Abstract Case study on the dock construction of Tungsha Island has been performed in the thesis. Evaluation of the optional location as well as the dock style was first studied according to the cost and the convenience to approach. The construction process and the environmental impact to the coastal line stability and marine ecology are also evaluated.

A dock is a structure that is built on the shore of a body of water, to provide access to the lake. Traditionally built using timber, dock structures use a number of materials to minimize costs and maximize usable space alongshore for mooring boats, swimming, sunbathing and fishing. Constructed in three distinct types on Lake of the Woods, crib docks, pile docks, and floating docks currently function as a hindrance to ecological function on the lake shore. The Lake of the Woods watershed region is a boreal water body straddling three distinct landscape characters; aspen parkland, industrial agriculture, and the Canadian Shield. Lake of the Woods traverses three political borders in an intricate system of islands, bays, and straights, as water flows into the lake body from the south. Meandering North, and ultimately exiting into Hudson’s bay, fresh water in this lake supplies drinking water to 3 major cities and towns; Fort Francis, Kenora, and the City of Winnipeg. There is a significant human impact on this sensitive environment and it is an ongoing task to maintain a healthy economic-ecological balance. Water level manipulation, pulp and paper manufacturing, hydroelectric potential, and recreation all hold controlling stakes in the performance of intricate lake system, while the value of drinking water quality is one that is often taken for granted. To ensure a drinking water source into the future, it is important to actively manage the human impact on the Lake of the Woods watershed system. Development on shorelands adjacent to the water of Lake of the Woods region is considered a luxury, and many property owners consider water access by constructing a dock to be a paramount requirement for enjoyment of the lake. The study of this freshwater lake ecosystem in this project provides evidence to support a more intensive consideration for the health of the shallow water zone. This project intends to create a new dock prototype to minimize and reverse ecological destruction on the shoreline of Lake of the Woods. / May 2017

Les protéines eucaryotes Elmo (Engulfment and Cell Motility) forment une famille de régulateurs conservés qui jouent un rôle central dans les processus biologiques reposant sur le remodelage du cytosquelette d'actine comme la phagocytose et la migration cellulaire et régulé par les GTPases de la famille Rho. Les protéines Elmo régulent la fonction des protéines Dock (Downstream of Crk), qui sont des Facteurs d'Echange de Guanine (GEF) atypiques pour les GTPases Rac1 et Cdc42. Le mécanisme de régulation connu à ce jour, repose sur l'interaction entre les 200 résidus C-terminaux d'Elmo et les 180 premiers résidus N-terminaux de Dock. Cependant, le rôle précis des différents domaines et motifs identifiés dans ces régions n'est pas encore défini. En effet, les données fonctionnelles, biochimiques et structurales rapportées à ce jour semblent contradictoires quant à la contribution de l'extrémité C-terminale d'Elmo qui comprend un motif polyproline et le domaine SH3 N-terminal de Dock. Nous avons donc étudié la contribution de l'extrémité C-terminale de Elmo1 à l'interaction entre Elmo1 et le domaine SH3 de Dock1 en utilisant notamment la résonance plasmonique de surface. Nos données démontrent la capacité du domaine SH3 de Dock1 à interagir avec Elmo1, indépendamment de l'extrémité C-terminale contenant le motif polyproline. Toutefois, la présence de cette région conduit à une augmentation significative du temps de demi-vie du complexe Elmo1/Dock1. En parallèle, des expériences de diffusion des rayons X aux petits angles nous ont permis de déterminer des enveloppes tridimensionnelles de la protéine Elmo1. Ces données nous permettent ainsi de proposer un premier modèle à basse résolution dans lequel nous localisons les parties N et C-terminales de Elmo1. De façon surprenante cette étude semble indiquer un changement de conformation de la région N-terminale de Elmo1 ainsi qu'une interaction possible de cette même région avec le domaine SH3 de Dock1. / The eukaryotic Elmo proteins (EnguLfment and cell MOtility) form a conserved regulatory family that plays a central role in a number of processes that depend on actin cytoskeleton remodeling, such as phagocytosis and cell migration. Elmo proteins regulate the function of Dock proteins (Downstream of CrK), a new family of atypical guanine exchange factors (GEF) for Rac1 and Cdc42 GTPases. The regulation of this mechanism is based on the interaction between the 200 C-terminal residues of Elmo and the 180 N-terminal residues of Dock. However, the precise role of the different domains and motifs identified in these regions is still not well defined. Indeed, functional, structural and biochemical data reported to date seem contradictory with respect to the contribution of the C-terminal end of Elmo, which includes a polyproline motif, and the N-terminal SH3 domain of Dock. We have therefore investigated the contribution of the C-terminal region of Elmo1 to the interaction between Elmo1 and the SH3 domain of Dock1 using surface plasmon resonance. Our data demonstrate the ability of the SH3 domain of Dock1 to interact with Elmo1 independently of the C-terminal polyproline containing region. However, the presence of this region induces a significant increase in the half-life of the Elmo1/Dock1 complex. In parallel, small angle X-ray experiments were recorded. These data allowed us to propose the first low-resolution model of Elmo1 in which we can locate N and C-terminal regions. Surprisingly, this study suggests a conformational change of the N-terminal region of Elmo1 and a possible interaction of this same region with the SH3 domain of Dock1

Future autonomous space missions will require autonomous rendezvous and docking operations. The servicing spacecraft must be able to determine the relative 6 degree-of-freedom (6 DOF) motion between the vehicle and the target spacecraft. One method to determine the relative 6 DOF position and attitude is with 3D ladar imaging. Ladar sensor systems can capture close-proximity range images of the target spacecraft, producing 3D point cloud data sets. These sequentially collected point-cloud data sets were then registered with one another using a point correspondence-less variant of the Iterative Closest Points (ICP) algorithm to determine the relative 6 DOF displacements. Simulation experiments were performed and indicated that the mean-squared error (MSE), angular error, mean, and standard deviations for position and orientation estimates did not vary as a function of position and attitude and meet most minimum angular and translational error requirements for rendezvous and dock. Furthermore, the computational times required by this algorithm were comparable to previously reported variants of the point-to-point and point-to-plane-based ICP variants for single iterations when the initialization was already performed.

Computer models are nowadays routinely used in harbor engineering applications. Models based on the two-dimensional elliptic mild-slope equation can simultaneously simulate refraction, diffraction, reflection, and dissipation in completely arbitrary coastal domains. However, floating structures such as floating breakwaters and docks are often encountered in the modeling domain. This makes the problem locally 3- dimensional. Hence it is problematic to incorporate a floating structure into the 2-d model. Tsay and Liu (1983) proposed a highly simplified but approximate approach to handle this problem practically. The validity of their approach is examined in detail and it is found that the actual solutions deviate considerably from the theoretical solutions, although their approximation provides results with the correct trend. Therefore, correction factors have been developed and may be used to produce more reliable results using the framework of Tsay and Liu (1983). The resulting method is applied to Douglas harbor in Alaska. The result shows that docks in the harbor distort the wave field considerably and create a reflective pattern that can affect navigation safety in some areas. Also plots are developed for the transmission coefficients for waves propagating past rectangular and cylindrical floating objects of infinite extent for a wide range of conditions encountered in practice.

