The efficiency of low voltage scanning electron microscopy, which presents near-surface information, has been well known for a long time. However, it is not widely known that the high resolution capability can only be achieved when the surface reveals the original characteristics of the materials without any deterioration due contamination. Therefore, initial attention in this study is directed at clarifying the efficient use of the ultra high resolution, low voltage SEM (UHRLV SEM), (Ultra55, Zeiss). The SEM images and the selected electrons for detection, and damage that occurs through UHRVL SEM observation are also researched. Subsequently, the most efficient specimen preparation technique, which is appropriate for the characteristics of the individual materials, is investigated for galvanized steel, ultrasonically welded alloys of Al6111 and AZ31 alloy, Ti6Al4V alloy honeycomb structure and a ceramic sensor. The outcomes of appropriate specimen preparation technique and use of the extremely Low-Voltage below 2.0 kV, are presented in the results section. The study also presented the challenge of improving the low compositional contrast for the dissimilar materials of aluminium and magnesium, and to reduce charging effects in an insulating material comprising a ceramic sensor. As an application of the surface prepared by the process in this study, 3D tomography is also introduced.

Current thinking suggests that specialised modules process visual information in a hierarchical manner, using local circuitry in order to maximise efficiency both in terms of wiring costs and stimulus coverage (Reichl et al. (2012)). The resulting organisation has been shown to contain structure in the form of stripes, columns and pinwheels, which in animal models have been linked to functional segregation and specificity. In human cortex, post-mortem investigations have assisted in the visualisation of two such key features: ocular dominance columns (ODC) within V1, and a stripe system within V2 (Adams et al. (2007); Hockfield et al. (1990)). However, functional observations in humans have until recently been beyond the investigatory scope of in-vivo methodology, and as such, a role of these networks has yet to be conclusively determined. In the small number of instances of in-vivo investigations of human ODC and V2 stripes (Cheng et al. (2001); Yacoub et al. (2001); Nasr et al. (2016)), data have been acquired for a small number of carefully selected participants over long scan durations. I aimed to overcome these limitations and explore the functional similarities further, employing a novel, ultra-high resolution fMRI sequence to do so. I measured the cortical response to monocular stimulation and recorded a robust response within V1. However, the regular and repeating functional patterns of ODCs were not observed. Using multivariate techniques I concluded, based on robust classification, that reliable monocular signals were present but that they were subtle and difficult to differentiate from noise. I then investigated the segregation of colour, form and motion within V2, where I found evidence for spatially segregated signals in response to colour and motion, but not to form. I hypothesised that the form stimulus was sub-optimal in driving the neural population of the associated stripes. Based on a limited number of samples, activity in response to colour and motion stimulation conformed on average to the neuroanatomical profile of the V2 stripe system. I suggest that my results offer encouragement for in-vivo investigations of small-scale functional organisation in visual cortex.

La cristallographie des rayons-X à ultra-haute résolution permet d'analyser la distribution de charge des molécules et d'étudier les interactions intermoléculaires avec précision. Des études structurales de plusieurs composés à base de thiophène ont été menées à bien, et le phénomène de désordre a été discuté. Des analyses expérimentales et théoriques de la densité de charge de deux molécules importantes ont été réalisées en utilisant le modèle d'atome multipolaire. Un nouveau modèle d'atomes virtuels est également testé : il permet le calcul rapide des propriétés électrostatiques. La liaison hydrogène avec l'oxygène comme accepteur est étudiée par l'analyse extensive de plus de 500.000 structures cristallines. Les résultats de stéréochimie sont comparés avec la densité électronique des atomes d'oxygène dans différents environnement chimiques, ce qui permet de montrer la dépendance directionnelle des liaisons hydrogène et des formes et orientations des paires d'électrons libres. Finalement, il est montré qu'en l'absence de données de diffraction des rayons X à haute résolution, le principe de transférabilité des paramètres de la densité électronique peut être exploité pour étudier les propriétés électrostatiques et les interactions intermoléculaires. Ce principe a été utilisé avec succès sur une petite molécule à base de thiophène et sur la protéine FAD-dépendante Cholestérol oxydase / Ultra high resolution X-ray crystallography allows for analyzing the charge distribution in the molecules and provides methods to study the intermolecular interactions at a deeper level. Structural studies of several thiophene based compounds have been carried out and the phenomenon of disorder has been discussed. Experimental and theoretical charge density analysis of two important molecules was performed using a multipolar atom model. A new virtual atom model is also tested which allows for a rapid calculation of the electrostatic properties. The hydrogen bonding with oxygen atom acceptor is studied through an extensive survey of more than 500,000 crystal structures. The stereo chemical results are compared with the electron density of the oxygen atoms in different chemical environments which give conclusive evidences for the dependence of directionality of hydrogen bonds on the shape and orientation of the electrons lone pairs. Finally, it has been shown that how in the absence of high resolution X-rays data, principle of transferability of electron density parameters between molecules can be used to study the electrostatic properties and the intermolecular interactions. This principle has been successfully applied to a small thiophene based molecule and the large FAD binding protein Cholesterol oxidase

