Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

<p>Abstract</p> <p>Background</p> <p>The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and <it>Nfe2l2</it>-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV₁) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV₁measurements during 3 surveys, respectively 7 FEV₁measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV₁measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV₁level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV₁level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV₁decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV₁in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV₁in the general population.</p

Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

Precise Measurement of the Neutrino Mixing Parameter theta(23) from Muon Neutrino Disappearance in an Off-Axis Beam

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter theta_{23}. Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57 x 10^{20} protons on target, T2K has fit the energy-dependent nu_mu oscillation probability to determine oscillation parameters. Marginalizing over the values of other oscillation parameters yields sin^2 (theta_{23}) = 0.514 +0.055/-0.056 (0.511 +- 0.055), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Delta m^2_{32} = (2.51 +- 0.10) x 10^{-3} eV^2/c^4 (inverted hierarchy: Delta m^2_{13} = (2.48 +- 0.10) x 10^{-3} eV^2/c^4). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty

Measurement of the intrinsic electron neutrino component in the T2K neutrino beam with the ND280 detector

The T2K experiment has reported the first observation of the appearance of electron neutrinos in a muon neutrino beam. The main and irreducible background to the appearance signal comes from the presence in the neutrino beam of a small intrinsic component of electron neutrinos originating from muon and kaon decays. In T2K, this component is expected to represent 1.2% of the total neutrino flux. A measurement of this component using the near detector (ND280), located 280 m from the target, is presented. The charged current interactions of electron neutrinos are selected by combining the particle identification capabilities of both the time projection chambers and electromagnetic calorimeters of ND280. The measured ratio between the observed electron neutrino beam component and the prediction is 1.01 +/- 0.10 providing a direct confirmation of the neutrino fluxes and neutrino cross section modeling used for T2K neutrino oscillation analyses. Electron neutrinos coming from muons and kaons decay are also separately measured, resulting in a ratio with respect to the prediction of 0.68 +/- 0.30 and 1.10 +/- 0.14, respectively

T2K neutrino flux prediction

cited By 15 art_number: 012001 affiliation: Centre for Particle Physics, Department of Physics, University of Alberta, Edmonton, AB, Canada; Albert Einstein Center for Fundamental Physics, Laboratory for High Energy Physics (LHEP), University of Bern, Bern, Switzerland; Department of Physics, Boston University, Boston, MA, United States; Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Physics and Astronomy, University of California Irvine, Irvine, CA, United States; IRFU, CEA Saclay, Gif-sur-Yvette, France; Institute for Universe and Elementary Particles, Chonnam National University, Gwangju, South Korea; Department of Physics, University of Colorado at Boulder, Boulder, CO, United States; Department of Physics, Colorado State University, Fort Collins, CO, United States; Department of Physics, Dongshin University, Naju, South Korea; Department of Physics, Duke University, Durham, NC, United States; IN2P3-CNRS, Laboratoire Leprince-Ringuet, Ecole Polytechnique, Palaiseau, France; Institute for Particle Physics, ETH Zurich, Zurich, Switzerland; Section de Physique, DPNC, University of Geneva, Geneva, Switzerland; H. Niewodniczanski Institute of Nuclear Physics PAN, Cracow, Poland; High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, Japan; Institut de Fisica d’Altes Energies (IFAE), Bellaterra (Barcelona), Spain; IFIC (CSIC and University of Valencia), Valencia, Spain; Department of Physics, Imperial College London, London, United Kingdom; INFN Sezione di Bari, Dipartimento Interuniversitario di Fisica, Università e Politecnico di Bari, Bari, Italy; INFN Sezione di Napoli and Dipartimento di Fisica, Università di Napoli, Napoli, Italy; INFN Sezione di Padova, Dipartimento di Fisica, Università di Padova, Padova, Italy; INFN Sezione di Roma, Università di Roma la Sapienza, Roma, Italy; Institute for Nuclear Research, Russian Academy of Sciences, Moscow, Russian Federation; Kobe University, Kobe, Japan; Department of Physics, Kyoto University, Kyoto, Japan; Physics Department, Lancaster University, Lancaster, United Kingdom; Department of Physics, University of Liverpool, Liverpool, United Kingdom; Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, United States; Université de Lyon, Université Claude Bernard Lyon 1, IPN Lyon (IN2P3), Villeurbanne, France; Department of Physics, Miyagi University of Education, Sendai, Japan; National Centre for Nuclear Research, Warsaw, Poland; State University of New York at Stony Brook, Stony Brook, NY, United States; Department of Physics and Astronomy, Osaka City University, Department of Physics, Osaka, Japan; Department of Physics, Oxford University, Oxford, United Kingdom; UPMC, Université Paris Diderot, Laboratoire de Physique Nucléaire et de Hautes Energies (LPNHE), Paris, France; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA, United States; School of Physics, Queen Mary University of London, London, United Kingdom; Department of Physics, University of Regina, Regina, SK, Canada; Department of Physics and Astronomy, University of Rochester, Rochester, NY, United States; III. Physikalisches Institut, RWTH Aachen University, Aachen, Germany; Department of Physics and Astronomy, Seoul National University, Seoul, South Korea; Department of Physics and Astronomy, University of Sheffield, Sheffield, United Kingdom; University of Silesia, Institute of Physics, Katowice, Poland; STFC, Rutherford Appleton Laboratory, Harwell Oxford, Warrington, United Kingdom; Department of Physics, University of Tokyo, Tokyo, Japan; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan; Institute for Cosmic Ray Research, Research Center for Cosmic Neutrinos, University of Tokyo, Kashiwa, Japan; Department of Physics, University of Toronto, Toronto, ON, Canada; TRIUMF, Vancouver, BC, Canada; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada; Faculty of Physics, University of Warsaw, Warsaw, Poland; Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland; Department of Physics, University of Warwick, Coventry, United Kingdom; Department of Physics, University of Washington, Seattle, WA, United States; Department of Physics, University of Winnipeg, Winnipeg, MB, Canada; Faculty of Physics and Astronomy, Wroclaw University, Wroclaw, Poland; Department of Physics and Astronomy, York University, Toronto, ON, Canada references: Astier, P., (2003) Nucl. Instrum. Methods Phys. Res., Sect. A, 515, p. 800. , (NOMAD Collaboration), NIMAER 0168-9002 10.1016/j.nima.2003.07.054; Ahn, M., (2006) Phys. Rev. D, 74, p. 072003. , (K2K Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.74.072003; Adamson, P., (2008) Phys. Rev. D, 77, p. 072002. , (MINOS Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.77.072002; Aguilar-Arevalo, A., (2009) Phys. Rev. D, 79, p. 072002. , (MiniBooNE Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.79.072002; (2003) Letter of Intent: Neutrino Oscillation Experiment at JHF, , http://neutrino.kek.jp/jhfnu/loi/loi_JHFcor.pdf, T2K Collaboration; Abe, K., (2011) Nucl. Instrum. Methods Phys. Res., Sect. A, 659, p. 106. , (T2K Collaboration), NIMAER 0168-9002 10.1016/j.nima.2011.06.067; Abe, K., (2011) Phys. Rev. Lett., 107, p. 041801. , (T2K Collaboration), PRLTAO 0031-9007 10.1103/PhysRevLett.107.041801; Abe, K., (2012) Phys. Rev. D, 85, p. 031103. , (T2K Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.85.031103; Fukuda, Y., (2003) Nucl. Instrum. Methods Phys. Res., Sect. A, 501, p. 418. , NIMAER 0168-9002 10.1016/S0168-9002(03)00425-X; Beavis, D., Carroll, A., Chiang, I., (1995), Physics Design Report, BNL 52459Abgrall, N., (2011) Phys. Rev. C, 84, p. 034604. , (NA61/SHINE Collaboration), PRVCAN 0556-2813 10.1103/PhysRevC.84.034604; Abgrall, N., (2012) Phys. Rev. C, 85, p. 035210. , (NA61/SHINE Collaboration), PRVCAN 0556-2813 10.1103/PhysRevC.85.035210; Bhadra, S., (2013) Nucl. Instrum. Methods Phys. Res., Sect. A, 703, p. 45. , NIMAER 0168-9002 10.1016/j.nima.2012.11.044; Van Der Meer, S., Report No. CERN-61-07Palmer, R., Report No. CERN-65-32, 141Ichikawa, A., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 690, p. 27. , NIMAER 0168-9002 10.1016/j.nima.2012.06.045; Matsuoka, K., (2010) Nucl. Instrum. Methods Phys. Res., Sect. A, 624, p. 591. , NIMAER 0168-9002 10.1016/j.nima.2010.09.074; Abe, K., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 694, p. 211. , (T2K Collaboration), NIMAER 0168-9002 10.1016/j.nima.2012.03.023; Abgrall, N., (2011) Nucl. Instrum. Methods Phys. Res., Sect. A, 637, p. 25. , (T2K ND280 TPC Collaboration), NIMAER 0168-9002 10.1016/j.nima.2011.02. 036; Amaudruz, P.-A., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 696, p. 1. , (T2K ND280 FGD Collaboration), NIMAER 0168-9002 10.1016/j.nima.2012.08. 020; Battistoni, G., Cerutti, F., Fasso, A., Ferrari, A., Muraro, S., Ranft, J., Roesler, S., Sala, P.R., (2007) AIP Conf. Proc., 896, p. 31. , APCPCS 0094-243X 10.1063/1.2720455; A. Ferrari, P. R. Sala, A. Fasso, and J. Ranft, Report No. CERN-2005-010A. Ferrari P. R. Sala A. Fasso J. Ranft Report No. SLAC-R-773A. Ferrari P. R. Sala A. Fasso J. Ranft Report No. INFN-TC-05-11R. Brun, F. Carminati, and S. Giani, Report No. CERN-W5013Zeitnitz, C., Gabriel, T.A., (1993) Proceedings of International Conference on Calorimetry in High Energy Physics, , in Elsevier Science B.V., Tallahassee, FL; Fasso, A., Ferrari, A., Ranft, J., Sala, P.R., Proceedings of the International Conference on Calorimetry in High Energy Physics, 1994, , in; Beringer, J., (2012) Phys. Rev. D, 86, p. 010001. , (Particle Data Group), PRVDAQ 1550-7998 10.1103/PhysRevD.86.010001; Eichten, T., (1972) Nucl. Phys. B, 44, p. 333. , NUPBBO 0550-3213 10.1016/0550-3213(72)90120-4; Allaby, J.V., Tech. Rep. 70-12 (CERN, 1970)Chemakin, I., (2008) Phys. Rev. C, 77, p. 015209. , PRVCAN 0556-2813 10.1103/PhysRevC.77.015209; Abrams, R.J., Cool, R., Giacomelli, G., Kycia, T., Leontic, B., Li, K., Michael, D., (1970) Phys. Rev. D, 1, p. 1917. , PRVDAQ 0556-2821 10.1103/PhysRevD.1.1917; Allaby, J.V., (1970) Yad. Fiz., 12, p. 538. , IDFZA7 0044-0027; Allaby, J.V., (1969) Phys. Lett. B, 30, p. 500. , PYLBAJ 0370-2693 10.1016/0370-2693(69)90184-1; Allardyce, B.W., (1973) Nucl. Phys. A, 209, p. 1. , NUPABL 0375-9474 10.1016/0375-9474(73)90049-3; Bellettini, G., Cocconi, G., Diddens, A.N., Lillethun, E., Matthiae, G., Scanlon, J.P., Wetherell, A.M., (1966) Nucl. Phys., 79, p. 609. , NUPHA7 0029-5582 10.1016/0029-5582(66)90267-7; Bobchenko, B.M., (1979) Sov. J. Nucl. Phys., 30, p. 805. , SJNCAS 0038-5506; Carroll, A.S., (1979) Phys. Lett. B, 80, p. 319. , PYLBAJ 0370-2693 10.1016/0370-2693(79)90226-0; Cronin, J.W., Cool, R., Abashian, A., (1957) Phys. Rev., 107, p. 1121. , PHRVAO 0031-899X 10.1103/PhysRev.107.1121; Chen, F.F., Leavitt, C., Shapiro, A., (1955) Phys. Rev., 99, p. 857. , PHRVAO 0031-899X 10.1103/PhysRev.99.857; Denisov, S.P., Donskov, S.V., Gorin, Yu.P., Krasnokutsky, R.N., Petrukhin, A.I., Prokoshkin, Yu.D., Stoyanova, D.A., (1973) Nucl. Phys. B, 61, p. 62. , NUPBBO 0550-3213 10.1016/0550-3213(73)90351-9; Longo, M.J., Moyer, B.J., (1962) Phys. Rev., 125, p. 701. , PHRVAO 0031-899X 10.1103/PhysRev.125.701; Vlasov, A.V., (1978) Sov. J. Nucl. Phys., 27, p. 222. , SJNCAS 0038-5506; Feynman, R., (1969) Phys. Rev. Lett., 23, p. 1415. , PRLTAO 0031-9007 10.1103/PhysRevLett.23.1415; Bonesini, M., Marchionni, A., Pietropaolo, F., Tabarelli De Fatis, T., (2001) Eur. Phys. J. C, 20, p. 13. , EPCFFB 1434-6044 10.1007/s100520100656; Barton, D.S., (1983) Phys. Rev. D, 27, p. 2580. , PRVDAQ 0556-2821 10.1103/PhysRevD.27.2580; Skubic, P., (1978) Phys. Rev. D, 18, p. 3115. , PRVDAQ 0556-2821 10.1103/PhysRevD.18.3115; Feynman, R.P., (1972) Photon-Hadron Interactions, , Benjamin, New York; Bjorken, J.D., Paschos, E.A., (1969) Phys. Rev., 185, p. 1975. , PHRVAO 0031-899X 10.1103/PhysRev.185.1975; Taylor, F.E., Carey, D., Johnson, J., Kammerud, R., Ritchie, D., Roberts, A., Sauer, J., Walker, J., (1976) Phys. Rev. D, 14, p. 1217. , PRVDAQ 0556-2821 10.1103/PhysRevD.14.1217; Abgrall, N., (2013) Nucl. Instrum. Methods Phys. Res., Sect. A, 701, p. 99. , NIMAER 0168-9002 10.1016/j.nima.2012.10.079; Hayato, Y., (2002) Nucl. Phys. B, Proc. Suppl., 112, p. 171. , NPBSE7 0920-5632 10.1016/S0920-5632(02)01759-0 correspondence_address1: Abe, K.; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan coden: PRVDA abbrev_source_title: Phys Rev D Part Fields Gravit Cosmol document_type: Article source: Scopu

Measurement of the neutrino-oxygen neutral-current interaction cross section by observing nuclear deexcitation gamma rays

We report the first measurement of the neutrino-oxygen neutral-current quasielastic (NCQE) cross section gamma It is obtained by observing nuclear deexcitation. rays which follow neutrino-oxygen interactions at the Super-Kamiokande water Cherenkov detector. We use T2K data corresponding to 3.01 x 10(20) protons on target. By selecting only events during the T2K beam window and with well-reconstructed vertices in the fiducial volume, the large background rate from natural radioactivity is dramatically reduced. We observe 43 events in the 4-30 MeV reconstructed energy window, compared with an expectation of 51.0, which includes an estimated 16.2 background events. The background is primarily nonquasielastic neutral-current interactions and has only 1.2 events from natural radioactivity. The flux-averaged NCQE cross section we measure is 1.55 x 10(-38) cm(2) with a 68% confidence interval of (1.22, 2.20) x 10(-38) cm(2) at a median neutrino energy of 630 MeV, compared with the theoretical prediction of 2.01 x 10(-38) cm(2)

Physics Potentials with the Second Hyper-Kamiokande Detector in Korea

We have conducted sensitivity studies on an alternative configuration of the Hyper-Kamiokande experiment by locating the 2nd Hyper-Kamiokande detector in Korea at $\sim$1100$-\$1300 km baseline. Having two detectors at different baselines improves sensitivity to leptonic CP violation, neutrino mass ordering as well as nonstandard neutrino interactions. There are several candidate sites in Korea with greater than 1 km high mountains ranged at an 1$-$3 degree off-axis angle. Thanks to larger overburden of the candidate sites in Korea, low energy physics, such as solar and supernova neutrino physics as well as dark matter search, is expected to be improved. In this paper sensitivity studies on the CP violation phase and neutrino mass ordering are performed using current T2K systematic uncertainties in most cases. We plan to improve our sensitivity studies in the near future with better estimation of our systematic uncertainties