Transdermal drug delivery (TDD) is limited by high resistance of the outer layer of the skin, namely stratum corneum which blocks any molecule that is larger than 500 Da. Research on TDD has become very active in recent years and various technologies have been developed to overcome the resistance of the stratum corneum. In particular, researchers have started to consider the possibility of combining the TDD technologies in order to achieve further increment for drug permeability. Microneedles (MNs) and sonophoresis are both promising technologies that can perform notable enhancement in drug permeation via different mechanisms and therefore give a good potential for combining with each other. We discuss the possible ways to achieve this combination as well as how this combination would increase the permeability. Some of the undeveloped (weaker) research areas of MNs and sonophoresis are also discussed in order to understand the true potential of combining the two technologies when they are developed further in the future. We propose several hypothetical combinations based on the possible mechanisms of MNs and sonophoresis.

This thesis investigates tsunami impact on shore-based, low-rise structures in coastal areas. The aims are to investigate tsunami wave inundation in built-up coastal areas with reference to structural response to wave inundation, to assess the performance of current design codes in comparison with validated state-of-the-art numerical models and to improve structural design of residential buildings in tsunami risk areas. Tsunami events over the past few decades have shown that a significant proportion of fatalities can be attributed to the collapse of building infrastructure due to various actions of the incident waves. Although major tsunami events have demonstrated the potential catastrophic effects on built infrastructure, current building codes have no detailed or consistent guidance on designing structures in tsunami-prone regions. Furthermore, considerable differences in existing empirical formulae highlight that new research is necessary to appropriately address the particularities of the tsunami-induced forces and structure response into the design standards. In this thesis, numerical modelling methods are used to simulate hydrodynamic impact on shore-based coastal structures. The hydrodynamic simulations were conducted using a novel meshless numerical method, smoothed particle hydrodynamics (SPH), which is coupled with the finite element (FE) method to model structural behaviour. The SPH method was validated with experimental data for bore impact on an obstacle using a convergence study to identify the optimum particle size to capture the hydrodynamics. The FE model was validated against experimental data for plates under transient blast loads which have similar load characteristics with impulsive tsunami-induced bore impacts. One of the contributions of the thesis is the use of a new coupling method of the SPH-based software DualSPHysics and FE-based software ABAQUS. Using SPH particle spacing of the same size as the FE mesh size, enables the SPH output pressure to be directly applied as an input to the structural response model. Using this approach the effects of arrangement and orientation of single and multiple low rise structures are explored. Test cases were performed in 2-D and 3-D involving a discrete structure and multiple structures. The 3-D SPH simulations with single and multiple structures used an idealised coastal structure in the form of a cube with different on-plan orientations (0°, 30°, 45° and 60°) relative to the oncoming bore direction. The single structure cases were intended to study the improvement of the resilience of coastal structures by reducing the acting pressures on the vertical surfaces by changing the structure’s orientation. It was found the pressure exerted on the vertical surface of structure can be reduced by up to 50% with the 60° orientation case. The multiple structure models were conducted to examine shielding and flow focusing phenomena in tsunami events. The results reveal that the distance between two adjacent front structures can greatly influence the pressure exerted on the rear structure. This thesis also demonstrates the capability of SPH numerical method in simulating standard coastal engineering problems such as storm waves impact on a recurve wall in 2-D. The idealised structures were represented as standard timber construction and the finite element modelling was used to determine the corresponding stress distributions under tsunami impact. Following the comparison of the method used in this thesis with commonly used design equations based on the quasi-static approach, large differences in stress prediction were observed. In some cases the loads according to the design equations predicted maximum stresses almost one order of magnitude lower. This large discrepancy clearly shows the potential for non-conservative design by quasi-static approaches. The new model for the simulation of tsunami impact on discrete and multiple structures shows that the resilience of a coastal structure can be improved by changing the orientation and arrangement. The characteristics of tsunami waves during propagation and bore impact pressures on structures can be assessed in great detail with the combined SPH and FE modelling strategy. The techniques outlined in this thesis will enable engineers to gain a better insight into tsunami wave-structure interaction with a view towards resilience optimisation of structures vulnerable to tsunami impact events.

