Abstract: Methods and compositions suitable for modulating angiogenesis in a mammalian tissue are provided. Further provided are methods suitable for inhibiting metastasis and fibrosis in a mammalian tissue and for assessing the malignancy of colon cancer tumors.

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

Abstract: Detection of ZAP-70 expression provides important information about disease progression and overall survival in patients with chronic lymphocytic leukemia (CLL). The invention provides methods for diagnosing CLL in a subject, as well as methods for clearly distinguishing CLL patients with aggressive form of the disease. A consistent number of B cells from patient blood is isolated and lysed to release all of the intracellular ZAP-70 protein. The released ZAP-70 protein is subsequently extracted by immunomagnetic separation followed by detection with fluorescence immunosandwich assay. The ZAP-70 fluorescence signal is measured with Signalyte™-II spectrofluorometer. The VeriZAP™ assay is a simple, reliable, and reproducible method for quantitative detection of ZAP-70 in patient leukemic cells, and can be used as a prognostic test to distinguish indolent versus aggressive CLL patients.

Abstract: The present disclosure provides lysyl oxidase-like-2 (LOXL2) polypeptide binding agents, including, for example, antibodies that specifically bind a LOXL2 polypeptide; and further provides compositions comprising same. The binding agents can be used in various treatment and diagnostic methods, which are also provided.

Abstract: The present invention relates to a method of in vitro determining functional deficiencies in the lectin pathway of the complement system, the method comprises the steps of (a) diluting a mammalian sample of body fluid with a diluent comprising one or more inhibitors of the activation of the classical and the alternative pathways of the complement system; (b) activating the lectin pathway of the complement system in the sample obtained from (a); and (c) determining in the sample obtained from (b) the activation of one or more of the complement factors C3, C4, or one or more of the components of the C5-C9 complex. The invention furthermore relates to kits for use in connection with the above-mentioned method, the first kit comprises i) a first component comprising a carrier, one or more inhibitors of the classical and the alternative complement pathways and a diluent; and ii) a second component comprising one or more substances for activation of the lectin complement pathway and optionally an inert carrier.

Abstract: The present invention refers to the gene cluster and genes comprised by the gene cluster which are involved in the biosynthesis of griselimycin and methylgriselimycin and to the use of the gene cluster, genes comprised thereby and proteins encoded thereby for the production of antibiotic agents.

Abstract: The present invention provides an antibody capable of specifically recognizing and detecting the highly specific cancer marker with respect to the epithelial ovarian cancer, or a fragment of the antibody. The present invention provides an anti-?1,3-N-acetylglucosaminyltransferase 3 antibody for diagnosis of epithelial ovarian cancer, i.e., an antibody for detection of a glycosyltransferase ?1,3-N-acetylglucosaminyltransferase 3 as an epithelial ovarian cancer marker. The antibody recognizes, as an epitope, a part of a polypeptide of the enzyme consisting of the amino acid sequence represented by SEQ ID NO: 1.

Abstract: Compounds that bind to phosphatidylinositol-4-kinase III? (PI4KIII?) and inhibit the binding of PI4KIII? to its substrate and/or inhibit PI4KIII? activity may be used in the treatment and/or prevention of an autoimmune or inflammatory disorder, or organ or cell transplant rejection. A new assay for identifying compounds for use in treating and/or preventing those pathological conditions, which comprises measuring the inhibition of PI4KIII? activity, is also disclosed.

Abstract: The present invention relates to ADAMTS-1 and uses thereof. The present invention also relates to fragments of ADAMTS-1 and methods of inhibiting cell growth and metastasis. The present invention also provide methods of identifying inhibitors and activators relating to the function of ADAMTS-1.

Abstract: Disclosed herein is a method of identifying a tumor biomarker. In one example, a tumor biomarker is identified by obtaining a peripheral biological fluid sample from a subject with a tumor as well as a tumor sample and an adjacent non-tumor sample from such subject. A protein expression profile is detected in the peripheral biological fluid sample, tumor sample and adjacent non-tumor sample. The protein expression profiles of the peripheral biological fluid sample, tumor sample and adjacent non-tumor sample are then compared, wherein an increase in expression of a specific protein in the tumor sample and peripheral biological fluid sample but not in the adjacent non-tumor sample indicates that the specific protein is a biomarker of the tumor. Also disclosed herein is a gene profiling signature that can be used to diagnosis a subject with renal cell carcinoma (RCC) or to identify agents with therapeutic potential to treat RCC. Thus, methods of diagnosing a subject with RCC are disclosed.

