Abstract: It is disclosed herein that isolated lymphocytes, such as human B-cells and CD4+ T-cell can be used to determine an amount of lymphocyte-associated anthrax lethal toxin activity present. Methods of using isolated lymphocytes to identify anthrax therapeutic agents and to determine the efficacy of a potential anthrax therapeutic are disclosed. Methods are also provided for diagnosing and treating anthrax infections.

Abstract: The invention relates to compounds of formula (I) R1 is methyl, n-hexyl, aminoethyl, methylaminoethyl, ethylaminoethyl, dimethylaminoethyl, acryloylaminoethyl, methacryloylaminoethyl, methoxyethyl, ethoxyethyl, d-C4-alkyl-sulfonyl, acryloyl, or methacryloyl; or R1 is aminoethyl, acryloyl or acryloylaminoethyl carrying a linker and a tag, and R2 and R3, independently of each other, are hydrogen or CrC4-alkyl, or R2 and R3 together form a methylene or an ethylene bridge; and tautomers, solvates and pharmaceutically acceptable salts thereof. These compounds are effective in preventing or treating a disease or disorder modulated by PI3 kinases and/or mTOR, in particular treating a hyperproliferative disorder.

Abstract: Biological and chemical sensors based on surface charge changes in a pore or channel, such as a nanopore or nanochannel, are employed to detect targeted analytes in an electrolyte solution having a low ion concentration. Receptors within the pore or channel capture a targeted analyte, causing a change in surface charge that affects ionic conductance. The change in ionic conductance is detected, evidencing the presence of the targeted analyte. A secondary tag may be introduced to the pore or channel for binding with a captured analyte in certain circumstances for causing a change in the surface charge.

Abstract: The present invention relates to the crystal structure of the serine protease kallikrein 7 and to the use of this crystal structure in drug discovery. The present invention also relates to compounds binding specifically to this active site of kallikrein 7.

Abstract: The gene associated and causative of classical late infantile neuronal ceroid lipofuscinosis (LINCL), CLN2, has been identified and characterized. The translation product of this gene is a novel protease and a deficiency in this activity results in LINCL. Identification of CLN2 will not only aid in the prevention of LINCL through genetic counseling but provides strategies and test systems for therapeutic intervention. In addition, further characterization of this previously unknown lysosothal enzyme may provide useful insights into other more common human neurodegenerative disorders. Finally, the utility of a general approach for determining the molecular bases for lysosomal disorders of unknown etiology has been demonstrated.

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins, nucleic acids and cellular organelles. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified to provide beneficial properties.

Abstract: The present invention relates to a novel method for screening for a therapeutic or prophylactic agent for an inflammatory disease. More particularly, the present invention relates to a method for screening for a therapeutic or prophylactic agent for an inflammatory disease by selecting a substance having an inhibitory activity specific to PIKfyve by using the presence or absence of the inhibitory activity as an indicator.

Abstract: Methods for identifying a therapeutic agent for treating a Germinal Center Kinase (GCK)-Like Kinase (GLK)-mediated disease are disclosed. Methods for detecting a modulation of GLK signaling by a lest compound are disclosed. Also disclosed are methods for detecting the presence and/or severity of an autoimmune disease and/or cancer.

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: The disclosure provides microstructured articles and methods useful for detecting an analyte in a sample. The articles include microwell arrays.

Abstract: Provided herein are seven high resolution crystal structures showing the cytokinin receptor AHK4 complexed with various naturally occurring and synthetic ligands. Further provided are strategies for modulating cytokinin receptor activity.

Abstract: Provided herein is the crystal structure for the brassinosteroid receptor BRI1, as well as strategies for modulating its activity.

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: This invention provides: novel protein homologous of a Kunitz domain, which are capable of binding kallikrein; polynucleotides that encode such novel proteins; and vectors and transformed host cells containing these polynucleotides.

Abstract: Methods and materials are disclosed for use in an enzyme fragment complementation assay using complementary fragments of ?-galactosidase to study the trafficking of proteins in a cell. Compounds that bind to a target peptide have been found to affect protein folding and therefore trafficking. ?-Galactosidase fragments, an enzyme donor (ED) and an enzyme acceptor (EA), are fused to a target peptide and to an intracellular compartment protein, wherein the compartment is involved in intracellular trafficking. Contacting the cell with a compound that binds to the target peptide results in enhanced movement of the protein through the cellular trafficking pathway comprised of the endoplasmic reticulum, Golgi apparatus, the plasma membrane, endosomes, etc. Using this approach, compounds that bind to a target peptide and alter its ability to traffic through the normal cellular pathway can be readily detected.

