Abstract: I Injection methods for determining biomolecular interaction parameters such in label-free biosensing systems are provided. The methods generally relate to analyte sample injection methods that generate well-defined analyte concentration gradients en route to a sensing region possessing an immobilized binding partner. The injections conditions are generally established according to a set of rules that create a dispersion event that can be accurately modeled by a dispersion term. The dispersion term is incorporated into the desired interaction model to provide a reliable representation of the analyte concentration gradient profile, The resulting interaction model is then fitted to a measured binding response curve in order to calculate the interaction parameters.

Abstract: This invention is directed to a general method for the chronic treatment, potential cure, or prevention of various metabolic and related diseases in people, including diabetes, by modulating IRS2 activity in cells and tissues in the body. IRS1 and IRS2 are part of the insulin or insulin-like growth factor signaling pathway. By upregulating the levels or functional activity of IRS2, insulin is used more efficiently by the body to control nutrient levels. By upregulating IRS2 levels or functional activity in pancreatic ?-cells, glucose sensing and insulin secretion are enhanced.

Abstract: As a means for treating diseases such as neurodegenerative diseases, malignant tumors and infectious diseases, a method for screening a substance increasing glutathione is provided. According to this method, by contacting a test substance with a cell expressing a GTRAP3-18 protein, a substance decreasing the amount of expression of the GTRAP3-18 protein or inhibiting a function of the GTRAP3-18 protein is specified as a target substance.

Abstract: Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: The present invention provides assays and devices for detection of substances in liquid samples. The assays and devices utilize passive diffusion between a porous material and a porous membrane containing a specific binding pair member to enable detection of the substance of interest.

Abstract: Methods and materials use template-directed assembly of polypeptides and optionally additional reagents to analyze the functionality of membrane-associated proteins, such as, for example, portions of transmembrane proteins, membrane-associated proteins, and others proteins that bind to transmembrane proteins and membrane-associated proteins, and to analyze the effect of test compounds or mutations on the functionality of same. The methods and materials of the present application provide a more native-like environment for analyzing the functionality of membrane-associated proteins, and thus provide effective tools for studies involving the detection of the level of enzyme activity of such proteins in an environment that closely resembles the native environment in the cell, and for novel manufacturing processes.

Abstract: The present invention relates to the identification of polynucleotides and polypeptides involved in insulin and adiponectin signaling and regulation of glucose production. The invention further relates to the use of the identified polynucleotides and polypeptides, and inhibitors of the polynucleotides and polypeptides, in the regulation of glucose production and the monitoring and treatment of metabolic disorders such as diabetes.

Abstract: A binding partner, especially an antibody fragment that specifically recognizes an antigen-antibody immune complex between anti-THC and THC (tetrahydrocannabinol), is disclosed. The binding partner facilitates a non-competitive homogenous immunoassay for detection of cannabis use. A test kit comprising the binding partner is also described. Preferably the immunoassay is applied for roadside testing of saliva from suspected drivers.

Abstract: The invention provides methods for treating humans in need of combined immunosuppressant and biological response modifier therapy.

Abstract: The present invention relates to novel uses of the MLN 51 gene or protein. The MLN 51 gene and protein is closely related to the development of rheumatoid arthritis and serve as biomarker and therapeutic target for rheumatoid arthritis, particularly chronic synovitis.

Abstract: Uses and applications derived from the discovery of a novel binding site of IKK-?, such as method of screening a therapeutic agent as drug candidate for treating cancer, inflammation, or other diseases/disorders, are provided.

Abstract: The invention is directed to aptamers, methods and kits comprising same for detecting Streptococcus pyogenes. The method of screening a subject for Streptococcus pyogenes involves obtaining a body sample from the subject; contacting the sample or a bacterial culture of the sample with an aptamer or a panel of aptamers specific to S. pyogenes; and detecting the presence or absence of S. pyogenes in the sample or the bacterial culture, wherein binding of the aptamer is indicative of the presence of S. pyogenes.

Abstract: The invention relates to thrombin inhibitors derived from the salivary glands of haematophagous arthropods and in particular to bivalent and trivalent thrombin inhibitors that act by interacting with thrombin at two or three different sites.

Abstract: It is disclosed herein that antibodies specific for preproproteins or preproteins, which are synthesized by certain types of cells or tissues, can be used in immunohistochemistry assays to discriminate between the intracellular component of the protein (including the preproprotein, preprotein and/or proprotein forms of the protein) from the secreted component of the same protein. Accordingly, provided herein is an immunohistochemical method for specific detection of the intracellular form of a protein in a biological sample using an antibody specific for the preproprotein or preprotein form of the protein. In particular examples, the protein is albumin or an immunoglobulin light chain. Also disclosed herein are preproprotein-specific ore preprotein-specific antibodies that can be used to detect specific cell types, tissue lesions or other pathological foci and metastases by IHC. In particular, antibodies that specifically bind human preproalbumin, but do not bind the secreted form of albumin are disclosed.

Abstract: Evaluation of VLP-I levels in combination with at least one of amyloid-? peptide (AB), hyperphosphorylated tau (pTau) or total tau (tTau) levels in samples of biological fluid improves the accuracy of diagnosis of Alzheimer's disease.

Abstract: The present invention relates to methods of treating a patient infected by Actinomycetes sp. by administering 6-aza-17-substituted-androst-4-en-3-one compounds to that patient. Another aspect of the invention relates to the screening for drug candidates to treat patients infected by Actinomycetes sp.

Abstract: In one or a plurality of embodiments, there is provided a target molecule of amylospheroid, which is expressed in mature neurons and to which the amylospheroid binds to induce death of cells. Further, in one or a plurality of embodiments, there is provided a method and a substance for inhibiting death of mature neurons induced by the amylospheroid. In one aspect, the present disclosure relates to a use of Na+/K+-ATPase ?3 as a binding target molecule of amylospheroid. In another aspect, the present disclosure relates to a method for suppressing death of mature neurons induced by the amylospheroid, including inhibiting protein-protein interaction between the amylospheroid and the Na+/K+-ATPase ?3, and the like.

Abstract: A binding partner, especially an antibody fragment that specifically recognizes an antigen-antibody immune complex between anti-THC and THC (tetrahydrocannabinol), is disclosed. The binding partner facilitates a non-competitive homogenous immunoassay for detection of cannabis use. A test kit comprising the binding partner is also described. Preferably the immunoassay is applied for roadside testing of saliva from suspected drivers.

Abstract: Described herein are the preparation and use of novel bromo-phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

Abstract: A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R?2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

Abstract: Embodiments of the invention are generally directed to compositions and methods of delivering one or more transgene to a target cell, such as a tumor cell, in a site-specific manner to achieve enhanced expression and to constructs and compositions useful in such applications. In certain aspects, expression from a therapeutic nucleic acid may be assessed prior to administration of a treatment or diagnostic procedure to or on a subject.

Abstract: The invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain of a KDR-1121 or DC101 antibody, an extracellular hinge domain, a T cell receptor transmembrane domain, and an intracellular domain T cell receptor signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are also disclosed.

Abstract: A method for regulating Src and its downstream signaling pathway which includes binding between Src and Na+/K+-ATPase is disclosed. The Na+/K+-ATPase/Src complex is a functional receptor for cardiotonic steroids such as ouabain. Also disclosed are Src inhibitors or activators which include either Na+/K+-ATPase or Src that interfere with the interaction between the Na/K-ATPase and Src, act via a different mechanism from ATP analogues, and is pathway (Na+/K+-ATPase) specific.

Abstract: This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Abstract: The invention provides, in certain embodiments, a method of detecting an indicator of renal injury or renal disease. The method entails assaying a urine sample for hematopoietic growth factor inducible neurokinin-1 (HGFIN), wherein the presence of HGFIN at an elevated level indicates the presence and/or degree of renal injury or renal disease, and/or the rate of loss of renal function. In other embodiments, the invention provides a method of detecting an indicator of systemic inflammation. This method entails assaying a biological sample for HGFIN, wherein the presence of HGFIN at an elevated level indicates the presence and/or degree of systemic inflammation. Also provided, are methods of determining progression of these conditions, as well as methods of determining subjects' response to treatment.

Abstract: The invention describes isolated mTOR-associated proteins (“mTOR-APs”) as well as isolated variants and fragments thereof and the isolated nucleic acids encoding them. The invention also describes vectors and host cells containing nucleic acid encoding an mTOR-AP polypeptide and methods for producing an mTOR-AP polypeptide. Also described are methods for screening for compounds which modulate mTOR-AP activity and methods for treating or preventing a disorder that is responsive to mTOR-AP modulation.