Abstract: The present invention provides compositions and methods for treating obesity in a subject by administering an inhibitor of UBE2L6 or an activator of adipocyte triglyceride lipase to the subject.

Abstract: A method of screening compounds or molecules comprising the steps of: translating a sequence encoding the amino acid sequence comprising SEQ ID No. 29 in a translation system in the presence of a test compound or molecule; and analysing the translation product(s) for the presence of one or more of (a) a peptide comprising the amino acids Pro-Gly at the C terminus and a peptide comprising the amino acid Pro at the N terminus: or (b) a peptide comprising the amino acid sequence of SEQ ID No. 29.

Abstract: Some aspects of this invention provide a non-human animal model of autism. Some aspects of this invention provide a non-human animal model for diseases or disorders associated with an overexpression or a copy number variance of a Ube3a gene. Transgenic mammals and transgenic mammalian cells comprising an exogenous copy or exogenous copies of a ube3a protein-encoding nucleic acid sequence are also provided. Some aspects of this invention further provide methods for using the animal models, cells, and transgenic animals for identifying agents or interventions that can alleviate a pathogenic characteristic observed in the animal model, cell, or transgenic animal.

Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.

Abstract: Disclosed are mammalian tau proteases, as well as proteolytically-active fragments, variants, and mutants thereof. Also disclosed are polynucleotides and recombinant expression vectors that encode these polypeptides, as well as methods for producing such proteins in selected recombinant host cells, and for using the compositions in a variety of diagnostic and analytical assays.

Abstract: The present invention pertains inter alia to a method for analysing a sample comprising biomolecules, which comprises the following steps: A a) lysing the sample to provide a lysed sample and optionally clearing the lysed sample; b) contacting at least a portion of the lysed sample with a dry composition comprising reagents for performing the analytical method, thereby providing a reconstituted composition; c) performing an analytical method using the reconstituted composition; or B a) contacting the sample with a lysis solution thereby providing a lysis mixture; b) using the lysis mixture to reconstitute a dry composition comprising reagents for performing the analytical method, thereby providing a reconstituted composition; c) performing an analytical method using the reconstituted composition, wherein the reconstituted composition is optionally cleared and wherein subsequent to step b) at least one step is performed which supports the lysis of the sample.

Abstract: The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of ?-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.

Abstract: The present invention relates to methods for the diagnosis, prevention and treatment of heart disease or heart failure in a subject. The present invention also relates to methods for the diagnosis, prevention and treatment of atherosclerosis with vulnerable plaque in a subject. Furthermore, the present invention relates to methods for the diagnosis, prevention and treatment of cardiomyopathies resulting from Chagas disease.

Abstract: Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

Abstract: The present disclosure is directed to detecting colon disorders by measuring the expression of SHIP1 in a sample of PBMCs. One method includes the following steps, obtaining a sample including peripheral blood mononuclear cells (PBMCs) from a subject and determining whether SHIP1 is underexpressed in the PBMCs or lacks normal enzymatic activity. The present disclosure is also directed to a method of determining the expression of SHIP1 protein expression and SHIP1 enzyme activity in PBMCs. This method includes the following steps, obtaining a sample comprising PBMCs from a subject and determining the amount of SHIP1 in the PBMCs.

Abstract: The disclosure relates to compounds, peptides or peptidomimetics that inhibit, reduce or prevent protease activity and the use of these compounds, peptides or peptidomimetics to treat or prevent a condition. In particular the condition may be periodontal disease. The protease activity may be activity of a gingipain. The compounds, peptides or peptidomimetics of the invention may also be used in assays for the identification of protease inhibitors.

