Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: A compound having the formula Ir(LA)n(LB)3?n, having the structure, Formula I, is disclosed. In Formula I, Z1, Z2, Z3, and Z4 each independently are N or CR2; X is O, S, or Se; n is an integer from 1 to 3; R1, R2, R3, R4, and R5 each independently represent mono- to a maximum possible number of substitutions, or no substitution; R1, R2, R3, R4, and R5 are each independently selected from a variety of substituents; any two substitutions in R1, R2, R3, R4, and R5 are optionally joined to form a ring; at least one pair of substitutions in R1, R2, R3, R4, and R5 are joined together to form a bridge structure comprising a backbone structure that forms a fused first ring, which can be further substituted; and the backbone structure is saturated. Organic light emitting devices and consumer products containing the compounds are also disclosed.

Abstract: The present invention includes novel phosphorescent metal complexes comprising fused imidazole-imidazole moieties. The invented compounds may be useful for application in organic electroluminescence devices.

Abstract: A complex represented by Formula I: wherein: each Ar1, Ar2, Ar3, Ar4, and Ar5 present independently represents a substituted or unsubstituted aryl or heterocyclic aryl; each n is independently an integer of 0 to 4, as limited by valence; X represents O, S, NR1a, SiR1bR1c, or CR1dR1e, where each of R1a, R1b, R1c, R1d, and R1e independently represents substituted or unsubstituted C1-C4 alkyl; Y1a, Y2a, Y3b, and Y4a each independently represents N or C; Y3a represents N, CR2a, or SiR2b, where R2a and R2b represent hydrogen or substituted or unsubstituted C1-C4 alkyl, aryl, or heterocyclic aryl; Y5a and Y5b each independently represents C or N; and Y5c, Y5d, and Y5e each independently represents C, N, O, or S. Light emitting devices for full color displays may include a complex represented by Formula I.

Abstract: Compositions and methods comprising metal organic frameworks (MOFs) and related uses are generally provided. In some embodiments, a MOF comprises a plurality of metal ions, each coordinated with at least one ligand comprising at least two sets of ortho-diimine groups arranged about an organic core.

Abstract: A compound as an SGLT1/SGLT2 dual inhibitor, and an application thereof in the preparation of a drug as the SGLT1/SGLT2 dual inhibitor. The compound is a compound represented by formula (I), an isomer thereof, or a pharmaceutically acceptable salt thereof.

Abstract: Lincosamides of general formula I, where R1 is selected from C2-C8 alkyl or C2-C8 alkenyl; R3 is selected from OH, O(C1-C4 alkyl), SH, S(C1-C4 alkyl) or halogen; R4 is H or C1-C3 alkyl; each of R21, R22, R23, R24, R25 is independently selected from the group consisting of H, OH, C1-C4 alkyl, C1-C4 alkenyl, C1-C4 alkynyl, halogen, O(C1-C4 alkyl), O(C1-C4 alkenyl), O(C1-C4 alkynyl), NH2, N(C1-C4 alkyl)2, N(C1-C4 alkenyl)2, N(C1-C4 alkynyl)2; and pharmaceutically acceptable salts thereof. A method of preparation thereof, in particular a biosynthetic method using newly discovered functions of celesticetin biosynthetic proteins Ccb1 and/or Ccb2. Lincosamides of general formula I are suitable for use as antibacterial and antiprotozoal substances.

Abstract: The present invention relates to a pharmaceutical composition comprising an acanthoside B compound as an effective ingredient for preventing or treating dementia or for improving a cognitive function. In the present invention, a desalted glasswort extract, and acanthoside B, which is isolated from the extract and acts as an effective ingredient inhibitory of acetylcholine esterase, were found to have an excellent neuroprotective activity through the inhibition of neuroinflammation and to improve memory retention and remarkably enhance spatial cognitive ability as measured by passive avoidance test and Y-maze test in a scopolamine-induced amnesic animal model. The acanthoside B or glasswort extract of the present invention can be applied to a pharmaceutical composition for preventing or treating dementia, a pharmaceutical composition for improving a cognitive function, or a health functional food or feed for improving memory retention and cognitive function.

Abstract: Disclosed are messenger RNA molecules and related compositions incorporating a 4?-thio modification in the furanose ring of at least one nucleotide residue, and methods of using these mRNAs to produce an encoded therapeutic protein in vivo and to treat or prevent diseases or disorders. In certain embodiments, the 4?-thio modified mRNA provides for enhanced stability and/or reduced immunogenicity in in vivo therapies.

