Role of proteinase-activated receptor-1-dependent secondary mediators in lung fibrosis.

Persistent local activation of the coagulation cascade typifies tibroproliferative lung disorders such as idiopathic pulmonary fibrosis and the acute respiratory distress syndrome. In addition to its role in coagulation, thrombin exerts potent pro inflammatory and pro-flbrotic effects via activation of its major cellular receptor proteinase-activated receptor-1 (PARi). In this thesis, the relevance of PARi activation to inflammation and fibrosis in a model of lung injury and fibrosis based on the intra-tracheal instillation of bleomycin was examined. Lung inflammation and fibrosis were substantially attenuated in PARi-deficient mice. The attenuated inflammatory response was manifest by substantial reductions in bronchoalveolar lavage protein content, total leukocyte numbers, and lung levels of the chemokine CCL2. The attenuated fibrotic response was manifest by a reduction in lung collagen accumulation of around 60%, and reduced mRNA and/or protein levels of the pro- fibrotic mediators connective tissue growth factor (CTGF) and transforming growth factor-beta-1 (TGF-beta1). These data suggest that PAR may promote inflammation and fibrosis, at least in part, via the expression of CCL2, CTGF, and TGFbeta1. Further studies demonstrated prominent immunostaining for PAR on lung epithelial cells following bleomycin injury, consistent with these cells being a potential source of PARi-dependent secondary mediators in the injured lung. Widespread epithelial injury is a prominent feature of fibroproliferative lung disorders, in which hyperplastic activated epithelial cells represent a major source of pro-inflammatory and pro-fibrotic mediators. The effect of PARi activation on lung epithelial expression of CCL2, CTGF and TGFbeta1 was therefore examined in vitro. Exposure to both thrombin and the PARi agonist peptide TFLLR-NH2 substantially increased mRNA levels of CCL2 and CTGF, but not TGFbeta1 in A549 and BEAS-2B human lung epithelial cells. Increases in CCL2 and CTGF mRNA levels in response to thrombin were attenuated with the PARi antagonist RWJ-58259. PAR 1-dependent increases in CCL2 and CTGF mRNA are apparently protein kinase C-dependent since increases in response to TFLLR-NH2 were inhibited by the protein kinase C inhibitor Ro-31-8425. Increases in CCL2 and CTGF mRNA in response to PARi activation were mirrorred by comparable increases at the protein level. Taken together, these data suggest that epithelial cells may represent a source of PARi-dependent pro-inflammatory and pro-fibrotic mediators following lung injury

Analysis of Ductile Bursting in Pressure Vessels of Texture-Hardening and Filament-Wrapped Materials

Analyses are presented for predicting the strength governed by the plastic tensile instability (PTI) phenomenon in thin-walled cylindrical and spherical pressure vessels constructed of texture- hardening alloys and with or without over-wrapped filaments. These analyses are important in predicting ductile bursting of pressure vessels used in such high-performance applications as high-pressure storage bottles, liquid-propellant tankage, and solid rocket casings. The analyses cover cylindrical pressure vessels subject to any ratio of biaxial stresses. Also means of estimating the effect of finite length is presented. Spherical vessels of texture- hardening material and cylindrical vessels with filaments over wrapped on a texture-hardening metallic substrate are treated as special cases. The analytical results are compared with available experimental results with good success.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters

Measurement of the production cross section of prompt j/psi mesons in association with a W (+/-) boson in pp collisions root s=7 TeV with the ATLAS detector

The process pp → W±J/ψ provides a powerful probe of the production mechanism of charmonium in hadronic collisions, and is also sensitive to multiple parton interactions in the colliding protons. Using the 2011 ATLAS dataset of 4.5 fb-1 of p s = 7TeV pp collisions at the LHC, the first observation is made of the production of W± + prompt J/ events in hadronic collisions, using W± → μ and J/ψ → μ+μ-. A yield of 27.4±7.5 -6.5 W± + prompt J/ψ events is observed, with a statistical significance of 5.1. The production rate as a ratio to the inclusive W± boson production rate is measured, and the double parton scattering contribution to the cross section is estimated. Copyright CERN, for the benefit of the ATLAS Collaboration

Measurement of D*+/- meson production in jets from pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

This paper reports a measurement of D*+/- meson production in jets from proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV at the CERN Large Hadron Collider. The measurement is based on a data sample recorded with the ATLAS detector with an integrated luminosity of 0.30 pb^-1 for jets with transverse momentum between 25 and 70 GeV in the pseudorapidity range |eta| < 2.5. D*+/- mesons found in jets are fully reconstructed in the decay chain: D*+ -> D0pi+, D0 -> K-pi+, and its charge conjugate. The production rate is found to be N(D*+/-)/N(jet) = 0.025 +/- 0.001(stat.) +/- 0.004(syst.) for D*+/- mesons that carry a fraction z of the jet momentum in the range 0.3 < z < 1. Monte Carlo predictions fail to describe the data at small values of z, and this is most marked at low jet transverse momentum.Comment: 10 pages plus author list (22 pages total), 5 figures, 1 table, matches published version in Physical Review

Search for scalar top quark pair production in natural gauge mediated supersymmetry models with the ATLAS detector in pp collisions at sqrt(s) = 7 TeV

The results of a search for pair production of the lighter scalar partners of top quarks in 2.05 fb-1 of pp collisions at sqrt(s) =7 TeV using the ATLAS experiment at the LHC are reported. Scalar top quarks are searched for in events with two same flavour opposite-sign leptons (electrons or muons) with invariant mass consistent with the Z boson mass, large missing transverse momentum and jets in the final state. At least one of the jets is identified as originating from a b-quark. No excess over Standard Model expectations is found. The results are interpreted in the framework of R-parity conserving, gauge mediated Supersymmetry breaking `natural' scenarios, where the neutralino is the next-to-lightest supersymmetric particle. Scalar top quark masses up to 310 GeV are excluded for the lightest neutralino mass between 115 GeV and 230 GeV at 95% confidence level, reaching an exclusion of the scalar top quark mass of 330 GeV for the lightest neutralino mass of 190 GeV. Scalar top quark masses below 240 GeV are excluded for all values of the lightest neutralino mass above the Z boson mass.Comment: 7 pages plus author list (20 pages total), 4 figures, 1 table, matches published PLB versio

Search for supersymmetry in final states with jets, missing transverse momentum and one isolated lepton in sqrt{s} = 7 TeV pp collisions using 1 fb-1 of ATLAS data

We present an update of a search for supersymmetry in final states containing jets, missing transverse momentum, and one isolated electron or muon, using 1.04 fb^-1 of proton-proton collision data at sqrt{s} = 7 TeV recorded by the ATLAS experiment at the LHC in the first half of 2011. The analysis is carried out in four distinct signal regions with either three or four jets and variations on the (missing) transverse momentum cuts, resulting in optimized limits for various supersymmetry models. No excess above the standard model background expectation is observed. Limits are set on the visible cross-section of new physics within the kinematic requirements of the search. The results are interpreted as limits on the parameters of the minimal supergravity framework, limits on cross-sections of simplified models with specific squark and gluino decay modes, and limits on parameters of a model with bilinear R-parity violation.Comment: 18 pages plus author list (30 pages total), 9 figures, 4 tables, final version to appear in Physical Review