L'évolution des versants est le résultat de l'action combinée des processus d'altération et de transport sédimentaire. Même si il est généralement admis que l'efficacité de ces processus varie en fonction du climat, la quantification de l'influence climatique sur l'érosion des versants reste encore peu développée aujourd'hui. S'inscrivant dans cette problématique, notre étude est consacrée au développement d'un nouveau modèle numérique d'érosion des versants, ayant pour objectif de mieux représenter, à différentes échelles de temps, les multiples aspects du contrôle climatique sur les processus de transport de sol. Ce modèle numérique permet de simuler l'évolution de l'épaisseur de sol et du relief à l'échelle d'un versant; il repose sur une paramétrisation simple de la production de sol couplée à une paramétrisation multi-processus du transport de sol, qui comprend plusieurs variables en étroite relation avec le climat (débit de ruissellement, épaisseur de couche active). Le calcul de ces variables est réalisé sur base de séries temporelles de précipitation et de température avec l'aide d'un modèle de transfert de chaleur et d'un modèle de bilan hydrologique. Le comportement du modèle a été étudié au travers de quelques exemples génériques et d'analyses de sensibilité. Les résultats obtenus montrent des différences significatives dans la façon dont se comporte chaque processus de transport sous conditions climatiques variables, et également dans la manière dont chaque processus affecte l'érosion globale des versants. Ces résultats mettent ainsi en lumière l'importance de la paramétrisation multi-processus du transport de sol dans la modélisation de la réponse des versants aux changements climatiques. Nous avons également développé une méthode associant le modèle d'érosion de versant à un algorithme d'inversion (Neighbourhood Algorithm). Cette méthode a permis de caractériser de manière quantitative l'évolution des versants ardennais (NE Belgique) lors du dernier cycle glaciaire-interglaciaire, sur base d'un scénario climatique simple et de nombreuses données topographiques et d'épaisseurs de sol. Les résultats de l'inversion produisent des prédictions en accord avec certaines observations sur la morphologie des versants ardennais ainsi qu'avec des taux d'érosion estimés indépendamment sur base de concentrations en isotopes cosmogéniques, même si on montre que la distribution actuelle des épaisseurs de sol ne renferme pas assez d'information pour déterminer entièrement les taux de production et de transport de sol lors des périodes froides et tempérées du dernier cycle climatique. Les résultats de l'inversion suggèrent des taux de transport de sol bien plus élevés lors de la période froide que lors de la période tempérée, produisant une succession de systèmes limités par la production de sol d'une part (période froide), et par le transport de sol d'autre part (période tempérée). Un pic de transport de sol est prédit lors des transitions entre ces périodes. Les résultats laissent également suggérer qu'un équilibre dynamique en terme d'épaisseur de sol a été récemment atteint dans les parties convexes des versants, alors que des sols peu épais observés dans les parties concaves pourraient correspondre à des traces de la distribution des épaisseurs de sol qui prévalait lors de la dernière glaciation. / Hillslope evolution results from the combined action of weathering and sediment transport processes, which are thought to be both influenced by climate. Yet, the strength and nature of the connection between climate and hillslope erosion remain poorly understood at a quantitative level. In this study, we present a new numerical model of soil production and transport, which aims to better represent, at different time scales, the climate control on soil transport. The numerical model operates at the scale of a single hill and predicts the rates of soil thickness and elevation change, by using a simple parametrization of soil production and a multi-process parametrization of soil transport which includes climate-dependent variables (overland flow discharge and active-layer depth). Simple ground heat transfer and water balance models are used for calculating these variables from time-series of precipitation and temperature. The behaviour of the model has been studied through a few simulation examples and sensitivity analysis. The results highlight the importance of considering multi-process parameterization of soil transport when modelling the response of the hillslope system to climate variations, as these results display significant differences on how each transport process behaves under various climatic conditions and on how each process affect the evolution of the system. Our numerical model has also been combined with an inversion scheme (Neighbourhood Algorithm) to extract quantitative information on the evolution of hillslopes in the Ardenne (Belgium, NW Europe) during the Last Glacial-Interglacial Cycle, using a simple climatic scenario and a unique set of topographic and soil thickness data. Model predictions based on inversion results are consistent with independent observations on hillslope morphology and cosmogenic nuclide-derived erosion rates, although the inversion results show that soil production and transport rates under both the cold and warm phases of the last climatic cycle cannot be fully constrained by the present-day soil thickness distribution. The inversion results suggest that soil transport is by far more efficient during the cold climatic phase than during the warm phase, resulting in the succession of weathering-limited (cold phase) and transport-limited (warm phase) systems. Maximum soil transport rates are predicted during the transitions between the cold-warm phases. The results also suggest that a soil thickness dynamic equilibrium has been recently reached on convex regions of the hillslopes, while shallow soils found in convergent areas may be the relics of the soil thickness distribution that formed during the cold phase.

