Abstract: Methods for identifying a compound capable of interacting with a Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance, adding test cells expressing a RTK to the device, measuring first impedances, adding a compound to at least one compound well and adding a vehicle control to at least one control well, measuring second impedances of the compound well and the control well, determining the change in the impedance for the compound well and the one control well, comparing the change in impedance between the compound well and the control well, and identifying the compound interacts with the RTK if the comparison demonstrates a significant difference between the change in impedance.

Abstract: Methods are provided of treating obesity or an obesity comorbidity in a mammalian subject comprising administering to the subject an amount of an agent effective to treat obesity or the obesity comorbidity, which agent inhibits (i) I?B kinase ? (IKK?) activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) or (ii) Notch signaling in a manner so as to permit the agent to enter the hypothalamus of the subject. Assays are also provided for identifying candidate agents for treating obesity.

Abstract: The present invention relates to the field of recombinant toxin protein production in bacterial hosts. In particular, the present invention relates to production processes for obtaining high levels of a recombinant CRM197, Diphtheria Toxin, Pertussis Toxin, Tetanus Toxoid Fragment C, Cholera Toxin B, Cholera holotoxin, and Pseudomonas Exotoxin A, from a bacterial host.

Abstract: There is provided a method for quantifying a subject substance, of which typical examples are amino acids. The method of the present invention comprises the following steps: the step of allowing an enzyme that can generate pyrophosphate by using adenosine triphosphate (ATP) as a substrate with converting the subject substance to act on the subject substance to generate pyrophosphate; the step of allowing pyruvate pyrophosphate dikinase (PPDK) to act on the generated pyrophosphate in the presence of adenosine monophosphate (AMP) and phosphoenolpyruvate (PEP) to generate ATP, phosphoric acid, and pyruvate; and the step of quantifying the generated pyruvate, and amount of the subject substance is determined on the basis of the obtained amount of pyruvate. According to the present invention, an amino acid in a biological sample containing a lot of various kinds of contaminants such as inorganic phosphoric acid and urea can be conveniently and quickly quantified without being influenced by the contaminants.

Abstract: Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

Abstract: A method for analyzing the polypeptide content of animal tissue is described. The method includes the steps of (a) providing an animal tissue specimen; (b) depositing one or more portions of a hydrogel mixture including a protease on spatially discrete portions of the animal tissue specimen; (c) allowing sufficient time to pass for animal tissue under the hydrogel mixture to be form a digested mixture of animal tissue and hydrogel mixture; (d) removing the digested mixture from the animal tissue and extracting the polypeptides from the digested mixture to provide an extract; and (e) analyzing the polypeptide content of the extract by mass spectrometry.

Abstract: The present invention relates to fluorescent dyes based on acridine and acridinium derivatives and use of such dyes in for example, biochemical and/or cell-based assays.

Abstract: The invention pertains to a near-infrared fluorescent dye that is cell permeable and can be attached to selected proteins in living cells. The dye has the general formula or its corresponding spirolactone wherein Y is chosen from the group consisting of Si, Ge and Sn; R0 is —COO? or COOH; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 and R16 are substituents, including hydrogen, independently from each other. The dye (i) absorbs and emits light at wavelengths above 600 nm; (ii) possesses high photostability; (iii) has high extinction coefficients and high quantum yields; (iv) can be derivatized with different molecules; and (v) is membrane-permeable and shows minimal background binding to biomolecules and biomolecular structures.

Abstract: The invention relates to novel compositions and methods for the detection of enzymes using the nuclear reorganization energy, ?, of an electron transfer process.

Abstract: Apparatuses are disclosed for performing calorimetric assays with plucked human hair using a device adapted for that purpose. This device may include a transparent reaction vessel connected via a capillary tube to a burst pack, and connected via another capillary tube to a funnel, into which a plucked human hair may be placed.

