133 research outputs found
Myeloperoxidase and oxidative stress in rheumatoid arthritis
Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and
whether it produces hypochlorous acid in SF.
Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls
supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins
and allantoin in plasma were measured by mass spectrometry.
Results. Plasma MPO concentrations were significantly higher in patients with RA compared with
healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.214.2; P < 0.05], but there was no significant
difference in plasma MPO protein concentrations between RA patients with high disease activity
(HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 43.2) (HDA 27.9 ng/ml,
20.234.1 vs LDA 22.1 ng/ml, 16.934.9; P > 0.05). There was a significant relationship between plasma
MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in
patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.42433.0 vs 30.2 ng/ml, IQR 25.150.9; P < 0.0001). The
MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was
present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls
in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3-chlorotyrosine (r = 0.66;
P = 0.003).
Conclusion. MPO is elevated in patients with RA and promotes oxidative stress through the production of
hypochlorous acid
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
First measurement of the νμ charged-current cross section on a water target without pions in the final state
This paper reports the first differential measurement of the charged-current interaction cross section of νμ on water with no pions in the final state. This flux-averaged measurement has been made using the T2K experiment’s off-axis near detector, and is reported in doubly differential bins of muon momentum and angle. The flux-averaged total cross section in a restricted region of phase space was found to be σ=(0.95±0.08(stat)±0.06(det syst)±0.04(model syst)±0.08(flux))×10−38 cm2/n
Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation γ rays
Neutrino- and antineutrino-oxygen neutral-current quasielastic-like
interactions are measured at Super-Kamiokande using nuclear de-excitation
-rays to identify signal-like interactions in data from a $14.94 \
(16.35)\times 10^{20}\langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+
{\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}\langle \sigma_{\bar{\nu} {\rm
-NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}}
({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy
of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are
the most precise to date, and the antineutrino result is the first cross
section measurement of this channel. They are compared with various theoretical
predictions. The impact on evaluation of backgrounds to searches for supernova
relic neutrinos at present and future water Cherenkov detectors is also
discussed
Search for electron antineutrino appearance in a long-baseline muon antineutrino beam
Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions
The DUNE Far Detector Interim Design Report, Volume 3: Dual-Phase Module
The DUNE IDR describes the proposed physics program and technical designs of the DUNE far detector modules in preparation for the full TDR to be published in 2019. It is intended as an intermediate milestone on the path to a full TDR, justifying the technical choices that flow down from the high-level physics goals through requirements at all levels of the Project. These design choices will enable the DUNE experiment to make the ground-breaking discoveries that will help to answer fundamental physics questions. Volume 3 describes the dual-phase module's subsystems, the technical coordination required for its design, construction, installation, and integration, and its organizational structure
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
- …