1,132 research outputs found

    Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

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    Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

    Highly Pathogenic Avian Influenza Virus Infection of Mallards with Homo- and Heterosubtypic Immunity Induced by Low Pathogenic Avian Influenza Viruses

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    The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 µl at 3 dpi: 3.0×102 vs. 2.3×104 vs. 8.7×104; p<0.05). Heterosubtypic immunity induced by an H4N6 infection mediated a similar but less pronounced effect. We conclude that the epidemiology of HPAIV H5N1 in mallards and probably other aquatic wild bird species is massively influenced by interfering immunity induced by prior homo- and heterosubtypic LPAIV infections

    Risk factors for childhood obesity: shift of the entire BMI distribution vs. shift of the upper tail only in a cross sectional study

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    Background: Previous studies reported an increase of upper body mass index (BMI) quantiles for formula fed infants compared to breastfed infants, while corresponding mean differences were low. The aim of this study was to assess the impact of known risk factors for childhood obesity on the BMI distribution. Methods: Data on 4,884 children were obtained at obligatory school entry health examinations in Bavaria (Germany). Exposure variables were formula feeding, maternal smoking in pregnancy, excessive TV-watching, low meal frequency, poor parental education, maternal overweight and high infant weight gain. Cumulative BMI distributions and Tukey mean-difference plots were used to assess possible shifts of BMI distributions by exposure. Results: Maternal overweight and high infant weight gain shifted the entire BMI-distribution with an accentuation on upper quantiles to higher BMI values. In contrast, parental education, formula feeding, high TV consumption, low meal frequency and maternal smoking in pregnancy resulted in a shift of upper quantiles only. Conclusion: The single shifts among upper parts of the BMI distribution might be due to effect modification of the corresponding exposures by another environmental exposure or genetic predisposition. Affected individuals might represent a susceptible subpopulation of the exposed

    Measurement of the top quark mass using the matrix element technique in dilepton final states

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    We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

    Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in Haemophilus

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    Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides

    Coral Colonisation of an Artificial Reef in a Turbid Nearshore Environment, Dampier Harbour, Western Australia

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    A 0.6 hectare artificial reef of local rock and recycled concrete sleepers was constructed in December 2006 at Parker Point in the industrial port of Dampier, western Australia, with the aim of providing an environmental offset for a nearshore coral community lost to land reclamation. Corals successfully colonised the artificial reef, despite the relatively harsh environmental conditions at the site (annual water temperature range 18-32°C, intermittent high turbidity, frequent cyclones, frequent nearby ship movements). Coral settlement to the artificial reef was examined by terracotta tile deployments, and later stages of coral community development were examined by in-situ visual surveys within fixed 25 x 25 cm quadrats on the rock and concrete substrates. Mean coral density on the tiles varied from 113 ± 17 SE to 909 ± 85 SE per m2 over five deployments, whereas mean coral density in the quadrats was only 6.0 ± 1.0 SE per m2 at eight months post construction, increasing to 24.0 ± 2.1 SE per m2 at 62 months post construction. Coral taxa colonising the artificial reef were a subset of those on the surrounding natural reef, but occurred in different proportions-Pseudosiderastrea tayami, Mycedium elephantotus and Leptastrea purpurea being disproportionately abundant on the artificial reef. Coral cover increased rapidly in the later stages of the study, reaching 2.3 ± 0.7 SE % at 62 months post construction. This study indicates that simple materials of opportunity can provide a suitable substrate for coral recruitment in Dampier Harbour, and that natural colonisation at the study site remains sufficient to initiate a coral community on artificial substrate despite ongoing natural and anthropogenic perturbations. © 2013 Blakeway et al

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Compressed representation of a partially defined integer function over multiple arguments

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    In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
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