113 research outputs found

    Закономерности изменения физико-механических свойств сплава Zr-1%Nb при комплексном ионно-плазменном модифицировании поверхности и наводороживании

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    В работе были изучены особенности изменения морфологии, структуры и физико-механических свойств циркониевого сплава Zr-1%Nb, подвергнутого комплексному ионно-плазменному модифицированию поверхности методами плазменно-иммерсионной ионной имплантации титана и осаждения покрытий нитрида титана. Показана высокая эффективность защиты сформированных структур от проникновения водорода в циркониевый сплав. Изучены механизмы сорбции и захвата водорода в титансодержащем модифицированном слое.In the present work, the features of the change in the morphology, structure, and physico-mechanical properties of zirconium alloy Zr-1%Nb subjected to complex ion-plasma surface modification by the methods of plasma-immersion titanium ion implantation and deposition of titanium nitride coatings were studied. The high protective properties of the formed structures against hydrogen permeation into the zirconium alloy is shown. Mechanisms of sorption and capture of hydrogen in a titanium-doped modified layer are studied

    Accurate and Fast Simulation of Channel Noise in Conductance-Based Model Neurons by Diffusion Approximation

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    Stochastic channel gating is the major source of intrinsic neuronal noise whose functional consequences at the microcircuit- and network-levels have been only partly explored. A systematic study of this channel noise in large ensembles of biophysically detailed model neurons calls for the availability of fast numerical methods. In fact, exact techniques employ the microscopic simulation of the random opening and closing of individual ion channels, usually based on Markov models, whose computational loads are prohibitive for next generation massive computer models of the brain. In this work, we operatively define a procedure for translating any Markov model describing voltage- or ligand-gated membrane ion-conductances into an effective stochastic version, whose computer simulation is efficient, without compromising accuracy. Our approximation is based on an improved Langevin-like approach, which employs stochastic differential equations and no Montecarlo methods. As opposed to an earlier proposal recently debated in the literature, our approximation reproduces accurately the statistical properties of the exact microscopic simulations, under a variety of conditions, from spontaneous to evoked response features. In addition, our method is not restricted to the Hodgkin-Huxley sodium and potassium currents and is general for a variety of voltage- and ligand-gated ion currents. As a by-product, the analysis of the properties emerging in exact Markov schemes by standard probability calculus enables us for the first time to analytically identify the sources of inaccuracy of the previous proposal, while providing solid ground for its modification and improvement we present here

    Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study

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    BACKGROUND: Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. METHODS: We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. RESULTS: In our patients EPCs were related only to age (r=0.154; p=0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p=0.03) and patient age (p=0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p=0.02). CONCLUSIONS: We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population

    Autoimmunity in CD73/Ecto-5′-Nucleotidase Deficient Mice Induces Renal Injury

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    Extracellular adenosine formed by 5′-ectonucleotidase (CD73) is involved in tubulo-glomerular feedback in the kidney but is also known to be an important immune modulator. Since CD73−/−mutant mice exhibit a vascular proinflammatory phenotype, we asked whether long term lack of CD73 causes inflammation related kidney pathologies. CD73−/−mice (13 weeks old) showed significantly increased low molecule proteinuria compared to C57BL6 wild type controls (4.8≥0.52 vs. 2.9±0.54 mg/24 h, p<0.03). Total proteinuria increased to 5.97±0.78 vs. 2.55±0.35 mg/24 h at 30 weeks (p<0.01) whereas creatinine clearance decreased (0.161±0.02 vs. 0.224±0.02 ml/min). We observed autoimmune inflammation in CD73−/−mice with glomerulitis and peritubular capillaritis, showing glomerular deposition of IgG and C3 and enhanced presence of CD11b, CD8, CD25 as well as GR-1-positive cells in the interstitium. Vascular inflammation was associated with enhanced serum levels of the cytokines IL-18 and TNF-α as well as VEGF and the chemokine MIP-2 (CXCL-2) in CD73−/−mice, whereas chemokines and cytokines in the kidney tissue were unaltered or reduced. In CD73−/−mice glomeruli, we found a reduced number of podocytes and endothelial fenestrations, increased capillaries per glomeruli, endotheliosis and enhanced tubular fibrosis. Our results show that adult CD73−/−mice exhibit spontaneous proteinuria and renal functional deterioration even without exogenous stress factors. We have identified an autoimmune inflammatory phenotype comprising the glomerular endothelium, leading to glomeruli inflammation and injury and to a cellular infiltrate of the renal interstitium. Thus, long term lack of CD73 reduced renal function and is associated with autoimmune inflammation

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Repurposing of approved cardiovascular drugs

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    Different Neighbourhoods via Ideals on Graphs

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    In this paper, we generate different approximations for j is an element of{r,l,,,u,i,, by using the concept of ideal, N(j-)neighbourhoods and P-j-neighbourhoods from vertices of a graph. Then, we compare these approximations with the previous one, and we see that these approximations are more accurate. Finally, we show that our approach is better with a real-life problem from the field of chemistry by using these new approximations

    Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease

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