In recent decades, a significant research has been carried out towards understanding the behaviour of plated beam. Initially designed to achieve a desired capacity, the plated beams prematurely fail in undesirable modes of failure, such as debonding and peeling. The uncertainty related with such modes of failure poses a real challenge towards quantifying them. This field is far from being clearly understood. Therefore, an attempt is made in this thesis to accurately predict the behaviour of adhesively plated beams.

The sustainable development of the offshore wind and wave energy sectors requires optimising the exploitation of the resources, and it is in relation to this and the shared challenge for both industries to reduce their costs that the option of integrating offshore wind and wave energy arose during the past decade. The relevant aspects of this integration are addressed in this work, and in particular the evaluation of the Wave Energy Converter (WEC) sub-system of a hybrid wind-wave energy converter: the state of the art of combined technologies; the definition of a novel hybrid prototype, based on a preliminary feasibility analysis of a conceptual proposal; and the evaluation of a simplified version of this prototype by means of physical and numerical modelling as a mean to set the reference and define new tools and methods for future evaluation and optimisation of the prototype. Because of the novelty of combined wave and offshore wind systems, fundamental knowledge was lacking as, for example a comprehensive review and classification, which was published as a journal paper framed in the present work. In particular, the core of this PhD thesis deals with the WEC sub-system of a hybrid device that integrates an Oscillating Water Column (OWC) device into the typical monopile substructure of an offshore wind turbine. A new prototype of the hybrid energy converter has been proposed, and a patent application was filled. Furthermore, an experimental set-up was designed, built and tested at a wave flume. On the basis of this experimental campaign the performance of the device is analysed. Finally, a full 3D-numerical mirror of the experimental set-up, including the hybrid energy converter, is defined and validated, and the flume enclosure effects studied for regular waves.

Modelling wastewater temperature variations in a network of 3048 sewer pipes was achieved in this project. Recovering heat from sewers presents attractive options for producing clean energy. However, heat recovery from sewerage may result in wastewater temperature drops which may reduce the influent temperature at the wastewater treatment plant (WWTP). This drop in the WWTP influent temperature may result in the degradation of the biological treatment stage. Therefore, it is vital to predict the impact of recovering heat from sewers on the wastewater temperature. Sewer temperatures along with hydraulic data were measured for up to a year in four different Belgian sites. The measured data was utilised to calibrate a deterministic sewer pipe model that estimates the wastewater temperature variation along the sewer pipe profiles. The latter model was calibrated using data from two sites and then validated using independent data from the other two sites. The sewer pipe model was then further developed to model wastewater temperature variations in a large (3048 pipe) network. The large network model was tested by implementing three different heat recovery scenarios. It was observed that 9 MW may be recovered from the 3048 pipe network, serving a catchment with a population equivalent of 79500 inhabitants, without impacting negatively on the biological processes.

Abstract The CAS-OB (composition adjustment by sealed argon bubbling - oxygen blowing) process is used in secondary steelmaking to adjust the composition and temperature of the steel melt. The steel melt can be heated by oxidizing aluminium in process which feeds aluminium particles and oxygen to the melt surface. Oxygen is in fed by a top lance, which is an important part of many metallurgical processes and is typically used to deliver oxygen to steel melt surface by supersonic blowing. Because observing and measuring the metallurgical processes is challenging due to the high temperature, numerical models predicting the processes are especially important. In this thesis, both top lances and the heat-up stage of the CAS-OB process were studied, and numerical models were constructed. CFD (computational fluid dynamics) were used to study top lances. A turbulence model was adjusted for supersonic flows with experimental data from literature. The CAS-OB process model involves chemical reactions and fluid flows. In order to keep the computation times reasonable, a full fluid flow calculation is not included in the model but is calculated in advance. Heat and mass transfer correlations are calculated with CFD, and the results are then used in the process simulation model. Chemical reactions are calculated based on the law of mass action and thermodynamics. The results were validated with industrial measurements. The CAS-OB heat-up stage model can be used in its current state in process development, and in the future for online control of the process. The CFD model for the top lance can be applied to a lance in any other process. / Tiivistelmä CAS-OB-prosessia (composition adjustment by sealed argon bubbling - oxygen blowing) käytetään teräksen valmistuksessa sulan teräksen koostumuksen ja lämpötilan säätämiseen. Terässulaa voidaan tarvittaessa lämmittää syöttämällä alumiinikappaleita ja happea sulan pinnalle. Hapen syöttö tapahtuu yliäänilanssilla, jota käytetään monissa metallurgisissa prosesseissa, yleensä toimittamaan happea sulan pinnalle yliäänisellä puhalluksella. Metallurgisten prosessien havainnointi ja mittaaminen ovat haastavia korkeiden lämpötilojen vuoksi, joten numeeriset mallit ovat erityisen tärkeitä prosessien ennustamisessa. Tässä työssä on tutkittu yliäänilansseja ja CAS-OB-prosessin lämmitysvaihetta ja luotu niille numeeriset mallit. Yliäänilanssien tutkimiseen käytettiin numeerista virtauslaskentaa (CFD, computational fluid dynamics). Lanssien mallinnusta varten olemassa olevaa turbulenssimallia muokattiin paremmin yliäänivirtausta kuvaavaksi kirjallisuudesta löytyvän mittaustiedon perusteella. CAS-OB-prosessimallissa huomioidaan virtaus ja kemialliset reaktiot. Koska laskenta-ajat haluttiin pitää käytännöllisinä, virtauslaskentaa ei suoriteta mallissa, vaan se tehdään etukäteen. Aineen- ja lämmönsiirtokertoimet lasketaan CFD-laskennalla, ja tuloksia käytetään prosessimallissa. Kemialliset reaktiot lasketaan perustuen massavaikutuksen lakiin ja termodynamiikkaan. CAS-OB-mallin tulokset on validoitu terästehtaalla tehtyjen kokeiden perusteella. Mallia voidaan käyttää nykyisessä muodossaan prosessin kehityksessä ja tulevaisuudessa myös prosessin ohjauksessa. Yliäänilanssin CFD-mallia voidaan soveltaa myös muihin metallurgisiin prosesseihin.

O impacto econômico da diluição não planejada está distribuído no aumento de custos diversos do processo, como carregamento, transporte, britagem e moagem, ocasionando um desperdício na capacidade total de processo. Esse trabalho tem como objetivo inicial quantificar a ocorrência de diluição não planejada existente no hangingwall de uma mina subterrânea de ouro com método Transversal Stope e recuperação de pilares com uso de enchimento cimentado. Posteriormente está o uso de modelagem numérica com o objetivo de reproduzir a ocorrência de diluição, além de proporcionar a verificação e otimização de diferentes geometrias para os stopes. A diluição pode ser atribuída tanto a forma de extração (desenho dos stopes, sequência, perfuração e desmonte), além de problemas geomecânicos (qualidade do maciço, cablebolts e estado tensional). Otimizações para reduzir a diluição não planejada requerem um entendimento de todos esses fatores que afetam direta e indiretamente o ingresso de material estéril do hangingwall nos stopes. Este trabalho tem como foco principal verificar a diluição proveniente de problemas geomecânicos e de desenho dos stopes. As ferramentas utilizadas para analisar e quantificar os fatores de diluição foram: escâner de cavidades (CMS - Cavity Monitoring System) e software 3D capaz de efetuar operações booleanas. A diluição no hangingwall foi quantificada por meio da metodologia do fator ELOS. Para reproduzir a diluição nos stopes foram utilizados modelos numéricos de elementos finitos sendo que cinco stopes primários foram selecionados e utilizados para calibração dos modelos. O volume da zona de relaxamento no hangingwall, produzido pelos modelos, apresentou uma boa correlação com o volume da diluição real, refletindo a realidade dos stopes produzidos na mina. Então, a partir dos modelos calibrados, foram produzidos novos modelos com diferentes geometrias de stopes onde foi possível observar diversas oportunidades de melhorias na redução da diluição do método, fazendose modificações no desenho dos stopes/galerias e nos cablebolts instalados no hangingwall. / The economic impact of unplanned dilution is distributed in an increase in many costs of the process, such as loading, transport, crushing and grinding, resulting in less overall process capability. This work has as main goal quantify the unplanned dilution in the hangingwall of an underground gold mine with pillar less Transversal Stopes method, using cemented rock fill. After, numerical modeling will be used in order to reproduce the occurrence of dilution, and provide verification and optimization of different geometries for stopes. Overbreak can be attributed to both the shape extraction (design of the stopes, sequence, drill and blast), and geotechnical problems (rock quality, cablebolts and tensional state). Efforts to reduce unplanned dilution require an understanding of all these factors that directly and indirectly affect the inflow of waste material from hangingwall to the open stopes. This work is mainly focused on checking the dilution from geomechanical problems and design of the stopes. The main tools used in the analysis of dilution factors were Cavity Monitoring System (CMS) and 3D software able to perform boolean operations. The dilution in the hanging wall was quantified by the ELOS methodology. To reproduce the dilution in the stopes, numerical finite element models were used and five primary stopes were selected as calibration models. The volume of the relaxation zone at the hanging wall, produced by the models, showed good correlation with the volume of actual dilution, reflecting the reality of stopes produced at the mine. Then, from the calibrated models were produced new models with different stopes geometries where we could see several opportunities for improvement in reducing the dilution of the method, making some modifications to the design of the stopes/galleries and in cablebolts of the hangingwall.

The global carbon cycle is a central part of the climate system which forms a direct link between human activity and climate change. This thesis presents my contribution to the field of research into the global carbon cycle with complex numerical models and its use to inform climate mitigation policy. Firstly, I present work I led to build, configure and apply the Hadley Centre Earth System Model, HadGEM2-ES, that successfully delivered the CMIP5 simulations. Then I present work that led to the design of the next generation of coupled carbon cycle intercomparison experiments. The aim of these experiments is to understand and quantify future centuryscale changes in land and ocean carbon storage and fluxes and their impact on climate projections. A set of ESM simulations was devised, with a common protocol, which all participating modelling centres should follow. A theoretical framework is commonly used to quantify carbon cycle feedbacks. I played an active role in its recommended use and definitions of terms. A feedback analysis I performed of future carbon cycle projections formed a central component of the IPCC’s Fifth Assessment Report. This is the first time that that the IPCC carbon cycle chapter had a section devoted to the feedbacks and future projections from coupled carbon cycle ESMs. Finally, I present three specific applications of my research and their relevance to climate mitigation policy. 1) I was the first to define the concept of committed ecosystem changes and demonstrate that ecosystems may continue to respond for many years or decades after climate is stabilised, leading to the recommendation that such committed change should be included in definitions of dangerous climate change. 2) I performed the first Earth System model analysis of the carbon emissions reductions required to follow the RCP pathways leading to the IPCC AR5 statement that, “For RCP2.6, an average 50% emission reduction is required by 2050 relative to 1990 levels”. 3) My research on carbon cycle feedbacks, especially the response of the carbon cycle to low CO2 pathways, found that models predict significant weakening, or even potential reversal, of natural carbon sinks in response to removal of CO2, which potentially hinders the effectiveness of the negative emissions. My research presented in this thesis has been influential in setting international research priorities in this field. It continues to inform global negotiations on climate mitigation policy.

