Abstract: Nanoparticles for a selective, two stage delivery to tumors have been developed. The nanoparticles are initially sized so that they preferentially accumulate in the tumor tissue as a result of leakage through the defective vascular in the solid tumors. Once in the tumor tissue, the nanoparticles are cleaved hydrolytically and/or by enzymatic cleavage over time to release smaller nanoparticles carrying therapeutic, prophylactic or diagnostic agents into the necrotic interior of the tumors. This provides a simple, elegant and highly effective means of delivery drug selectively not just to tumors generally, but, more importantly, into the poorly vascularized necrotic interiors which drugs are normally unable to penetrate. The nanoparticles have a number of advantages: less toxicity due to selective accumulation only in the tumors; access into the poorly vascularized necrotic interiors of the tumor; and sustained release over a period of time within the tumor.

Abstract: The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3? or GSK3?) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychriatic disorders, metabolic disorders, and cancer.

Abstract: Methods and compositions are generally provided for treating metabolic disorders, e.g., obesity. One aspect discloses methods and compositions for obtaining a biological sample from the subject, evaluating the sample for the presence or absence of a genetic indicator, wherein the genetic indicator is selected from a single nucleotide polymorphism and a level of gene expression, and performing a first metabolic procedure if the genetic indicator is present, or performing an alternative second metabolic procedure if the genetic indicator is absent. One aspect discloses methods and compositions for obtaining a sample including deoxyribonucleic acids (DNA) from the subject, evaluating the DNA for an absence or presence of one or more genetic indicators and performing a first metabolic procedure or an alternative second metabolic procedure based on the absence or presence of the genetic indicator(s). Other aspects are also disclosed.

Abstract: The present invention provides various biomarkers of inflammatory bowel disease, including biomarkers for Crohn's disease and biomarkers for Ulcerative colitis. The present invention also provides various methods of using the biomarkers, including methods for diagnosis of inflammatory bowel disease, methods for distinguishing between inflammatory bowel diseases, methods of determining predisposition to inflammatory bowel disease, methods of monitoring progression/regression of inflammatory bowel disease, methods of assessing efficacy of compositions for treating inflammatory bowel disease, methods of screening compositions for activity in modulating biomarkers of inflammatory bowel disease, methods of treating inflammatory bowel disease, as well as other methods based on biomarkers of inflammatory bowel disease.

Abstract: Modulation of PD-1 activity in the presence or absence of an agent as measured by a gene expression profile of at least two genes is provided. Reagents, kits, methods and uses thereof for the modulation of immune function comprise the identification of modulators of PD-1 activity.

Abstract: This invention is directed to ?-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The ?-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.

Abstract: The present invention generally provides methods and systems for performing in vivo flow cytometry by using blood vessels as flow chambers through which flowing cells can be monitored in a live subject in vivo without the need for withdrawing a blood sample. In some embodiments, one or more blood vessels are illuminated with radiation so as to cause a multi-photon excitation of an exogenous fluorophore that was previously introduced into the subject to label one or more cell types of interest. In some other embodiments, rather than utilizing an exogenous fluorophore, endogenous (intrinsic) cellular fluorescence can be employed for in vivo flow cytometry. The emission of fluorescence radiation from such fluorophores in response to the excitation can be detected and analyzed to obtain information regarding a cell type of interest.

Abstract: Methods and devices are provided for activating brown adipose tissue with targeted substance delivery. Generally, the methods and devices can activate BAT to increase thermogenesis, e.g., increase heat production in the patient, which over time can lead to weight loss and/or improved metabolic function. In one embodiment, a chemical configured to stimulate nerves that activate the BAT and/or to stimulate brown adipocytes directly can be delivered to a patient, thereby increasing thermogenesis in the BAT and inducing weight loss and/or improved metabolic function through energy expenditure. The chemical can be delivered to the patient locally and/or systemically to stimulate the nerves and/or the brown adipocytes.

