1,111 research outputs found
Axon guidance receptors: Endocytosis, trafficking and downstream signaling from endosomes
During the development of the nervous system, axons extend through complex environments. Growth cones at the axon tip allow axons to find and innervate their appropriate targets and form functional synapses. Axon pathfinding requires axons to respond to guidance signals and these cues need to be detected by specialized receptors followed by intracellular signal integration and translation. Several downstream signaling pathways have been identified for axon guidance receptors and it has become evident that these pathways are often initiated from intracellular vesicles called endosomes. Endosomes allow receptors to traffic intracellularly, re-locating receptors from one cellular region to another. The localization of axon guidance receptors to endosomal compartments is crucial for their function, signaling output and expression levels. For example, active receptors within endosomes can recruit downstream proteins to the endosomal membrane and facilitate signaling. Also, endosomal trafficking can re-locate receptors back to the plasma membrane to allow re-activation or mediate downregulation of receptor signaling via degradation. Accumulating evidence suggests that axon guidance receptors do not follow a pre-set default trafficking route but may change their localization within endosomes. This re-routing appears to be spatially and temporally regulated, either by expression of adaptor proteins or co-receptors. These findings shed light on how signaling in axon guidance is regulated and diversified - a mechanism which explains how a limited set of guidance cues can help to establish billions of neuronal connections. In this review, we summarize and discuss our current knowledge of axon guidance receptor trafficking and provide directions for future research
Neuronal Subset-Specific Migration and Axonal Wiring Mechanisms in the Developing Midbrain Dopamine System
The midbrain dopamine (mDA) system is involved in the control of cognitive and motor behaviors, and is associated with several psychiatric and neurodegenerative diseases. mDA neurons receive diverse afferent inputs and establish efferent connections with many brain areas. Recent studies have unveiled a high level of molecular and cellular heterogeneity within the mDA system with specific subsets of mDA neurons displaying select molecular profiles and connectivity patterns. During mDA neuron development, molecular differences between mDA neuron subsets allow the establishment of subset-specific afferent and efferent connections and functional roles. In this review, we summarize and discuss recent work defining novel mDA neuron subsets based on specific molecular signatures. Then, molecular cues are highlighted that control mDA neuron migration during embryonic development and that facilitate the formation of selective patterns of efferent connections. The review focuses largely on studies that show differences in these mechanisms between different subsets of mDA neurons and for which in vivo data is available, and is concluded by a section that discusses open questions and provides directions for further research
A Parametric Structural Design Tool (Grasshopper Interface) for Plate Structures
The thesis presents a parametric design tool for plate structural analysis. The goal of the thesis is to establish a real-time visualized program for structural calculation and to make it parameterized. The tool is based on a visualized drawing program Rhino with Grasshopper plug-in to generate the parametric environment for the plate structural analysis. The solution of plate analysis is computed by membrane analogy. Followed by rain-flow analysis, the relation between shear force flows and the structural geometry is presented. Two computational programs will be introduced. One is out-of-plane tool; the other is for in-plane calculation.Structural and Building EngineeringStructural EngineeringCivil Engineering and Geoscience
Analysis of drainage system in Georgetown, Guyana
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
Kinetic and spectroscopic characterization of the putative monooxygenase domain of human MICAL-1
Analysis of the structural design process of the adaptive reuse of building structures
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
Blast-resistant building design: Methods and solutions for the blast-resistant design of buildings subjected to an LPG tank truck explosion
Because of the wish for, and the necessity of the multiple use of space the amount of tunnels and buildings in close proximity of roads are increasing. Meanwhile the number of transports of dangerous goods is also increasing. Therefore it would be desirable to have a highway network which is fully accessible for the transport of dangerous goods. In order to make this possible the effect of an incident with dangerous goods on the buildings along the road should be known. This study focuses on the effect of an explosion blast on a building. It aims to propose a method to determine this effect, and to propose several structural solutions for buildings, situated alongside the road, to make them more resistant against the blast load from an explosion on the road as a result of an incident with an LPG tank truck. Of all the possible situations on the Dutch highway network some are discussed and three are chosen to study the effect of an explosion. These situations are: in the tunnel, at the tunnel mouth and on the open road with buildings beside the road. Of all types of explosions and effects that can occur, this study only focuses on the effect of a blast wave on a building as a result of a BLEVE of an LPG tank truck of 50 m3. A BLEVE is a Boiling Liquid Expanding Vapour Explosion. The to liquid compressed gas will evaporate explosively when the vessel ruptures, which results in a blast wave. The overpressure at the building can be schematised by in instant increase of the pressure to the peak overpressure, after which it decreases linearly to zero after a certain positive phase duration. The impulse is the surface under the pressure-time curve. An explosion in a tunnel results in the building-up of pressure. To determine how the overpressure exits the tunnel and reaches the building, an estimation of the increase of volume and the wave front surface is made. For an explosion in the open field five different methods are discussed. These range from a TNT equivalence method to a gas-dynamic modelling. The calculated values for the overpressure differ a lot and not all methods give a value for the impulse. Based on the described methods it is concluded that an explosion on the open road gives a larger blast load on the building than an explosion in the tunnel or the tunnel mouth. The blast-wave of an explosion of an LPG tank truck can cause damage to the buildings. Several aspects of the blast-wave are discussed, and how they determine the load that is transferred to the main load bearing structure. These aspects are among others the reflection, dynamic blast load, adjacent buildings, distribution of the blast load on the façade of a building, and glass failure. For several of these aspects methods are given to determine the load on the building. The peak reflected overpressure on a defined model building of 35 m high is 101 kPa and the impulse is 1,97 kPa*s. After this the mechanical properties of a building as a whole and of the building elements that determine its response to this load are determined. These are the static strength, natural frequency and ductility. After the loading, all the response aspects and the structural properties are determined and an estimation of the damage to the building and its elements is given with methods that calculate the chance of collapse, the equivalent static load and the required ductility. From sensitivity analyses of the damage methods it is concluded that it is possible to make a building able to withstand the blast from an LPG explosion by choosing the right parameters. The most sensitive parameters of the blast load and the mechanical properties of the building are the tank volume, the distance to the explosion, the horizontal design load and the height of the building. A higher building results in a larger design load and a smaller angular rotationDesign and ConstructionCivil Engineering and Geoscience
Usage of Lifts for the Evacuation of High-Rise Projects: An International Discussion from a Dutch Perspective
The concept of using lifts for evacuation purposes in buildings is a major point of international discussion in the field of fire safety engineering. While building heights in the Netherlands are increasing, the population is ageing and people with (temporary) physical limitations expect to be able to fully participate in society. This rises the question whether total building evacuation via only stairs remains as safe as it is perceived to be. In my thesis research I was able to determine that lifts are both a viable and desirable option for emergency egress in the Netherlands.Building EngineeringCivil Engineering and Geoscience
Composite Floors: A Theoretical Research into the Design of Steel-Concrete Composite Floors with a Bigger Unpropped Span of 7.2 m
In the Netherlands buildings are designed using a grid with multiples of 3.6 meter. Within these designs floor spans of 7.2 meter are popular (double grid size). The deep decks of composite floors at this moment in time are designed to reach an unpropped span of 5.5 meter. This master research is focused on finding a possible deck design for a steel-concrete composite floor slab that can span 7.2 m and that is constructed without the need of temporary supports. This resulted in the JorFlor, a light-weight, big span steel-concrete composite floor that can compete with current floor systems.Design & ConstructionStructural EngineeringCivil Engineering and Geoscience
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