Abstract: In certain embodiments, the present disclosure provides compounds and methods of increasing the amount or activity of a target protein in a cell. In certain embodiments, the compounds comprise a translation suppression element inhibitor. In certain embodiments, the translation suppression element inhibitor is a uORF inhibitor. In certain embodiments, the uORF inhibitor is an antisense compound.

Abstract: Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.

Abstract: The present invention discloses a solid-phase process for the preparation of a Near Infra-Red (NIR) fluorescent probe characterized by an aza-bicycloalkane based cyclic peptide labelled with a Cy5.5 dye moiety and used in the guided surgery of tumors and pathologic regions.

Abstract: One subject of the present invention is the use of a combination of a polyol (i) consisting of 12 carbon atoms and of a polyol (ii) consisting of 4 to 6 carbon atoms, as protein stabilizer. Another subject of the present invention is protein compositions comprising such a combination. A final subject of the present invention is a process for preparing protein compositions using such a combination.

Abstract: Methods for synthesizing phycocyanin using a biological substance include first synthesizing the phycocyanin by receiving a source containing phycocyanin, forming a solution by adding the source to water, extracting the phycocyanin from the source containing phycocyanin, such as by lysing cell walls and adding chemical reagents to assist in the extraction process, separating the phycocyanin from the solution by using a filter, processing the solution through a centrifuge, and sterilizing the phycocyanin.

Abstract: Compositions and methods for increasing p53-dependent transcriptional activity in a cell.

Abstract: This invention provides novel compounds and methods for promoting cell survival and/or plasticity, especially in neuronal cells, by targeting the microtubule End Binding (EB) proteins and other associated proteins (e.g., drebrin). Methods for identifying potential modulators of cell death/plasticity are also described.

Abstract: A peptide or peptide derivative comprising: (i) WDLYFEIVW (SEQ ID NO:1); or (ii) a variant amino acid sequence comprising one, two, three or four L-amino acid substitutions in WDLYFEIVW (SEQ ID NO: 1); or (iii) the retro-inverso variant of the peptide or peptide derivative of either one of parts (i) and (ii), wherein said peptide or peptide derivative has procoagulant activity. A peptide or peptide derivative comprising: (i) an amino acid sequence comprising imfwydcye; or (ii) a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye, wherein said peptide or peptide derivative has procoagulant activity.

Abstract: In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the ClpP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention is related to a structural protein of a parvovirus with an amino acid insertion at the insertion site I-453, a library comprising the protein, a multimeric structure comprising the protein, a nucleic acid encoding the protein, a vector, virus or cell comprising the nucleic acid, a process for the preparation of the protein, a medicament comprising the protein, nucleic acid or multimeric structure as well as methods and uses involving the protein, nucleic acid or multimeric structure.

Abstract: This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, and/or antibody domain) to a SARS-CoV-2 antigen. For example, binders (e.g., antibodies, antigen binding fragments, and antibody domains) that bind to a SARS-CoV-2 polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having COVID-19 (or a viral infection caused by SARS-CoV-2) are provided.

Abstract: As disclosed herein, stapled peptides targeting the interaction interface between proteins that maintain the integrity of Wiskott-Aldrich syndrome protein family member 3 (WASF3) leads to destabilization of WASF3 and suppression of invasion. Disclosed are stapled peptides that inhibit the binding of Cytoplasmic FMR1-interacting protein 1 (CYFIP1) to either WASF3 or NCK-associated protein (NCKAP1). Also disclosed are methods for treating or suppressing invasion and metastasis of a cancer in a subject that involve administering to the subject a therapeutically effective amount of a stapled peptide disclosed herein.

Abstract: Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.

Abstract: Liposomal and/or nano-liposomal encapsulated peptides of HSP90a, HPf polypeptide (115 aa) and novel polypeptides HPf?C1 (101 aa) and HPf?C2 (87 aa), and methods for manufacturing/preparing and using the compositions, are disclosed. Chimeric fusion proteins that include HSP90a, HPf, HPf?C, HPf?C2 polypeptide, or combinations thereof, are presented. Transformed cell lines and expression vectors capable of expressing the chimeric fusion proteins, are provided. Methods for producing large amounts of recombinant HSP90a, HPf polypeptide, HPf?C1 or HPf?C2 polypeptide, using expression vectors and transformed cell lines, are described.

Abstract: Disclosed herein are proteins capable of forming glucans having alpha-1,2 linkages/branches, reactions and methods for producing such glucan, compositions comprising such glucan, and various applications thereof.

Abstract: The present invention provides the following: a method for efficiently producing a reagent for detecting an antibody that specifically binds with an insoluble antigen protein present in a liquid sample; a reagent for antibody detection produced by the production method; and a use of the antibody. In a step for solubilizing an antigen protein, it is possible to efficiently solubilize and recover the antigen protein by using a cationizing agent; therefore, when compared to conventional methods, it is possible to efficiently produce a reagent for detecting an antibody that has bound to multiple antigen protein molecules in a carrier.

