420 research outputs found

    Autoimmune and autoinflammatory mechanisms in uveitis

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    The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

    Laser clad and HVOF sprayed Stellite 6 coating in chlorine rich environment with KCI at 700 °C

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    Laser clads and HVOF coatings from a stellite 6 alloy (Co–Cr–W–C alloy) on 304 stainless steel substrates were exposed both bare and with KCl deposits in 500 ppm HCl with 5% O2 for 250 h at 700 C. SEM/EDX and PXRD analyses with Rietveld refinement were used for assessment of the attack and for analysis of the scales. The bare samples suffered from scale spallation and the scale was mostly composed of Cr2O3, CoCr2O4 and CoO, although due to dilution haematite (Fe2O3) was detected in the scale formed on the laser clad sample. A small amount of hydrated HCl was detected in bare samples. While the corrosion of the bare surfaces was limited to comparatively shallow depths and manifested by g and M7C3 carbide formation, the presence of KCl on the surface led to severe Cr depletion from the HVOF coating (to 1 wt%). Both inward and outward diffusion of elements occurred in the HVOF coating resulting in Kirdendall voids at the coating–steel interface. The laser clad sample performed significantly better in conditions of the KCl deposit-induced corrosion. In addition to the oxides, CoCl2 was detected in the HVOF sample and K3CrO4 was detected in the laser clad sample. Thermodynamic calculations and kinetic simulations were carried out to interpret the oxidation and diffusion behaviours of coatings

    Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

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    We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep

    Measurement of the proton form factor by studying e+eppˉe^{+} e^{-}\rightarrow p\bar{p}

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    Using data samples collected with the BESIII detector at the BEPCII collider, we measure the Born cross section of e+eppˉe^{+}e^{-}\rightarrow p\bar{p} at 12 center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective electromagnetic form factor of the proton is deduced under the assumption that the electric and magnetic form factors are equal (GE=GM)(|G_{E}|= |G_{M}|). In addition, the ratio of electric to magnetic form factors, GE/GM|G_{E}/G_{M}|, and GM|G_{M}| are extracted by fitting the polar angle distribution of the proton for the data samples with larger statistics, namely at s=\sqrt{s}= 2232.4 and 2400.0 MeV and a combined sample at s\sqrt{s} = 3050.0, 3060.0 and 3080.0 MeV, respectively. The measured cross sections are in agreement with recent results from BaBar, improving the overall uncertainty by about 30\%. The GE/GM|G_{E}/G_{M}| ratios are close to unity and consistent with BaBar results in the same q2q^{2} region, which indicates the data are consistent with the assumption that GE=GM|G_{E}|=|G_{M}| within uncertainties.Comment: 13 pages, 24 figure

    An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays

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    An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays is presented. In particular, a piecewise function that describes the dynamics of the π0π0\pi^{0}\pi^{0} system is determined as a function of Mπ0π0M_{\pi^{0}\pi^{0}} from an analysis of the (1.311±0.011)×109(1.311\pm0.011)\times10^{9} J/ψJ/\psi decays collected by the BESIII detector. The goal of this analysis is to provide a description of the scalar and tensor components of the π0π0\pi^0\pi^0 system while making minimal assumptions about the properties or number of poles in the amplitude. Such a model-independent description allows one to integrate these results with other related results from complementary reactions in the development of phenomenological models, which can then be used to directly fit experimental data to obtain parameters of interest. The branching fraction of J/ψγπ0π0J/\psi \to \gamma \pi^{0}\pi^{0} is determined to be (1.15±0.05)×103(1.15\pm0.05)\times10^{-3}, where the uncertainty is systematic only and the statistical uncertainty is negligible.Comment: Submitted to Phys. Rev. D 19 pages, 4 figure

    Observation of the isospin-violating decay J/ψϕπ0f0(980)J/\psi \to \phi\pi^{0}f_{0}(980)

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    Using a sample of 1.31 billion J/ψJ/\psi events collected with the BESIII detector at the BEPCII collider, the decays J/ψϕπ+ππ0J/\psi \to \phi \pi^{+}\pi^{-}\pi^{0} and J/ψϕπ0π0π0J/\psi \to \phi \pi^{0}\pi^{0}\pi^{0} are investigated. The isospin violating decay J/ψϕπ0f0(980)J/\psi \to \phi \pi^{0} f_{0}(980) with f0(980)ππf_{0}(980) \to \pi\pi, is observed for the first time. The width of the f0(980)f_{0}(980) obtained from the dipion mass spectrum is found to be much smaller than the world average value. In the π0f0(980)\pi^{0} f_{0}(980) mass spectrum, there is evidence of f1(1285)f_1(1285) production. By studying the decay J/ψϕηJ/\psi \to \phi\eta', the branching fractions of ηπ+ππ0\eta' \to \pi^{+}\pi^{-}\pi^{0} and ηπ0π0π0\eta' \to \pi^{0}\pi^{0}\pi^{0}, as well as their ratio, are also measured.Comment: 10 pages, 10 figures, published in Phys. Rev.

    Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

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    Background: Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. Methods: We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results: WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P <0.001). Functional annotation identified pathways enlightening the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E(-7)), and immune-related complications (e. g. Natural killer cell mediated cytotoxity, P = 3.8E(-5); B cell receptor signaling pathway, P = 7.2E(-5)). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and 34.58). Moreover, detection of differentially connected genes identified various genes previously identified to be associated with obesity in humans and rodents, e.g. CSF1R and MARC2. Conclusions: To our knowledge, this is the first study to apply systems biology approaches using porcine adipose tissue RNA-Sequencing data in a genetically characterized porcine model for obesity. We revealed complex networks, pathways, candidate and regulatory genes related to obesity, confirming the complexity of obesity and its association with immune-related disorders and osteoporosis

    Prediction of 3D grinding temperature field based on meshless method considering infinite element

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    © 2018, Springer-Verlag London Ltd., part of Springer Nature. A three-dimensional numerical model to calculate the grinding temperature field distribution is presented. The finite block method, which is developed from meshless method, is used to deal with the stationary and the transient heat conduction problems in this paper. The influences of workpiece feed velocity, cooling coefficient, and the depth of cut on temperature distribution are considered. The model with temperature-dependent thermal conductivity and specific heat is presented. The Lagrange partial differential matrix from the heat transfer governing equation is obtained by using Lagrange series and mapping technique. The grinding wheel-workpiece contact area is assumed as a moving distributed square heat source. The Laplace transformation method and Durbin’s inverse technique are employed in the transient heat conduction analysis. The results of the developed model are compared with others’ finite element method solutions and analytical solutions where a good agreement is demonstrated. And the finite block method was proved a better convergence and accuracy than finite element method by comparing the ABAQUS results. In addition, the three-dimensional infinite element is introduced to perform the thermal analysis, and there is a great of advantages in the simulation of large boundary problems.The work was funded by China Scholarship Council, the Fundamental Research Funds for the Central Universities (N160306006), National Natural Science Foundation of China (51275084), and Science and technology project of Shenyang (18006001)

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns
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