183 research outputs found

    Molecular Dynamics Simulation of Polymer-Metal Bonds

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    Molecular simulation is becoming a very powerful tool for studying dynamic phenomena in materials. The simulation yields information about interaction at length and time scales unattainable by experimental measurements and unpredictable by continuum theories. This is especially meaningful when referring to bonding between a polymer and a metal substrate. A very important characteristic of polymers is that their physical properties do not rely on the detailed chemical structure of the molecular chains but only on their flexibility, and accordingly they will be able to adopt different conformations. In this paper, a molecular simulation of the bonding between vinyl ester polymer and steel is presented. Four different polymers with increasing chain lengths have been studied. Atomic co-ordinates are adjusted in order to reduce the molecular energy. Conformational changes in the macromolecules have been followed to obtain the polymer pair correlation function. Radius of gyration and end-to-end distance distributions of the individual chains have been used as a quantitative measurement of their flexibility. There exists a correlation between flexibility of the molecular chains and the energy of adhesion between the polymer and the metal substrate. Close contacts between the two materials are established at certain points but every atom up to a certain distance from the interface contributes to the total value of the adhesion energy of the system

    Ontwikkeling van methoden voor het monitoren van voetzoollaesies bij vleeskuikens = Development of methods to monitor foot pad lesions in broiler chickens

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    This report describes different methods for classification and monitoring foot pad dermatitis in broiler chickens, including an automatic system using video imaging

    Shallow rainwater lenses in deltaic areas with saline seepage

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    In deltaic areas with saline seepage, freshwater availability is often limited to shallow rainwater lenses lying on top of saline groundwater. Here we describe the characteristics and spatial variability of such lenses in areas with saline seepage and the mechanisms that control their occurrence and size. Our findings are based on different types of field measurements and detailed numerical groundwater models applied in the south-western delta of the Netherlands. By combining the applied techniques we could extrapolate measurements at point scale (groundwater sampling, temperature and electrical soil conductivity (TEC)-probe measurements, electrical cone penetration tests (ECPT)) to field scale (continuous vertical electrical soundings (CVES), electromagnetic survey with EM31), and even to regional scale using helicopter-borne electromagnetic measurements (HEM). The measurements show a gradual mixing zone between infiltrating fresh rainwater and upward flowing saline groundwater. The mixing zone is best characterized by the depth of the centre of the mixing zone <i>D</i><sub>mix</sub>, where the salinity is half that of seepage water, and the bottom of the mixing zone <i>B</i><sub>mix</sub>, with a salinity equal to that of the seepage water (Cl-conc. 10 to 16 g l<sup>−1</sup>). <i>D</i><sub>mix</sub> is found at very shallow depth in the confining top layer, on average at 1.7 m below ground level (b.g.l.), while <i>B</i><sub>mix</sub> lies about 2.5 m b.g.l. The model results show that the constantly alternating upward and downward flow at low velocities in the confining layer is the main mechanism of mixing between rainwater and saline seepage and determines the position and extent of the mixing zone (<i>D</i><sub>mix</sub> and <i>B</i><sub>mix</sub>). Recharge, seepage flux, and drainage depth are the controlling factors

    A conserved role for LRRK2 and Roco proteins in the regulation of mitochondrial activity

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    Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in the multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are the most frequent cause of hereditary PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. Isolated mitochondria of tissue samples from PD patients carrying LRRK2 mutations display a significant impairment of mitochondrial function. However, due to the complexity of the mitochondrial signaling network, the role of LRRK2 in mitochondrial metabolism is still not well understood. Previously we have shown that D. discoideum Roco4 is a suitable model to study the activation mechanism of LRRK2 in vivo. To get more insight in the LRRK2 pathways regulating mitochondrial activity we used this Roco4 model system in combination with murine RAW macrophages. Here we show that both Dictyostelium roco4 knockout and cells expressing PD-mutants show behavioral and developmental phenotypes that are characteristic for mitochondrial impairment. Mitochondrial activity measured by Seahorse technology revealed that the basal respiration of D. discoideum roco4- cells is significantly increased compared to the WT strain, while the basal and maximal respiration values of cells overexpressing Roco4 are reduced compared to the WT strain. Consistently, LRRK2 KO RAW 264.7 cells exhibit higher maximal mitochondrial respiration activity compared to the LRRK2 parental RAW264.7 cells. Measurement on isolated mitochondria from LRRK2 KO and parental RAW 264.7 cells revealed no difference in activity compared to the parental cells. Furthermore, neither D. discoideum roco4- nor LRRK2 KO RAW 264.7 showed a difference in either the number or the morphology of mitochondria compared to their respective parental strains. This suggests that the observed effects on the mitochondrial respiratory in cells are indirect and that LRRK2/Roco proteins most likely require other cytosolic cofactors to elicit mitochondrial effects

    Parmodulins Inhibit Thrombus Formation Without Inducing Endothelial Injury Caused by Vorapaxar

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    Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet activation during myocardial infarction and to endothelial inflammation during sepsis. This receptor demonstrates marked signaling bias. Its activation by thrombin stimulates prothrombotic and proinflammatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is to inhibit detrimental signaling while sparing beneficial pathways. We now characterize a novel class of structurally unrelated small-molecule PAR1 antagonists, termed parmodulins, and compare the activity of these compounds to previously characterized compounds that act at the PAR1 ligand–binding site. We find that parmodulins target the cytoplasmic face of PAR1 without modifying the ligand-binding site, blocking signaling through Gαq but not Gα13 in vitro and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic and proinflammatory signaling without blocking APC-mediated pathways or inducing endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier dysfunction and apoptosis. These studies demonstrate how functionally selective antagonism can be achieved by targeting the cytoplasmic face of a G-protein–coupled receptor to selectively block pathologic signaling while preserving cytoprotective pathways

    Healthcare practitioners' views and experiences of barriers and facilitators to weight management interventions for adults with intellectual disabilities

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    Background Obesity is common in adults with intellectual disabilities, yet little is known about how weight management interventions are provided for this population. Methods Semi‐structured interviews were held with 14 healthcare practitioners involved in weight management interventions in an English county. A study topic guide was developed to elicit practitioners' views and experiences of barriers and facilitators to weight management for adults with intellectual disabilities. Responses were analysed using thematic analysis. Results Several barriers are involved in weight management for people with intellectual disabilities including communication challenges, general practitioners' lack of knowledge and awareness of weight management services, inconsistencies in caring support, resource constraints, wider external circumstances surrounding the individuals and motivational issues. Facilitators include reasonable adjustments to existing weight management services. However, there is a need for specialist weight management provision for people with intellectual disabilities. Conclusions This study provides suggestions for future research, policy and practice consideration
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