735 research outputs found

    Model Unspecific Search in CMS

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    We present the results of a model independent analysis, which systematically scans the data taken by CMS for deviations from the Standard Model predictions. Due to the minimal theoretical bias this approach is sensitive to a variety of models for new physics. Events with at least one electron or muon are classified according to their content of reconstructed objects (muons, electrons, photons, jets and missing transverse energy). A broad scan of three kinematic distributions in those classes is performed by identifying deviations from Standard Model expectations, accounting for systematic uncertainties.Comment: Presented at the 2011 Hadron Collider Physics symposium (HCP-2011), Paris, France, November 14-18 2011, 2 pages, 3 figur

    Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.

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    Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-ÎČ pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention

    AMP-activated protein kinase inhibits K<sub>v</sub>1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation

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    KEY POINTS: Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K(v)) in pulmonary arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear. AMP‐activated protein kinase (AMPK) has been proposed to couple inhibition of mitochondrial metabolism by hypoxia to acute hypoxic pulmonary vasoconstriction and progression of pulmonary hypertension. Inhibition of complex I of the mitochondrial electron transport chain activated AMPK and inhibited K(v)1.5 channels in pulmonary arterial myocytes. AMPK activation by 5‐aminoimidazole‐4‐carboxamide riboside, A769662 or C13 attenuated K(v)1.5 currents in pulmonary arterial myocytes, and this effect was non‐additive with respect to K(v)1.5 inhibition by hypoxia and mitochondrial poisons. Recombinant AMPK phosphorylated recombinant human K(v)1.5 channels in cell‐free assays, and inhibited K(+) currents when introduced into HEK 293 cells stably expressing K(v)1.5. These results suggest that AMPK is the primary mediator of reductions in K(v)1.5 channels following inhibition of mitochondrial oxidative phosphorylation during hypoxia and by mitochondrial poisons. ABSTRACT: Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K(v)) in pulmonary arterial smooth muscle cells that is mediated by the inhibition of mitochondrial oxidative phosphorylation. We sought to determine the role in this process of the AMP‐activated protein kinase (AMPK), which is intimately coupled to mitochondrial function due to its activation by LKB1‐dependent phosphorylation in response to increases in the cellular AMP:ATP and/or ADP:ATP ratios. Inhibition of complex I of the mitochondrial electron transport chain using phenformin activated AMPK and inhibited K(v) currents in pulmonary arterial myocytes, consistent with previously reported effects of mitochondrial inhibitors. Myocyte K(v) currents were also markedly inhibited upon AMPK activation by A769662, 5‐aminoimidazole‐4‐carboxamide riboside and C13 and by intracellular dialysis from a patch‐pipette of activated (thiophosphorylated) recombinant AMPK heterotrimers (α2ÎČ2Îł1 or α1ÎČ1Îł1). Hypoxia and inhibitors of mitochondrial oxidative phosphorylation reduced AMPK‐sensitive K(+) currents, which were also blocked by the selective K(v)1.5 channel inhibitor diphenyl phosphine oxide‐1 but unaffected by the presence of the BK(Ca) channel blocker paxilline. Moreover, recombinant human K(v)1.5 channels were phosphorylated by AMPK in cell‐free assays, and K(+) currents carried by K(v)1.5 stably expressed in HEK 293 cells were inhibited by intracellular dialysis of AMPK heterotrimers and by A769662, the effects of which were blocked by compound C. We conclude that AMPK mediates K(v) channel inhibition by hypoxia in pulmonary arterial myocytes, at least in part, through phosphorylation of K(v)1.5 and/or an associated protein

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

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    Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð„with constraintsð ð ð„ „ ðandðŽð„ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV