428 research outputs found

    Nonlocal symmetries of a class of scalar and coupled nonlinear ordinary differential equations of any order

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    In this paper we devise a systematic procedure to obtain nonlocal symmetries of a class of scalar nonlinear ordinary differential equations (ODEs) of arbitrary order related to linear ODEs through nonlocal relations. The procedure makes use of the Lie point symmetries of the linear ODEs and the nonlocal connection to deduce the nonlocal symmetries of the corresponding nonlinear ODEs. Using these nonlocal symmetries we obtain reduction transformations and reduced equations to specific examples. We find the reduced equations can be explicitly integrated to deduce the general solutions for these cases. We also extend this procedure to coupled higher order nonlinear ODEs with specific reference to second order nonlinear ODEs.Comment: Accepted for publication in J. Phys. A Math. Theor. 201

    Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer

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    Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II–IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet

    A Tale of Three Cities : OmegaCAM discovers multiple sequences in the color-magnitude diagram of the Orion Nebula Cluster

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    Reproduced with permission from Astronomy & Astrophysics, © 2017 ESO. Published by EDP Sciences.As part of the Accretion Discs in Hα\alpha with OmegaCAM (ADHOC) survey, we imaged in r, i and H-alpha a region of 12x8 square degrees around the Orion Nebula Cluster. Thanks to the high-quality photometry obtained, we discovered three well-separated pre-main sequences in the color-magnitude diagram. The populations are all concentrated towards the cluster's center. Although several explanations can be invoked to explain these sequences we are left with two competitive, but intriguing, scenarios: a population of unresolved binaries with an exotic mass ratio distribution or three populations with different ages. Independent high-resolution spectroscopy supports the presence of discrete episodes of star formation, each separated by about a million years. The stars from the two putative youngest populations rotate faster than the older ones, in agreement with the evolution of stellar rotation observed in pre-main sequence stars younger than 4 Myr in several star forming regions. Whatever the final explanation, our results prompt for a revised look at the formation mode and early evolution of stars in clusters.Peer reviewedFinal Published versio

    Vascular Endothelial Dysfunction in β-Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO

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    The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside) produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO). While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS) in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression

    Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

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    Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

    Control of star formation by supersonic turbulence

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    Understanding the formation of stars in galaxies is central to much of modern astrophysics. For several decades it has been thought that stellar birth is primarily controlled by the interplay between gravity and magnetostatic support, modulated by ambipolar diffusion. Recently, however, both observational and numerical work has begun to suggest that support by supersonic turbulence rather than magnetic fields controls star formation. In this review we outline a new theory of star formation relying on the control by turbulence. We demonstrate that although supersonic turbulence can provide global support, it nevertheless produces density enhancements that allow local collapse. Inefficient, isolated star formation is a hallmark of turbulent support, while efficient, clustered star formation occurs in its absence. The consequences of this theory are then explored for both local star formation and galactic scale star formation. (ABSTRACT ABBREVIATED)Comment: Invited review for "Reviews of Modern Physics", 87 pages including 28 figures, in pres

    Attentional capture by alcohol-related stimuli may be activated involuntarily by top-down search goals

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    Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to Incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience, and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be congruent or incongruent with the current search goal. Applying a meta-analysis, we combined the results across the three experiments and found consistent evidence of goal-driven attentional capture; whereby alcohol distractors impeded target detection when the search goal was for alcohol. By contrast, alcohol distractors did not interfere with target detection while participants were searching for a non-alcoholic category. A separate experiment revealed that the goal-driven capture effect was not found when participants held alcohol features active in memory but did not intentionally search for them. These findings suggest a strong goal-driven account of attentional capture by alcohol cues in social drinkers

    Fluorescence Dequenching Makes Haem-Free Soluble Guanylate Cyclase Detectable in Living Cells

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    In cardiovascular disease, the protective NO/sGC/cGMP signalling-pathway is impaired due to a decreased pool of NO-sensitive haem-containing sGC accompanied by a reciprocal increase in NO-insensitive haem-free sGC. However, no direct method to detect cellular haem-free sGC other than its activation by the new therapeutic class of haem mimetics, such as BAY 58-2667, is available. Here we show that fluorescence dequenching, based on the interaction of the optical active prosthetic haem group and the attached biarsenical fluorophor FlAsH can be used to detect changes in cellular sGC haem status. The partly overlap of the emission spectrum of haem and FlAsH allows energy transfer from the fluorophore to the haem which reduces the intensity of FlAsH fluorescence. Loss of the prosthetic group, e.g. by oxidative stress or by replacement with the haem mimetic BAY 58-2667, prevented the energy transfer resulting in increased fluorescence. Haem loss was corroborated by an observed decrease in NO-induced sGC activity, reduced sGC protein levels, and an increased effect of BAY 58-2667. The use of a haem-free sGC mutant and a biarsenical dye that was not quenched by haem as controls further validated that the increase in fluorescence was due to the loss of the prosthetic haem group. The present approach is based on the cellular expression of an engineered sGC variant limiting is applicability to recombinant expression systems. Nevertheless, it allows to monitor sGC's redox regulation in living cells and future enhancements might be able to extend this approach to in vivo conditions

    Seeing versus Doing: How Businesses Manage Tensions in Pursuit of Sustainability

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    Management of organizational tensions can facilitate the simultaneous advancement of economic, social, and environmental priorities. The approach is based on managers identifying and managing tensions between the three priorities, by employing one of the three strategic responses. Although recent work has provided a theoretical basis for such tension acknowledgment and management, there is a dearth of empirical studies. We interviewed 32 corporate sustainability managers across 25 forestry and wood-products organizations in Australia. Study participants were divided into two groups: (1) those considered effective at corporate sustainability and (2) a status-quo group. Contrary to current theory, our findings showed that acknowledgment of organizational tensions was widespread in the Australian forestry and wood-products industry and not limited to those managers who are effective at managing corporate sustainability. What differed was the degree to which managers did something about the perceived tensions—with the effective group more consistently acting to manage and resolve paradoxical scenarios. Our findings suggest that existing theoretical constructs of tension management may not adequately capture the individual-level complexity involved with managing tensions in practice
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