Abstract: A method for characterizing a carcinoma in a subject. The method comprises assaying a sample of a bodily fluid derived from the subject for extracellular PKA activity and comparing the activity to a reference value. In the assay, a reaction mixture is prepared comprising the previously unfrozen sample, a PKA peptide substrate, a phosphorylation agent, the prepared mixture is incubated, and phosphorylated substrate formed in the incubated mixture is detected. The reference value is the amount of phosphorylated substrate formed in a mixture under equivalent redox conditions for a sample of bodily fluid derived from a population of normal subjects of the same species.

Abstract: The present invention describes oligosaccharide sequences, which are specifically expressed by human tumors. The present invention is related to a method of determining an oligosaccharide sequence, which comprises a tumor specific terminal N-acetylglucosamine residue, in a biological sample, the presence of said sequence in said sample being an indication of the presence of cancer. The present invention provides antigenic substances comprising said oligosaccharide sequences in a polyvalent form and it further provides diagnostic agents, pharmaceutical compositions and cancer vaccines comprising said oligosaccharide sequences or substances binding to said oligosaccharide sequences. The present invention is also related to methods for the treatment of cancer.

Abstract: Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.

Abstract: The present invention provides, inter alia, methods for detecting whether a subject has an infection. These methods include (a) incubating a test sample from a subject suspected of having an infection with a labeled molecule, such as a labeled nucleoside analog, that is preferentially incorporated into a pathogenic microorganism for a period of time sufficient for the pathogenic microorganism to incorporate the labeled molecule; (b) removing any unincorporated labeled molecule from the test sample; and (c) detecting the labeled molecule within the pathogenic microorganism, if any, in the test sample, wherein the presence of labeled molecule within the pathogenic microorganism indicates that the subject has an infection.

Abstract: Described herein are compounds, compositions and methods for treatment of cancer. Also described are methods and uses for identifying subject with cancer that are suitable for treatment with the compounds, composition and methods are described herein. In one aspect of the present invention, there is provided a method of treating a subject having a cancer deficient in NMT2, comprising: administering to said subject an NMT inhibitor.

Abstract: Biomarkers for screening subjects for Parkinson's disease and providing companion diagnostic tools for therapies using LRRK2 modulators, and assays for screening compounds and compositions for modulation of LRRK2 activity.

Abstract: The invention provides compositions and methods to determine or detect the activity of enzymes, including phosphotransferases such as kinases (e.g., protein, lipid, and sugar kinases) and ATP hydrolases such as ATPases, e.g., HSP90, that employ ATP as a substrate and form ADP as a product by monitoring changes in ADP. Methods, kits and compositions for monitoring changes in metabolites such as ADP are disclosed.

Abstract: In order to identify a gene that can serve as an indicator for predicting the effectiveness of a drug treatment of cancer and to provide a novel method for predicting the effectiveness of a drug treatment targeting said gene, lung adenocarcinomas were subjected to whole-transcriptome sequencing. As a result, in-frame fusion transcripts between the KIF5B gene and the RET gene were identified. The KIF5B-RET gene fusions were detected in 6 out of 319 (2%) LADC specimens from Japanese individuals and 1 out of 80 (1%) LADC specimens from U.S.A. individuals. None of the seven subjects revealed known activating mutations such as EGFR, KRAS or ALK oncogenes; thus, said gene fusions were found to be responsible mutations (driver mutations) for oncogenesis. Since said gene fusions are considered to induce constitutive activation of RET tyrosine kinase protein, it was found that treatments with RET tyrosine kinase inhibitors are effective in patients with detection of said gene fusions.

Abstract: Described herein are methods for diagnosing melanoma or basal cell carcinoma based on mutations in the DDR2 gene. Further, a distinct subgroup of BRAF-mutated melanomas have somatic mutations in the DDR2 gene as well. Applications of this finding to routine diagnostics include the molecular stratification of melanoma, and the tissue identification of targetable DDR2 kinase mutations in routine formalin-fixed paraffin-embedded sections. Described herein are methods, compositions and kits related to the discovery that DDR2 mutations may be markers for melanoma generally, and BRAF-mediated melanoma in particular, opening up the possibility of dual therapy for melanoma by targeting both DDR2 and BRAF.

