Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: Described herein are compounds and chemical entities of Formula (I), methods of their synthesis, compositions comprising them, and their use in treating numerous diseases and disorders, including cognitive deficits associated with CNS diseases and disorders.

Abstract: 4-(pentafluorosulfanyl)benzenediazonium tetrafluoroborate salt was synthesized and isolated. The pentafluorosulfanyl salt was examined in a wide assortment of reactions to form novel SF5-bearing alkenes, alkynes, and biaryl derivatives using Heck-Matsuda, Sonogashira, and Suzuki coupling protocols. Dediazoniation of the salt furnished the corresponding p-SF5—C6H4X, C6H4OS(O)(CF3)?NSO2CF3, and p-SF5—C6H4—NTf2 derivatives. The azide derivative p-SF5—C6H4N3 entered into click chemistry with phenylacetylenes to furnish the corresponding triazoles. Various SF5-bearing alkenes were synthesized by coupling reactions using a metal catalyst. Fluorodediazoniation selectively furnished the fluoro derivative p-SF5—C6H4F. Homolytic dediazoniation gave the unsymmetrical biaryls, thus demonstrating the broad utility of pentafluorosulfanyl diazonium salts as building blocks of SF5-aromatics that are in high demand in many branches of chemistry including biomedicine and materials chemistry.

Abstract: Disclosed is a method of treating cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound that inhibits a plurality of mammalian dipeptidyl peptidase (DPP) IV activity and/or structural homologues thereof (DASH) serine proteases. Also disclosed is a method of (a) increasing antitumor immunity, (b) stimulating or enhancing an immune response, (c) treating a condition characterized by abnormal cell proliferation, (d) increasing cytokine and/or chemokine production, or (e) stimulating or enhancing production of T-cells, in a mammal, comprising administering to a mammal in need thereof an effective amount of a compound that inhibits a plurality of mammalian DASH serine proteases. For example, the compound that inhibits a plurality of mammalian DASH serine proteases may be t-butylGly-boroPro.

Abstract: One of the purposes of the present invention is to provide a compound which is a polymerizable monomer having a specific number of silicon atoms and a specific number of fluorine atoms, has a higher purity, is suitable as an ophthalmic monomer, is well compatible with another (meth)acryl monomer, and provides a polymer having excellent hydrophilicity, anti-staining property and durability of mechanical strength and to provide a method for preparing the compound. The present invention provides a compound represented by the following formula (1). Further, the present invention provides a method for preparing the compound, a polymer having repeating units derived from the aforesaid compound and an ophthalmic device composed of the polymer.

Abstract: The purpose is to provide a silicone compound which is well compatible with polymerizable silicone monomers and other polymerizable monomers to provide a polymer having high oxygen permeability, excellent hydrophilicity and anti-staining property, excellent dimension stability, and enough durability of mechanical strength not to deteriorate in a phosphate buffer solution. The other purpose is to provide a silicone compound having a high blocked terminal ratio and a high ratio of one specific structure and a method for preparing the silicone compound. The invention provides a compound represented by the following formula (1). Further, the invention provides a method for preparing the compound, use of the compound as an ophthalmic monomer, a polymer having repeating units derived from the aforesaid compound and an ophthalmic device composed of the polymer.

Abstract: Oxasilacycles are prepared by the intramolecular condensation of silanes bearing Si-bonded hydrogen and ethylenically unsaturated radicals in the presence of a triorganoborane, aminoborane complex, or phosphine-borane complex as a hydrosilylation catalyst. Spirocyclic oxasilacycles, and alkoxy-substituted oxaspirocycles with quaternary substitution of a C atom adjacent to oxygen may be prepared.

Abstract: The present invention relates to a pharmaceutical dosage form which may comprise carbamoyl glycinated chitosan, and particularly it relates to a pharmaceutical dosage form comprising the novel polymer in a lyophilized polymeric wafer form which shows rapid disintegration and dissolution characteristics in use.

Abstract: Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, wherein at least one of R1-R3 is —CH2—O—N?CHR. The compounds are useful as intermediates in oligonucleotide synthesis. Also disclosed is a method of preparing the compounds from nucleosides via a process comprising conversion of a hydroxyl group to a methylthiomethoxy group, and a method of preparing oligonucleotides such as RNA starting from the compounds. The —CH2—O—N?CHR group is stable during oligonucleotide synthesis and can be easily removed after synthesis via, for example, treatment with a base.

Abstract: A nucleic acid synthesis method enabling a reaction in a fluid (flow) with a highly dispersible liquid-phase support to improve coupling efficiency is provided. The method for synthesizing an oligonucleotide comprising: sequentially condensing and oxidizing a nucleoside phosphoramidite compound in the presence of an acid/azole complex compound using a starting raw material, i.e.

Abstract: Compounds having the structure, their salts or N-oxide derivatives: are used to treat or reduce le likelihood of acquiring androgen-dependent diseases, such as prostate cancer, benign prostatic hyperplasia, polycystic ovarian syndrome, acne, hirsutism, seborrhea, androgenic alopecia and male baldness. They can be formulated together with pharmaceutically acceptable diluent or carrier or otherwise made into any pharmaceutical dosage form. Combinations with other active pharmaceutical agents are also disclosed.

Abstract: A chromatography column that captures components in a process liquid in a free flow state and allows elution in steps is described.

Abstract: The present invention relates to methods of depleting impurities, in particular host cell proteins (HCP) and DNA from cell culture supernatants by means of protein A chromatography using a novel washing buffer.

Abstract: Disclosed are a carrier for use for separation purpose and a method for separation of a compound which enable a chemical reaction to be performed in a liquid phase, enable a compound of interest to be separated from the liquid phase after the completion of the reaction readily, enable the separated compound to be evaluated by structural analysis or the like while the compound being bound to the carrier, and enable the compound to be separated from the carrier readily. A carrier for separation which has a reaction site capable of reacting with other compound on a benzene ring, and a long-chain group having a specified carbon atom(s) at each of the ortho-position and the para-position of the reaction site through an oxygen atom.

Abstract: The present invention provides peptides having an amino acid sequence as set forth in SEQ ID NO: 19, 22, 30, 34, 344, 358, 41, 44, 46, 48, 78, 376, 379, 80, 100, 101, 110, 111, 387, 112, 394, 114, 116, 117, 121, 395, 133, 135, 137, 426, 143, 147, 148, 149, 150, 152, 153, 154, 156, 160, 161, 162, 163, 166, 174, 178, 186, 194, 196, 202, 210, 213, 214, 217, 223, 227, 228, 233, 254, 271, 272 or 288, as well as peptides having the above-mentioned amino acid sequences in which 1, 2, or several (e.g., up to 5) amino acids are substituted, deleted, or added, provided the peptides possess cytotoxic T cell inducibility. The present invention also provides drugs for treating or preventing a disease associated with over-expression of the CDH3, EPHA4, ECT2, HIG2, INHBB, KIF20A, KNTC2, TTK and/or URLC10, e.g. cancers containing as an active ingredient one or more of these peptides. The peptides of the present invention find further utility as vaccines.

Abstract: A compound of Formula 1: (I) or salt thereof, as well as methods of making compounds of Formula 1, methods of using compounds of Formula 1 to treat proliferative disorders such as cancer, and related compounds, composition, and methods.

Abstract: Compositions comprising a protein or isolated peptide, and methods using the same for preventing, dispersing or detaching a biofilm, are disclosed.

Abstract: ?-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Cys4-Xaa5-Xaa6-Xaa7-Xaa8-Arg9-Tyr10-Cys11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa3, Xaa5, Xaa6, Xaa7, Xaa8, Xaa12, Xaa13, Xaa14, Xaa15 and Xaa16 being amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair.

Abstract: Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated NpHR-based molecule comprising a nucleic acid sequence that codes for light-activated NpHR-based molecule and a promoter. Either a high expression of the molecule manifests a toxicity level that is less than about 75%, or the light-activated NpHR-based proteins are expressed using at least two NpHR-based molecular variants. Each of the variants characterized in being useful for expressing a light-activated NpHR-based molecule that responds to light by producing an inhibitory current to dissuade depolarization of the neuron. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion pumps or for controlling inhibitory currents in a cell (e.g., in in vivo and in vitro environments).

Abstract: An object of the present invention is to provide novel polypeptides that are capable of binding to an immunoglobulin and have high stability against alkali. The present invention relates to proteins having the amino acid sequence of SEQ ID No:1 or 2.

Abstract: This invention provides vaccines comprising two or more recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of vaccinating a subject against HSV and treating, impeding, inhibiting, reducing the incidence of, or suppressing an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.

Abstract: Described herein is the identification and of a potent West Nile virus (WNV) CD4 positive T cell epitope and its use for increasing the immunogenicity of heterologous flavivirus vaccines, such as dengue virus type 2 (DENV-2) DNA and virus-like particle (VLP) vaccines. Also described are methods for the identification of potent T cell epitopes to enhance immunogenicity of multivalent vaccines.

Abstract: The invention in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the invention relates to gene transfer methods using the recombinant adeno-associate viruses. In some aspects, the invention relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Abstract: The present invention relates conotoxin peptides that are analogs of the ?-conotoxin peptide RgIA. These conotoxin peptides block the ?9?10 subtype of the nicotinic acetylcholine receptor (nAChR) and can be used for treating pain, such as neuropathic pain and inflammatory pain, inflammatory disorders, such as rheumatic diseases, and in the treatment of breast cancer.

Abstract: An object of the present invention is to efficiently extract proteoglycan from aquatic animal tissues. The method of the present invention is a method for extracting proteoglycan from fish cartilage, comprising the step of (A) heating small pieces of frozen fish cartilage in water. This method of the present invention enables easy extraction of proteoglycan from fish cartilage with very high efficiency. In particular, the method of the present invention enables extraction of high-molecular-weight proteoglycan. Further, since in the method of the present invention, extraction is performed using only water, it ensures safety in the extraction and safety of the resulting proteoglycan product, compared with hitherto known extraction methods using organic solvents or acids/alkali. Furthermore, the cumbersome step of removing organic solvents is not necessary in the method of the present invention.

Abstract: The invention relates to an isolated or recombinant protein from the shark Heterodontus francisci, which has bovine-erythrocyte-recognition activity and which can bind to sequences of antigens and/or proteins that are characteristic of infectious diseases. Once the aforementioned protein is bound to specific antigens of infectious diseases, it can haemagglutinate upon recognizing the bovine erythrocytes and antibodies characteristic of said diseases, which are present in the active state in biological samples such as whole blood, plasma or serum of bovine origin. The invention also relates to methods for protecting the detection of antibodies characteristic of infectious diseases, using the purified periplasmic extract or fusion protein, optionally purifying the recombinant protein.

Abstract: New designed repeat proteins with binding specificity for serum albumin are described, as well as nucleic acids encoding such serum albumin binding proteins, pharmaceutical compositions comprising such proteins, the use of such proteins to modify the pharmacokinetics of therapeutic relevant polypeptides and the use of such proteins in the treatment of diseases. The repeat proteins of the invention have a substantially increased half-life in plasma compared to proteins not binding serum albumin.

Abstract: Described are ?/?-peptide mimics of Z-domain scaffold peptides, methods of making them, and methods of using them. The ?/?-peptide mimics include ?-amino acid residues and, optionally, disulfide bonds to stabilize the conformation of the mimics. The compounds may be truncated as compared to conventional Z-domain scaffold peptides and are resistant to proteolytic degradation due to the presence of ?-amino acid residues. The mimics can be made so as to bind selectively to a desired target.

Abstract: A light-sensitive G-protein coupled receptor includes a light sensitive extracellular domain and a heterologous intracellular domain capable of modulating an intracellular signaling pathway.

Abstract: The present invention provides novel activin IIB5 receptor polypeptides capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the receptor polypeptides. Compositions and methods for treating muscle-wasting, metabolic and other disorders are also provided.

Abstract: The present invention provides anti-hemagglutinin antibodies, compositions comprising anti-hemagglutinin antibodies, and methods of using the same.

Abstract: This invention includes, in part, methods of preparing acetylated Huntingtin (Htt) polypeptides, acetylated Htt polypeptide antigens, and antibodies that specifically recognize acetylated epitopes on Htt polypeptides. The invention also relates, in part, to the preparation and use of antibodies that specifically recognize and bind to acetylated epitopes on acetylated Htt polypeptides when an acetylated residue on the Htt polypeptide is a lysine that corresponds to K444 residue of full-length, wild-type Htt polypeptide. In some aspects, the invention includes hybridoma cell lines that produce antibodies that specifically bind acetylated Htt polypeptide and also includes antibodies and antigen-binding fragments thereof produced using polypeptides of the invention.

Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: This invention provides for a method of preventing or treating a cadherin-11 related disease in a subject, which includes administering to the subject an effective amount of a compound of the following formula: or a pharmaceutically acceptable salt or prodrug thereof, where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, X1 and X2 are as defined herein.

Abstract: The present invention relates generally to the inhibition of inflammatory cell-mediated angiogenesis. In particular, the invention concerns the prevention or treatment of tumor angiogenesis, and the inhibition of tumor development, using Bv8 antagonists, such as anti-Bv8 antibodies.

Abstract: The invention provides methods and compositions for the treatment of juvenile idiopathic arthritis (JIA) where a TNF? inhibitor, such as a human TNF? antibody, or antigen-binding portion thereof, is used to treat JIA. In particular, the invention is directed to methods and compositions relating to a fixed dosing regimen for treating JIA with a TNF? inhibitor.

Abstract: The invention describes improved methods and compositions for producing a recombinant protein, e.g., an antibody, in mammalian cell culture. In addition, the invention provides improved cell culture media, including improved production media, feed solutions, and combination feeds, which may be used to improve protein productivity in mammalian cell culture.

Abstract: The present disclosure provides compositions and methods relating to antigen binding proteins which bind to human thymic stromal lymphopoietin (TSLP), including antibodies. In particular embodiments, the disclosure provides fully human, humanized and chimeric anti-TSLP antibodies and derivatives of such antibodies. The disclosure further provides nucleic acids encoding such antibodies and antibody fragments and derivatives, and methods of making and using such antibodies including methods of treating and preventing TSLP-related inflammatory and fibrotic disorders.

Abstract: The present invention provides a method capable of producing a natural or recombinant protein in high yield. The present invention relates to a method of producing a polypeptide, comprising culturing a cell which strongly expresses alanine aminotransferase and has a transferred DNA encoding a desired polypeptide and thereby allowing the cell to produce the polypeptide.

Abstract: The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

Abstract: The present invention relates to the use of VEGF antagonists and a novel anti-?5?1 antibody for treating cancer and inhibiting angiogenesis and/or vascular permeability, including inhibiting abnormal angiogenesis in diseases. The present invention also relates to compositions and kits comprising novel anti-?5?1 antibodies and methods of making and using them.

Abstract: The invention provides methods for modulation interactions between MDL-1 and its binding partner, Gal9. Also provided are methods to screen for modulators of MDL-1/Gal9 interaction.

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4.

Abstract: The present invention relates to FGFR4 antibodies including fragments or derivatives thereof and the polynucleotides encoding the antibodies. Expression vectors and host cells comprising the polynucleotides are provided. Further, the invention refers to pharmaceutical compositions comprising the FGFR4 antibodies and methods for the treatment, prevention or diagnosis of disorders associated with FGFR4 expression.

Abstract: The present invention provides antibodies that bind to ErbB3 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human ErbB3. In certain embodiments, the antibodies of the present invention block the interaction of ErbB3 with an ErbB3 ligand such as neuregulin 1. The antibodies of the invention are useful for the treatment of various cancers.

Abstract: Multifunctional probes include a substrate (e.g., a nanoparticle, polymer, antibody, protein, low molecular weight compound, drug) and a multifunctional single-attachment-point (MSAP) reagent. The MSAP reagents can include three components: (i) a peptide scaffold, (ii) a single chemically reactive group on the peptide scaffold for reaction of the MSAP with a substrate having a complementary reactive group, and (iii) multiple functional groups on the peptide scaffold. The peptide scaffold can include any number of residues; however, for ease of synthesis and reproducibility in clinical trials, it is preferred to limit the residues in the peptide to 20 or less.

Abstract: Disclosed is an apparatus for continuously processing a lignocellulosic material, and particularly to an apparatus for continuously processing a lignocellulosic material by using of a single-stage or two-stage pretreatment processing with related to the acid-catalyzed steam explosion processing combined with dilute acid hydrolysis and steam explosion, in which parameters are adjusted to maintain in a state where lignocellulosic material feeding, acid mixing pre-heating, dilute acid hydrolysis reaction, steam explosion and flash discharge, to solid and liquid separation are simultaneously and continuously operated, so as to achieve in the results of acquiring xylose hydrolyzate by hydrolyzing hemicellulose, destroying lignocellulosic material structure, increasing surface area and porosity.

Abstract: The present invention provides an apparatus and a method for conversion of cellulosic material, such as chopped straw and corn stover, and household waste, to ethanol and other products. The cellulosic material is subjected to continuous hydrothermal pre-treatment without addition of chemicals, and a liquid and a fiber fraction are produced. The fiber fraction is subjected to enzymatic liquefaction and saccharification. The method of the present invention comprises: performing the hydrothermal pre-treatment by subjecting the cellulosic material to at least one soaking operation, and conveying the cellulosic material through at least one pressurized reactor, and subjecting the cellulosic material to at least one pressing operation, creating a fiber fraction and a liquid fraction; selecting the temperature and residence time for the hydrothermal pretreatment, so that the fibrous structure of the feedstock is maintained and at least 80% of the lignin is maintained in the fiber fraction.

Abstract: A method for producing a polymer containing silica that does not involve long kneading time, and a polymer composition having an intended low heat generation property. A polymerization catalyst composition is produced by mixing and aging a second element and a third element, and then adding a first element to the mixture to react the first element with the mixture. The first element contains a compound that contains a rare earth metal element, the second element contains a compound represented by the following formula (X), and the third element contains silica. YR1aR2bR3c (X) (In the formula, Y is a metal; R1 and R2 are hydrogen atoms or hydrocarbon groups; and R3 is a hydrocarbon group, and R1, R2, and R3 are the same as or different from each other, a, b, and c are 0 or 1.).