Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature

Calibration and performance tests of the Very-Front-End electronics for the CMS electromagnetic calorimeter

The Very-Front-End electronics processing signals from photodetectors of the CMS electromagnetic calorimeter have been put through an extensive test programme to guarantee functionality and reliability. The final characteristics of the VFE boards designed for the calorimeter barrel and endcaps are presented. The results, which have been also verified during test beam at CERN, confirm the high quality of the boards production and show that the CMS detector specifications are reached

Performance of Glass Resistive Plate Chambers for a high granularity semi-digital calorimeter

A new design of highly granular hadronic calorimeter using Glass Resistive Plate Chambers (GRPCs) with embedded electronics has been proposed for the future International Linear Collider (ILC) experiments. It features a 2-bit threshold semi-digital read-out. Several GRPC prototypes with their electronics have been successfully built and tested in pion beams. The design of these detectors is presented along with the test results on efficiency, pad multiplicity, stability and reproducibility.Comment: 16 pages, 15 figure

Air shower simulation for background estimation in muon tomography of volcanoes

International audienceOne of the main sources of background for the radiography of volcanoes using atmospheric muons comes from the accidental coincidences produced in the muon telescopes by charged particles belonging to the air shower generated by the primary cosmic ray. In order to quantify this background effect, Monte Carlo simulations of the showers and of the detector are developed by the TOMUVOL collaboration. As a first step, the atmospheric showers were simulated and investigated using two Monte Carlo packages, CORSIKA and GEANT4.We compared the results provided by the two programs for the muonic component of vertical proton-induced showers at three energies: 1, 10 and 100 TeV. We found that the spatial distribution and energy spectrum of the muons were in good agreement for the two codes

Inner structure of the Puy de Dˆome volcano: cross-comparison of geophysical models (ERT, gravimetry, muon imaging)

International audienceMuon imaging of volcanoes and of geological structures in general is actively being developed by several groups in the world. It has the potential to provide 3-D density distributions with an accuracy of a few percent. At this stage of development, comparisons with established geophysical methods are useful to validate the method. An experiment has been carried out in 2011 and 2012 on a large trachytic dome, the Puy de Dˆome volcano, to perform such a comparison of muon imaging with gravimetric tomography and 2-D electrical resistivity tomography. Here, we present the preliminary results for the last two methods. North-south and east-west resistivity profiles allow us to model the resistivity distribution down to the base of the dome. The modelling of the Bouguer anomaly provides models for the density distribution within the dome that are directly comparable with the results from the muon imaging. Our ultimate goal is to derive a model of the dome using the joint interpretation of all sets of data

High rate, fast timing Glass RPC for the high {\eta} CMS muon detectors

The HL-LHC phase is designed to increase by an order of magnitude the amount of data to be collected by the LHC experiments. To achieve this goal in a reasonable time scale the instantaneous luminosity would also increase by an order of magnitude up to $6.10^{34} cm^{-2} s^{-1}$ . The region of the forward muon spectrometer ($|{\eta}| > 1.6$) is not equipped with RPC stations. The increase of the expected particles rate up to $2 kHz/cm^{2}$ (including a safety factor 3) motivates the installation of RPC chambers to guarantee redundancy with the CSC chambers already present. The actual RPC technology of CMS cannot sustain the expected background level. The new technology that will be chosen should have a high rate capability and provides a good spatial and timing resolution. A new generation of Glass-RPC (GRPC) using low-resistivity (LR) glass is proposed to equip at least the two most far away of the four high ${\eta}$ muon stations of CMS. First the design of small size prototypes and studies of their performance in high-rate particles flux is presented. Then the proposed designs for large size chambers and their fast-timing electronic readout are examined and preliminary results are provided.Comment: 14 pages, 11 figures, Conference proceeding for the 2016 Resistive Plate Chambers and Related Detector

Construction and commissioning of a technological prototype of a high-granularity semi-digital hadronic calorimeter

A large prototype of 1.3m3 was designed and built as a demonstrator of the semi-digital hadronic calorimeter (SDHCAL) concept proposed for the future ILC experiments. The prototype is a sampling hadronic calorimeter of 48 units. Each unit is built of an active layer made of 1m2 Glass Resistive Plate Chamber(GRPC) detector placed inside a cassette whose walls are made of stainless steel. The cassette contains also the electronics used to read out the GRPC detector. The lateral granularity of the active layer is provided by the electronics pick-up pads of 1cm2 each. The cassettes are inserted into a self-supporting mechanical structure built also of stainless steel plates which, with the cassettes walls, play the role of the absorber. The prototype was designed to be very compact and important efforts were made to minimize the number of services cables to optimize the efficiency of the Particle Flow Algorithm techniques to be used in the future ILC experiments. The different components of the SDHCAL prototype were studied individually and strict criteria were applied for the final selection of these components. Basic calibration procedures were performed after the prototype assembling. The prototype is the first of a series of new-generation detectors equipped with a power-pulsing mode intended to reduce the power consumption of this highly granular detector. A dedicated acquisition system was developed to deal with the output of more than 440000 electronics channels in both trigger and triggerless modes. After its completion in 2011, the prototype was commissioned using cosmic rays and particles beams at CERN.Comment: 49 pages, 41 figure

The Time Structure of Hadronic Showers in highly granular Calorimeters with Tungsten and Steel Absorbers

The intrinsic time structure of hadronic showers influences the timing capability and the required integration time of hadronic calorimeters in particle physics experiments, and depends on the active medium and on the absorber of the calorimeter. With the CALICE T3B experiment, a setup of 15 small plastic scintillator tiles read out with Silicon Photomultipliers, the time structure of showers is measured on a statistical basis with high spatial and temporal resolution in sampling calorimeters with tungsten and steel absorbers. The results are compared to GEANT4 (version 9.4 patch 03) simulations with different hadronic physics models. These comparisons demonstrate the importance of using high precision treatment of low-energy neutrons for tungsten absorbers, while an overall good agreement between data and simulations for all considered models is observed for steel.Comment: 24 pages including author list, 9 figures, published in JINS

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated