Abstract: The present invention provides methods of regulating plant stress tolerance.

Abstract: The invention relates to assays for measuring ubiquitin ligase activity and for identifying modulators of ubiquitin ligase enzymes.

Abstract: The PhoU protein is a widely expressed protein in bacteria, but not in eukaryotes. The PhoU protein is required for persister formation in bacteria. The invention includes compositions to reduce persister formation and their use as therapeutic agents. The invention further includes methods for identification of compounds to reduce persister formation. The invention further includes kits for the identification of agents that modulate the activity and expression of PhoU.

Abstract: The present invention disclosed herein provides a method for producing a plant with increased yield as compared to a corresponding wild type plant comprising increasing or generating one or more activities in a plant or a part thereof. The present invention further relates to nucleic acids enhancing or improving one or more traits of a transgenic plant, and cells, progenies, seeds and pollen derived from such plants or parts, as well as methods of making and methods of using such plant cell(s) or plant(s), progenies, seed(s) or pollen. Particularly, said improved trait(s) are manifested in an increased yield, preferably by improving one or more yield-related trait(s), e.g. low temperature tolerance.

Abstract: The present invention relates to a generic method for detecting a kinase or phosphatase activity. The method comprises the following steps: incubating a kinase or phosphatase activity sample with a kinase or phosphatase substrate molecule comprising either a fluorophore having a detectable readout or molecule with an aromatic group which serves as a quencher of the fluorophore, incubating the mixture of step a) with a detection entity comprising either a fluorophore or a molecule with an aromatic group and a binding partner, wherein the substrate molecule and the detection entity are capable of binding to the binding partner and the binding of the substrate molecule and the detection entity to the binding partner lead to an altered readout of the fluorophore, and measuring the readout of the fluorophore in the mixture of step b), wherein an altered readout of the fluorophore compared to a blank is indicative for the presence of a kinase or phosphatase activity in the sample.

Abstract: Division arrested cells are used in screening assays to determine the effect of a substance of interest on the cells. The division arrested cells can be used in drug screening assays, signal transduction assays, and are especially useful in large scale, high throughput assays.

Abstract: The present invention provides methods of affecting gluconeogenesis by altering the levels or activity of DUSP4 and/or EGR1. Pharmaceutical compositions comprising or encoding modulators of gluconeogenesis are also disclosed.

Abstract: The invention provides pharmacological compositions comprising PDE-5 inhibitors for the treatment of hearing impairment i.e. hearing loss and tinnitus. The invention also provides methods of screening for such PDE-5 inhibitors for use in the preparation of medicaments for the treatment of hearing impairment i.e. hearing loss and tinnitus.

Abstract: Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.

Abstract: Provided are compounds capable of covalently binding to a protein tyrosine phosphatase (PTP). The compounds comprise Formula A: Also provided are compositions comprising one of the above compounds covalently bound to a member of the PTP superfamily, methods of labeling a PTP using the compounds, methods of isolating a PTP from a mixture of proteins using the compounds, methods of evaluating whether a substance is an inhibitor of a PTP using the compounds, methods of evaluating the specificity of an inhibitor of a PTP using the compounds, methods of identifying a PTP involved in a disease in a mammal using the compounds, and methods of diagnosing a disease in a mammal using the compounds.

Abstract: Disclosed herein are agents, methods, and kits for determining the presence or concentration of a target, or multiple targets, in a sample, in a uniplexed or multiplexed fashion. In general, the methods enable the analysis of small molecules produced or consumed in liquid-phase that may be analyzed using gas or vapor phase detection methods.

Abstract: The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts, including bone formation enhancing pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean bone density in a subject.

Abstract: The invention relates in general to tyrosine dephosphorylation. More specifically, the invention relates to methods and compositions for monitoring intracellular tyrosine dephosphorylation at the single cell level. The invention further relates to techniques that can be used as aid in the development of novel therapeutics, and monitor regulation of intracellular tyrosine phosphatase activity at the single cell level.

Abstract: This invention relates to methods for activation of T cell protein tyrosine phosphatase (TCPTP) and for inhibiting tyrosine kinase signalling in an individual. The invention concerns a method for preventing or treating a disease or disorder in an individual, wherein said disease or disorder is curable by inhibiting tyrosine kinase signalling, and a method for preventing cancer, or preventing or inhibiting cancer growth, invasion or metastasis in an individual, based on activating T cell protein tyrosine phosphatase (TCPTP). The invention also concerns pharmaceutical compositions useful in the methods.

Abstract: The present invention relates to assays that can measure the activity of enzymes that catalyze phosphate modifications, such as kinases, phosphatases, cyclases and phosphodiesterases. The assays can also be used to identify and screen for substances that modulate the activity of kinases, phosphatases, cyclases and phosphodiesterases.

Abstract: The present disclosure provides systems for the rapid and sensitive detection of organisms and molecules in samples. Reactants that produce Raman-active products are used in combination with Raman light scattering. Such compounds may comprise phosphates permitting the detection of phosphatases. The present disclosure can also be used to measure enzyme-kinetics.

Abstract: An assay in which alkaline phosphatase is detected on one of a number of membranes held on a holder. A liquid sample and a substrate are combined on the membrane. If the enzyme is present, the substrate is cleaved. The products of this cleavage are optically detectable.

Abstract: The invention is directed to enhanced methods for detecting an analyte of interest in situ, by immunoassay, or by hybridization comprising binding an enzyme-labeled conjugate molecule to an analyte of interest in the presence of a redox-inactive reductive species and a soluble metal ion. The enzyme catalyzes the conversion of the inactive reductive species to an active reducing agent, which in turn reduces the metal ion to a metal atom thereby providing an enhanced means of detecting the analyte via metal deposition.

Abstract: The present invention is to provide a novel phosphodiesterase and a gene thereof, specifically, Type 11 phosphodiesterase (PDE11) and a gene thereof, more specifically, a phosphodiesterase selected from (A) a protein having an amino acid sequenced shown by SEQ.ID.NO: 2, SEQ.ID.NO: 4, SEQ.ID.NO: 6 or SEQ.ID.NO: 39, and (B) a protein having an amino acid sequence shown by SEQ.ID.NO: 2, SEQ.ID.NO: 4, SEQ.ID.NO: 6 or SEQ.ID.NO: in which one or several amino acids are deleted, substituted or added, and having an activity of hydrolyzing a cyclic nucleotide, and a gene thereof, and a method of characterizing, identifying and selecting a phosphodiesterase inhibitor by using the same.

Abstract: Provided are means and methods for in vitro and in vivo detection of chemically induced effects on embryonic development and differentiation for the purpose of embryotoxicity/teratogenicity screening as well as for the identification of pharmaceuticals such as growth and tissue promoting factors based on differentiating pluripotent embryonic stem (ES) cells. The assays are based on the use of transgenic ES cells and non-human animals comprising such ES cells or derivatives thereof, wherein said ES cells are characterized by the differentiation-dependent expression of a secreted reporter protein; in particular secreted embryonic alkaline phosphatase (SEAP).

Abstract: A method for making hepatocytes from extrahepatic somatic stem cells comprises: a) culturing somatic stem cells in a medium comprising hepatic growth factor to cause the stem cells to differentiate toward hepatocytes; b) culturing cells from a) in a medium comprising HGF and oncostatin M to facilitate the cell differentiation toward hepatocytes; and c) culturing cells from b) in a medium comprising oncostatin M to cause the differentiated cells to mature into hepatocytes, thereby producing a cell population that has morphological features of hepatocytes and at least four of the following characteristics: i) antibody-detectable expression of albumin; ii) real-time reverse transcriptase-polymerase chain reaction-detectable expression of ?-fetoprotein, HNF-1?, HNF-3?, HNF-4, HNF-6, ?1-antitrypsin, alkaline phosphatase, tryptophan 2,3-dioxygenase, tyrosine aminotransferase, cytochrome P450 family 2 subfamily E polypeptide 1, glutamine synthetase, and/or low density lipoprotein receptor; iii) urea secretion; iv) c

Abstract: Systems for detecting molecular modifications and the presence and/or activity of enzymes and/or other agents involved in facilitating or otherwise regulating such modifications.