Abstract: The invention relates to compounds derived from the EGF(A) domain of LDL-R, in particular compounds comprising a peptide analogue of the wild-type EGF(A) (LDL-R(293-332)) sequence and at least one substituent comprising at least one fatty acid group. The invention also relates to a pharmaceutical composition thereof and use a medicament. The novel EGF(A) compounds of the invention are useful as treatment e.g. in the field of cholesterol lowering, dyslipidaemia and cardiovascular disease.

Abstract: A polypeptide comprises an insulin B-chain sequence having the substitutions: Asp at position B10, Ala at position B12, and Glu at position B29, relative to wild type insulin. The polypeptide may additionally comprise a substitution of a halogenated phenylalanine at position B24, such as ortho-fluoro-phenylalanine. Optionally, the polypeptide may additionally comprise a C-terminal dipeptide extension wherein at least one amino acid in the dipeptide contains an acidic side chain, such as Glu-Glu, and/or an N-terminal deletion of one, two or three residues from the B chain. An insulin analogue may comprise any of these polypeptides with an insulin A-chain polypeptide that optionally contains a Glu A8 substitution. The A-chain sequence may be a separate polypeptide or it may be joined to the B-chain polypeptide by a two amino acid linker. The linker may be Trp-Lys or Ala-Lys. The insulin analogue may be used to treat a patient with diabetes mellitus.

Abstract: The present disclosure provides binding-triggered transcriptional switch polypeptides, nucleic acids comprising nucleotide sequences encoding the binding-triggered transcriptional switch polypeptides, and host cells genetically modified with the nucleic acids. The present disclosure also provides chimeric Notch receptor polypeptides, nucleic acids comprising nucleotide sequences encoding the chimeric Notch receptor polypeptides, and host cells transduced and/or genetically modified with the nucleic acids. The present disclosure provides transgenic organisms comprising a nucleic acid encoding a binding triggered transcriptional switch polypeptide and/or a chimeric Notch receptor polypeptide of the present disclosure. Binding triggered transcriptional switch polypeptides and chimeric Notch receptor polypeptides of the present disclosure are useful in a variety of applications, which are also provided.

Abstract: The present invention is further directed to methods and compositions for modulating the activity of the Toso protein. The invention further encompasses treatment of disorders associated with inflammation, autoimmune disorders, and cancer using compositions that include a soluble Toso protein.

Abstract: The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: Fusion proteins including an IL-17 receptor with a multimerization domain, or an IL-23 receptor and a multimerization domain, and recombinant viral vectors encoding such fusions, are described. The fusion proteins and vectors encoding such fusions, alone or in combination, can be used in methods for modulating the IL-17 and IL-23 signaling pathways and for treating or preventing diseases mediated by interleukin-17 and interleukin-23, such as immune-related and inflammatory diseases.

Abstract: Disclosed herein are chimeric antigen receptors (CARs) comprising an intracellular segment comprising an interleukin receptor chain, a JAK-binding motif, a Signal Transducer and Activator of Transcription (STAT) 5 association motif and/or a CD3? intracellular signaling domain comprising an exogenous STAT3 association motif, as well as cells and 5 compositions comprising said CARs and uses thereof.

Abstract: A process for manufacturing of a Factor VIII product having a ratio of FVIII:C/FVIII:Ag of at least 0.7 in the Factor VIII product by using chromatography wherein at least one chromatographic step is performed by means of employing; An affinity chromatography resin having an affinity for specifically binding of Factor VIII which is effected by an affinity ligand which is immobilised on the affinity chromatography resin, said affinity ligand is a 13 kD yeast derived Fab antibody fragment directed to the Factor VIII molecule. An anionic chromatography resin. A size exclusion resin. A Factor VIII product obtainable according to the process with a monomer content of >98% for treatment of haemophilia and avoiding formation of inhibitors.

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.

Abstract: A modified Ac-TMP-2 protein lacks one or a plurality of acidic C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein and may also lack one or a plurality of N-terminal amino acids while retaining the amino acid sequence C—S—C at or near the N-terminus. The modified Ac-TMP-2 protein may be useful in method and composition for reducing or alleviating inflammation in a subject. Inflammation may be associated with a disease is a disease of the digestive tract such as chronic gastritis or an inflammatory bowel disease such as Crohn's disease or ulcerative colitis, or a disease of the respiratory system, such as asthma, emphysema, chronic bronchitis, and chronic obstructive pulmonary disease.

