6 research outputs found

    On Black Hole Detection with the OWL/Airwatch Telescope

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    In scenarios with large extra dimensions and TeV scale gravity ultrahigh energy neutrinos produce black holes in their interactions with the nucleons. We show that ICECUBE and OWL may observe large number of black hole events and provide valuable information about the fundamental Planck scale and the number of extra dimensions. OWL is especially well suited to observe black hole events produced by neutrinos from the interactions of cosmic rays with the 3 K background radiation. Depending on the parameters of the scenario of large extra dimensions and on the flux model, as many as 28 events per year are expected for a Planck scale of 3 TeV.Comment: 8 pages, including 7 color figures, three figure captions corrected, minor changes for clarification, one reference adde

    Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides

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    Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock. One approach to inhibit an uncontrolled inflammatory reaction is the use of appropriate polycationic and amphiphilic antimicrobial peptides, here called synthetic anti-LPS peptides (SALPs). We designed various SALP structures and investigated their ability to inhibit LPS-induced cytokine secretion in vitro, their protective effect in a mouse model of sepsis, and their cytotoxicity in physiological human cells. Using a variety of biophysical techniques, we investigated selected SALPs with considerable differences in their biological responses to characterize and understand the mechanism of LPS inactivation by SALPs. Our investigations show that neutralization of LPS by peptides is associated with a fluidization of the LPS acyl chains, a strong exothermic Coulomb interaction between the two compounds, and a drastic change of the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate sizes, inhibiting the binding of LBP and other mammalian proteins to the endotoxin. At the same time, peptide binding to phospholipids of human origin (e.g., phosphatidylcholine) does not cause essential structural changes, such as changes in membrane fluidity and bilayer structure. The absence of cytotoxicity is explained by the high specificity of the interaction of the peptides with LPS

    New antiseptic peptides to protect against endotoxin-mediated shock

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    Systemic bacterial infections are associated with high mortality. The access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment. Lipid A, the "endotoxic principle" of bacterial lipopolysaccharide (LPS), is one of the major bacterial immunostimuli. Here we demonstrate the biological efficacy of rationally designed new synthetic antilipopolysaccharide peptides (SALPs) based on the Limulus anti-LPS factor for systemic application. We show efficient inhibition of LPS-induced cytokine release and protection from lethal septic shock in vivo, whereas cytotoxicity was not observed under physiologically relevant conditions and concentrations. The molecular mechanism of LPS neutralization was elucidated by biophysical techniques. The lipid A part of LPS is converted from its "endotoxic conformation," the cubic aggregate structure, into an inactive multilamellar structure, and the binding affinity of the peptide to LPS exceeds those of known LPS-binding proteins, such as LPS-binding protein (LBP). Our results thus delineate a novel therapeutic strategy for the clinical management of patients with septic shock

    Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides

    No full text
    Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock. One approach to inhibit an uncontrolled inflammatory reaction is the use of appropriate polycationic and amphiphilic antimicrobial peptides, here called synthetic anti-LPS peptides (SALPs). We designed various SALP structures and investigated their ability to inhibit LPS-induced cytokine secretion in vitro, their protective effect in a mouse model of sepsis, and their cytotoxicity in physiological human cells. Using a variety of biophysical techniques, we investigated selected SALPs with considerable differences in their biological responses to characterize and understand the mechanism of LPS inactivation by SALPs. Our investigations show that neutralization of LPS by peptides is associated with a fluidization of the LPS acyl chains, a strong exothermic Coulomb interaction between the two compounds, and a drastic change of the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate sizes, inhibiting the binding of LBP and other mammalian proteins to the endotoxin. At the same time, peptide binding to phospholipids of human origin (e.g., phosphatidylcholine) does not cause essential structural changes, such as changes in membrane fluidity and bilayer structure. The absence of cytotoxicity is explained by the high specificity of the interaction of the peptides with LPS

    Search for new resonances decaying to a WW or ZZ boson and a Higgs boson in the +bbˉ\ell^+ \ell^- b\bar b, νbbˉ\ell \nu b\bar b, and ννˉbbˉ\nu\bar{\nu} b\bar b channels with pppp collisions at s=13\sqrt s = 13 TeV with the ATLAS detector

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    See paper for full list of authors, 18 pages (plus author list + cover pages: 36 pages total), 13 figures, 1 table. Submitted to PLB. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/EXOT-2015-18/International audienceA search is presented for new resonances decaying to a WW or ZZ boson and a Higgs boson in the +bbˉ\ell^+ \ell^- b\bar b, νbbˉ\ell\nu b\bar b, and ννˉbbˉ\nu\bar{\nu} b\bar b channels in pppp collisions at s=13\sqrt s = 13 TeV with the ATLAS detector at the Large Hadron Collider using a total integrated luminosity of 3.2 fb1^{-1}. The search is conducted by looking for a localized excess in the WHWH/ZHZH invariant or transverse mass distribution. No significant excess is observed, and the results are interpreted in terms of constraints on a simplified model based on a phenomenological Lagrangian of heavy vector triplets

    Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H??????? and H???ZZ*???4??? Decay Channels at s\sqrt{s}=8??????TeV with the ATLAS Detector

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    Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3~fb1^{-1} of pppp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8\sqrt{s} = 8 TeV and recorded by the ATLAS detector. Cross sections are obtained from measured HγγH \rightarrow \gamma \gamma and HZZ4H \rightarrow ZZ ^{*}\rightarrow 4\ell event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σppH=33.0±5.3(stat)±1.6(sys)pb\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb-1 of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ*→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σpp→H=33.0±5.3 (stat)±1.6 (syst)  pb. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb1^{-1} of pppp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8\sqrt{s} = 8 TeV and recorded by the ATLAS detector. Cross sections are obtained from measured HγγH \rightarrow \gamma \gamma and HZZ4H \rightarrow ZZ ^{*}\rightarrow 4\ell event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σppH=33.0±5.3(stat)±1.6(sys)pb\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}. The measurements are compared to state-of-the-art predictions
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