Abstract: Objective methods for diagnosing a predisposition to developing cancer, for example, bladder cancer, breast cancer, cholangiocellular carcinoma, CML, esophageal cancer, HCC, NSCLC, SCLC, osteosarcoma, pancreatic cancer, prostate cancer, renal cell carcinoma, soft tissue tumor and lymphoma, are described herein. In one embodiment, the diagnostic method involves determining an expression level of a WHSC1 or WHSC1L1 gene. The present invention further provides methods of screening for therapeutic agents useful in the treatment of WHSC1 or WHSC1L1 associated disease, such as a cancer, e.g., bladder cancer, breast cancer, cholangiocellular carcinoma, CML, esophageal cancer, HCC, NSCLC, SCLC, osteosarcoma, pancreatic cancer, prostate cancer, renal cell carcinoma, soft tissue tumor and lymphoma. The present invention further provides methods of inhibiting the cell growth and treating or alleviating symptoms of WHSC1 or WHSC1L1 associated diseases.

Abstract: Materials and methods related to diagnosing a clinical condition in a subject, or determining the subject's predisposition to develop the clinical condition, using a multi-parameter system to measure a plurality of parameters and an algorithm to determine a disease score.

Abstract: A method of screening a compound having a hypoglycemic effect (hereinafter referred to as “hypoglycemic compound”), a remedy for diabetes which contains a compound having a novel function mechanism, etc. More specifically speaking, a method of screening a hypoglycemic compound capable of binding to the ? subunit of a trimeric GTP-binding protein, a remedy for diabetes comprising a hypoglycemic compound, which is characterized by being capable of binding to the ? subunit of a trimeric GTP-binding protein, as the active ingredient, etc.

Abstract: Materials and methods for using combinations of metabolic syndrome and HPA axis biomarkers for monitoring major depressive disorder.

Abstract: Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.

Abstract: A PEPCK inhibitor can include identifying a molecule that has a size capable of fitting into and interacting with the PEPCK binding site and at least one of the following: (a) a first terminal substituent having co-planar atoms acting as metal ligands to the active site metal ion PEPCK; (b) at least one of an atom or substituent at positions 2 or 3 from the first terminal substituent includes a neutral carbon center or include an oxygen, sulfur, selenium, or other atom with similar physiochemical properties; (c) at least one of an atom or substituent at positions 2 or 3 from the first terminal substituent is devoid of an electropositive atom or substituents; or (d) a second terminal substituent opposite of the first terminal substituent, said second terminal substituent having an atom that is a hydrogen boding acceptor and/or is negatively charged.

Abstract: The present invention relates to methods for increasing the therapeutic efficacy of immunoglobulin G class 3 (IgG3) antibodies, immunoglobulin G class 3 (IgG3) antibodies with an improved therapeutic efficacy and the use thereof as a medicament, in particularly a medicament for immunotherapy. Specifically, the present invention relates to methods for increasing the therapeutic efficacy of an immunoglobulin G class 3 (IgG3) antibody comprising providing a mutated immunoglobulin G class 3 (IgG3) antibody, wherein the mutation, as compared to the parent immunoglobulin G class 3 (IgG3) antibody, comprises a replacement of the amino acid arginine (R) at position 435 in the CH3 domain with the amino acid histidine (H), and antibodies obtained by the present methods and their use as a medicament.

Abstract: Provided herein are zymogen activating molecules such as zymogen activating peptides, and methods of identifying and using these zymogen activating molecules such as zymogen activating peptides.

Abstract: An isolated polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 and an isolated polynucleotide encoding same are disclosed. A polynucleotide comprising a nucleic acid sequence capable of specifically hybridizing to the isolated polynucleotide and an isolated antibody comprising an antigen recognition domain which specifically binds the isolated polypeptide are also disclosed. Pharmaceutical compositions, methods of diagnosing and treating comprising same are also disclosed.

Abstract: Systems and methods are provided for sample processing. A device may be provided, capable of receiving the sample, and performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing multiple assays. The device may comprise one or more modules that may be capable of performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing the steps using a small volume of sample.

Abstract: Systems and methods are provided for sample processing. A device may be provided, capable of receiving the sample, and performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing multiple assays. The device may comprise one or more modules that may be capable of performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing the steps using a small volume of sample.

Abstract: The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

Abstract: Use of a polynucleotide encoding or a polypeptide comprising at least the extracellular IPT-3 and IPT-4 domains of hepatocyte growth factor receptor for the screening and/or development of pharmacologically active agents useful in the treatment of cancer, preferably a cancer with dysregulation of hepatocyte growth factor receptor.

Abstract: The invention pertains to a method of measuring A? protofibrils in a sample. The method includes the steps of (a) providing a labeled monoclonal antibody or fragment thereof that binds wildtype A? 42/40 protofibril and A?42/40 Arc protofibril and has no or little cross-reactivity to A? 42/40 monomers with an agent that generates a measurable signal, (b) contacting said labeled antibody or fragment thereof with the fluid or tissue having or suspected of comprising A? protofibrils, and (c) measuring the amount of protofibrils bound to the antibody by measuring the signal generated by the agent.

