RIPK3-mediated cell death is involved in DUX4-mediated toxicity in facioscapulohumeral dystrophy

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro-apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non-apoptotic pathways may be also involved. METHODS: We explored DUX4-mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3-deficient transgenic mouse model. RESULTS: We showed in vitro that DUX4 expression causes a caspase-independent and RIPK3-mediated cell death in both myoblasts and myotubes. In vivo, RIPK3-deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology. CONCLUSIONS: These results provide evidence for a role of RIPK3 in DUX4-mediated cell death and open new avenues of research

Solutions of the Faddeev-Yakubovsky equations for the four nucleons scattering states

The Faddeev-Yakubowsky equations in configuration space have been solved for the four nucleon system. The results with an S-wave interaction model in the isospin approximation are presented. They concern the bound and scattering states below the first three-body threshold. The elastic phase-shifts for the N+NNN reaction in different ($S,T$) channels are given and the corresponding low energy expansions are discussed. Particular attention is payed to the n+t elastic cross section. Its resonant structure is well described in terms of a simple NN interaction. First results concerning the S-matrix for the coupled N+NNN-NN+NN channels and the strong deuteron-deuteron scattering length are obtained.Comment: latex.tar.gz, 36 pages, 10 figures, 11 tables. To be published in Physical Review

A novel application of Fiber Bragg Grating (FBG) sensors in MPGD

We present a novel application of Fiber Bragg Grating (FBG) sensors in the construction and characterisation of Micro Pattern Gaseous Detector (MPGD), with particular attention to the realisation of the largest triple (Gas electron Multiplier) GEM chambers so far operated, the GE1/1 chambers of the CMS experiment at LHC. The GE1/1 CMS project consists of 144 GEM chambers of about 0.5 m2 active area each, employing three GEM foils per chamber, to be installed in the forward region of the CMS endcap during the long shutdown of LHC in 2108-2019. The large active area of each GE1/1 chamber consists of GEM foils that are mechanically stretched in order to secure their flatness and the consequent uniform performance of the GE1/1 chamber across its whole active surface. So far FBGs have been used in high energy physics mainly as high precision positioning and re-positioning sensors and as low cost, easy to mount, low space consuming temperature sensors. FBGs are also commonly used for very precise strain measurements in material studies. In this work we present a novel use of FBGs as flatness and mechanical tensioning sensors applied to the wide GEM foils of the GE1/1 chambers. A network of FBG sensors have been used to determine the optimal mechanical tension applied and to characterise the mechanical tension that should be applied to the foils. We discuss the results of the test done on a full-sized GE1/1 final prototype, the studies done to fully characterise the GEM material, how this information was used to define a standard assembly procedure and possible future developments.Comment: 4 pages, 4 figures, presented by Luigi Benussi at MPGD 2015 (Trieste, Italy). arXiv admin note: text overlap with arXiv:1512.0848

Development and performance of Triple-GEM detectors for the upgrade of the muon system of the CMS experiment

The CMS Collaboration is evaluating GEM detectors for the upgrade of the muon system. This contribution will focus on the R&D performed on chambers design features and will discuss the performance of the upgraded detector

Design of a constant fraction discriminator for the VFAT3 front-end ASIC of the CMS GEM detector

In this work the design of a constant fraction discriminator (CFD) to be used in the VFAT3 chip for the read-out of the triple-GEM detectors of the CMS experiment, is described. A prototype chip containing 8 CFDs was implemented using 130 nm CMOS technology and test results are shown. © CERN 2016

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO