L'étude de contacts atomiques ajustables est rendue possible par la réalisation de jonctions à cassure. Ce type de structure est constitué d'un conducteur métallique, tel que l'aluminium ou l'or, déposé sur un substrat, et dans lequel une constriction localement sous-gravée forme un pont suspendu. En déformant le substrat, cette constriction est étirée de façon contrôlée. De cette manière l'étirement de la jonction peut être stabilisé au stade d'un contact de taille atomique. Le travail de recherche présenté ici est scindé en deux parties. D'une part, des jonctions à cassure simples en aluminium sur substrat en bronze ont été étudiées aux très basses températures. A l'aide du phénomène de réflexions d'Andreev nous arrivons à la conclusion que l'aluminium, à l'inverse de l'or, ne forme pas de chaînes monoatomiques plus longues qu'un dimère. Une structure double de type transistor à un électron (SET) a également été mesurée aux très basses températures. D'autre part, un système composé d'une ou de deux jonctions à cassure sur membranes fines en silicium monocrystallin a été développé et caractérisé à température ambiante. Ce système constitue un nanosystème électromécanique, ou NEMS, intégrable en technologie silicium. Des membranes, d'une épaisseur de 340 nm seulement, ont été fabriquées à partir de substrats SOI. Les propriétés mécaniques statiques et dynamiques de ces membranes sont étudiées. Plusieurs actionnements mécaniques stables, constitués d'une pointe déplacée par un piézo, ont été développés. Ils permettent à chaque jonction à cassure sur membrane d'être adressée individuellement, y compris aux très basses températures. L'influence d'une illumination en lumière laser sur la conductance de contacts point en or est étudiée. Une augmentation de la conductance est mesurée. L'influence du substrat peut être exclue grâce à l'utilisation de membranes fines. Cet effet est relié à un phénomène de transmission assistée par photons. Dans ce travail, des jonctions à cassure, initialement développées pour la physique fondamentale, sont intégrées sur des membranes en silicium, permettant ainsi une utilisation en tant que capteurs électromécaniques.

Les travaux de recherche présentés pour l'habilitation à diriger des recherches, visent à proposer de nouveaux outils pour simuler des interventions médicales et chirurgicales. Ces outils ont plusieurs applications dont l'amélioration de la formation des praticiens, la planification d'interventions pour la préparation et la validation d'une thérapie ou encore l'assistance au geste médical durant une intervention. Or, pour simuler ces interventions de manière réaliste voire prédictive, il faut tenir compte de la déformation des structures anatomiques et des interactions mécaniques entre les outils et les organes. En même temps, la simulation doit être interactive et calculée en temps-réel pour garder le geste du praticien dans la boucle de la simulation. Le défi majeur de notre travail est donc de garantir un calcul précis au niveau de la simulation tout en gardant un temps de calcul très court, qui soit compatible avec le temps-réel. D'abord, nous proposons une formulation optimisée de la méthode par éléments finis (FEM) et de nouveaux outils numériques (pré-conditionneurs, couplage entre modèles...) dédiés à au calcul FEM temps-réel. Cette approche est utilisée pour calculer la biomécanique des déformations des tissus anatomiques et les instruments flexibles. Nous abordons ensuite un autre point clé de ces simulations que sont les conditions aux limites. Les interactions mécaniques entre organes et/ou entre les outils chirurgicaux et les tissus sont souvent complexes à modéliser. Or, une mauvaise prise en compte de ces interactions peut aboutir à des erreurs importantes. Notre approche suit les bases de la mécanique non-régulière pour gérer, notamment, le contact et le frottement entre solides. Nous étendons l'approche à d'autres modèles d'interaction (comme l'insertion d'aiguille par exemple). Dans ce contexte, nous mettons l'accent sur le calcul de la compliance des structures en temps-réel. Par ailleurs, pour certaines interventions où le retour visuel n'est pas parfait, le praticien se guide aussi avec le sens du toucher. Il est donc important de reproduire au moins partiellement cette sensation - dite haptique - avec des interfaces à retour d'effort, pilotée à partir des données de la simulation. Dans ce domaine, nous proposons une approche centrée sur le rendu haptique des interactions mécaniques entre outil chirurgical et tissus humain. Cette approche se base notamment sur une désynchronisation du calcul de la boucle de simulation et de la boucle de retour d'effort qui demande un rafraichissement à haute fréquence (1kHz). Finalement, nous présentons ces résultats de recherche sur des exemples concrets d'application et nous présentons les défis à venir pour permettre à la simulation de devenir un outil utilisé par les praticiens à l'avenir. Le manuscrit est en anglais.

Proteins have an indispensable role in the cell. They carry out a wide variety of structural, catalytic and signaling functions in all known biological systems. To perform their biological functions, proteins establish interactions with other bioorganic molecules including other proteins. Therefore, protein-protein interactions is one of the central topics in molecular biology. My thesis is devoted to three different topics in the field of protein-protein interactions. The first one focuses on solvent contribution to protein interfaces as it is an important component of protein complexes. The second topic discloses the structural and functional potential of fluorine's unique properties, which are attractive for protein design and engineering not feasible within the scope of canonical amino acids. The last part of this thesis is a study of the impact of charged amino acid residues within the hydrophobic interface of a coiled-coil system, which is one of the well-established model systems for protein-protein interactions studies. I. The majority of proteins interact in vivo in solution, thus studies of solvent impact on protein-protein interactions could be crucial for understanding many processes in the cell. However, though solvent is known to be very important for protein-protein interactions in terms of structure, dynamics and energetics, its effects are often disregarded in computational studies because a detailed solvent description requires complex and computationally demanding approaches. As a consequence, many protein residues, which establish water-mediated interactions, are neither considered in an interface definition. In the previous work carried out in our group the protein interfaces database (SCOWLP) has been developed. This database takes into account interfacial solvent and based on this classifies all interfacial protein residues of the PDB into three classes based on their interacting properties: dry (direct interaction), dual (direct and water-mediated interactions), and wet spots (residues interacting only through one water molecule). To define an interaction SCOWLP considers a donor–acceptor distance for hydrogen bonds of 3.2 Å, for salt bridges of 4 Å, and for van der Waals contacts the sum of the van der Waals radii of the interacting atoms. In previous studies of the group, statistical analysis of a non-redundant protein structure dataset showed that 40.1% of the interfacial residues participate in water-mediated interactions, and that 14.5% of the total residues in interfaces are wet spots. Moreover, wet spots have been shown to display similar characteristics to residues contacting water molecules in cores or cavities of proteins. The goals of this part of the thesis were: 1. to characterize the impact of solvent in protein-protein interactions 2. to elucidate possible effects of solvent inclusion into the correlated mutations approach for protein contacts prediction To study solvent impact on protein interfaces a molecular dynamics (MD) approach has been used. This part of the work is elaborated in section 2.1 of this thesis. We have characterized properties of water-mediated protein interactions at residue and solvent level. For this purpose, an MD analysis of 17 representative complexes from SH3 and immunoglobulin protein families has been performed. We have shown that the interfacial residues interacting through a single water molecule (wet spots) are energetically and dynamically very similar to other interfacial residues. At the same time, water molecules mediating protein interactions have been found to be significantly less mobile than surface solvent in terms of residence time. Calculated free energies indicate that these water molecules should significantly affect formation and stability of a protein-protein complex. The results obtained in this part of the work also suggest that water molecules in protein interfaces contribute to the conservation of protein interactions by allowing more sequence variability in the interacting partners, which has important implications for the use of the correlated mutations concept in protein interactions studies. This concept is based on the assumption that interacting protein residues co-evolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. The study presented in section 2.2 has been carried out to prove that an explicit introduction of solvent into the correlated mutations concept indeed yields qualitative improvement of existing approaches. For this, we have used the data on interfacial solvent obtained from the SCOWLP database (the whole PDB) to construct a “wet” similarity matrix. This matrix has been used for prediction of protein contacts together with a well-established “dry” matrix. We have analyzed two datasets containing 50 domains and 10 domain pairs, and have compared the results obtained by using several combinations of both “dry” and “wet” matrices. We have found that for predictions for both intra- and interdomain contacts the introduction of a combination of a “dry” and a “wet” similarity matrix improves the predictions in comparison to the “dry” one alone. Our analysis opens up the idea that the consideration of water may have an impact on the improvement of the contact predictions obtained by correlated mutations approaches. There are two principally novel aspects in this study in the context of the used correlated mutations methodology : i) the first introduction of solvent explicitly into the correlated mutations approach; ii) the use of the definition of protein-protein interfaces, which is essentially different from many other works in the field because of taking into account physico-chemical properties of amino acids and not being exclusively based on distance cut-offs. II. The second part of the thesis is focused on properties of fluorinated amino acids in protein environments. In general, non-canonical amino acids with newly designed side-chain functionalities are powerful tools that can be used to improve structural, catalytic, kinetic and thermodynamic properties of peptides and proteins, which otherwise are not feasible within the use of canonical amino acids. In this context fluorinated amino acids have increasingly gained in importance in protein chemistry because of fluorine's unique properties: high electronegativity and a small atomic size. Despite the wide use of fluorine in drug design, properties of fluorine in protein environments have not been yet extensively studied. The aims of this part of the dissertation were: 1. to analyze the basic properties of fluorinated amino acids such as electrostatic and geometric characteristics, hydrogen bonding abilities, hydration properties and conformational preferences (section 3.1) 2. to describe the behavior of fluorinated amino acids in systems emulating protein environments (section 3.2, section 3.3) First, to characterize fluorinated amino acids side chains we have used fluorinated ethane derivatives as their simplified models and applied a quantum mechanics approach. Properties such as charge distribution, dipole moments, volumes and size of the fluoromethylated groups within the model have been characterized. Hydrogen bonding properties of these groups have been compared with the groups typically presented in natural protein environments. We have shown that hydrogen and fluorine atoms within these fluoromethylated groups are weak hydrogen bond donors and acceptors. Nevertheless they should not be disregarded for applications in protein engineering. Then, we have implemented four fluorinated L-amino acids for the AMBER force field and characterized their conformational and hydration properties at the MD level. We have found that hydrophobicity of fluorinated side chains grows with the number of fluorine atoms and could be explained in terms of high electronegativity of fluorine atoms and spacial demand of fluorinated side-chains. These data on hydration agrees with the results obtained in the experimental work performed by our collaborators. We have rationally engineered systems that allow us to study fluorine properties and extract results that could be extrapolated to proteins. For this, we have emulated protein environments by introducing fluorinated amino acids into a parallel coiled-coil and enzyme-ligand chymotrypsin systems. The results on fluorination effect on coiled-coil dimerization and substrate affinities in the chymotrypsin active site obtained by MD, molecular docking and free energy calculations are in strong agreement with experimental data obtained by our collaborators. In particular, we have shown that fluorine content and position of fluorination can considerably change the polarity and steric properties of an amino acid side chain and, thus, can influence the properties that a fluorinated amino acid reveals within a native protein environment. III. Coiled-coils typically consist of two to five right-handed α-helices that wrap around each other to form a left-handed superhelix. The interface of two α-helices is usually represented by hydrophobic residues. However, the analysis of protein databases revealed that in natural occurring proteins up to 20% of these positions are populated by polar and charged residues. The impact of these residues on stability of coiled-coil system is not clear. MD simulations together with free energy calculations have been utilized to estimate favourable interaction partners for uncommon amino acids within the hydrophobic core of coiled-coils (Chapter 4). Based on these data, the best hits among binding partners for one strand of a coiled-coil bearing a charged amino acid in a central hydrophobic core position have been selected. Computational data have been in agreement with the results obtained by our collaborators, who applied phage display technology and CD spectroscopy. This combination of theoretical and experimental approaches allowed to get a deeper insight into the stability of the coiled-coil system. To conclude, this thesis widens existing concepts of protein structural biology in three areas of its current importance. We expand on the role of solvent in protein interfaces, which contributes to the knowledge of physico-chemical properties underlying protein-protein interactions. We develop a deeper insight into the understanding of the fluorine's impact upon its introduction into protein environments, which may assist in exploiting the full potential of fluorine's unique properties for applications in the field of protein engineering and drug design. Finally we investigate the mechanisms underlying coiled-coil system folding. The results presented in the thesis are of definite importance for possible applications (e.g. introduction of solvent explicitly into the scoring function) into protein folding, docking and rational design methods. The dissertation consists of four chapters: ● Chapter 1 contains an introduction to the topic of protein-protein interactions including basic concepts and an overview of the present state of research in the field. ● Chapter 2 focuses on the studies of the role of solvent in protein interfaces. ● Chapter 3 is devoted to the work on fluorinated amino acids in protein environments. ● Chapter 4 describes the study of coiled-coils folding properties. The experimental parts presented in Chapters 3 and 4 of this thesis have been performed by our collaborators at FU Berlin. Sections 2.1, 2.2, 3.1, 3.2 and Chapter 4 have been submitted/published in peer-reviewed international journals. Their organization follows a standard research article structure: Abstract, Introduction, Methodology, Results and discussion, and Conclusions. Section 3.3, though not published yet, is also organized in the same way. The literature references are summed up together at the end of the thesis to avoid redundancy within different chapters.

La simulation numérique des systèmes multicorps en présence d'interactions complexes, dont le contact frottant, pose de nombreux défis, tant en terme de modélisation que de temps de calcul. Dans ce manuscrit de thèse, nous étudions deux familles de décomposition de domaine adaptées au formalisme de la dynamique non régulière des contacts (NSCD). Cette méthode d'intégration implicite en temps de l'évolution d'une collection de corps en interaction a pour caractéristique de prendre en compte le caractère discret et non régulier d'un tel milieu. Les techniques de décomposition de domaine classiques ne peuvent de ce fait être directement transposées. Deux méthodes de décomposition de domaine, proches des formalismes des méthodes de Schwarz et de complément de Schur sont présentées. Ces méthodes se révèlent être de puissants outils pour la parallélisation en mémoire distribuée des simulations granulaires 2D et 3D sur un centre de calcul haute performance. Le comportement de structure des milieux granulaires denses est de plus exploité afin de propager rapidement l'information sur l'ensemble des sous domaines via un schéma semi-implicite d'intégration en temps.

La dégradation géométrique de la voie ferrée sur les Lignes à Grande Vitesse (LGV) est un phénomène qui entraîne des coûts de maintenance importants pour assurer une qualité de circulation et de sécurité. Cette dégradation géométrique est imputable, en partie au tassement de la couche de ballast qui constitue l'une des parties de la voie ferrée. Le tassement du ballast est un phénomène difficile à estimer et à prédire car sa nature granulaire et ses caractéristiques particulières entraînent des variabilités de ses propriétés mécaniques. Ce travail de thèse est consacré à l'étude du comportement mécanique du ballast, pour le développement d'un modèle prédictif du tassement sur voie ferrée à partir de la caractérisation mécanique initiale du matériau (grâce à l'utilisation du pénétromètre léger Panda) et des sollicitations auxquelles la voie est soumise. Grâce à l'étude paramétrique développée sur un banc d'essais à échelle réelle, nous avons constitué et validé un modèle de prédiction qui est basé sur une loi de relaxation logarithmique. La modélisation numérique par éléments discrets en utilisant la méthode de la Dynamique des Contacts permet d'étudier les propriétés mécaniques du matériau ballast à l'échelle des grains. L'analyse des déformations transitoires montre une dépendance claire de la déformation moyenne par rapport à la contrainte appliquée et au rapport d'aspect en raison de l'action du frottement aux frontières. Les fluctuations de ces déformations, sont très importantes et semblent évoluer avec la déformation moyenne. Finalement, la pertinence de la caractérisation du ballast à partir de l'essai Panda a été vérifiée à partir d'une étude paramétrique sur les mécanismes d'enfoncement grâce à l'utilisation de cette approche numérique discrète.

