Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of inclusive jet production and nuclear modifications in pPb collisions at root s(NN)=5.02 TeV

Peer reviewe

Phenomenological MSSM interpretation of CMS searches in pp collisions at √s=7 and 8 TeV

Searches for new physics by the CMS collaboration are interpreted in the framework of the phenomenological minimal supersymmetric standard model (pMSSM). The data samples used in this study were collected at root s = 7 and 8 TeV and have integrated luminosities of 5.0 fb(-1) and 19.5 fb(-1), respectively. A global Bayesian analysis is performed, incorporating results from a broad range of CMS supersymmetry searches, as well as constraints from other experiments. Because the pMSSM incorporates several well-motivated assumptions that reduce the 120 parameters of the MSSM to just 19 parameters defined at the electroweak scale, it is possible to assess the results of the study in a relatively straightforward way. Approximately half of the model points in a potentially accessible subspace of the pMSSM are excluded, including all pMSSM model points with a gluino mass below 500 GeV, as well as models with a squark mass less than 300 GeV. Models with chargino and neutralino masses below 200 GeV are disfavored, but no mass range of model points can be ruled out based on the analyses considered. The nonexcluded regions in the pMSSM parameter space are characterized in terms of physical processes and key observables, and implications for future searches are discussed

Search for dark matter particles in proton-proton collisions at √s=8 TeV using the razor variables

A search for dark matter particles directly produced in proton-proton collisions recorded by the CMS experiment at the LHC is presented. The data correspond to an integrated luminosity of 18.8 fb−1, at a center-of-mass energy of 8 TeV. The event selection requires at least two jets and no isolated leptons. The razor variables are used to quantify the transverse momentum balance in the jet momenta. The study is performed separately for events with and without jets originating from b quarks. The observed yields are consistent with the expected backgrounds and, depending on the nature of the production mechanism, dark matter production at the LHC is excluded at 90% confidence level for a mediator mass scale Λ below 1 TeV. The use of razor variables yields results that complement those previously published

Search for lepton flavour violating decays of heavy resonances and quantum black holes to an eμ pair in proton–proton collisions at √s = 8 TeV

A search for narrow resonances decaying to an electron and a muon is presented. The eμ mass spectrum is also investigated for non-resonant contributions from the production of quantum black holes (QBHs). The analysis is performed using data corresponding to an integrated luminosity of 19.7 fb-1 collected in proton-proton collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC. With no evidence for physics beyond the standard model in the invariant mass spectrum of selected eμ pairs, upper limits are set at 95 % confidence level on the product of cross section and branching fraction for signals arising in theories with charged lepton flavour violation. In the search for narrow resonances, the resonant production of τ sneutrino in R-parity violating supersymmetry is considered. The τ sneutrino is excluded for masses below 1.28 TeV for couplings λ132= λ231= λ311′= 0.01 , and below 2.30 TeV for λ132= λ231= 0.07 and λ311′= 0.11. These are the most stringent limits to date from direct searches at high-energy colliders. In addition, the resonance searches are interpreted in terms of a model with heavy partners of the Z boson and the photon. In a framework of TeV-scale quantum gravity based on a renormalization of Newton’s constant, the search for non-resonant contributions to the eμ mass spectrum excludes QBH production below a threshold mass Mth of 1.99 TeV. In models that invoke extra dimensions, the bounds range from 2.36 TeV for one extra dimension to 3.63 TeV for six extra dimensions. This is the first search for QBHs decaying into the eμ final state

Measurements of t(t)over-bar charge asymmetry using dilepton final states in pp collisions at root s=8 TeV

Peer reviewe

Measurement of the integrated and differential t(t)over-bar production cross sections for high-p(T) top quarks in pp collisions at root s=8 TeV

Peer reviewe

Study of Z boson production in pPb collisions at √sNN=5.02 TeV

The production of Z bosons in pPb collisions at root S-NN = 5.02 TeV is studied by the CMS experiment via the electron and muon decay channels. The inclusive cross section is compared to pp collision predictions, and found to scale with the number of elementary nucleon-nucleon collisions. The differential cross sections as a function of the Z boson rapidity and transverse momentum are measured. Though they are found to be consistent within uncertainty with theoretical predictions both with and without nuclear effects, the forward-backward asymmetry suggests the presence of nuclear effects at large rapidities. These results provide new data for constraining nuclear parton distribution functions