Abstract: The present invention relates to compounds of the formula (I), or pharmaceutically acceptable salts, enantiomer or diastereomer thereof, wherein R1 to R4 are as described above. The compounds may be useful for the treatment or prophylaxis of hepatitis B virus infection.

Abstract: The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as ERK (MAPK). Also provided are methods of using such compounds or compositions, and methods of using these compositions to modulate the activities of one or more of these kinases, especially for therapeutic applications such as the treatment disorders such as cancer.

Abstract: A pharmaceutical composition is provided which includes perillyl alcohol conjugated with a therapeutic agent and further includes and a hydrolyzable acylated aliphatic tail. A method of using the pharmaceutical composition is also provided for treating a condition or disease of a patient, e.g., cancer.

Abstract: Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.

Abstract: Described herein are compounds of Formula (I)-(III), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating and/or preventing diseases are also provided.

Abstract: The invention provides novel inhibitors of ROCK1 and/or ROCK2. Also provided are methods of treating diseases and disorders involving inhibiting ROCK1 and/or ROCK2. The present invention includes pharmaceutical compositions comprising the compounds of the invention and a pharmaceutically acceptable carrier and/or diluents. The present invention includes compositions comprising a substantially pure compound of the invention and a pharmaceutically acceptable salt, steroisomer, or hydrate thereof: and a pharmaceutically acceptable excipient and/or diluents.

Abstract: A compound satisfying formula I, a prodrug, N-oxide, addition salt, quaternary amine, metal complex, or a stereochemically isomeric form thereof; compositions contain these compounds as active ingredient and processes for preparing these compounds and compositions.

Abstract: A borate compound for use as photoinduced chemical bleaching reagent is disclosed having improved bleaching performance under certain conditions, compared to neutral borates. The compounds are comprised of Formula I; R1R2R3R4BXa??I where each R1, R2, and R3 and R4 is, independently, an alkyl, alkylaryl, or arylalkyl, with the proviso that at least one of R1, R2, and R3 and R4 is an alkyl group and at least two of R1, R2, R3 and R4 group is positively charged; X is an anion; and a equals 1, 2, or 3.

Abstract: Provided are a lithium secondary battery having improved initial capacity and excellent cycle property, an electrolyte solution for the lithium secondary battery, and an additive for the electrolyte solution for the lithium secondary battery. The lithium secondary battery includes positive and negative electrodes both having a lithium-ion intercalation/de-intercalation ability, and a non-aqueous electrolyte solution contacted with the positive and negative electrodes. The non-aqueous electrolyte solution contains lithium hexafluorophosphate and a boroxine compound represented by (RO)3(BO)3 liquefying at 25° C. R(s) each independently represent an organic group of a linear chain alkyl group having 3 or more carbon atoms. Herein, the chain alkyl group may have a branch, and when the branch is included, the number of carbon atoms of the chain alkyl group constructing a linear portion thereof is 3 or more.

Abstract: Halogen free amine substituted trisilylamine and tridisilylamine compounds and a method of their preparation via de-hydrogenative coupling between the corresponding unsubstituted tnsilylames and amines catalyzed by transition metal catalysts is described. This new approach is based on the catalytic dehydrocoupling of a Si—H and a N—H moety to form an Si—N containing compound and hydrogen gas. The process can be catalyzed by transition metal heterogenous catalysts such as Ru(0) on carbon, Pd(0) on MgO) as well as transition metal organometallic complexes that act as homogeneous catalysts. The —Si—N containing products are halide free. Such compounds can be useful for the deposition of thin films by chemical vapor deposition or atomic layer deposition of Si containing films.

Abstract: Bisaminoalkoxysilanes of Formula I, and methods using same, are described herein: R1Si(NR2R3)(NR4R5)OR6??I where R1 is selected from hydrogen, a C1 to C10 linear alkyl group, a C3 to C10 branched alkyl group, a C3 to C10 cyclic alkyl group, a C3 to C10 alkenyl group, a C3 to C10 alkynyl group, a C4 to C10 aromatic hydrocarbon group; R2, R3, R4, and R5 are each independently selected from hydrogen, a C4 to C10 branched alkyl group, a C3 to C10 cyclic alkyl group, a C3 to C10 alkenyl group, a C3 to C10 alkynyl group, and a C4 to C10 aromatic hydrocarbon group; R6 is selected from a C1 to C10 linear alkyl group, a C3 to C10 branched alkyl group, a C3 to C10 cyclic alkyl group, a C3 to C10 alkenyl group, a C2 to C10 alkynyl group, and a C4 to C10 aromatic hydrocarbon group.

