Abstract: The present invention generally relates to compounds to treat viral infections and methods of their use. In particular, compounds of the present invention inhibit the activity of NS1 protein, thereby mitigating viral infection and, in particular, influenza virus infection. Accordingly, NS1 protein inhibitors and methods of treatment that employ such inhibitors are contemplated by the present invention.

Abstract: The present invention relates to a modulator, in particular an inhibitor, of microRNA-24 (miR-24) and to direct and indirect miR-24 targets for use in a method of treatment and/or prevention of ischemia, in a method of prevention of endothelial apoptosis or in a method of induction of angiogenesis. The present invention further relates to a precursor of miR-24 and to siRNAs or shRNAs against direct or indirect miR-24 targets for use in a method of treatment of angiogenesis associated with cancer. The present invention also relates to an in vitro method for diagnosing ischemia or prevalence or disposition for ischemia, and to a method for identifying a modulator of miR-24 and/or direct or indirect miR-24 targets. In addition, the present invention relates to pharmaceutical compositions or kits comprising any of the above agents, to endothelial cells devoid of expressing functional miR-24, and to a non-human, transgenic animal comprising these endothelial cells.

Abstract: The present invention relates to a method for diagnosing the risk of cancer recurrence in a mammalian patient, comprising detecting the expression of macroH2A1.1 and/or macroH2A2 in a biological sample obtained from said patient, wherein a low or reduced expression of said macroH2A1.1 and/or macroH2A2 is indicative for an increased risk of cancer recurrence in said patient. The present invention is further directed at improved methods for treating cancer, in particular breast and/or lung cancer, based on said diagnostic method.

Abstract: The invention is directed to compositions to screen for small molecule drugs that inhibit proteases, such as viral proteases, e.g., HIV proteases; and methods for making and using these compositions. The invention provides compositions and methods for identifying compositions, e.g., drug molecules, that can inhibit proteases, e.g., HIV proteases. In alternative embodiments, the invention provides cell-based assays to screen for compositions, e.g., small molecules or drugs, that inhibit or modify the activity of enzymes such as calcium-dependent protein convertases involved in HIV envelop protein processing, including cleavage of the HIV gp160 envelope precursor, resulting in gp120 and gp41 envelope products.

Abstract: Described are compositions and methods for detecting or monitoring the ability of an individual to mount a cell mediated immune response to a target antigen. Methods rely in part upon the physical association, e.g., by fusion, of a Lethal Factor (LF) polypeptide with a target antigen. The LF polypeptide moiety, including, for example, an LFn polypeptide moiety, serves as a transport factor to deliver target antigens, including full length target polypeptides, to the cytosol of an intact, living immune cell from an individual. Measurement of a cytokine response by the immune cell from the individual provides a read out of a cell cell from mediated immune response. The methods and compositions described provide diagnostic as well as prognostic information and can guide the direction of therapy.

Abstract: The present invention refers to human EGLN2 variants having at position 58 of the amino acid sequence a serine or a leucine and their use in the prevention or treatment of thromboembolic or coronary heart diseases, in particular stroke, prolonged reversible ischemic neurological deficit (PRIND), transitoric ischemic attack (TIA), myocardial infarction and/or early myocardial infarction.

Abstract: The present invention provides compositions and methods for investigating the structural basis of the activation process of CRAC channels, which are essential for T-lymphocyte activation and adaptive immunity. The invention also provides compositions and methods to design, identify and evaluate agents that modulate calcium signaling by regulating the interaction between STIM and Orai proteins. The invention also provides therapeutic agents for cases of immunological disorders, compromised immune function, organ transplantation, or thrombosis.

Abstract: A system, a composition, a method and a kit for identifying anti-bacterial agents are provided. The invention described herein is useful in identifying inhibitors of any bacterial stress response. Moreover, the invention can be applied to any sRNA and its target, any transcription factor and its target, and any transcription factor/sRNA pair (i.e., a transcription factor that regulates a sRNA). In particular, the present invention provides a system, a composition, a method and a kit for the identification of cyclic peptides that block the ?E pathway in Escherichia coli.

Abstract: The invention provides a method of analyzing interactions between pairs of target and effector cells utilizing high-throughput screenings methods for profiling large numbers of single cells in microarrays.

Abstract: The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins.

