Abstract: An oral combination therapy or oral composition that protects orally administered exogenous leptin from the environment of the gastrointestinal tract, allowing delivery of the exogenous leptin to the bloodstream. The oral combination therapy includes (a) leptin or a leptin functional derivative; (b) a stomach acid-neutralizing agent such as a buffer; and (c) a pancreatic protease inhibitor that protects the exogenous leptin from degradation by pancreatic enzymes; and (d) a bile acid or a bile acid analog that facilitates absorption of the exogenous leptin. The oral combination therapy or oral composition may also include at least one agent that stimulates endogenous leptin secretion; as well as at least one agent capable of promoting, enhancing or improving adherence to treatment such as a sweetener or a satiety triggering agent.

Abstract: The present invention relates to novel biosensors that are based on bioluminescence resonance energy transfer (BRET). These biosensors may be used to monitor rapid interaction and conformational changes within G protein-coupled receptor/G protein complexes and, in this way, reflect the activation status of the receptor. Advantageously, the biosensors may be used as a highly sensitive and quantitative assay for the identification of ligands (agonists, antagonists, inverse agonists, partial agonists, etc.) targeting G protein-coupled receptors (GPCRs) as well as for the analysis of the activation status of these receptors. Moreover, multiplexing different biosensors within receptors/G protein complexes allows for mapping ligand textures. Additionally, the biosensors permit the direct, real-time examination of interactions between receptors and G protein in their natural environment, the living cell.

Abstract: Disclosed herein is a compound of Formula I: wherein X, R1, R2, and R3 are as defend herein, or a pharmaceutically acceptable salt thereof to allow the drug to penetrate the cell membrane; or a prodrug, or the compound is labeled with a detectable label or an affinity tag thereof. Also disclosed is a pharmaceutical composition, a method of treating a disorder mediated by melanocortin-4 receptors, and a method of treating obesity using the compounds described.

Abstract: Pyrimido[4,5-b]indole derivatives are provided. These compounds are useful to expand hematopoietic stem cell populations, particularly, human hematopoietic stem cell populations. The compounds are also useful in the medical treatment of diseases that involve hematopoietic stem cells.

Abstract: Disclosed herein are mutated RAF and KSR nucleic acids and polypeptides. Also disclosed are methods of using the mutated RAF and KSR to inhibit the dimerization of RAF/RAF and RAF/KSR. Also disclosed are methods of using the mutated RAF and KSR to screen for inhibitors of dimerization.

Abstract: A method for characterizing ultrasound scatterers in a medium comprises receiving ultrasound data representing a region of interest comprising a plurality of scatterers in a medium, the plurality of scatterers including aggregates of the scatterers. The ultrasound data is modeled data using an effective medium theory combined with the structure factor model, the structure factor model defining the spatial organization and concentration of the aggregates. The modeled ultrasound data is compared to theoretical data obtained with the effective medium theory combined with the structure factor model. From the comparison, dimensional data of the aggregates of the scatterers and the volume concentration of scatterers in the medium is determined.

Abstract: The present invention relates to pharmaceutical compositions and combination therapies for treating patents having a neoplasm or proliferative disorder, the combination comprises an inhibitor of the eIF4E gene product and a chemotherapeutic agent, wherein said combination therapy overcomes resistance developed in patients during anti-neoplastic treatment. The present invention also provides for the use of a combination therapy for treating patients having a neoplasm, a proliferative disorder, pre-neoplasm or a precancerous lesion, comprising an inhibitor of the eIF4E gene product, a chemotherapeutic agent, and a therapeutically effective amount of a hedgehog pathway inhibitor, and the method of using said combination therapy.

Abstract: The present invention relates to a novel biosensor. A resonance energy transfer (RET) biosensor comprising a beta(?)-arrestin tagged with a first and a second chromophore, wherein said first chromophore is a fluorophore and said second chromophore is a fluorophore or a bioluminophore is described.

Abstract: The present invention relates to an injectable pharmaceutical composition with gelling properties containing: -an active principle; a hydrophobic and bio-compatible organic liquid; and an organogelling substance, the molecules of which have the capacity to bind together via bonds of low energy, wherein the organogelling substance is chosen among L-tyrosine derivatives responding to the following formula (I) wherein: R1 is an alkyl group containing 1 to 3 carbon atoms, linear or branched; and R2 is a hydrophobic group chosen among aliphatic saturated or unsaturated fatty chains or aryl or arylalkyl groups. Its use as a vector for the release of active principles, as well as its process of preparation.

Abstract: Compositions and methods for reducing or preventing graft-versus-host disease associated with allogeneic stem cell transplantation are described. A method includes harvesting hematopoietic cells from a patient with an immunologic disorder and harvesting hematopoietic cells from a donor. The harvested hemaptopoietic cells from the patient and the donor are mixed ex vivo for a period of time sufficient to activate lymphocytes within the hematopoietic cells harvested from the donor such that an immune reaction occurs and an activated portion and an unactivated portion is produced. A rhodamine B derivative is then added to the mixture of cells and the mixture is irradiated at a suitable wavelength and intensity for the selective destruction and/or inactivation of the activated portion without substantially affecting the unactivated portion or causing systemic toxicity in said patient. The irradiated cells are then infused into the patient.

Abstract: The present invention relates to a process for making an alkali metal oxyanion comprising iron. In one aspect of the invention, hydrothermal methods are used with a nanoscale iron precursor in order to provide desirably low particle size and high purity and crystallinity.

Abstract: The present invention is concerned with novel polar solvents and novel electrolytic compositions comprising such solvents, and having a high range of stability, as required for applications in the field of electrochemistry. The present solvents have a highly polar amide function, and preferably combine with a salt soluble in the solvent and having an anion with a delocalized charge, and at least one polymer, to form an electrolytic composition.

Abstract: Disclosed herein is a substantially pure nucleic acid encoding a eukaryotic protein kinase having at least one mutated amino-acid residue located in its subdomain IX. Also disclosed is a substantially pure eukaryotic protein kinase polypeptide having at least one mutation in its subdomain IX, the kinase being encoded by the nucleic acid.

Abstract: Disclosed herein is a compound of Formula I: wherein X, R1, R2, and R3 are as defend herein, or a pharmaceutically acceptable salt thereof to allow the drug to penetrate the cell membrane; or a prodrug, or the compound is labeled with a detectable label or an affinity tag thereof. Also disclosed is a pharmaceutical composition, a method of treating a disorder mediated by melanocortin-4 receptors, and a method of treating obesity using the compounds described.

Abstract: Hybrid molecules comprising a retinoic acid receptor agonist moiety and a histone deacetylase inhibitor (HDAC) moiety are disclosed. Hybrid molecule 3 (6-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)naphthalene-2-hydroxamic acid) was proven to posses HDAC activity while maintaining RAR agonist activity. Hybrid molecule 3 and pharmaceutical compositions thereof can be used in the treatment of breast cancer, leukemia, non-small cell lung cancer, colon cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and cancer of the CNS.

Abstract: A compound of Formula I or Formula II:

Abstract: A compound of Formula, (I) or Formula: (II).

Abstract: Methods of assessing and reducing risk of graft versus host disease (GVHD) based on gene expression profiling are described, as well as methods of selecting a suitable transplant donor. Corresponding reagents and kits are also described.

Abstract: A method for segmenting an image comprising: determining an initial estimation of a boundary between at least two components in a region of an image to be segmented; providing image data from the region of the image to be segmented, the image data representing gray level values of a plurality of image elements of the components; modelling the image data on a mixture of at least two statistical distributions, each statistical distribution having more than one parameter, and each component being associated with certain weights of the statistical distributions in the mixture; estimating the parameters of the statistical distributions in the mixture; for each component, estimating the weights of the statistical distributions in the mixture based on the estimated parameters and the image data of each image element; and optimizing the initial estimation of the boundary between the components based on the estimated parameters and estimated weights.

Abstract: Compositions and methods for reducing or preventing graft-versus-host disease associated with allogeneic stem cell transplantation are described. A method includes harvesting hematopoietic cells from a patient with an immunologic disorder and harvesting hematopoietic cells from a donor. The harvested hemaptopoietic cells from the patient and the donor are mixed ex vivo for a period of time sufficient to activate lymphocytes within the hematopoietic cells harvested from the donor such that an immune reaction occurs and an activated portion and an unactivated portion is produced. A rhodamine B derivative is then added to the mixture of cells and the mixture is irradiated at a suitable wavelength and intensity for the selective destruction and/or inactivation of the activated portion without substantially affecting the unactivated portion or causing systemic toxicity in said patient. The irradiated cells are then infused into the patient.