Abstract: Methods, processes, systems, and apparatuses are disclosed for predicting minoxidil response in the treatment of androgenetic alopecia based on colorimetric assay for sulfotransferase activity. In particular, SULT1A1 activity may be used as an indicator of minoxidil response. A genetic test for alleles of the SULT1A1 gene may be performed to provide a more personalized therapy.

Abstract: Methods for screening for agents that modulate the activation state, i.e., active growth or persistence, of Mycobacterium tuberculosis (Mtb), methods of treating an Mtb infection in a subject using agents identified by the screening methods, and methods for screening for a latent Mtb infection in a subject are disclosed. The screening methods involve contacting a Mtb sensor kinase with an agent to be tested, then detecting the response of the Mtb sensor kinase to modulating ligands or detecting changes in the oxidation state of the heme iron of the Mtb sensor kinase. The methods for treating an Mtb infection in a subject involve administering a therapeutically effective amount of an agent identified by the screening methods. The methods for screening for a latent Mtb infection in a subject involve detecting carbon monoxide or nitric oxide binding to heme iron of Mtb sensor kinases.

Abstract: The present invention provides, inter alia, methods for treating, preventing, or ameliorating the effects of a lymphoid malignancy, such as those associated with a mutated phosphatase and tensin homolog (PTEN) gene, or T-cell acute lymphoblastic leukemia (T-ALL). These methods include administering to a subject an effective amount of a phosphoinositide 3-kinase-delta (PI3K?) inhibitor and a phosphoinositide 3-kinase-gamma (PI3K?) inhibitor. The present invention also provides pharmaceutical compositions for treating the effects of a lymphoid malignancy. This invention further provides a method for identifying a subject who may benefit from co-treatment with a PI3K? inhibitor and a PI3K? inhibitor. This method includes determining from a sample of the subject whether the subject has a mutated PTEN gene. Additionally, this invention provides methods for identifying a compound that has both PI3K? and PI3K? inhibitory activity.

Abstract: Embodiments herein provide methods, apparatuses, and systems for detecting, monitoring, measuring, and/or characterizing the activity of phosphoproteins, such as tyrosine kinases (TKs) and downstream proteins in TK signal transduction pathways (e.g., TK pathway proteins). In various embodiments, the methods, apparatuses, and systems may use nanoparticles, such as quantum dots (QD), to detect and/or characterize the abnormally overactive TK signaling pathways that underlie tumorgenesis and tumor progression. In various embodiments, the QD-based methods, apparatuses, and systems may have a sufficiently high degree of sensitivity to enable the identification of new TK signaling pathway markers, for example for use in diagnosing, staging, monitoring, and/or prognosing cancers, or in evaluating the efficacy of cancer therapeutics.

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-4 Protein (HER4) protein are provided that are particularly advantageous for quantifying the HER4 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: An assay to detect ghrelin O-acyltransferase activity using an acrylodan-labeled peptide mimic of ghrelin that provides for high-throughput screening for ghrelin O-acyltransferase inhibitors and detection via high performance liquid chromatography. Alternatively, the assay for ghrelin acylation may be based on a synthetic peptide substrate that mimics the N-terminal sequence of ghrelin and has an environmentally-sensitive fluorophore attached to its C-terminal amino acid through chemoselective ligation.

Abstract: Methods to assay kinase activity are provided herein. The methods employ elemental analysis, including inductively charged plasma mass spectrometry (ICP-MS). The methods allow for the convenient and accurate analysis of post-translation modifications of substrates by kinase enzymes involved in post-translational modifications.

Abstract: The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor.

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: The invention provides a method for determining the activity of an inhibitor of a target protein that has a deleterious effect on cell growth. The principle of the claimed method is that a compound that inhibits the function of an overexpressed protein will relieve the detrimental effect of such overexpression in a concentration-dependent manner, thereby allowing the determination of the activity of the compound in inhibiting its target protein in live cells.