Abstract: The invention is directed to novel compositions of matter and methods of detecting in situ an immunohistochemical epitope or nucleic acid sequence of interest in a biological sample comprising binding an enzyme-labeled conjugate molecule to the epitope or sequence of interest in the presence of a redox-inactive reductive species and a soluble metal ion, thereby facilitating the reduction of the metal ion to a metal atom at or about the point where the enzyme is anchored. Novel phosphate derivatives of reducing agents are described that when exposed to a phosphatase are activated to their reducing form, thereby reducing metal ions to insoluble metal.

Abstract: A cancer is evaluated for selection of appropriate therapy by evaluating a sample of cancerous tissue to determine an expression of level of phosphatase and tensin homologue deleted from chromosome 10 (PTEN); and in the case where the expression level of functional PTEN is below a threshold level, identifying the cancer as susceptible to an active agent that inhibits the expression of heat shock protein 27 (hsp27). The evaluation may be included as part of a method of treatment, in which an hsp27 inhibitor is selected as a therapeutic agent when the PTEN level is below the threshold.

Abstract: Embodiments of the present invention relate to atomic coordinates for PME-1 alone or in complex with PP2A, as well as methods for using these atomic coordinates to prepare inhibitors of PME-1 and/or PP2A and inhibitors prepared using such methods. Further embodiments relate to biochemical analyses of the interactions of PME-1 alone or in complex with PP2A. Further embodiments relate to compositions including mimetics and small molecules, optionally, secondary agents, which may be used to treat disorders in which PME-1 and/or PP2A activity plays a contributing role.

Abstract: Provided are a method of isolating and identifying hepatic oval cells from the liver, and a method of single cell culture of hepatic oval cells. A method of separating and/or acquiring hepatic oval cells from a mammal, comprising a step for examining the expression of CD133, CD45 and Ter119. Particularly, hepatic oval cells that exhibit the pattern of CD133+, CD45? and Ter119? for the three cell surface markers CD133, CD45 and Ter119 are separated and/or acquired, from a mammal. A method of single cell culture of hepatic oval cells, comprising culturing the hepatic oval cells obtained by the above-described method, in the presence of a growth factor and an extracellular matrix.

Abstract: Using two types of antibodies, i.e., a first antibody having a higher affinity for a target substance than for a competitive substance and a second antibody having a higher affinity for the competitive substance than for the target substance, a specimen is treated with these two antibodies. Then, the competitive substance in the specimen first binds to the second antibody and thus the ratio of the target substance to the competitive substance in the specimen is enlarged. As a result, the target substance becomes liable to bind to the first antibody and, in its turn, the reactivity of the target substance is elevated compared with the case of using the first antibody alone. Thus, the target substance in the specimen can be accurately assayed while avoiding the effects of the competitive substance contained in the specimen.

Abstract: Methods of determining health status based on analysis of single cells in a sample or set of samples from an individual are described.

Abstract: The invention concerns methods, agents and kits for qualitative and quantitative detection and identification of pathogens and pathogen spectra based on endotoxins and other pyrogens.

Abstract: Disclosed are assays useful for detecting kinase activity. The assays utilize thiol-reactive fluorescent reagents and include reacting a reaction mixture that contains an ATP analog such as ATP?S to form an ADP analog such as ADP?S if kinase activity is present in the reaction mixture. The ADP analog reacts with the thiol-reactive fluorescent reagent and the reagent exhibits a change in fluorescence, thereby indicating that kinase activity is present in the reaction mixture.

Abstract: The present invention is directed to methods and compositions for improving pulmonary surfactant catabolism. More specifically, the specification describes methods and compositions for making and using a lysosomal phospholipase A2 in methods for the diagnosis, and treatment of disorders of phospholipid catabolism such as pulmonary alveolar proteinosis.

Abstract: The present invention relates to a package of screening methods for developing drugs against pathogenic microbes having two-component system of DevR-DevS and/or DevR-Rv2027c and its homologues, said method comprising steps of over-expressing DevR, DevS, and Rv2027c and their single domain derivatives including mutant variant proteins, autophosphorylating DevS, and Rv2027c proteins and thereafter, phosphotransfering to DevR and its derivatives in SDS-PAGE or High-throughput format in the presence of a test compound, and determining the drug-potential of the test compound, wherein the potential of the drug is inversely proportional to (i) the degree of autophosphorylation of DevS and Rv2027c, (ii). the degree of phosphotransfer-based dephosphorylation of DevR and/its single domain derivative, and (iii). the degree of dephosphorylation of phosphorylated species of DevS and Rv2027c and/their single domain derivatives, and a method of treatment, and a composition thereof.

Abstract: An alizarin-based chromogenic substrate, a composition containing the substrate, and its use to detect the presence of an enzymatic activity are disclosed. The substrate is particularly applicable in the field of biological diagnosis.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: Provided is a method of storing a reagent in a microfluidic device. The reagent, in a liquid form, is loaded into reaction chambers arranged on the microfluidic device; followed by lyophilization as being contained in the microfluidic device.

Abstract: The present invention relates to a forensic test kit and method for the detection of semen. This kit is comprised of two main components: acid phosphatase (AP) test strips and prostate specific antigen (PSA) test strips, which work together to provide evidence of semen on fabrics and other surfaces. The AP strips are used first to test an item, which provides presumptive evidence of semen, while follow-on testing by the more sensitive and specific PSA strips provides confirmatory evidence.

Abstract: A method for measuring sphingomyelin and phosphatidylcholine comprising incubating sphingomyelin and phosphatidylcholine with bacterial sphingomyelinase and bacterial phospholipase D, alkaline phosphatase, choline oxidase, peroxidase, N-Ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline, and 4-aminoantipyrine, preferably for about 45 minutes. A blue dye is generated.

Abstract: In order to make a process of capturing and testing air-borne microorganisms more convenient and quick, a capturing device which comprises the capturing carrier comprising a polymer which is in a gel phase at the time of capturing the microorganisms but undergoes a phase transition under heating to a sol phase at the temperature at or less than 40° C. (especially in the temperature range between 15° C. and 37° C.), and a vessel to contain the capturing carrier is used. Further, by comprising a test reagent in the polymer, the test reagent can be eluted upon said phase transition from a gel phase to a sol phase. By heating the capturing carrier, a phase transition to a sol phase can occur at or less than 40° C. As such, since recovery of microorganisms and addition of a test reagent to the microorganisms can be carried out simultaneously, the process can be simplified and the process time can be shortened.

Abstract: This invention relates generally to the field of mineralization, and specifically to the role of TNAP in regulating the levels of extracellular inorganic pyrophosphate. The invention provides methods for modulating the activity of TNAP activity; methods for screening for modulators of TNAP activity; modulators of TNAP activity; and methods for treating pathologic conditions known of suspected to be affected by modulation of TNAP activity.

Abstract: The present invention relates to a novel pharmaceutical composition of compounds having the biological activity of interferon gamma (IFN-?) or pirfenidone in combination with a diagnostic array of candidate polynucleotides for the improved treatment of all forms of interstitial lung disease, in particular of idiopathic pulmonary fibrosis (IPF).

Abstract: A chimeric protein comprising in sequence a signal peptide, a first amino acid tag, a proteinase bait, a second amino acid tag, a transmembrane domain and a cytosolic domain, wherein the cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes. A cell line expressing the chimeric protein and an assay using the cell line.

