Synthesis of diacylated γ-glutamyl-cysteamine prodrugs, and in vitro evaluation of their cytotoxicity and intracellular delivery of cysteamine

To overcome the major disadvantages of cysteamine, the only registered treatment for the rare genetic disease cystinosis, nine prodrugs of γ-glutamyl-cysteamine (4) were synthesized for evaluation. Esterification of the thiol conferred oxidative stability, while sufficient lipophilicity for oral bioavailability was achieved by acylation of the α-carboxyl group of γ-glutamyl-cysteamine (4). Low cytotoxicity was observed in cultured HaCaT keratinocytes using the MTT assay, with EC50 values higher than or similar to that of cysteamine. Successful uptake of the esterified prodrugs and the subsequent release of cysteamine into cultured human proximal tubule epithelial cells were demonstrated using CMQT derivatisation and HPLC with UV detection. These prodrugs show potential as novel delivery vehicles of cysteamine to improve the treatment of the genetic disorder nephropathic cystinosis

Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceMeasurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb$^{−1}$. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant $\textrm{t}\overline{\textrm{t}}$ background. A cross section of $79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right)$ pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext

Search for nonresonant Higgs boson pair production in final state with two bottom quarks and two tau leptons in proton-proton collisions at <math altimg="si1.svg"><msqrt><mrow><mi>s</mi></mrow></msqrt><mo linebreak="goodbreak" linebreakstyle="after">=</mo><mn>13</mn><mtext> TeV</mtext></math>

International audienceA search for the nonresonant production of Higgs boson pairs (HH ) via gluon-gluon and vector boson fusion processes in final states with two bottom quarks and two tau leptons is presented. The search uses data from proton-proton collisions at a center-of-mass energy of s=13TeV recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 138fb−1. Events in which at least one tau lepton decays hadronically are considered and multiple machine learning techniques are used to identify and extract the signal. The data are found to be consistent, within uncertainties, with the standard model (SM) predictions. Upper limits on the HH production cross section are set to constrain the parameter space for anomalous Higgs boson couplings. The observed (expected) upper limit at 95% confidence level corresponds to 3.3 (5.2) times the SM prediction for the inclusive HH cross section and to 124 (154) times the SM prediction for the vector boson fusion HH cross section. At 95% confidence level, the Higgs field self-coupling is constrained to be within −1.7 and 8.7 times the SM expectation, and the coupling of two Higgs bosons to two vector bosons is constrained to be within −0.4 and 2.6 times the SM expectation

Measurement of the <math altimg="si1.svg"><mi mathvariant="normal">t</mi><mover accent="true"><mrow><mi mathvariant="normal">t</mi></mrow><mrow><mo stretchy="false">¯</mo></mrow></mover></math> charge asymmetry in events with highly Lorentz-boosted top quarks in pp collisions at <math altimg="si2.svg"><msqrt><mrow><mi>s</mi></mrow></msqrt><mo linebreak="goodbreak" linebreakstyle="after">=</mo><mn>13</mn></math> TeV

International audienceThe measurement of the charge asymmetry in top quark pair events with highly Lorentz-boosted top quarks decaying to a single lepton and jets is presented. The analysis is performed using proton-proton collisions at s=13TeV with the CMS detector at the LHC and corresponding to an integrated luminosity of 138 fb−1. The selection is optimized for top quarks produced with large Lorentz boosts, resulting in nonisolated leptons and overlapping jets. The top quark charge asymmetry is measured for events with a tt¯ invariant mass larger than 750 GeV and corrected for detector and acceptance effects using a binned maximum likelihood fit. The measured top quark charge asymmetry of (0.42−0.69+0.64)% is in good agreement with the standard model prediction at next-to-next-to-leading order in quantum chromodynamic perturbation theory with next-to-leading-order electroweak corrections. The result is also presented for two invariant mass ranges, 750–900 and &gt;900GeV

