Abstract: The present disclosure is directed to salts of N-{4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetamide and process for the preparation thereof (formula II).

Abstract: The present invention relates to inhibitors of the activity of Complex (III) of the mitochondrial electron transport chain and use thereof in treatment and/or prevention of cancers presenting tumor-initiating cells. The present invention further relates to pharmaceutical compositions containing said inhibitors alone or in combination with other pharmaceutically active agents, and their use as medicaments or as agrochemicals where their properties as inhibitors of the mitochondrial respiration is of benefit.

Abstract: The present invention provides compounds, compositions thereof, and methods of using the same.

Abstract: A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof works as an mGluR2 antagonist, and is applicable as a therapeutic agent for neurological disorders related to glutamate dysfunction and diseases involving the mGluR2, such as Alzheimer's disease: wherein R is a hydrogen atom, a C1-6 alkyl group or the like, R1 is a C1-6 alkyl group, a C1-6 alkoxy group or the like, R2 is a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group or the like, R3 is a hydrogen atom, a C1-6 alkyl group or the like, and R4 is a C1-6 alkyl group or the like.

Abstract: The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K.

Abstract: This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Abstract: The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic ?7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

Abstract: The invention discloses a method for preparation of cyano compounds of the 13th group of the periodic table with 1, 2, 3 or 4 cyano residues, represented by formula (I): [Catn+][Z1F4-m(CN)m)?]n by a reaction of [(Z1F4)?] with trimethylsilylcyanide in the presence of a Lewis acid and in the presence of the cation Catn+; Cat2+ is a cation, Z1 is B, Al, Ga, In or Tl, m is 1, 2, 3 or 4 and n is 1, 2, 3 or 4.

Abstract: This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

Abstract: The present invention relates to silyl- and heteroatom-substituted compounds selected from carbazoles, dibenzofurans, dibenzothiophenes and disilylbenzophospholes of the formula (I) or (I*), to the use of the compounds of the formula (I) or (I*) in organic electronics applications, preferably in organic light-emitting diodes, to an organic light-emitting diode comprising at least one compound of the formula (I) or (I*), to a light-emitting layer comprising at least one compound of the formula (I) or (I*), to a blocking layer for holes/excitons comprising at least one compound of the formula (I) or (I*), and to an apparatus selected from the group consisting of stationary visual display units, mobile visual display units, illumination units, keyboards, items of clothing, furniture and wallpaper, comprising at least one inventive organic light-emitting diode.

Abstract: A method for preparation and polymerization of siloxane monomers of Formula I is presented. The synthesis includes the selective reaction between silanol containing unit and alkoxy containing units in the presence of basic catalyst. The siloxane monomers of the invention can be used for preparation of siloxane polymers with good flexibility and cracking threshold, and functional sites, useful for applications requiring low metal content in semiconductor industry.

Abstract: A conjugated compound of formula Q-Z—R4 wherein Q is a TLR7 and/or TLR8 agonist and Z—R4 is a lipid covalently linked to an amino acid or peptide coupled to a polyamine group, and a process for the manufacture of the conjugated compound, as well as a complex formed between the conjugated compound and a polyanionic molecule and a pharmaceutical composition containing the conjugated compound or complex. Also described is the use of the conjugated compound or complex in the treatment of infection, cancer or immune disorders or for use in vaccines.

Abstract: In various embodiments, the invention provides phosphine ligand supported first row metal catalysts with surprising and efficacious catalytic activity for hydrosilylation of pi-bonded substrates. Also provided are methods of using the catalysts of the invention to prepare hydrosilylated compounds.

Abstract: An object of the present invention is to provide a novel polysaccharide derivative used for a separating agent for optical isomers. The novel polysaccharide derivative contains a structure in which a hydrogen atom of a hydroxyl group or an amino group at the 2-position in a structural unit of the polysaccharide is substituted with a monovalent group represented by the following general formula (1), and a hydrogen atom of a hydroxyl group or an amino group at the 3-position in the structural unit is substituted with a monovalent group represented by the following general formula (2): R1—NH—CO—??(1) R2—NH—CO—??(2) where R1 and R2 represent substituted or unsubstituted aryl groups which are different from each other.

Abstract: The present invention relates to methods of treatment of inflammatory conditions using S-[4-(3-fluoro-3-methylbutyryloxy)-but-2-ynyl]6?,9?-difluoro-17?-(furan-2-yl)carbonyloxy-11?-hydroxy-16?-methyl-3-oxoandrosta-1,4-diene-17?-carbothioate (compound of formula I), a novel anti-inflammatory compound of the androstane series and its processes of preparation.

Abstract: A new method for the synthesis of L-Glutamyl-?-D-Glutamic acid and its use in the synthesis of (2R)-((4S)-carboxy-4-(4,N-(((6S)-2-(hydroxymethyl)-4-oxo-3,4,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino)benzamido)butanamido)pentanedioic acid, 1 are provided. Also provided is an efficient method for the isolation and purification of the trisodium salt of the abovementioned acid, 2, in a form suitable for long term storage and use in a parenteral dosing form.

Abstract: The present invention provides technology for making large (e.g., greater than 50 amino acids), semi-synthetic, stapled or stitched proteins. The method essentially involves ligating a synthetically produced stapled or stitched peptide to a larger protein. Modified version of IL-13 and MYC are provided as illustrative examples.

Abstract: Methods of extracting a component of interest from a plurality of components are described.

Abstract: Provided herein are methods and systems for assembling, solubilizing and/or purifying a membrane associated protein in a nanolipoprotein particle, which comprise a temperature transition cycle performed in presence of a detergent, wherein during the temperature transition cycle the nanolipoprotein components are brought to a temperature above and below the gel to liquid crystalling transition temperature of the membrane forming lipid of the nanolipoprotein particle.

Abstract: Covalent Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. A method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Abstract: Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Abstract: Compounds of general formula (I): their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts, cosmetic and/or pharmaceutical compositions which contain them and their use in medicine, and in the treatment and/or care of the skin, particularly in the aging and photoaging of the skin, and more particularly for the treatment and/or prevention of wrinkles and/or stretch marks.

Abstract: The present invention is directed to compounds according to formula, (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1, and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

Abstract: The invention provides peptides capable of binding with influenza hemagglutinin (HA) protein blocking pH-induced shape change or aggregation of the influenza hemagglutinin (HA) protein. The invention also provides a druggable site in influenza Hemagglutinin protein, said druggable site comprises peptide sequences comprising conserved residues.

Abstract: The present invention provides compositions for the therapeutic and/or cosmetic treatment of Elastin comprising tissues. Therapeutic and cosmetic compositions comprising an elastin digest stimulate the endogenous production of Elastin and appear to enhance the elasticity of the skin and provide an external supply of peptide precursors of Elastin that penetrate into the tissue to which it is applied. The present invention describes compositions containing an elastin digest derived from proteolytic digestion of insoluble elastin derived from mammalian ligaments with a protein digesting composition, such as proteinase K. The elastin digest is a mixture of elastin peptides wherein the elastin peptide mixture comprises peptides of the sequence GXXPG, wherein X represents one of the natural amino acids. The elastin digest of the present invention may also comprise epitopes of cytokines, growth factors and di-peptides.

Abstract: Disclosed are cyclic, peptide-based novel compounds having NPR-B agonistic activity. Preferred compounds are cyclic peptides containing conventional or non-conventional L- or D-amino acid residues connected to one another via peptide bonds. In some embodiments, provided herein are a cyclic peptide compound with a ring size that is significantly reduced as compared to known NPR-B agonists, such as CNP.

Abstract: The present invention provides for the identification of an antigen surrogate to the native antigens for the autoimmune disease pemphigus vulgaris. Ligands are discovered using large random peptoid or cyclic peptoid libraries that are screened against known antibodies to autoimmune diseases. The ligands may be useful as drugs in the treatment of such diseases and can also be used in combination with the comcomitant removal of T-cells associated with autoimmune disorders.

Abstract: The present invention relates to the use of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof, for a treatment in a variety of conditions, such as the induction of immunotolerance, autoimmune diseases, bacterial infections, and proliferative diseases, such as cancers.

Abstract: Melanocortin receptor-specific cyclic heptapeptides of the formula Z-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Y??(II) or a pharmaceutically acceptable salt thereof, where Z, Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, Xaa6, Xaa7 and Y are as defined in the specification, compositions and formulations including the peptides of the foregoing formula, and methods of preventing, ameliorating or treating melanocortin receptor-mediated diseases, indications, conditions and syndromes.

Abstract: The present invention provides biologically active peptidomimetic macrocycles with improved properties relative to their corresponding polypeptides. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

Abstract: A series of integrin blockers that present strong angiogenesis inhibiting performance, high integrin affinity and integrin-bonding capacity is provided. This series of integrin blockers can be adopted in treatment of solid tumors and rheumatoid arthritis. Specifically, said series of integrin blockers include polypeptide I, polypeptide II and polypeptide III (see SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3) that can be adopted in treatment of solid tumors and rheumatoid arthritis. This invention also relates to application of these three integrin-blocking polypeptides in preparation of anti-tumor drugs, wherein the tumors that can be treated include those primary or secondary cancers originated from head and neck region or other organs such as brain, thyroid, esophagus, pancreas, lung, liver, stomach, breast, kidney, gallbladder, colon, rectum, ovary, cervix, uterus, prostate, bladder and testicle, as well as melanoma and sarcomas.

