Tissue engineering and regenerative medicine have emerged as viable approaches to repairing osteochondral tissue damage, especially with the implementation of biomaterials and mesenchymal stem cells (MSCs). Poly(vinyl alcohol) (PVA) is a synthetic and non-biodegradable polymer that has received attention as a tissue engineering scaffold and cartilage replacement due to its inherent viscoelasticity and biocompatibility. This work investigated the use of mechanical cues to trigger mechanotransduction pathways and thereby guide human MSCs towards a desired differentiation lineage. PVA scaffolds with a range of compressive moduli (1 - 600 kPa) were fabricated by varying molecular weight, solution concentration, and freeze-thaw cycles. Mass loss rates and changes in stiffness were not significantly different after 7 days of dynamic compression or static culture in standard MSC culture medium. Short-term dynamic loading of human MSC-seeded PVA scaffolds resulted in an increase in cell viability and collagen production for loaded versus static samples over 7 days of culture. Through a simple dynamic compressive loading sequence MSC viability and matrix protein production may increase on synthetic, bioinert PVA scaffolds. Lastly upstream processing of polymer fabrication and cell culture was conducted in preparation for studies on a custom designed dynamic compressive loading machine for cell-seeded scaffolds.

Rivers deliver significant macronutrients and sediments to lakes that can vary substantially throughout the year. These nutrient and sediment loadings, exacerbated by winter and spring runoff, impact aquatic ecosystem productivity and drive the formation of harmful algae blooms. The source, extent and magnitude of nutrient and sediment loading can vary drastically due to extreme weather events and hydrologic processes, such as snowmelt or high flow storm events, that dominate during a particular time period, making the temporal component (i.e., time over which the loading is estimated) critical for accurate forecasts. In this work, we developed a data-driven framework that leverages the temporal variability embedded in these complex hydrologic regimes to improve loading estimates. Identifying the "correct" time scale is an important first step for providing accurate estimates of seasonal nutrient and sediment loadings. We use water quality concentration and associated 15-minute discharge data from nine watersheds in Vermont's Lake Champlain Basin to test our proposed framework. Optimal time periods were selected using a hierarchical cluster analysis that uses the slope and intercept coefficients from individual load-discharge regressions to derive improved linear models. These optimized linear models were used to improve estimates of annual and "spring" loadings for total phosphorus, dissolved phosphorus, total nitrogen, and total suspended loads for each of the nine study watersheds. The optimized annual regression model performed ~20% better on average than traditional annual regression models in terms of Nash-Sutcliffe efficiency, and resulted in ~50% higher cumulative load estimates with the largest difference occurring in the "spring". In addition, the largest nutrient and sediment loadings occurred during the "spring" unit of time and were typically more than 40% of the total annual estimated load in a given year. The framework developed here is robust and may be used to analyze other units of time associated with hydrologic regimes of interest provided adequate water quality data exist. This, in turn, may be used to create more targeted and cost-effective management strategies for improved aquatic health in rivers and lakes.

In order to achieve the UK Government’s legally bound framework of greenhouse gas reduction targets, the transport sector is undergoing drastic changes. The key action taken by the Department of Transport in addressing the issue was the introduction of Ultra-low emission vehicles (ULEV) concept. Office for Low Emission Vehicles (OLEV) was introduced to support early market for ULEV and development of efficient recharging network through Plugged-in Places programme. The massive deployment of EV charging stations across GB will have direct impact on GB power system as they require electricity supply for their operation. It is therefore deemed necessary to carry out investigations on the capacity of the network assets to handle this load and to develop policies to manage the future EV charging infrastructure efficiently. This thesis provides an overview of the EV technology introducing various technicalities behind EVs and the associated charging stations. The extended theory about interoperability between EVs and power networks is also presented. Investigation of an 11kV networked site and 66/11 kV networked area is performed to determine their potential in accommodating future EV charging infrastructure. A methodology has been proposed to carry out investigations in 11kV networked site. For analysis purpose both the real networks are modelled in detail using power system analysis software Electrical Transient Analyzer Programme (ETAP). Scottish and Southern Energy (SSE) and Northern Power Grid (NPG) are the owners of the distribution networks respectively. Collaboration with DNOs has taken place to collect the existing network data. Finally, a university based EV charging bays management policy has been proposed.