Abstract: The invention provides methods for determining whether a subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene comprising contacting isolated fibroblasts from the subject with a molecule or pool of molecules directed to the BRAF oncogene; and culturing the sample in the presence of the agent and determining whether BRAF oncogene expression by the cell is decreased and/or whether cells in the sample return to a less transformed phenotype, exhibit decreased cell proliferation and/or exhibit increased contact inhibition, any of which is indicative that the subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene.

Abstract: Enzyme substrates and associated technology of the present invention are provided. An enzyme substrate of the invention may comprise a biologically functional fluorescent dye and an enzyme-specific substrate moiety attached in such a way that the functionality of the functional dye is diminished. An enzymatic reaction may cleave at least a portion of the substrate moiety from the enzyme substrate to provide a more functional product dye. This product dye may be nonfluorescent or weakly fluorescent, in general, and relatively fluorescent, in a particular condition, such as when bound to a partner biological molecule or an assembly of partner biological molecules. An enzyme substrate of the present invention may thus be useful in fluorescence detection, and/or in any of a variety of useful applications, such as the detection of enzymatic activity in a cell-free system or in a living cell, the screening of drugs, or the diagnosis of disease.

Abstract: Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.

Abstract: The present invention provides methods for the preselection of a subject for therapeutic treatment with an agent based on modulated levels of hypoxia in cancerous cells in the subject. In one embodiment, the invention provides methods for the preselection of a subject for therapeutic treatment with an agent based on modulated levels of lactate dehydrogenase (LDH) in a cell, e.g., a cancerous cell. The invention also provides methods for treating cancer in a subject by administering an effective amount of an agent to the subject, wherein the subject has been selected based on a modulated level of hypoxia. The invention further provides kits to practice the methods of the invention.

Abstract: Methods detecting covalent lysine modifications in DNA polymerases are provided. These methods are particularly useful in determining the extent and location of a lysine modification in a DNA polymerase.

Abstract: A novel therapeutic agent for ectopic pregnancy having a therapeutic effect for ectopic pregnancy, especially unruptured ectopic pregnancy, and a novel method of screening a therapeutic agent for ectopic pregnancy are disclosed. The therapeutic agent for ectopic pregnancy contains as an effective ingredient a suppressor of brain-derived neurotrophic factor (BDNF) and/or of brain-derived neurotrophic factor receptor (TrkB). The method of screening a therapeutic agent for ectopic pregnancy includes measuring the kinase activity of TrkB in the presence of a test substance and the kinase activity of TrkB in the absence of the test substance; and selecting the test substance which decreases the kinase activity of TrkB.

Abstract: A method for determining the ischemic levels of suspected stroke patients comprises the following steps: Taking a blood sample from the suspected stroke patients, Determining the concentration of Glycogen Phosphorylase BB (GPBB) in this blood sample

Abstract: The object of the present invention is to provide a method of determining the dose and/or administration of statins to a patient suffering from a cardiovascular disease. The object is achieved by the method of determining the dose and/or administration of statins to a patient suffering from a cardiovascular disease comprising Step (1) of measuring the intracellular SmgGDS expression level of a patient suffering from a cardiovascular disease before and after administration of statin; and Step (2) of determining the type and/or the dose of statin for the patient in reference to the SmgGDS expression level measured in the Step (1).

Abstract: A diagnostic test kit for detecting the presence or quantity of an enzyme or enzyme inhibitor is provided. The diagnostic kit utilizes substrate conjugates to facilitate the detection of the enzyme or enzyme inhibitor via direct detection of the substrate and/or a product formed in an enzyme-catalyzed reaction of the substrate. The substrate conjugates include a substrate joined (e.g., covalently bonded, physically adsorbed, etc.) to a reporter. In one embodiment, for example, a peptide, protein, or glycoprotein substrate is joined to a reporter (e.g., dyed latex particle). In this embodiment, the substrate provides a cleavage target for an enzyme. Specifically, upon contacting the substrate conjugate, the enzyme catalyzes a reaction with the substrate and forms a product conjugate that includes the product of the enzyme catalyzed reaction joined to the reporter. The signal exhibited by the reporters may then be used to indicate the presence or quantity of an enzyme or enzyme inhibitor within the test sample.

Abstract: Methods for multiplexed delivery of agents to a solid tissue in vivo followed by assessment of efficacy with mass spectrometry are described.

Abstract: Described are compounds capable of modulating (a) the biological activity of ADP-dependent glucokinase (ADPGK) and/or glycerol-3-phosphate dehydrogenase (GPD2) or (b) the expression of the gene encoding ADPGK or GPD2 for use in treating a disease (a) associated with aberrant cell proliferation, e.g., a neoplasm, or (b) of the immune system, e.g., an autoimmune disease.

Abstract: An immobilized enzymatic reactor can include a wall defining a chamber having an inlet and an outlet; a solid stationary phase covalently linked to an enzyme and disposed within the chamber; and a pressure modulator in fluid communication with the chamber and adapted to support continuous flow of a liquid sample comprising a polymer analyte through the inlet, over the solid stationary phase, and out of the outlet under a pressure between about 2,500 and 35,000 psi. In one example, the solid stationary phase includes inorganic/organic hybrid particles in an ultra performance liquid chromatography system, the enzyme is a protease, and the polymer analyte is a polypeptide. The immobilized enzymatic reactor can prepare an analyte for applications such as for hydrogen deuterium exchange mass spectrometry.

Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

Abstract: The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.

Abstract: This invention relates to an isolated nucleic acid fragment encoding a diacylglycerol acyltransferase. The invention also relates to the construction of a chimeric gene encoding all or a portion of the diacylglycerol acyltransferase, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the diacylglycerol acyltransferase in a transformed host cell.

Abstract: Provided herein is a novel mTOR-comprising complex, mT-ORC3, which comprises mTOR and the Ets transcription factor TEL2. Specific mTORC3 binding agents and modulating agents are provided, along with kits and methods for the detection of mTORC3. Methods of modulating the activity of mTORC3 or modulating cell growth and/or survival are also provided. Further provided are methods for screening for mTORC3 binding agents and for mTORC3 modulating agents. Various methods of diagnosis and treatment are further provided.

Abstract: The present invention relates to drug discovery methods, particularly methods for assaying compounds for activity as Aurora kinase inhibitors. This invention also relates to a pharmacophore describing compounds that are able to promote a conformational change in the protein AuroraB and whose binding constant for the two-step process is given as Ki*. Finally, this invention also relates to compounds having the features of the pharmacophore.

Abstract: A transformed yeast cell includes: a nucleic acid sequence coding for a reverse transcriptase; a reverse transcription indicator; a nucleic acid sequence coding for deoxycytidine kinase (dCK); and at least one nucleic acid sequence coding for nucleoside transporter. Methods for screening a compound with the ability to inhibit reverse transcription and for predicting the sensitivity of a reverse transcriptase to a NRTI compound, particularly a reverse transcriptase derived from a virus infecting a subject using the transformed Yeast cell are also described.

Abstract: The present disclosure relates to methods for detecting and measuring the activity of lecithin:cholesterol acyltransferase (LCAT) in solution (e.g. serum, plasma, cell culture media, aqueous solution) with fluorescent sterol substrates. The present disclosure also relates to a method for evaluating efficacy of a therapeutic agent for stimulating LCAT and for determining endogenous LCAT activity in a patient. Also disclosed are kits that are used to carry out the aforementioned methods and methods.

Abstract: The invention provides a method and system for developing and using diagnoses of one or more underlying health affections in humans or an animal specie using a plurality of biomarkers. A target one or more affections are defined and a set of biomarkers is selected. An index is computed based on the measured levels of the biomarkers. The biomarkers levels are discretized, and each discrete value is multiplied by a corresponding coefficient. The index scale is divided into ranges that are matched with health statuses. A subject's health affection status is subsequently determined by measuring the level of each biomarker in the set, computing the index and matching the index value to the predefined index scale.

