942 research outputs found

    The influence of substrate temperature on growth of para-sexiphenyl thin films on Ir{111} supported graphene studied by LEEM

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    The growth of para-sexiphenyl (6P) thin films as a function of substrate temperature on Ir{111} supported graphene flakes has been studied in real-time with Low Energy Electron Microscopy (LEEM). Micro Low Energy Electron Diffraction (\mu LEED) has been used to determine the structure of the different 6P features formed on the surface. We observe the nucleation and growth of a wetting layer consisting of lying molecules in the initial stages of growth. Graphene defects -- wrinkles -- are found to be preferential sites for the nucleation of the wetting layer and of the 6P needles that grow on top of the wetting layer in the later stages of deposition. The molecular structure of the wetting layer and needles is found to be similar. As a result, only a limited number of growth directions are observed for the needles. In contrast, on the bare Ir{111} surface 6P molecules assume an upright orientation. The formation of ramified islands is observed on the bare Ir{111} surface at 320 K and 352 K, whereas at 405 K the formation of a continuous layer of upright standing molecules growing in a step flow like manner is observed.Comment: 9 pages, 7 figures, Revised Version as accepted for publication in Surface Scienc

    Parametric study of modelling structural timber in fire with different software packages

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    In a bid to accurately model structural behaviour of timber buildings in fire, a number of obstacles have been identified which must be fully understood before advanced computer modelling can accurately be used to represent physical behaviour. This paper discusses the obstacles, with suggestions on how to mitigate them, incorporating the challenges of using general purpose finite element software. The paper examines modelling with ANSYS, SAFIR and ABAQUS and the individual and collective challenges related to thermal analyses of timber structures in fire conditions. It considers the effects various model parameters (thermal and structural) may have on physical interpretation of experimental data in comparison with the accuracy of numerical solutions. In detail, the study looks at the effects of 1D and 2D heat transfer analyses, finite element mesh sizes, time steps and different thermal property approaches on thermal models of timber members in fires. It further recommends how best to model these structures using the different finite element software packages

    Clinical applications of population pharmacokinetic models of antibiotics: Challenges and perspectives

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    Because of increasing antimicrobial resistance and the shortage of new antibiotics, there is a growing need to optimize the use of old and new antibiotics. Modelling of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of antibiotics can support the optimization of dosing regimens. Antimicrobial efficacy is determined by susceptibility of the drug to the microorganism and exposure to the drug, which relies on the PK and the dose. Population PK models describe relationships between patients characteristics and drug exposure. This article highlights three clinical applications of these models applied to antibiotics: 1) dosing evaluation of old antibiotics, 2) setting clinical breakpoints and 3) dosing individualization using therapeutic drug monitoring (TDM). For each clinical application, challenges regarding interpretation are discussed. An important challenge is to improve the understanding of the interpretation of modelling results for good implementation of the dosing recommendations, clinical breakpoints and TDM advices. Therefore, also background information on PK/PD principles and approaches to analyse PK/PD data are provided

    Onderzoek beschikbaarheid glasaal bij RWZI's t.b.v. herstel aalstand en uitzet binnenvisserij

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    Uit een literatuurstudie blijkt dat het zeer aannemelijk is dat RWZI-effluent een aantrekkende werking heeft op glasaal. In de maanden april en mei 2013 heeft Visserij Service Nederland bij vier lozingspunten van effluent van rioolwaterzuiveringen verspreid door Nederland onderzoeken uitgevoerd naar de aanwezigheid en vangbaarheid van glasaal. De doelstelling van het project is het ontwikkelen van een methode voor het economisch rendabel vangen van glasaal bij RWZI's, wat ten goede komt aan het herstel van de aalstand en de visserij in de Nederlandse binnenwateren

    Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention or after acute coronary syndrome