Les filtres plissés à très haute efficacité (THE) jouent un rôle essentiel dans le maintien du confinement des installations industrielles à risques, les réacteurs nucléaires par exemple. Ces filtres permettent le piégeage des aérosols, qui sont la principale source de contamination externe. Dans ce cadre, l’IRSN (Institut de Radioprotection et de Sûreté Nucléaire) conduit des études pour caractériser les performances des filtres THE. L’objectif de la présente thèse a été de développer un modèle prédictif décrivant l’évolution de la résistance aéraulique du filtre au cours de son colmatage. Le colmatage d’un filtre plissé THE est piloté, d’une part par les conditions aérauliques imposées dans les réseaux de ventilation, d’autre part par la nature du média et les propriétés des particules collectées par le filtre. Ainsi, les travaux réalisés ont été répartis sur deux volets. La première partie a été dédiée à l’étude de l’aéraulique du filtre suivant une approche double expérimentale et numérique. Un banc expérimental permettant de mesurer les champs de vitesse dans un pli de filtre plissé THE a été développé. Les mesures réalisées ont servi à la validation des codes de calcul utilisés (ANSYS CFX® et GeoDict®) et au développement d’un modèle de perte de charge initiale des filtres plissés vierges. Une validation du modèle à l’échelle de filtres complets avec des géométries différentes a ensuite été effectuée. La deuxième partie a porté sur l’étude du colmatage des filtres plissés THE suivant une approche expérimentale et numérique. Un banc expérimental a été développé pour la détermination des paramètres entrant en jeu dans les modèles de colmatage (porosité, taille de particules …), puis des simulations numériques à l’aide du logiciel GeoDict ont été réalisées pour caractériser la croissance du dépôt sur la média. La combinaison des résultats expérimentaux et numériques a conduit au développement d’un modèle décrivant l’évolution de la résistance aéraulique du filtre THE au cours de son colmatage avec des particules microniques / High Efficiency Particulate Air (HEPA) pleated filters are used to ensure the containment of airborne contamination within nuclear facilities. These filters are often the last barrier before a potential release of radioactive substances into the environment. Predicting their performances (pressure drop and efficiency) is a main thrust of research for IRSN which aims at avoiding any unexpected failure of those devices on French nuclear facilities. The clogging phenomenon is mainly influenced, on one side, by the flow conditions imposed in the ventilation network and, on the other side, by the media characteristics and the particles properties which are collected by the filter. Consequently, the work carried out has been divided into two parts. In the first part, we focused on the study of the airflow behavior within a HEPA pleated filter with an experimental and numerical approach. An experimental bench has been developed to measure the airflow field at the entrance channel of a HEPA filter pleat. Then, the experimental measurements have been used to validate GeoDict® and ANSYS CFX® simulations. The combination of the experimental and the numerical results have been used to develop a model to predict the evolution of the initial HEPA filter pressure drop. The work performed in the second part deals with the clogging of the filter. An experimental bench, dedicated to the characterization of the parameters that intervene in the clogging models such as the porosity, the pressure drop and the particles size, has been developed. Then, numerical simulations conducted with GeoDict® have been realized to describe the cake formation on the surface of a HEPA pleated filter. Finally, we developed a model to predict the evolution of HEPA pressure drop during clogging with micronic particles