Abstract: The present invention relates to drug screening assays, therapeutic protocols and pharmaceutical compositions designed to target non-receptor tyrosine family kinases and components of the tyrosine kinase family signal transduction pathways. This includes primarily diseases or conditions associated with immune responses and can include treatment for cancers as well as various immune disorders. The invention reports a novel substrate SH2 domain docking mechanism apart from the kinase active site that is required for appropriate tyrosine phosphorylation by these tyrosine kinases.

Abstract: The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

Abstract: Compositions and methods comprising polynucleotides and polypeptides having dicamba decarboxylase activity are provided. Further provided are nucleic acid constructs, host cells, plants, plant cells, explants, seeds and grain having the dicamba decarboxylase sequences. Various methods of employing the dicamba decarboxylase sequences are provided. Such methods include, for example, methods for decarboxylating an auxin-analog, method for producing an auxin-analog tolerant plant, plant cell, explant or seed and methods of controlling weeds in a field containing a crop employing the plants and/or seeds disclosed herein. Methods are also provided to identify additional dicamba decarboxylase variants.

Abstract: We provide an antibody capable of binding to an intracellular PRL-I or PRL-3 polypeptide, in which the antibody is capable of binding to an epitope bound by antibody 269, antibody 223 or antibody 318. Such anti-PRL antibodies may be capable of binding to intracellular PRL-I or PRL-3. They may be suitable for use as therapies against cancer or metastasis thereof, or in clinical diagnosis to identify PRL-3 or PRL-I positive patients.

Abstract: This invention relates to a method of determining presence, amount and/or activity of a clostridial neurotoxin in a sample, the method comprising or consisting of the following steps: (a) bringing said sample into contact with a liposome, said liposome comprising (aa) at least one receptor on its outer surface, said receptor being capable of binding said neurotoxin and comprising or consisting of (i) a glycolipid and (ii) a peptide or protein; and (ab) a substrate in its interior, said substrate (i) being cleavable by the peptidase comprised in said neurotoxin and (ii) generating a detectable signal upon cleavage, said detectable signal preferably being generated by (1) the donor of a FRET pair, said donor exhibiting increased fluorescence upon cleavage by said peptidase, (2) a luminescent compound formed upon said cleavage, or (3) an enzyme formed upon said cleavage; and (b) determining whether an increase in signal occurs as compared to the absence of said sample, wherein such increase is indicative of the

Abstract: Methods for diagnosing cancer and monitoring treatment efficacy based on detecting the presence of increased levels of expression of satellite correlated genes.

Abstract: Provided herein are methods and kits for evaluating potential for invasiveness, metastasis, or recurrence of an epithelial cell cancer. In the methods the expression profile of giant obscurins is detected in a tissue sample of tumor cells or suspected tumor cells and assessed for giant obscuring expression level and distribution therein. Decreased levels or altered distribution of giant obscurins in the cells compared to a control non-invasive standard or to a sample taken at a different point in time is indicative of increased potential of at least one of the invasiveness, metastasis, or recurrence of the epithelial cell cancer. The kit comprises a detection reagent suitable for detecting the presence and distribution of giant obscurins or an amount of the gene product(s) encoding giant obscurins in cells of a tissue sample and instructions for using the detection reagent.

Abstract: Disclosed herein are methods of detecting and/or prognosing myocardial infarction by detecting a proteolytic fragment of caspase-3 such as the p17 fragment or the p12 fragment. The myocardial infarction can be STEMI or NSTEMI.

Abstract: Disclosed herein are novel synthetic prostate specific antigen (PSA)-targeted capture agents that specifically bind PSA. In certain embodiments, these PSA capture agents are biligand or triligand capture agents containing two or three target-binding moieties, respectively.

Abstract: This invention provides methods of making and using a fluorescent probe from the Sandercyanin protein as set forth in SEQ ID NO: 1 or SEQ ID NO: 2. In one embodiment, the invention provides a method of creating a fluorescent probe, comprising the steps of attaching a Sandercyanin moiety to a probe, wherein the probe is specific to a desired target.

Abstract: A diagnostic test system, apparatus and method for identifying individuals at risk for developing or having breast cancer by detection of at least one marker associated with increased breast cancer risk in nipple aspirate fluid is provided. A testing device for screening nipple aspirate fluid for the presence of biomarkers associated with breast cancer and methods of identifying individual biomarkers and biomarker panels for evaluating the risk that an individual has developed or will develop breast cancer by assaying nipple aspirate fluid is described.

