578 research outputs found
IL11 (Interleukin-11) causes emphysematous lung disease in a mouse model of marfan syndrome.
BACKGROUND: Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common in MFS, but their pathogenesis is poorly understood. IL11 (interleukin-11) causes aortic disease in a mouse model of MFS and was studied here in the lung. METHODS: We examined histological and molecular phenotypes in the lungs of Fbn1C1041G/+ mice (mouse model of Marfan Syndrome [mMFS]), an established mouse model of MFS. To identify IL11-expressing cells, we used immunohistochemistry on lungs of 4- and 16-week-old Fbn1C1041G/+:Il11EGFP/+ reporter mice. We studied the effects of IL11 inhibition by RT-qPCR, immunoblots and histopathology in lungs from genetic or pharmacologic models: (1) 16-week-old IL11 receptor (IL11RA) knockout mMFS mice (Fbn1C1041G/+:Il11ra1-/- mice) and (2) in mMFS mice administered IgG control or interleukin-11 receptor antibodies twice weekly from 4 to 24 weeks of age. RESULTS: mMFS lungs showed progressive loss and enlargement of distal airspaces associated with increased proinflammatory and profibrotic gene expression as well as matrix metalloproteinases 2, 9, and 12. IL11 was increased in mMFS lungs and localized to smooth muscle and endothelial cells in young mMFS mice in the Fbn1C1041G/+:Il11EGFP/+ reporter strain and in fibroblasts, in older mice. In mMFS mice, genetic (Fbn1C1041G/+:Il11ra1-/-) or pharmacologic (anti-interleukin-11 receptor) inhibition of IL11 signaling reduced lung emphysema, fibrosis, and inflammation. This protective effect was associated with reduced pathogenic ERK1/2 signaling and lower metalloproteinase 2, 9, and 12 expression. CONCLUSIONS: IL11 causes lung disease in mMFS. This reveals a shared IL11-driven disease mechanism in lung and aorta in MFS and suggests inhibition of IL11 signaling as a holistic approach for treating multiorgan morbidity in MFS
Yielding and irreversible deformation below the microscale: Surface effects and non-mean-field plastic avalanches
Nanoindentation techniques recently developed to measure the mechanical
response of crystals under external loading conditions reveal new phenomena
upon decreasing sample size below the microscale. At small length scales,
material resistance to irreversible deformation depends on sample morphology.
Here we study the mechanisms of yield and plastic flow in inherently small
crystals under uniaxial compression. Discrete structural rearrangements emerge
as series of abrupt discontinuities in stress-strain curves. We obtain the
theoretical dependence of the yield stress on system size and geometry and
elucidate the statistical properties of plastic deformation at such scales. Our
results show that the absence of dislocation storage leads to crucial effects
on the statistics of plastic events, ultimately affecting the universal scaling
behavior observed at larger scales.Comment: Supporting Videos available at
http://dx.plos.org/10.1371/journal.pone.002041
Assessment of pollution risk ascribed to Santa Margarida Military Camp activities (Portugal)
Santa Margarida Military Camp (S.M.M.C.) is
the only one Portuguese military training area, including
firing ranges for tactical military manoeuvres of mechanised
divisions. For this reason, various negative effects on
the environment were expected due to the military activities,
as the Military Campâs area is classified as a high
vulnerability area to pollution of its multilayer porous
aquifers. The aim of this study was to identify and characterise
local/regional geochemical impacts caused by the
continuing military training activities performed at
S.M.M.C. in the course of 52 years. An overview of the
geochemical research issues as a basis for risk assessment
is presented. A special attention has been put on the
quality of local and regional surface waters, shallow
groundwaters and groundwaters. Local soils and sediments
as well as fragments of shells and bullets were sampled
and analysed. The results so far obtained, indicated that none pollution effects were a consequence of the military
training activities. Till now, the geochemical signatures
such as, high levels of K, Cl and NO3 in waters, detected
in particular sites, should be faced as tracers of diffuse
pollution ascribed to urban waste disposal and cattle
breading
Effects of an Early Handling-Like Procedure and Individual Housing on Anxiety-Like Behavior in Adult C57BL/6J and DBA/2J Mice
Manipulations of rearing conditions have been used to examine the effects of early experience on adult behavior with varying results. Evidence suggests that postnatal days (PND) 15â21 are a time of particular susceptibility to environmental influences on anxiety-like behavior in mice. To examine this, we subjected C57BL/6J and DBA/2J mice to an early handling-like procedure. Pups were separated from dams from PND 12â20 for 30 minutes daily or received standard care. On PND 21, pups were weaned and either individually- or group- housed. On PND 60, anxiety-like behavior was examined on the elevated zero-maze. Although individually- housed animals took longer to enter an open quadrant of the maze, they spent more time in the open than group-housed animals. Additionally, we observed a trend of reduced anxiety-like behavior in C57BL/6J, but not DBA/2J mice that underwent the handling-like procedure
Search for CP violation in D+âÏÏ+ and D+sâK0SÏ+ decays
A search for CP violation in D + â ÏÏ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fbâ1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (â0.04 ± 0.14 ± 0.14)% for candidates with K â K + mass within 20 MeV/c 2 of the Ï meson mass. A search for a CP -violating asymmetry that varies across the Ï mass region of the D + â K â K + Ï + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+sâK0SÏ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%
Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.
OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
Surgical treatment for acromioclavicular joint osteoarthritis: patient selection, surgical options, complications, and outcome
Osteoarthritis is one of the most common causes of pain originating from the acromioclavicular (AC) joint. An awareness of appropriate diagnostic techniques is necessary in order to localize clinical symptoms to the AC joint. Initial treatments for AC joint osteoarthritis, which include non-steroidal anti-inflammatory drugs (NSAIDS) and corticosteroids, are recommended prior to surgical interventions. Distal clavicle excision, the main surgical treatment option, can be performed by various surgical approaches, such as open procedures, direct arthroscopic, and indirect arthroscopic techniques. When choosing the best surgical option, factors such as avoidance of AC ligament damage, clavicular instability, and post-operative pain must be considered. This article examines patient selection, complications, and outcomes of surgical treatment options for AC joint osteoarthritis
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of âs = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pTâ„20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60â€pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2â€{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
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