Abstract: Disclosed is a method for predicting the optimal amounts of radiopharmaceutical and/or chemotherapy agents to administer to a patient, by determining the level of saturation of the therapeutic agents in the patient's cells. The method comprises measuring cellular incorporation of the candidate therapeutic agents in a target cell population on a cell-by-cell basis. The method is able to identify an optimal cocktail of therapeutic agents for treatment of a disease. A method of high-throughput drug discovery incorporating this method, and a 2-stage targeting method of treating a disease using this method are also disclosed.

Abstract: Provided here in are, inter alia, methods of determining whether a patient is resistant or sensitive to glucocorticoid therapy.

Abstract: The present invention provides a feeder cell for target cell induction, wherein the feeder cell is transduced with an immortalizing gene and a suicide gene; and a production process for a target cell sheet using the feeder cell for target cell induction.

Abstract: In response to the need for highly-sensitive antibiotic susceptibility assays and identification assays that do not require extensive incubation times, the present invention provides automated assay methods and systems that permit the determination of antibiotic susceptibilities and/or microorganism identification in a timeframe that is substantially shorter than has previously been attainable using a hybrid system that combines turbimetric and fluorescence determinations using a single, clear-plastic assay platform. Related devices, kits, and components thereof are also disclosed.

Abstract: Heterocyclic compounds having a relatively flexible backbone are used to create combinatorial libraries that permit screening for lead compounds and selection of drug candidates for a variety of uses in human and veterinary medicine as well as in agriculture. The compounds of the library generally differ in ring size and chirality of substituents on the ring. Also disclosed are methods for providing and screening these libraries, preferably in an automated or computerizable manner, such as by using a computer program to virtually screen the compounds in order to identify those that are predicted to have bioactive conformations that should give rise to desirable biological effects.

Abstract: The invention provides methods and compositions for modulating the activity of XBP-I protein, or a protein in a signal transduction pathway involving XBP-I to modulate the TLR-mediated activation of cells of the innate immune system. Enhancing the TLR-mediated activation of cells of the innate immune system enhance inflammatory responses. The present invention also pertains to methods for identifying compounds that modulate Toll-like receptor-mediated signaling.

Abstract: Materials and Methods for identifying and using MHC molecule variants for activating self-reactive T cells in a peptide-specific manner, and their use to focus autoimmune cellular responses against diseases such as cancers and persisting viral infections, are described.

Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for use in these assays.

Abstract: Method and systems provide improved cell handling in microfluidic systems and devices using lateral cell trapping and methods of fabrication of the same that allow for selective low voltage electroporation and electrofusion.

Abstract: The present invention relates to methods of selecting and developing a chemically defined media (“CDM”) for use in the manufacture of biological products. In particular, the present invention is directed to screening methods to determine cell culture technique media supplement blends with enhanced performance characteristics. The present invention is also directed to identifying CDM supplement blends that demonstrate significant increases in harvest titer and/or viable cell density.

Abstract: High-content time-lapse assays on whole animals require their repeated immobilization for high-resolution imaging and manipulation. Here, we present a simple, rapid, and minimally invasive method for repeatedly immobilizing and imaging Caenorhabditis elegans (C. elegans) over extended periods of time inside standard multiwell plates, which are compatible with industrial high-throughput screening platforms and robotics. We use this method to perform subcellular-resolution femtosecond laser microsurgery, and to image the regeneration dynamics of single neurons in vivo at cellular resolution. Our analysis shows that mechanosensory neurons often regenerate in single short bursts that occur stochastically within the first two days post-surgery. In vivo observation of many such physiological processes requires multi-time-point immobilization and imaging of large numbers of animals throughout extended periods of time.

Abstract: A method of screening a compound for effectiveness in treating amyloid beta neurotoxicity comprises culturing mammalian neurons in serum-free defined medium until the neurons are electrically functional, exposing the electrically stable neurons to amyloid beta, monitoring the exposed neurons for impairment of electrical functionality, and treating the exposed neurons with the candidate drug while monitoring their electrical activity for reversal of impairment.

Abstract: In a first aspect, the present invention relates to a method for screening bacteria on their susceptibility against candidate compounds. In a further aspect, the present invention relates to a method for screening the antibiotic efficacy of candidate compounds suppose to have an antibiotic activity on bacteria. Moreover, the present invention relates to a method for forming a bacterial biofilm on a support, a system allowing in vitro and in vivo evaluation of biofilms formed by bacteria as well as methods for the stratification of the treatment regimen against bacterial infections.

