3,115 research outputs found

    WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in obese humans

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    Experimental studies have suggested that Wingless-related integration site 5A (WNT5A) is a proinflammatory secreted protein that is associated with metabolic dysfunction in obesity. Impaired angiogenesis in fat depots has been implicated in the development of adipose tissue capillary rarefaction, hypoxia, inflammation, and metabolic dysfunction. We have recently demonstrated that impaired adipose tissue angiogenesis is associated with overexpression of antiangiogenic factor VEGF-A165b in human fat and the systemic circulation. In the present study, we postulated that upregulation of WNT5A is associated with angiogenic dysfunction and examined its role in regulating VEGF-A165b expression in human obesity. We biopsied subcutaneous and visceral adipose tissue from 38 obese individuals (body mass index: 44 ± 7 kg/m2, age: 37 ± 11 yr) during planned bariatric surgery and characterized depot-specific protein expression of VEGF-A165b and WNT5A using Western blot analysis. In both subcutaneous and visceral fat, VEGF-A165b expression correlated strongly with WNT5A protein (r = 0.9, P \u3c 0.001). In subcutaneous adipose tissue where angiogenic capacity is greater than in the visceral depot, exogenous human recombinant WNT5A increased VEGF-A165b expression in both whole adipose tissue and isolated vascular endothelial cell fractions (P \u3c 0.01 and P \u3c 0.05, respectively). This was associated with markedly blunted angiogenic capillary sprout formation in human fat pad explants. Moreover, recombinant WNT5A increased secretion of soluble fms-like tyrosine kinase-1, a negative regulator of angiogenesis, in the sprout media (P \u3c 0.01). Both VEGF-A165b-neutralizing antibody and secreted frizzled-related protein 5, which acts as a decoy receptor for WNT5A, significantly improved capillary sprout formation and reduced soluble fms-like tyrosine kinase-1 production (P \u3c 0.05). We demonstrated a significant regulatory nexus between WNT5A and antiangiogenic VEGF-A165b in the adipose tissue of obese subjects that was linked to angiogenic dysfunction. Elevated WNT5A expression in obesity may function as a negative regulator of angiogenesis

    Differential Cross Sections for Electron Capture from Helium by 25- to 100-keV Incident Protons

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    Experimentally and theoretically determined differential cross sections are reported for electron capture in collisions of protons with helium atoms for incident proton energies of 25, 30, 50, and 100 keV and for center-of-mass scattering angles of 0.0 to 2.0 mrad. The magnitudes of the experimentally determined differential cross sections decrease from 10-10 to 10-12 cm2/sr within the 0.0-0.8-mrad range of the center-of-mass scattering angle. At approximately 0.8 mrad a distinct change in the slope of the differential cross section is observed. The experimental results which are for capture into all bound states of hydrogen are compared with the theoretical results of a calculation for capture into the ground state using the two-state two-center atomic expansion method in the eikonal approximation. Good agreement between the theoretical and the experimental results is obtained with a static potential which accounts for screening of the helium nucleus by a single passive electron

    Structural Health Monitoring for Performance Assessment of Bridges under Flooding and Seismic Actions

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    Bridges can be subjected to damaging environmental actions due to flooding and seismic hazards. Flood actions that result in scour are a leading cause of bridge failure, while seismic actions that induce lateral forces may lead to high ductility demand that exceeds pier capacity. When combined, seismic actions and scour can lead to effects that depend on the governing scour condition affecting a bridge. Loss of stiffness under scour can reduce the ductility capacity of a bridge but can also lead to an increase in flexibility that may reduce seismic inertial forces. Conversely, increased flexibility can lead to deck collapse due to support loss, so there exists some uncertainty about the combined effect of both phenomena. A necessary step towards the performance assessment of bridges under flooding and seismic actions is to calibrate numerical models that can reproduce structural responses under different actions. A further step is verifying the achievement of performance goals defined by codes. Structural health monitoring (SHM) techniques allow the computation of performance parameters that are useful for calibrating numerical models and performing direct checks of performance goal compliance. In this paper, various strategies employed to monitor bridge health against scour and seismic actions are discussed, with a particular focus on vibration-based damage identification methods

    Solar fusion cross sections II: the pp chain and CNO cycles

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    We summarize and critically evaluate the available data on nuclear fusion cross sections important to energy generation in the Sun and other hydrogen-burning stars and to solar neutrino production. Recommended values and uncertainties are provided for key cross sections, and a recommended spectrum is given for 8B solar neutrinos. We also discuss opportunities for further increasing the precision of key rates, including new facilities, new experimental techniques, and improvements in theory. This review, which summarizes the conclusions of a workshop held at the Institute for Nuclear Theory, Seattle, in January 2009, is intended as a 10-year update and supplement to Reviews of Modern Physics 70 (1998) 1265.Comment: 54 pages, 20 figures, version to be published in Reviews of Modern Physics; various typos corrected and several updates mad

    WNT5A-JNK regulation of vascular insulin resistance in human obesity

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    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (pWNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p

    Towards an Intelligent Tutor for Mathematical Proofs

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    Computer-supported learning is an increasingly important form of study since it allows for independent learning and individualized instruction. In this paper, we discuss a novel approach to developing an intelligent tutoring system for teaching textbook-style mathematical proofs. We characterize the particularities of the domain and discuss common ITS design models. Our approach is motivated by phenomena found in a corpus of tutorial dialogs that were collected in a Wizard-of-Oz experiment. We show how an intelligent tutor for textbook-style mathematical proofs can be built on top of an adapted assertion-level proof assistant by reusing representations and proof search strategies originally developed for automated and interactive theorem proving. The resulting prototype was successfully evaluated on a corpus of tutorial dialogs and yields good results.Comment: In Proceedings THedu'11, arXiv:1202.453

    Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

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    We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

    Measurement of the Charge Asymmetry in B→K∗(892)±π∓B\to K^* (892)^{\pm}\pi^{\mp}

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    We report on a search for a CP-violating asymmetry in the charmless hadronic decay B -> K*(892)+- pi-+, using 9.12 fb^-1 of integrated luminosity produced at \sqrt{s}=10.58 GeV and collected with the CLEO detector. We find A_{CP}(B -> K*(892)+- pi-+) = 0.26+0.33-0.34(stat.)+0.10-0.08(syst.), giving an allowed interval of [-0.31,0.78] at the 90% confidence level.Comment: 7 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

    Search for CP Violation in D^0--> K_S^0 pi^+pi^-

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    We report on a search for CP violation in the decay of D0 and D0B to Kshort pi+pi-. The data come from an integrated luminosity of 9.0 1/fb of e+e- collisions at sqrt(s) ~ 10 GeV recorded with the CLEO II.V detector. The resonance substructure of this decay is well described by ten quasi-two-body decay channels (K*-pi+, K*0(1430)-pi+, K*2(1430)-pi+, K*(1680)-pi+, Kshort rho, Kshort omega, Kshort f0(980), Kshort f2(1270), Kshort f0(1370), and the ``wrong sign'' K*+ pi-) plus a small non-resonant component. We observe no evidence for CP violation in the amplitudes and phases that describe the decay D0 to K_S^0 pi+pi-.Comment: 10 pages, 3 figures, also available at http://w4.lns.cornell.edu/public/CLNS/, submitted to PR
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