Targeting trimeric transmembrane domain 5 of oncogenic latent membrane protein 1 using a computationally designed peptide

Protein–protein interactions are involved in diverse biological processes. These interactions are therefore vital targets for drug development. However, the design of peptide modulators targeting membrane-based protein–protein interactions is a challenging goal owing to the lack of experimentally-determined structures and efficient protocols to probe their functions. Here we employed rational peptide design and molecular dynamics simulations to design a membrane-insertable peptide that disrupts the strong trimeric self-association of the fifth transmembrane domain (TMD5) of the oncogenic Epstein–Barr virus (EBV) latent membrane protein-1 (LMP-1). The designed anti-TMD5 peptide formed 1 : 2 heterotrimers with TMD5 in micelles and inhibited TMD5 oligomerization in bacterial membranes. Moreover, the designed peptide inhibited LMP-1 homotrimerization based on NF-κB activity in EVB positive lymphoma cells. The results indicated that the designed anti-TMD5 peptide may represent a promising starting point for elaboration of anti-EBV therapeutics via inhibition of LMP-1 oligomerization. To the best of our knowledge, this represents the first example of disrupting homotrimeric transmembrane helices using a designed peptide inhibitor

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Sensitivity of the T2K accelerator-based neutrino experiment with an Extended run to 20×102120\times10^{21} POT

18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figuresRecent measurements at the T2K experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We explore the physics program of an extension to the currently approved T2K running of $7.8\times 10^{21}$ protons-on-target to $20\times 10^{21}$ protons-on-target,aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. With accelerator and beam line upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026.We acknowledge the support of MEXT, Japan; NSERC (Grant No. SAPPJ-2014-00031), NRC and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SERI, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, and GridPP in the United Kingdom. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), H2020 Grant No. RISE-GA644294-JENNIFER, EU; JSPS, Japan; Royal Society, UK; and the DOE Early Career program, USA. CNRS/IN2P3: Centre National de la Recherche ScientifiqueInstitut National de Physique Nucleaire et de Physique des Particules RSF: Russian Science Foundation MES: Ministry of Education and Science, Russia ERDF: European Regional Development Fund SNSF: Swiss National Science Foundation SER (should be SERI): State Secretariat for Education, Research and Innovatio

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