Abstract: The present invention provides for up- and down-regulation of cellular autophagy, e.g., for treating cancer or neurological disease. The invention results, in part, from discovery of two novel proteins, ATG14L (previously called “BISC”) and Rubicon (previously called “BIRC”), which bind to a Class III phophatidylinositol 3?-kinase (PI3K)/Vps34-Beclin 1 autophagic complex. ATG14L and Rubicon each regulate autophagic activity in an opposing manner. ATG14L and Rubicon can be used, for example, to increase/decrease autophagic activity, to increase/decrease PI3K/Vps34 kinase activity, and in so doing, treat diseases and disorders, such as cancer, neurodegenerative disease, stroke, metabolic disease, and age-related disease. ATG14L can increase autophagic activity and PI3K/Vps34 kinase activity; and Rubicon can decrease autophagic activity and PI3K/Vps34 kinase activity.

Abstract: The present invention provides cell populations that are enriched for mesendoderm and mesoderm, and cell populations that are enriched for endoderm. The cell populations of the invention are useful for generating cells for cell replacement therapy. The present invention further provides a method of generating hepatocytes, cell populations enriched for hepatocytes, and a method of hepatocyte replacement therapy.

Abstract: The invention provides a use of a long-circulating microvesicle comprising a sterol, partially synthetic or wholly synthetic vesicle-forming phospholipids, and a corticosteroid in water soluble form, which microvesicle has a mean particle diameter size range of between about 75 and 150 nm and which microvesicle is non-charged or negatively charged at physiological conditions, for the preparation of a medicament for the treatment of atherosclerosis and/or cardiovascular disease. A method for treating a subject suffering from, or at risk of suffering from, atherosclerosis and/or cardiovascular disease, comprising administering to said subject a therapeutically effective amount of such long-circulating microvesicles is also provided.

Abstract: The present invention relates to methods of suppressing the transcriptional expression of one or more genes by methylating the chromatin histone proteins of the one or more genes. Specifically, a viral SET domain histone lysine mehtyltransferase (vSET or vSET-like protein) methylates lysine 27 of a gene's histone protein 3 (H3-K27) thereby suppressing the transcription of the gene.

Abstract: The present invention is directed to compositions useful as imaging agents for use in monitoring atherosclerotic plaque regression using, for example, MRI, CT, Gamma-scintigraphy, or optical imaging techniques. Methods and compositions of using the same are described.

Abstract: The present invention relates to compounds that modulate the replication of negative-sense, single-stranded RNA viruses, such as influenza virus, and the use of such compounds. The invention relates to methods for increasing the titer of negative-sense, single-stranded RNA viruses, such as influenza virus, in substrates for virus propagation (e.g., tissue culture). The invention also relates to the use of compounds that decrease virus replication as antiviral agents. The invention further relates to methods for identifying compounds that modulate the replication of negative-sense, single-stranded RNA viruses, in particular, influenza virus.

Abstract: Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compounds are effective to enhance glucocerebrosidase activity.

Abstract: Methods for performing epitope mapping, and for characterizing the antibody binding affinity and epitope diversity of antibodies in a sample using peptide microarray are provided. In some aspects, methods are provided for the specific characterization of IgE and IgG4. Also disclosed are methods for diagnosing whether a milk-allergic individual will outgrow his or her allergy based on the characterization of the individual's milk allergen-specific IgE antibodies.

Abstract: The present invention provides cell populations that are enriched for mesendoderm and mesoderm, and cell populations that are enriched for endoderm. The cell populations of the invention are useful for generating cells for cell replacement therapy.

Abstract: The present invention concerns conjugate compounds comprising a bisphosphonate covalently bonded to a prostatic acid phosphatase inhibitor and compositions comprising such conjugates. Methods for treating and inhibiting prostate cancer bone metastases, and determining whether a conjugate is useful for such treatment are also provided. In some instances, the bisphosphonate is alendronate, and it is covalently bonded to either tartaric acid or glyceric acid.

Abstract: The present invention is directed to methods of diagnosing Noonan-like syndrome with loose anagen hair comprising detecting a mutation in SHOC2 gene. One specific diagnostic mutation disclosed is an A-to-G transition at position 4 resulting in a mutation at position 2 of SHOC2 amino acid sequence from serine to glycine. The invention also provides related sequences and kits.

Abstract: The present invention relates to identification of tumor suppressor activity of a protein, KLF6 (KLF6), and to related diagnostic and therapeutic compositions and methods. The discovery of this tumor suppressor activity provides screening targets as well, particularly screening for compounds that overcome gene inactivation or alteration.

Abstract: The present invention provides polypeptides and peptides derived from cadherin. The polypeptides and peptides are useful in a method of inhibiting amyloid deposition and a method of inhibiting tumor metastasis. A method of determining susceptibility to Alzheimer's disease and a method of screening for agents that modify cadherin processing are also provided.

Abstract: It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by masking the site with a compound that prevents IgE binding or by altering as little as a single amino acid within the protein, most typically a hydrophobic residue towards the center of the IgE-binding epitope, to eliminate IgE binding. The method allows the protein to be altered as minimally as possible, other than-within the IgE-binding sites, while retaining the ability of the protein to activate T cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity The examples use peanut allergens to demonstrate alteration of IgE binding sites. The critical amino acids within each of the IgE binding epitopes of the peanut protein that are important to immunoglobulin binding have been determined.

Abstract: Methods, systems and apparatus for characterizing networks are presented. For example, a method of characterizing a network represented by a plurality of nodes and a plurality of edges is provided. The method may be implemented on a processor device and includes calculating, for example, by the processor device, a passthrough count of at least a portion of the network. The passthrough count includes a count of a number of passthroughs in the at least a portion of the network. A passthrough includes one of the plurality of nodes, a directed edge of the plurality of edges coupled to the one of the plurality of nodes, and another edge of the plurality of edges coupled to the one of the plurality of nodes. At most one of the directed edge and the other edge is directed towards the one of the plurality of nodes. At most one of the directed edge and the other edge is directed away from the one of the plurality of nodes.

Abstract: The invention relates generally to the THAP1 gene and mutations in this gene, as well as the THAP1 protein and mutations in this protein, that are associated with dystonia. The invention relates to the identification, isolation, cloning and characterization of the DNA sequence corresponding to the wild type and mutant THAP1 genes, as well as isolation and characterization of their transcripts and gene products. The invention further relates to methods and kits useful for detecting mutations in THAP1 that are associated with dystonia, as well as to methods and kits useful for diagnosing dystonia. The present invention also relates to therapies for treating dystonia, including gene therapeutics and protein/antibody based therapeutics.

Abstract: The present invention relates, in general, to a screening method for identifying novel viral proteins with interferon antagonizing function using a transfection-based assay, and the use of such proteins in isolating various types of attenuated viruses for the development of vaccine and pharmaceutical formulations. The invention also relates to the use of viral interferon antagonists in screening assays to identify potential anti-viral agents. The invention further relates to protocols utilizing interferon antagonists, e.g., NS1, to enhance gene therapy or DNA vaccination based on their ability to increase gene expression.

Abstract: Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compoiunds are effective to enhance glucocerebrosidase activity.

Abstract: The present invention relates to the discovery, identification and characterization of a receptor protein, referred to herein as T1R3, which is expressed in taste receptor cells and associated with the perception of bitter and sweet taste. The invention encompasses transgenic animals and cells that do not express functional T1R3 protein, particularly knock-out animals and cells, and transgenic animals and cells that express a non-native T1R3 protein. Experimental model systems based on these animals and cells can be used to study T1R3-mediated taste transduction and responses of the components of the T1R3 signal transduction pathway to various tastants, furthering our understanding of the molecular biology and biochemistry of taste. Such model systems would also be useful for screening for novel tastants and taste modulators, such as enhancers of desirable flavors, and blockers of undesirable flavors.

Abstract: Disclosed herein is a novel method of treating vitiligo by using an excimer laser that emits light in the UVB range. The invention includes a method of incrementally increasing exposure of affected vitiligo areas with UVB laser light from an excimer laser to restore pigmentation to skin areas afflicted with vitiligo.