Abstract: The subject invention provides point-of-care assays for assessing the topographical distribution of microbial biofilm and/or specific microorganisms in wounds.

Abstract: A diagnostic marker for determining of a patient with amyotrophic lateral sclerosis (ALS), comprising an autoantibody against a human protein HMGB1 is described. A diagnostic kit for determining of a patient with ALS, comprising: (a) an HMGB1 protein; and (b) an HMGB1 antibody standard is also presented. A method of determining ALS in a subject, comprising the steps: (a) detecting autoantibody against HMGB1 in a biological sample taken from the subject and normal control individuals; and (b) statistically comparing concentrations of the autoantibody against HMGB1 in the subject with that of the normal control individuals obtained from step (a); wherein a higher concentration of the autoantibody against HMGB1 in the subject than a cut-off concentration indicates the subject suffers from ALS is further described.

Abstract: The present invention relates to a composition comprising an inhibitor of the expression or activity of SH3 domain containing ring finger 2 (SH3RF2) for preventing or treating cancers. More specifically, since the SH3RF2 protein, of which the expression level increases in various cancer tissues, binds to PAK4, which is a cancer-associated gene, to regulate an apoptosis inhibitory function of the PAK4 protein by ubiquitination activity of SH3RF2 RING domain, cancer cells, in which the expression of SH3RF2 is inhibited, sensitively respond to the induction of apoptosis to promote apoptosis and reduce in vivo tumorigenicity, such that the inhibitor of the expression or activity of SHRF2 can be useful as a composition for preventing or treating cancers.

Abstract: The invention provides a target and methods for specific binding and inhibition of RNAP from bacterial species. The invention is directed to a method for identifying agents that bind to a bacterial RNAP homologous RNA-exit-channel amino-acid sequence, comprising preparing a reaction solution comprising the agent to be tested and an entity comprising a bacterial RNAP homologous RNA-exit-channel amino-acid sequence, and detecting presence or amount of binding. The invention has applications in control of bacterial gene expression, control of bacterial growth, antibacterial chemistry, and antibacterial therapy.

Abstract: Methods and reagents are disclosed for pretreating a sample suspected of containing a hydrophobic drug for conducting an assay method for detecting the hydrophobic drug. A combination is provided in a medium that includes the sample, a releasing agent for releasing the hydrophobic drug and the metabolites from endogenous binding moieties, and a selective solubility agent that provides for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The selective solubility agent includes a water miscible, non-volatile organic solvent and is present in the medium in a concentration sufficient to provide for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The medium, which may further include a hemolytic agent, is incubated under conditions for releasing the hydrophobic drug and the metabolites from endogenous binding moieties. The pretreated sample may be subjected to an assay for determining the hydrophobic drug.

Abstract: Methods for producing polypeptides in vitro are described that use free template nucleic acids that are not immobilized on a substrate. Polypeptides that are produced can be captured on particles without the use of capture agents and can be used to produce polypeptide arrays.

Abstract: The present invention relates to a dual activity domain JAK proteins, namely JH2. It is provided that the JH2 domain is a true and important target for drug development, especially for diseases caused by aberrant JAK signalling, such as myeloproliferative disorders and leukemias.

Abstract: The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins.

Abstract: The present invention provides a novel method for diagnosing renal cell carcinoma. The method of the invention allows evaluation of the presence of renal cell carcinoma or the degree of malignancy of renal cell carcinoma, by conducting comprehensive analysis of N-linked sugar chains in serum of a patient and utilizing an expression level of detected sugar chain as an index of the evaluation.

Abstract: The present invention relates to methods of modulating binding of Son of sevenless to phosphatidic acid and identifying compounds that modulate such binding. In particular, the present invention relates to a method of controlling pleckstrin homology domain-dependent membrane recruitment of Son of sevenless or histone folds domain-dependent membrane recruitment of Son of sevenless. Also disclosed are methods of controlling Ras and treating a subject for a condition mediated by Ras. The present invention also relates to a method of identifying compounds potentially effective in treating a condition mediated by Ras.

Abstract: We describe examples using aptamers for capturing and reporting the presence of a target, such as a pathogen. Examples described here include a set of aptamers that are specific to F. tularensisis. Other examples described here include an Aptamer-Linked Immobilized Sorbent Assay (ALISA) and dot blot assay. An example of a method provided here comprises: providing a set of DNA sequences that exhibit high binding affinity to target antigen, placing the DNA sequences in a sandwich aptamer-linked immobilized sorbent assay (ALISA), contacting the DNA sequences with a sample, and detecting whether the target is present in the sample. Some alternative implementations may include dot blots and different reporters. Quantum dot sandwich assays and quantum dot de-quenching reporters can be used.

Abstract: Assay methods may generally comprise forming homogeneous assay mixtures comprising target SAM-utilizing protein, fluorescent detection analyte, and test compound, incubating, and measuring FP or TR-FRET signal emitted in order to determine a measure of test compound-SAM-utilizing protein binding. Assay mixtures comprise a SAM-utilizing protein, and a fluorescent detection analyte that binds with the SAM-utilizing protein in the absence of test compound. Assay mixtures may further comprise a test compound. Assay mixture embodiments may generate FP or TR-FRET signal properties that are a function of the inherent binding interactions of both the test compound and the detection analyte with the SAM-utilizing protein. Fluorescent detection analytes comprise a fluorophore moiety, a covalent linker moiety, and a SAM-utilizing protein ligand moiety and could be utilized in FP or TR-FRET assays to measure test compound binding.

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: New antiviral peptides interfering the binding of the virus to DLC8. A high number of pathogenic agents of viral origin use the dynein based intracellular transport machinery at some point of their infective cycle. The present invention consists of a new antiviral therapy consisting in the inhibition of viral infections produced by those virus that use the dynein system by mechanisms of interference mainly by preventing the interaction between the viral protein and the cellular DLC8 protein. The present invention discloses for the first time the blocking of the function of this interaction by peptides whose sequence comprises or consists of the totality or a partial sequence of the viral protein corresponding to the binding domain with DLC8.

Abstract: The invention provides methods of preparing a test sample for use in an assay for detecting an analyte bound by an intracellular ligand. The methods typically involve contacting the test sample with an assay reagent comprising: a lysis reagent; and a protease that has proteolytic activity for said intracellular ligand; to form a mixture compatible for use in an immunoassay without subsequent extraction steps. Other aspects of the invention include related immunoassays and test kits.

Abstract: The invention concerns multimers developed from recombinant proteins analogues of MHC class I.

Abstract: The present invention relates to the detection of traumatic brain injury by detecting A? protein aggregates associated with traumatic brain injury. These A? protein aggregates are detected using peptide and peptide mimic probes that preferentially associate with A? protein aggregates associated with traumatic brain injury.

Abstract: The present invention relates to a method for screening an anticancer compound and an anticancer compound screened using the method, and more particularly, to a method for screening an anticancer compound, the method comprising: culturing cancer cells expressing the oncogenic protein transmembrane 4 L6 family member 5 (TM4SF5), expressed as the polypeptide of SEQ ID NO: 2, treating the cancer cells with an anticancer candidate, and determining that the anticancer candidate is an anticancer substance when the candidate exhibits antagonistic activity against tumor formation and metastasis based on several events through the molecular mechanism of TM4SF5. The present invention also relates to chalcone compounds screened to have anticancer activity using the method, and an anticancer composition comprising the compound as an effective ingredient.

Abstract: The present invention relates to a method for diagnosing cancer using information on aberrant glycosylation of glycoproteins, which is related with cancer progression. More particularly, the present invention relates to a peptide marker for cancer diagnosis and a method for diagnosing cancer using the peptide marker, wherein glycoproteins aberrantly glycosylated due to cancer incidence and progression is isolated using lectin; and marker peptides generated by hydrolysis of the glycoproteins isolated by the lectin is selected and quantified.

Abstract: Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.

Abstract: An in vitro process for the detection and early detection of neurodegenerative diseases, for determination of the severity, and to evaluate the progression of and render a prognoses of neurogenerative diseases, in a patient suffering from a subjectively or objectively detectable cognitive impairment, by determining the concentration of an analyte selected from natriuretic peptides, in particular ANP, and, if necessary, BNP and/or CNP in a biological fluid of the patient, whereby the determination of the analyte is performed directly and/or indirectly as the determination of a relevant co-peptide generated from a mutual propeptide, and is based upon the measured concentration of the determined analyte thus making it possible to form conclusions about a neurodegenerative disease or an early form typical of such a disease or the course of the disease and/or the success of the efforts to relieve or prevent the disease.

Abstract: The invention provides methods for predicting, diagnosing or monitoring acute cardiac disorders, cardiac transplant rejection, or distinguishing acute cardiac disorders from pulmonary disorders, by measuring BNP signal peptide levels in a sample taken from a subject shortly after onset of, or presentation with the disorder or transplant rejection.

