Development of electric vehicles is motivated by global concerns over the need for environmental protection. In addition to its zero-emission characteristics, an electric propulsion system enables high performance torque control that may be used to maximize vehicle performance obtained from energy-efficient, low rolling resistance tires typically associated with degraded road-holding ability. A simultaneous plant/controller optimization is performed on an electric vehicle traction control system with respect to conflicting energy use and performance objectives. Due to system nonlinearities, an iterative simulation-based optimization approach is proposed using a system model and a genetic algorithm (GA) to guide search space exploration. The system model consists of: a drive cycle with a constant driver torque request and a step change in coefficient of friction, a single-wheel longitudinal vehicle model, a tire model described using the Magic Formula and a constant rolling resistance, and an adhesion gradient fuzzy logic traction controller. Optimization is defined in terms of the all at once variable selection of: either a performance oriented or low rolling resistance tire, the shape of a fuzzy logic controller membership function, and a set of fuzzy logic controller rule base conclusions. A mixed encoding, multi-chromosomal GA is implemented to represent the variables, respectively, as a binary string, a real-valued number, and a novel rule base encoding based on the definition of a partially ordered set (poset) by delta inclusion. Simultaneous optimization results indicate that, under straight-line acceleration and unless energy concerns are completely neglected, low rolling resistance tires should be incorporated in a traction control system design since the energy saving benefits outweigh the associated degradation in road-holding ability. The results also indicate that the proposed novel encoding enables the efficient representation of a fix-sized fuzzy logic rule base within a GA.

This dissertation aims to study the benefit of rail grinding on service life of railroad rails, focusing on failures due to rolling contact fatigue (RCF) at the rail head. Assuming a tangent rail with one-point contact at the running surface, a finite element analysis of a full-scale wheel-rail rolling contact with a nonlinear isotropic kinematic hardening material model is performed to simulate the accumulation of residual stresses and strains in the rail head. Using rolling stress and strain results from the sixth loading cycle, in which residual stresses and strains are at their steady-state, as input, two critical plane fatigue criteria are proposed for fatigue analyses. The first fatigue criterion is the stress-based approach—namely the Findley fatigue criterion. It suggests an important role of tensile residual stresses on subsurface crack nucleation and early growth in the rail head, but applications of the criterion to the near-running-surface region are limited because of plastic deformation from wheel-rail contact. The second fatigue criterion is the strain-based approach—namely the Fatemi-Socie fatigue criterion. Contributed mainly from shear strain amplitudes and factorized by normal stress components, the criterion also predicts fatigue crack nucleation at the subsurface as a possible failure mode as well as fatigue crack nucleation at the near-surface, while maintaining its validity in both regions. A collection of fatigue test data of various types of rail steel from literature is analyzed to determine a relationship between fatigue damages and number of cycles to failure. Considering a set of wheel loads with their corresponding number of rolling passage as a loading unit (LU), optimizations of grinding schedules with genetic algorithm (GA) show that fatigue life of rail increases by varying amount when compared against that from the no-grinding case. Results show that the proposed grinding schedules, optimized with the exploratory and local-search genetic algorithms, can increase fatigue life of rail by 240 percent. The optimization framework is designed to be able to determine a set of optimal grinding schedules for different types of rail steel and different contact configurations, i.e. two-point contact occurred when cornering.

In der Präsentation werden typische Engineeringaufgaben präsentiert, die mit modernen IT-Werkzeugen erledigt werden. Es wird auf die Einführung und die Durchgängigkeit eines 3D-CAD-Systems eingegangen und gezeigt, wie mit diesem System Simulations- und Prozesskettenthemen in der Praxis bei der SMS Siemag AG behandelt werden. Ebenfalls anhand von Beispielen wird die Thematik der großen Baugruppen und der Anlagenplanung im 3D-Engineering dargestellt.

