Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype

Abstract Background Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefore sought to determine whether MSCs are present in the lungs of ovalbumin (OVA)-sensitized and challenged mice, a model of allergic airways disease. Methods Balb/c mice were sensitized and challenged with PBS or OVA over a 25 day period. Flow cytometry as well as colony forming and differentiation potential were used to analyze the emergence of MSCs along with gene expression studies using immunochemical analyses, quantitative polymerase chain reaction (qPCR), and gene expression beadchips. Results A CD45-negative subset of cells expressed Stro-1, Sca-1, CD73 and CD105. Selection for these markers and negative selection against CD45 yielded a population of cells capable of adipogenic, osteogenic and chondrogenic differentiation. Lungs from OVA-treated mice demonstrated a greater average colony forming unit-fibroblast (CFU-F) than control mice. Sorted cells differed from unsorted lung adherent cells, exhibiting a pattern of gene expression nearly identical to bone marrow-derived sorted cells. Finally, cells isolated from the bronchoalveolar lavage of a human asthma patient showed identical patterns of cell surface markers and differentiation potential. Conclusions In summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.http://deepblue.lib.umich.edu/bitstream/2027.42/78265/1/1465-9921-11-127.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78265/2/1465-9921-11-127.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78265/3/1465-9921-11-127-S1.DOCPeer Reviewe

Mesenchymal Stromal Cells from Neonatal Tracheal Aspirates Demonstrate a Pattern of Lung-Specific Gene Expression

We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. Although isolation of MSCs correlates with the development of bronchopulmonary dysplasia, the physiologic role of these cells remains unclear. To address this, we further characterized the cells, focusing on the issues of gene expression, origin, and cytokine expression. Microarray comparison of early passage neonatal lung MSC gene expression to cord blood MSCs and human fetal and neonatal lung fibroblast lines demonstrated that the neonatal lung MSCs differentially expressed 971 gene probes compared with cord blood MSCs, including the transcription factors Tbx2, Tbx3, Wnt5a, FoxF1, and Gli2, each of which has been associated with lung development. Compared with lung fibroblasts, 710 gene probe transcripts were differentially expressed by the lung MSCs, including IL-6 and IL-8/CXCL8. Differential chemokine expression was confirmed by protein analysis. Further, neonatal lung MSCs exhibited a pattern of Hox gene expression distinct from cord blood MSCs but similar to human fetal lung fibroblasts, consistent with a lung origin. On the other hand, limiting dilution analysis showed that fetal lung fibroblasts form colonies at a significantly lower rate than MSCs, and fibroblasts failed to undergo differentiation along adipogenic, osteogenic, and chondrogenic lineages. In conclusion, MSCs isolated from neonatal tracheal aspirates demonstrate a pattern of lung-specific gene expression, are distinct from lung fibroblasts, and secrete pro-inflammatory cytokines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90487/1/scd-2E2010-2E0494.pd

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Calibration of the CMS hadron calorimeters using proton-proton collision data at root s=13 TeV

Methods are presented for calibrating the hadron calorimeter system of theCMSetector at the LHC. The hadron calorimeters of the CMS experiment are sampling calorimeters of brass and scintillator, and are in the form of one central detector and two endcaps. These calorimeters cover pseudorapidities vertical bar eta vertical bar ee data. The energy scale of the outer calorimeters has been determined with test beam data and is confirmed through data with high transverse momentum jets. In this paper, we present the details of the calibration methods and accuracy.Peer reviewe

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions

Search for dark matter in events with a leptoquark and missing transverse momentum in proton-proton collisions at 13 TeV

A search is presented for dark matter in proton-proton collisions at a center-of-mass energy of root s= 13 TeV using events with at least one high transverse momentum (p(T)) muon, at least one high-p(T) jet, and large missing transverse momentum. The data were collected with the CMS detector at the CERN LHC in 2016 and 2017, and correspond to an integrated luminosity of 77.4 fb(-1). In the examined scenario, a pair of scalar leptoquarks is assumed to be produced. One leptoquark decays to a muon and a jet while the other decays to dark matter and low-p(T) standard model particles. The signature for signal events would be significant missing transverse momentum from the dark matter in conjunction with a peak at the leptoquark mass in the invariant mass distribution of the highest p(T) muon and jet. The data are observed to be consistent with the background predicted by the standard model. For the first benchmark scenario considered, dark matter masses up to 500 GeV are excluded for leptoquark masses m(LQ) approximate to 1400 GeV, and up to 300 GeV for m(LQ) approximate to 1500 GeV. For the second benchmark scenario, dark matter masses up to 600 GeV are excluded for m(LQ) approximate to 1400 GeV. (C) 2019 The Author(s). Published by Elsevier B.V.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

Search for an L-mu - L-tau gauge boson using Z -> 4 mu events in proton-proton collisions at root s=13 TeV

A search for a narrow Z' gauge boson with a mass between 5 and 70 GeV resulting from an L-mu - L-tau U (1) local gauge symmetry is reported. Theories that predict such a particle have been proposed as an explanation of various experimental discrepancies, including the lack of a dark matter signal in direct-detection experiments, tension in the measurement of the anomalous magnetic moment of the muon, and reports of possible lepton flavor universality violation in B meson decays. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV is used, corresponding to an integrated luminosity of 77.3 fb(-1) recorded in 2016 and 2017 by the CMS detector at the LHC. Events containing four muons with an invariant mass near the standard model Z boson mass are analyzed, and the selection is further optimized to be sensitive to the events that may contain Z -> Z'mu mu -> 4 mu decays. The event yields are consistent with the standard model predictions. Upper limits of 10(-8)-10(-7) at 95% confidence level are set on the product of branching fractions B(Z -> Z'mu mu)B(Z' -> mu mu), depending on the Z' mass, which excludes a Z' boson coupling strength to muons above 0.004-0.3. These are the first dedicated limits on L-mu - L-tau models at the LHC and result in a significant increase in the excluded model parameter space. The results of this search may also be used to constrain the coupling strength of any light Z' gauge boson to muons. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

Measurement of electroweak WZ boson production and search for new physics in WZ + two jets events in pp collisions at √s=13TeV

A measurement of WZ electroweak (EW) vector boson scattering is presented. The measurement is performed in the leptonic decay modes WZ→ℓνℓ′ℓ′, where ℓ,ℓ′=e,μ. The analysis is based on a data sample of proton-proton collisions at √s=13 TeV at the LHC collected with the CMS detector and corresponding to an integrated luminosity of 35.9 fb−1. The WZ plus two jet production cross section is measured in fiducial regions with enhanced contributions from EW production and found to be consistent with standard model predictions. The EW WZ production in association with two jets is measured with an observed (expected) significance of 2.2 (2.5) standard deviations. Constraints on charged Higgs boson production and on anomalous quartic gauge couplings in terms of dimension-eight effective field theory operators are also presented

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2-and 3-jet events in pp collisions at root s=13TeV

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Delta phi(12), is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1) are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with themeasurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 degrees <Delta phi(12) <180 degrees. The 2- and 3-jet measurements are not simultaneously described by any of models.Peer reviewe