Abstract: Methods, kits, and active ingredients for diagnosing or treating arthritis or a degenerative disease of the skeletal system, or for selection of subjects for therapy. The methods for diagnosing arthritis involve the detection of an autoantibody, which is associated with arthritis, or excluding the presence of an autoantibody against collagen II. The methods for diagnosing a degenerative disease of the skeletal system, involve the detection of an autoantibody against thrombospondin-4 or COMP. The kits contain a detection agent for an autoantibody and can be used for diagnosing arthritis or a degenerative disease of the skeletal system. The active ingredient can be used for treating or preventing autoimmune-associated arthritis.

Abstract: The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.

Abstract: The present invention relates to MRI based imaging. In particular, the present invention provides MRI contrast agents targeted to a HaloTag protein with tunable relaxation properties thereby providing optimal relaxivity for low field strength imaging and the other optimal relaxivity for high field strength imaging. Moreover, the MRI contrast agents are used to detect gene expression (of a gene of interest) in real time in vivo, to detect changes in gene expression (of a gene of interest) over time in, for example, an individual organism, to detect gene expression changes (of a gene of interest) in response to therapeutics, in cell labeling for MR imaging, in clinical diagnostics, and in theranostics.

Abstract: The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).

Abstract: A biosensor according to the present invention includes a first base material having an insulating surface; an adhesive layer located on the insulating surface of the first base material; and an electrode system and wiring sections fixed to the first base material via the adhesive layer. The electrode system includes top electrode layers and bottom electrode layers, and the bottom electrode layers are formed of a material having a higher conductivity than that of the top electrode layers; the electrode system includes a working electrode and a counter electrode, and also includes an enzyme reaction section located on the working electrode, the enzyme reaction section containing an enzyme and an electron acceptor; and the bottom electrode layers and the wiring sections are integral with each other.

Abstract: Disclosed is a novel method for detecting interactions of biomolecules. More particularly, the disclosed method includes (a) preparing a cell comprising (i) a first construct comprising a bait, a first labeling material and a translocation module; and (ii) a second construct comprising a prey and a second labeling material; (b) detecting the distribution of the first construct and the second construct in the cell. the present invention provides a method capable of detecting bindings and interactions occurring in a living cell in real time, and a method for screening a material that alters the binding and the interaction. The method of the present invention overcomes the disadvantages including inaccuracy and complexity of existing biomaterial interaction detection techniques. By labeling both constructs to promote accuracy, the present invention provides a novel real-time, antibody-free analysis.

Abstract: The invention provides a method of determining the prognosis of cancer in a subject. The method comprises (a) obtaining a sample from the subject, (b) analyzing the sample for the expression level of a carboxypeptidase E (CPE) splice variant, and (c) correlating the expression level in the sample with the prognosis of cancer in the subject. The invention further provides a method of diagnosing cancer, methods of treatment, kits for detecting mRNA expression of a CPE-?N, and inhibitors of CPE-?N and compositions thereof.

Abstract: The present invention is related to compositions and methods to stimulate the immune system. For example, antigen-specific antibodies may be produced by stimulating B cell populations with specific antigenic compounds, such as an adjuvant comprising a macromolecule capable of activating a Toll-Like receptor (TLR). For example, a BCR adapter IgM (BCRAM) is described to exemplify delivery of autoantigens to polyclonal B cell populations resulting in immunoactivation by TLR activation. Alternatively, a compound is described that inhibits TLR activation.

Abstract: The present invention describes an unbiased catalytic tagging system to search for target substrates. Identification of substrates for specific baits is accomplished by utilizing an orthogonal system consisting of an E1 activating enzyme, an E2 ubiquitin-like conjugating enzyme, and baits that are fused to the E2 ubiquitin-like conjugating enzyme. The present invention thus reveals important mutually antagonistic substrates of specific baits.