Abstract: A method of detecting sulfotransferase activity including conducting a first reaction comprising, measuring free phosphate produced by the first reaction, and comparing the measured free phosphate to a free phosphate standard curve or equation or to a free phosphate level obtained in a separate reaction. The first reaction includes combining the sulfotransferase, Golgi-resident PAP-phosphatase (gPAPP), a 5?-nucleotidase, a substrate of the sulfotransferase, and 3?-phosphoadenosine-5?-phosphosulfate (PAPS) under conditions to produce 3?-phosphoadenosine-5?-phosphate (PAP).

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Ephrin Type-A Receptor 2 (EPHA2) protein are provided that are particularly advantageous for quantifying the EPHA2 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 and apparatus for detecting cancer using the measurement of acute-phase proteins (APPs) and the measurement of thymidine kinase activiy level in body fluids. An index is calculated based on the measured data and compared with a pre-established reference that allows a pratitioner to determine a high probabilty that a patient is a carrier of cancer.

Abstract: The invention relates to a compound of Formula I: F1-X1-L1-X2-P1-X3-G1??(Formula I).

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: The present invention provides genetically engineered strains of methylotrophic yeast including Pichia and especially Pichia pastoris capable of producing proteins with reduced or modified glycosylation. Methods of producing glycoproteins with reduced and/or modified glycosylation using such genetically engineered strains of Pichia are also provided. Vectors, which comprise coding sequences for ?-1,2-mannosidase I, glucosidase II, GlcNAc-tranferase I and mannosidase II or comprising OCH1 disrupting sequence, for transforming methylotrophic yeasts are contemplated by the present invention. Kit for providing the comtemplated vectors are also included in this invention.

Abstract: The present invention relates to a new diagnosis method in the field of hepatology, combining measurement of serum markers and of liver elasticity.

Abstract: This invention is in the field of medical devices. Specifically, the present invention provides portable medical devices that allow real-time detection of analytes from a biological fluid. The methods and devices are particularly useful for providing point-of-care testing for a variety of medical applications.

Abstract: A test strip to assist in determining the concentration of an analyte in a fluid sample comprises a base, at least one tab and a break line. The base includes a capillary channel and a test element. The capillary channel is in fluid communication with the test element. The test element is adapted to receive the fluid sample. The at least one tab is removably attached to the base. The capillary channel extends from the base into a portion of the tab. The break line intersects the capillary channel in which an inlet to the capillary channel is exposed along the break line when the tab is separated from the base.

Abstract: A method for selecting in vitro compounds is capable of potentiating the effect of a DNA damage inducing chemotherapy agent for the treatment of cancer, and includes selecting compounds inhibiting the interaction between MyD88 and ERK MAP KINASE.

Abstract: Methods and kits for enzymes involved in post-translational modifications are provided. The methods employ elemental analysis, including ICP-MS.

Abstract: A method for assaying activity of the enzyme spermidine/spermine N1-acetyltransferase (SSAT) uses SSAT substrates by detecting their acetylated forms. SSAT substrates may include rimantadine and tocainide wherein their metabolism occurs in part by the action of the inducible enzyme SSAT to produce the acetylated metabolites N-acetylrimantadine and N-acetyltocainide respectively. SSAT activity may be correlated to pathologic conditions.

Abstract: This invention relates to a testing system arrangement for assessing the level of a biochemical marker, comprising a disposable device (2) with a sample inlet (4) and a at least one visible detection compartment (5A, 5B), for detection of said bio-chemical marker, a mobile unit (8) including a digital camera arranged to capture a digital picture (60) of said at least one visible detection compartment (5A, 5B), software run on a processor for analysing said picture (60) to assess said level and means arranged to present the result (70) of said assessment in a display (8A) of or connected to, said mobile unit (8), wherein said disposable device (2) is arranged with at least one reference surface (12) having a predetermined colour setting that is known to said software to enable exact assessment of the colour within said detection compartment (5A, 5B) by the use of said reference surface (12) within said digital picture as a basis reference.

Abstract: Provided herein are methods for treating or preventing head and neck squamous cell carcinoma characterized by deletion of chromosome 11q22 or loss of ataxia telangiectasia mutated expression, comprising administering an effective amount of a dihydropyrazino-pyrazine to a patient having head and neck squamous cell carcinoma characterized by deletion of chromosome 11q22 or loss of ataxia telangiectasia mutated expression.

Abstract: The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

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 relates to methods of diagnosing a kidney disorder in a patient, as well as methods of monitoring the progression of a kidney disorder and/or methods of monitoring a treatment protocol of a therapeutic agent or a therapeutic regimen. The invention also relates to assay methods used in connection with the diagnostic methods described herein.

Abstract: The invention relates to biomarkers measurable in a human subject that have prognostic value with respect to efficacy of therapeutic treatments for Hepatitis C viral infection. The markers also are believed to have value for diagnosis liver health/liver damage.

Abstract: The invention relates to methods for the determination of vitamin B6 in samples as well as to reagent compositions for assaying a sample for vitamin B6 and to a test kit suitable for carrying out the methods according to the present invention. Further, the invention relates to the use of such methods for the application to different analyzing devices such as micro-titer plate readers and fully automated clinical chemistry analyzers (autoanalyzers).

Abstract: Devices contain dried reagents that may be reconstituted and used in the calibration and quality control of sensors. Methods of producing and using the devices are also disclosed.

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

Abstract: A method and kit are provided for enhancing the tolerance of an assay reagent to compounds in an assay sample, the assay reagent including a luciferase enzyme. The method includes contacting the luciferase with a tolerance enhancement agent in an amount sufficient to substantially protect luciferase enzyme activity from interference of the compound and minimize interference by at least about 10% relative to an assay not having tolerance enhancement agent.

Abstract: Described are methods and kits for determining the likelihood of the presence of cardiovascular disease (CVD) or pulmonary disease (PD) in a subject using ST2/Interleukin 1 Receptor Like 1 (IL1RL1) and/or Interleukin 33 (IL-33), and a biomarker for CVD, e.g., a natriuretic peptide, e.g., brain natriuretic peptide (BNP), prohormone BNP (proBNP), N-Terminal proBNP (NT-proBNP), atrial natriuretic peptide (ANP), proANP, or NT-proANP.

Abstract: A method of producing an antibody comprises immunizing a mammal with an amine-derivative of acetylamantadine, immunizing the mammal with acetylamantadine, and producing the antibody from the mammal. The antibody recognizes acetylamantadine but does not recognize amantadine.

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: A non-radioactive, ultrasensitive methodology for the quantification of protein kinase catalytic activity of any protein kinase in, for example, biological/clinical samples or recombinant/purified proteins, based on using near-infrared-fluorescence (NIRF)-labeled peptide substrates that are selective for individual protein kinases and using a combination of kinase-selective inhibitors to define the catalytic activity of individual protein kinases, including but not limited to, a substrate for phosphorylation by a protein kinase comprising a core peptide having the formula: (N-terminus)-Arginine-Lysine-Arginine-Serine-Arginine-Lysine-Glutamic-acid-(C-terminus); and an indicator component covalently bonded to the core peptide.

Abstract: A “breadboard” approach by which a biochemical signaling process, pathway, or network under study is separated or segmented into interconnected smaller portions, at least one of which can to a degree of approximation be accurately emulated with a replica microscale and/or nanoscale fluidic implementation whose constituent species can be closely controlled and at least one aspect of whose behavior can be measured. Control and measurement information interfaces with a computer that executes algorithms comprising one or more of a control process, control event-script, experiment, data recording, and mathematical model. A model can be used to simulate the actions, behavior, or other aspects of another portion of the biochemical signaling process, pathway, or network.

Abstract: Provided herein are method for measuring the rate of synthesis, breakdown, transport, or other kinetic parameters of a protein in a tissue of medical interest, without requiring physical sampling of the tissue, by a measurement of the protein in a body fluid.

Abstract: Provided herein are methods of determining NAT acetylation status of a subject with a 3,4-DAP-sensitive disease, methods of selecting a dose of 3,4-DAP or a pharmaceutically acceptable salt thereof adjusted to a subject's acetylation status, methods of administering 3,4-diaminopyridine or a pharmaceutically acceptable salt thereof to a patient in need thereof, and methods of treating 3,4-DAP sensitive diseases.

Abstract: A peptide for synthesizing silica and use thereof are provided. The peptide for synthesizing silica can polymerize silica from a silica precursor in an aqueous solution having conditions of normal temperature, normal pressure and near-neutral weak base. The peptide for synthesizing silica can form a self-assembled structure during silica synthesis, and thus can be used as various biomaterials such as a silica-based protein immobilizer, a biosensor, and a drug delivery system.

Abstract: Although it can be farnesylated, the mutant lamin A protein expressed in Hutchinson Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression.

Abstract: Embodiments of the invention include a PET/SPECT reporter gene system that uses enhanced non-immunogenic versions of a human mitochondrial thymidine kinase 2 expressed in cytoplasm to preferentially trap novel PET/SPECT radiolabeled L and D-enantiomer analogs of the natural substrate thymidine. Such highly sensitive, non-immunogenic reporter genes function in combination with a set of novel, radiolabeled probes in whole body molecular imaging applications using positron emission tomography (PET) or single photon emission computed tomography (SPECT).

Abstract: Polypeptides with tubulin acetyltransferase activity are described, as are nucleic acids encoding said polypeptides, and methods of use. The invention further provides enhancers and inhibitors of tubulin acetyltransferase activity, as well as cells having altered tubulin transferase activity.

Abstract: Methods for screening for substances capable of modulating the phosphorylation of tau protein are disclosed, and in particular paired helical filament (PHF) tau, and the use of such modulators in the treatment of tauopathies. The assays and screening methods are based on the identification of new phosphorylation sites in PHF tau and new kinases and combinations of kinases as therapeutic targets, in particular the identification of casein kinase 1 as a kinase which phosphorylates tau protein.

Abstract: Compounds and compositions for the transient expression of exogenous telomerase activity in a cell are provided. The compounds and compositions, which relate to a ribonucleic acid coding for a telomerase reverse transcriptase, are useful in the extension of telomeres in cells needing such treatment. Such cells include, for example, cells that contain shortened telomeres and cells from subjects that may benefit from telomere extension, for example subjects that suffer from, or are at risk of suffering from, age-related or other illnesses. Also provided are methods of extending telomeres through the administration of the provided compounds and compositions to animal cells, either in vitro or in vivo, and kits including the compounds or compositions and instructions for use.

Abstract: The invention relates to kinase ligands and polyligands. In particular, the invention relates to ligands, homopolyligands, and heteropolyligands that modulate AKT activity. The ligands, homopolyligands, and heteropolyligands are utilized as research tools or as therapeutics. The invention includes linkage of the ligands, homopolyligands, and heteropolyligands to a cellular localization signal, epitope tag and/or a reporter. The invention also includes polynucleotides encoding the ligands, homopolyligands, and heteropolyligands.

Abstract: Assays and methods for detecting and/or quantifying activity of a test sulfotransferase comprising by releasing a free phosphate from the PAP produced by the sulfotransferase reaction and detecting the free phosphate. The assay can includes gPAPP, a free phosphate detector and an optional control sulfotransferase. The method includes combining a test sulfotransferase with the substrate of the sulfotransferase, PAPS and gPAPP and detecting the free phosphate. The level of free phosphate directly correlates to the activity of the sulfotransferase. The assay and methods can be used to screen agents for their effect upon sulfotransferase activity.

Abstract: Embodiments of the invention provide lateral flow and flow-through bioassay devices based on patterned porous media, methods of making same, and methods of using same. Under one aspect, an assay device includes a porous, hydrophilic medium; a fluid impervious barrier comprising polymerized photoresist, the barrier substantially permeating the thickness of the porous, hydrophilic medium and defining a boundary of an assay region within the porous, hydrophilic medium; and an assay reagent in the assay region.

Abstract: A biosensing system that measures the concentration of halogenated alkenes is disclosed.

Abstract: This invention relates generally to a novel serine/threonine protein kinase, specifically to hormonally up-regulated, neu-tumor-associated kinase (HUNK); and to the role of HUNK in tumor metastasis, primary tumor development, and the prediction of tumor behavior.