Abstract: The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tissues, organs, or tumors. In another embodiment, the invention relates to methods of imaging tissues, organs, or tumors using radiolabeled metal complexes, particularly tissues, organs, or tumors which express certain receptors to which the compounds or complexes of the invention have an affinity. The present invention also relates to methods of treating cancer, particularly those cancer lines which express certain receptors to which the compounds or complexes of the invention have an affinity. In yet another embodiment, the present invention provides methods of imaging and/or inhibiting receptors or neuroreceptors using compounds or complexes of the invention which have an affinity for the receptor or neuroreceptor to be imaged and/or inhibited.

Abstract: The present invention relates to methods of controlling tumorigenesis, including preventing, inhibiting, arresting or reversing tumorigenesis. The present invention also provides methods of treatment, prevention and diagnosis of neoblastoma, including cancer, such as metastatic cancer. In one method one or more cells having a predisposition to turn tumorigenic are identifyied. In the one or more cells an altered amount, an altered subcellular localisation or an altered activity of a Rab binding protein is detected. In a method of diagnosing the risk of developing a neoplasmt at least one of the expression level, the activity level and the subcellular localisation of a Rab binding protein is determined. In an in-vitro method of identifying a compound capable of forming a complex with a Rab binding protein the components that form the respective complex are contacted with each other.

Abstract: The present invention relates to immobilization compounds (I), immobilization products and preparations thereof as well as methods and uses for the identification of kinase interacting compounds or for the purification or identification of kinase proteins.

Abstract: The invention relates to mutant G-protein coupled receptors with increased conformational stability, and methods of use thereof. In some aspects, polynucleotides encoding the mutant G-protein coupled receptors are provided. In some aspects, host cells comprising the polynucleotides are provided. In some aspects, the invention relates to crystallized forms of the mutant G-protein coupled receptors, and methods of preparing the same.

Abstract: The invention is directed to polypeptides having any cellulolytic activity, e.g., a cellulase activity, e.g., endoglucanase, cellobiohydrolase, beta-glucosidase, xylanase, mannanse, ?-xylosidase, arabinofuranosidase, and/or oligomerase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides of the invention can be used in a variety of pharmaceutical, agricultural, food and feed processing and industrial contexts. The invention also provides compositions or products of manufacture comprising mixtures of enzymes comprising at least one enzyme of this invention.

Abstract: The present invention relates to a peptide marker for cancer diagnosis and a cancer diagnosis method using the same, more precisely to a peptide marker for cancer diagnosis screened by the following steps: separating and concentrating glycoproteins including a certain glycan chain related to the occurrence of cancer; hydrolyzing the glycoproteins to obtain polypeptides; and quantitatively analyzing the polypeptides to identify certain polypeptides that can track quantitative changes in glycoproteins glycosylated in a specific manner by the occurrence of cancer, and to a cancer diagnosis method using the said peptide marker.

Abstract: Mutations in the p53 tumor suppressor gene are frequently found in human tumors and mutant p53 proteins actively collaborate with tumor progression. Interfering with mutant p53 function may represent a valid strategy to block tumor growth and development of aggressive phenotypes. As a consequence of the characteristic of peptide aptamers (PAs) to efficiently and selectively bind a target protein, they are able to interfere with its function and in its ability to interact with other partners. In the present application isolated peptides and aptamers thereof able to interact with structural and conformational p53 mutants within the region of the wild-type p53 DNA binding core domain comprised from amino acids 74 to amino acids 298 using the yeast two-hybrid method are disclosed. These PAs are able to efficiently recognize several different p53 point mutants but not wild-type p53.

Abstract: The present invention provides for the in vitro establishing of a prognosis for a subject in severe sepsis with at least two organ failures or in septic shock with at least two organ failures. Embodiments of the invention comprise the steps of measuring the level of the S100A8/A9 complex from a biological sample from a subject, and comparing the measured level to a predetermined threshold in which the measured level of the S100A8/A9 complex above the predetermined threshold is indicative of a bad prognosis and a measured level of the S100A8/A9 complex below the predetermined threshold is indicative of a good prognosis.

Abstract: The present invention relates to compounds of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

Abstract: The present invention is directed to a composition comprising a vanadium-containing phosphatase inhibitor and a polyol. In the presence of the polyol the effect of the inhibitor is enhanced, even in the presence of chelating agents or reducing agents. The invention also concerns the use of the inventive composition for inhibiting a phosphatase, as well as kits comprising the composition.

Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-1? converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

Abstract: The c-Jun NH2-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal response to seizure activity. Methods of screening for molecules and compounds that decrease JNK3 expression or activity are described. Such molecules or compounds are useful for treating disorders involving excitotoxicity such as seizure disorders, Alzheimer's disease, Huntington disease, Parkinson's disease, and ischaemia.

Abstract: The invention relates to a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.