High throughput screening for identification of mycolactone targets : Relations between M. ulcerans and nervous system

Buruli ulcer is an infectious disease transmitted by arthropod vectors harboring Mycobacterium ulcerans, a mycobacterium which belong to the same family of bacteria causing tuberculosis and leprosy. The infection causes painless swelling and severe skin lesions. One key feature of M. ulcerans bacterium is its ability to secrete a necrotic toxin, the mycolactone within small lipophilic vesicles, which are critical for the bacterial induced cytotoxicity. The biological knowledge as well as the preventive and therapeutic means for this invalidating disease is still very limited.   Our first approach was to investigate whether the mycolactone toxin could be involved in the neutralization of pain by acting directly on the peripheral nervous system without causing destruction of nervous fibers. By use of live time fluorescence microscopy and appropriate markers, we showed that the addition of toxin at sub-toxic dose provokes modification of ionic currents of neuron cells. Based on this ability of the toxin, a molecular high throughput methodology was developed for the screening of a genome wide siRNA library and small molecules inhibitors to enable the search of the cellular targets for the toxin. The cell-based assay relies on automated confocal microscopy on macrophages coupled with dedicated image analysis. These two screening allowed us to identify a putative toxin target, and a toxin inhibitor. A binding assay confirmed that the putative target is a receptor of the toxin. Together these results allowed us to build a potential signaling pathway activated by the mycolactone and implicated in ionic channel activities.   The second approach was to confirm this model in the mouse model of M. ulcerans infection and its role in the hypoesthesia of the lesions. Toxin inhibitor, daily administered to mice, which were experimentally infected by M. ulcerans, conducted to the absence of the hypoesthesia of the lesions. Furthermore, a histological study of neuronal fibers did not show a destruction of neuronal cells. Moreover, in vitro studies have showed that M. ulcerans are able to colonize neuronal cells. Then, these results suggested that the hypoesthesia of the M. ulcerans lesions could be caused by a non-destructive process of nervous cells.

Measurement of the mass difference between top quark and antiquark in pp collisions at root s=8 TeV

Peer reviewe

Measurements of the ϒ(1S), ϒ(2S), and ϒ(3S) differential cross sections in pp collisions at s=7TeV

Differential cross sections as a function of transverse momentum pTpT are presented for the production of ϒ(nS)ϒ(nS) (n = 1, 2, 3) states decaying into a pair of muons. Data corresponding to an integrated luminosity of 4.9View the MathML sourcefb−1 in pp collisions at View the MathML sources=7TeV were collected with the CMS detector at the LHC. The analysis selects events with dimuon rapidity |y|<1.2|y|<1.2 and dimuon transverse momentum in the range View the MathML source10<pT<100GeV. The measurements show a transition from an exponential to a power-law behavior at View the MathML sourcepT≈20GeV for the three ϒ states. Above that transition, the ϒ(3S)ϒ(3S) spectrum is significantly harder than that of the ϒ(1S)ϒ(1S). The ratios of the ϒ(3S)ϒ(3S) and ϒ(2S)ϒ(2S) differential cross sections to the ϒ(1S)ϒ(1S) cross section show a rise as pTpT increases at low pTpT, then become flatter at higher pTpT

Search for W ' -> tb in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for a Higgs boson decaying into γ*γ→ℓℓγ with low dilepton mass in pp collisions at √s=8 TeV

A search is described for a Higgs boson decaying into two photons, one of which has an internal conversion to a muon or an electron pair ( ℓℓγ ). The analysis is performed using proton–proton collision data recorded with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb −1 . The events selected have an opposite-sign muon or electron pair and a high transverse momentum photon. No excess above background has been found in the three-body invariant mass range 12

Search for stealth supersymmetry in events with jets, either photons or leptons, and low missing transverse momentum in pp collisions at 8 TeV

The results of a search for new physics in final states with jets, either photons or leptons, and low missing transverse momentum are reported. The study is based on a sample of proton-proton collisions collected at a center-of-mass energy s=8 TeV with the CMS detector in 2012. The integrated luminosity of the sample is 19.7 fb-1. Many models of new physics predict the production of events with jets, electroweak gauge bosons, and little or no missing transverse momentum. Examples include stealth models of supersymmetry (SUSY), which predict a hidden sector at the electroweak energy scale in which SUSY is approximately conserved. The data are used to search for stealth SUSY signatures in final states with either two photons or an oppositely charged electron and muon. No excess is observed with respect to the standard model expectation, and the results are used to set limits on squark pair production in the stealth SUSY framework

Measurement of the t-channel single-top-quark production cross section and of the |Vtb| CKM matrix element in pp collisions at SQR = 8 TeV

Measurements are presented of the t -channel single-top-quark production cross section in proton-proton collisions at s&#8730; = 8 TeV. The results are based on a data sample corresponding to an integrated luminosity of 19.7 fb &#8722;1 recorded with the CMS detector at the LHC. The cross section is measured inclusively, as well as separately for top (t) and antitop (t¯) , in final states with a muon or an electron. The measured inclusive t -channel cross section is &#963; t -ch. = 83 . 6 ± 2 . 3 (stat.) ± 7 . 4 (syst.) pb. The single t and t¯ cross sections are measured to be &#963; t -ch. ( t ) = 53 . 8 ± 1 . 5 (stat.) ± 4 . 4 (syst.) pb and &#963; t -ch. (t¯) = 27 . 6 ± 1 . 3 (stat.) ± 3 . 7 (syst.) pb, respectively. The measured ratio of cross sections is R t -ch. = &#963; t -ch. (t) /&#963; t -ch. (t¯) = 1 . 95 ± 0 . 10 (stat.) ± 0 . 19 (syst.), in agreement with the standard model prediction. The modulus of the Cabibbo-Kobayashi-Maskawa matrix element V tb is extracted and, in combination with a previous CMS result at s&#8730; = 7 TeV, a value | V tb | = 0 . 998 ± 0 . 038 (exp.) ± 0 . 016 (theo.) is obtained

Search for top squark pair production in compressed-mass-spectrum scenarios in proton-proton collisions at √s=8 TeV using the αT_{T} variable

An inclusive search is performed for supersymmetry in final states containing jets and an apparent imbalance in transverse momentum, (p) over right arrow (miss)(T),due to the production of unobserved weakly interacting particles in pp collisions at a centre-of-mass energy of 8 TeV. The data, recorded with the CMS detector at the CERN LHC, correspond to an integrated luminosity of 18.5fb(-1). The dimensionless kinematic variable alpha(T) is used to discriminate between events with genuine (p) over right arrow (miss)(T)associated with unobserved particles and spurious values of (p) over right arrow (miss)(T) Tarising from jet energy mismeasurements. No excess of event yields above the expected standard model backgrounds is observed. The results are interpreted in terms of constraints on the parameter space of several simplified models of supersymmetry that assume the pair production of top squarks. The search provides sensitivity to a broad range of top squark ((t) over tilde) decay modes, including the two-body decay (t)over tilde> -> c (chi) over tilde (0)(1),where c is a charm quark (chi) over tilde (0)(1) and is the lightest neutralino, as well as the four-body decay (t)over tilde> -> bf (f) over bar' (chi) over bar (0)(1),where b is a bottom quark and f and (f) over bar' are fermions produced in the decay of an intermediate off-shell W boson. These modes dominate in scenarios in which the top squark and lightest neutralino are nearly degenerate in mass. For these modes, top squarks with masses as large as 260 and 225 GeV are excluded, respectively, for the two-and four-body decays. (C) 2017 The Author. Published by Elsevier B.V