The gene for a novel epidermal antigen maps near the neurofibromatosis 1 gene

Recently the M17S1 gene, encoding an epidermal antigen thought to play a role in cell adhesion, was mapped to chromosome bands 17q11-q12, placing it in the vicinity of the gene for the genetic disorder neurofi-bromatosis 1 (NF1). The pleomorphic cutaneous lesions of NF1 and the precedent for other genes being embedded within the NF1 gene prompted us to investigate whether the M17S1 gene mapped near, or within, the NF1 gene. Genetic linkage analyses revealed that M17S1 was tightly linked to NF1 and mapped within the interval bounded by D17S58 and D17S54. Physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast artificial chromosomes, and an NF1 patient with a deletion involving an entire NF1 allele demonstrated that M17S1 is located at least 180 kb centromeric to the NF1 gene. The distance between the genes suggests that M17S1 is unlikely to contribute to the NF1 phenotype since a gross chromosomal rearrangement would be required to disrupt expression of both genes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29816/1/0000162.pd

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of b jet shapes in proton-proton collisions at root s=5.02 TeV

We present the first study of charged-hadron production associated with jets originating from b quarks in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data sample used in this study was collected with the CMS detector at the CERN LHC and corresponds to an integrated luminosity of 27.4 pb(-1). To characterize the jet substructure, the differential jet shapes, defined as the normalized transverse momentum distribution of charged hadrons as a function of angular distance from the jet axis, are measured for b jets. In addition to the jet shapes, the per-jet yields of charged particles associated with b jets are also quantified, again as a function of the angular distance with respect to the jet axis. Extracted jet shape and particle yield distributions for b jets are compared with results for inclusive jets, as well as with the predictions from the pythia and herwig++ event generators.Peer reviewe

Measurement of the Jet Mass Distribution and Top Quark Mass in Hadronic Decays of Boosted Top Quarks in pp Collisions at root s=13 TeV

A measurement is reported of the jet mass distribution in hadronic decays of boosted top quarks produced in pp collisions at root s = 13 TeV. The data were collected with the CMS detector at the LHC and correspond to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lepton + jets channel of t (t) over bar events, where the lepton is an electron or muon. The products of the hadronic top quark decay t -> bW -> bq (q) over bar' are reconstructed as a single jet with transverse momentum larger than 400 GeV. The t (t) over bar cross section as a function of the jet mass is unfolded at the particle level and used to extract a value of the top quark mass of 172.6 +/- 2.5 GeV. A novel jet reconstruction technique is used for the first time at the LHC, which improves the precision by a factor of 3 relative to an earlier measurement. This highlights the potential of measurements using boosted top quarks, where the new technique will enable future precision measurements.Peer reviewe

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The second-order Fourier coefficients (v(2)) characterizing the azimuthal distributions of Y(1S) and Y(2S) mesons produced in PbPb collisions at root s(NN) = 5.02 TeV are studied. The Y mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb(-1). The scalar product method is used to extract the v2 coefficients of the azimuthal distributions. Results are reported for the rapidity range vertical bar y vertical bar < 2.4, in the transverse momentum interval 0 < pT < 50 GeV/c, and in three centrality ranges of 10-30%, 30-50% and 50-90%. In contrast to the J/psi mesons, the measured v(2) values for the Y mesons are found to be consistent with zero. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for charged Higgs bosons decaying into a top and a bottom quark in the all-jet final state of pp collisions at root s=13 TeV

A search for charged Higgs bosons (H-+/-) decaying into a top and a bottom quark in the all-jet final state is presented. The analysis uses LHC proton-proton collision data recorded with the CMS detector in 2016 at root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No significant excess is observed above the expected background. Model-independent upper limits at 95% confidence level are set on the product of the H-+/- production cross section and branching fraction in two scenarios. For production in association with a top quark, limits of 21.3 to 0.007 pb are obtained for H-+/- masses in the range of 0.2 to 3 TeV. Combining this with a search in leptonic final states results in improved limits of 9.25 to 0.005 pb. The complementary s-channel production of an H-+/- is investigated in the mass range of 0.8 to 3 TeV and the corresponding upper limits are 4.5 to 0.023 pb. These results are interpreted using different minimal supersymmetric extensions of the standard model.Peer reviewe

Measurement of properties of B(s)(0)s -> mu(+)mu(-) decays and search for B-0 -> mu(+)mu(-) with the CMS experiment

Results are reported for the B 0s ! + branching fraction and effective lifetime and from a search for the decay B0 ! + . The analysis uses a data sample of proton-proton collisions accumulated by the CMS experiment in 2011, 2012, and 2016, with center-of-mass energies (integrated luminosities) of 7TeV (5 fb), 8TeV (20 fb), and 13TeV (36 fb). The branching fractions are determined by measuring event yields relative to B+ ! J= K+ decays (with J= ! + ), which results in the reduction of many of the systematic uncertainties. The decay B 0s ! + is observed with a significance of 5.6 standard deviations. The branching fraction is measured to be B (B 0s ! + ) = [2:9 0:7(exp) 0:2(frag)] 10, where the first uncertainty combines the experimental statistical and systematic contributions, and the second is due to the uncertainty in the ratio of the B 0s and the B+ fragmentation functions. No significant excess is observed for the decay B0 ! + , and an upper limit of B(B0 ! + ) <3:6 10 is obtained at 95% confidence level. The B 0s ! + effective lifetime is measured to be + = 1:70 +0:61 ps. These results are consistent with standard model predictions.Peer reviewe

Measurement of the top quark pair production cross section in dilepton final states containing one τ lepton in pp collisions at √s = 13 TeV

© 2020, The Author(s). The cross section of top quark pair production is measured in the tt¯→(ℓνℓ)(τhντ)bb¯ final state, where τh refers to the hadronic decays of the τ lepton, and ℓ is either an electron or a muon. The data sample corresponds to an integrated luminosity of 35.9 fb−1 collected in proton-proton collisions at s = 13 TeV with the CMS detector. The measured cross section is σtt ¯ = 781 ± 7 (stat) ± 62 (syst) ± 20 (lumi) pb, and the ratio of the partial width Γ(t → τντb) to the total decay width of the top quark is measured to be 0.1050 ± 0.0009 (stat) ± 0.0071 (syst). This is the first measurement of the t t ¯ production cross section in proton-proton collisions at s = 13 TeV that explicitly includes τ leptons. The ratio of the cross sections in the ℓτh and ℓℓ final states yields a value Rℓτh/ll = 0.973 ± 0.009 (stat) ± 0.066 (syst), consistent with lepton universality. [Figure not available: see fulltext.]SCOAP

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P &lt; 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P &lt; 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P &lt; 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344)