Abstract: Disclosed herein are mutated RAF and KSR nucleic acids and polypeptides. Also disclosed are methods of using the mutated RAF and KSR to inhibit the dimerization of RAF/RAF and RAF/KSR. Also disclosed are methods of using the mutated RAF and KSR to screen for inhibitors of dimerization.

Abstract: The present invention provides method and compositions for detecting target molecules present on cells and tissues. In particular, the methods involve adding primary antibodies such as scFv-targeted lactamase that are directed against a target of interest (e.g., cancer markers) to a tissue sample, followed by adding a lactam-containing compound and finally a lactamase reporter system. In some preferred embodiments, the lactamase reporters are fluorescent reporters that bind to the test tissue. In some particularly preferred embodiments, the test tissue contains at least once cancer cell and/or at least one cancer-associated marker.

Abstract: Methods and genetic constructs are provided for detecting the binding of nuclear hormone receptors to a coactivator/corepressor. The methods employ enzyme fragment complementation using fragments of ?-galactosidase as the detection system. Cells are transformed to express the large fragment of ?-galactosidase fused to a member of the complex with NHR for initiation of transcription and have it localized in the nucleus and to express the small fragment of ?-galactosidase fused to the nuclear hormone receptor for binding to the member upon stimulation with a ligand.

Abstract: The present disclosure encompasses systems, and their methods of use, for detecting a target analyte. The systems include a first and second oligonucleotide probe that associate together to form a complex that binds to a target analyte; a cleavable reporter molecule that binds to the complex; and cleaving agent.

Abstract: Provided are methods of diagnosing lung cancer, particularly at an early stage, such as stage I, by detecting the presence and/or amount of at least four biomarkers of lung cancer in a sample from a subject as well as determining the number of smoking pack years for the subject. The methods and biomarkers may be used to develop an accurate prognosis for a patient having lung cancer or suspected of having lung cancer or accurately diagnose a subject having or suspected of having lung cancer. The methods and biomarkers may be used to identify and/or classify a patient as a candidate for lung cancer treatment therapy.

Abstract: Disclosed are compositions and methods for the labeling of two or more targets with different labels. Specifically, disclosed are compositions for biotin and the protection of biotin within multilabel assays which employ the biotin-biotin binding protein binding relationship for each distinct label in relation to targets such as nucleic acids, polypeptides, antibodies or cells. These multilabel assays are enabled through the use of biotin with desthiobiotin, orthogonal protecting schemes for biotin, or a combination of the approaches.

Abstract: Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

Abstract: Disclosed are DNA polymerases having increased reverse transcriptase efficiency relative to a corresponding, unmodified polymerase. The polymerases are useful in a variety of disclosed primer extension methods. Also disclosed are related compositions, including recombinant nucleic acids, vectors, and host cells, which are useful, e.g., for production of the DNA polymerases.

Abstract: Probe 1 for detection and quantification of nitric oxide, which comprises two subunits 21 and 22 of soluble guanylate cyclase 2 and cGMP-visualization probes 3 respectively connected with each subunit, wherein the cGMP-visualization probe generates signal upon recognizing guanosine 3?,5?-cyclic monophospate.

Abstract: The present invention provides the TWEAK receptor and methods for identifying and using agonists and antagonists of the TWEAK receptor. In particular, the invention provides methods of screening for agonists and antagonists and for treating diseases or conditions mediated by angiogenesis, such as solid tumors and vascular deficiencies of cardiac or peripheral tissue.

Abstract: The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform-selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.

Abstract: The present invention relates to human Janus Kinase 3 (JAK3) and JAK3-like binding pockets. The present invention provides a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen for and design compounds, including inhibitory compounds, that bind to JAK3 protein or JAK3 protein homologues, or complexes thereof. The invention also relates to crystallizable compositions and crystals comprising JAK3 kinase domain and JAK3 kinase domain complexes with AMP-PNP.

