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The identification and characterization of genetic factors influencing natural susceptibility to infectious diseases in humans and in model organisms, such as the laboratory mouse, can provide new insight into the basic mechanisms of host defense against infections. In the mouse, resistance or susceptibility to infection with intracellular pathogens such as Salmonella, Mycobacterium and Leishmnania is controlled by the Natural resistance associated macrophage protein (Nramp1) gene on chromosome 1, which influences the rate of intracellular replication of these parasites in macrophages. Nramp1 codes for an integral membrane protein, which is expressed exclusively in macrophage/monocytes and polymorphonuclear leukocytes. The protein is localized to the endosomal/lysosomal compartment of the macrophage and is rapidly recruited to the membrane of the particle-containing phagosome upon phagocytosis. Nramp defines a novel family of functionally related membrane proteins including Nramp2, which was recently shown to be the major transferrin-independent uptake system of the intestine in mammals. This observation supports the hypothesis that the phagocyte-specific Nramp1 protein may regulate the intraphagosomal replication of antigenically unrelated bacteria by controlling divalent cation concentrations at that site. Recent genetic studies have found that allelic variants at the human NRAMP1 locus are associated with susceptibility to leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis) and possibly with the onset of rheumatoid arthritis.

A bstract We present a parton-level study of electro-weak production of vector-boson pairs at the Large Hadron Collider, establishing the sensitivity to a set of dimension-six operators in the Standard Model Effective Field Theory (SMEFT). Different final states are statistically combined, and we discuss how the orthogonality and interdependence of different analyses must be considered to obtain the most stringent constraints. The main novelties of our study are the inclusion of SMEFT effects in non-resonant diagrams and in irreducible QCD backgrounds, and an exhaustive template analysis of optimal observables for each operator and process considered. We also assess for the first time the sensitivity of vector-boson-scattering searches in semileptonic final states.

A bstract We present the first parton-level study of anomalous effects in triboson production in both fully and semi-leptonic channels in proton-proton collisions at 13 TeV at the Large Hadron Collider (LHC). The sensitivity to anomalies induced by a minimal set of bosonic dimension-6 operators from the Warsaw basis is evaluated with specific analyses for each final state. A likelihood-based strategy is employed to assess the most sensitive kinematic observables per channel, where the contribution of Effective Field Theory operators is parameterized at either the linear or quadratic level. The impact of the mutual interference terms of pairs of operators on the sensitivity is also examined. This benchmark study explores the complementarity and overlap in sensitivity between different triboson measurements and paves the way for future analyses at the LHC experiments. The statistical combination of the considered final states allows setting stringent bounds on five bosonic Wilson coefficients.

A MW 6.3 earthquake struck on April 6, 2009 the Abruzzi region (central Italy) producing vast damage in the L'Aquila town and surroundings. In this paper we present the location and geometry of the fault system as obtained by the analysis of main shock and aftershocks recorded by permanent and temporary networks. The distribution of aftershocks, 712 selected events with ML ≥ 2.3 and 20 with ML ≥ 4.0, defines a complex, 40 km long, NW trending extensional structure. The main shock fault segment extends for 15–18 km and dips at 45° to the SW, between 10 and 2 km depth. The extent of aftershocks coincides with the surface trace of the Paganica fault, a poorly known normal fault that, after the event, has been quoted to accommodate the extension of the area. We observe a migration of seismicity to the north on an echelon fault that can rupture in future large earthquakes.

Galaxy clusters are the most massive gravitationally bound structures in the Universe.They grow by accreting smaller structures in a merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wavelengths that illuminates the magnetic ridge.

Background CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). Methods This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study. Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months. Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler). Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32. Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32. Results Of 61 randomised patients, 54 (88.5%) completed the study. There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes. CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo. In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα). In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo. CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide). Conclusion The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy. Trial registration The study is registered on ClinicalTrials.gov ( NCT03004417 ).