Proteomics boosts translational and clinical microbiology

The application of proteomics to translational and clinical microbiology is one of the most advanced frontiers in the management and control of infectious diseases and in the understanding of complex microbial systems within human fluids and districts. This new approach aims at providing, by dedicated bioinformatic pipelines, a thorough description of pathogen proteomes and their interactions within the context of human host ecosystems, revolutionizing the vision of infectious diseases in biomedicine and approaching new viewpoints in both diagnostic and clinical management of the patient.Indeed, in the last few years, many laboratories have matured a series of advanced proteomic applications, aiming at providing individual proteome charts of pathogens, with respect to their morph and/or cell life stages, antimicrobial or antimycotic resistance profiling, epidemiological dispersion. Herein, we aim at reviewing the current state-of-the-art on proteomic protocols designed and set-up for translational and diagnostic microbiological purposes, from axenic pathogens' characterization to microbiota ecosystems' full description. The final goal is to describe applications of the most common MALDI-TOF MS platforms to advanced diagnostic issues related to emerging infections, increasing of fastidious bacteria, and generation of patient-tailored phylotypes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. © 2013 The Authors

Molecular epidemiology of meticillin-resistant Staphylococcus aureus in Italian cystic fibrosis patients: A national overview

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Power Test of the First Two HL-LHC Insertion Quadrupole Magnets Built at CERN

The High-Luminosity project (HL-LHC) of the CERN Large Hadron Collider (LHC), requires low β* quadrupole magnets in Nb$_3$Sn technology that will be installed on each side of the ATLAS and CMS experiments. After a successful shortmodel magnet manufacture and test campaign, the project has advanced with the production, assembly, and test of full-size 7.15- m-long magnets. In the last two years, two CERN-built prototypes (MQXFBP1 and MQXFBP2) have been tested and magnetically measured at the CERN SM18 test facility. These are the longest accelerator magnets based on Nb$_3$Sn technology built and tested to date. In this paper, we present the test and analysis results of these two magnets, with emphasis on quenches and training, voltage-current measurements and the quench localization with voltage taps and a new quench antenna

Organization of Patient Management and Fungal Epidemiology in Cystic Fibrosis

The achievement of a better life for cystic fibrosis (CF) patients is mainly caused by a better management and infection control over the last three decades. Herein, we want to summarize the cornerstones for an effective management of CF patients and to give an overview of the knowledge about the fungal epidemiology in this clinical context in Europe. Data from a retrospective analysis encompassing 66,616 samples from 3235 CF patients followed-up in 9 CF centers from different European countries are shown

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF

Active Compensation of field errors within +-2 ppm in Superconducting Magnets

A system for the active compensation of magnetic field errors within ±2 ppm relative to the main field in superconducting magnets is proposed. A high-performance rotating coils system is exploited in order to combine high time resolution and integral field measurements. The compensation is based on an enhanced characterization of the corrector magnets and the measured field: this allows the system to be used as off-line reference in accelerator facilities. As an experimental case study, the measurement system and the procedure for compensating field errors of dipole magnets of the Large Hadron Collider at the European Organization for Nuclear Research (CERN) are illustrated

Decay and snapback in Nb3_{3}Sn dipole magnets

Decay and snapback have been discovered in Tevatron approximately 30 years ago; since then significant advancements have been done in understanding and controlling these effects. The main sources of concern are the dynamic effects in the main dipoles and quadrupoles. For the dipole, the decay of sextupole gives a large chromaticity change during injection and ramp if it is not controlled properly. For the quadrupoles, main concern is the normal quadrupole gradient, giving a change of tune. Both effects can affect beam stability. In Nb$_{3}$Sn magnets, the experience is less wide and the set of available data is smaller. Here, we review the CERN experience concerning the recently built 11 T dipoles. These studies are relevant to establishing target values for decay and snapback in the future circular collider study, and probe the possibility of injecting below or around the penetration field, thus possibly reducing the injection energy