Abstract: The present invention relates to methods, compositions, and diagnostic tests for treating and diagnosing proliferative disorders, such as cancel-, that result in dysregulation of malic enzyme 2. In particular, the methods and compositions include monotherapy with malate, or a derivative thereof, as well as combination therapy, such as malate, or a derivative thereof, combined with another therapeutic agent, such as a malic enzyme 2 inhibitor, an antineoplastic agent, a glycolysis inhibitor, an antiangiogenic agent, an immunomodulatory agent, an antibody, or a cytokine.

Abstract: Dietary formulations in the form of an oil emulsion providing total enteral or parenteral nutrition, or in the form of food oil suitable for oral administration is provided. The formulations include about 2-60% by calories of a C20 or longer omega-3 fatty acid and about 0.05% to 1% by calories of arachidonic acid, where the formulation provides less than 1% of total calories from linoleic acid and alpha-linolenic acid, and where the fatty acids provide 5-60% of the total calories of said dietary formulation. Methods for treatment of diseases and disorders using the dietary formulations are also provided.

Abstract: The invention relates to compositions and methods to prevent enteric infection in a subject at risk of such infection. In particular, the invention relates to the prevention of recurrence of infection by Clostridium difficile.

Abstract: Some embodiments are based on the discovery that proliferative diseases (e.g., neoplastic diseases, for example, tumors or cancers) having an FBW7 mutation or other FBW7 deficiency are sensitive to Mcl1 inhibiting agents, but resistant to pro-apoptotic drugs that do not inhibit Mcl1. Some embodiments provide methods of treating a proliferative disease based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of classifying a hyperproliferative cell or cell population, for example, a malignant cell or cell population based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of selecting a treatment regimen for treating a proliferative disease, for example, a malignant disorder, based on an assessment of FBW7 expression level or mutation status.

Abstract: The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to poly-N-acetyl glucosamine (PNAG), such as Staphylococcal PNAG, in acetylated, partially acetylated and/or fully deacetylated form. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of infections by bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Some antibodies of the invention enhance opsonophagocytic killing and in vivo protection against bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.

Abstract: Mycobacterium bovis BCG is a potent stimulator of the cellular immune response and has potential as a recombinant vaccine vector. Disclosed are BCG strains that generate greater MHC class I presentation of a transgenic protein, relative to the unmutated parental strain, and that improve a recipient's CD8+ T cell response against the transgenic protein following vaccination. The mycobacterial constructs and their respective t/ansposon mutant BCG strains exhibit increased immunogenicity that is several times greater than responses generated by the parental strain and other existing modified rBCG strains. Furthermore, upon introducing the SIV gag gene into these novel strains, we observed that these strains primed for increased CD8+ T cell responses in a heterologous prime/boost regimen, comparable to levels generated by plasmid DNA vaccines. Creation of a second generation rBCG vector that may be utilized as a vaccine vector for immunizing against a variety of pathogens.

Abstract: The present invention relates to recombinant adenovirus serotype 5 (Ad5) vectors which harbor chimeric capsid proteins including substitutions of the corresponding regions from adenovirus serotypes having a lower seroprevalence relative to Ad5. In particular, the chimeric capsid includes modifications of both the adenoviral hexon and fiber proteins. The invention also provides methods for the treatment of diseases or disorders caused by infective agent(s) by administering the adenoviral vector(s) to a subject (e.g., a mammal, such as a human).

Abstract: The invention features methods of diagnosing inflammatory disease based on the elevated presence microparticles (MP) expressing certain receptors. The invention also features methods of decreasing fibrosis in the liver by administering MP to subjects with liver fibrosis.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: Typical neurological examinations focus on qualitative and subjective assessments, including obtaining a patient history, assessing the patient's cognitive status, motor and sensory skills, and cranial nerve functionality. A quantitative assessment of neurological condition includes recording a subject performing a visuomotor task and processing the performance data to determine a level of complexity in the task activity and determine a complexity index. For a sample healthy population, a baseline level of complexity and baseline complexity index can be determined. A patient's complexity index can be compared to this baseline complexity index as an indication of disease or disability. A baseline complexity index can be determined for a patient at part of a health maintenance examination and used as the baseline complexity to detect disease or disability in the future based on lower complexity index values in future examinations.

