1,466 research outputs found

    Chronic lung diseases:entangled in extracellular matrix

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    The extracellular matrix (ECM) is the scaffold that provides structure and support to all organs, including the lung; however, it is also much more than this. The ECM provides biochemical and biomechanical cues to cells that reside or transit through this micro-environment, instructing their responses. The ECM structure and composition changes in chronic lung diseases; how such changes impact disease pathogenesis is not as well understood. Cells bind to the ECM through surface receptors, of which the integrin family is one of the most widely recognised. The signals that cells receive from the ECM regulate their attachment, proliferation, differentiation, inflammatory secretory profile and survival. There is extensive evidence documenting changes in the composition and amount of ECM in diseased lung tissues. However, changes in the topographical arrangement, organisation of the structural fibres and stiffness (or viscoelasticity) of the matrix in which cells are embedded have an undervalued but strong impact on cell phenotype. The ECM in diseased lungs also changes in physical and biomechanical ways that drive cellular responses. The characteristics of these environments alter cell behaviour and potentially orchestrate perpetuation of lung diseases. Future therapies should target ECM remodelling as much as the underlying culprit cells

    Behaviour of heavy metals in soils

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    Fractions of Zn, Cd, Cu, Pb, Fe and Mn extractable with water, a salt solution and dilute acid, and residual fractions were determined in soils with raised contents of heavy metals, near zinc smelters, along a river formerly discharging heavy metals, and in a sewage farm. Special attention was paid to the role of oxides of Fe and Mn in the binding of other heavy metals.The theory of regular solid solutions was applied to exchange adsorption of ions in soil and some approximative equations of practical interest were derived. The possible role. of hydrolysis and the adsorption of hydrolysis products was studied. Ion exchange in soil was described in terms of sites of high and low selectivity (two-site model) giving rise to a decreasing free enthalpy of adsorption with increasing surface coverage (Freundlich behaviour).Cation-exchange experiments with Ca 2+, Zn 2+, Cd 2+, Cu 2+and Pb 2+on Winsum clay soil showed that heavy metals were subject to regular and selective (specific) exchange adsorption, and to superequivalent adsorption. A pronounced lowering of pH upon adsorption of heavy metals was assumed to be by desorption of weakly acidic protons or selective adsorption of hydrolysis products, in combination with a diminished acid-neutralizing capacity. Results may be of interest for environmental control of heavy metals

    Бароосмотичний аналіз як новий метод гідрогеологічних досліджень

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    Запропоновано методику бароосмотичного аналiзу гiдрогеологiчних даних для окремих свердловин, за якою визначаються величина бароосмотичного напору H2O у пластових (порових) водах i ступiнь вiдхилення їх вiд стану бароосмотичної рiвноваги на кiлькох водоносних горизонтах. Результати аналiзу для чотирьох свердловин з рiзних регiонiв пiдтвердили iснування вертикальних бароосмотичних потокiв у глинистих товщах усiх розрiзiв i дали змогу визначити напрями цих потокiв та виявити зони впливу особливих локальних гiдрогеологiчних процесiв.Methods of baroosmotic analysis of hydrogeological data for separate boreholes have been proposed. They can be applied to determine the baroosmotic pressure of H2O in formational (porous) waters and the degree of their defection from the state of baroosmotic balance at several water-bearing horizons. The results of analysis conducted at 4 boreholes from different regions have confirmed the existence of vertical baroosmotic flows in clayey units of all sections and have allowed us to determine the directions of these flows and to reveal the zones affected by specific local hydrogeological processes

    An in vitro model of fibrosis using crosslinked native extracellular matrix-derived hydrogels to modulate biomechanics without changing composition

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    Extracellular matrix (ECM) is a dynamic network of proteins, proteoglycans and glycosaminoglycans, providing structure to the tissue and biochemical and biomechanical instructions to the resident cells. In fibrosis, the composition and the organization of the ECM are altered, and these changes influence cellular behaviour. Biochemical (i. e. protein composition) and biomechanical changes in ECM take place simultaneously in vivo. Investigating these changes individually in vitro to examine their (patho)physiological effects has been difficult. In this study, we generated an in vitro model to reflect the altered mechanics of a fibrotic microenvironment through applying fibre crosslinking via ruthenium/sodium persulfate crosslinking on native lung ECM-derived hydrogels. Crosslinking of the hydrogels without changing the biochemical composition of the ECM resulted in increased stiffness and decreased viscoelastic stress relaxation. The altered stress relaxation behaviour was explained using a generalized Maxwell model. Fibre analysis of the hydrogels showed that crosslinked hydrogels had a higher percentage of matrix with a high density and a shorter average fibre length. Fibroblasts seeded on ruthenium-crosslinked lung ECM-derived hydrogels showed myofibroblastic differentiation with a loss of spindle-like morphology together with greater α-smooth muscle actin (α-SMA) expression, increased nuclear area and circularity without any decrease in the viability, compared with the fibroblasts seeded on the native lung-derived ECM hydrogels. In summary, ruthenium crosslinking of native ECM-derived hydrogels provides an exciting opportunity to alter the biomechanical properties of the ECM-derived hydrogels while maintaining the protein composition of the ECM to study the influence of mechanics during fibrotic lung diseases. STATEMENT OF SIGNIFICANCE: Fibrotic lung disease is characterized by changes in composition and excessive deposition of extracellular matrix (ECM). ECM fibre structure also changes due to crosslinking, which results in mechanical changes. Separating the changes in composition and mechanical properties has been difficult to date. In this study, we developed an in vitro model that allows alteration of the mechanical changes alone by applying fibre crosslinking in native lung ECM-derived hydrogels. Characterisations of the crosslinked hydrogels indicated the model mimicked mechanical properties of fibrotic lung tissue and reflected altered fibre organisation. This ECM-based fibrosis model provides a method to preserve the native protein composition while altering the mechanical properties providing an important tool not only for lung but also other organ fibrosis

    Enabling Personalized Composition and Adaptive Provisioning of Web Services

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    The proliferation of interconnected computing devices is fostering the emergence of environments where Web services made available to mobile users are a commodity. Unfortunately, inherent limitations of mobile devices still hinder the seamless access to Web services, and their use in supporting complex user activities. In this paper, we describe the design and implementation of a distributed, adaptive, and context-aware framework for personalized service composition and provisioning adapted to mobile users. Users specify their preferences by annotating existing process templates, leading to personalized service-based processes. To cater for the possibility of low bandwidth communication channels and frequent disconnections, an execution model is proposed whereby the responsibility of orchestrating personalized processes is spread across the participating services and user agents. In addition, the execution model is adaptive in the sense that the runtime environment is able to detect exceptions and react to them according to a set of rules
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