Abstract: The present invention relates to methods of decreasing inflammation by inhibiting polo-like kinase (PlK)

Abstract: The present invention provides polymers for use in preventing damage to the membranes of cells in fat grafts. Mixing of a triblock copolymer such as poloxymer P188 with adipocytes or adipose tissue to be transplanted into a subject is thought to stabilize the membranes of the cells leading to more successful fat transplantation in soft tissue reconstruction or augmentation. Such methods may also be used in the transplantation of adult stem cells or other cells derived from fat tissue. Other agents such as lipoic acid may also be added to the polymer/cell compositions for cell transplantation.

Abstract: A novel pathway in cancer cell metabolism is identified. Targeting of any gene, protein, or enzyme that modulates activity or flux through this pathway, including, but not limited to IDH1, isocitrate dehydrogenase 2 (IDH2), aconitase 1 (ACO1), aconitase 2 (ACO2), glutaminase (GLS), glutamate dehydrogenase (GDH) and transaminase, provides effective means of inhibiting tumor growth.

Abstract: The invention relates to methods and compositions for promoting cognitive function and/or treating cognitive function disorders and impairments. In particular the methods are accomplished by administering to a subject CI-994 or dinaline or a pharmaceutically acceptable salt, ester, prodrug or metabolite thereof.

Abstract: Methods and compositions are generally provided for treating metabolic disorders, e.g., obesity. One aspect discloses methods and compositions for obtaining a biological sample from the subject, evaluating the sample for the presence or absence of a genetic indicator, wherein the genetic indicator is selected from a single nucleotide polymorphism and a level of gene expression, and performing a first metabolic procedure if the genetic indicator is present, or performing an alternative second metabolic procedure if the genetic indicator is absent. One aspect discloses methods and compositions for obtaining a sample including deoxyribonucleic acids (DNA) from the subject, evaluating the DNA for an absence or presence of one or more genetic indicators and performing a first metabolic procedure or an alternative second metabolic procedure based on the absence or presence of the genetic indicator(s). Other aspects are also disclosed.

Abstract: Control agents for immuno-precipitation assays, methods of using the control agents and kits comprising the control agents are provided.

Abstract: This invention relates generally to populations of microvesicles containing or otherwise associated with viral particles, methods of producing these purified populations, and methods of using these purified populations in a variety of diagnostic, therapeutic and/or prophylactic indications.

Abstract: A bundle of drawn fibers that have X-ray scintillating unagglommerated nanocrystallite particles in plastic or glass cores of down to 0.1 micron spacing and claddings of X-ray absorbing compounds in the cladding composition. Optional is a cover to the bundle that blocks light from leaving the bundle at the X-ray side while allowing X-rays to pass into the cores. To image the light exiting the fiber bundle at the sub-micron level, light expansion is preferable using either a lens system or a fiber bundle expander.

Abstract: Methods and compositions are provided for treating metabolic disorders by modulating bile acid levels. Generally, the methods and compositions can modulate bile acid levels, such as serum bile acid levels, to treat a metabolic disorder. In one embodiment, a method of modulating a bile acid level includes measuring a bile acid level and delivering a composition effective to modulate the bile acid level. A method for modulating a bile acid profile includes comparing a bile acid profile to a target profile and delivering a bile acid cocktail to increase bile acid levels. In another embodiment, a pharmaceutical composition for increasing bile acid levels includes a bile acid cocktail effective to increase bile acid levels. The composition is further useful as part of an implantable system.

Abstract: The invention relates to methods and products for diagnosing, preventing, and treating Alzheimer's disease and abnormal production of amyloid ?.

Abstract: Methods and devices are provided for knee joint replacement with anterior cruciate ligament (ACL) substitution. Generally, the methods and devices can allow a knee joint to be partially or totally replaced in conjunction with substitution of the knee joint's ACL. In one embodiment, a knee replacement prosthesis can include a medial or lateral femoral implant, a femoral intercondylar notch structure, a medial or lateral tibial insert, and an ACL-substitution member. The ACL-substitution member can be configured to engage with the femoral intercondylar notch structure during a full range of knee motion and/or during only early knee flexion.

Abstract: The invention relates to compounds and composition for the treatment and prevention of cancer. The invention also covers all diseases that may be treated by selective modulation of levels of reactive oxygen species in diseased cells versus normal cells. Methods for the preparation and administration of such compositions are also disclosed.