An organ culture system to model early degenerative changes of the intervertebral disc

ABSTRACT: INTRODUCTION: Back pain, a significant source of morbidity in our society, is related to the degenerative changes of the intervertebral disc. At present, the treatment of disc disease consists of therapies that are aimed at symptomatic relief. This shortcoming stems in large part from our lack of understanding of the biochemical and molecular events that drive the disease process. The goal of this study is to develop a model of early disc degeneration using an organ culture. This approach is based on our previous studies that indicate that organ culture closely models molecular events that occur in vivo in an ex vivo setting. METHODS: To mimic a degenerative insult, discs were cultured under low oxygen tension in the presence of TNF-α, IL-1β and serum limiting conditions. RESULTS: Treatment resulted in compromised cell survival and changes in cellular morphology reminiscent of degeneration. There was strong suppression in the expression of matrix proteins including collagen types 1, 2, 6 and 9, proteoglycans, aggrecan and fibromodulin. Moreover, a strong induction in expression of catabolic matrix metalloproteinases (MMP) 3, 9 and 13 with a concomitant increase in aggrecan degradation was seen. An inductive effect on NGF expression was also noticed. Although similar, nucleus pulposus and annulus fibrosus tissues showed some differences in their response to the treatment. CONCLUSIONS: Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2

Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.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 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

Studies of Beauty Suppression via Nonprompt D-0 Mesons in Pb-Pb Collisions at root s(NN)=5.02 TeV

The transverse momentum spectra of D-0 mesons from b hadron decays are measured at midrapidity (vertical bar y vertical bar D-0 yield is found to be suppressed in the measured p(T) range from 2 to 100 GeV/c as compared to pp collisions. The suppression is weaker than that of prompt D-0 mesons and charged hadrons for p(T) around 10 GeV/c. While theoretical calculations incorporating partonic energy loss in the quark-gluon plasma can successfully describe the measured B -> D-0 suppression at higher p(T), the data show an indication of larger suppression than the model predictions in the range of 2 <p(T) <5 GeV/c.Peer reviewe

Search for new phenomena in final states with two opposite-charge, same-flavor leptons, jets, and missing transverse momentum in pp collisions at √s=13 TeV

Search results are presented for physics beyond the standard model in final states with two opposite-charge, same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb−1 of proton-proton collisions at s√=13 TeV collected with the CMS detector at the LHC in 2016. The analysis uses the invariant mass of the lepton pair, searching for a kinematic edge or a resonant-like excess compatible with the Z boson mass. The search for a kinematic edge targets production of particles sensitive to the strong force, while the resonance search targets both strongly and electroweakly produced new physics. The observed yields are consistent with the expectations from the standard model, and the results are interpreted in the context of simplified models of supersymmetry. In a gauge mediated supersymmetry breaking (GMSB) model of gluino pair production with decay chains including Z bosons, gluino masses up to 1500–1770 GeV are excluded at the 95% confidence level depending on the lightest neutralino mass. In a model of electroweak chargino-neutralino production, chargino masses as high as 610 GeV are excluded when the lightest neutralino is massless. In GMSB models of electroweak neutralino-neutralino production, neutralino masses up to 500-650 GeV are excluded depending on the decay mode assumed. Finally, in a model with bottom squark pair production and decay chains resulting in a kinematic edge in the dilepton invariant mass distribution, bottom squark masses up to 980–1200 GeV are excluded depending on the mass of the next-to-lightest neutralino

Inclusive Search for a Highly Boosted Higgs Boson Decaying to a Bottom Quark-Antiquark Pair

© 2018 CERN. An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (pT) and decaying to a bottom quark-antiquark pair (bb) is performed using a data set of pp collisions at s=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb-1. A highly Lorentz-boosted Higgs boson decaying to bb is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Z→bb decays. The Z→bb process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of H→bb with reconstructed pT > 450 GeV and in the pseudorapidity range -2.5 < η < 2.5 is 74±48(stat)-10+17(syst) fb, which is consistent within uncertainties with the standard model prediction