Abstract: The invention provides a method of detecting the effect of an agent of interest on the interaction between two or more polypeptides introduced into a cell. The invention also provides a method for quantifying the interaction between at least two molecules of interest, which are introduced into a cell. A method for quantifying the effects of an agent of interest or the interaction between two molecules of interest on cellular constituents or functions in the same cells is also provided. The above inventive methods can be automatically quantified by a device, such as a HCS device, and utilized in the construction of a database.

Abstract: Method for identifying myeloid or plasmacytoid dendritic cells provided by a mammal, stimulated or unstimulated, comprising the steps of: a) preparing a cell sample; b) contracting the cell sample myeloid or plasmacytoid dendritic cells to form a complex; c) detecting the complex; characterized in that the phosphatase is the Receptor type Tyrosine Phosphatase Gamma Protein (PTPRG), acting as a specific marker of said dendritic cells, and in that the compound is a polypeptide capable of selectively bind to the PTPRG or to a fragment thereof or to a oligonucleotide complementary to a PTPRG mRNA logonucleotide in such a manner as to allow the selective recognizing of the dendritic cells in the cell sample.

Abstract: To gain a better understanding of breast tumor angiogenesis, breast endothelial cells (ECs) were isolated and evaluated for gene expression patterns. When transcripts from breast ECs derived from normal and malignant breast tissues were compared, genes that were specifically elevated in tumor-associated breast endothelium were revealed. These results confirm that neoplastic and normal endothelium in human breast are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

Abstract: Cdc25A is herein identified as a substrate for ?-TrCP1- or ?-TrCP2-mediated ubiquitination and subsequent degradation via the ubiquitin-proteasome pathway. In particular, it has been found that interfering with ?-TrCP expression or function, or increasing ?-TrCP degradation, leads to accumulation of Cdc25A in a cell. Since degradation of Cdc25A is a key feature of the response to DNA damage, leading to a stall in the cell cycle during which the cell can repair the damage, Cdc25A accumulation can abolish this response, thereby sensitizing the cell to DNA damage. Described herein are assays for identifying ?-TrCP inhibitors, and method of using such inhibitors for modulating Cdc25A degradation, sensitization of tumor cells, and as adjuvants in cancer therapy based on DNA damaging agents.

Abstract: The present invention relates to methods of measuring the activity of a hydrolytic agent comprising contacting a biomolecule with a hydrolytic agent in the presence of a fluorescent dye under conditions that allow digestion of the biomolecule by the hydrolytic agent. The fluorescence of the dye is monitored over time and a change in fluorescence signifies digestion of the biomolecule by the hydrolytic agent. The biomolecule is preferably a protein, peptide or proteome but can also be a carbohydrate, oligonucleotide or lipid. Further methods relate to determining an end point for digestion of a biomolecule by a hydrolytic agent, and methods of monitoring digestion of a biomolecule by a hydrolytic agent. The monitoring can be performed on the reaction mixture in real time or via sampling. The invention also relates to kits for carrying out the method.

Abstract: Provided are methods and compositions for assaying for ubiquitin agents that are enzymatic components of ubiquitin-mediated proteolysis and, more particularly, methods and compositions for assaying for agents that modulate the activity of such ubiquitin agents.

Abstract: The present disclosure relates to methods for treating leukemia, pre-leukemic conditions, as well as myelodysplastic syndrome and acute myelogenous leukemia. The present disclosure further relates to compounds that can be used for treating leukemia, pre-leukemic conditions, as well as myelodysplastic syndrome and acute myelogenous leukemia. The present disclosure also relates to methods for identifying compounds that can be used for treating leukemia, pre-leukemic conditions, as well as myelodysplastic syndrome.

Abstract: There is provided a method for the detection of phytase activity in a sample, which comprises bringing into association a phytase substrate and said sample, and measuring the level of an organic metabolite of said phytase substrate.

Abstract: Provided are methods for determining the amount of total thiamine in a body fluid sample using liquid chromatography and mass spectrometry. Total thiamine is converted to free thiamine by treatment with an acid phosphatase prior to thiamine separation and quantification.