Abstract: The present invention is directed to a method of identifying tissue targeting domains. In particular, the invention relates to methods for identifying a polynucleotide encoding a targeting domain which directs tumor cell localization to secondary sites, to methods of utilizing the polynucleotide and corresponding polypeptide or fragments thereof and compositions comprising the same.

Abstract: The claimed invention comprises a single molecule-format bioluminescent probe for detecting a target-specific ligand in a living cell, which comprises, a ligand-binding molecule of which conformation is changed upon binding to the ligand, wherein the ligand-binding molecule comprises a ligand-binding domain (LBD) of a nuclear receptor and an LBD-interacting domain that is a co-activator peptide of said nuclear receptor, and an N-terminal polypeptide and a C-terminal polypeptide of a click beetle luciferase (N-CBLuc and C-CBLuc), which flank each end of the ligand-binding molecule, respectively, wherein the N-CBLuc and the C-CBLuc self-complement to generate a luminescent signal only upon binding of the ligand to the ligand-binding molecule.

Abstract: The invention is comprised, in part, of a surface that contains more than one component or construct. Such heterogenous surface compositions and configurations, related systems and methods for sensing particle or analyte interaction therewith can selectively and/or differentially interact with a range of particles/analytes, in lieu of specific molecular sensor-analyte interactions for each particle. These interactions of various analytes or particles can differ sufficiently in strength and range between multiple analyte types or particles to effect a separation of analytes or particles mixtures, in a way that requires no sensing or detection. With incorporation of a sensing mechanism, discrimination/detection of different compounds within an analyte mixture can be accomplished.

Abstract: The present invention discloses a dysregulation of a PRKX gene and the protein products thereof in Alzheimer's disease patients and individuals being at risk of developing Alzheimer's disease. Based on this finding, the invention provides methods for diagnosing and prognosticating Alzheimer's disease in a subject, and for determining whether a subject is at increased risk of developing Alzheimer's disease. Furthermore, this invention provides therapeutic and prophylactic methods for treating and preventing Alzheimer's disease and related neurodegenerative disorders using a PRKX gene and its corresponding gene products. Screening methods for modulating agents of neurodegenerative diseases are also disclosed.

Abstract: TGD2 proteins of Arabidopsis are proposed to be a substrate binding component of a lipid transfer complex in the inner chloroplast envelope membrane. Loss of function of this protein or other components of this complex may disrupt the endoplasmic reticulum (ER)-pathway of thylakoid lipid biosynthesis. In one embodiment, the present invention contemplates a minimal binding domain capable of specifically binding phosphatidic acid. Alternatively, the minimal binding domain may further comprise accessory binding domains that, in combination, create a complete TGD2 phosphatidic acid binding domain. Consequently, phosphatidic acid may be quantitatively detected from samples as described in the methods herein.

Abstract: Provided herein are methods for detecting and/or measuring the inhibition of TOR kinase activity in a subject and uses associated therewith.

Abstract: The molecules of formula (I) are useful in treating diabetes, obesity, hypercholesterolaemia, hyperlipidaemia, cancer, inflammation or other conditions in which modulation of lipis of eicosanoid status or functions may be desirable. Formula (I): Z1—Z1—Z2 wherein a) Z1 represents CO2H or a derivative thereof; b) Z2 represents F, H, —CO2H or a derivative thereof; and c) X represents fluorinated alkylene; or a solvate thereof, for example a perfluorinated fatty acid or derivative thereof.

Abstract: The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.

Abstract: This invention relates to methods for identifying agents useful for treatment of diseases and pathological conditions affected by Retinoid X Receptor apoptosis. The invention also relates to methods for treating diseases and pathological conditions affected by RXR apoptosis. The invention includes compositions that are useful in the study and treatment of diseases and pathological conditions affected by RXR apoptosis.

Abstract: The present invention provides the three-dimensional structure of human ?-N-acetylglucosaminidase (NAGLU) protein. This crystallographic information is useful in the identification and development of novel binding compounds of NAGLU, NAGLU mutants, for example, those associated with Sanfilippo syndrome type B (mucopolysaccharidosis III B (MPS III-B)), and other NAGLU family members (family 89 ?-N-acetylglucosaminidase) which may modulate the activity and/or stability of mutated NAGLU. Such compounds may be useful for the treatment of Sanfilippo syndrome type B (mucopolysaccharidosis III B (MPS III-B)).

Abstract: The present invention provides for methods and systems for detecting steroids. Examples of such steroids include estrogen, progesterone, androgen, testosterone, and derivatives and analogs thereof. Systems useful for carrying out the method include tripartite constructs including a DNA-binding domain, a ligand binding domain, and an activation domain. The present invention provides numerous improvements over previous diagnostic systems for detection of steroids, such advantages include that the method allows for detection of steroid analogs and derivatives, whose structures may not yet be known, the method is generally applicable to a wide variety of organisms, and numerous ligand binding domains may be used in conjunction with the present system.

Abstract: A method of in situ immunohistochemical analysis of a biological sample is provided. The method allows for the multiplex and simultaneous detection of multiple antigens, including multiple nuclear antigens, in a tissue sample.

Abstract: The present invention provides a mutant form of a protein kinase its production and its use for identifying compounds that bind to the PIF-binding pocket allosteric site of the protein kinase.

Abstract: The present invention relates to a method for diagnosing cancers by measuring proteins associated with tumorigenesis and metastasis, and a diagnostic kit using the same, particularly relates to the method for diagnosing cancers by measuring the changes of glycosylation of proteins and the kit for diagnosis of cancers using the said method. The method and kit of the present invention can effectively be used for the sensitive diagnosis of cancers comprising colon cancer, stomach cancer, lung cancer and liver cancer.

Abstract: The present invention is directed to methods of modulating HSF1 activity comprising modifying the acetylation of the DNA binding domain of the HSF1.

Abstract: Briefly described, embodiments of this disclosure include ligand-regulable transactivation systems, methods of producing ligand-regulable transactivation systems, methods of using ligand-regulable transactivation systems, reporter polynucleotides, method of producing reporter polynucleotides, activator fusion proteins, methods of producing activator fusion proteins, methods of regulating gene expression in vitro and in vivo for gene therapy, methods of screening estrogen receptor modulators with therapeutic treatments (e.g., anticancer, antiosteoporosis, and hormone replacement treatments), method of screening compounds (e.g., drugs and environmental pollutants) for the estrogenic effect, methods of evaluating the estrogen receptor pathway under different pathological conditions are provided, and the like.

Abstract: In general, the present invention relates to compounds capable of inhibiting p38 in vivo or in vitro, and methods for treating conditions associated with p38 activity or cytokine activity.

Abstract: Nanocrystals having a ZnTe core and methods for making and using them to construct core-shell nanocrystals are described. These core-shell nanocrystals are highly stable and provide quantum yields and stability suitable for applications such as flow cytometry, cellular imaging, and protein blotting, medical imaging, and other applications where cadmium toxicity is an issue.

Abstract: A rapid method for the quantitation of various live cell types is described. This new cell fluorescence method correlates with other methods of enumerating cells such as the standard plate count, the methylene blue method and the slide viability technique. The method is particularly useful in several applications such as: a) quantitating bacteria in milk, yogurt, cheese, meat and other foods, b) quantitating yeast cells in brewing, fermentation and bread making, c) quantitating mammalian cells in research, food and clinical settings. The method is especially useful when both total and viable cell counts are required such as in the brewing industry. The method can also be employed to determine the metabolic activity of cells in a sample. The apparatus, device, and/or system used for cell quantitation is also disclosed.

Abstract: There is provided methods and uses for promoting cell death, when combined with chemotherapeutic agents, in an abnormally proliferating cell, and for treating a proliferative disorder in a subject, which methods and uses involve contacting a cell with, or administering to a subject, an agent that modulates glycogen synthase kinase-3? activity to a cell that is being treated with a chemotherapeutic agent.

Abstract: Methods for detecting phosphorylation of receptor tyrosine kinases (“RTKs”) upon activation are provided. The method employs cells comprising two fusion products: (1) an RTK fused to a small fragment of ?-galactosidase and (2) a phosphotyrosine binding peptide fused to the large fragment of ?-galactosidase, where the 2 fragments weakly complex to form an active enzyme, and optionally a construct for a cytosolic RTK phosphorylating kinase, when the RTK does not autophosphoryate. To detect phosphorylation a ?-galactosidase substrate is added to the cells, whereby product formation indicates the occurrence of phosphorylation.