Abstract: A method and biomarker for evaluating metastasis, and an siRNA compound for inhibiting metastasis. The method of the present invention includes: providing a sample of a subject, which includes a normal tissue and a tissue to be detected; detecting expression of a biomarker of the normal tissue and the tissue to be detected, respectively, wherein the biological marker is SERPINA1; and comparing the expression of the biological marker of the normal tissue and the tissue to be detected. When the expression of the biological marker of the tissue to be detected is higher than the normal tissue, it represents that the subject is at a risk of suffering from metastasis.

Abstract: The present invention provides moieties that bind to the most membrane-proximal Ig-like domain of the ectodomain (D7) of vascular endothelial growth factor (VEGF) receptors, wherein the moieties antagonize the activity of the VEGF receptor.

Abstract: According to the invention, autoantibodies, the appearance of which is characteristic of neurological autoimmune diseases, especially multiple sclerosis, are detected and the respective autoantigens identified. It can further be shown that many of these autoantigens are expressed specifically in the brain. The identification of the autoantigens and autoantibodies is useful for diagnosis and treatment. A brain-specific expression of the autoantigens further emphasizes an important role of the antigens and antibodies in the origin and development of neurological autoimmune diseases.

Abstract: The present invention relates to a kit and a probe for detecting porous dental hydroxyapatite, comprising a protein capable of binding porous dental hydroxyapatite or a detector thereof. The invention also relates to a method for detecting a condition involving porous dental hydroxyapatite comprising detecting in or on a tooth or a sample of the tooth of a subject a protein bound to porous dental hydroxyapatite. The invention also relates to methods for detecting a hypomineralisation developmental dental defect or detecting intact and/or broken MIH enamel, and to a kit and method for removing a protein bound to porous dental hydroxyapatite.

Abstract: A method of determining kinetic parameters for a reversible molecular interaction between a ligand immobilized to a solid support surface and a binding partner to the ligand in solution, comprises sequentially, without intermediate regeneration or renewal of the immobilized ligand, flowing a plurality of fluid volumes containing different known concentrations of the binding partner over the solid support surface, monitoring the momentary amount of binding partner bound to the solid support surface related to time and solution concentration of binding partner and collecting the binding data, and determining the kinetic parameters by globally fitting a predetermined kinetic model for the interaction between the binding partner and the immobilized ligand to the collected binding data, which model allows for mass transport limitation at the solid support surface.

Abstract: Described are methods for identifying targets in RNA molecules based on differences in RNA secondary structure related to sequence variances between different allelic forms. Also described are methods for identifying or developing small molecules which can be used to modulate a target RNA by creation of protein-small-molecule-RNA complexes, as well as compositions which include such small molecules and methods of using those small molecules and compositions.

Abstract: Delivery proteins are provided for transferring a protein, antibody or foreign substance into a cell without impairing the function or structure thereof. Further, methods of transferring a foreign substance into a cell at a high efficiency by using the delivery protein or an envelope virus or inactivated envelope virus in combination with said delivery protein are provided. The inventors discovered that a protein containing a polypeptide having an affinity for a constituent of the envelope virus contributes to the efficient enclosure of the foreign substance in the envelope. Moreover, the inventors discovered that use of the delivery protein enables foreign substances to be included in an envelope virus or inactivated envelope virus and therefore makes it possible to efficiently transfer the substances into cells without damaging the physiological function thereof.

Abstract: Methods of identifying inhibitors of polypeptide-of-interests are provided.

Abstract: A carbonic anhydrase IX (CA IX) inhibitor which comprises a compound of general formula: R—NH—CX—NH—(CH2)n—Ar-Q-SO2—NH2 or a pharmaceutically-acceptable salt, derivative or prodrug thereof; wherein n=0, 1 or 2; Q is O or NH; X is O or S; and R comprises an organic substituent group.

Abstract: The present invention relates to a method for detecting protein-protein interactions in living cells, and more particularly, to a method for providing cells comprising a first construct and a second construct, wherein the first construct comprises a polynucleotide encoding a first fusion protein which comprises a bait protein, a first fluorescent protein and a CBD (cellulose-binding domain) protein, and wherein the second construct comprises a polynucleotide encoding a second fusion protein which comprises a prey protein and a second fluorescent protein so as to allow formation of inclusion bodies, and detecting interactions between the bait protein and the prey protein that are displayed by inclusion bodies, a method for isolating the prey protein bound to the bait protein using the cells comprising the constructs, the cells, and a kit for detecting protein-protein interactions, comprising the constructs.