The principal objective of this investigation is to develop a constitutive model to simulate the hysteresis behaviour of unbonded flexible risers. A new constitutive model for flexible risers is proposed and a procedure for the identification of the related input parameters is developed using a multi-scale approach. The constitutive model is formulated in the framework of an Euler-Bernoulli beam model, with the addition of suitable pressure terms to the generalised stresses to account for the internal and external pressures, and therefore can be efficiently used for large-scale analyses. The developed non-linear relationship between generalised stresses and strains in the beam is based on the analogy between frictional slipping between different layers of a flexible riser and frictional slipping between micro-planes of a continuum medium in nonassociative elasto-plasticity. Hence, a linear elastic relationship is used for the initial response in which no-slip occurs; an onset-slip function is introduced to define the ‘noslip’ domain, i.e. the set of generalised stresses for which no slip occurs; a nonassociative rule with linear kinematic hardening is used to model the full-slip phase. The results of several numerical simulations for a riser of small-length, obtained with a very detailed (small-scale) non-linear finite-element model, are used to identify the parameters of the constitutive law, bridging in this way the small scale of the detailed finite-element simulations with the large scale of the beam model. The effectiveness of the proposed method is validated by the satisfactory agreement between the results of various detailed finite-element simulations for a short riser, subject to internal and external uniform pressures and cyclic bending and tensile loadings, with those given by the proposed constitutive law. The merit of the present constitutive law lies in the capturing of many important aspects of risers structural response, including the energy dissipation due to frictional slip between layers and the hysteretic response. This privilege allows one to accurately study the cyclic behavior of unbonded flexible risers subject to axial tension, bending moment, internal and external pressures.

Background: Tendinosis is a painful chronic, degenerative condition characterized by objective changes in the tissue structure of a tendon. Hallmark features in tendinosis tendons include increased number of cells (hypercellularity), extracellular matrix (ECM) degradation and disorganized collagen. The progression of these pathological changes seen in tendinosis is neither well characterized nor fully understood. Studies have suggested that there are biochemical and mechanical elements involved in tendinosis. From a biochemical perspective, studies have shown that the tendon cells, tenocytes, produce a number of neuronal signal substances/neuromodulators, such as substance P (SP) and acetylcholine (ACh), traditionally thought to be confined to the nervous system. Furthermore, it has been shown that the expression of these neuromodulators is elevated in tendinosis tendons as compared to normal healthy tendons. Interestingly, studies on other tissue types have revealed that both SP and ACh can induce tissue changes seen in tendinosis, such as hypercellularity and collagen disorganization. From a mechanical angle, it has been suggested that overload of tendons, including extensive strain on the primary tendon cells (tenocytes), causes the degenerative processes associated with tendinosis. In vivo studies have shown that in overloaded tendons, the presence of neuromodulators is elevated, not least SP, which also precedes the development of the tissue changes seen in tendinosis. This further supports the importance of combining biochemical factors and mechanical factors in the pathogenesis of tendinosis. Hypotheses: In this thesis project, we hypothesize: 1) that neuromodulators, such as SP and ACh when stimulating their preferred receptors, the neurokinin 1 (NK-1 R) and muscarinic receptors (mAChRs), respectively, can cause increased tenocyte proliferation; 2) that the effects of SP and ACh on tenocyte proliferation converge mechanistically via a shared signalling pathway; 3) that mechanical loading of tenocytes results in increased production of SP by the tenocytes; and 4) that SP enhances collagen remodelling by tenocytes via NK-1 R. Model system: In vitro studies offer insight into the function of healthy tendon matrix and the etiology of tendinopathy. Using a cell culture model of human primary tendon cells, highly controlled experiments were performed in this thesis project to study a subset of biological and mechanical parameters that are implicated in tendinosis. The FlexCell® Tension System was used to study the influence of mechanical loading on tenocytes. As well, a collagen gel contraction assay was used to examine the intrinsic ability of tenocytes to reorganise type I collagen matrices under the influence of the neuromodulator SP. Results: The studies showed that exogenous administration of SP and ACh results in increased tenocyte proliferation that is mediated via activation of the ERK1/2 mitogenic pathway when the preferred receptors of SP and ACh, the NK-1 R and mAChRs, respectively, are stimulated. Furthermore, the studies resulted in the novel finding that SP and ACh both converge mechanistically via transforming growth factor (TGF)-β1 and that a negative feedback mechanism is present in which TGF-β1 downregulates the expression of mAChRs and NK-1 R. The studies also showed that SP can increase collagen remodelling and upregulate expression of genes related to tendinosis. Finally, it was established that tenocytes are mechanoresponsive by showing that cyclic mechanical loading increases the expression of SP by human tenocytes. Conclusions: This thesis work concludes that stimulation of NK-1 R and mAChRs results in proliferation of human tenocytes, which both involve the ERK1/2 signalling pathway. It also shows that SP and ACh converge mechanistically via TGF-β1 in their contribution to tenocyte proliferation. The role of hypercellularity in tendinosis tissue is unknown. Possibly, it has different roles at different stages of the disease. The findings also show that SP increases collagen remodelling, suggesting that increased SP not only results in hypercellularity but also contributes to the collagen morphology in tendinosis.

Dans de nombreux domaines industriels et scientifiques, en particulier dans les domaines du génie civil et de génie mécanique, des matériaux à l’échelle de la microstructure, un très hétérogène par rapport à la nature du comportement mécanique. Cette fonctionnalité peut faire la prédiction du comportement de la structure soumise à différents types de chargement, nécessaires pour la conception durable, assez difficile. Le contrôle du comportement des ouvrages de génie civil est très complexe en raison de la diversité de la charge à laquelle ils sont soumis. La construction est maintenant réglementée partout dans le monde: les normes sont plus strictes et pris en compte, jusqu’à un état limite, en raison de différentes charges, par exemple des charges sévères tels que l’impact ou tremblement de terre. Modèles de comportement des matériaux et des structures doivent inclure l’élaboration de ces critères de conception et deviennent plus complexe. Ces modèles sont souvent basées sur des approches phénoménologiques, sont capables de reproduire la réponse du matériau au niveau ultime. Réponses de contrainte-déformation des matériaux sous sollicitations cycliques, dont de nombreuses recherches ont été exécutées dans les années précédentes afin de caractériser et le modèle, sont définies par différents types de propriétés de plasticité cycliques tels que l’écrouissageue, l’effet rochet et de de relaxation. En utilisant les modèles de comportement existants, ces réponses mentionnées peuvent être simulés d’une manière raisonnable. Cependant, il peut y avoir échec dans certains simulation des réponses structurelles et la déformation locale et globale. Insuffisance de ces études peut être résolu par le développement de solides modèles de comportement à l’aide d’expériences et de la connaissance des principes de fonctionnement des différents mécanismes de comportement inélastique ensemble. Dans ce travail, nous présentons un modèle phénoménologique constitutive qui est capable de coupler deux principaux mécanismes de comportement inélastique, plasticité et endommagement. Le modèle vise les applications de chargement cycliques. Ainsi, dans une partie de plasticité ou de dommages, les effets de durcissement isotropes et linéaires cinématiques à la fois sont pris en compte. Le principal avantage de ce modèle est l’utilisation de la plasticité indépendante contre les critères de l’endommagement pour décrire les mécanismes inélastiques. Un autre avantage concerne la mise en oeuvre numérique d’un tel modèle fourni en hybride-stress variationnel, obtenu avec une précision très améliorée et calcul efficace du stress et des variables internes dans chaque élément. Plusieurs exemples sont présentés afin de confirmer l’exactitude et l’efficacité de la formulation proposée en application à un chargement cyclique. / In many industrial and scientific domains, especially in civil engineering and mechanical engineering fields, materials that can be used on the microstructure scale, are highly heterogeneous by comparison to the nature of mechanical behavior. This feature can make the prediction of the behavior of the structure subjected to various loading types, necessary for sustainable design, difficult enough. The construction of civil engineering structures is regulated all over the world: the standards are more stringent and taken into account, up to a limit state, due to different loadings, for example severe loadings such as impact or earthquake. Behavior models of materials and structures must include the development of these design criteria and thereby become more complex, highly nonlinear. These models are often based on phenomenological approaches, are capable of reproducing the material response to the ultimate level. Stress-strain responses of materials under cyclic loading, for which many researches have been executed in the previous years in order to characterize and model, are defined by different kind of cyclic plasticity properties such as cyclic hardening, ratcheting and relaxation. By using the existing constitutive models, these mentioned responses can be simulated in a reasonable way. However, there may be failure in some simulation for the structural responses and local and global deformation. Inadequacy of these studies can be solved by developing strong constitutive models with the help of the experiments and the knowledge of the principles of working of different inelastic behavior mechanisms together. This dissertation develops a phenomenological constitutive model which is capable of coupling two basic inelastic behavior mechanisms, plasticity and damage by studying the cyclic inelastic features. In either plasticity or damage part, both isotropic and linear kinematic hardening effects are taken into account. The main advantage of the model is the use of independent plasticity versus damage criteria for describing the inelastic mechanisms. Another advantage concerns the numerical implementation of such model provided in hybrid-stress variational framework, resulting with much enhanced accuracy and efficient computation of stress and internal variables in each element. The model is assessed by simulating hysteresis loop shape, cyclic hardening, cyclic relaxation, and finally a series of ratcheting responses under uniaxial loading responses. Overall, this dissertation demonstrates a methodical and systematic development of a constitutive model for simulating a broad set of cycle responses. Several illustrative examples are presented in order to confirm the accuracy and efficiency of the proposed formulation in application to cyclic loading.

Title: Human axial system: identification of connective tissues changes Objectives: The main objective of this thesis was to compile a review of techniques and methods currently used in identification of connective tissues changes. Methods: The method used in this thesis is a critical literature review - a study of research papers from available information sources accompanied by author's comments. Foreign sources are represented mostly by research papers accessible via electronic archives such as ScienceDirect, Pubmed, Springer, Wiley. Also other foreign publications were used. The theoretical part is focused on basic anatomy and physiology of the spine and states main methods of identification of connective tissues changes involved in this area. The main part describes particulars of researches dedicated to identification of functional and morphological characteristics of different spinal components. Results: In addition to classic methods of spinal research, the thesis introduces also new developing techniques and methods. Procedures used in current research are described; their advantages and limits are explained. Key words: spine, biomechanics, loading, intervertebral disc, method

The solar wind interaction with an icy comet is studied through a model problem. A hybrid simulation is done of a box with evenly distributed water ions and protons, where initially the water ions are stationary, and protons move with the speed of the solar wind. The purpose of the thesis is to investigate the interaction between the two species through the convective electric field, and focus is on early acceleration of pick-up ions, and deflection of the solar wind. It is relevant to the cometary case, because it enables study of the physics of this interaction, without involving other mechanisms, such as bow shock, magnetic field pile-up and draping. The species are found to exchange kinetic energy similar to a damped oscillator, where the dampening is caused by kinetic energy being transferred to the magnetic field. At early times, i.e. times smaller than the gyration time for the water ions, the solar wind does not lose much speed when it is deflected. For comparable number densities, the solar wind can be deflected more than 90° at early times, and loses more speed, and water ions are picked up faster. The total kinetic energy of the system decreases when energy builds up in the magnetic field. The nature of the energy exchange is strongly dependent on the number density ratio between water ions and protons. A density instability with behaviour similar to a plasma beam instability forms as energy in the magnetic field increases, and limits the amount of time the simulation preserves total energy, for the particular hybrid solver used. There is a discussion on the structure of the density instability, and it is compared to cometary simulations.