Anthropogenic activities have drastically altered chemical exposure, with traces of synthetic chemicals detected ubiquitously in the environment. Many of these chemicals are thought to perturb endocrine function, leading to declines in reproductive health and fertility, and increases in the incidence of cancer, metabolic disorders and diabetes. There are over 90 million unique chemicals registered under the Chemical Abstracts Service (CAS), of which only 308,000 were subject to inventory and/or regulation, in September 2013. However, as a specific aim of the EU REACH regulations, the UK is obliged to reduce the chemical safety initiatives reliance on in vivo apical endpoints, promoting the development and validation of alternative mechanistic methods. The human health cost of endocrine disrupting chemical (EDC) exposure in the EU, has been estimated at €31 billion per annum. In light of the EU incentives, this study aims to evaluate current in silico and in vitro tools for EDC screening and hazard characterisation; testing the hypothesis that in silico virtual screening accurately predicts in vitro mechanistic assays. Nuclear receptor binding interactions are the current focus of in silico and in vitro tools to predict EDC mechanisms. To the author’s knowledge, no single study has quantitatively assessed the relationship between in silico nuclear receptor binding and in vitro mechanistic assays, in a comprehensive manner. Tripos ® SYBYL software was used to develop 3D-molecular models of nuclear receptor binding domains. The ligand binding pockets of estrogen (ERα and ERβ), androgen (AR), progesterone (PR) and peroxisome proliferator activated (PPARγ) receptors were successfully modelled from X-ray crystal structures. A database of putative-EDC ligands (n= 378), were computationally ‘docked’ to the pseudo-molecular targets, as a virtual screen for nuclear receptor activity. Relative to in vitro assays, the in silico screen demonstrated a sensitivity of 94.5%. The SYBYL Surflex-Dock method surpassed the OECD Toolbox ER-Profiler, DfW and binary classification models, in correctly identifying endocrine active substances (EAS). Aiming to evaluate the current in vitro tools for endocrine MoA, standardised ERα transactivation (HeLa9903), stably transfected AR transactivation (HeLa4-11) assays in addition to novel transiently transfected reporter gene assays, predicted the mechanism and potency of test substances prioritised from the in silico results (n = 10 potential-EDCs and 10 hormone controls). In conclusion, in silico SYBYL molecular modelling and Surflex-Dock virtual screening sensitively predicted the binding of ERα/β, AR, PR and PPARγ potential EDCs, and was identified as a potentially useful regulatory tool, to support EAS hazard identification.

Countless centuries has sailed by since humanity first discovered the method of travelling across the far stretched oceans that divided undiscovered continents. As noted by Le Corbusier, these liners were deemed being an engineering feat of the twentieth century, as their design resembled an epitome of indulgence and hospitality. As the average lifespan of a commercial liner is 25 years, the shipping industry is reaching a pinnacle point in time where countless ships will be decommissioned. As these vessels were originally built to be both functional and appealing in nature, why have them reduced to hazardous scrap metal, when they can be repurposed on land? In order to physically implement such an interior endeavor, both a decommissioned ship ideal in typology and status, along with a suited location for docking was to be advocated. The selection of Robinson Dry Dock as host and the SS Nomadic as habitant allowed for the spatial intervention