1,025 research outputs found

    Kinetic and spectroscopic characterization of the putative monooxygenase domain of human MICAL-1

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    MICALs form a conserved multidomain protein family essential for cytoskeletal rearrangements. To complement structural information available, we produced the FAD-containing monooxygenase-like domain of human MICAL-1 (MICAL-MO) in forms differing for the presence and location of a His-tag, which only influences the protein yields. The K(m) for NADPH of the NADPH oxidase reaction is sensitive to ionic strength and type of ions. The apparent k(cat) (pH 7) is limited by enzyme reduction by NADPH, which occurs without detectable intermediates, as established by anaerobic rapid reaction experiments. The sensitivity to ionic strength and type of ions and the pH dependence of the steady-state kinetic parameters extend MICAL-MO similarity with enzymes of the p-hydroxybenzoate hydroxylase class at the functional level. The reaction is also sensitive to solvent viscosity, providing a tool to monitor the conformational changes predicted to occur during turnover. Finally, it was confirmed that MICAL-MO promotes actin depolymerization, and it was shown that F-actin, but not G-actin, stimulates NADPH oxidation by increasing k(cat) and k(cat)/K(NADPH) (approximate to 15 and approximate to.200-fold, respectively) with an apparent K(m) for actin of 4.7 mu M, under conditions that stabilize F-actin. The time-course of NADPH oxidation shows substrate recycling, indicating the possible reversibility of MICAL effect

    Tunnel induced settlement damage: A case study to improve damage prediction for facades

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    The tunnel boring process introduces soil settlements. Damage to nearby building could occur if settlements become too large. A reliable damage prediction model is necessary too asses the risks of damage to tunnel induced settlements. A widely used method for damage prediction is the Limiting Tensile Strain Method (LTSM). The LTSM models a masonry building as a weightless, isotropic, linear-elastic, rectangular beam on 2 supports. Although the LTSM is an easy method to use, it has its limitations. For facades for instance the perforation of the wall, which introduces weak spots in the wall and reduces the stiffness, is neglected. In this project the applicability of the LTSM in the case of facades is studied to improve damage predictions in the case of facades. A case study is performed to examine the response of facades in the Daniel Stalpertstraat due to settlements caused by the tunnelling process of the North/Southline. This field data is used to find a calibrated 2D numerical model of the facades. The calibrated numerical model is then subjected to larger settlements to obtain the behaviour of the facades at large settlements. Using linear and nonlinear analyses of the numerical model it is evaluated how accurate and how conservative 4 damage prediction models are. The first two LTSM models were examined: the standard LTSM model with E/G=2.6 and one with E/G=12.5. Based on the findings in the linear analyses also two models based on conventional beam theory were examined for their applicability: portal frame model and Forget-Me-Not model. With linear analyses it is checked how reliable the methods are in terms of strains and deformation under the imposed settlements. With nonlinear analyses the conservativeness of each method in terms of damage is evaluated by comparing the crack with found I the numerical model to the crack width calculated with the damage prediction models. The LTSM with E/G=12.5 gives the best results according to linear numerical analyses results. The LTSM with E/G provided the same curvature and shear distortion as found din the numerical analyses, the strains were approximated with 90%. The Forget-Me-Not model shows the best results according to the nonlinear analyses results. At large settlements this model provides the same results as found in the nonlinear numerical analysis results.Structural MechanicsStructural EngineeringCivil Engineering and Geoscience

    Reassessing the Mechanisms of Acute Coronary Syndromes : The "vulnerable plaque" and superficial erosion

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    The mechanisms that underlie superficial erosion, a cause of coronary thrombosis distinct from plaque rupture, have garnered recent interest. In an era of improved control of traditional risk factors, such as LDL (low-density lipoprotein), plaque erosion may assume greater clinical importance. Plaques complicated by erosion tend to be matrix-rich, lipid-poor, and usually lack prominent macrophage collections, unlike plaques that rupture, which characteristically have thin fibrous caps, large lipid pools, and abundant foam cells. Thrombi that complicate superficial erosion seem more platelet-rich than the fibrinous clots precipitated by plaque rupture. The pathogenesis of plaque rupture probably does not pertain to superficial erosion, a process heretofore little understood mechanistically. We review here data that support a substantial shift in the mechanisms of the thrombotic complications of atherosclerosis. We further consider pathophysiologic processes recently implicated in the mechanisms of erosion. Multiple processes likely predispose plaques to superficial erosion, including experiencing disturbed flow, basement membrane breakdown, endothelial cell death, and detachment potentiated by innate immune activation mediated through pattern-recognition receptors and endothelial-to-mesenchymal transition. Monocytes/macrophages predominate in the pathogenesis of plaque rupture and consequent thrombosis, but polymorphonuclear leukocytes likely promote endothelial damage during superficial erosion. The formation of neutrophil extracellular traps probably perpetuates and propagates intimal injury and potentiates thrombosis due to superficial erosion. These considerations have profound clinical implications. Acute coronary syndromes because of erosion may not require immediate invasive therapy. Understanding the biological bases of erosion points to novel therapies for acute coronary syndrome caused by erosion. Future research should probe further the mechanisms of superficial erosion, and develop point-of-care tests to distinguish acute coronary syndromes provoked by erosion versus rupture that may direct more precision management. Future clinical investigations should evaluate intervening on the targets that have emerged from experimental studies and the management strategies that they inform

    The Tyre As Sensor To Estimate Friction

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    Mechanical Maritime and Materials Engineerin

    Analysis of the structural design process of the adaptive reuse of building structures

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    In the field of structural building engineering there is a market shift taking place as a result of the growing number of buildings that are listed as cultural heritage, secularization, the economic situation and the increasing office vacancy rate in Europe and the US. More and more structural engineering firms that were designing and constructing new buildings now move to maintenance and adaptive reuse of existing building structures. But how does this shift influence the way in which engineering firms work? What is the influence of adaptive reuse of existing building structures on the structural design process? Unlike fields like architecture and especially industrial design that have a strong design tradition, in structural engineering until now engineering design has been regarded more as a craft that has to be learned in practice than as science. As a result of this, arguments to answer those questions are hard to find in literature (with a few notable but little cited exceptions such as the paper How designs develop by S.J. Macpherson c.s.[2]). To fill this gap an analysis has been made of the way in which the design process of adaptive reuse projects is supposed to work according to literature and professional associations, and of the way it really works in practice. Grounded theory method is used to generate concepts to explain the way structural designers work in such projects. Preliminary results show that standard descriptions of the engineering design process (generally from abstract to detail as for instance suggested in The Architect’s Handbook by J.A. Demkin c.s.[3]) do not correctly describe the way in which this design process really works. Not only did the redesign process of existing building structures not work as expected by both clients and practitioners; even the structural design process of new building projects can be seen in a different light. It is expected that the results of this research eventually might lead to different contracts between clients and engineering firms in the future.Structural EngineeringCivil Engineering and Geoscience

    Analysis of drainage system in Georgetown, Guyana

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    In 2015 Georgetown, Guyana suffered from major flooding due to heavy rainfall. The use of a centuries-old agricultural drainage system for the urban drainage of the largest urbanized area of Guyana, poses problems considering flood safety. In 2016 a report was published by a ‘Dutch Risk Reduction Team’ (DRR Team) with recommendations on how to reduce the current flood vulnerability. Based on the recommendations from this DRR report. A team of seven students from the Delft University of Technology, the Netherlands, went to Georgetown and analysed the drainage system in more detail. Several methods were developed in collaboration with local students and experts which can be used to analyse the system. This was done to increase the local capability of knowledge-based decision making on drainage issues in Guyana. This student’s induced project comprises three elements of the urban drainage system: the primary drainage channels, the local (secondary and tertiary) drainage canals, and the outlet structures. The work focussed primarily on the catchment area named South-Ruimveldt.Civil Engineering and GeosciencesHydraulic Engineering / Structural EngineeringMaster project repor

    Supplemental Material, 20171119_Supl_fig_2 - Hematological Parameters Outperform Plasma Markers in Predicting Long-Term Mortality After Coronary Angiography

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    Supplemental Material, 20171119_Supl_fig_2 for Hematological Parameters Outperform Plasma Markers in Predicting Long-Term Mortality After Coronary Angiography by Crystel M. Gijsberts, Hester M. den Ruijter, Dominique P. V. de Kleijn, Albert Huisman, Maarten ten Berg, Mark de Groot, Richard H. A. van Wijk, Folkert W. Asselbergs, Michiel Voskuil, Gerard Pasterkamp, Wouter W. van Solinge, and Imo E. Hoefer in Angiology</p

    Three-dimensional numerical analysis of tunnelling induced damage: The influence of masonry building geometry and location

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    Recent tunnelling projects have received a great amount of media attention due to settlement induced damage. Due to the simplified approach of existing risk assessment methods, a new assessment system is in development, which can account for three-dimensional structural aspects of buildings. The aim of this study is to investigate the influence of the position and geometry of masonry buildings on the development of damage, while undergoing tunnelling induced settlements. In line with previous research, three-dimensional finite element analyses are used as a tool to perform a parametric study. A parametric study consists of an evaluation of the parameters position, aspect-ratio, grouping and orientation. The position parameter is divided into three characteristics: the sagging zone, a combined settlement profile and the hogging zone. The aspect-ratio parameter is also divided into three characteristics: shallow buildings, square buildings and deep buildings. The grouping effect parameter also distinguishes three characteristics: small and large isolated buildings and grouped buildings. The orientation parameter includes seven different increasing angles of the building main axis with respect to the tunnelling axis. The maximum measured crack width in the buildings gives input for a classification of damage, according the system of Burland et al. (1977). An average trend in the damage classification indicates the sensitivity to tunnelling induced settlements of the parameters. Both during and after tunnelling, a position of the building in the combined settlement profile appears to be the most sensitive to differential settlements. Buildings far away from the tunnelling axis generally obtain no more than slight damage. Structures with a low aspect-ratio seem on average to obtain equal amounts of damage as buildings with an aspect-ratio of 1. Structures with a higher aspect-ratio are less affected, both during and after tunnelling. Grouping of the buildings seems to be an influential parameter. Small isolated buildings obtain far less damage than large or grouped buildings. In relation to the numerical analyses, the empirical Limiting Tensile Strain Method (LTSM) seems to overestimate the damage for an isolated small building, but underestimate the damage in large or grouped buildings. For buildings in the sagging zone, a building with a low orientation angle is the least sensitive to differential settlement, while the maximum measured crack width increases by increasing the angle. The difference in maximum crack width can grow to a factor 3. A building in the combined settlement profile or in the hogging zone displays opposite behaviour. Cases with low orientation angles are the most susceptible to damage, while increasing the angle to 90 degrees lowers the maximum measured crack width. The difference in results can grow up to a factor 2.Structural MechanicsStructural EngineeringCivil Engineering and Geoscience

    Tissue engineering

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    Tissue engineering is the process of manipulating cellular and/or scaffold material, biological or synthetic, in order to produce tissue analogs, either in vivo or in vitro. It is also one of the most dynamic fields within the domains of biotechnology and medicine. Tissue engineering is all pervasive; attempts have been made to tissue engineer almost every organ, from the bladder to bone, and from the heart to cartilage. In this review, recent efforts to tissue engineer structures of the cardiovascular system - vascular grafts, cardiac valves, and myocardium - will be explored
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