Abstract: The invention provides a method for preparing a super-complex which comprises repeat-chains containing single or multiple kinds of monomer-specific protein binding domains having at least two binding sites for a monomer repeated therein; preparing single complexes of the repeat-chains and a protein monomer having at least two binding sites for the monomer-specific binding domain of the repeat-chains, by mixing the repeat-chains and the protein monomer, and then generating the super-complex by forming cross-binding between the single complexes of repeat-chains and the protein monomers.

Abstract: This invention provides antibodies or fragments thereof that are capable of specifically binding to at least one conformational epitope of Human Enterovirus 71 (EV71), wherein the antibody individually comprises at least one variable light chain and at least one variable heavy chain. There is also provided a method of producing an antibody capable of specifically binding to at least one conformational epitope of Human Enterovirus 71 (EV71).

Abstract: Polyclonal antibodies specific for serogroup X of N. meningitidis and uses thereof in diagnosis. The present invention is directed to polyclonal antibodies, specific for the capsular polysaccharides of Neisseria meningitidis serogroup X (NmX), wherein said antibodies are suitable for in vitro detection of Neisseria meningitidis serogroup X in biological fluids without culture. The invention also concerns said polyclonal antibodies in different diagnostic tests and methods, in order to detect Nm X. The invention discloses also a rapid diagnostic test for detecting NmX in a biological fluid, as well as a method for obtaining polyclonal antibodies useful for detecting NmX in biological fluids such as cerebrospinal fluid, serum and urine.

Abstract: The present invention concerns IgA multi-specific binding molecules. In particular, the invention concerns multi-specific, including bispecific, binding molecules comprising IgA heavy chain sequences, and methods for their preparation and use.

Abstract: The present disclosure relates to an inhibitor of Dynamin 2 or composition comprising the same for use in the treatment of Duchenne's muscular dystrophy.

Abstract: The marginal zone (MZ) and B1 subsets of B cells, which differ from conventional follicular (FO) B cells both developmentally and functionally, are involved in early responses to infectious pathogens and the production of self-reactive antibodies. A novel gene, mzb1, is expressed at high levels in MZ and B1 B cells but at low level, if at all, in FO B cells. MZB1 is involved in the regulation of proliferation, BCR-mediated signal transduction, and antibody production in B cells. Inhibitors, activators and enhancers of MZB1 expression or activity can be used as immune modulators for research and therapeutic purposes.

Abstract: The invention provides humanized anti-human Tau(pS422) antibodies and methods of using the same.

Abstract: Provided herein are methods of using the antibodies that bind to RGMc to treat and diagnose iron-related disorders.

Abstract: Purified recombinant polypeptides isolated from Chinese hamster ovary host cells, including antibodies, such as therapeutic antibodies, and methods of making and using such polypeptides are provided.

Abstract: Aspects of the disclosure relate to the treatment, prevention or alleviation of conditions such as fibrosis in a subject. In some embodiments, the treatment, prevention or alleviation of fibrosis in a subject through the administration of an agent capable of inhibiting the action of Interleukin 11 (IL-11) is disclosed.

Abstract: The invention relates to methods of treating chronic intestinal inflammation and/or inflammatory bowel disease by administering an antagonist of oncostatin-M (OSM) and/or OSM receptor-? (OSMR). The invention also relates to methods for diagnosing or prognosing chronic intestinal inflammation and/or inflammatory bowel disease in an individual and for predicting whether or not an individual will respond to an anti-TNF? therapy. The methods comprise measuring OSM and/or OSMR in the individual.

Abstract: The present invention relates to the field of pulmonary, cardiac and inflammatory disorders. More specifically, the present invention provides methods and compositions for treating disorders associated with Resistin. In a specific embodiment, the present invention provides an antibody that binds human Resistin.

Abstract: The present invention relates to monoclonal antibodies that specifically bind to human pituitary adenylate cyclase activating polypeptide (PACAP) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the monoclonal antibodies are also described.

Abstract: The inventors have produced two high specificity and high affinity monoclonal antibodies that bind to human neuromedin U (NMU). Methods and compositions are provided for treating an individual in need thereof (e.g., an individual who is obese and/or has diabetes) by administering an anti-NMU/NMUR agent (e.g., an anti-NMU antibody). For example, methods and compositions are provided for increasing circulating insulin in an individual. Methods and compositions are also provided for detecting neuromedin U (NMU) (e.g., in a biological sample such as serum). Methods and compositions are also provided for predicting whether an individual will develop diabetes and/or PDAC, and for identifying an individual who would benefit from administration of an anti-NMU/NMUR agent.