Abstract: Provided is a therapeutic method exclusively targeting an amyloid ? protein (A?) having a specific turn structure of A?. Specifically provided is an antibody which specifically recognizes an amyloid ? having a turn structure at amino acids positions 22 and 23. Also provided are a medicinal composition comprising, as the active ingredient, an antibody specifically recognizing a toxic conformer of amyloid ?, an assay kit for a toxic conformer of amyloid ?, a diagnostic for Alzheimer's disease, etc.

Abstract: The invention relates to an ADP binding molecule comprising a polypeptide, said polypeptide comprising amino acid sequence corresponding to at least amino acids 11 to 310 of SEQ ID NO:1, wherein said polypeptide comprises a substitution relative to SEQ ID NO:1 at amino acid C287, and wherein said polypeptide comprises a further cysteine residue for attachment of at least one reporter moiety, and wherein said polypeptide has at least 68% sequence identity to SEQ ID NO:1 at the amino acid residues corresponding to those shown in column III of table A.

Abstract: The present invention provides and includes monoclonal antibodies (MoAbs or mAbs) specific or preferentially selective for PCBP-1 antigens, hybridoma lines that secrete these PCBP-1 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect PCBP-1 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble form of PCBP-1. The present invention further includes chimeric and humanized antibodies, processes for producing monoclonal, chimeric, and humanized antibodies using recombinant DNA technology, and their therapeutic uses, particularly in the treatment or diagnosis of cancer progression. The present invention further includes methods and kits for the immunodetection and immunotherapy of cells for samples which express PCBP-1 antigens.

Abstract: The present invention relates to a succinic acid-producing mutant microorganism that is able to utilize sucrose and glycerol simultaneously as carbon sources. More particularly, the present invention relates to a succinic acid-producing mutant microorganism that is able to utilize sucrose and glycerol simultaneously for succinic acid production, the mutant organism being obtained by relieving the mechanism of sucrose-mediated catabolite repression of glycerol in a succinic acid-producing microorganism. As described above, when the succinic acid-producing mutant microorganism is cultured, it utilizes sucrose and glycerol simultaneously so that succinic acid can be produced with high productivity in a maximum yield approaching the theoretical yield while the production of byproducts is minimized. In addition, according to the present invention, various reduced chemicals which have been produced in low yields in conventional methods can be more effectively produced.

Abstract: This invention provides general methods for selective labeling of proteins on their N-termini with synthetic peptides. The methods of this invention can be applied to the global proteomic profiling of complex mixtures of proteins and polypeptides.

Abstract: Disclosed are methods useful in multiplex cell-based assays for compound screening employing imaging instrumentation. The methods described herein offer high content information relating to the biological potency of test agents, off-target effects and cellular toxicity of potential drug candidates.

Abstract: This invention comprises the novel compounds of formula (I) wherein n, m, t, R1, R2, R3, R4, L, Q, X, Y, Z and have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

Abstract: The present invention provides an assay for the identification of agents which can modulate TOR-mediated phosphorylation of substrate proteins. The assays of the invention utilize substrate proteins whose amino acid sequence contains the Ser/Thr motif recognized by TOR. Naturally occurring TOR which may be used in the methods of the invention include TOR isolated from a variety of species, particularly mammalian tissues.

Abstract: Described herein are variants of H. jecorina CBH I, a Cel7 enzyme. The present invention provides novel cellobiohydrolases that have improved thermostability and reversibility.

Abstract: The invention relates, in part, to monovalent streptavidin compositions. The invention also relates to methods of preparing and using monovalent streptavidin compositions. In some aspects of the invention, the compositions are monovalent streptavidin with a single femtomolar biotin-binding site.

Abstract: Provided is a novel ubiquitin ligase which has linear polyubiquitination activity and can be efficiently expressed and purified. It was found out that a complex of (a) a protein having a part of HOIP and at least having a UBA region and a RING-IBR-RING region thereof, and (b) One or more kinds of proteins which individually form a complex with the above (a) is a novel ubiquitin ligase which has linear polyubiquitination activity and can be efficiently expressed and purified.