La commande de la ventilation chez l'humain est capable d'adaptation persistante qui repose sur des mécanismes de type LTP. Différentes techniques permettant l'induction de plasticité sont couramment utilisées mais leur application au contrôle ventilatoire n'a fait l'objet que de très peu de travaux.L'objectif de cette thèse est (1) examiner la possibilité d'induire des mécanismes de type LTP par la rTMS et la tsDCS en deux sites de la commande ventilatoire destinée au diaphragme, l'AMS et les métamères C3-C5 ; (2) évaluer les conséquences sur le profil ventilatoire en ventilation de repos et lorsque la ventilation est artificiellement contrainte. Nous avons examiné les effets d'un conditionnement inhibiteur appliqué par rTMS en regard de l'AMS sur l'excitabilité corticophrénique. Nous avons observé la présence d'une diminution persistante de cette excitabilité et en avons tiré la proposition qu'en ventilation de repos l'AMS augmente l'excitabilité de la commande ventilatoire à l'éveil. Nous avons alors considéré les conséquences de la rTMS sur la ventilation expérimentalement contrainte. Les modifications du profil ventilatoire induites par la rTMS sont en faveur d'une participation de l'AMS à la production ou au traitement de la copie d'efférence. Dans une 3ème étude, nous avons examiné les effets de la tsDCS au niveau C3-C5 sur l'excitabilité corticophrénique et sur le profil ventilatoire. L'augmentation de cette excitabilité et du volume courant nous a conduit à suggérer la possibilité d'induire une plasticité respiratoire au niveau spinal.L'ensemble de ces résultats nous permet d'envisager des perspectives thérapeutiques à l'utilisation de la rTMS et de la tsDCS. / A salient feature of the ventilatory control system is its ability to persistently adapt its behaviour. This stems from long-term plasticity mechanisms similar to those described for the neural control in general. Plasticity can be induced by various non-invasive stimulation techniques(e.g. rTMS, TDCS, tsDCS) that are commonly used but have not be systematically applied to ventilatory plasticity. The aim of this thesis is twofold: (1) to examine the possibility of inducing LTP by rTMS and tsDCS at two sites of the ventilatory control system, namely the SMA and the phrenic motoneurons: (2) to evaluate the impact of such plasticity on breathing pattern during spontaneous ventilation and inspiratory threshold loading. We examined the effects of an inhibitory rTMS paradigm applied to the SMA on corticophrenic excitability. We observed a persistent decrease in corticophrenic excitability and therefore proposed that the SMA participates in the increased resting state of the ventilatory motor system during wake. Then we considered the consequences of rTMS on breathing pattern during ITL. The corresponding modifications support a contribution of the SMA to the production or processing of an ventilatory efference copy. In a third study, we examined the effects of a tsDCS delivered to C3-C5 on the corticophrenic excitability and on the respiratory pattern. Increased corticophrenic excitability and tidal volume were observed. This suggests that respiratory plasticity takes place at the spinal level. Taken together, these results open the perspective of harnessing respiratory plasticity as a therapeutic tool in disorders altering the ventilatory command.

Les structures aéronautiques peuvent être soumises à des sollicitations sévères telles que les collisions, les impacts de volatiles, etc … Sous l’effet de ces sollicitations rapides, qui du fait de leurs temps caractéristiques très courts limitent les transferts thermiques, le matériau peut dissiper l’énergie dans des zones de déformation localisée qui peuvent conduire à une ruine prématurée de la structure. Le travail de la thèse porte sur la définition d’une méthodologie expérimentale destinée à étudier les conditions de rupture de matériaux à haute résistance à vocation aéronautique consécutives à un endommagement dynamique. Ce travail comprend : •la mise au point d’essais rapides de cisaillement ; •des observations microstructurales des matériaux avant et après sollicitation ; •la simulation numérique des essais. / Aeronautical structures may be submitted to severe loading such as collisions, bird strike, etc. Under dynamic loading, involving quasi adiabatic conditions, the material may dissipate energy within zones of localised deformation wich may lead to the premature failure of the structure. The PhD work aims at defining an experimental methodology devoted to study the conditions of fracture of aeronautical, high strength materials intervening after dynamic damage. Tasks include notably: * definition of dynamic shear tests * microstructural observation of the material before and after loading * numerical simulation * Development of fracture criterion