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    To prevent recurrent ischaemic events, dual antiplatelet therapy (DAPT) is the standard of care after percutaneous coronary intervention and in the treatment of acute coronary syndrome. Recent evidence supports an adjusted DAPT duration in selected patients. The current paper aims to encourage cardiologists to actively search for patients benefiting from either shorter or prolonged duration DAPT and proposes an algorithm to identify patients who are likely to benefit from such an alternative strategy. Individualised DAPT duration should be considered in high-risk anatomic and/or clinical subgroups or in patients at increased haemorrhagic risk with low ischaemic risk. Both thrombotic and haemorrhagic risk should be assessed in all patients. In patients undergoing percutaneous coronary intervention, the interventional cardiologist could advise on the minimal duration of DAPT. However, in contrast to the minimum duration of DAPT for stent thrombosis prevention, longer duration DAPT is aimed at prevention of spontaneous myocardial infarction, and not at stent thrombos

    Shortlist Masterplan Wind. Effect of pilling noise on the survival of fish larvae( pilot study) progress report

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    Fish can suffer lethal damage to swimming bladder or other organs due to extreme loud impulse sounds caused by e.g. pile driving (Popper & Hastings 2009). Juvenile and adult fish can actively swim away from a sound source, but planktonic larvae are not able to do this. As a result, fish larvae may suffer more from underwater noise than the older life stages. Despite the many indications for adverse effects, detailed information on the effect of different sound levels on fish is still scarce, especially for the early life stages. Within the framework of the Appropriate Assessment of Dutch offshore wind farms, the effect of piling noise on the southern North Sea population of herring, sole, and plaice larvae was simulated (Prins et al. 2009). For this, an existing larval transport model (Bolle et al. 2005, 2009, Dickey-Collas et al. 2009, Erftemeijer et al. 2009) was expanded with crude assumptions on larval mortality caused by pile driving. The model results were extrapolated to other fish species and older life stages, based on “expertjudgment", in an attempt to assess the effect of offshore piling on the prey availability for birds and marine mammals in Natura 2000 areas (Bos et al. 2009). This assessment involved a large number of uncertainties. The first and most important uncertainty was the range around a piling site in which larval mortality occurs. It was assumed that 100% mortality occurs up to a distance of 1 km from the piling site. However, little is known about larval mortality rates in relation to the level of exposure to piling noise. In general, there is an urgent need to obtain more knowledge on the effect of sound on fish (survival, distribution, and behaviour) during different life stages. More particularly, in view of the rapid extension of offshore wind farms, there is an urgent need to fill the knowledge gap on lethal effects of loud impulse noises caused by pile driving. The broader aim of the current project is to examine the effect of piling noise on the survival of fish larvae. However, within the limited resources and time frame of the Shortlist research programme it is not possible to carry out field experiments, nor is it possible to execute elaborate series of experiments. The first goal within the Shortlist programme is to examine the feasibility of laboratory experiments with pile driving noise and fish larvae. The second goal is to use the laboratory set-up in a pilot study aiming at determining the threshold at which mortality of fish larvae occurs. This shortlist study is limited to laboratory experiments, lethal effects, larvae of 1 species (sole, Solea solea) and 3 series of experiments (trials). The study consists of exposure-effect experiments only; the effects of pile driving at the population level will not be modelled, nor will the results be extrapolated to other species or life stages. The progress to date has been documented in a series of memo’s. These memos are included in this report as Appendices and are summarised in the sections of the report

    Disruption of a structurally important extracellular element in the Glycine Receptor leads to decreased synaptic integration and signaling resulting in Severe Startle Disease

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    Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorders. We found that a lack of synaptic integration of GlyRs, together with disrupted receptor function, is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation, Q177K, located in the extracellular β8–β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8–β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in Cys-loop receptors. We identified the underlying neuropathological mechanisms in male and female shaky mice through a combination of protein biochemistry, immunocytochemistry, and both in vivo and in vitro electrophysiology. Increased expression of the mutant GlyR α1Q177K subunit in vivo was not sufficient to compensate for a decrease in synaptic integration of α1Q177Kβ GlyRs. The remaining synaptic heteromeric α1Q177Kβ GlyRs had decreased current amplitudes with significantly faster decay times. This functional disruption reveals an important role for the GlyR α1 subunit β8–β9 loop in initiating rearrangements within the extracellular–transmembrane GlyR interface and that this structural element is vital for inhibitory GlyR function, signaling, and synaptic clustering
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