Ce sujet est d’actualité suite à une évolution rapide des types de conception de structures élancées utilisées dans les installations provisoires. C’est seulement depuis une vingtaine d’années que ces structures sont préfabriquées en cadres multidirectionnels (de sections tubulaires en acier ou en aluminium). Ces structures sont légères et leur stabilité réside seulement dans les raideurs internes au niveau des files de montants et au niveau horizontal par les planchers ainsi que dans les liaisons avec l’ouvrage. Ce travail concerne l’étude des instabilités (flambement-déversement) en tenant compte de différents types d’imperfections. De nouvelles courbes de flambement ainsi que les facteurs d’imperfection associés sont proposés dans cette thèse. Ces courbes sont obtenues en imposant une déformée initiale représentant les défauts géométriques et mécaniques (contraintes résiduelles). Les résultats expérimentaux confrontés avec les prévisions théoriques de l’Eurocode 3 montrent que les valeurs des imperfections figurant dans la littérature sont extrêmement exagérées. Les valeurs préconisées dans ce travail pourraient présenter un certain intérêt pour une modification éventuelle des courbes européennes de flambement pour ce type de structure. En ce qui concerne l’instabilité latérale, une méthodologie originale d’essais en vraie grandeur de poutres à treillis formés d’éléments tubulaires a été également mise au point. Le système de chargement à « roues libres » développé permet de libérer le point d’application de l’effort dès le début de l’instabilité. Cette technique conduit à des mesures plus précises du moment critique de déversement. / This subject becomes topical following a rapid evolution of design procedures for slender structures used widely in the temporary installations. Only through the last twenty years that these structures are prefabricated of multidirectional frames (steel or aluminium tubular sections). These structures are lightweight and their stability lies only in the internal stiffness at rows of posts and horizontally by the planking as well as the links with the building. This work concerns the study of instabilities (buckling - lateral torsional buckling) taking into account different types of imperfections. New buckling curves and the associated imperfection factors are proposed in this thesis. These curves are obtained by imposing an initial deformed representing the geometrical and mechanical defects (residual stress). The experimental results were confronted with theoretical predictions of Eurocode 3 which show that the values of the imperfections in the literature are extremely exaggerated. The values advocated in this work could be of interest for a possible adjustment of the European buckling curves for this type of structure. Regarding the lateral instability, an original methodology in real scale tests of trusses consist of tubular elements was also developed. The developed loading system of "free wheels" allows releasing the point of application of the force from the beginning of instability. This technique leads to more accurate measurements of the critical lateral torsional buckling moment.

L’angiogenèses par bourgeonnement est associée à une réorganisation majeure de la matrice extracellulaire (MEC). Nous avons déjà démontré que la lysyl oxydase-like 2 (LOXL2), une enzyme responsable du crosslinking de la MEC, régule la formation de vaisseaux intersomitiques dans les embryons de poisson zèbre et de capillaires en hydrogels 3D. Dans ce manuscrit, nous avons examiné les mécanismes impliqués dans cette régulation. Nous avons constaté l’association intracellulaire de LOXL2 avec la fibronectine et le collagène IV, avant d’être incorporée dans des structures fibrillaires dès l’exocytose. De plus, l’inhibition de l’expression de LOXL2 entraine des défauts de déposition de la MEC et diminue sa rigidité, inhibant secondairement la maturation des structures d'adhésion cellulaire. Alors que LOXL2 n‘est pas nécessaire pour la formation de capillaires dans un modèle 2D sur MEC de fibroblastes, les défauts de déposition de MEC sont corrélés à l'inhibition de formation des capillaires en hydrogel 3D. Ni l’addition de LOXL2 exogène, ni l’augmentation de la rigidité des hydrogels ne compense la perte d’expression de LOXL2. Enfin, nous avons pu montrer que ni l'activité catalytique ni le domaine catalytique de LOXL2 ne sont essentiels pour la formation de capillaire dans le poisson zèbre et dans les hydrogels et pour l’assemblage du collagène IV par des cellules endothéliales. L’ensemble de ces données suggère donc que les domaines SRCR de LOXL2 exprimés par des cellules endothéliales régulent l’échafaudage de fibronectine et de collagène IV dans la MEC qui est nécessaire à la formation de capillaires. / Sprouting angiogenesis is associated with major extracellular matrix (ECM) remodelling, consisting in both degradation of the microenvironment and generation of a new basement membrane. We have previously reported that lysyl oxidase-like 2 (LOXL2), an enzyme responsible for ECM crosslinking, regulates formation of intersomitic vessels (ISV) of zebrafish embryos and of capillaries in 3D hydrogels. In this manuscript we investigated the mechanisms involved. We found that LOXL2 associates with fibronectin and collagen IV intracellulary before direct incorporation in fibrillar structures of the ECM upon exocytosis. In addition, silencing LOXL2 demonstrated its involvement in ECM deposition as both composition and stiffness of the ECM were affected, which subsequently altered maturation of cell adhesion structures. Whereas LOXL2 is not required for formation of capillaries on top of a fibroblast monolayer, in a 2D assay, ECM defaults were associated with altered formation of capillaries in 3D hydrogels.Neither addition of exogenous LOXL2, nor increasing the stiffness of hydrogels could restore capillary formation. Moreover, we could show that neither the catalytic activity nor the catalytic domain were required for capillary formation in vivo and in 3D hydrogels, and for collagen IV deposition by endothelial cells. Altogether, these data suggest that the SRCR domains of LOXL2 expressed by endothelial cells regulate 3D capillary morphogenesis through scaffolding of fibronectin and collagen IV in the ECM.

L’ingénierie protéique servant autrefois à comprendre les relations structures-fonctions des protéines connait un tournant majeur depuis plusieurs années. L’ingénierie protéique évolue pour créer des nouvelles fonctions protéiques : c’est la naissance de l’ingénierie protéique moderne. L’objectif de ma thèse a consisté à mettre en place et caractériser deux approches indépendantes d’ingénierie protéique dans le domaine du vaccin et du diagnostic. Le premier projet consistait à générer des ligands protéiques à partir d‘échafaudages moléculaires (des alternatifs aux anticorps) en couplant le ribosome display au NGS et en développant des outils d’analyses bio-informatiques. Des sélections contre des cibles protéiques d’origine bactérienne et virale ont conduit à l’identification de ligands Affibodies affins (µM au nM). Leur caractérisation a validé leur potentiel comme outil de recherche et de réactif diagnostique. Ces études ont permis de valider la plateforme de génération des ligands mise en place, en augmentant l’exploration de l’espace de diversité des interactions des ligands. Le second projet portait sur le développement d’une plateforme de présentation et de vectorisation à partir de particules d’encapsuline. Elles ont été génétiquement modifiées pour présenter de manière répétée à leur surface l’ectodomaine de la protéine de matrice M2 (M2e) du virus Influenza A H1N1 tout en encapsulant une protéine hétérologue : l’eGFP. Les nanoparticules modifiées sont correctement formées et encapsulent l’eGFP. Des souris immunisées par ces particules induisent une réponse anticorps spécifique contre l’épitope M2e et l’eGFP. L’utilisation de ces nanoparticules comme plateforme vaccinale de présentation et de vectorisation est prometteuse et ouvre la voie pour d’autres applications en biotechnologie / In the past, protein engineering used to understand function and structure relationship. But since few years, protein engineering was used to create new protein functions: modern protein engineering was born. The aim of my thesis was to set up and characterize two approaches of protein engineering in diagnostic and vaccine field. The first project was to generate artificial binder using protein scaffolds as an alternative to antibodies by coupling ribosome display (RD) to NGS and developing bio-informatics tools. Screening and selection against bacterial and viral targets have led to affibody binder’s identification with an affinity range from µM to nM. Their characterization has validated their potential as research tools and protein reagents for diagnostic assay. Coupling ribosome display to high throughput sequencing as means to directly identify selected binder coding sequences, enormously enhance binder discovery depth. The second project was to generate an innovative nanocarrier based on encapsulin nanoparticle, for customized peptide display and cargo protein vectorization. Encapsulin particles from T.maritima were genetically modified for simultaneous display of the matrix protein 2 ectodomain of the influenza H1N1 A virus and heterologous protein eGFP packaging. Genetically engineered encapsulin nanoparticles were well-formed and abled to efficiently load eGFP. Immunogenicity studies revealed antibody responses against both the surface epitope and the loaded cargo protein. Taken together, this display system is a versatile tool for rational vaccine design and paves the way for new applications in the research fields of vaccine, antimicrobial research and other biotechnological applications

This thesis concerns the development of a new series of Sr-doped phosphate-based glasses for biomedical applications. Such glasses in powder form are envisaged to have applications in novel composite restorations where the following is achievable: dentin cell-mediated bioremineralization, dental pulp regeneration and as carrier for therapeutics or antibacterial ions.The initial aim was to produce soluble porous phosphate glasses using the sol-gel method (phosphate-alkoxide based sol-gel process). Knowing the effect that the variation of Ca content has on the dissolution properties of the glass, a series of glasses where Ca was progressively increased at the expense of Na was produced. The structure of the prepared samples was probed by XRD, XRF and FTIR to confirm the successful synthesis of the target phosphate-based glass compositions. After that a promising methodology was established, attempts were made to replace Ca with Sr. Different Sr sources were used without success due to the difficulty to fully dissolve those precursors in the sol-gel mixture. Subsequently, the issue of the toxicity of some precursors and solvents used in the sol-gel procedure was recognised. To overcome this obstacle, efforts were made to replace the toxic precursor chemicals with safer ones. Nevertheless, due to the low solubility of some new precursors and the low reactivity of others, the sol-gel process did not proceed in a predictable and reproducible fashion. At this stage, the sol-gel route was put aside, and two alternative soft and water-based chemical approaches were experimented: the precipitation method and the coacervation process. The first one was found to be unsuitable for our needs for two main reasons: 1) the presence of Na in the composition generated a crystalline material (instead of a glassy amorphous one); 2) the Ca/P ratio of our composition fell in the range of crystalline phase by using this method. In addition, the yield was really low. The second method (coacervation process) was a complete success. The glassy nature of the materials obtained was proved by XRD and XRF and the surface features were tested by BET and SEM. The process was retained for a while as the preferred synthesis route and both the scale-up effect and the possibility to add Sr were analysed. The production scale of the material was increased by 5 times and different Sr sources were tested to find the best one. XRD and XRF analysis proved both the success of the scale-up and the incorporation of the Sr in glass composition / This thesis concerns the development of a new series of Sr-doped phosphate-based glasses for biomedical applications. Such glasses in powder form are envisaged to have applications in novel composite restorations where the following is achievable: dentin cell-mediated bioremineralization, dental pulp regeneration and as carrier for therapeutics or antibacterial ions.The initial aim was to produce soluble porous phosphate glasses using the sol-gel method (phosphate-alkoxide based sol-gel process). Knowing the effect that the variation of Ca content has on the dissolution properties of the glass, a series of glasses where Ca was progressively increased at the expense of Na was produced. The structure of the prepared samples was probed by XRD, XRF and FTIR to confirm the successful synthesis of the target phosphate-based glass compositions. After that a promising methodology was established, attempts were made to replace Ca with Sr. Different Sr sources were used without success due to the difficulty to fully dissolve those precursors in the sol-gel mixture. Subsequently, the issue of the toxicity of some precursors and solvents used in the sol-gel procedure was recognised. To overcome this obstacle, efforts were made to replace the toxic precursor chemicals with safer ones. Nevertheless, due to the low solubility of some new precursors and the low reactivity of others, the sol-gel process did not proceed in a predictable and reproducible fashion. At this stage, the sol-gel route was put aside, and two alternative soft and water-based chemical approaches were experimented: the precipitation method and the coacervation process. The first one was found to be unsuitable for our needs for two main reasons: 1) the presence of Na in the composition generated a crystalline material (instead of a glassy amorphous one); 2) the Ca/P ratio of our composition fell in the range of crystalline phase by using this method. In addition, the yield was really low. The second method (coacervation process) was a complete success. The glassy nature of the materials obtained was proved by XRD and XRF and the surface features were tested by BET and SEM. The process was retained for a while as the preferred synthesis route and both the scale-up effect and the possibility to add Sr were analysed. The production scale of the material was increased by 5 times and different Sr sources were tested to find the best one. XRD and XRF analysis proved both the success of the scale-up and the incorporation of the Sr in glass composition

La résolution de problèmes complexes (RPC) est une compétence du 21e siècle essentielle chez les gestionnaires. Or, bien que les programmes en gestion visent à développer cette compétence, de nombreux diplômés récents éprouvent des lacunes lorsqu’ils arrivent sur le marché du travail. Si leur manque de connaissances disciplinaires et leur faible niveau de compétences métacognitives peuvent les expliquer en partie, ces lacunes sont aussi possiblement attribuables aux méthodes pédagogiques couramment utilisées en gestion, qui n’enseignent pas explicitement un processus de RPC. Considérant l’importance d’enseigner explicitement une démarche générale de RPC et le développement des compétences métacognitives, cette recherche est fondée sur la théorie de l’échafaudage. Ainsi, des outils d’échafaudage numériques visant à assister temporairement les apprenants, afin qu’ils puissent internaliser un processus de RPC et développer leurs compétences métacognitives, ont été intégrés à une application numérique utilisée par des apprenants de 1er cycle universitaire en gestion. Cette recherche mixte a permis d’évaluer l’influence de ces outils d’échafaudage numériques sur l’apprentissage de la RPC et le développement de compétences métacognitives, de comprendre leur influence durant le processus de résolution, et de décrire l’intention d’utilisation des apprenants. Les résultats quantitatifs montrent que l’accès aux outils a amélioré la performance de RPC à une reprise et soutenu le développement de la compétence métacognitive de planification. Les résultats qualitatifs suggèrent que les apprenants considéraient que les outils les aidaient à améliorer la qualité de leurs évaluations, mais ils ne percevaient pas qu’ils visaient aussi à développer leurs compétences métacognitives. Les résultats suggèrent que ces apprenants peuvent être qualifiés