Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis

Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKTcells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis

Measurement of Energy Correlators inside Jets and Determination of the Strong Coupling Formula Presented

Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of $\sqrt{s}$=13 TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3 fb$^{−1}$. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom. By comparing the ratio of the measured three- and two-particle energy correlator distributions with theoretical calculations that resum collinear emissions at approximate next-to-next-to-leading-logarithmic accuracy matched to a next-to-leading-order calculation, the strong coupling is determined at the Z boson mass: α$_S$ (m$_Z$)=0.1229 $\frac{0.0040}{-0.0050}$ , the most precise α$_S$m$_Z$ value obtained using jet substructure observable

Search for heavy neutral leptons in final states with electrons, muons, and hadronically decaying tau leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for heavy neutral leptons (HNLs) of Majorana or Dirac type using proton-proton collision data at = 13 TeV is presented. The data were collected by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 138 fb−1. Events with three charged leptons (electrons, muons, and hadronically decaying tau leptons) are selected, corresponding to HNL production in association with a charged lepton and decay of the HNL to two charged leptons and a standard model (SM) neutrino. The search is performed for HNL masses between 10 GeV and 1.5 TeV. No evidence for an HNL signal is observed in data. Upper limits at 95% confidence level are found for the squared coupling strength of the HNL to SM neutrinos, considering exclusive coupling of the HNL to a single SM neutrino generation, for both Majorana and Dirac HNLs. The limits exceed previously achieved experimental constraints for a wide range of HNL masses, and the limits on tau neutrino coupling scenarios with HNL masses above the W boson mass are presented for the first time

Measurement of the polarizations of prompt and non-prompt J/ψ and ψ (2S) mesons produced in pp collisions at s\sqrt{s} = 13 TeV

The polarizations of prompt and non-prompt J∕ψ and ψ(2S) mesons are measured in proton-proton collisions at √ = 13 TeV, using data samples collected by the CMS experiment in 2017 and 2018, corresponding to a total integrated luminosity of 103.3 fb$^{−1}$. Based on the analysis of the dimuon decay angular distributions in the helicity frame, the polar anisotropy, , is measured as a function of the transverse momentum, $_T$, of the charmonium states, in the 25–120 and 20–100 GeV ranges for the J∕ψ and ψ(2S), respectively. The non-prompt polarizations agree with predictions based on the hypothesis that, for T ≳ 25 GeV, the non-prompt J∕ψ and ψ(2S) are predominantly produced in two-body B meson decays. The prompt results clearly exclude strong transverse polarizations, even for $_T$ exceeding 30 times the J∕ψ mass, where tends to an asymptotic value around 0.3. Taken together with previous measurements, by CMS and LHCb at √ = 7 TeV, the prompt polarizations show a significant variation with $_T$, at low $_T$

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at √s = 13 TeV

The central exclusive production of charged-hadron pairs in ⁢ collisions at a center-of-mass energy of 13 TeV is examined, based on data collected in a special high-* run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, +⁢−1.8  GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and +⁢− are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities ||<2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton

Search for long-lived particles using displaced vertices and missing transverse momentum in proton-proton collisions at √s = 13 TeV

A search for the production of long-lived particles in proton-proton collisions at a center-of-mass energy of 13 TeV at the CERN LHC is presented. The search is based on data collected by the CMS experiment in 2016–2018, corresponding to a total integrated luminosity of 137  fb−1. This search is designed to be sensitive to long-lived particles with mean proper decay lengths between 0.1 and 1000 mm, whose decay products produce a final state with at least one displaced vertex and missing transverse momentum. A machine learning algorithm, which improves the background rejection power by more than an order of magnitude, is applied to improve the sensitivity. The observation is consistent with the standard model background prediction, and the results are used to constrain split supersymmetry (SUSY) and gauge-mediated SUSY breaking models with different gluino mean proper decay lengths and masses. This search is the first CMS search that shows sensitivity to hadronically decaying long-lived particles from signals with mass differences between the gluino and neutralino below 100 GeV. It sets the most stringent limits to date for split-SUSY models and gauge-mediated SUSY breaking models with gluino proper decay length less than 6 mm

Search for long-lived particles decaying in the CMS muon detectors in proton-proton collisions at √s = 13 TeV

A search for long-lived particles (LLPs) decaying in the CMS muon detectors is presented. A data sample of proton-proton collisions at √=13  TeV corresponding to an integrated luminosity of 138  fb−1, recorded at the LHC in 2016–2018, is used. The decays of LLPs are reconstructed as high multiplicity clusters of hits in the muon detectors. In the context of twin Higgs models, the search is sensitive to LLP masses from 0.4 to 55 GeV and a broad range of LLP decay modes, including decays to hadrons, leptons, electrons, or photons. No excess of events above the standard model background is observed. The most stringent limits to date from LHC data are set on the branching fraction of the Higgs boson decay to a pair of LLPs with masses below 10 GeV. This search also provides the best limits for various intervals of LLP proper decay length and mass. Finally, this search sets the first limits at the LHC on a dark quantum chromodynamic sector whose particles couple to the Higgs boson through gluon, Higgs boson, photon, vector, and dark-photon portals, and is sensitive to branching fractions of the Higgs boson to dark quarks as low as 2×10−3

Measurement of multijet azimuthal correlations and determination of the strong coupling in proton-proton collisions at s=13 TeV\sqrt{s}=13\,\text {Te}\hspace{-.08em}\text {V}

A measurement is presented of a ratio observable that provides a measure of the azimuthal correlations among jets with large transverse momentum pT . This observable is measured in multijet events over the range of pT=360–3170 GeV based on data collected by the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 134 fb$^{−1}$ . The results are compared with predictions from Monte Carlo parton-shower event generator simulations, as well as with fixed-order perturbative quantum chromodynamics (pQCD) predictions at next-to-leading-order (NLO) accuracy obtained with different parton distribution functions (PDFs) and corrected for nonperturbative and electroweak effects. Data and theory agree within uncertainties. From the comparison of the measured observable with the pQCD prediction obtained with the NNPDF3.1 NLO PDFs, the strong coupling at the Z boson mass scale is α$_S$(m$_Z$) = 0.1177 ± 0.0013 (exp)$\frac {+0.0116}{−0.0073}$ (theo) = 0.1177$\frac {+0.0117}{−0.0074}$ , where the total uncertainty is dominated by the scale dependence of the fixed-order predictions. A test of the running of α$_S$ in the TeV region shows no deviation from the expected NLO pQCD behaviour