Abstract: The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and/or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.

Abstract: It has now been found that the p53 pathway is inactivated in ocular cancers such as retinoblastoma. As such, the present invention is a method for inducing ocular cancer cell death using a p53 activator. In particular embodiments, the p53 activator blocks the interaction between DM2 or DMX and p53. As the p53 activator induces ocular cancer cell death, a method for preventing or treating ocular cancer is also provided.

Abstract: A vaccine composition and method which is effective in preventing or ameliorating Avian Influenza Virus infection is set forth herein. The vaccine contains at least two inactivated strains of avian influenza virus, wherein the combined hemagglutinin (HA) total is at least about 200 HA/dose of the vaccine composition, and wherein each of the strains presents at least about 128 HA/dose, and further wherein one of the strains has the same HA subtype as that of a challenge virus, and wherein at least one of the strains has a different NA subtype than the challenge virus.

Abstract: Polynucleotides encoding a mutant human carboxylesterase enzyme and polypeptides encoded by the polynucleotides which are capable of metabolizing a prodrug and inactive metabolites thereof to active drug are provided. Compositions and methods for sensitizing cells to a prodrug agent, inhibiting cell growth, treating drug addiction, and facilitating the metabolism of an organophosphate with this enzyme are also provided. In addition, a screening assay for identification of drugs activated by this enzyme is described.

Abstract: Disclosed herein are chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8?); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3?). Also provided herein are nucleic acids encoding such chimeric receptors and immune cells expressing the chimeric receptors. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy.

Abstract: A valve installation system including a bracket and a wrench. The bracket has a bottom section from which left and right side sections extend perpendicularly. The left and right sections terminate with prongs defining a recess therebetween for receiving and supporting an arm of a valve when the valve is engaged with the bracket. The wrench includes a generally rectangular body with a cutout proximate an end of the body. The cutout is preferably angled into the body and away from the proximate end.

Abstract: Immunohistochemical methods and compositions for the typing of molecular subgroups of medulloblastomas are provided. The methods comprise determining a protein expression profile for a sample obtained from a medulloblastoma by detecting expression of GAB1, filamin A, or at least two biomarker proteins selected from the group consisting of ?-catenin, YAP1, GAB1, and filamin A, and typing the medulloblastoma as a WNT pathway tumor, a SHH pathway tumor, or a non-WNT/non-SHH tumor based on this protein expression profile. Kits for typing a medulloblastoma according to these three molecular subgroups are provided. The kits comprise at least two antibodies, wherein each of said antibodies specifically binds to a distinct biomarker protein selected from the group consisting of ?-catenin, YAP1, GAB1, and filamin A, and can optionally comprise one or more of instructions for use, reagents for detecting antibody binding to one or more of said biomarker proteins, and one or more positive control samples.

Abstract: Mammals with cancer are treated with an antibody which specifically binds to CD223 protein and inhibits negative T cell regulatory function of CD223. The mammal may be a human. The antibody may be a monoclonal antibody. The amount of the antibody administered may be sufficient to enhance an immune T cell response to the cancer.

Abstract: The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.

Abstract: In one aspect, the invention relates to compounds having anticancer activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with uncontrolled cellular proliferation using the compounds and compositions. This abstract is intended to be used as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention relates to novel methods for modulating the activity of p53 tumor suppressor protein by affecting p53 translational regulation. More specifically, the invention relates to novel methods for modulating p53 mRNA translation in a cell by affecting a function of a p53 5?-untranslated region (5?UTR), including its interaction with proteins such as Ribosomal Protein L26 (RPL26), nucleolin, and p53. The invention also relates to the use of these methods for treating cancer, neurodegenerative disorders and minimizing the negative effects of cellular stresses.

Abstract: Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile.

Abstract: The present invention embraces methods for the diagnosis and treatment of learning or mental disorders, as well as the identification of agents useful in the treatment of such disorders based upon the identified involvement of Sarcoplasmic Ca2+-ATPase type 2 Protein in synaptic plasticity and neurotransmitter release in 22q11 deletion/DiGeorge Syndrome.

Abstract: In one aspect, the invention relates to substituted 4-phenoxyphenol analogs, derivatives thereof, and related compounds, which are useful as inhibitors of proliferating cell nuclear antigen (PCNA); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating hyperproliferative disorders associated with PCNA using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Apparatus, methods, and other embodiments associated with the spectral analysis of T2 spectral data are described. One example magnetic resonance imaging (MRI) method includes accessing a data set comprising T2 spectral data associated with a magnetic resonance imaging (MRI) signal received from an object. The T2 spectral data is decomposed with multi-exponential functions to determine T2 spectra. The T2 spectral amplitude is regularized with a regularized constant. The regularized constant is sufficiently large to smooth the T2 spectra so adjacent pixels of the T2 spectral data have similar characteristics. The T2 spectral data is weighted so that the regularization is uniformly weighted for the spectral amplitudes. The T2 spectra is partitioned into intervals corresponding to myelin water fraction (MWF), tissue water fraction (TWF), Long T2 water fraction (LWF), and cerebrospinal fluid fraction (CSF). Parametric maps are generated based, at least in part, on the T2 spectral data.

Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R21 or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.

Abstract: In one aspect, the invention relates to novel substituted 2-alkyl-1-oxo-N-phenyl-3-heteroaryl-1,2,3,4-tetrahydroisoquinoline-4-carboxamides; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating and/or preventing malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.

Abstract: Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile.