1,001 research outputs found

    ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

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    Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional activity in head and neck squamous carcinomas (HNSC). Many additional tumor types showed significant association between NRF2 signaling and mutation of specific components of the SWI/SNF complex. Different effects of BAF and PBAF mutations on the polarity of NRF2 signaling were observed. Overall, our results support a context-dependent functional link between SWI/SNF and NRF2 mutations across human cancers and implicate ARID1A inactivation in HPV-negative HNSC in promoting tumor progression and survival through activation of the KEAP1-NRF2 signaling pathway. The tumorspecific effects of these mutations open a new area of study for how mutations in the KEAP1-NRF2 pathway and the SWI/SNF complex contribute to cancer

    The nature of an object-oriented program:how do practitioners understand the nature of what they are creating?

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    Object-oriented programming is seen as a difficult skill to master. There is considerable debate about the most appropriate way to introduce novice programmers to object-oriented concepts. Is it possible to uncover what the critical aspects or features are that enhance the learning of object-oriented programming? Practitioners have differing understandings of the nature of an object-oriented program. Uncovering these different ways of understanding leads to agreater understanding of the critical aspects and their relationship tothe structure of the program produced. A phenomenographic studywas conducted to uncover practitioner understandings of the nature of an object-oriented program. The study identified five levels of understanding and three dimensions of variation within these levels. These levels and dimensions of variation provide a framework for fostering conceptual change with respect to the nature of an object-oriented program

    Anomalous dimensions and phase transitions in superconductors

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    The anomalous scaling in the Ginzburg-Landau model for the superconducting phase transition is studied. It is argued that the negative sign of the η\eta exponent is a consequence of a special singular behavior in momentum space. The negative sign of η\eta comes from the divergence of the critical correlation function at finite distances. This behavior implies the existence of a Lifshitz point in the phase diagram. The anomalous scaling of the vector potential is also discussed. It is shown that the anomalous dimension of the vector potential ηA=4d\eta_A=4-d has important consequences for the critical dynamics in superconductors. The frequency-dependent conductivity is shown to obey the scaling σ(ω)ξz2\sigma(\omega)\sim\xi^{z-2}. The prediction z3.7z\approx 3.7 is obtained from existing Monte Carlo data.Comment: RevTex, 20 pages, no figures; small changes; version accepted in PR

    Grain Surface Models and Data for Astrochemistry

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    AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

    A Measurement of Coherent Neutral Pion Production in Neutrino Neutral Current Interactions in NOMAD

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    We present a study of exclusive neutral pion production in neutrino-nucleus Neutral Current interactions using data from the NOMAD experiment at the CERN SPS. The data correspond to 1.44×1061.44 \times 10^6 muon-neutrino Charged Current interactions in the energy range 2.5Eν3002.5 \leq E_{\nu} \leq 300 GeV. Neutrino events with only one visible π0\pi^0 in the final state are expected to result from two Neutral Current processes: coherent π0\pi^0 production, {\boldmath ν+Aν+A+π0\nu + {\cal A} \to \nu + {\cal A} + \pi^0} and single π0\pi^0 production in neutrino-nucleon scattering. The signature of coherent π0\pi^0 production is an emergent π0\pi^0 almost collinear with the incident neutrino while π0\pi^0's produced in neutrino-nucleon deep inelastic scattering have larger transverse momenta. In this analysis all relevant backgrounds to the coherent π0\pi^0 production signal are measured using data themselves. Having determined the backgrounds, and using the Rein-Sehgal model for the coherent π0\pi^0 production to compute the detection efficiency, we obtain {\boldmath 4630±522(stat)±426(syst)4630 \pm 522 (stat) \pm 426 (syst)} corrected coherent-π0\pi^0 events with Eπ00.5E_{\pi^0} \geq 0.5 GeV. We measure {\boldmath σ(νAνAπ0)=[72.6±8.1(stat)±6.9(syst)]×1040cm2/nucleus\sigma (\nu {\cal A} \to \nu {\cal A} \pi^0) = [ 72.6 \pm 8.1(stat) \pm 6.9(syst) ] \times 10^{-40} cm^2/nucleus}. This is the most precise measurement of the coherent π0\pi^0 production to date.Comment: 23 pages, 9 figures, accepted for publication in Phys. Lett.

    Dilepton mass spectra in p+p collisions at sqrt(s)= 200 GeV and the contribution from open charm

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    The PHENIX experiement has measured the electron-positron pair mass spectrum from 0 to 8 GeV/c^2 in p+p collisions at sqrt(s)=200 GeV. The contributions from light meson decays to e^+e^- pairs have been determined based on measurements of hadron production cross sections by PHENIX. They account for nearly all e^+e^- pairs in the mass region below 1 GeV/c^2. The e^+e^- pair yield remaining after subtracting these contributions is dominated by semileptonic decays of charmed hadrons correlated through flavor conservation. Using the spectral shape predicted by PYTHIA, we estimate the charm production cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) \mu b, which is consistent with QCD calculations and measurements of single leptons by PHENIX.Comment: 375 authors from 57 institutions, 18 pages, 4 figures, 2 tables. Submitted to Physics Letters B. v2 fixes technical errors in matching authors to institutions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

    Inclusive cross section and double helicity asymmetry for \pi^0 production in p+p collisions at sqrt(s)=200 GeV: Implications for the polarized gluon distribution in the proton

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    The PHENIX experiment presents results from the RHIC 2005 run with polarized proton collisions at sqrt(s)=200 GeV, for inclusive \pi^0 production at mid-rapidity. Unpolarized cross section results are given for transverse momenta p_T=0.5 to 20 GeV/c, extending the range of published data to both lower and higher p_T. The cross section is described well for p_T < 1 GeV/c by an exponential in p_T, and, for p_T > 2 GeV/c, by perturbative QCD. Double helicity asymmetries A_LL are presented based on a factor of five improvement in uncertainties as compared to previously published results, due to both an improved beam polarization of 50%, and to higher integrated luminosity. These measurements are sensitive to the gluon polarization in the proton, and exclude maximal values for the gluon polarization.Comment: 375 authors, 7 pages, 3 figures. Submitted to Phys. Rev. D, Rapid Communications. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
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