L’industrie forestière est un secteur qui, même s’il est en déclin, se trouve au cœur du débat sur la mondialisation et le développement durable. Pour de nombreux pays tels que le Canada, la Suède et le Chili, les objectifs sont de maintenir un secteur florissant sans nuire à l’environnement et en réalisant le caractère fini des ressources. Il devient important d’être compétitif et d’exploiter de manière efficace les territoires forestiers, de la récolte jusqu’à la fabrication des produits aux usines, en passant par le transport, dont les coûts augmentent rapidement. L’objectif de ce mémoire est de développer un modèle de planification tactique/opérationnelle qui permet d’ordonnancer les activités pour une année de récolte de façon à satisfaire les demandes des usines, sans perdre de vue le transport des quantités récoltées et la gestion des inventaires en usine. L’année se divise en 26 périodes de deux semaines. Nous cherchons à obtenir les horaires et l’affectation des équipes de récolte aux blocs de coupe pour une année. Le modèle mathématique développé est un problème linéaire mixte en nombres entiers dont la structure est basée sur chaque étape de la chaine d’approvisionnement forestière. Nous choisissons de le résoudre par une méthode exacte, le branch-and-bound. Nous avons pu évaluer combien la résolution directe de notre problème de planification était difficile pour les instances avec un grand nombre de périodes. Cependant l’approche des horizons roulants s’est avérée fructueuse. Grâce à elle en une journée, il est possible de planifier les activités de récolte des blocs pour l’année entière (26 périodes). / Forest industry is a sector located at the heart of the debate on globalisation and sustainable development, even if it is in decline. For many countries like Canada, Sweden and Chile, the objectives are to maintain a flourishing sector without damaging the environment and to realize the finite nature of resources. It is important to be competitive and to operate effectively on forest territories, from harvesting to manufacturing products, through transport, in a context where costs increase rapidly. This master’s thesis is developing a tactical operational planning model to organize activities for a year to meet requests for factories, without losing sight of the transport of harvested quantities and inventory management factory. The year is divided into 26 periods of two weeks. We seek harvest teams schedules and assignment to harvest areas (units) for a year. The problem is formulated as a mixed integer programming model, whose structure is based on each stage of the forest supply chain. We choose to solve it by an exact method, branch-and-bound. We were able to assess how the direct resolution of our planning problem was difficult for instances with a large number of periods. However the rolling horizon approach has proved successful. In a day, we obtained the harvest activities planning for 26 periods.

過去實證研究顯示，匯率轉嫁程度並非一成不變，而是具有隨時間變動的特性。因此，有別於過去文獻大多採用滾動相關係數，本文則是使用Engle(2002)提出的動態條件相關係數模型，估計台灣於1982年至2014年間匯率變動與進口價格變動間的動態條件相關係數；並以其做為匯率轉嫁的代理變數，進而探討台灣匯率轉嫁的時間變動趨勢。我們的實證結果顯示，不論是用滾動相關係數還是動態條件相關係數，台灣的匯率轉嫁都明顯具有隨時間變動的特性。雖然5年期與10年期的滾動相關係數均在1997年前後分別呈現上升與下降的趨勢，動態條件相關係數則無類似的現象。然而，由於滾動相關係數容易受到滾動視窗樣本大小或滾動視窗有無包含極端值的影響，使得此方法較無法看出匯率轉嫁變動的準確時間點，而動態條件相關係數模型則可避免此問題。此外，本文實證發現，通膨環境與匯率波動是造成台灣匯率轉嫁隨時間變動的主要因子，對匯率轉嫁皆有顯著的正向影響。在排除1986年匯率轉嫁與進口滲透率呈現短暫負向關係的資料後，進口滲透率與匯率轉嫁的正向關係變為顯著，而進口滲透率也成為影響匯率轉嫁的原因之一。 / According to past empirical studies, it is believed that exchange rate pass -through (ERPT) has the time-varying nature. In this paper, we apply the Dynamic Conditional Correlation (DCC) model of Engle (2002), rather than the rolling correlation coefficient prevalently used by other studies, to analyze the time trend of ERPT for Taiwan. We estimate the dynamic condition correlation between the changes of exchange rate and the changes of import price using monthly data from 1982 to 2014 and use this correlation as a proxy for the degree of ERPT. Our empirical results show that ERPT for Taiwan, whether measured by the DCC or the rolling correlation coefficient, has a significant time- varying nature. In addition, both 5-year and 10-year window rolling correlation coefficient increase before 1997 and decline after 1997, which does not show in the DCC. However, the rolling correlation coefficient does not provide precise timings in the changes in ERPT, because of the dependence on the size of windows and whether or not outliers exist in the window. In contrast, the DCC does not have this kind of problem. Another important empirical result of this paper is that the inflation environment and the exchange rate volatility are main factors which explain the time-varying ERPT, and both of them have positive relation with ERPT. Moreover, the import penetration becomes positively significant after excluding data which shows temporary negative impact of the import penetration on ERPT in 1986.

This thesis is focused on the design and development of an approach, allowing the fabrication of biocompatible/biodegradable self-rolled polymer tubes, which are sensitive to stimuli at physiological conditions, can be homogenously filled with cells and are able to self-assemble into a complex 3D construct with uniaxially aligned pores. These constructs are aimed to recreate the microstructure of tissues with structural anisotropy, such as of muscles and bones. The approach consists of two steps of self-assembly. As a first step, cells are adsorbed on the top of an unfolded bilayer; triggered rolling results in a parallel encapsulation of cells inside the tubes. As a second step, the formed self-rolled tubes with encapsulated cells can be assembled in a uniaxial tubular scaffold. Three polymer systems were designed and investigated in the present work in order to allow triggered folding of the bilayer. These systems allow either reversible or irreversible tube formation. The possibility to encapsulate microobjects inside self-rolled polymer tubes was demonstrated on the example of silica particles, yeast cells and mammalian cells. At conditions when bilayer film is unfolded, particles or cells were deposited from their aqueous dispersion on the top of bilayer. An appropriate change of conditions triggers folding of the bilayer and results in encapsulation of particles or cells inside the tubes. One way swelling of an active polymer allows irreversible encapsulation of cells in a way that tubes do not unroll and cells cannot escape. It was demonstrated that encapsulated cells can proliferate and divide inside the tubes for a long period of time. Since used polymers are optically transparent, encapsulated cells can be easily observed using optical and fluorescent microscopy. Reversible swelling of an active polymer provides the possibility to release encapsulated objects. It was demonstrated that in aqueous media microtubes possessing small amount of negatively charged groups on external walls self-assemble in the presence of oppositely charged microparticles that results in a formation of 3D constructs. In obtained aggregates tubes and therefore pores were well-aligned and the orientation degree was extremely high. Moreover, the approach allows the design of porous materials with complex architectures formed by tubes of different sorts. The assembly of cell-laden microtubes results in a formation of uniaxial tubular scaffold homogeneously filled with cells. The results presented in this work demonstrate that the proposed approach is of practical interest for biotechnological applications. Self-rolled tubes can be filled with cells during their folding providing the desired homogeneity of filling. Individual tubes of different diameters could be used to investigate cell behaviour in confinement in conditions of structural anisotropy as well as to mimic blood vessels. Due to their directionality tubes could be used to guide the growth of cells that is of interest for regeneration of neuronal tissue. Reversibly foldable films allow triggered capture and release of the cells that could be implemented for controlled cell delivery. In perspective, self-assembled 3D constructs with aligned pores could be used for bottom-up engineering of the scaffolds, mimicking such tissues as cortical bone and skeletal muscle, which are characterized by repeating longitudinal units. Such constructs can be also considered as a good alternative of traditional 2D flat cell culture.

Genomic DNA is the template of life - the entity which is characterized by a self-sustaining anatomical development, regulated signaling processes, the ability to reproduce and to respond to stimuli. Through what is classically known as the central dogma, the genome is transcribed into mRNA, which in turn is translated into proteins. The proteins take part in most, if not all, cellular processes, and it is by unraveling these processes that we can begin to understand life and disease-causing mechanisms. In vitro and in vivo assays are two levels at which protein communication may be studied, and which permit manipulation and control over the proteins under investigation. But in order to retrieve a representation of the processes as close to reality as possible, in situ analysis may instead be applied as a complement to the other two levels of study. In situ PLA offers the ability to survey protein activity in tissue samples and primary cell lines, at a single cell level, detecting single targets in their natural unperturbed environment.   In this thesis new developments of the in situ PLA are described, along with a new technique offering in situ enzyme-free detection of proximity between biomolecules. The dynamic range of in situ PLA has now been increased by several orders of magnitude to cover analogous ranges of protein expression; the output signals have been modified to offer a greater signal-to-noise ratio and to limit false-positive-rates while also extending the dynamic range further; simultaneous detection of multiple protein complexes is now possible; proximity-HCR is presented as a robust and inexpensive enzyme-free assay for protein complex detection. The thesis also covers descriptions on how the techniques may be simultaneously applied, also together with other techniques, for the multiple data-point acquisition required by the emerging realm of systems biology. A future perspective is presented for how much more information may be simultaneously acquired from tissue samples to describe biomolecular interactions in a new manner. This will allow new types of biomarkers and drugs to be discovered, and a new holistic understanding of life.

La quête de minimisation du ratio poids-puissance, omniprésente dans l'industrie aéronautique, conduit à une plus grande souplesse structurelle des boîtes de transmission de puissance d'hélicoptères.Cette souplesse structurelle, associée aux sollicitations sévères mises en jeu, entraîne des déformations non négligeables des arbres et carters, et nuit naturellement à la tenue en service des roulements.S'il n’est pas maîtrisé, le désalignement des portées de roulements accroît fortement les efforts vus par la cage et peut conduire à sa rupture en fatigue.Le travail proposé s'intéresse à la modélisation du comportement dynamique des roulements de réducteurs aéronautiques et vise plus particulièrement à anticiper ce mode de ruine.Le modèle développé permet d'estimer les sollicitations de la cage en fonctionnement.Ces informations, précieuses aux ingénieurs, permettront de mieux maîtriser, et donc d'optimiser le processus de dimensionnement des roulements. / The quest for minimizing the power to weight ratio, omnipresent in the aircraft industry, has led to greater structural flexibility of helicopter gearboxes.This increasing flexibility combined with the severe loads which it involves, causes significant strains on shafts and housings, and may be detrimental to rolling bearing service life expectancy.An unchecked misalignment of bearing seats greatly increases cage stresses and it may cause its premature fatigue failure.The present work focuses on modeling the dynamic behavior of rolling bearings of aeronautical gearboxes and it specifically anticipates this failure mode.The model developed is able to estimate cage stresses in operation. This information is valuable to engineers, it allows a better control and thus an optimization of the rolling bearings design process.

Les récepteurs ionotropiques du glutamate sont responsables de la vaste majorité de la neurotransmission excitatrice rapide dans le système nerveux central. Parmi eux, les récepteurs NMDA (rNMDA) sont les médiateurs de la plasticité synaptique, fondement cellulaire des processus d’apprentissage et de mémoire. Leurs dysfonctionnements sont impliqués dans de nombreuses pathologies neurologiques et psychiatriques comme les maladies d’Alzheimer et de Parkinson, l’épilepsie et la schizophrénie. Les rNMDA forment des complexes hétérotétramériques massifs (>500 kDa) dotés de propriétés allostériques uniques grâce à un ensemble de 8 domaines extracellulaires bilobés organisé en deux strates superposées : la couche de domaines N-terminaux (NTD) et la couche de domaines de liaison de l’agoniste (ABD). Malgré un nombre croissant de structures complètes de rNMDA, le mécanisme de transduction permettant aux interactions entre ces domaines de contrôler l’activité du récepteur restait inconnu. En combinant analyse expérimentale et computationnelle, nous montrons qu’un mouvement de roulis à l’interface entre les deux dimères de la couche d’ABD est un déterminant clé du processus d’activation et de modulation des rNMDA. Cette rotation des deux dimères d’ABD constitue un commutateur conformationnel qui règle l’ouverture du canal en fonction de la conformation des NTD situés à l’opposé. Ce travail révèle comment des changements conformationnels concertés entre couches de domaines gouvernent l’activité des rNMDA. Il illumine notre compréhension d’un récepteur synaptique majeur du système nerveux central et ouvre la voie à la conception de nouveaux agents pharmacologiques ciblant le mécanisme allostérique élucidé. / Ionotropic glutamate receptors are responsible for the vast majority of fast excitatory neurotransmission in the central nervous system. Among them, NMDA receptors (NMDARs) are key mediators of synaptic plasticity, which is considered as the cellular basis of learning and memory. NMDAR dysfunction is implicated in numerous neurological and psychiatric brain disorders such as Alzheimer and Parkinson’s disease, epilepsy and schizophrenia. NMDAR form massive hetero tetrameric complexes (>500 kDa) endowed with unique allosteric capacity provided by a cluster of eight extracellular clamshell-like domains arranged as two superimposed layers: the Nterminal domain (NTD) layer and the agonist binding domain (ABD) layer. Despite an increasing number of full-length NMDAR structures, the transduction mechanism by which these domains interact in an intact receptor to control its activity remained poorly understood. Combining experimental and in silico analysis, we identify a rolling motion at an interface between the two constitute dimers in the ABD layer as a key determinant in NMDAR activation and modulation pathways. This rotation of the two ABD dimers acts as a conformational switch that tunes channel opening depending on the conformation of the membrane-distal NTD layer. This work unveils how NMDAR domains move and operate in a concerted manner to transduce conformational changes between layers and command receptor activity. It illuminates our understanding of a major synaptic receptor of the central nervous system and paves the way for the development of new pharmacological tools targeting the elucidated allosteric mechanism.

Magister Scientiae - MSc (Biotechnology) / The vaginal mucosa is dominated by Gram positive, rod shaped lactobacilli which serve as a natural barrier against infection. In both healthy and BV infected women Lactobacillus crispatus and Lactobacillus jensennii has been found to be the predominant Lactobacillus species. Many studies have been conducted to assess factors influencing lactobacilli dominance in the vaginal microbiome. However, no study has evaluated the impact of plasmids on the vaginal lactobacilli. In the present study two plasmids, pLc17 and pLc4, isolated from vaginal Lactobacillus species of both healthy and BV infected women were characterized. pLc4 was present in both Lactobacillus crispatus and Lactobacillus jensennii while pLc17 was only present in Lactobacillus crispatus. pLc17 (16663 bp in size) encoded a ribonucleotide diphosphate reductase (RNR), a filamentation induced by cAMP-like (FIC-like) protein and numerous mobile elements. The FIC-like protein may assist pLc17 to persist within the bacterial population, while RNR is commonly associated with phages and may indicate phage infection. pLc4 (4224 bp in size) encodes for a replication initiator protein and a plasmid partitioning protein. The replication protein on pLc4 shows 44% identity with the replication initiation protein of pSMQ173b_03. On further phylogenetic and sequence analysis with other Rolling Circle Replication (RCR) plasmids, pLc4 appears to be novel as the plasmid shows a low degree of similarity to these RCR plasmids. pLc17 appears to carry both a RCR replicon as well as a theta replicon, similar to pIP501, the broad-host-range plasmid from Bacillus subtilis. The relative Plasmid Copy Number (PCN) for pLc4 and pLc17 was analysed using quantitative polymerase chain reaction (qPCR) for the healthy state relative to the disease state from twentyeight vaginal swab samples obtained from the National Institute for Communicable Diseases (NICD). The relative PCN for pLc4 and pLc17 had a fold increase of ~2.803 and ~1.693, respectively in the healthy patient samples relative to BV infected patient samples. However, there were not found to be significant differences when taking the standard error into account Due to the novelty of these plasmids further analysis and characterisation is required for both plasmids, to establish what role they may play in the health of the vaginal milieu.