941 research outputs found

    Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice

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    Sphingosine kinase (SphK) 2 has been implicated in the development of a range of cancers and inhibitors of this enzyme are currently in clinical trial. We have previously demonstrated a role for SphK2 in the development of acute lymphoblastic leukemia (ALL).In this and our previous study we use mouse models: in the previous study the disease was driven by the proto-oncogene BCR/ABL1, while in this study cancer risk was elevated by deletion of the tumor suppressor ARF.Mice lacking ARF and SphK2 had a significantly reduced incidence of ALL compared mice with wild type SphK2.These results show that the role of SphK2 in ALL development is not limited to BCR/ABL1 driven disease extending the potential use of inhibitors of this enzyme to ALL patients whose disease have driver mutations other than BCR/ABL1.Vicki Xie, Daochen Tong, Craig T. Wallington-Beddoe, Ken F. Bradstock and Linda J. Bendal

    From Predicting Solar Activity to Forecasting Space Weather: Practical Examples of Research-to-Operations and Operations-to-Research

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    The successful transition of research to operations (R2O) and operations to research (O2R) requires, above all, interaction between the two communities. We explore the role that close interaction and ongoing communication played in the successful fielding of three separate developments: an observation platform, a numerical model, and a visualization and specification tool. Additionally, we will examine how these three pieces came together to revolutionize interplanetary coronal mass ejection (ICME) arrival forecasts. A discussion of the importance of education and training in ensuring a positive outcome from R2O activity follows. We describe efforts by the meteorological community to make research results more accessible to forecasters and the applicability of these efforts to the transfer of space-weather research.We end with a forecaster "wish list" for R2O transitions. Ongoing, two-way communication between the research and operations communities is the thread connecting it all.Comment: 18 pages, 3 figures, Solar Physics in pres

    The effect of the spin-orbit interaction on the band gap of half-metals

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    The spin-orbit interaction can cause a nonvanishing density of states (DOS) within the minority-spin band gap of half-metals around the Fermi level. We examine the magnitude of the effect in Heusler alloys, zinc-blende half metals and diluted magnetic semiconductors, using first-principles calculations. We find that the ratio of spin-down to spin-up DOS at the Fermi level can range from below 1% (e.g. 0.5% for NiMnSb) over several percents (4.2% for (Ga,Mn)As) to 13% for MnBi.Comment: 5 pages, 3 figure

    Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

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    Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

    Isolation, Characterization and Quantity Determination of Aristolochic Acids, Toxic Compounds in Aristolochia bracteolata L.

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    Background Aristolochic Acids (AAs) are major components of plants in Aristolochia and have been found to be nephrotoxic, carcinogenic and mutagenic. Herein reported are the isolation, identification and quantity determination methods of Aristolochic Acid-I (AA-I) and Aristolochic Acid-II (AA-II) toxic compounds of Aristolochia bracteolata indigenous to Central Sudan and medicinally used in diverse biological functions including analgesic and diuretic effects, treatment of tumors, malaria and/or fevers. Methods and results AAs mixture was extracted with methanol from the defatted material of Aristolochia bracteolata whole plant at room temperature and was isolated from the aqueous methanol extract by chloroform. Moreover, Silica-gel column chromatography and Preparative Thin Layer Chromatography (PTLC) using chloroform/methanol gradient mixtures were used to isolate AAs mixtures as a yellow crystalline solid. A preliminary detection of AAs was made by Thin Layer Chromatography (silica-gel, chloroform: methanol (6:1)). The Rf value of the acids mixture was 0.43-0.46. The presence of AAs in plant sample was confirmed by High Performance Liquid Chromatography/Ultraviolet (HPLC/UV) analysis using 1% acetic acid and methanol (40:60) as mobile phase and maximum absorption wave length of 250 nm. Quantitative determination of AA-II (49.03 g/kg) and AA-I (12.98 g/kg) was also achieved by HPLC/UV. Recommendation It is recommended that the use of Aristolochia bracteolata as a medicinal plant should be extremely limited or strictly prohibited. The chromatograms obtained in this study can serve as fingerprints to identify AAs in plant samples

    Tunneling of quantum rotobreathers

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    We analyze the quantum properties of a system consisting of two nonlinearly coupled pendula. This non-integrable system exhibits two different symmetries: a permutational symmetry (permutation of the pendula) and another one related to the reversal of the total momentum of the system. Each of these symmetries is responsible for the existence of two kinds of quasi-degenerated states. At sufficiently high energy, pairs of symmetry-related states glue together to form quadruplets. We show that, starting from the anti-continuous limit, particular quadruplets allow us to construct quantum states whose properties are very similar to those of classical rotobreathers. By diagonalizing numerically the quantum Hamiltonian, we investigate their properties and show that such states are able to store the main part of the total energy on one of the pendula. Contrary to the classical situation, the coupling between pendula necessarily introduces a periodic exchange of energy between them with a frequency which is proportional to the energy splitting between quasi-degenerated states related to the permutation symmetry. This splitting may remain very small as the coupling strength increases and is a decreasing function of the pair energy. The energy may be therefore stored in one pendulum during a time period very long as compared to the inverse of the internal rotobreather frequency.Comment: 20 pages, 11 figures, REVTeX4 styl

    A Measurement of Psi(2S) Resonance Parameters

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    Cross sections for e+e- to hadons, pi+pi- J/Psi, and mu+mu- have been measured in the vicinity of the Psi(2S) resonance using the BESII detector operated at the BEPC. The Psi(2S) total width; partial widths to hadrons, pi+pi- J/Psi, muons; and corresponding branching fractions have been determined to be Gamma(total)= (264+-27) keV; Gamma(hadron)= (258+-26) keV, Gamma(mu)= (2.44+-0.21) keV, and Gamma(pi+pi- J/Psi)= (85+-8.7) keV; and Br(hadron)= (97.79+-0.15)%, Br(pi+pi- J/Psi)= (32+-1.4)%, Br(mu)= (0.93+-0.08)%, respectively.Comment: 8 pages, 6 figure

    Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

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    Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of sNN=5\sqrt{s_{\text{NN}}}=5TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, Δη\Delta\eta, and relative azimuthal angle, Δϕ\Delta\phi, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, Δϕ0\Delta\phi \approx 0, is observed in the pseudorapidity range 2.0<η<4.92.0<\eta<4.9. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to η=4.9\eta=4.9. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm
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