The rockefeller university

The operation and performance of the Compact Muon Solenoid (CMS) electromagnetic calorimeter (ECAL) are presented, based on data collected in pp collisions at root s = 13 TeV at the CERN LHC, in the years from 2015 to 2018 (LHC Run 2), corresponding to an integrated luminosity of 151 fb(-1). The CMS ECAL is a scintillating lead-tungstate crystal calorimeter, with a silicon strip preshower detector in the forward region that provides precise measurements of the energy and the time-of-arrival of electrons and photons. The successful operation of the ECAL is crucial for a broad range of physics goals, ranging from observing the Higgs boson and measuring its properties, to other standard model measurements and searches for new phenomena. Precise calibration, alignment, and monitoring of the ECAL response are important ingredients to achieve these goals. To face the challenges posed by the higher luminosity, which characterized the operation of the LHC in Run 2, the procedures established during the 2011-2012 run of the LHC have been revisited and new methods have been developed for the energy measurement and for the ECAL calibration. The energy resolution of the calorimeter, for electrons from Z boson decays reaching the ECAL without significant loss of energy by bremsstrahlung, was better than 1.8%, 3.0%, and 4.5% in the vertical bar eta vertical bar intervals [ 0.0, 0.8], [0.8, 1.5], [1.5, 2.5], respectively. This resulting performance is similar to that achieved during Run 1 in 2011-2012, in spite of the more severe running conditions.

Cancer cells frequently alter their lipids to grow and adapt to their environment(1-3). Despite the critical functions of lipid metabolism in membrane physiology, signalling and energy production, how specific lipids contribute to tumorigenesis remains incompletely understood. Here, using functional genomics and lipidomic approaches, we identified de novo sphingolipid synthesis as an essential pathway for cancer immune evasion. Synthesis of sphingolipids is surprisingly dispensable for cancer cell proliferation in culture or in immunodeficient mice but required for tumour growth in multiple syngeneic models. Blocking sphingolipid production in cancer cells enhances the anti-proliferative effects of natural killer and CD8(+) T cells partly via interferon-gamma (IFN gamma) signalling. Mechanistically, depletion of glycosphingolipids increases surface levels of IFN gamma receptor subunit 1 (IFNGR1), which mediates IFN gamma-induced growth arrest and pro-inflammatory signalling. Finally, pharmacological inhibition of glycosphingolipid synthesis synergizes with checkpoint blockade therapy to enhance anti-tumour immune response. Altogether, our work identifies glycosphingolipids as necessary and limiting metabolites for cancer immune evasion.

Background Most smokers attempting to quit will quickly relapse to tobacco use even when treated with the most efficacious smoking cessation agents currently available. This highlights the need to develop effective new smoking cessation medications. Evidence suggests that positive allosteric modulators (PAM) and other enhancers of nicotinic acetylcholine receptor (nAChR) signaling could have therapeutic utility as smoking cessation agents.Methods 3-[3-(3-pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283) was used as a starting point for medical chemistry efforts to develop novel small molecule enhancers of alpha 4 beta 2* nAChR stoichiometries containing a low-affinity agonist binding site at the interface of alpha 4/alpha 4 and alpha 4/alpha 5 subunits.Results The NS9283 derivative SR9883 enhanced the effect of nicotine on alpha 4 beta 2* nAChR stoichiometries containing low-affinity agonist binding sites, with EC50 values from 0.2-0.4 mu M. SR9883 had no effect on alpha 3 beta 2* or alpha 3 beta 4* nAChRs. SR9883 was bioavailable after intravenous (1 mg kg-1) and oral (10-20 mg kg-1) administration and penetrated into the brain. When administered alone, SR9883 (5-10 mg kg-1) had no effect on locomotor activity or intracranial self-stimulation (ICSS) thresholds in mice. When co-administered with nicotine, SR9883 enhanced locomotor suppression and elevations of ICSS thresholds induced by nicotine. SR9883 (5 and 10 mg kg-1) decreased responding for intravenous nicotine infusions (0.03 mg kg-1 per infusion) but had no effect on responding for food rewards in rats.Conclusions These data suggest that SR9883 is useful for investigating behavioral processes regulated by certain alpha 4 beta 2* nAChR stoichiometries. SR9883 and related compounds with favorable drug-like physiochemical and pharmacological properties hold promise as novel treatments of tobacco use disorder.

A search is described for the production of a pair of bottom-type vectorlike quarks (B VLQs) with mass greater than 1000 GeV. Each B VLQ decays into a b quark and a Higgs boson, a b quark and a Z boson, or a t quark and a W boson. This analysis considers both fully hadronic final states and those containing a charged lepton pair from a Z boson decay. The products of the H -> bb boson decay and of the hadronic Z or W boson decays can be resolved as two distinct jets or merged into a single jet, so the final states are classified by the number of reconstructed jets. The analysis uses data corresponding to an integrated luminosity of 138 fb(-1) collected in proton-proton collisions at root s = 13 TeV with the CMS detector at the LHC from 2016 to 2018. No excess over the expected background is observed. Lower limits are set on the B VLQ mass at the 95% confidence level. These depend on the B VLQ branching fractions and are 1570 and 1540 GeV for 100% B -> bH and 100% B -> bZ, respectively. In most cases, the mass limits obtained exceed previous limits by at least 100 GeV.