Abstract: Methods and compositions for enhancing viral gene transfer, such as lentiviral gene transfer, and improving the efficacy of gene delivery to cells such as primitive hematopoietic cells, are described. These methods and compositions are based on the use of pyrimido[4,5-b]indole derivatives. Cell-based compositions and methods useful for therapeutic indications amenable to treatment with gene therapies, including hematopoietic stem cell therapies, are also described.

Abstract: The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.

Abstract: Method for measuring the visually-induced postural instability of a person is described, the method comprising a display providing step (S1) during which a visual display device is provided. The display device is arranged so as to display a dynamic visual pattern in at least 50% of the lower half of the visual field of the person, leaving an upper half of the visual field of the person free. The method also comprises a display step (S2) during which a dynamic visual pattern is displayed on the visual display device. The method further comprises a measuring step (S3) during which a parameter representative of the postural instability is measured when the person is gazing at a fix target straight in front while having the dynamic visual pattern displayed on the visual display device.

Abstract: There is provided a process for preparing a crystalline electrode material, the process comprising: providing a liquid bath comprising the electrode material in a melted state; and introducing a precursor of the electrode material into the liquid bath, wherein the electrode material comprises lithium, a metal and phosphate. There is also provided a crystalline electrode material, comprising lithium substituted by less than 0.1 atomic of Na or K; Fe and/or Mn, substituted by less than 0.1 atomic ratio of: (a) Mg, Ca, Al and B, (b) Nb, Zr, Mo, V and Cr, (c) Fe(III), or (d) any combinations thereof; and PO4, substituted by less than 20% atomic weight of an oxyanion selected from SO4, SiO4, BO4, P2O7, and any combinations thereof, the material being in the form of particles having a non-carbon and non-olivine phase on at least a portion of the surface thereof.

Abstract: The present invention provides imidazothiadiazole compounds of Formula (I) wherein A, B, D, Rx, R1, R2, R3, X1, X2 and s are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments.

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: Novel methods for modulating acute myeloid leukemia stem/progenitor cell expansion and/or differentiation are disclosed. These methods are based on the use of aryl hydrocarbon receptor (AhR) modulators and/or compounds of formula I or II Screening assays to identify compounds that may be useful for inhibiting and/or eliminating AML initiating cells using AhR modulators and/or the compounds of formula I or II are also disclosed. The use of pharmaceutically acceptable agonists of the AhR for preventing or inhibiting minimal residual disease (MRD) in an AML patient is also disclosed.

Abstract: The present invention is concerned with novel compounds derived from polyquinonic ionic compounds and their use in electrochemical generators.

Abstract: There is provided a process for producing LiMXO4, comprising the steps of reacting a source of lithium, a source of M, and a source of X together, in a melted state at a reaction temperature between 900 to 1450 C, in the presence of an excess of (A) a solid-solid reducing couple having an oxygen partial process at equilibrium (pO2) comprised between 10?8 and 10?15 atm at said reaction temperature according to an Ellingham-Richardson diagram for oxides, or (B) one component of the solid-solid reducing couple together with a gas-gas reducing couple having an oxygen partial pressure equilibrium (pO2) between 10?8 and 10?15 atm at said reaction temperature according to an Ellingham-Richardson diagram of oxides, and under thermic equilibrium and thermodynamic equilibrium. There is also provided a LiMXO4 melt-solidified product free from off-composition impurities.

Abstract: The disclosure relates to recombinant vectors and methods for using the same. In certain embodiments, the recombinant vectors are immunogenic.

Abstract: The present invention provides thiazole compounds of Formula I wherein X, Y, Z, X1, X2, X3, X4, X5, R1, R2, R4, R5, R6, R7, and W, are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug, ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

Abstract: The present invention relates to pharmaceutical compositions and combination therapies for treating patients having a neoplasm or a proliferative disorder, the combination comprises an inhibitor of the e1F4E gene product, such as ribavirin, and a chemotherapeutic agent, such as cytarabine, 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 e1F4E gene product, a chemotherapeutic agent, and a therapeutically effective amount of a hedgehog pathway inhibitor, such as GDC-0449; and the method of using said combination therapy.

Abstract: A method for diagnosing the presence of hereditary spastic paraplegia (HSP) or predicting the risk of developing HSP in a human subject, comprising detecting the presence or absence of a defect in a gene encoding a polypeptide comprising the sequence of FIG. 9 (SEQ ID NO: 19), in a nucleic acid sample of the subject, whereby the detection of the defect is indicative that the subject has or is at risk of developing HSP.

Abstract: The present invention provides imidazothiadiazole compounds of Formula (I); Wherein W, Y, R0, R2, R4, Ra, Rb, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

Abstract: There are provided herein transgenic non-human animals and cells comprising a transgene encoding either a mutated human melanocortin type-4 receptor (hMC4R) protein, wherein the mutated protein is misfolded and retained intracellularly, or a wild-type human melanocortin type-4 receptor (hMC4R) protein. Transgenes and targeting constructs used to produce such transgenic animals and cells are also provided, as well as methods for using the transgenic animals in pharmaceutical screening and as commercial research animals for modeling obesity.

Abstract: A novel method for human minor histocompatibility antigen (MiHA) discovery, novel MiHAs identified using this method, as well as uses of the novel MiHAs, are described. One of the features of the novel method is the inclusion of personalized translated transcriptome and/or exome in the database used for peptide identification by mass spectroscopy (MS). Candidate MiHAs are identified by comparing the personalized transcriptome and/or exome to a reference genome and/or to the transcriptome and/or exome of an HLA-matched subject.

Abstract: Disclosed herein is a compound of Formula I: wherein X, R1, R2, and R3 are as defined 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: Disclosed is a compound of Formula I: or a salt thereof, in which X, X1, X2, R1, R2, and R3 are described herein. Also disclosed are pharmaceutical compositions and methods of using the compounds of Formula I to treat disorders mediated by melanocortin-4 receptors.

Abstract: Disclosed herein are biosensors useful for detecting the dimerization of RAF and/or KSR polypeptides. These biosensors comprise fusion proteins comprising RAF and/or KSR proteins fused to bioluminescent or fluorescent proteins. Also disclosed are methods of using the biosensors to detect and measure the dimerization of RAF/RAF and RAF/KSR polypeptides by resonance energy transfer such as BRET or FRET, for example to screen for inhibitors of dimerization.

Abstract: An assay and system compatible with high throughput screening (HTS) that is capable of identifying inhibitors, such as small-molecule inhibitors, of the degradation of the Cdk inhibitor p21, are described. The assay is based on the use of fusion protein comprising (i) a p2 polypeptide; and (i) a reporter protein linked to the C-terminal of said p21 polypeptide, wherein the fusion protein has a half-life that is similar to that of the p21 polypeptide. Inhibitors identified by this assay may be useful to inhibit the proliferation of tumor cells, and thus for the treatment of cancers.