Abstract: The present invention relates to a novel Phytophthora phospholipase C and uses thereof, methods of identifying modulators and inhibitors of a biological function of the phospholipase C, and methods of inhibiting Phytophthora growth comprising inhibiting a biological function of a novel Phytophthora phospholipase C.

Abstract: The invention relates to quality control of analytical assays, particularly NAT assays of blood samples containing nucleic acids. A control panel containing quantified amounts of substances known to interfere with an analytical assay is used and compared with a reference sample in the analytical assay. A comparison of the assay results interference panel validates the assay and can serve as a periodic quality control check for the analytical assay as well as related methods and protocols. The use of the control panel of the invention can also determine whether interfering substances are present and establish under what conditions the analytical assay reliable.

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

Abstract: This document relates to methods and materials involved in modulating deubiquitinases (e.g., USP10 polypeptides) and/or ubiquitinated polypeptides (e.g., tumor suppressor polypeptides or mutant versions of tumor suppressor polypeptides). For example, methods and materials for increasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for decreasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for stabilizing tumor suppressor polypeptides (e.g., wild-type p53 polypeptides), methods and materials for de-stabilizing mutant versions of tumor suppressor polypeptides (e.g., mutant p53 polypeptides), and methods and materials for reducing cancer cell proliferation, increasing cancer cell apoptosis, and/or treating cancer (e.g., cancers having reduced levels of wild-type p53 polypeptides or cancers having increased levels of mutant p53 polypeptides) are provided.

Abstract: Compounds of Formulas I-XLIII are identified as direct inhibitors of p97 ATPase or of the degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate. Methods and compositions are disclosed for inhibiting p97 ATPase and the degradation of a p97-dependent UPS substrate, and for identifying inhibitors thereof.

Abstract: Methods and compositions for detection of the modulators of proteolytic enzymes, particularly cysteine proteases, are disclosed.

Abstract: The present disclosure identifies caspase-1/ICE as a therapeutic target for ?-synuclein associated diseases and disorders. Related methods and compositions are also provided.

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 microfluidic sensor includes a microchannel that includes a reaction site with a reagent and a sample inlet. A liquid substance is received at the sample inlet and travels by capillary action to the reaction site. A temperature sensor measures a temperature as a result of a reaction between the reagent and a chemical in the liquid substance. A controller is communicatively connected to the temperature sensor, receives the temperature measured by the temperature sensor, and derives a concentration of the chemical in the liquid substance from the temperature.

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: The invention provides compounds with enhanced permeability for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

Abstract: Provided are a support for supporting a metal, a metal-supported catalyst, a methanation reaction apparatus, and a method relating thereto that realize effective methanation of carbon monoxide. The support for supporting a metal includes a carbonized material obtained by carbonizing raw materials containing an organic substance and a metal, in which the support is used for supporting a metal that exhibits a catalytic activity for a methanation reaction of carbon monoxide. The metal-supported catalyst includes: a support formed of a carbonized material obtained by carbonizing raw materials containing an organic substance and a metal; and a metal that exhibits a catalytic activity for a methanation reaction of carbon monoxide, the metal being supported on the support.

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 includes compositions and methods for fluorescence-based multiplex probe to simultaneously detect one or more enzymatic activities comprising: a first enzymatic target having a first end and a second end, wherein the first end of the first enzymatic target is attached to a central body and the second end of the first enzymatic target is attached to a first fluorophore; a second enzymatic target having a first end and a second end, wherein the first end of the second enzymatic target is attached to the central body and the second end of the second enzymatic target is attached to a third fluorophore; wherein the central body comprises at least one second fluorophore; wherein the first enzymatic target comprises a specific cleavage site of a first enzyme that cleaves the first enzymatic target; and wherein the second enzymatic target comprises a specific cleavage site of a second enzyme.

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: A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.

Abstract: The invention provides a method of incorporating nonstandard amino acids into a protein by utilizing a modified aminoacyl-tRNA synthetase to charge the nonstandard amino acid to a modified tRNA, which forms strict Watson-Crick base-pairing with a codon that normally forms wobble base-pairing with natural tRNAs.

Abstract: Methods and kits for determining a risk of a subject, or subjects for developing lung cancer is disclosed. The method comprises determining a level of catalytic activity of N-methylpurine DNA glycosylase (MPG), or apurinic/apyrimidinic endonuclease 1 (APE1), or both, or MPG and 8-oxoguanine DNA glycosylase (OGG1), or MPG and APE1 and OGG1 in peripheral blood cells of a subject, wherein levels of MPG above a predetermined reference value, or APE1 or OGG1, or a integrated DNA repair score below a predetermined reference value is indicative of an increased risk of developing lung cancer.

Abstract: Multiplex enzyme assay methods and compositions for simultaneously assaying the activities of a plurality of lysosomal enzymes.

Abstract: The present invention relates to methods for determining the concentration of a free beta-lactam antibiotic in a biological sample. In particular, the present invention relates to methods for measuring a free beta-lactam antibiotic in a biological sample, comprising the steps of: (a) providing at least one class C beta-lactamase, a functional fragment or variant thereof; (b) providing at least one biological sample; (c) contacting said at least one class C beta-lactamase with said at least one biological sample; and (d) determining the concentration of said free beta-lactam antibiotic in said at least one biological sample.

Abstract: Apparatus, systems, and methods for detecting, screening and sampling of cells are disclosed.

Abstract: Biosensors and methods of producing biosensors for use in detecting one or more analytes in a solution are disclosed herein.

Abstract: A method of performing high-throughput screening of various enzymatic activities with high sensitivity using artificial genetic circuits is provided. Particularly, the invention is screening and quantifying the activity of isoprene biosynthesis enzymes using an artificial genetic circuit capable of sensing isoprene. The artificial genetic circuit comprises an isoprene-sensing transcriptional regulator which recognizes isoprene, at least one reporter gene, a isoprene-sensing transcriptional regulator binding region and promoters for genes encoding isoprene-sensing transcriptional regulators and reporter proteins. The artificial genetic circuit detects isoprene liberated from many enzymatic reactions and measures the activity of reporter genes. This system is widely applicable for high throughput and quantitative screening of isoprene biosynthesis enzymes and MEP/MVA pathway enzymes. Therefore, the invention can be advantageously used in the protein engineering technology for enzyme modification.

Abstract: The present invention provides methods for reducing the level of amyloid beta protein in a cell or tissue, the methods generally involving contacting the cell or tissue with an agent that reduces cystatin C levels and/or activity. The present invention provides methods for treating Alzheimer's disease (AD), and methods for treating cerebral angiopathy, in an individual, the methods generally involving administering to an individual having AD a therapeutically effective amount of an agent that reduces cystatin C levels and/or activity. The present invention further provides methods for identifying an agent that reduces cystatin C levels and/or activity.

Abstract: The present invention generally relates to bacterial polypeptide display systems, libraries using these bacterial display systems, and methods of making and using these systems, including methods for improved display of polypeptides on the extracellular surface of bacteria using circularly permuted transmembrane bacterial polypeptides that have been modified to increase resistance to protease degradation and to enhance polypeptide display characteristics.

Abstract: This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique ?-N-acetylgalactosaminidases and ?-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique ?-N-acetylgalactosaminidases and ?-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof: (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells: and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates.

Abstract: Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

Abstract: Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

Abstract: The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having the desired activity using a change in the optical properties of the genetic elements. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Abstract: The disclosure relates to a method for selecting, isolating and/or recovering a peptide or polypeptide from a library or a repertoire of peptides and polypeptides (e.g., a display system) that is resistant to degradation by a protease such as a protease found in the serum. Generally, the method comprises providing a library or repertoire of peptides or polypeptides, incubating the library or repertoire with a protease under conditions suitable for protease activity, and selecting, isolating and/or recovering a peptide or polypeptide that is resistant to degradation by the protease and has a desired biological activity. The selected peptides and polypeptides have utility as therapeutics, e.g., for treating disease in humans.