Abstract: The present invention provides new immunological compositions and vaccines comprising selected M. tuberculosis antigens and antigenic peptides as well as nucleic acids encoding said antigens for use in the prevention, prophylaxis and treatment of mycobacterial infection, especially tuberculosis. In particular the invention provides recombinant BCG based vaccines in which one or more of the selected M. tuberculosis antigens are over expressed. The invention further provides isolated peptides for use in methods for diagnosing, characterizing, or classifying mycobacterial infections.

Abstract: The invention provides a method and system for developing and using diagnoses of cancer and sepsis in canine subjects using Thymidine kinase (TK), c-reactive protein (CRP), and C-type natriuretic peptide (CNP) as biomarkers. The level of each biomarker may be measured and an index may be computed using a two- or a three-biomarker method. The invention provides a predefined scale for the index where each range of the index matches a health condition. The latter allows a practitioner, through computing an index value of a patient, to determine the health status of the patient by comparing the index value to the predefined scale.

Abstract: The present invention provides materials and methods for treating Alzheimer's disease and other tau related neurodegenerative disorders. A tau kinase, Brain Derived Tau Kinase (BDTK) is provided. BDTK can cause hyperphosphorylation of tau protein, which leads to formation of neurofibrillary tangles, which are implicated in the degenerative symptoms of Alzheimer's and other neurodegenerative disorders. Methods of diagnosis and treatment based on the discovery of this novel tau kinase are also provided.

Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.

Abstract: Alkyl amines act to release formaldehyde cross-linking that occurs in biological samples. Thus, contacting alkyl amines to formaldehyde fixed samples is a useful way to render biological components of the samples, including nucleic acids or proteins, more accessible to detection and characterization.

Abstract: Described herein, inter alia, are compositions and methods for detecting levels of AXL and GAS6.

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: Methods of treating a disease in a subject are provided comprising administering to the subject an amount of an agent which reduces, or prevents, interaction of a G?? with a pi 110? effective to treat the disease. Methods are also provided for identifying an inhibitor of interaction between a G?? and a ?110?. Compositions are provided comprising a peptide comprising amino acid residues having the KAAEIASSDSANVSSRGGKKFLPV (SEQ ID NO:6).

Abstract: The present invention provides methods for the preselection of a subject for therapeutic treatment with elesclomol based on modulated levels of hypoxia in the subject. In one embodiment, the invention provides methods for the preselection of a subject for therapeutic treatment with elesclomol based on modulated levels of lactate dehydrogenase (LDH). The invention also provides methods for treating cancer in a subject by administering an effective amount of elesclomol to the subject, wherein the subject has a modulated level of hypoxia. The invention further provides kits to practice the methods of the invention.

Abstract: A method is disclosed for classifying and distinguishing between type I and type II kinase inhibitors. The method involves the use of non-linear optical techniques, in particular second-harmonic generation (SHG) to identify conformational changes in kinase proteins obtained from known type I or type II inhibitors. The method further involves deducing the manner of binding of unknown inhibitors by comparison with the signal changes produced by known ligands. The method is also applied to comparing the conformational changes induced by the binding of generic and branded kinase inhibitor drugs to a target kinase.

Abstract: The invention relates to a method for selecting compounds having a modulating effect on the activation state of a dimer of VFT-domain proteins expressed in cell membranes present in a measuring medium, said dimer consisting of a first protein and of a second protein, said proteins being identical or different, wherein this method comprises the following steps: (a) labeling the first and second proteins in the N-terminal portion of their VFT domains with the members of a pair of FRET partners, the Förster radius (R0) of said pair being between 20 and 55 ?; (b) measuring the FRET signal in the absence and in the presence of the test compound within a predetermined time window; (c) selecting the test compound as a modulating compound if a difference in FRET signal in the absence and in the presence of test compound is measured in step (b). The invention can be used in the search for new medicaments and new taste modulators.