Abstract: The present invention relates to methods of identifying candidate compounds for the treatment of leukemia and diagnostic methods based on histone methylation and HoxA5 promoter activity.

Abstract: The invention describes a method for assaying HCV NS3 protease activity using an NS3•4A protease molecule. The invention also provides a method for screening and identifying modulators of NS3 protease.

Abstract: The fusion protein comprising (1) a first region comprising the amino acid sequence of SEQ ID NO: 18 and (2) a second region comprising an amino acid sequence for a polypeptide containing at least one cysteine residue for binding to other useful compound via the thiol group can be modified by chemical modification, and thus has a high catalytic ability for a luminescence activity and is highly available for general purposes.

Abstract: An exemplary embodiment may be directed to a fluorescence polarization assay that screens compounds or agents for their affinity to hematopoietic prostaglandin D synthase (H-PGDS) based on their ability to displace a fluorophore-containing detection analyte bound to an enzyme comprising the primary amino acid sequence of H-PGDS. Another exemplary embodiment utilizes an enzyme having a maltose binding protein amino-acid sequence fused with an N-terminus of the enzyme.

Abstract: The invention relates to the use of carbamoyl synthetase 1 (CPS 1) as a humoral biomarker in in vitro methods for early diagnosis and detection, progress prognosis, the evaluation of the severity, and the progress evaluation of tumor diseases and chronic inflammatory intestinal diseases.

Abstract: The present invention relates to variants of Glycoside Hydrolase family 53 galactanases, e.g., variants of the galactanases from strains of Yersinia, Aspergillus, Humicola, Meripilus, Myceliophthora, Thermomyces, Bacillus, Bifidobacterium, Cellvibrio, Clostridium, Pseudomonas, Thermotoga, or Xanthomonas.

Abstract: Disclosed herein are methods, systems and kits to measure the presence and/or activity of recombinant polypeptides comprising a modification.

Abstract: The present disclosure relates to chimeric bacteriophage lysins useful for the identification and/or reduction of staphylococcal populations. For example, a chimeric bacteriophage lysin was engineered and shown to effectively kill all strains of staphylococci tested including antibiotic resistant methicillin-resistant S. Aureus and VISA.

Abstract: A mutant hydrolase optionally fused to a protein of interest is provided. The mutant hydrolase is capable of forming a bond with a substrate for the corresponding nonmutant (wild-type) hydrolase which is more stable than the bond formed between the wild-type hydrolase and the substrate. Substrates for hydrolases comprising one or more functional groups are also provided, as well as methods of using the mutant hydrolase and the substrates of the invention. Also provided is a fusion protein capable of forming a stable bond with a substrate and cells which express the fusion protein.

Abstract: A development of an Artificial SUMO Ligase (ASUL) to increase the ability of Ubc9 to interact with the SUMO target protein, therefore increasing the rate of SUMOylation of the target and a net increase in the total amount of SUMOylated target protein in the cell is described herein. The method of the present invention involves the creation of a protein fusion between a protein domain known to interact with the target protein to be SUMOylated (ID) and the SUMO conjugating enzyme Ubc9. Compositions and methods involving an ASUL comprising a fusion of the N-terminal domain of influenza A virus non-structural protein (NS1) and Ubc9 is also described.

Abstract: The present invention provides a method for detecting autoprocessed, secreted PCSK9, a protein involved in cholesterol homeostasis, and for effectively identifying compounds that inhibit autocleavage and secretion from cells. The disclosed method involves the insertion of an epitope tag into a PCSK9 expression construct immediately C-terminal to the pro domain ending at an amino acid residue corresponding to Q152 of human PCSK9. Upon autoprocessing, the epitope tag is exposed and capable of recognition by anti-epitope antibodies or other suitable identification system, allowing for the selective and exclusive identification and/or quantification of processed PCSK9. The present disclosure thus advances the goal of providing enabling technology to the art for the effective identification of therapeutics effective in combating coronary heart disease.

