Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Measurement of the running of the QED coupling in small-angle Bhabha scattering at LEP

Using the OPAL detector at LEP, the running of the effective QED coupling alpha(t) is measured for space-like momentum transfer from the angular distribution of small-angle Bhabha scattering. In an almost ideal QED framework, with very favourable experimental conditions, we obtain: Delta alpha(-6.07GeV^2) - Delta alpha(-1.81GeV^2) = (440 pm 58 pm 43 pm 30) X 10^-5, where the first error is statistical, the second is the experimental systematic and the third is the theoretical uncertainty. This agrees with current evaluations of alpha(t).The null hypothesis that alpha remains constant within the above interval of -t is excluded with a significance above 5sigma. Similarly, our results are inconsistent at the level of 3sigma with the hypothesis that only leptonic loops contribute to the running. This is currently the most significant direct measurment where the running alpha(t) is probed differentially within the measured t range.Comment: 43 pages, 12 figures, Submitted to Euro. Phys. J.

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Variability in school closure decisions in response to 2009 H1N1: a qualitative systems improvement analysis

<p>Abstract</p> <p>Background</p> <p>School closure was employed as a non-pharmaceutical intervention against pandemic 2009 H1N1, particularly during the first wave. More than 700 schools in the United States were closed. However, closure decisions reflected significant variation in rationales, decision triggers, and authority for closure. This variability presents the opportunity for improved efficiency and decision-making.</p> <p>Methods</p> <p>We identified media reports relating to school closure as a response to 2009 H1N1 by monitoring high-profile sources and searching Lexis-Nexis and Google news alerts, and reviewed reports for key themes. News stories were supplemented by observing conference calls and meetings with health department and school officials, and by discussions with decision-makers and community members.</p> <p>Results</p> <p>There was significant variation in the stated goal of closure decision, including limiting community spread of the virus, protecting particularly vulnerable students, and responding to staff shortages or student absenteeism. Because the goal of closure is relevant to its timing, nature, and duration, unclear rationales for closure can challenge its effectiveness. There was also significant variation in the decision-making authority to close schools in different jurisdictions, which, in some instances, was reflected in open disagreement between school and public health officials. Finally, decision-makers did not appear to expect the level of scientific uncertainty encountered early in the pandemic, and they often expressed significant frustration over changing CDC guidance.</p> <p>Conclusions</p> <p>The use of school closure as a public health response to epidemic disease can be improved by ensuring that officials clarify the goals of closure and tailor closure decisions to those goals. Additionally, authority to close schools should be clarified in advance, and decision-makers should expect to encounter uncertainty disease emergencies unfold and plan accordingly.</p

Culex pipiens development is greatly influenced by native bacteria and exogenous yeast

Culex pipiens is the most cosmopolitan mosquito of the Pipiens Assemblage. By studying the nature of interactions between this species and microorganisms common to its breeding environment we can unravel important pitfalls encountered during development. We tested the survival rate of larval stages, pupae and adults of a Cx. pipiens colony exposed to a variety of microorganisms in laboratory conditions and assessed the transmission to offspring (F1) by those organisms that secured development up to adulthood. Three complementary experiments were designed to: 1) explore the nutritional value of yeasts and other microorganisms during Cx. pipiens development; 2) elucidate the transstadial transmission of yeast to the host offspring; and 3) to examine the relevance of all these microorganisms in female choice for oviposition-substratum. The yeast Saccharomyces cerevisiae proved to be the most nutritional diet, but despite showing the highest survival rates, vertical transmission to F1 was never confirmed. In addition, during the oviposition trials, none of the gravid females was attracted to the yeast substratum. Notably, the two native bacterial strains, Klebsiella sp. and Aeromonas sp., were the preferred oviposition media, the same two bacteria that managed to feed neonates until molting into 2nd instar larvae. Our results not only suggest that Klebsiella sp. or Aeromonas sp. serve as attractants for oviposition habitat selection, but also nurture the most fragile instar, L1, to assure molting into a more resilient stage, L2, while yeast proves to be the most supportive diet for completing development. These experiments unearthed survival traits that might be considered in the future development of strategies of Cx. pipiens control. These studies can be extended to other members of the Pipiens Assemblag

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal