Comparing different approaches for generating random numbers device-independently using a photon pair source

What is the most efficient way to generate random numbers device-independently using a photon pair source based on spontaneous parametric down conversion (SPDC)? We consider this question by comparing two implementations of a detection-loophole-free Bell test. In particular, we study in detail a scenario where a heralded single photon source (HSPS) is used to herald path-entangled states, i.e. entanglement between two spatial modes sharing a single photon and where non-locality is revealed using photon counting preceded by small displacement operations. We start by giving a theoretical description of such a measurement. We then show how to optimize the Bell-CHSH violation through a non-perturbative calculation, taking the main experimental imperfections into account. We finally bound the amount of randomness that can be extracted and compare it to the one obtained with the conventional scenario using photon pairs entangled e.g. in polarization and analyzed through photon counting. While the former requires higher overall detection efficiencies, it is far more efficient in terms of both the entropy per experimental run and the rate of random bit generation.Comment: 12 pages, 5 figure

Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Although genetic predisposition and epigenetic factors contribute to the development of NAFLD, our understanding of the molecular mechanism involved in the pathogenesis of the disease is still emerging. Here we investigated a possible role of a microRNAs-STAT3 pathway in the induction of hepatic steatosis. Differentiated HepaRG cells treated with the fatty acid sodium oleate (fatty dHepaRG) recapitulated features of liver vesicular steatosis and activated a cell-autonomous inflammatory response, inducing STAT3-Tyrosine-phosphorylation. With a genome-wide approach (Chromatin Immunoprecipitation Sequencing), many phospho-STAT3 binding sites were identified in fatty dHepaRG cells and several STAT3 and/or NAFLD-regulated microRNAs showed increased expression levels, including miR-21. Innovative CARS (Coherent Anti-Stokes Raman Scattering) microscopy revealed that chemical inhibition of STAT3 activity decreased lipid accumulation and deregulated STAT3-responsive microRNAs, including miR-21, in lipid overloaded dHepaRG cells. We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis. Our results identified a microRNAs-phosphoSTAT3 pathway involved in the development of hepatic steatosis, which may represent a molecular marker for both diagnosis and therapeutic targeting

Factors associated with SARS-CoV-2 infection risk among healthcare workers of an italian university hospital

We report the results of a study on the cumulative incidence of SARS-CoV-2 infections in about 6000 workers of the University Hospital of Modena, Northern Italy, in the period March 2020–January 2021, and the relations with some individual and occupational factors. Overall, in healthcare workers (HCW) the cumulative incidence of COVID-19 during the period was 13.8%. Results confirm the role of overweight and obesity as significant risk factors for SARS-CoV-2 infection. Chronic respiratory diseases, including asthma, also proved to be significantly associated with the infection rate. Considering occupational factors, the COVID-19 risk was about threefold (OR: 2.7; 95% CI 1.7–4.5) greater in nurses and nurse aides than in non-HCW, and about double (OR: 1.9; 95% CI 1.2–3.2) in physicians. Interestingly, an association was also observed between infection risk and nightshifts at work (OR: 1.8; 95% CI 1.4–2.3), significantly related to the total number of shifts in the whole eleven-month period. Even if the vaccination campaign has now greatly modified the scenario of SARS-CoV-2 infections among HCW, the results of this study can be useful for further development of health and policy strategies to mitigate the occupational risk related to the new variants of coronavirus, and therefore the evolution of the pandemic

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Background The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. Objectives In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. Methods Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. Results Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. Conclusions These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications

The CLIC Positron Sources Based on Compton Schemes

International audienceThe CLIC polarized positron source is based on a positron production scheme in which polarized photons are produced by Compton process. Compton backscattering happens in a so-called "Compton ring" where an electron beam of 1.06 GeV interacts with a powerful laser beam amplified in an optical resonator. The circularly-polarized gamma rays are sent on to a target, producing pairs of longitudinally polarized electrons and positrons. An Adiabatic Matching Device maximizes the capture of the positrons. A normal-conducting 2 GHz Linac accelerates the beam up to 2.424 GeV before injection into the Pre-Damping Ring (PDR). The nominal CLIC bunch population is 4.4x10**9 particles per bunch. Since the photon flux coming out from a "Compton ring" is not sufficient to obtain the requested charge, a stacking process is required in the PDR. Another option is to use a "Compton Energy Recovery Linac" where a quasi-continual stacking in the PDR could be achieved. A third option is to use a "Compton Linac" which would not require stacking. We describe the overall scheme as well as advantages and constraints of the three different options

The CLIC positron source based on compton schemes

The CLIC polarized positron source is based on a positron production scheme in which polarized photons are produced by a Compton process. In one option, Compton backscattering takes place in a so-called “Compton ring”, where an electron beam of 1 GeV interacts with circularly-polarized photons in an optical resonator. The resulting circularly-polarized gamma photons are sent on to an amorphous target, producing pairs of longitudinally polarized electrons and positrons. The nominal CLIC bunch population is 4.2x109 particles per bunch at the exit of the Pre-Damping Ring (PDR). Since the photon flux coming out from a "Compton ring" is not sufficient to obtain the requested charge, a stacking process is required in the PDR. Another option is to use a Compton Energy Recovery Linac (ERL) where a quasicontinual stacking in the PDR could be achieved. A third option is to use a "Compton Linac" which would not require stacking. We describe the overall scheme as well as advantages and constraints of the three options

A Large Hadron Electron Collider at CERN

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBACKGROUND: The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. OBJECTIVES: In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. METHODS: Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. RESULTS: Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. CONCLUSIONS: These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications.UK Ministry of DefenceNorth Atlantic Treaty Organization (NATO)Deutsche Forschungsgemeinschaft (DFG)Federal Ministry of Education and ResearchDMTC Limited (Australia