Abstract: The present disclosure relates to methods of developing terpene synthase variants through engineered host cells. Particularly, the disclosure provides methods of developing terpene synthase variants with improved in vivo performance that are useful in the commercial production of terpene products. Further encompassed in the present disclosure are superior terpene synthase variants and host cells comprising such terpene synthase variants.

Abstract: Described herein are variants of H. jecorina CBH I, a Cel7 enzyme. The present invention provides novel cellobiohydrolases that have improved thermostability and reversibility.

Abstract: A mutant hydrolase optionally fused to a protein of interest is provided. The mutant hydrolase is capable of forming a bond with a substrate for the corresponding nonmutant (wild-type) hydrolase which is more stable than the bond formed between the wild-type hydrolase and the substrate and has at least two amino acid substitutions relative to the wild-type hydrolase. Substrates for hydrolases comprising one or more functional groups are also provided, as well as methods of using the mutant hydrolase and the substrates of the invention. Also provided is a fusion protein capable of forming a stable bond with a substrate and cells which express the fusion protein.

Abstract: Methods and compositions are provided for assaying for enzymes capable of releasing an enzyme donor fragment (ED) conjugated to a nucleic acid strand bonded to a surface. Conveniently, the beads are magnetic allowing segregation of the beads during the determination. Upon addition of enzyme acceptor fragment (EA) and substrate to the assay mixture, the method allows for discrimination between ED free in solution and ED bound to the bead. The complexing of ED and EA provides an active ?-galactosidase enzyme. The method permits the assay of any substance involved in a pathway that can result in a reaction releasing the ED.

Abstract: The present invention relates to a kinase labelled at an amino acid naturally present or introduced in the P-loop of said kinase, wherein said labelling is effected at a free thiol or amino group of said amino acid and said label is (a) a thiol- or amino-reactive fluorophore sensitive to polarity changes in its environment; or (b) a thiol-reactive spin label, an isotope or an isotope-enriched thiol- or amino-reactive label, such that said fluorophore, spin label, isotope or isotope-enriched label does not inhibit the catalytic activity and does not interfere with the stability of the kinase. The invention furthermore relates to a method of screening for kinase inhibitors, a method of determining the kinetics of ligand binding and/or of dissociation of a kinase inhibitor and a method of generating mutated kinases suitable for the screening of kinase inhibitors using the kinase of the present invention.

Abstract: This invention relates to a method for assessing risk of prostate cancer. Specifically, it relates to utilizing both Pro108 and Prostate Specific Antigen (PSA) in combination to determine the risk of prostate cancer. In addition, it is directed to a method for assessing risk of ovarian, colon, breast or stomach cancer utilizing Pro108 or specific antibodies to Pro108. The invention provides isolated anti-prostate, ovarian, colon, breast or stomach cancer antigen (Pro108) antibodies that bind to Pro108 on a mammalian cell in vivo. The invention also encompasses compositions comprising an anti-Pro108 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Pro108 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Pro108 antibodies. The invention encompasses a method of producing the anti-Pro108 antibodies.

Abstract: A target and methods for specific binding and inhibition of RNA polymerase from bacterial species are provided, including methods for identifying agents that bind to a bacterial RNA polymerase, and that inhibit an activity of a bacterial RNA polymerase, through interactions with a bacterial RNA polymerase homologous switch-region amino-acid sequence. The methods can include preparation of a reaction solution comprising the compound to be tested and an entity containing a bacterial RNAP homologous switch-region amino-acid sequence, and detection of binding or inhibition. Applications in control of bacterial gene expression, control of bacterial viability, control of bacterial growth, antibacterial chemistry, and antibacterial therapy are also provided.