Search for pair production of vector-like quarks in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A search is presented for vector-like $\mathrm{T}$ and $\mathrm{B}$ quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for $\mathrm{T}$ quark masses up to 1.54 TeV and $\mathrm{B}$ quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T} \overline{\mathrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B} \overline{\mathrm{B}}$ production with $\mathrm{B}$ quark decays to tW.A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016–2018, with an integrated luminosity of 138 fb$^{−1}$. Events are separated into single-lepton, same-sign charge dilepton, and multi-lepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\textrm{T}\overline{\textrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\textrm{B}\overline{\textrm{B}}$ production with B quark decays to tW.[graphic not available: see fulltext]A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T\overline{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B\overline{B}}$ production with B quark decays to tW

Search for new heavy resonances decaying to WW, WZ, ZZ, WH, or ZH boson pairs in the all-jets final state in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for new heavy resonances decaying to WW, WZ, ZZ, WH, or ZH boson pairs in the all-jets final state is presented. The analysis is based on proton-proton collision data recorded by the CMS detector in 2016-2018 at a centre-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 138 fb$^{-1}$. The search is sensitive to resonances with masses between 1.3 and 6 TeV, decaying to bosons that are highly Lorentz-boosted such that each of the bosons forms a single large-radius jet. Machine learning techniques are employed to identify such jets. No significant excess over the estimated standard model background is observed. A maximum local significance of 3.6 standard deviations, corresponding to a global significance of 2.3 standard deviations, is observed at masses of 2.1 and 2.9 TeV. In a heavy vector triplet model, spin-1 Z' and W' resonances with masses below 4.8 TeV are excluded at the 95% confidence level (CL). These limits are the most stringent to date. In a bulk graviton model, spin-2 gravitons and spin-0 radions with masses below 1.4 and 2.7 TeV, respectively, are excluded at 95% CL. Production of heavy resonances through vector boson fusion is constrained with upper cross section limits at 95% CL as low as 0.1 fb

Search for medium effects using jets from bottom quarks in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

The first study of the shapes of jets arising from bottom (b) quarks in heavy ion collisions is presented. Jet shapes are studied using charged hadron constituents as a function of their radial distance from the jet axis. Lead-lead (PbPb) collision data at a nucleon-nucleon center-of-mass energy of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV were recorded by the CMS detector at the LHC, with an integrated luminosity of 1.69 nb$^{-1}$. Compared to proton-proton collisions, a redistribution of the energy in b jets to larger distances from the jet axis is observed in PbPb collisions. This medium-induced redistribution is found to be substantially larger for b jets than for inclusive jets

Search for pair production of vector-like quarks in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016–2018, with an integrated luminosity of 138 fb$^{−1}$. Events are separated into single-lepton, same-sign charge dilepton, and multi-lepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\textrm{T}\overline{\textrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\textrm{B}\overline{\textrm{B}}$ production with B quark decays to tW.[graphic not available: see fulltext

Measurements of the azimuthal anisotropy of prompt and nonprompt charmonia in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

International audienceThe second-order ($v_2$) and third-order ($v_3$) Fourier coefficients describing the azimuthal anisotropy of prompt and nonprompt (from b-hadron decays) J/$\psi$, as well as prompt $\psi$(2S) mesons are measured in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The analysis uses a data set corresponding to an integrated luminosity of 1.61 nb$^{-1}$ recorded with the CMS detector. The J/$\psi$ and $\psi$(2S) mesons are reconstructed using their dimuon decay channel. The $v_2$ and $v_3$ coefficients are extracted using the scalar product method and studied as functions of meson transverse momentum and collision centrality. The measured $v_2$ values for prompt J/$\psi$ mesons are found to be larger than those for nonprompt J/$\psi$ mesons. The prompt J/$\psi$$v_2$ values at high $p_\mathrm{T}$ are found to be underpredicted by a model incorporating only parton energy loss effects in a quark-gluon plasma medium. Prompt and nonprompt J/$\psi$ meson $v_3$ and prompt $\psi$(2S) $v_2$ and $v_3$ values are also reported for the first time, providing new information about heavy quark interactions in the hot and dense medium created in heavy ion collisions

Search for central exclusive production of top quark pairs in proton-proton collisions at s= \sqrt{s} = 13 TeV with tagged protons

A search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t} \bar{\mathrm{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t} \bar{\mathrm{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%.A search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%