On s'intéresse à la modélisation des matériaux granulaires composé d'agrégats non convexes et cohésifs en vue d'application à la rhéologie des poudres d'UO2 . L'influence du degré de non-convexité des particules est analysé en termes de grandeurs macroscopiques (frottement interne et cohésion de Coulomb) et de paramètres micro-mécaniques tels que l'anisotropie de la texture et la transmission des efforts. Il apparaît en particulier que la compacité évolue d'une manière complexe avec la non-convexité et que la résistance au cisaillement augmente mais sature sous l'effet d'imbrication entre agrégats. Des modèles simples sont introduits pour décrire ces comportements en termes de paramètres micro-mécaniques. De même, des études systématiques par cisaillement, compaction uniaxiale et compression simple montrent que la cohésion interne augmente avec la non-convexité mais est fortement contrôlée par les conditions aux limites et l'apparition de bandes de cisaillement ou de concentrations de contraintes.

The astronomical increase in the number of wireless devices such as smart phones in 21th century has revolutionized the way people communicate with one another and share information. The new wireless technologies have also enabled researchers to collect real data about how people move and meet one another in different social settings. Understanding human mobility has many applications in different areas such as traffic planning in cities and public health studies of epidemic diseases. In this thesis, we study the fundamental properties of human contact graphs in order to characterize how people meet one another in different social environments. Understanding human contact patterns in return allows us to propose a cost-effective routing algorithm for spreading information in Delay Tolerant Networks. Furthermore, we propose several contact predictors to predict the unobserved parts of contact graphs when only partial observations are available. Our results show that we are able to infer hidden contacts of real contact traces by exploiting the underlying properties of contact graphs. In the last few years, we have also witnessed an explosion in the number of people who use social media to share information with their friends. In the last part of this thesis, we study the running times of several information spreading algorithms in social networks in order to find the fastest strategy. Fast information spreading has an obvious application in advertising a product to a large number of people in a short amount of time. We prove that a fast information spreading algorithm should efficiently identify communication bottlenecks in order to speed up the running time. Finally, we show that sparsifying large social graphs by exploiting the edge-betweenness centrality measure can also speed up the information spreading rate. / Graduate

Designs for deep ultraviolet (DUV) edge emitting laser diodes (LDs) based on the wurtzite III-nitride (III-N) material system are presented. A combination of proprietary and commercial advanced semiconductor LD simulation software is used to study the operation of III-N based DUV LDs theoretically. Critical factors limiting device performance are identified based on an extensive literature survey. A comprehensive design parameter space is investigated thoroughly with the help of advanced scripting capabilities. Several design strategies are proposed to eliminate the critical problems completely or partially. A DUV LD design is proposed based exclusively on AlInN active layers grown epitaxially on bulk AlN substrates because AlInN offers a promising alternative to AlGaN for the realization of LDs and LEDs operating in the DUV regime. The proposed AlInN-based design also features a tapered electron blocking layer (EBL) instead of a homogeneous one. Tapered EBLs redistribute the interfacial polarization charge volumetrically throughout the entire EBL thickness via compositional grading, and eliminate the parasitic inversion layer charge. AlGaN based DUV LD designs are explored also because at present, it may be difficult to grow AlInN epitaxially with superior crystalline quality. Polarization charge matching is proposed to improve electron and hole wavefunction overlap within the active region. Although the strategy of polarization charge matching has already been proposed in the literature to enhance performance of visible wavelength LEDs and LDs, the proposed design presents the first demonstration that polarization charge matching is also feasible for DUV LDs operating at sub-300 nm wavelengths. A lateral current injection (LCI) LD design is proposed featuring polarization-charge-matched barriers and regrown Ohmic contacts to avoid a group of issues related to the highly inefficient p-type doping of wide bandgap III-N materials in vertical injection designs. The proposed design partially decouples the problem of electrical injection from that of optical confinement. Although the idea of an LCI LD design has been proposed in the literature in the 90s to be used as longer wavelength active sources in optoelectronic integrated circuits using GaInAsP/InP and related material systems, the proposed design is the first theoretical demonstration that this concept can be applied to DUV LDs based on III-N material system. To solve the problem of hole transport in vertical injection designs, a DUV LD design based exclusively on AlGaN material system is presented, featuring an inverse-tapered p-waveguide layer instead of an EBL. Several EBL designs are investigated, and compared with conventionally-tapered EBL design. Through judicious volumetric redistribution of fixed negative polarization charge, inverse tapering may be exploited to achieve nearly flat valence band profiles free from barriers to hole injection into the active region, in contrast to conventional designs. Numerical simulations demonstrate that the inverse tapered strategy is a viable solution for efficient hole injection in vertical injection DUV LDs operating at shorter wavelengths (< 290 nm).

The interrelation between space and culture represents the central question of this doctoral thesis. To interpret this relationship the author approaches the issue by virtue of actual identity attributes of the selected ethnic groups, namely Slovak and Hungarian minorities living in Prague. The aim of the work is to define the relevance and unique representation of the spatial and cultural phenomenon in the context of existing relations, including determining the extent of observability this mutual connection. The hypothesis of this doctoral is to present culture as a spatially unbounded, and the phenomenon of space as a medium, which can influence the intensity of interest in relation to the own ethno-identifying components. The verification of this assumption author carries out within social and virtual space, on the basis of registered discourses. Discourses, sorted into thematic categories, represent the most common attributes of ethnicity and ethnic identity of the given target groups. The empirical part of this thesis contains the analysis and interpretation of the discourses, which are supported with the theory of articulation. More comprehensive definitions of applied theoretical approaches, together with terminology, research methods and ethics or netiquette, are situated in the...

During the past thirty years several models for lifelong education after retirement have been developed worldwide, one of them being the University of the Third Age (U3A). This study explored the contributions of the U3A to the educational needs of older adults and evaluated the benefits they perceived from their participation in U3A by means of a literature study and an empirical investigation. The latter used a survey to explore the experiences of U3A members of two U 3As and presidents of 68 U3As in Victoria, Australia by means of two different questionnaires. As only 1.47 percent of the over-55 population of Victoria are U3A members, the survey also investigated barriers to U3A participation in general and with special reference to the male population. The findings indicated that member respondents were very satisfied with their U3A experiences which had made substantial differences in their lives. Both male and female respondents saw personal, mental, social, and physical improvement as a result of U3A participation. The majority indicated that participation had improved their intellectual development. Significant differences in the perceptions of male and female participants emerged: female members outnumbered males by three to one. Both the presidents and the members expressed some programmatic concerns, primarily obtaining tutors and classroom availability. The subject areas covered by courses presented were extensive. There was a difference in the subjects desired by males and female respondents; very few courses are offered in science and economics. Some barriers to participation identified are a lack of awareness of U3A, the stereotypical attitudinal barrier of `I am too old' and negative past educational experiences. Moreover, U3As should increase marketing endeavours. Although most U3As advertise, almost a third of the respondents indicated that they would have joined earlier if aware of U3As. A contributing factor appears to be a virtual lack of research and information provided in educational academic journals and other media about lifelong education after retirement. Based on the findings, recommendations were made for future research and for improved practice in the U3A environment as a means to enhance the quality of life for older adults. / Educational Studies / D.Ed. (Comparative Education)