de novices quant à leur compétence de RPC. En effet, ils semblent accorder un temps insuffisant à l’analyse de la situation problème, n’évaluent pas les autres solutions possibles, ne considèrent pas les conséquences négatives de leur solution et mobilisent peu leurs compétences métacognitives de monitoring et d’autocontrôle et d’autoévaluation. La perception d’utilité serait corrélée avec la perception de pertinence, d’amélioration de la qualité du travail et du caractère agréable des OÉN. Considérant la perception de facilité d’utilisation fortement élevée parmi tous les participants, cela suggère que l’intention d’utilisation serait principalement liée à la perception d’utilité Les résultats suggèrent que ces OÉN seraient davantage pertinents en formation à distance, plutôt qu’en présentiel. Les questions incitatives influenceraient davantage le processus de RPC, comparativement à une liste de vérification et des vidéos de solutions d’experts. Plusieurs recommandations ont été élaborées pour améliorer la conception et l’usage des OÉN. Les apprenants doivent être formés par leur enseignant à utiliser les OÉN, qui doit leur montrer la pertinence et la manière de les exploiter adéquatement. Les OÉN doivent offrir un niveau de soutien cognitif suffisant et constant à toutes les étapes de la RPC. L’application doit être dotée de fonctionnalités qui permettent de comprendre pourquoi les outils doivent être mobilisés. Les concepteurs doivent considérer les déterminants qui influencent la PU pour susciter leur usage. En somme, bien que cette recherche comporte plusieurs limites, notamment une collecte de données pendant la COVID-19, elle contribue significativement à la littérature grâce à ses recommandations visant la conception et l’usage des outils d’échafaudage numériques en enseignement supérieur. / Complex problem-solving (CPS) is an essential 21st century skill for all managers. Although most of the business administration programs aim to develop this skill, many graduates still feel gaps when they enter the labour market. If their lack of content knowledge and their low level of metacognitive skills can explain in part these gaps, they might also be caused by the teaching methods commonly used in business administration education. Indeed, these methods do not demonstrate a process for CPS explicitly. Considering the importance of teaching a CPS process explicitly and the development of metacognitive skills, this research is based on the scaffolding theory. Thus, digital scaffolds aiming at temporary assisting learners to internalize a CPS process and to develop their metacognitive skills were integrated to a digital application that has been used by undergrad students in business administration. By using a mix method, this research evaluated the influence of these scaffolds on the learning of CPS and the development of metacognitive skills. It also contributes to understand how these scaffolds influence learners during their problem-solving process and to describe their intention of use. Quantitative results indicate that access to scaffolds improved the performance on one assessment and show that it led to the development of the planning metacognitive skill. Qualitative results suggest that learners considered that these scaffolds were helping them to improve the quality of their assessments, although they did not perceive that these tools were also designed to develop their metacognitive skills. The results suggest that these learners can be called novices regarding their CPS skill. Indeed, they seem to allocate insufficient time to analyze the situation, they do not evaluate alternative solutions nor consider the negative consequences of their chosen solution and they insufficiently used their metacognitive skills of monitoring, self-regulation, and self-evaluation. The perceived utility of these scaffolds seem correlated with the perceived relevance, the perceived output quality, and the perceived enjoyment of using them. Considering a high perceived ease-of-use amongst all participants, this suggests that intention of use is mostly linked to the perceived utility. The results suggest that these scaffolds are more relevant in online learning, compared to face-to-face learning. Prompts, compared to a check list and videos of experts’ solutions, seem to have more influence on CPS process. Several recommendations are proposed to improve the design and the use of digital scaffolds. Learners should be trained by their teacher to use them efficiently. Teachers should demonstrate their relevance and the manner that students should use them for learning purposes. Digital scaffolds should offer a sufficient cognitive support throughout the CPS process. The application should include functions that allow students to understand why these should use these tools. Designers should consider the determinants of perceived usefulness when they conceptualize scaffolds to foster their usage. In sum, although this research has some limitations, notably a data collection done during the COVID-19 pandemic, it significantly contributes to the literature by proposing several recommendations aiming at improving the design and the use of digital scaffolds in higher education.