MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

Naftali Kaminski and colleagues find increased levels of specific proteins in the bloodstream of individuals with idiopathic pulmonary fibrosis, and suggest that these proteins may ultimately provide a biomarker for the disease

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Mechanical stability of the CMS strip tracker measured with a laser alignment system

Peer reviewe

MUSiC: a model-unspecific search for new physics in proton–proton collisions at √s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton–proton collision data recorded at the LHC at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 35.9fb-1, are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches

Measurements of (tt)over-barH Production and the CP Structure of the Yukawa Interaction between the Higgs Boson and Top Quark in the Diphoton Decay Channel

The first observation of the (tt) over barH process in a single Higgs boson decay channel with the full reconstruction of the final state (H -> gamma gamma) is presented, with a significance of 6.6 standard deviations (sigma). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2 sigma. The measurements are based on a sample of protonproton collisions at a center-of-mass energy root s = 13 TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross section times branching fraction of the (tt) over barH process is measured to be sigma B-(tt) over barH(gamma gamma) = 1.56(-0.32)(+0.34) th, which is compatible with the standard model prediction of 1.13(-0.11)(+0.08) fb. The fractional contribution of the CP-odd component is measured to be f(CP)(Hu) = 0.00 +/- 0.33.Peer reviewe

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton–proton collisions at √s=13TeV

A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton–proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 fb−1, at a center-of-mass energy √s = 13 TeV. No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported

Precision luminosity measurement in proton–proton collisions at √s=13TeV in 2015 and 2016 at CMS

The measurement of the luminosity recorded by the CMS detector installed at LHC interaction point 5, using proton–proton collisions at √s=13TeV in 2015 and 2016, is reported. The absolute luminosity scale is measured for individual bunch crossings using beam-separation scans (the van der Meer method), with a relative precision of 1.3 and 1.0% in 2015 and 2016, respectively. The dominant sources of uncertainty are related to residual differences between the measured beam positions and the ones provided by the operational settings of the LHC magnets, the factorizability of the proton bunch spatial density functions in the coordinates transverse to the beam direction, and the modeling of the effect of electromagnetic interactions among protons in the colliding bunches. When applying the van der Meer calibration to the entire run periods, the integrated luminosities when CMS was fully operational are 2.27 and 36.3 fb$^{-1}$ in 2015 and 2016, with a relative precision of 1.6 and 1.2%, respectively. These are among the most precise luminosity measurements at bunched-beam hadron colliders

Search for decays of the 125 GeV Higgs boson into a Z boson and a ρ or ϕ meson

Decays of the 125 GeV Higgs boson into a Z boson and a ρ^0(770) or ϕ(1020) meson are searched for using proton-proton collision data collected by the CMS experiment at the LHC at √s = 13 TeV. The analysed data set corresponds to an integrated luminosity of 137 fb⁻¹. Events are selected in which the Z boson decays into a pair of electrons or a pair of muons, and the ρ and ϕ mesons decay into pairs of pions and kaons, respectively. No significant excess above the background model is observed. As different polarization states are possible for the decay products of the Z boson and ρ or ϕ mesons, affecting the signal acceptance, scenarios in which the decays are longitudinally or transversely polarized are considered. Upper limits at the 95% confidence level on the Higgs boson branching fractions into Zρ and Zϕ are determined to be 1.04–1.31% and 0.31–0.40%, respectively, where the ranges reflect the considered polarization scenarios; these values are 740–940 and 730–950 times larger than the respective standard model expectations. These results constitute the first experimental limits on the two decay channels