Abstract: A method of treating neoplastic growth in a subject includes administering a glutamine synthetase (GS) inhibitor to the subject having neoplastic growth. A glutamine synthetase inhibitor may be administered in combination with thalidomide, lenalidomide and/or pomalidomide. Responsiveness to thalidomide, lenalidomide or pomalidomide therapy is determined by the expression levels of glutamine synthetase in neoplastic cells.

Abstract: Flow chambers are provided. In some embodiments, the flow chambers include an inner panel having at least one flow channel having an inlet/outlet opening on each end thereof formed therein, wherein the inlet/outlet openings are adapted to releasably receive a septum; one or more ports adapted to releasably receive a plug and for at least liquid communication with the at least one flow channel, and an outer frame that defines an outer portion of the at least one flow channel and that defines a perimeter of the flow chamber. In some embodiments, the flow chamber has overall dimensions of a standard multiwell plate and the at least one flow channel is located in a position that corresponds to a column location of the standard multiwell plate. Also provided are methods for producing the presently disclosed flow chambers and employing the same to assay biological features of cultured cells and/or tissues.

Abstract: Provided herein are methods for detecting an Aspergillus protease in a sample, diagnosing a subject with aspergillosis caused by an Aspergillus infection based on the presence of an Aspergillus protease in a sample, and methods of aspergillosis treatment that incorporate these diagnostic methods. In certain embodiments, the Aspergillus protease is Asp f2, and the Aspergillus infection is caused A. fumigatus, A. flavus, A. versicolor, A. niger, or A. terreus. Also provided herein are antibodies and kits for use in these methods, including novel antibodies specific for Asp f2.

Abstract: Methods for identifying subjects having, or at risk for developing, osteoarthritis or other cartilage degenerative conditions by measuring levels of expression of F-spondin are provided. Assays, kits and methods for determining and assaying the presence of F-spondin in individual patients are disclosed. Oligonucleotide probes and primers for use in the assays, kits and methods are described. Assays and methods are disclosed for identifying candidate compounds that modulate F-spondin levels of expression and/or function or for determining and evaluating an individual's response to drugs and therapeutic agents, are provided. The invention further relates to the modulation of F-spondin, particularly the inhibition of F-spondin, for increasing or stimulating bone formation and/or growth and mediating the alleviation of bone disease, disorders or conditions.

Abstract: Substrates are provided that include compounds suitable for detecting the activity of an enzyme such as a lysosomal storage enzyme where the substrates include: a sugar moiety; a linker moiety allowing the conjugation of sugar moiety with the remaining structure of the substrate; and two or more fatty acid chains or derivatives thereof at least one of which is sufficiently structured to provide improved solubility in aqueous or organic solvent systems. Also provided are methods for using substrates for detecting enzymatic activity using the inventive substrates.

Abstract: This application relates to methods of predicting susceptibility or likelihood of a clinically-relevant mannose-binding lectin (MBL)-deficient subject to develop a cardiovascular disease and/or cardiodiabetes. The methods include measuring MBL mass or concentration and, optionally, measuring MBL activity, at least one other biomarker and/or genotyping of MBL gene and its promoters; combining the information obtained into a calculated MBL-inclusive index score that involves mathematical transformation; and assigning a risk of cardiadiabetic status and clinical endpoints based on the determination and comparison of the MBL inclusive index to reference values from a population.

Abstract: Methods to assess biological enzyme activity directly in a complex clinical sample. To such a sample, e.g., plasma, an exogenous synthetic peptide substrate for an enzyme present in the sample and to be assessed is added. The sample then undergoes mass spectrometric immunoassay (MSIA) to monitor the mass spectral profile of the immuno-purified exogenous synthetic peptide substrate directly from the sample. Using the resulting profile, parameters such as enzyme activity and effect of enzyme modulators, including therapeutics administered to an individual for a condition involving the enzyme, may be determined.