Abstract: The present invention provides isolated polypeptides isolatable from a Fusobacterium spp. Also provided by the present invention are compositions that include one or more of the polypeptides, and methods for making and methods for using the polypeptides.

Abstract: Disclosed herein are enhanced polypeptides, polynucleotides encoding these polypeptides, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

Abstract: A bacterium belonging to the family Enterobacteriaceae, which has an ability to produce an amino acid such as L-cysteine and has been modified to have specific mutation in the yeas gene, is cultured in a medium, and the L-amino acid is collected from the medium.

Abstract: New methods for the refolding of recombinant granulocyte colony stimulating factor (G-CSF) from inclusion bodies are disclosed. The methods comprise two refolding steps. In particular, the methods comprise the solubilizing of G-CSF with a solubilizing agent, the oxidative refolding (first refolding step) of G-CSF in the presence of the solubilizing agent and an oxidizing agent, the efficient removal of the solubilizing agent, and a second refolding step to complete the folding of G-CSF in the absence of the solubilizing agent. Various methods are described for the efficient removal of the solubilizing agent from partially refolded G-CSF.

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 molecule comprising a nucleic acid sequence that codes for light-activated molecule. The light-activated molecule includes a modification to a location near the all-trans retinal Schiff base, e.g., to extends the duration time of the open state. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion channels or pumps or for controlling currents in a cell (e.g., in in vivo and in vitro environments).

Abstract: The present invention is directed to fusion polypeptides comprising a Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.

Abstract: An immunological measurement is performed using anti-CTP antibody characterized by recognizing an antigenic determinant included in the polypeptide represented by amino acid numbers 118-132 of SEQ ID NO: 1, and reacting with native Cochlin-tomoprotein (CTP).

Abstract: New designed ankyrin repeat domains with binding specificity for serum albumin, recombinant binding proteins comprising at least two designed ankyrin repeat domains with binding specificity for serum albumin, as well as recombinant binding proteins comprising at least one designed ankyrin repeat domain with binding specificity for hepatocyte growth factor (HGF), at least one designed ankyrin repeat domain with binding specificity for vascular endothelial growth factor (VEGF-A), and at least two designed ankyrin repeat domain with binding specificity for serum albumin are described, as well as nucleic acids encoding such designed ankyrin repeat domains and recombinant binding proteins, pharmaceutical compositions comprising such designed ankyrin repeat domains, recombinant binding proteins or nucleic acids and the use of such designed ankyrin repeat domains, recombinant binding proteins, nucleic acids or pharmaceutical compositions in the treatment of diseases.

Abstract: The present invention relates to nanoparticles containing a P140 peptide and to carriers, with or without dispersant, containing the nanoparticles. The present invention also relates to pharmaceutical and therapeutic uses of the nanoparticles, in particular for the treatment of systemic lupus erythematosus.

Abstract: RNA transcripts representing a fusion of a human SLC45A3 nucleic acid and a human ELK4 nucleic acid that are associated with prostate cancer are described. Compositions and methods useful for detection of fusion transcripts of human SLC45A3 and ELK4 genetic sequences associated with cancer and useful for cancer therapy are provided.

Abstract: The present invention relates to dual function fusions proteins comprising fibroblast growth factor 21 (FGF21) and Exenatide, Exendin-4, or GLP-1. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: Featured herein are non-naturally occurring cytokine domains that can be used, inter alia, to modulate cellular signalling responsive to interleukin-1 receptor I (IL-1RI), to treat disorders, and to detect and/or bind to cellular receptors, as well as other agents. Exemplary cytokine domains can contain amino acid residues from at least two parental cytokines domains, for example, receptor binding features, surface features, ? strands, and loops from at least two parental cytokines domains.

Abstract: This disclosure relates to the use of drugs to prevent graft versus host disease (GVHD) in a subject after, before, or during a hematopoietic stem cell transplant. In certain embodiments, the drugs are antagonist of vasoactive intestinal peptide signaling. In certain embodiments, the subject has a blood or bone marrow cancer or condition.

Abstract: The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

Abstract: The present invention provides a human insulin analog, an acylated derivative thereof and a physiologically acceptable salt. The present invention further provides a preparation method for the insulin analog and an application of the insulin analog as a therapeutic agent, and particularly as a diabetes mellitus therapeutic agent.

Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.