219 research outputs found

    Effects of HER2 overexpression on cell signaling networks governing proliferation and migration

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    Although human epidermal growth factor receptor 2 (HER2) overexpression is implicated in tumor progression for a variety of cancer types, how it dysregulates signaling networks governing cell behavioral functions is poorly understood. To address this problem, we use quantitative mass spectrometry to analyze dynamic effects of HER2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). Data generated from this analysis reveal that EGF stimulation of HER2-overexpressing cells activates multiple signaling pathways to stimulate migration, whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network. Self-organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER2-overexpressing cells in comparison with parental cells for EGF and HRG treatment. Partial least-squares regression analysis of the same data set identified quantitative combinations of signals within the networks that strongly correlate with cell proliferation and migration measured under the same battery of conditions. Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration

    The deuteron: structure and form factors

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    A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

    Long-Term climate change commitment and reversibility: An EMIC intercomparison

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    This is the final version of the article. Available from the American Meteorological Society via the DOI in this record.This paper summarizes the results of an intercomparison project with Earth System Models of Intermediate Complexity (EMICs) undertaken in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). The focus is on long-term climate projections designed to 1) quantify the climate change commitment of different radiative forcing trajectories and 2) explore the extent to which climate change is reversible on human time scales. All commitment simulations follow the four representative concentration pathways (RCPs) and their extensions to year 2300. MostEMICs simulate substantial surface air temperature and thermosteric sea level rise commitment following stabilization of the atmospheric composition at year-2300 levels. The meridional overturning circulation (MOC) is weakened temporarily and recovers to near-preindustrial values in most models for RCPs 2.6-6.0. The MOC weakening is more persistent for RCP8.5. Elimination of anthropogenic CO2 emissions after 2300 results in slowly decreasing atmospheric CO2 concentrations. At year 3000 atmospheric CO2 is still at more than half its year-2300 level in all EMICs forRCPs 4.5-8.5. Surface air temperature remains constant or decreases slightly and thermosteric sea level rise continues for centuries after elimination ofCO2 emissions in allEMICs.Restoration of atmosphericCO2 fromRCPto preindustrial levels over 100-1000 years requires large artificial removal of CO2 from the atmosphere and does not result in the simultaneous return to preindustrial climate conditions, as surface air temperature and sea level response exhibit a substantial time lag relative to atmospheric CO2. © 2013 American Meteorological Society.KZ and AJW acknowledge support from the National Science and Engineering Research Council (NSERC) Discovery Grant Program. AJW acknowledges support from NSERC's G8 Research Councils Initiative on Multilateral Research Funding Program. AVE and IIM were supported by the President of Russia Grant 5467.2012.5, by the Russian Foundation for Basic Research, and by the programs of the Russian Academy of Sciences. EC, TF, HG, and GPB acknowledge support from the Belgian Federal Science Policy Office. FJ, RS, and MS acknowledge support by the Swiss National Science Foundation and by the European Project CARBOCHANGE (Grant 264879), which received funding from the European Commission's Seventh Framework Programme (FP7/2007–2013). PBH and NRE acknowledge support from EU FP7 Grant ERMITAGE 265170

    Declining uncertainty in transient climate response as CO2 forcing dominates future climate change

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    Carbon dioxide has exerted the largest portion of radiative forcing and surface temperature change over the industrial era, but other anthropogenic influences have also contributed. However, large uncertainties in total forcing make it difficult to derive climate sensitivity from historical observations. Anthropogenic forcing has increased between the Fourth and Fifth Assessment Reports of the Intergovernmental Panel of Climate Change (IPCC; refs,), although its relative uncertainty has decreased. Here we show, based on data from the two reports, that this evolution towards lower uncertainty can be expected to continue into the future. Because it is easier to reduce air pollution than carbon dioxide emissions and because of the long lifetime of carbon dioxide, the less uncertain carbon dioxide forcing is expected to become increasingly dominant. Using a statistical model, we estimate that the relative uncertainty in anthropogenic forcing of more than 40% quoted in the latest IPCC report for 2011 will be almost halved by 2030, even without better scientific understanding. Absolute forcing uncertainty will also decline for the first time, provided projected decreases in aerosols occur. Other factors being equal, this stronger constraint on forcing will bring a significant reduction in the uncertainty of observation-based estimates of the transient climate response, with a 50% reduction in its uncertainty range expected by 2030

    Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

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    In an exclusive measurement of the reaction Îłd→K+K−pn\gamma d \to K^+ K^- p n, a narrow peak that can be attributed to an exotic baryon with strangeness S=+1S=+1 is seen in the K+nK^+n invariant mass spectrum. The peak is at 1.542±0.0051.542\pm 0.005 GeV/c2^2 with a measured width of 0.021 GeV/c2^2 FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is 5.2±0.6σ5.2 \pm 0.6 \sigma. The mass and width of the observed peak are consistent with recent reports of a narrow S=+1S=+1 baryon by other experimental groups.Comment: 5 pages, 5 figure

    Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

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    We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the sinâĄÏ•\sin\phi modulation increases with the momentum of the pion relative to the virtual photon, zz, with an average amplitude of 0.038±0.005±0.0030.038 \pm 0.005 \pm 0.003 for 0.5<z<0.80.5 < z < 0.8 range.Comment: 5 pages, RevTEX4, 3 figures, 2 table

    Measurement of the Polarized Structure Function σLTâ€Č\sigma_{LT^\prime} for p(e⃗,eâ€Čp)πop(\vec{e},e'p)\pi^o in the Δ(1232)\Delta(1232) Resonance Region

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    The polarized longitudinal-transverse structure function σLTâ€Č\sigma_{LT^\prime} has been measured in the Δ(1232)\Delta(1232) resonance region at Q2=0.40Q^2=0.40 and 0.65 GeV2^2. Data for the p(e⃗,eâ€Čp)πop(\vec e,e'p)\pi^o reaction were taken at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. For the first time a complete angular distribution was measured, permitting the separation of different non-resonant amplitudes using a partial wave analysis. Comparison with previous beam asymmetry measurements at MAMI indicate a deviation from the predicted Q2Q^2 dependence of σLTâ€Č\sigma_{LT^{\prime}} using recent phenomenological models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid Communications. Version 2 has revised Q^2 analysi
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