Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD

RATIONALE: Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. METHODS: Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed. RESULTS: Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD versus controls (log2 fold change (log2FC) -2.0, -2.2, -1.5, -0.5, -0.7 and -0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= -0.56, r= -0.58, r= -0.45, r= -0.36, r= -0.44, r= -0.37, r= -0.40 and r= -0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= -0.55, r= -0.61, r= -0.48, r= -0.51, r= -0.41, r= -0.31 and r= -0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPD versus controls (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPD versus healthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85). CONCLUSIONS: Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease

Crustal imaging of a mobile belt using magnetotellurics: An example of the Fowler Domain in South Australia

Extent: 18p.A long-period magnetotelluric data set was obtained in 2005 along a two-dimensional profile across the western part of the late Archaean-early Proterozoic Gawler Craton, South Australia. The study is aimed at delineating the electrical conductivity structure of the crust and upper mantle underneath an east-west trending profile extending from the Gawler Range Volcanics in the east, crossing the Nuyts Domain and the highly prospective Meso-Proterozoic Fowler Domain, and terminating in the Eucla Basin to the west. The resistivity model shows a very electrically resistive crust and upper mantle underneath the Nuyts and Fowler Domain, possibly representing the cratonic root of the Gawler Craton extending to depths of ∼160 km. The resistive cratonic root is closer to the surface underneath the Fowler Domain compared to the Nuyts Domain which supports findings from outcrops of metasediments of higher metamorphic grade in the Fowler Domain. A subvertical conductor marks the western terminus of the Fowler Domain and is imaged to upper mantle depths. On the eastern side of the Fowler Domain, another subvertical conductor extends to similar depths. These features spatially coincide with the Tallacootra and Coorabie shear zone at the surface, respectively, and their higher conductivity is likely due to a reduction in grain size of olivine associated with an increase in influence of grain boundary diffusion and thus enhanced conductivity. A comparison of the results with other surveys across mobile belts worldwide shows a more resistive response of the interpreted mobile belt of the Fowler Domain raising questions as to the nature of the domain.Stephan Thiel and Graham Heinso

Search for Electroweak Production of Single Top Quarks in ppbar Collisions

We present a search for electroweak production of single top quarks in the electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with the DZero detector between 1992 and 1995. We use events that include a tagging muon, implying the presence of a b jet, to set an upper limit at the 95% confidence level on the cross section for the s-channel process ppbar->tb+X of 39 pb. The upper limit for the t-channel process ppbar->tqb+X is 58 pb.Comment: 11 pages, 2 figures. This is the published versio

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

A Quasi-Model-Independent Search for New Physics at Large Transverse Momentum

We apply a quasi-model-independent strategy ("Sleuth") to search for new high p_T physics in approximately 100 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV collected by the DZero experiment during 1992-1996 at the Fermilab Tevatron. Over thirty-two e mu X, W+jets-like, Z+jets-like, and 3(lepton/photon)X exclusive final states are systematically analyzed for hints of physics beyond the standard model. Simultaneous sensitivity to a variety of models predicting new phenomena at the electroweak scale is demonstrated by testing the method on a particular signature in each set of final states. No evidence of new high p_T physics is observed in the course of this search, and we find that 89% of an ensemble of hypothetical similar experimental runs would have produced a final state with a candidate signal more interesting than the most interesting observed in these data.Comment: 28 pages, 17 figures. Submitted to Physical Review

Search for R-parity Violating Supersymmetry in Dimuon and Four-Jets Channel

We present results of a search for R-parity-violating decay of the neutralino chi_1^0, taken to be the Lightest Supersymmetric Particle. It is assumed that this decay proceeds through one of the lepton-number violating couplings lambda-prime_2jk (j=1,2; k=1,2,3). This search is based on 77.5 pb-1 of data, collected by the D0 experiment at the Fermilab Tevatron in ppbar collisions at a center of mass energy of 1.8 TeV in 1992-1995.Comment: 10 pages, 3 figure

Search for Large Extra Dimensions in Dielectron and Diphoton Production

We report a search for effects of large extra spatial dimensions in ppbar collisions at a center-of-mass energy of 1.8 TeV with the DZero detector, using events containing a pair of electrons or photons. The data are in good agreement with the expected background and do not exhibit evidence for large extra dimensions. We set the most restrictive lower limits to date, at the 95% confidence level, on the effective Planck scale between 1.0 TeV and 1.4 TeV for several formalisms and numbers of extra dimensions.Comment: 6 pages, 2 figures, submitted to Phys. Rev. Let

Search for New Physics Using Quaero: A General Interface to D0 Event Data

We describe Quaero, a method that i) enables the automatic optimization of searches for physics beyond the standard model, and ii) provides a mechanism for making high energy collider data generally available. We apply Quaero to searches for standard model WW, ZZ, and ttbar production, and to searches for these objects produced through a new heavy resonance. Through this interface, we make three data sets collected by the D0 experiment at sqrt(s)=1.8 TeV publicly available.Comment: 7 pages, submitted to Physical Review Letter

Direct Search for Charged Higgs Bosons in Decays of Top Quarks

We present a search for charged Higgs bosons in decays of pair-produced top quarks in pbar p collisions at sqrt(s) = 1.8 TeV using 62.2 pb^-1 of data recorded by the D0 detector at the Fermilab Tevatron collider. No evidence is found for signal, and we exclude at 95% confidence most regions of the (M higgs, tan beta) parameter space where the decay t->H b has a branching fraction greater than 0.36 and B(H -> tau nu) is large.Comment: 11 pages, 4 figures, submitted to Phys. Rev. Let