310 research outputs found

    ADAMTS -1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

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    ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggests that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein was up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contribute to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.</p

    Semi-Analytic Stellar Structure in Scalar-Tensor Gravity

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    Precision tests of gravity can be used to constrain the properties of hypothetical very light scalar fields, but these tests depend crucially on how macroscopic astrophysical objects couple to the new scalar field. We develop quasi-analytic methods for solving the equations of stellar structure using scalar-tensor gravity, with the goal of seeing how stellar properties depend on assumptions made about the scalar coupling at a microscopic level. We illustrate these methods by applying them to Brans-Dicke scalars, and their generalization in which the scalar-matter coupling is a weak function of the scalar field. The four observable parameters that characterize the fields external to a spherically symmetric star (the stellar radius, R, mass, M, scalar `charge', Q, and the scalar's asymptotic value, phi_infty) are subject to two relations because of the matching to the interior solution, generalizing the usual mass-radius, M(R), relation of General Relativity. We identify how these relations depend on the microscopic scalar couplings, agreeing with earlier workers when comparisons are possible. Explicit analytical solutions are obtained for the instructive toy model of constant-density stars, whose properties we compare to more realistic equations of state for neutron star models.Comment: 39 pages, 9 figure

    Pseudocholinesterase as a biomarker for untreated Wilson's disease

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    The aim of this study was to demonstrate that pseudocholinesterase (CHE) serum level is a useful diagnostic biomarker for untreated Wilson's disease (WD). Between 2013 and 2019, about 75 patients were referred to the outpatient department of the University of Düsseldorf with suspected Wilson's disease. In 31 patients with suspected Wilson's disease (WD-SUS-group), WD was excluded by means of investigations other than analysis of blood and urine. A total of 27 parameters of blood and urine in these 31 patients were compared to those of 20 de novo patients with manifest WD (WD-DEF-group), which parameter showed the highest significance level of difference between the WD-DEF-group and the WD-SUS-group. Thereafter, receiver operating characteristics (ROC-curves) were analyzed to evaluate which parameter showed the largest area under the curve (AUC) to detect WD. Finally, a logistic regression analysis was performed to analyze which combination of parameters allowed the best classification of the 51 patients either into the WD-DEF-group or into the WD-SUS-group. CHE showed the highest significance level for a difference between the WD-DEF- and WD-SUS-group, had the highest AUC, and, in combination with ceruloplasmin, allowed 100% correct classification. Without CHE, no other combination of parameters reached this level of correct classification. After the initiation of treatment, which regularly results in an improvement in CHE, the high diagnostic accuracy of this biomarker was lost. Cholinesterase turns out to be an excellent biomarker for differentiation between untreated de novo patients with manifest WD and heterozygotic gene carriers

    Crossing of shears bands in 197Pb: B(M1) values and semiclassical description

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    Subpicosecond lifetimes of states in shears band 1 in 97Pb were measured by means of the recoil distance method employing Gammasphere and the New Yale Plunger Device. The extracted reduced matrix elements, B(M1), show a clear sensitivity to the crossing of different shears configurations reflecting the closing and reopening of the shears blades. The energies and B(M1) values in the band crossing region are successfully described in the framework of the semiclassical model of the shears bands. The relevance of core rotation contributions are shown. The results point to the existence of shears states with an angular momentum coupling angle larger than 90°

    Brain potentials before and during memory scanning

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    Brain potentials were recorded from 10 normal subjects engaged in a 3-item auditory verbal short-term memory task. A fixed interval (3 s) between the last memory item and the probe was compared to a random interval (1.8-4.2 s with a mean of 3 s). Subjects indicated by button press whether the probe was or was not a member of the memory-set. The same 3-item task was also presented as a counting task and required a button press to the "fourth stimulus' (the probe). The amplitudes of several slow potential shifts preceding and following the probe, and the amplitudes and latencies of the accompanying short duration components (N100, P200) were measured. When the probe appeared at a fixed interval, the amplitude of a slow negative potential in the 300 ms period preceding the probe was slightly larger in the memory than in the counting task. When the probe appeared at a random interval in the memory task, the slow negative shift preceding the probe was absent. Another slow negative shift that peaked at approximately 376 ms after the probe was present in the memory tasks but was absent in the counting task. The amplitude of a late positive shift that peaked at approximately 700 ms after the probe was not different within the memory tasks, or between the memory and counting tasks. N100 amplitude but not P200 amplitude was larger in the memory task when the probe occurred at a fixed than at a random interval. These results suggest that the amplitude of a slow negative shift preceding the probe was related primarily to a temporal expectancy for the appearance of the probe and to a lesser extent to memory processes. In contrast, a slow negative shift that followed the probe occurred only during the memory tasks

    CD4/CD8 Ratio and Cancer Risk among Adults with HIV

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    Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P <. 05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker

    Demonstration of surface electron rejection with interleaved germanium detectors for dark matter searches

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    The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two 210 Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8–115 keV signal region, giving upper limit leakage fraction 1.7 × 10−5 at 90% C.L., corresponding to < 0.6 surface event background in the future 200-kg SuperCDMS SNOLAB experiment

    Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

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    A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

    Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

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    This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

    Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

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    This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio
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