.sub.1-6), and at least one R has the formula I: ##STR1## wherein n is an integer from four to eighteen; each R'.sub.1 and R'.sub.2 is independently hydrogen, alkyl (C.sub.1-4) or alkenyl (C.sub.1-4), the alkyl or alkenyl groups being preferably substituted by a halogen, hydroxyl, ketone or dimethylamino group and/or may be interrupted by an oxygen or hydrogen atom or an alkyl (C.sub.1-4) group; and each R'.sub.3 and R'.sub.4 is independently hydrogen or methyl. Preferably, n is an integer from six to ten, R'.sub.1 and R'.sub.