Abstract: The present invention describes an improved method of screening of anti HCV agents that may have an efficacy for treatment of hepatitis C virus. The invention includes cryogenic hepatocyte bank, wherein the bank includes multiple hepatocytes collected from multiple HCV patients and the hepatocyte bank includes more than one genotype of HCV. The method involves the isolation and cryopreservation of HCV infected hepatocytes from multiple infected individuals. The isolated and cryopreserved hepatocytes are stored in a cryopreservation bank. These stored hepatocytes then are cultured in a culture medium, and anti-HCV screening of the hepatocytes is done by subjecting HCV infected hepatocytes in parallel to action of different anti-HCV compounds at various concentrations. Effective anti-HCV agents will lead to a decrease in HCV content in the cultures.

Abstract: A method of treating cancer comprises: (a) providing allogenic or autologous white blood cells from a suitable donor; and then (b) administering the white blood cells to the subject in an amount effective to treat the cancer. Preferably the white blood cells comprise innate immune cells. Preferably the white blood cells comprise less than 10% by number of cytotoxic T lymphocytes. Preferably the white blood cells, or more particularly the innate immune cells, are preselected in vitro to kill cancer cells in vitro (for example, by collecting white blood cells from the patient and determining that the white blood cells kill cancer cells in vitro before and thereby pre-selecting the donor, before collecting a subsequent population of cells from the donor for administration).

Abstract: A novel herbal extract, MF101, is effective in the treatment of symptoms of menopause.

Abstract: The present invention relates to a method of identifying a substance altering glucose uptake and/or GLUT4 translocation to the plasma membrane of a cell comprising contacting a test system comprising AKT substrate 160 kDa-protein (AS160-protein) with a test substance, and identifying a test substance as a substance altering glucose uptake of a cell by detecting a signal indicative for altered glucose uptake of a cell; a test system comprising a gene coding for the AKT substrate 160 kDa-protein (AS160-protein) and an inducible promoter providing for controllable expression of the gene; the use of the test system for the identification of a substance improving glucose uptake and/or GLUT4 translocation to the plasma membrane of a cell; and the use of AS 160-protein in a model for type 2 diabetes.

Abstract: The present invention relates to high-throughput methods of screening biological samples to identify microorganisms having potential utilities as biocontrol agents. The methods include, for example, the use of multitest platforms for the simultaneous identification of microorganisms having biocontrol activity, including those useful in improving plant, animal, and human health. In particular, the present invention provides screening methods suitable for identification of microorganisms having potential applications in combating diseases caused by plant pathogens. The disclosure also provides microorganisms having biocontrol activity that are identified by the screening methods disclosed herein.

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: This invention provides compositions and methods for generating components of protein biosynthetic machinery including orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases. Methods for identifying orthogonal pairs are also provided. These components can be used to incorporate unnatural amino acids into proteins in vivo.

Abstract: Provided herein are uses of genes for HOG, Ras and cAMP signal transduction pathways to treat fungal infection. To regulate the HOG pathway of Cryptococcus neoformans, roles of SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 and NHA1 genes were investigated to find that a biosynthesis level of ergosterol is increased when these genes are inhibited. When the genes are inhibited, a large amount of ergosterol is distributed on a fungal cell membrane. Accordingly, since there are many working points of an ergosterol-binding antifungal agent, an efficiency of the ergosterol-binding antifungal agent can be considerably improved. To regulate the Ras and cAMP pathways of Cryptococcus neoformans, roles of RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 and HSP122 genes were investigated to find that a sensitivity to a polyene- or azole-based drug is increased when these genes are inhibited.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: The invention relates to a method for stimulating antigen-specific T cell responses by using accelerated co-cultured dendritic cells, and to uses thereof, such as a method for diagnosing a disease and a method for producing isolated T cell clones displaying specific immunological properties.

Abstract: The application describes therapeutic compositions and methods for treating cancer. For example, therapeutic compositions and methods related to inhibition of FAM83A (family with sequence similarity 83) are provided. The application also describes methods for diagnosing cancer resistance to EGFR inhibitors. For example, a method of diagnosing cancer resistance to EGFR inhibitors by detecting increased FAM83A levels is described.

Abstract: The present invention provides a method of identifying host cell molecules which may be modulated to inhibit viral replication and method of testing antiviral compounds. In addition, the invention provides compositions, methods and medicaments for treating viral infections and/or diseases or conditions caused or contributed to by viruses.

Abstract: The invention concerns an isolated complex comprising an HIV or HTLV protein and a human protein. Corresponding nucleic acids, vectors, host cells, host organisms, compositions, kits, medical uses, diagnostic uses, and methods of screening agents are also contemplated. Disclosed are 212 interactions between 19 retroviral proteins and 131 human proteins.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: Glioblastoma multiforme biomarkers, methods, and compositions are provided. Methods of selecting a treatment for a patient with a brain neoplasm, including Glioblastoma multiforme, are provided. Methods of treating a patient at risk for Glioblastoma multiforme are provided.

Abstract: Provided is a process for creating a 3D metabolically active microtissue perfused with living microvessels which have a direct fluidic connection with neighboring microfluidic channels. The process comprises preparing a template comprising a plurality of channels, and creating a network within said channels, said network comprising microfluidic channels, metabolically active living microvessels, and microtissues. The microvessels can sprout from said microvessels and/or form within the microtissue in response to a stimulus applied from said microfluidic channels or stimulus derived from the said tissues. In another embodiment, a device is provided comprising a supportive structure, one or more microfluidic channels, one or more microtissue compartments, and one or more microvessels, whereby the microvessels connect said microfludic channels and microtissue and perfuse the microtissue to deliver fluid from the microfluidic channels to the microtissues.

Abstract: This invention pertains to screening methods for identifying autophagy inducing compounds.

Abstract: Described is a device comprising a quorum sensor array and a method of using such a device. Also described are methods for calibrating a camera for microstructures.

Abstract: The present invention provides for rapid and large scale evaluation of expression of, or function of, nucleotide sequences in plants. The invention comprises three specific components which provide for fast and large scale evaluation of nucleotide sequences. The first component includes delivery in either a single event a library of different engineered vectors or a single engineered vector for a single target nucleotide sequence comprising sequences the function of which is desired to be known in plant cells. Surprisingly, applicants have discovered that, the introduction of multiple vectors to plant cells predominantly results in individual transgenic plants which contain only a single transformation event. The second feature of the invention involves a highly transformable, fast cycling and/or miniature size plant and the final step involves mass scale analysis of T0 plants for various phenotypes and plasmid rescue to identify the nucleotide sequence present in a particular phenotype.

Abstract: The present invention discloses novel mechanisms in the aging process and describes novel methods for high-throughput screening to identify, detect, and purify agents to be used for improving mitochondrial function, maintaining the cell cycle-arrested state in senescent and post mitotic cells, and thus preventing or treating age-related diseases or disorders associated with accelerated mitochondrial function loss, telomere dysfunction, and/or deterioration of the growth-arrested state. The present invention also discloses a number of compounds or compositions identified from this method. The present invention further provides the use of low doses of rapamycin or its analogs as a mimic of caloric restriction in preventing age-related diseases or disorders.

Abstract: Methods and compositions comprising chemical compounds that modulate the silencing of a polynucleotide of interest in a cell are provided. Such chemical compounds when used in combination with an appropriate silencing element can be used to modulate (increase or decrease) the level of the polynucleotide targeted by the silencing element. Methods of using such compositions both in therapies involving RNAi-mediated suppression of gene expression, as well as, in vitro methods that allow for the targeted modulation of expression of a polynucleotide of interest are provided. Pharmaceutical or cosmetic compositions comprising such compounds and silencing elements also are disclosed. Methods for screening a compound of interest for the ability to modulate the activity of a heterologous silencing element also are provided.

Abstract: Disclosed are compositions and methods for using label free optical biosensors for performing cell assays. In certain embodiments the assays can be performed in highthough put methods and can be multiplexed.

Abstract: Isolated and enriched tumor-initiating cell populations, methods for preparing the same, and uses thereof.

Abstract: Methods are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: A method for the analysis of neurite growth is described, in which a substrate having an array pattern is provided, which has first regions on which neurons and cells similar to neurons can adhere, whereby the first regions are surrounded by second regions, in each instance, on which neurons and cells similar to neurons cannot adhere, whereby neurons or cells similar to neurons adhere only on the first regions of the array, and subsequently, the neurons or cells similar to neurons are exposed to one or multiple or no treatment(s), and during this/these treatment(s) and/or afterwards, the neurite outgrowths from the neurons or cells similar to neurons are analyzed by recognizing and quantifying the connections that are formed between the first regions by means of the neurite outgrowths.

Abstract: Methods of producing populations of predominantly astrocytes, neurons or oligodendrocytes are provided. In addition, methods of treating mammals having astroglial tumors, oligodendrocyte tumors, or neuronal tumors are provided.