Abstract: The invention provides pharmaceutical compositions, kits, and methods of treating cancer, diabetes, obesity, autoimmune disease, and benign prostatic hyperplasia using compounds that selectively inhibit pyruvate kinase M2 and an assay measuring chemical modulation of pyruvate kinase activity.

Abstract: The present invention is related to compositions and methods for treating or reducing the likelihood of a migraine, reducing the severity of migraine, reducing the frequency of migraines, reducing the duration of migraine, and ameliorating the symptoms of a migraine. The methods and compositions of the present invention may also be used to treat or prevent a condition characterized by increased cardiovascular risk or endothelial dysfunction and musculoskeletal symptoms.

Abstract: The invention features stabilized human immunodeficiency virus (HIV) envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV Env trimers. In addition, the invention features methods of making and using the stabilized HIV Env trimers of the invention.

Abstract: The present invention provides, in one embodiment, a method of inhibiting apoptosis in kidney epithelial cells after acute injury by modulating/inhibiting Nur77 induction/expression or function/activity in the cells. The invention further provides a method of preventing or treating an acute kidney injury in a subject in need thereof, comprising administering to the subject an effective amount of a retinoic acid or retinoic acid derivative, and a method of preserving a kidney for transplant, comprising contacting the kidney with a solution that comprises a retinoic acid or a, retinoic acid derivative.

Abstract: Some aspects of this invention provide a non-human animal model of autism. Some aspects of this invention provide a non-human animal model for diseases or disorders associated with an overexpression or a copy number variance of a Ube3a gene. Transgenic mammals and transgenic mammalian cells comprising an exogenous copy or exogenous copies of a ube3a protein-encoding nucleic acid sequence are also provided. Some aspects of this invention further provide methods for using the animal models, cells, and transgenic animals for identifying agents or interventions that can alleviate a pathogenic characteristic observed in the animal model, cell, or transgenic animal.

Abstract: The invention features thrombospondin-1 (TSP-1) polypeptides (e.g., 3TSR-Fc fusion proteins), nucleic acid molecules encoding the TSP-1 polypeptides, and compositions thereof. The invention also features methods of making and using the TSP-1 polypeptides of the invention (e.g., using 3TSR-Fc fusion proteins to treat a subject having a disorder associated with pathological angiogenesis, e.g., cancer, e.g., epithelial ovarian cancer (EOC)).

Abstract: The present invention features methods and compositions for the generation of conformation-specific antibodies.

Abstract: The present invention relates to methods and compositions of treating patients suffering from, or at risk for, DNA damage and to increase life span, i.e., prevent or slow the aging process in all species. The treatment includes administering to the patient a pharmaceutical composition that includes carbon monoxide.

Abstract: The present invention is directed to a bi-stable coupling for controlling the depth of a tool insertion, such as drilling, and similar processes. The bi-stable coupling can be used to penetrate (e.g., drill or push) through a material layer of unknown thickness without plunging the tool into the adjacent layer. In accordance with the invention, in a first state, force is applied to the tool to initiate penetration and a reactive force maintains the device in the first state during penetration and when tool penetrates the material, the reactive force is diminished enabling the device to transition to a second state in which the tool becomes retracted. In medical applications, the invention allows for drilling through bone of unknown thickness without plunging into the adjacent soft tissue.

Abstract: Disclosed herein are assays for and methods of monitoring the relaxation response in a subject by measuring the expression level of one or more genes that are modulated in a relaxation response. Primers, probes and kits for use in the assays and methods are also provided.