Abstract: The present invention provides methods for protein engineering. Specifically, the invention provides methods utilizing site evaluation libraries to design libraries that optimize two or more properties of a protein.

Abstract: The present invention relates generally to hydrogen production for use in fuel cells, foodstuffs and chemical production, and more particularly, to biologically and photosynthetically produced hydrogen. Specifically, disclosed is a method for producing bacteria and green alga that can produce hydrogen in quantities that exceed four hundred percent of the hydrogen produced by green alga in nature; thus, producing organisms which can serve as hydrogen generators for fuel cells, chemical production and numerous other applications.

Abstract: Cell lines harboring a range of polymorphisms using recombinant cytochrome P450 or other chemical-metabolizing enzymes in a parent cell line that is minimally expressing or devoid of its own cytochrome P450 protein or other chemical-metabolizing enzymes of interest can be placed into an array format to enable high throughput screening of one or more chemicals for CYP450 or other enzyme-dependent metabolism (FIG. 9). Processing of the cells can be automated, done en-masse through use of an array having a substrate upon which a plurality of cell lines with exogenous chemical-metabolizing enzymes are coupled, and both relative and quantitative metabolism rates determined using mass spectrometry over time. Thus, methods are disclosed to measure, for example, the effects of cytochrome P450 polymorphisms on clinical drug metabolism in a high throughput manner for drug development and genetically personalized diagnostics and treatment regimens.

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: The present disclosure provides compositions and methods for producing and expressing variant or engineered I-OnuI endonucleases, variant or engineered I-OnuI homologues, and hybrids of two I-OnuI or I-OnuI homologue domains that have a target site altered from the wild-type. A method for selecting a variant or engineered I-OnuI endonuclease, I-OnuI endonuclease homologue, and a hybrid of two I-OnuI or I-OnuI homologue domains that have a target site altered from the wild-type and directed to a site within a gene of interest is also provided.

Abstract: Highly specific and novel methods for reversible hydrazone solid-phase extraction (rHSPE) are provided for glycan or glycopeptide isolation from proteins, peptides, and other contaminants for glycan and glycopeptide analysis. Glycans or glycopeptides in complex mixtures can be conjugated onto solid support or affinity or chemical tags via reversible hydrazone bond. The conjugation methods of the present invention are chemically specific and provide unique means for the removal of other non-glycan containing molecules in the complex sample before the glycans or glycopeptides are hydrolyzed and recovered for analysis. The hydrazone formation and hydrolysis of the novel methods allows for the analysis of glycans and glycopeptides. The hydrazide coating on the solid-phase surfaces are useful for surface glycan capture and on target glycan analysis. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.

Abstract: The present invention provides a novel technique by which the redox activity of a nucleic acid molecule can be evaluated. An evaluation method of the present invention includes: a detection step of electrochemically detecting a redox reaction to a substrate, the redox reaction being catalyzed by a nucleic acid molecule to be evaluated, using a device that electrochemically detects a redox reaction; and an evaluation step of evaluating redox activity of the nucleic acid molecule from a result of the detection of the redox reaction. As the device, a device in which a base provided with a detection portion is included, the detection portion. includes an electrode system, and the nucleic acid molecule to be evaluated is arranged on the base is used. In the present invention, it is preferred that a plurality of kinds of nucleic acid molecule to be evaluated is arranged on the base, and the plurality of kinds of nucleic acid molecules to be evaluated is evaluated by a single device.

Abstract: A method is provided to construct libraries of nucleic acids that comprise a plurality of mutations, each of which may be identified with particularity, such as following a selection or screening.

