7,673 research outputs found

    Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

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    Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

    Was the Progenitor of the Sagittarius Stream a Disc Galaxy?

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    We use N-body simulations to explore the possibility that the Sagittarius (Sgr) dwarf galaxy was originally a late-type, rotating disc galaxy, rather than a non-rotating, pressure-supported dwarf spheroidal galaxy, as previously thought. We find that bifurcations in the leading tail of the Sgr stream, similar to those detected by the SDSS survey, naturally arise in models where the Sgr disc is misaligned with respect to the orbital plane. Moreover, we show that the internal rotation of the progenitor may strongly alter the location of the leading tail projected on the sky, and thus affect the constraints on the shape of the Milky Way dark matter halo that may be derived from modelling the Sgr stream. Our models provide a clear, easily-tested prediction: although tidal mass stripping removes a large fraction of the original angular momentum in the progenitor dwarf galaxy, the remnant core should still rotate with a velocity amplitude ~20 km/s that could be readily detected in future, wide-field kinematic surveys of the Sgr dwarf.Comment: Letter accepted by MNRAS. N-body model animations can be downloaded from http://www.ast.cam.ac.uk/~jorpega/files/sgr

    The MATHUSLA Test Stand

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    The rate of muons from LHC pppp collisions reaching the surface above the ATLAS interaction point is measured and compared with expected rates from decays of WW and ZZ bosons and bb- and cc-quark jets. In addition, data collected during periods without beams circulating in the LHC provide a measurement of the background from cosmic ray inelastic backscattering that is compared to simulation predictions. Data were recorded during 2018 in a 2.5 ×\times 2.5 ×\times 6.5~m3\rm{m}^3 active volume MATHUSLA test stand detector unit consisting of two scintillator planes, one at the top and one at the bottom, which defined the trigger, and six layers of RPCs between them, grouped into three (x,y)(x,y)-measuring layers separated by 1.74 m from each other. Triggers selecting both upward-going tracks and downward-going tracks were used.Comment: 18 pages, 11 figures, 1 tabl

    GaN Homoepitaxy on Freestanding (11̄00) Oriented GaN Substrates

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    We report homoepitaxialGaNgrowth on freestanding (11̄00) oriented (M-plane GaN) substrates using low-pressure metalorganic chemical vapor deposition.Scanning electron microscopy,atomic-force microscopy, and photoluminescence were used to study the influence of growth conditions such as the V/III molar ratio and temperature on the surface morphology and optical properties of the epilayers. Optimized growth conditions led to high quality (11̄00) oriented GaN epilayers with a smooth surface morphology and strong band-edge emission. These layers also exhibited strong room temperature stimulated emission under high intensity pulsed optical pumping. Since for III-N materials the (11̄00) crystal orientation is free from piezoelectric or spontaneous polarization electric fields, our work forms the basis for developing high performance III-N optoelectronic devices

    Light Stop NLSPs at the Tevatron and LHC

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    How light can the stop be given current experimental constraints? Can it still be lighter than the top? In this paper, we study this and related questions in the context of gauge-mediated supersymmetry breaking, where a stop NLSP decays into a W, b and gravitino. Focusing on the case of prompt decays, we simulate several existing Tevatron and LHC analyses that would be sensitive to this scenario, and find that they allow the stop to be as light as 150 GeV, mostly due to the large top production background. With more data, the existing LHC analyses will be able to push the limit up to at least 180 GeV. We hope this work will motivate more dedicated experimental searches for this simple scenario, in which, for most purposes, the only free parameters are the stop mass and lifetime.Comment: 31 pages, 11 figures; v2: added minor clarifications and reference
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