Abstract: A method for rapid collection and assay of oral fluids is disclosed. The method comprising the steps of: (a) placing an assay device into an oral cavity, (b) removing said assay device from said oral cavity; and (c) determining the presence or absence of at least one analyte.

Abstract: The present invention relates to novel compounds 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. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

Abstract: The present invention provides target proteins and target genes for bioactive substances such as drugs, and means that enable the development of novel bioactive substances using the same. To be specific, the present invention provides target proteins and target genes for bioactive substances; screening methods for substances capable of regulating bioactivities; bioactivity regulators; a bioactive substance derivative production method; a complex comprising a bioactive substance and a target protein, and a method of producing the complex; and kits comprising a bioactive substance or a salt thereof; determination methods for the onset or risk of onset of a specified disease or condition, determination methods for susceptibility to a bioactive substance, and determination kits used for the determination methods, and the like.

Abstract: Cells are genetically modified to express a luminophore, e.g., a modified (F64L, S65T, Y66H) Green Fluorescent Protein (GFP, EGFP) coupled to a component of an intracellular signalling pathway such as a transcription factor, a cGMP- or cAMP-dependent protein kinase, a cyclin-, calmodulin- or phospholipid-dependent or mitogen-activated serine/threonin protein kinase, a tyrosine protein kinase, or a protein phosphatase (e.g. PKA, PKC, Erk, Smad, VASP, actin, p38, Jnk1, PKG, IkappaB, CDK2, Grk5, Zap70, p85, protein-tyrosine phosphatase 1C, Stat5, NFAT, NFkappaB, RhoA, PKB). An influence modulates the intracellular signalling pathway in such a way that the luminophore is being redistributed or translocated with the component in living cells in a manner experimentally determined to be correlated to the degree of the influence.

Abstract: The present invention provides polypeptide binding agents, e.g. antibodies, that exhibit the ability to kinetically modulate the binding and signaling of biological signaling complexes, e.g., receptor-ligand complexes; methods of identifying such polypeptide binding agents, methods of making such polypeptide binding agents, compositions comprising such polypeptide binding agents, and methods of using such polypeptide binding agents.

Abstract: Provided herein are a method and system to detect an active protease in a sample, and related methods and systems to diagnose a condition in an individual, the condition being associated to abnormal protease activity in the individual.

Abstract: The present invention relates to novel synthetic or natural peptides for use in treating viral or parasitic infections or in the treatment of tumors. The peptides of the present invention are less than 30 amino acids in size, preferably less than 20 amino acids, in particular 15 to 20 amino acids, and in vitro the peptides specifically bind a type 2A protein phosphatase holoenzyme or one of its subunits. The invention also relates to a method for identifying said peptides, and to their uses.

Abstract: Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise a phenol-modified opioid prodrug that provides enzymatically-controlled release of a phenolic opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the phenolic opioid from the phenol-modified opioid prodrug so as to modify enzymatic cleavage of the phenol-modified opioid prodrug.

Abstract: The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.

Abstract: A method of determining a concentration of analytes of interest in a sample reaction mixture is disclosed. The method can include measuring intensities of the polarized fluorescence of at least one comparative reaction mixture containing different, known amounts of the analytes of interest, and measuring the intensities of the polarized fluorescence of a sample reaction mixture. The method can also include determining the preliminary concentrations of the analytes of interest in the sample reaction mixture by comparing the measured intensities of the sample reaction mixtures at various time points. The margin of error for the preliminary concentration of the analytes of interest in the sample can be determined at the various time points. Finally, the concentration of the analytes of interest in the sample reaction mixture can be determined by comparing the preliminary concentrations and the respective margin of error at the given time points.

Abstract: Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an opioid prodrug that provides enzymatically-controlled release of an opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the opioid from the opioid prodrug so as to attenuate enzymatic cleavage of the opioid prodrug.

Abstract: The present invention provides methods of identifying markers indicative of the risk of developing a neurodevelopmental disorder caused in part by antibody- or autoantibody-mediated damage of neural tissue, including autism spectrum disorder (ASD). The invention further provides methods of diagnosing whether an individual has a neurodevelopmental disorder, including an ASD, and methods for determining the risk that a mother's future offspring will develop an a neurodevelopmental disorder, including an ASD.

Abstract: Immunogenic T-cell receptor gamma Alternate Reading Frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.

Abstract: A method for the manufacture of at least one sorbent having at least two different groups, which are capable of binding, for the selective binding of a substrate, characterized in that it comprises the steps (i) to (ii): (i) determining at least two groups capable of binding a sorbent from a synthetic or natural first substrate, (ii) respectively applying at least two different groups capable of binding a second synthetic or natural substrate to one respective carrier, thereby forming at least one sorbent, whereby the groups are the same groups of step (i) or are groups that are complementary thereto, and the second substrate of step (ii) is the same or different from the first substrate according to step (i), and whereby the groups are determined such that the contributions of the Gibbs energies of the individual groups to the non-covalent bond with the second substrate yield a negative value of the Gibbs energy ?G, such that a binding strengthening occurs that results in an improved separation selectivity

Abstract: A method for assessing the effect of a test compound on LRRK2 in a cell-based system, the method comprising the steps of a) assessing the effect of exposing the cell-based system comprising LRRK2 to the test compound on the phosphorylation state of Ser910 and/or Ser935 of the LRRK2; and/or b) assessing the effect of exposing the cell-based system comprising LRRK2 to the test compound on the binding of the LRRK2 to a 14-3-3 polypeptide. The method is considered to be useful in assessing the effect of putative LRRK2 inhibitors in cell based systems, including in vivo systems.

Abstract: The present invention relates to novel compounds 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. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

Abstract: The subject invention relates in part to the surprising and unexpected discovery that insects that are resistant to Bacillus thuringiensis Cry toxins have measurably altered alkaline phosphatase (ALP) activity as compared to insects that are susceptible to Cry toxins. This and other surprising discoveries reported herein have broad implications in areas such as managing and monitoring the development of insect resistance to B.t. toxins. For example, the subject invention provides a simple and fast assay (enzymatic or otherwise) for detecting ALP activity levels and thereby monitoring the development of resistance by insects to crystal protein insect toxins. There was no prior motivation or suggestion to go about resistance monitoring using this simple and easy approach.

Abstract: The present invention relates to the roles played by TTLL4 genes in pancreatic cancer carcinogenesis and features a method for treating or preventing pancreatic cancer by administering a double-stranded molecule against one or more of the TTLL4 genes or a composition, vector or cell containing such a double stranded molecule. Also, disclosed are methods of identifying compounds for treating and preventing pancreatic cancer, using as an index their effect on the over-expression of TTLL4 in the pancreatic cancer cell.

Abstract: The invention provides compositions comprising a TERT-RMRP or TERT-RNA complex and methods of treating subjects with genetic diseases in which gene silencing is either increased by administering the compositions of the invention or decreased by administering an inhibitor of the RNA-dependent RNA polymerase (RdRP) activity of these compositions. Moreover, the invention provides methods of screening for agonists and antagonists of RdRP activity and TERT-RMRP complex formation. Finally, the invention provides a method of identifying a RNA molecule that forms a complex with a TERT polypeptide and has RdRP activity.

Abstract: The invention provides kits and methods for detecting or monitoring the number of cells in sample. The cell comprises a cell surface associated protein (CSAP) comprising a cytoplasmic (cytosolic) and an extracellular (ecto) domain. The kit comprises: (i) a chromatographic device; and (ii) a CSAP-binding agent. The method comprises: (i) optionally contacting the sample with an agent capable of lysing or permeabilizing CSAP bearing cells; (ii) contacting the sample with a CSAP-binding agent that binds to the cytoplasmic domain of the CSAP; and (iii) directly or indirectly evaluating the level or presence of bound CSAP in the sample.

Abstract: The present invention relates to methods for testing for the binding of a ligand to a G Protein-Coupled Receptor. In particular, the methods of the invention are useful in high throughput screening for ligands which bind to G Protein-Coupled Receptors.

Abstract: Coelenterazine analogues with different luminescence properties from conventional ones and coelenteramide analogues with different fluorescence properties from conventional ones have been desired. The invention provides coelenterazine analogues modified at the 8-position of coelenterazine and coelenteramide analogues modified at the 2- or 3-position of coelenteramide.

Abstract: The present invention relates to a screening method for a compound and includes a step of detecting binding between a vitamin D receptor and CDP. A novel method enabling screening in vitro of a compound having strong bone forming action and low side effects, a compound participating in osteoblast differentiation and selected by the method of screening, a therapeutic agent containing the compound for diseases intervening in the increase in vitamin D-mediated transcriptional activity by a complex of a vitamin D receptor and CDP, and a kit for performing the screening method are provided.

Abstract: When relatively hard Au bump electrodes are mass-produced by electrolytic plating while ensuring usually required properties such as a non-glossy property and shape-flatness, combination of conditions, such as low liquid temperature, high current density, and low concentration of added Tl (thallium) that is an adjuvant, will be selected by itself. However, in such conditions, there is a problem that it is difficult to maintain the Tl concentration in a plating solution and, when the Tl concentration is reduced, defective appearance of the Au bump electrodes is generated by anomalous deposition. Conventionally, there has been no means to directly monitor minute Tl concentration and the Tl concentration has been controlled by analyzing the plating solution periodically. However, this can not prevent generation of a lot of defective products.

Abstract: Provided is an age-related apolipoprotein B oxidase (apoBNOX) found tightly associated with the low-density lipoprotein particles and believed to be responsible for oxidizing lipoprotein particles and initiating atherogenesis. It causes damage by directly oxidizing the apolipoprotein B protein and indirectly oxidizing the lipids in the particles due to superoxide formation by the apoBNOX and its conversion into hydrogen peroxide. apoBNOX activity is inhibited by tyrosol and hydroxytyrosol and components of white wine, important components of French and Mediterranean diets, which seem to be a very good source of inhibitors of the apolipoprotein B oxidase. Agents comprising at least one naturally-occurring apoBNOX inhibitor and compositions lessen, ameliorate or treat disorders and complications resulting from cell damage caused by oxidation of apolipoprotein B.

Abstract: Evidence demonstrating that elevated expression of dUTPase protects breast cancer cells from the expansion of the intracellular uracil pool, translating to reduced growth inhibition following treatment with 5-FU is provided. The implementation of in silica drug development techniques to identify and develop small molecule inhibitors of dUTPase are reported. As 5-FU and the oral 5-FU pro-drug capecitabine remain central agents in the treatment of a variety of malignancies, the clinical utility of a small molecule inhibitor to dUTPase represents a viable strategy to improve the clinical efficacy of these mainstay chemotherapeutic agents.

Abstract: A method and article to immobilize a protein, including, for example, combining the protein and a mixture comprised of an activated spacer compound having a maleimide group in a buffer solution, to form a maleimide-modified protein; and contacting the maleimide-linker-modified protein and a buffer swollen, thiol-modified, surface bound polymer to immobilize the maleimide-linker-modified protein on the polymer surface of the article. Also disclosed are articles having an immobilized protein thereon, and to methods of using the articles having an immobilized protein, as defined herein.

Abstract: The present invention discloses a method for diagnosing a cardiac complication in a patient due to coronary catheterization, comprising the steps of (a) obtaining at least one baseline sample from the patient during or after coronary catheterization, and then (b) obtaining at least one test sample from the patient after coronary catheterization, (c) determining a change of the level of an ANP-type peptide between the baseline sample and the test sample, wherein a significant decrease in the level of the ANP-type peptide according to step c) indicates a cardiac complication.

Abstract: The disclosure features a variety of compositions and methods for modulating an interaction between MUC1 and caspase-8 and/or an interaction between MUC1 and a DED-containing protein (e.g., an anti-apoptotic DED-containing protein or a pro-apoptotic DED-containing protein). Such methods and compositions are useful for the treatment or prevention of, e.g., a variety of pathological disorders characterized by elevated or decreased levels of apoptosis. Moreover, the compositions and methods are also useful to identify, design, and generate compounds that modulate the interactions. The compounds and/or pharmaceutical compositions containing the compounds can be used in the treatment of disease.