Yes / Although batch reactive distillation process outperforms traditional reactor-distillation processes due to simultaneous reaction and separation of products for many reaction systems, synthesis of Methyl lactate (ML) through esterification of lactic acid (LA) with methanol in such process is very challenging due to difficulty of keeping the reactants together when one of the reactants (in this case methanol) has the lowest boiling point than the reaction products. To overcome this challenge, two novel reactive distillation column configurations are proposed in this work and are investigated in detail. These are: (1) integrated conventional batch distillation column (i-CBD) with recycled methanol and (2) integrated semi-batch and conventional batch distillation columns (i-SBD) with methanol recovery and recycle. Performances of each of these configurations are evaluated in terms of profitability for a defined separation task. In i-SBD column, an additional constraint is included to avoid overflow of the reboiler due to continuous feeding of methanol into the reboiler as the reboiler is initially charged to its maximum capacity. This study clearly indicates that both integrated column configurations outperform the traditional column configurations (batch or semi-batch) in terms of batch time, energy consumption, conversion of LA to ML, and the achievable profit.

Yes / Methyl Decanoate (MeDC) is a Fatty Acid Methyl Ester (FAME) and is an important chemical compound with global production of 31 million tons per year. However, synthesis of methyl decanoate (MeDC) via esterification of Decanoic Acid (DeC) with methanol by reactive distillation is operationally challenging due to difficulty of keeping the reactants together in the reaction zone as methanol being the lightest component in the mixture can separate itself easily form the other reactant deteriorating significantly the conversion of DeC using either conventional batch or continuous distillation column. This is probably the main reason for not applying the conventional route for MeDC synthesis. Whether Semi-batch Distillation column (SBD) and the recently developed Integrated Conventional Batch Distillation column (i-CBD) offer the possibility of revisiting such chemical reactions for the synthesis of MeDC is the focus of this paper. The minimum energy consumption (Qtot) as the performance measure is used to evaluate the performances of each of these reactive column configurations for different range of methyl decanoate purity and the amount of product. It is observed that the use of i-CBD column provides much better performance than SBD column in terms of the production time and the maximum energy savings when excess methanol is used in the feed. However, the SBD column is found to perform better than the i-CBD column when both reactants in the feed are in equal amount. Also, the optimization results for a given separation task show that the performance of two-reflux intervals strategy is superior to the single-reflux interval in terms of operating batch time, and energy usage rate in the SBD process at equimolar ratio.

The synthesis of a number of alkyl esters such as methyl lactate, methyl decanoate, and ethyl benzoate via esterification in a reactive distillation is quite challenging. It is due to the complexity in the thermodynamic behaviour of the chemical species in the reaction mixture in addition to the difficulty of keeping the reactants together in the reaction section. One of the reactants (in these esterification reactions) having the lowest boiling point can separate from the other reactant as the distillation continues. This can result in a significant drop in the reaction conversion in a conventional reactive distillation whether it is a batch or a continuous column. To overcome this challenge, new different types of batch reactive distillation column configurations: (1) integrated conventional (2) semi-batch (3) integrated semi-batch (4) integrated dividing-wall batch distillation columns have been proposed here. Four esterification reaction schemes such as (a) esterification of lactic acid (b) esterification of decanoic acid (c) esterification of benzoic acid (d) esterification of acetic acid are investigated here. A detailed dynamic model based on mass, energy balances, chemical reaction, and rigorous thermodynamic (chemical and physical) properties is considered and incorporated in the optimisation framework within gPROMS (general PROcess Modelling System) software. It is found that for the methyl lactate system, the i-SBD operation outperforms the classical batch operations (CBD or SBD columns) to satisfy the product constraints. While, for the methyl decanoate system, the i-DWCBD operation outperforms all CBD, DWBD and sr-DWBD configurations by achieving the higher reaction conversion and the maximum product purity. For the ethyl benzoate system, the performance of i-CBD column is superior to the CBD process in terms of product quality, and conversion rate of acid. The CBD process is found to be a more attractive in terms of operating time saving, and annual profit improvement compared to the IBD, and MVD processes for the benzyl acetate system. / The Higher Committee for Education Development in Iraq (HCED)

<p>The automotive field is becoming more and more complex and cars are no longer just pure mechanical artifacts. Today much more than 50 % of the functionality of a car is computerized, so, a modern car system is obviously based on mixed technologies which emphasize the need for new approaches to the design process compared to the processes of yesterday. A corresponding technology shift has been experienced in the aerospace industry starting in the late sixties and today aircraft could not fly without its computers and the pilots’ environment has turned to a so called glass cockpit with no iron-made instrumentation left. A very similar change is still going on in the automotive area.</p><p>Simulator-Based Design (SBD) refers to design, development and testing new products, systems and applications which include an operator in their operation. Simulator-Based Design has been used for decades in the aviation industry. It has been a common process in this field. SBD may be considered as a more specific application of simulation-based design, where the specific feature is a platform, the simulator itself. The simulator could consist of a generic computer environment in combination with dedicated hardware components, for instance a cockpit. This solution gives us the possibility of including the human operator in the simulation.</p><p>The name of the project is Simulator-Based Design in Practice. The purpose of this master thesis is to get a complete practice in how to use a human-in-the-loop simulator as a tool in design activities focusing on the automotive area. This application area may be seen as an example of systems where an operator is included in the operation and thus experience from the car application could be transferred to other areas like aviation or control rooms in the process industry.</p><p>During the performance of the project we have gone through the main parts of the SBD process. There are many steps to complete the whole cycle and many of them have iterative loops that connect these steps with the previous one. This process starts with a concept (product/system) and continues with a virtual prototyping stage followed by implementation, test design, human-in-the-loop simulation, data analysis, design synthesis and in the end a product/system decision. An iterative process approach makes the cycle flexible and goal oriented.</p><p>We have learnt how to use the simulator and how to perform the whole cycle of SBD. We first started getting familiar with the simulator and the ASim software and then we were trying to reduce the number of computers in the simulator and changing the network in order to find good optimization pf the computer power. The second step has been to implement a new application to the simulator. This new application is the rear mirror view and consists of a new LCD monitor and the rear view vision that must be seen in the new monitor. Finally we updated the cockpit to the new language program Action Script 3.0.</p><p>The information gathering consisted of the course Human-System interaction in the University, the introduction course to ASim software and the course of Action Script 3.0.</p>

The automotive field is becoming more and more complex and cars are no longer just pure mechanical artifacts. Today much more than 50 % of the functionality of a car is computerized, so, a modern car system is obviously based on mixed technologies which emphasize the need for new approaches to the design process compared to the processes of yesterday. A corresponding technology shift has been experienced in the aerospace industry starting in the late sixties and today aircraft could not fly without its computers and the pilots’ environment has turned to a so called glass cockpit with no iron-made instrumentation left. A very similar change is still going on in the automotive area. Simulator-Based Design (SBD) refers to design, development and testing new products, systems and applications which include an operator in their operation. Simulator-Based Design has been used for decades in the aviation industry. It has been a common process in this field. SBD may be considered as a more specific application of simulation-based design, where the specific feature is a platform, the simulator itself. The simulator could consist of a generic computer environment in combination with dedicated hardware components, for instance a cockpit. This solution gives us the possibility of including the human operator in the simulation. The name of the project is Simulator-Based Design in Practice. The purpose of this master thesis is to get a complete practice in how to use a human-in-the-loop simulator as a tool in design activities focusing on the automotive area. This application area may be seen as an example of systems where an operator is included in the operation and thus experience from the car application could be transferred to other areas like aviation or control rooms in the process industry. During the performance of the project we have gone through the main parts of the SBD process. There are many steps to complete the whole cycle and many of them have iterative loops that connect these steps with the previous one. This process starts with a concept (product/system) and continues with a virtual prototyping stage followed by implementation, test design, human-in-the-loop simulation, data analysis, design synthesis and in the end a product/system decision. An iterative process approach makes the cycle flexible and goal oriented. We have learnt how to use the simulator and how to perform the whole cycle of SBD. We first started getting familiar with the simulator and the ASim software and then we were trying to reduce the number of computers in the simulator and changing the network in order to find good optimization pf the computer power. The second step has been to implement a new application to the simulator. This new application is the rear mirror view and consists of a new LCD monitor and the rear view vision that must be seen in the new monitor. Finally we updated the cockpit to the new language program Action Script 3.0. The information gathering consisted of the course Human-System interaction in the University, the introduction course to ASim software and the course of Action Script 3.0.

La progressivité du claquage des oxydes de grille d'épaisseurs inférieures à 20 nm permet d'envisager une prolongation de la durée de vie des circuits. Cet enjeu majeur de la fiabilité contemporaine requiert des modèles adaptés afin de contrôler la variabilité des paramètres induites par le claquage. Après avoir étudié l'impact d'une fuite de courant sur une couche chargée, nous avons mis au point un modèle bas niveau de simulation par éléments finis, capable de reproduire la dérive des paramètres mesurée sur des dispositifs du nœud 45 nm. Des lois empiriques de ces dérives ont été injectées dans un modèle compact du transistor dégradé, simplifié par nos observations originales de la dépolarisation du canal et de la répartition des courants. Finalement nous avons simulé l'impact du claquage sur le fonctionnement de circuits simples et estimés la dérive de leurs paramètres tels que l'augmentation de la consommation due au claquage.

97% des articles publiés sur les études climatiques racontent que le réchauffement climatique est entièrement causé par les activités humaines. Les gaz émis lors de la production d'énergie électrique ainsi que d'autres gaz rejetés par les voitures ont un réel impact sur l'atmosphère. Une solution consiste à mettre au point des composants présentant des pertes de conduction plus faibles et des caractéristiques de claquage plus élevées qui pourraient être utilisés dans des centrales nucléaires, des cellules de commutation à haute puissance, des voitures hybrides (électriques), etc.De nos jours, les composants à base de silicium contrôlent environ 95% des dispositifs électroniques. Le carbure de silicium SiC et le nitrure de gallium GaN sont actuellement à l’étape de R&D, et commencent à être intégrés dans certains circuits électroniques. D'autres matériaux tels que Ga2O3, AlN ou le diamant sont encore à l’étape de recherche. Les derniers sont connus sous le nom de matériaux à bande ultra large et semblent être la solution requise pour les faibles pertes de puissance. Le diamant est reconnu comme le matériau ultime pour la prochaine génération de composants de puissance en raison de ses propriétés physiques exceptionnelles telles qu'un champ de claquage élevé (>10 MV/cm) permettant d'utiliser le dispositif pour une commande de puissance élevée, une mobilité de porteurs élevée (2 000 cm^2/V.s pour les trous), une vitesse de saturation élevée, une conductivité thermique élevée (22 W/cm.K) pour une parfaite dissipation de chaleur et une faible constante diélectrique. Théoriquement, le diamant est le semi-conducteur offrant le meilleur compromis entre résistance à l'état passant et tension de claquage. En particulier, en raison de l'ionisation incomplète des dopants, il est encore plus efficace à haute température. Diverses diodes Schottky en diamant (SBD) avec de bonnes performances à l’état passant et bloqué (7,7 MV/cm) ont été rapportées. En plus des SBDs, des transistors à effet de champ (FET) ont également été étudiés à travers des oxyde-métal semi-conducteur FETs (MOSFETs) utilisant une surface hydrogénée avec des densités de courant élevées à l'état passant ou des surface oxygéné avec de bonnes caractéristiques de blocage. Pour les composants de haute-tension, il est nécessaire de changer l’architecture de l’électrode afin d’éviter un claquage prématuré due à l’encombrement du champ électrique aux bords. Dans ce but, les techniques de terminaison de bord sont utilisées pour atteindre les caractéristiques idéales. La tâche évidente avant toute fabrication de composant est la partie simulation qui prédit l’optimisation de l’architecture et les caractéristiques attendues. Une bonne prédiction nécessite la connaissance des paramètres du matériau. Les paramètres importants pour le claquage sont les coefficients d'ionisation par impact. Plusieurs coefficients ont été publiés pour le diamant. Toutefois, ils ont été extraits en « fittant » des structures non optimisées, d'où un manque de précision.Dans cette étude, deux structures de terminaisons de bord pour des diodes Schottky, appelées plaque de champ et anneaux à champ flottant, ont été étudiées. Leur efficacité de distribution du champ de surface par analyse de courant induit par faisceau d'électrons (EBIC) a été observée. De plus, des FETs ont été fabriqués et caractérisés, un MESFET et un RB-MESFET. Les FETs présentent un claquage élevé, jusqu’à 3 kV et une faible résistance. Le développement des transistors est indissociable de la diode Schottky, car ils sont tous deux nécessaires à la fabrication de cellules de commutation. Et enfin, les coefficients d'ionisation par impact pour les électrons ont été mesurés à l'aide d’EBIC pour un champ >0,5 MV/cm dans une région sans défaut. Les valeurs mesurées sont (sous l’equation de Chynoweth) an = 971 /cm et bn=2,39x10^6 V/cm. Ces valeurs sont proches des coefficients mesurés expérimentalement et rapportés dans la littérature. / 97% of the published climate studies articles agree with the fact that recent global warming is entirely caused by human activities. The gases emitted to produce electrical energy plus other gases rejected by cars impact considerably on the atmosphere by greenhouse effect (without referring other factors). A solution to this problem is the development of components with lower power conduction losses and higher breakdown characteristics that could be used in nuclear power plants, high power commutation cells, hybrid (electric) cars and so on.The choice of the material to reach low power conduction losses and higher breakdown is of great importance. Nowadays, silicon-based devices control about 95% of all electronic components. Silicon carbide SiC and gallium nitride GaN are at present under research and development and start to be integrated into some electronic circuits. Other materials like Ga2O3, AlN or diamond are under research for power electronic application. The last ones are known as ultra wide bandgap materials and they seem to be the required solution to low power losses. Diamond is recognized as the ultimate material for the next next-generation of power devices owing to its exceptional physical properties such as high breakdown field (>10 MV/cm) to use the device for high power control, high carrier mobility (2000 cm^2/V.s for holes) for fast switching and high frequency devices, high saturation velocity, high thermal conductivity (22 W/cm.K) for a perfect heat dissipation and low dielectric constant. Theoretically, diamond is the best semiconducting material showing the best trade-off between on-resistance and breakdown voltage. Especially, due to the incomplete ionization of the dopant, it is even more efficient at high temperature. Various diamond Schottky barrier diodes (SBDs) with good forward and reverse performances (7.7 MV/cm) were reported. In addition to SBDs, switches diamond field effect transistors (FETs) were also investigated through metal-oxide-semiconductor FETs (MOSFETs) using either an H-terminated diamond surface with high current densities in on-state or an O-terminated one with high blocking characteristics. For the high blocking voltage devices, one needs to properly terminate the edge of the electrode at the surface in order to avoid premature breakdown of the devices due to electric field crowding at the borders. In that aim, edge termination (ET) techniques are used to push the limit of the devices and reach ideal features. The obvious task before any device fabrication if the simulation part that predicts the device optimization and expected characteristics. A good device prediction requires knowledge of the material parameters. Important parameters for device breakdown in the off-state are the impact ionization coefficients. At present, several ionization coefficients were reported for diamond, however, they were extracted by fitting non-optimized structures and hence there is a lack of accuracy.In this study, two edge terminations structures for Schottky barrier diodes called field plate (FP) oxide and floating field rings were investigated. Their effectiveness in surface field distribution via electron beam induced current (EBIC) analysis was observed. In addition, normally-on FETs were fabricated and characterized, a MESFET and a reverse blocking (RB)-MESFET. The FETs exhibited a high BV, up to 3 kV and a low on-resistance. The development of transistors is inseparable from the Schottky diode since both are required to fabricate commutation cells. And finally, impact ionization coefficients for electrons were measured using EBIC for a field >0.5 MV/cm in a defect-free region. The measured values are (in a Chynoweth form) an = 971 /cm and bn = 2.39x10^6 V/cm. These values are close to the experimentally measured coefficients reported in the literature.

Human-in-the-loop simulators have long been used in the research community as well as in industry. The aviation field has been the pioneers in the use of simulators for design purposes. In contrast, corresponding activities in the automotive area have been less widespread. Published reports on experimental activities based on human-in-the-loop simulations have focused on methods used in the study, but nobody seems to have taken a step back and looked at the wider methodological picture of Simulator-Based Design. The purpose of this thesis is to fill this gap by drawing, in part, upon the author’s long experience in this field. In aircraft and lately also in ground vehicles there has been a technology shift from pure mechanics to computer-based systems. The physical interface has turned into screen-based solutions. This trend towards glass has just begun for ground vehicles. This development in vehicle technology has opened the door for new design approaches, not only for design itself, but also for the development process. Simulator-Based Design (SBD) is very compatible with this trend. The first part of this thesis proposes a structure for the process of SBD and links it to the corresponding methodology for software design. In the second part of the thesis the focus changes from methodology to application and specifically to the design of three-dimensional situation displays. Such displays are supposed to support the human operator with a view of a situation beyond the more or less limited visual range. In the aircraft application interest focuses on the surrounding air traffic in the light of the evolving free-flight concept, where responsibility for separation between aircraft will be (partly) transferred from ground-based flight controllers to air crews. This new responsibility must be supported by new technology and the situational view must be displayed from the perspective of the aircraft. Some basic design questions for such 3D displays were investigated resulting in an adaptive interface approach, where the current situation and task govern the details of information presentation. The thesis also discusses work on situation displays for ground vehicles. The most prominent example may be the Night Vision system, where the road situation ahead is depicted on a screen in the cab. The existing systems are based on continuous presentation, an approach that we have questioned, since there is strong evidence for negative behavioral adaptation. This means, for example, that the driver will drive faster, since vision has been enhanced, and thereby consume the safety margins that the system was supposed to deliver. Our investigation supports a situation-dependant approach and no continuous presentation. In conclusion, the results from our simulator-based studies showed advantages for adaptive interface solutions. Such design concepts are much more complicated than traditional static interfaces. This finding emphasizes the need for more dynamic design resources in order to have a complete understanding of the situation-related interface changes. The use of human-in-the-loop simulators and deployment of Simulator-Based Design will satisfy this need.

Silicon carbide (SiC) has higher breakdown field strength than silicon (Si), which enables thinner and more highly doped drift layers compared to Si. Consequently, the power losses can be reduced compared to Si-based power conversion systems. Moreover, SiC allows the power conversion systems to operate at high temperatures up to 250 oC. With such expectations, SiC is considered as the material of choice for modern power semiconductor devices for high efficiencies, high temperatures, and high power densities. Besides the material benefits, the typeof the power device also plays an important role in determining the system performance. Compared to the SiC metal-oxide semiconductor field-effect transistor (MOSFET) and bipolar junction transistor (BJT), the SiC junction field-effect transistor (JFET) is a very promising power switch, being a voltage-controlled device without oxide reliability issues. Its channel iscontrolled by a p-n junction. However, the present JFETs are not optimized yet with regard to on-state resistance, controllability of threshold voltage, and Miller capacitance. In this thesis, the state-of-the-art SiC JFETs are introduced with buried-grid (BG) technology.The buried grid is formed in the channel through epitaxial growth and etching processes. Through simulation studies, the new concepts of normally-on and -off BG JFETs with 1200 V blocking capability are investigated in terms of static and dynamic characteristics. Additionally, two case studies are performed in order to evaluate total losses on the system level. These investigations can be provided to a power circuit designer for fully exploiting the benefit of power devices. Additionally, they can serve as accurate device models and guidelines considering the switching performance. The BG concept utilized for JFETs has been also used for further development of SiC junctionbarrier Schottky (JBS) diodes. Especially, this design concept gives a great impact on high temperature operation due to efficient shielding of the Schottky interface from high electric fields. By means of simulations, the device structures with implanted and epitaxial p-grid formations, respectively, are compared regarding threshold voltage, blocking voltage, and maximum electric field at the Schottky interface. The results show that the device with an epitaxial grid can be more efficient at high temperatures than that with an implanted grid. To realize this concept, the device with implanted grid was optimized using simulations, fabricated and verified through experiments. The BG JBS diode clearly shows that the leakage current is four orders of magnitude lower than that of a pure Schottky diode at an operation temperature of 175 oC and 2 to 3 orders of magnitude lower than that of commercial JBS diodes. Finally, commercialized vertical trench JFETs are evaluated both in simulations andexperiments, while it is important to determine the limits of the existing JFETs and study their performance in parallel operation. Especially, the influence of uncertain parameters of the devices and the circuit configuration on the switching performance are determined through simulations and experiments. / Kiselkarbid (SiC) har en högre genombrottsfältstyrka än kisel, vilket möjliggör tunnare och mer högdopade driftområden jämfört med kisel. Följaktligen kan förlusterna reduceras jämfört med kiselbaserade omvandlarsystem. Dessutom tillåter SiC drift vid temperatures upp till 250 oC. Dessa utsikter gör att SiC anses vara halvledarmaterialet för moderna effekthalvledarkomponenter för hög verkningsgrad, hög temperature och hög kompakthet. Förutom materialegenskaperna är också komponenttypen avgörande för att bestämma systemets prestanda. Jämfört med SiC MOSFETen och bipolärtransistorn i SiC är SiC JFETen en mycket lovande component, eftersom den är spänningsstyrd och saknar tillförlitlighetsproblem med oxidskikt. Dess kanal styrs an en PNövergång. Emellertid är dagens JFETar inte optimerade med hänseende till on-state resistans, styrbarhet av tröskelspänning och Miller-kapacitans. I denna avhandling introduceras state-of-the-art SiC JFETar med buried-grid (BG) teknologi. Denna åstadkommes genom epitaxi och etsningsprocesser. Medelst simulering undersöks nya concept för normally-on och normally-off BG JFETar med blockspänningen 1200 V. Såvä statiska som dynamiska egenskper undersöks. Dessutom görs två fallstudier vad avser totalförluster på systemnivå. Dessa undersökningar kan vara värdefulla för en konstruktör för att till fullo utnyttja fördelarna av komponenterna. Dessutom kan resultaten från undersökningarna användas som komponentmodeller och anvisningar vad gäller switch-egenskaper. BG konceptet som använts för JFETar har också använts för vidareutveckling av så kallade JBS-dioder. Speciellt ger denna konstruktion stora fördelar vid höga temperature genom en effektiv skärmning av Schottkyövergången mot höga elektriska fält. Genom simuleringar har komponentstrukturer med implanterade och epitaxiella grids jämförst med hänseende till tröskelspänning, genombrottspänning och maximalt elektriskt fält vid Schottky-övergången. Resultaten visar att den epitaxiella varianten kan vara mer effektiv än den implanterade vid höga temperaturer. För att realisera detta concept optimerades en komponent med implanterat grid med hjälp av simuleringar. Denna component tillverkades sedan och verifierades genom experiment. BG JBS-dioden visar tydligt att läckströmmen är fyra storleksordningar lägre än för en ren Schottky-diod vid 175 oC, och två till tre storleksordningar lägre än för kommersiella JBS-dioder. Slutligen utvärderas kommersiella vertical trench-JFETar bade genom simuleringar och experiment, eftersom det är viktigt att bestämma gränserna för existerande JFETar och studera parallelkoppling. Speciellt studeras inverkan av obestämda parametrar och kretsens konfigurering på switchegenskaperna. Arbetet utförs bade genom simuleringar och experiment. / <p>QC 20150915</p>