Abstract: The present invention relates to novel metathesis catalysts with an imidazolidine-based ligand and to methods for making and using the same.

Abstract: The present invention generally provides methods of improving lignin separation during biomass fractionation with an acid to release sugars and a solvent for lignin (such as ethanol). In some embodiments, a digestor is employed to fractionating a feedstock in the presence of a solvent for lignin, sulfur dioxide, and water, to produce a liquor containing hemicellulose, cellulose-rich solids, and lignin. A solid additive is added to the digestor, wherein the solid additive combines with at least a portion of the lignin. Then a mixture of lignin and the solid additive is separated from the liquor, prior to hemicellulose recovery. Optionally, a solid additive may also be introduced to a hydrolysis reactor for converting hemicellulose oligomers to monomers, to improve separation of acid-catalyzed lignin. In some embodiments, the solid additive is gypsum or a gypsum/lignin mixture.

Abstract: Biomass feedstocks (e.g., plant biomass, animal biomass, and municipal waste biomass) are processed to produce useful products, such as fuels. For example, systems are described that can use feedstock materials, such as cellulosic and/or lignocellulosic materials and/or starchy materials, to produce a product or intermediate, e.g., energy, a food, a fuel, or a material.

Abstract: The present application discloses a process for the purification of a neutral human milk oligosaccharide (neutral HMO). The process uses simulated moving bed (SMB) chromatography which allows the continuous purification of large quantities of HMOs with high purity. Contrary to chemical synthesis routes of neutral HMOs, and their subsequent purification, the presented process allows the provision of HMOs free of noxious chemicals, such as e.g. trace amounts of heavy metals or organic solvents. The individual neutral HMO product may be obtained in solid form by spray drying or as a concentrated syrup. The provided neutral HMO is very well-suited for use in food applications.

Abstract: The present invention provides novel ruthenium compounds of Formula (I): or salts, isomers, hydrates, or solvates thereof, or combinations thereof; wherein E, R1, R2, R3, R4, R5, X1, and X2 are as defined herein, and pharmaceutical compositions thereof. Also provided are methods of use and treatment. Such compounds have been found useful in the treatment of malaria infection. Such compounds may also be useful in the treatment of inflammatory conditions, such as acute lung injury and acute resipiratory distress syndrome, which optionally may be associated with a malaria infection.

Abstract: The application discloses compounds of Formula I wherein the variable substituents are as defined herein. The compounds of Formula I and pharmaceutical compositions comprising compounds of Formula I are useful for the treatment of diseases mediated by Filoviruses such as Ebolavirus.

Abstract: The present invention relates to methods and intermediates for synthesizing 2?-deoxy-2?,2?-difluorotetrahydrouridine compounds.

Abstract: The present disclosure provides alternative sugar moieties and polynucleotides comprising such sugar moieties, and methods of use thereof.

Abstract: A method for preparing abiraterone acetate.

Abstract: Described herein are microreactors and methods of modifying support particles using acoustic standing waves. A liquid medium containing suspended support particles is flowed along a flow path through a channel, and an acoustic standing wave is applied to the channel to hold the suspended particles at a point in the channel. The held particles are then subjected to one or more reactions by flowing biochemical reactants through the channel. Unbound biological reactant is optionally washed from the channel. The reacted support particles can be released from the acoustic standing wave for further processing using, for example, flow cytometry or fluorescence microscopy.

Abstract: Large-scale downstream processing of secreted recombinant proteins is provided in a single device, wherein the contents of a plurality of bioreactors are combined simultaneous to their harvesting and purification resulting in significant savings of time and the cost of manufacturing.

Abstract: A sample is provided that can be purified by preparative reversed phase high performance liquid chromatography (Prep-RP-HPLC) in a single run in spite of recent advances in the production of reversed phase derivatized silica stationary supports: (1) The traditional approach is to use a bigger column (greater amount of stationary phase); and (2) Use displacement chromatography which (while labor intensive to develop) uses the stationary phase more effectively. This disclosure describes a unique Prep-RP-HPLC technique that uses a C-18/C-8 derivatized silica coated with a surfactant such as Triton X-100 to result in 7 to 10 fold increase in sample loading (of the crude mixture of organic compounds including synthetic crude peptides) in contrast to the conventional Prep-RP-HPLC technique. This increase in sample loading capacity and output is due to the additional surrogate stationary phase characteristic of the C-18/C8 adsorbed (bound) surfactant.

Abstract: The first embodiment of the present invention is a method for purifying an antibody or a substance derive from an antibody, wherein a carrier 1 having an affinity ligand with affinity for the antibody or the substance derived from the antibody and a carrier 2 having a cation exchange group are used to prepare an integrated column 1 connecting a column containing the carrier 1 and a column containing the carrier 2 or a column 2 having the mixture of the carrier 1 and carrier 2, the antibody or the substance derived from the antibody is applied to the column 1 or the column 2, and then the adsorbed antibody or substance derived from the antibody is eluted from the column 1 or the column 2. The second embodiment of the present invention is a method for using a carrier having a cation exchange group, wherein a solution containing an antibody or a substance derived from an antibody is applied to a carrier having a cation exchange group having a carboxyl group-containing ligand and pKa of 4.

Abstract: Disclosed herein are protein enrichment substrates and methods for making the same that can be used to enrich proteins of interest. Also disclosed herein are methods for protein purification using these protein enrichment substrates.

Abstract: The present invention relates to particulate forms of anamorelin monohydrochloride or a composition comprising anamorelin monohydrochloride having controlled chloride content, preferably isolated in an amorphous and/or fine particulate state, processes for making the particulate forms, and pharmaceutical compositions comprising the particulate forms.

Abstract: The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

Abstract: Novel peptides are described which comprise an amino acid motif selected from the group consisting of “PG”, “GP”, “PI” and “IG” and having up to 10 amino acids upstream and/or downstream of the amino acid motif, wherein “P” in the motif is proline or hydroxyproline and the peptide stimulates the development, maintenance and repair of bone, cartilage and associated connective tissue. The invention further relates to pharmaceutical compositions of these peptides, as well as therapeutic and prophylactic uses of such peptides.

Abstract: The present invention is directed to C-type lectin-like molecule-1 (CLL1) specific ligand peptides, comprising the amino acid motif LR(S/T), and methods of their use, e.g., for imaging detection for diagnosis of leukemia and the presence of leukemic stem cells (LSCs) and targeted therapy against leukemia mediated at least in part by CLL1-expressing LSCs.

Abstract: Object of the present invention is to provide a peptide functioning as a c-Met agonist. The present invention provides a peptide complex comprising two or more peptides that bind to a c-Met protein and a linker that links the two or more peptides to one another. Such a peptide complex promotes autophosphorylation of the c-Met protein and induces cell growth.

Abstract: The current invention concerns the identification of B-cell epitopes (as linear peptides) from human polyoma virus proteins and their use in an immune diagnostic assay.

Abstract: Disclosed herein are compounds (such as peptides or peptide mimetics) that bind to HIV RRE RNA. In some examples, the compounds inhibit (for example, decrease) binding of Rev to the RRE RNA. In some embodiments, the compounds include two moieties, each of which bind to one of the Rev binding sites in the RRE. In some examples, the moieties include peptides or small molecules. In some examples, the peptides include an arginine-rich motif. The RRE binding compounds may be further linked to a detectable label or cargo moiety. Also disclosed are methods of treating or inhibiting HIV including administering one or more of the disclosed compounds to a subject.

Abstract: The present disclosure relates to novel fusion proteins that bind to the HIV-1 gp120 antigen. The present disclosure also relates to nucleic acids, plasmids and host cells that comprise a sequence that encodes the fusion proteins of the disclosure. The fusion proteins of the disclosure can be used in applications to detect the presence of HIV-1 gp120 protein, to detect an HIV-1 infection and to monitor treatment of an HIV-1 infection.

Abstract: The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized ?-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha-helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.

Abstract: A series of protein A mutants having high alkali resistance, and methods of using the protein A mutants are provided. The protein A mutants have a high binding affinity for regions of immunoglobulin proteins other than the complementarity determining regions. The protein A mutants can be coupled to a solid support for immunoglobulin isolation, or conjugated to a label for immunoglobulin detection. This series of protein A mutants has high chemical stability under alkaline conditions of pH 13-14, and can also be used as chromatography ligands for purification procedures that use alkaline solutions under harsh conditions, such as Clean-In-Place (CIP). Also provided are methods of immunoglobulin separation and purification, and alkali regeneration of affinity chromatography medium that uses protein A as a ligand.

Abstract: The present invention provides a recombinant protein capable of binding to complement factor H (CFH), and thereby inducing increased binding of C3d and C3b by bound CFH compared to unbound CFH. Methods and medical devices for using utilising the same are also described.

Abstract: Provided herein are compositions comprising light-activated chimeric proteins expressed on plasma membranes and methods of using the same to selectively depolarize excitatory or inhibitory neurons.

Abstract: The present invention relates to the field of biotechnology and genetic engineering, and particularly to the expression of recombinant peptides. The inoculation thereof in cattle results in the production of an immune response capable of adversely affecting Rhipicephalus microplus ticks, which feed on the inoculated cattle, decreasing the number and reproductive capacity of this tick species. Such recombinant immunogen can be used as an effective vaccine for tick control. The technical goal is the design and construction of two synthetic genes made with preferred codons for Pichia pastoris and expression thereof from a recombinant peptide, which consists in a continuous sequence and of a recombinant peptide, respectively, and the drug composition based of said recombinant polypeptide.

Abstract: The present application relates to silk fibroin-based hydrogels, methods for making and using the same.

Abstract: The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.

Abstract: The invention provides a fusion protein or polypeptide comprising an apelin peptide fused to a multimerizing component. The invention also provides a fusion protein or polypeptide comprising an apelin peptide fused to an Fc domain, a fragment of an Fc domain, or a variant of an Fc domain. Apelin Fc-fusion polypeptides are capable of binding to the apelin receptor (APLNR). Apelin Fc-fusion polypeptides are capable of activating the APLNR and have improved pharmacokinetic properties compared to apelin peptides that are not fused to an Fc or an Fc fragment. Apelin Fc-fusion polypeptides are useful in diseases and conditions related to cardiovascular function, diabetes, cancer, obesity and other apelin-related conditions.

Abstract: Expression vector systems are provided for increased production of a recombinant GDF-5 (rhGDF-5) protein. Also provided are transformed host cells that were engineered to produce and express high levels of rhGDF-5 protein. Methods for isolating recombinant GDF-5 protein from an inclusion body of a cell are disclosed herein. The methods as disclosed are cost-effective, time-saving and are of manufacturing quality.

Abstract: The invention provides fusion proteins having improved bioactivity comprising a first polypeptide fusion partner and a second polypeptide fusion partner wherein the first fusion partner is linked to the second fusion partner by a mucin-domain polypeptide linker and wherein the bioactivity of the fusion protein of the invention is improved as compared to fusion of the first polypeptide fusion partner and the second polypeptide fusion partner in the absence of the mucin-domain polypeptide linker. Mucin-domain polypeptide linkers comprise a mucin domain that is rich in potential glycosylation sites, and has a high content of serine and/or threonine and proline, which can represent greater than 40% of the amino acids within the mucin domain and further comprise at least about 60% of its mass due to the glycans.

Abstract: The present disclosure provides chimeric proteins having an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor (FGF) 2 and the C-terminus comprises a portion of an FGF1 protein. Such FGF2/FGF1 chimeras can further include a fibroblast growth factor receptor (FGFR) 1c-binding protein, a ?-Klotho-binding protein, or both. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.

Abstract: The present invention relates to interleukin-4 receptor-binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 or interleukin-13 protein moiety joined to an anti-apoptotic Bcl-2 family member protein moiety.

Abstract: Cell lines that stably express ENaC and methods for using those cell lines are disclosed herein. The invention includes cell lines that express various subunit combinations and various proteolyzed isoforms of ENaC and techniques for creating cell lines. The ENaC-expressing cell lines are highly sensitive, physiologically relevant and produce consistent results.

Abstract: The present invention relates to, in part, artificial antigen presenting cells that are useful in treating disease (including cancers) and have uses, for example, directly in vivo and/or in the expansion of a patients cells for re-introduction ex vivo.

Abstract: The present invention provides for prevention and/or treatment of neurological or neuropsychiatric disorders involving abnormal D1-D2 dopamine receptor coupling and/or activation. Methods and agents are provided for modulating dopamine receptor function arising from D1-D2 coupling and/or activation. Agents of the present invention include fragments of D2 receptor or D1 receptor that can disrupt D1-D2 coupling.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.