Abstract: Methyl-lysine affinity reagents created by engineering the 3×MBT methyl-lysine binding domain repeat of lethal (3) malignant brain tumor-like protein 1 (L3MBTL1) are disclosed. In particular, the invention relates to affinity reagents and affinity chromatography media comprising the 3×MBT domain repeat and methods of using such affinity reagents in detection, purification, and proteomic profiling of methylated proteins and peptides.

Abstract: The present disclosure provides methods of treating cancer and modifying a cancer treatment for a cancer with an anti-EGFR drug by creating PRDX6 expression profiles and using the profiles to evaluate and optionally modify treatment. The present disclosure also provides assays and systems for assessing sensitivity of a cancer to an anti-EGFR therapy.

Abstract: This invention is based in part on the elucidation of new structural conformations and functions of the sodium/potassium adenosine triphosphate synthase (Na/K ATPase), and especially elucidation of new binding sites and interactions. The present invention provides practical applications of several surprising structural and functional relationships between Na/K ATPase and compounds which interact with Na/K ATPase. Disclosure of these structures and relationships provides insight and practical solutions to chemically affecting not only the Na/K ATPase interactions, but also regulators known to be upstream and downstream.

Abstract: Dual-functional nonfouling surfaces and materials, methods for making dual-functional nonfouling surfaces and materials, and devices that include dual-functional nonfouling surfaces and materials. The dual-functional surfaces are nonfouling surfaces that resist non-specific protein adsorption and cell adhesion. The dual-functional surfaces and materials include covalently coupled biomolecules (e.g., target binding partners) that impart specific biological activity thereto. The surfaces and materials are useful in medical diagnostics, biomaterials and bioprocessing, tissue engineering, and drug delivery.

Abstract: The present invention relates to methods of identifying gene targets, including methods of using ribonucleoprotein (RNP) immunoprecipitation-microarrays to identify cancer gene targets, such as subsets of RNP-associated mRNAs in breast cancer cell lines. Also presented, are ribonucleotide binding protein-associated biomarkers, panels or sets of ribonucleotide binding protein-associated biomarkers, methods and compositions comprising ribonucleotide-binding protein, associated nucleotides, nucleotide arrays, and kits, plus methods of using HuR-associated biomarkers to facilitate the diagnosis of, monitoring the disease status of, and the progression of treatment of breast cancers to facilitate the diagnosis of and monitoring the disease status or progression of treatment of breast cancers, including drug-resistant breast cancers.

Abstract: Methods and compositions are described for categorizing and treating autoimmune disease, using single cell network profiling (SCNP), where activation levels of one or more activatable elements are determined in single cells, with or without modulation, to categorize or determine treatment for the autoimmune disease.

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 disclosure provides lysyl oxidase-like-2 (LOXL2) polypeptide binding agents, including, for example, antibodies that specifically bind a LOXL2 polypeptide; and further provides compositions comprising same. The binding agents can be used in various treatment and diagnostic methods, which are also provided.

Abstract: The invention relates to carbon nanotube-containing composites as biosensors to detect the presence of target clinical markers, methods of their preparation and uses in the medical field. The invention is particularly suitable for the detection in patient biological specimens of bone markers and tissue markers. The biosensors of the invention include carbon nanotubes deposited on a substrate, gold nanoparticles deposited on the carbon nanotubes and, binder material and biomolecule deposited on the gold-coated carbon nanotubes. The biomolecule is selected to interact with the target clinical markers. The biosensor can be used as an in-situ or an ex-situ device to detect and measure the presence of the target clinical markers.

Abstract: A method for identifying a subject being at risk for or having a chronic inflammatory disease, fibrillinopathy, atherosclerosis, or coronary artery disease is provided. The method may include determining the concentration of GrA and/or GrB in a blood or serum sample from said subject; and comparing the concentrations to the corresponding concentration in a control sample, wherein an elevated concentration of GrA and/or GrB may be indicative of a chronic inflammatory disease, fibrillinopathy, atherosclerosis, or coronary artery disease. The method may further include identifying concentrations of fibrinogen, elastin and/or fibrillin.

Abstract: The invention relates generally to compositions and methods for detecting protease activity in a subject or a biological sample using activatable antibodies, and the use of these compositions and methods in a variety of diagnostic indications.