Abstract: The invention provides compounds for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

Abstract: Synthetic protease substrates and methods which facilitate the identification of substrates of a protease, particularly ubiquitin, ubiquitin-like, or proteasome protein are provided.

Abstract: A novel reaction discovery system that does not depend on DNA duplex formation is provided. The advantages of this system include exploring reactions conditions not possible where DNA hybridization is required. For example, the inventive reaction discovery system allows for reaction conditions using organic solvents, higher temperatures, and water-insoluble reagents, catalysts, and ligands. The invention also provides single-stranded oligonucleotide templates with substrate pairs covalently attached and methods of screening for reaction conditions that result in a direct covalent bond between the substrates. Kits are also provided for practicing this novel reaction discovery system.

Abstract: Described are methods and means for enhancing enzyme activity toward insoluble substrates. This is achieved by means of in vitro compartmentalization in which an insoluble microparticle functions both as the enzyme substrate and as a structure for negative selection. Enhanced enzymes expressed from a microparticle-linked polynucleotide library preferentially degrade the microparticle releasing specific gene variants into solution. Gene variants encoding less active enzyme variants remain linked to the microparticle and may be removed through centrifugation, thus enriching the polynucleotide library for more active enzyme variants. These methods may be used to enhance cellulase and ligninase activity toward insoluble cellulosic biomass.

Abstract: Methods and devices for determining the healing status of wounds, in particular of chronic wounds are provided. Also provided are kits comprising the diagnostic devices, and methods of wound diagnosis and treatment using the diagnostic devices and methods. A diagnostic apparatus (device) for monitoring wounds that exude a wound fluid and determining whether said wounds would be responsive to treatment with wound therapy such as oxidized cellulose therapy is also provided along with kits comprising the diagnostic apparatus and a wound dressing. Furthermore, methods of prognosing and treating wounds that exude a wound fluid are also provided.

Abstract: The present invention provides methods for protein engineering. Specifically, the invention provides methods utilizing site evaluation libraries to design libraries that optimize two or more properties of a protein.

Abstract: Methods and systems for evaluating and predicting the reactivity of natural and engineered monooxygenase enzymes are provided. Methods are provided for acquiring a functional profile (fingerprint) of monooxygenases that encode information regarding the active site configuration of such monooxygenases. Methods are also provided for carrying out analysis of a monooxygenase fingerprint, to formulate predictions regarding the reactivity properties (e.g., substrate reactivity, chemo-, regio, and stereoselectivity properties) of the fingerprinted monooxygenases.

Abstract: The invention relates to a method to screen for a nucleic acid molecule encoding a polypeptide involved in the synthesis of naringenin chalcone which demonstrates altered expression, activity or substrate specificity. The invention further relates to nucleic acid molecules identified by said screen and to transgenic plants modified to express said nucleic acid molecule.

Abstract: The invention provides compositions and methods for engineering E. coli or other host production bacterial strains to produce fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection.

Abstract: The present invention relates to methods for treatment or prevention of autoimmune and inflammatory diseases and conditions by inhibiting or modifying histone demethylation. In a further aspect the invention relates to a method for identifying agents useful in said methods of treatment. The invention particularly describes the role of certain histone demethylase enzymes in these diseases and conditions and their use as therapeutic and screening targets.

Abstract: The present invention relates to a method for the display of recombinant functional polypeptides containing a prosthetic group selected from metal porphyrin and flavin containing groups on the surface of a host cell using the transporter domain of an autotransporter.

Abstract: This invention pertains to the in vitro detection of proteases using a single peptide-conjugate nanocrescent surface enhanced Raman scattering (SERS) probes with at least nanomolar sensitivity. The probe enables detection of proteolytic activity in extremely small volume and at low concentration. In certain embodiments the probes comprise an indicator for the detection of an active protease, where the indicator comprises a nanocrescent attached to a peptide, where said peptide comprises a recognition site for the protease and a Raman tag attached to the peptide.