Trois protéines de la famille TRIM (Motif TRIpartite), TIF1α, β (Transcriptional Intermediary Factor 1) et PML (ProMyelocytic Leukaemia¬), font l’objet de cette étude. TIF1α est connu comme un coactivateur des récepteurs nucléaires et TIF1β comme le corépresseur universel des protéines KRAB-multidoigt de zinc dont le prototype étudié ici est ZNF74. PML possède divers rôles dont le plus caractérisé est celui d’être l’organisateur principal et essentiel des PML-NBs (PML-Nuclear Bodies), des macrostructures nucléaires très dynamiques regroupant et coordonnant plus de 40 protéines. Il est à noter que la fonction de TIF1α, β et PML est régulée par une modification post-traductionnelle, la sumoylation, qui implique le couplage covalent de la petite protéine SUMO (Small Ubiquitin like MOdifier) à des lysines de ces trois protéines cibles. Cette thèse propose de développer des méthodes utilisant le BRET (Bioluminescence Resonance Energy Transfert) afin de détecter dans des cellules vivantes et en temps réel des interactions non-covalentes de protéines nucléaires mais aussi leur couplage covalent à SUMO. En effet, le BRET n’a jamais été exploré jusqu’alors pour étudier les interactions non-covalentes et covalentes de protéines nucléaires. L’étude de l’interaction de protéines transcriptionnellement actives est parfois difficile par des méthodes classiques du fait de leur grande propension à agréger (famille TRIM) ou de leur association à la matrice nucléaire (ZNF74). L’homo et l’hétérodimérisation de TIF1α, β ainsi que leur interaction avec ZNF74 sont ici testées sur des protéines entières dans des cellules vivantes de mammifères répondant aux résultats conflictuels de la littérature et démontrant que le BRET peut être avantageusement utilisé comme alternative aux essais plus classiques basés sur la transcription. Du fait de l’hétérodimérisation confirmée de TIF1α et β, le premier article présenté ouvre la possibilité d’une relation étroite entre les récepteurs nucléaires et les protéines KRAB- multidoigt de zinc. Des études précédentes ont démontré que la sumoylation de PML est impliquée dans sa dégradation induite par l’As2O3 et dépendante de RNF4, une E3 ubiquitine ligase ayant pour substrat des chaînes de SUMO (polySUMO). Dans le second article, grâce au développement d’une nouvelle application du BRET pour la détection d’interactions covalentes et non-covalentes avec SUMO (BRETSUMO), nous établissons un nouveau lien entre la sumoylation de PML et sa dégradation. Nous confirmons que le recrutement de RNF4 dépend de SUMO mais démontrons également l’implication du SBD (Sumo Binding Domain) de PML dans sa dégradation induite par l’As2O3 et/ou RNF4. De plus, nous démontrons que des sérines, au sein du SBD de PML, qui sont connues comme des cibles de phosphorylation par la voie de la kinase CK2, régulent les interactions non-covalentes de ce SBD mettant en évidence, pour la première fois, que les interactions avec un SBD peuvent dépendre d’un évènement de phosphorylation (“SBD phospho-switch”). Nos résultats nous amènent à proposer l’hypothèse que le recrutement de PML sumoylé au niveau des PML-NBs via son SBD, favorise le recrutement d’une autre activité E3 ubiquitine ligase, outre celle de RNF4, PML étant lui-même un potentiel candidat. Ceci suggère l’existence d’une nouvelle relation dynamique entre phosphorylation, sumoylation et ubiquitination de PML. Finalement, il est suggéré que PML est dégradé par deux voies différentes dépendantes de l’ubiquitine et du protéasome; la voie de CK2 et la voie de RNF4. Enfin une étude sur la sumoylation de TIF1β est également présentée en annexe. Cette étude caractérise les 6 lysines cibles de SUMO sur TIF1β et démontre que la sumoylation est nécessaire à l’activité répressive de TIF1β mais n’est pas impliquée dans son homodimérisation ou son interaction avec la boîte KRAB. La sumoylation est cependant nécessaire au recrutement d’histones déacétylases, dépendante de son homodimérisation et de l’intégrité du domaine PHD. Alors que l’on ne connaît pas de régulateur physiologique de la sumoylation outre les enzymes directement impliquées dans la machinerie de sumoylation, nous mettons en évidence que la sumoylation de TIF1β est positivement régulée par son interaction avec le domaine KRAB et suggérons que ces facteurs transcriptionnels recrutent TIF1β à l’ADN au niveau de promoteur et augmentent son activité répressive en favorisant sa sumoylation. / Three TRIM proteins (TRIpartite Motif), TIF1α, β (Transcriptional Intermediary Factor 1) and PML (ProMyelocytic Leukaemia¬), were studied in this thesis. TIF1α is a nuclear receptor coactivator and TIF1β is the universal corepressor of the KRAB-zinc finger repressor family of which, ZNF74 is studied here as a prototypic member. PML functions as a tumor suppressor and is the essential organiser of PML-NBs (PML-Nuclear Bodies) which are very dynamic nuclear macrostructures containing more than 40 proteins. The function of these three TRIM proteins is regulated by sumoylation, a post-translational modification involving the covalent linkage of SUMO (Small Ubiquitin like MOdifier) to specific targets lysine. In this thesis, we propose to develop new methods based on BRET (Bioluminescence Resonance Energy Transfer) to detect non-covalent nuclear protein interactions but also covalent linkage to SUMO in real time in living cells. To date, BRET was never used to assess non-covalent or covalent nuclear protein interactions. Studying transcriptionally active protein interactions represents a challenge by classical methods in particular when proteins have a tendency to aggregate (TRIM family) or when characterizing nuclear matrix proteins (ZNF74). In the first article, homo- and heterodimerisation of TIF1 α and β as well as their interaction with ZNF74 was assessed by BRET using full length proteins in living mammalian cells. We ascertained the heterodimerisation of TIF1α and β. Whereas ZNF74 interacts strongly with TIF1β, no interaction was detected with TIF1α. However, we unravelled the existence of ternary complexes involving ZNF74, TIF1α and TIF1β. This suggested that a mechanisms for cross-talk between nuclear receptors and KRAB-zinc finger proteins. Thus, we showed that BRET can be advantageously used as a non-transcription-based interaction system for studying transcriptionally active proteins, including nuclear matrix proteins, in living cells. Previous studies have shown that the sumoylation of PML (a tumour suppressor) is involved in its proteasome degradation that is As2O3-inducible and dependent on the polySUMO E3 ubiquitin ligase, RNF4. In the second article, we describe the development of a new application of the BRET method for the detection of covalent and non-covalent interactions with SUMO. Owing to this SUMO BRET assay, we established that the As2O3 / RNF4-mediated degradation of PML, not only depends on PML sumoylation as previously demonstrated, but also on the integrity of its SUMO binding domain. We also demonstrated that As2O3 which increases PML sumoylation, also enhances PML / RNF4 interaction. Our study revealed that most PML SBD non covalent interactions with sumoylated proteins required the phosphorylation of serines within PML SBD that were previously described as target sites for CK2 kinase and involved in PML degradation. Despites the involvement of PML SBD in RNF4-mediated degradation, these serines which function as an SBD phospho-switch, were not required for RNF4-mediated degradation. This suggested that CK2- and RNF4-mediated PML degradation represents two distinct pathways triggering PML ubiquitin / proteasome-dependent degradation. At last, our study led to the hypothesis that the recruitment of sumoylated PML at PML-Nuclear Bodies subnuclear structures via the PML SBD and / or possibly an E3 ubiquitin ligase activity other than RNF4 (PML itself being candidate) may favour PML degradation. Our study also stresses the dynamic involvement of three PML post-translational modifications, phosphorylation, sumoylation and ubiquitination in its degradation. A third article addressing the role of TIF1β sumoylation is presented in the Appendix. We characterized the 6 SUMO targets lysine of TIF1β and demonstrated that sumoylation is required for TIF1β transcriptional repressive activity. This is in part explained by the fact that TIF1β sumoylation is a pre-requisite for histone deacetylases recruitment since TIF1β repressive activity is partly dependent on histone deacetylases. We found that TIF1β sumoylation does not influence its homodimerisation or interaction with the KRAB box of KRAB zinc finger proteins recruiting TIF1β to promoters. TIF1β sumoylation is however relying on the integrity of TIF1β PHD finger and on its self-oligomerisation. Interestingly, we demonstrated that TIF1β sumoylation is positively regulated by its interaction with KRAB domain. It is thus suggested that KRAB-zinc finger proteins recruit TIF1β at DNA promoters where they trigger increase of TIF1β sumoylation and thus enhance its repressive activity.