1,081 research outputs found

    Orally active antischistosomal early leads identified from the open access malaria box.

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    BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

    Search for supersymmetry in proton-proton collisions at 13 TeV using identified top quarks

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    A search for supersymmetry is presented based on proton-proton collision events containing identified hadronically decaying top quarks, no leptons, and an imbalance p(T)(miss) in transverse momentum. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). Search regions are defined in terms of the multiplicity of bottom quark jet and top quark candidates, the p(T)(miss) , the scalar sum of jet transverse momenta, and themT2 mass variable. No statistically significant excess of events is observed relative to the expectation from the standard model. Lower limits on the masses of supersymmetric particles are determined at 95% confidence level in the context of simplified models with top quark production. For a model with direct top squark pair production followed by the decay of each top squark to a top quark and a neutralino, top squark masses up to 1020 GeVand neutralino masses up to 430 GeVare excluded. For amodel with pair production of gluinos followed by the decay of each gluino to a top quark-antiquark pair and a neutralino, gluino masses up to 2040 GeVand neutralino masses up to 1150 GeVare excluded. These limits extend previous results.Peer reviewe

    Search for resonances in the mass spectrum of muon pairs produced in association with b quark jets in proton-proton collisions at root 8 and 13 TeV

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    A search for resonances in the mass range 12-70 GeV produced in association with a b quark jet and a second jet, and decaying to a muon pair, is reported. The analysis is based on data from proton-proton collisions at center-of-mass energies of 8 and 13 TeV, collected with the CMS detector at the LHC and corresponding to integrated luminosities of 19.7 and 35.9 fb(-1), respectively. The search is carried out in two mutually exclusive event categories. Events in the first category are required to have a b quark jet in the central region (|| 2.4) and at least one jet in the forward region (|| > 2.4). Events in the second category are required to have two jets in the central region, at least one of which is identified as a b quark jet, no jets in the forward region, and low missing transverse momentum. An excess of events above the background near a dimuon mass of 28 GeV is observed in the 8 TeV data, corresponding to local significances of 4.2 and 2.9 standard deviations for the first and second event categories, respectively. A similar analysis conducted with the 13 TeV data results in a mild excess over the background in the first event category corresponding to a local significance of 2.0 standard deviations, while the second category results in a 1.4 standard deviation deficit. The fiducial cross section measurements and 95% confidence level upper limits on those for a resonance consistent with the 8 TeV excess are provided at both collision energies

    Search for top squark pair production in pp collisions at root s=13 TeV using single lepton events

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    Measurement of vector boson scattering and constraints on anomalous quartic couplings from events with four leptons and two jets in proton-proton collisions at root s=13 TeV

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    Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at root s=13 TeV

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    Pseudorapidity distributions of charged hadrons in proton-lead collisions at root s(NN)=5:02 and 8.16 TeV

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    The pseudorapidity distributions of charged hadrons in proton-lead collisions at nucleon-nucleon center-of-mass energies root s(NN) = 5.02 and 8.16 TeV are presented. The measurements are based on data samples collected by the CMS experiment at the LHC. The number of primary charged hadrons produced in non-single-diffractive proton-lead collisions is determined in the pseudorapidity range vertical bar eta(lab)vertical bar vertical bar(vertical bar eta cm vertical bar) <0.5 are 17.1 +/- 0.01 (stat) +/- 0.59 (syst) and 20.10 +/- 0.01 (stat) +/- 0.5(syst) at root s(NN) = 5.02 and 8.16 TeV, respectively. The particle densities per participant nucleon are compared to similar measurements in proton-proton, proton-nucleus, and nucleus-nucleus collisions.Peer reviewe

    Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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    Search for a light pseudoscalar Higgs boson produced in association with bottom quarks in pp collisions at root s=8 TeV

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