No association of a set of candidate genes on haloperidol side effects

We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 ( 3c one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p\u200a=\u200a0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effect

N4-Substituted Piperazinyl Norfloxacin Derivatives with Broad-Spectrum Activity and Multiple Mechanisms on Gyrase, Topoisomerase IV, and Bacterial Cell Wall Synthesis

Fluoroquinolones are an important class of antibiotics with broad-spectrum antibacterial and antitubercular activity. Here, we describe the design and synthesis of a series of 38 N4-substituted piperazinyl norfloxacin derivatives. Their activity and mechanism of action were characterized using in silico, in vitro, and in vivo approaches. Several compounds displayed interesting activities against both Gram-negative and Gram-positive bacteria, and few displayed antimycobacterial activity, whereby some were as potent as norfloxacin and ciprofloxacin. Molecular docking experiments suggested that the new derivatives inhibit both DNA gyrase and DNA topoisomerase IV in a similar manner as norfloxacin. Selecting the most promising candidates for experimental mode of action analysis, we confirmed DNA gyrase and topoisomerase IV as targets of all tested compounds using enzymatic in vitro assays. Phenotypic analysis of both Escherichia coli and Bacillus subtilis confirmed a typical gyrase inhibition phenotype for all of the tested compounds. Assessment of possible additional targets revealed three compounds with unique effects on the B. subtilis cell wall synthesis machinery, suggesting that they may have an additional target in this pathway. Comparison with known cell wall synthesis inhibitors showed that the new compounds elicit a distinct and, so far, unique phenotype, suggesting that they act differently from known cell wall synthesis inhibitors. Interestingly, our phenotypic analysis revealed that both norfloxacin and ciprofloxacin displayed additional cellular effects as well, which may be indicative of the so far unknown additional mechanisms of fluoroquinolones

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Correlated long-range mixed-harmonic fluctuations measured in pp, p+Pb and low-multiplicity Pb+Pb collisions with the ATLAS detector

For abstract see published article

Combined measurements of Higgs boson couplings in proton- proton collisions at v s=13TeV

Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton-proton collision data set recorded with the CMS detector in 2016 at fb-1. The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a W or Z boson, or a top quark-antiquark pair) and the following decay modes: H, ZZ, WW, , bb, and . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be =1.17 +/- 0.10, assuming a Higgs boson mass of 125.09. Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.Peer reviewe

Performance of top-quark and W -boson tagging with ATLAS in Run 2 of the LHC

The performance of identification algorithms (“taggers”) for hadronically decaying top quarks and W bosons in pp collisions at √s=13 TeV recorded by the ATLAS experiment at the Large Hadron Collider is presented. A set of techniques based on jet shape observables are studied to determine a set of optimal cut-based taggers for use in physics analyses. The studies are extended to assess the utility of combinations of substructure observables as a multivariate tagger using boosted decision trees or deep neural networks in comparison with taggers based on two-variable combinations. In addition, for highly boosted top-quark tagging, a deep neural network based on jet constituent inputs as well as a re-optimisation of the shower deconstruction technique is presented. The performance of these taggers is studied in data collected during 2015 and 2016 corresponding to 36.1 fb −1 for the tt ¯ and γ+jet and 36.7 fb −1 −1 for the dijet event topologies

Measurements of the charge asymmetry in top-quark pair production in the dilepton final state at s √ =8 TeV with the ATLAS detector

Measurements of the top-antitop quark pair production charge asymmetry in the dilepton channel, characterized by two high-pT leptons (electrons or muons), are presented using data corresponding to an integrated luminosity of 20.3  fb−1 from pp collisions at a center-of-mass energy s√=8  TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. Inclusive and differential measurements as a function of the invariant mass, transverse momentum, and longitudinal boost of the tt¯ system are performed both in the full phase space and in a fiducial phase space closely matching the detector acceptance. Two observables are studied: AℓℓC based on the selected leptons and Att¯C based on the reconstructed tt¯ final state. The inclusive asymmetries are measured in the full phase space to be AℓℓC=0.008±0.006 and Att¯C=0.021±0.016, which are in agreement with the Standard Model predictions of AℓℓC=0.0064±0.0003 and Att¯C=0.0111±0.0004

In situ calibration of large-radius jet energy and mass in 13 TeV proton–proton collisions with the ATLAS detector

The response of the ATLAS detector to largeradius jets is measured in situ using 36.2 fb−1 of √s = 13 TeV proton–proton collisions provided by the LHC and recorded by the ATLAS experiment during 2015 and 2016. The jet energy scale is measured in events where the jet recoils against a reference object, which can be either a calibrated photon, a reconstructed Z boson, or a system of well-measured small-radius jets. The jet energy resolution and a calibration of forward jets are derived using dijet balance measurements. The jet mass response is measured with two methods: using mass peaks formed by W bosons and top quarks with large transverse momenta and by comparing the jet mass measured using the energy deposited in the calorimeter with that using the momenta of charged-particle tracks. The transversemomentum and mass responses in simulations are found to be about 2–3% higher than in data. This difference is adjusted for with a correction factor. The results of the different methods are combined to yield a calibration over a large range of transverse momenta (pT). The precision of the relative jet energy scale is 1–2% for 200 GeV < pT < 2 TeV, while that of the mass scale is 2–10%. The ratio of the energy resolutions in data and simulation is measured to a precision of 10–15% over the same pT range

Evidence for electroweak production of W±W±jj in pp collisions at s√=8 TeV with the ATLAS detector

This Letter presents the first study of W±W±jj, same-electric-charge diboson production in association with two jets, using 20.3  fb−1 of proton-proton collision data at s√=8  TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with two reconstructed same-charge leptons (e±e±, e±μ±, and μ±μ±) and two or more jets are analyzed. Production cross sections are measured in two fiducial regions, with different sensitivities to the electroweak and strong production mechanisms. First evidence for W±W±jj production and electroweak-only W±W±jj production is observed with a significance of 4.5 and 3.6 standard deviations, respectively. The measured production cross sections are in agreement with standard model predictions. Limits at 95% confidence level are set on anomalous quartic gauge couplings

Search for three-jet resonances in pp collisions at √s=7 TeV

This is a Pre-Print version of the Article - Copyright @ 2011 APSA model-independent search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 inverse picobarns. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed. The number of expected standard model background events is found to be in good agreement with the observed events. Limits are set on a model describing the production of R-parity-violating supersymmetric gluino pairs, and gluino masses in the range of 200 to 280 GeV/c^2 are excluded at a 95% confidence level for the first time.This work is supported by the FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF andWCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)