of a retail-orientated and recreational facility to be envisioned. As opposed to the mere institution of a heritage approach, the appendage of a new layer is proposed that will allow for past recollection and future addition thereon - thus a palimpsest of design in terms of programmatic response and actual materiality. As the spatial and structural formation of vessels primarily rely on steel and the construction of a dock on concrete, these materials will be probed comprehensively in standings of their vulnerability to degradation. Proposed avenues of material investigation permits corrosion protection, historic decay preservation and intentional oxidation techniques that can conceivably ground potential design implementations. The decisive spatial outcome aims to endorse the idea that corrosion can act as a tool of architectural beautification, rather than a mere entity of intimidation. This idea is heightened by the insertion of a microbrewery that factually exemplifies the splendor of aging. Rather than promoting slavish alternative shipbreaking approaches and mere demolition practices, layered architectural alteration, as outlined by Fred Scott in his book, On Altering Architecture, will allow for the creation of a spatial intervention that is honest, nonintrusive and profound. / Ontelbare eeue het verby geseil sedert die mensdom 'n reismetode ontwikkel het wat hul in staat sou stel om uitgestrekte oseane, wat onontdekte kontinente verdeel, te verken. Soos opgeteken deur Le Corbusier, was hierdie lynbote beskou as 'n kordaatstuk vir ingenieurswese in die 20ste eeu, aangesien die ontwerp daarvan getuig van toegeeflikheid en gasvryheid. Omdat die gemiddelde leeftyd van 'n kommersi?le boot 25 jaar is, het die skeepindustrie 'n punt bereik waar heelwat skepe onaktief verklaar is. As hierdie werktuie oorspronklik bedoel was om funksioneel sowel as aantreklik van aard te wees, waarom dit dan reduseer tot 'n hoop skrootmetaal as dit vir 'n ander doel op land aangewend kan word? Ten einde so 'n poging te implementeer, moes 'n onaktiewe boot, tesame met 'n gepaste ligging vir die dok daarvan, voorgestel word. Die keuse van Robinson Droogdok as gasheer en die SS Nomadic as inwoner, laat ruimte vir 'n omgewings-vriendelike produk waarin die moontlikheid van kleinhandel en fasiliteite vir vermaak, voorkeur geniet. Teenoor die blote ingesteldheid van 'n erfenis-aanslag, is die byvoeging van 'n nuwe laag voorgestel, wat ruimte laat vir dit wat in die verlede gevestig is, sowel as toekomstige byvoeging ? dus 'n palimpses van ontwerp in terme van 'n programmatiese oplossing en materialiteit. Soos wat die ruimtelike en struktuele formasie van werktuie hoofsaaklik afhanklik is van staal en die konstruksie van 'n dok uit beton, sal hierdie materiale deeglik en omvattend ondersoek word in terme van hul kwesbaarheid wat degradering betref. Voorgestelde maniere om hierdie materiale te ondersoek en te toets, sal beskerming teen roes, asook historiese verval en doelbewuste oksidasie-tegnieke insluit, wat moontlik die grondslag kan l? vir potensi?le ontwerp implementering. Die uitkoms kan die idee bevorder dat verval en agteruitgang kan bydra tot argitektuele verfraaiing, eerder as om 'n blote entiteit vir intimidasie te wees. Hierdie idee word verder bevorder deur die 'n mikro-brouery by te voeg, wat die glorie van oudword beklemtoon. Eerder as om skeepsloping en blote vernietiging voor te staan, sal argitektuele verandering, soos uiteen gesit deur Fred Scott in sy boek, On Altering Architecture, die skep van 'n ruimtelike ingryping toelaat wat eerlik, nie-opdringerig en grondig sal wees. / Mini Dissertation (MInt (Prof))--University of Pretoria, 2016. / Architecture / MInt (Prof) / Unrestricted

Container vessel motions need to be small when loading and offloading cargo while moored to wharfs. Waves and their reflections from structures can induce ship motions. These motions are characterized by six degrees of freedom, including translations of surge, sway, and heave and rotations of pitch, roll, and yaw. Monitoring and quantifying these motions offer a reference for design and selection of the mooring system and wharf types. To measure the six degrees of freedom motions of a container ship moored to a dock, a 1:50 scale model is moored to two types of dock, solid wall dock and pile supported dock. Irregular waves of TMA spectrum with various periods, heights, and directions are generated in the wave basin to induce the motions of the model container ship. Optical motion capturing cameras are used to measure and quantify the six degree of freedom motions. Results of the effects of wave period, significant wave height, and wave direction on the motion characteristics of the model container ship moored at the solid dock and a pile supported dock are described in detail. A numerical simulation called aNySIM is applied to numerically predict the motion characteristics of the container ship moored to a solid wall dock only. The physical model experimental results of solid dock are also compared with the numerical simulation. These comparisons indicate that the motion characteristics of the model container ship represent similar trends for both rotations and translations. The experimental and numerical prediction values of motions of the ship moored to a solid wall dock display the same tendencies while differing in magnitude.

La gestion d’une plate-forme selon une stratégie de cross dock est un processus logistique efficace et dynamique qui vise à transférer directement les produits d'un fournisseur à un client. Cette thèse aborde les problèmes d'affectation aux portes et de gestion des ressources sous contraintes de fenêtres du temps dans un cross dock spécifique. Les problèmes sont formulés comme des modèles de programmation mathématique mixte (MIP). L’objectif est de minimiser la somme de la distance parcourue dans l’entrepôt et du coût qui contient les coûts liés aux ressources et un coût de pénalité. Une heuristique basée sur les algorithmes génétiques est proposée pour résoudre ce problème. Deux méthodes de réparation des gènes sont décrites pour rendre les solutions irréalisables réalisables. Les résultats montrent que l’algorithme génétique surpasse la résolution du modèle MIP à l’aide du solveur CPLEX en un temps donné, pour des instances de taille moyenne et de grande taille. Afin de décrire le comportement et de recueillir des informations pertinentes sur la gestion en cross docks, nous proposons un modèle basé sur réseau de Pétri. Un modèle par réseau de Pétri est construit et la simulation est réalisée avec le logiciel Tina. Par simulation, avec différents nombres de ressources, nous obtenons des temps pertinents pour améliorer les fenêtres de temps originales, le makespan de chacun des postes de travail, l'intervalle de temps libre dans le cross dock et la quantité de ressources disponible à chaque période de temps, ce qui peut fournir des conseils utiles à la gestion des ressources. A partir des résultats de la simulation, la formulation MIP est améliorée. / Cross docking is an efficient and dynamic logistic process that directly transfers goods from a supplier to a customer. This thesis addresses the door assignment and resource management problem with truck time windows constraints for a specific cross dock. The problems are formulated as mixed integer programming (MIP) models. The objective is to minimize the weighted sum of the total travel distance and cost which includes labor cost and penalty cost. A heuristic based on genetic algorithm (GA) is developed to solve the problems. Two gene repair methods are proposed to repair infeasible solutions. The computational results show that genetic algorithms outperforms the solution of MIP model with CPLEX in a given CPU time, for medium and large size instances, and that the second gene repair method outperforms the first one. In order to describe the behavior and gather information on the cross dock, a model based on Petri net is built to study the cross docks and simulations are carried out with Tina. The simulation results for different resource number lead us to obtain the relevant times to improve the original time windows, the makespan at each work station, the free time interval in the cross dock and the free resource number at each time period, which provide relevant information on the resource management. Besides, according to the simulation results, the original MIP formulations are improved. Then we propose a new MIP formulation, which determine not only door assignment, but also resources at each time period at each work station. Computational results reveal that the new MIP model control resources in cross dock more efficiently and outperforms the first model.

The dopamine signalling pathway has been implicated in the pathophysiology of neuropsychiatric conditions including bipolar disorder and schizophrenia. A detailed analysis of this pathway is essential for understanding these conditions. Previous work (Zhan et al., 2008) has identified eleven novel human dopamine receptor interacting proteins (DRIPs), but their role in cell signalling remains unclear. In this project we have employed a biomedical model, Dictyostelium discoideum, to help elucidate the cellular signalling of two DRIPs, the Zizimin GEF (DRIP2) and MARK (DRIP9) proteins. Bioinformatics analysis of these proteins shows conservation of the domain structure in the human and Dictyostelium gene products. To investigate the function of these proteins during development, two Dictyostelium homologues within each family (ZizA and ZizB; MrkA and MrkC) were ablated and changes in developmental for resulting null mutants were analysed. Development was unaltered following ablation of zizA, mrkA and mrkC, however, ablation of zizB gave rise to a clear change in developmental morphology. To further understand the developmental defect of zizB, directional cell movement (chemotaxis) was analysed in the zizA and zizB null mutants. Ablation of zizA caused no gross phenotypic change in chemotaxis, whereas zizB ablation gave rise to a reduction in cell speed, directionality and aspect (roundness). Furthermore, expression studies showed zizA and zizB were constantly expressed throughout development. Overexpression of each gene (labelled with the fluorescent tag, GFP) demonstrated a cytosolic localisation the gene products, with the ZizB-GFP fusion protein additionally exhibiting enrichment of the cortex, causing a large increase in filopodia formation and a partial inhibition of cytokinesis. Analysis of protein binding partners for ZizB indicates specific interaction with Rac1 A and a range of actin-interacting proteins. In conclusion this project provides the first insight into the molecular and cellular functions of Zizimin proteins, potential dopamine receptor interacting protein.