Im Rahmen dieser Arbeit wurde ein neuartiges 3D Fluoreszenz Mikroskop, OMX gennant, entworfen und gebaut. Ein umfassender Design-Neuansatz erlaubt es den neuen Anforderungen der aktuellen Biologie bezüglich erhöhter Auflösung in Zeit und Raum Rechnung zu tragen. Mit Ausnahme vom Auflegen des Objektträgers sind alle Aspekte des Mikroskops Computer-gesteuert. Einen Großteil der Software floß in ein neues, eigenständiges Open-Source Projekt ein. Es erlaubt die Verarbeitung sehr großer, mehrdimensionaler Bilddaten, und die Entwicklung neuartiger Algorithmen in einer flexiblen Oberfläche. OMX hat zwei Betriebsarten: Im ersten Modus können bis zu 100 Bilder pro Sekunde mit optischer Auflösung in mehreren Farbkanälen aufgenommen werden. Dies entspricht etwa 10 3D Bildern pro Sekunde. Im zweiten Modus können mit der Structured Illumination Mikroskopie fixierte Präparate mit eine Auflösung unterhalb des Abbe-Limits untersucht werden. Im zweiten Teil dieser Arbeit, stelle ich erste Forschungsergebnisse von OMX vor. Drosophila X-chromosomen markiert mit GFP-MSL3 wurden in situ im sub-Sekunden Bereich beobachtet. Mit Hilfe neuentwickelter Algorithmen konnte ich die Chromosomendynamik analysieren. Das Falten und Entfalten von Bereichen eines Chromosoms wurde als Funktion der Zeit darstellen. Chromosomenstrukturen wurden mit Hilfe der SIM an fixierten primären embryonalen Kulturen untersucht. Unterstrukturen von 100-200nm sind erkennenbar. Viele Bilder zeigen eine DNA-reiche Hülle die einen DNA-armen Chromosomenkern umgibt. Ausserdem habe ich polytäne Chromosomen mit SIM aufgenommen. Bandstrukturen zeigen sich mit deutlich erhöhter Detailklarheit, und Längsfasern sind sichtbar, die ansonsten nur vom Elektronenmikroskop her bekannt sind. Als weiteres Beispiel der verbesserten Auflösungsfähigkeit habe ich Kernporen untersucht. In mit DAPI gefärbten Mauszellen zeigen diese sich als dunkle Punkte mit einer Größe von etwa 120nm. / A novel fluorescence 3D wide-field light microscope called OMX, was designed and implemented. The novel design addresses improved speed and resolution requirements of current biology research. After designing and building the microscope body I designed and implemented the needed computer software for the eight computers required to operate OMX. Over the course of the project I also designed and implemented a new Open-Source software platform for algorithm development and image analysis. It focuses on very large multi-dimensional image data handling and visualization in general. OMX can operate in two modes: In the first mode a live specimen can be observed at optical resolution (approx. 250nm) at speeds up to 100 sections per second simultaneously in multiple wavelength channels. This equals about 10 3D images per second. The second mode is for observing fixed preparations at resolutions below the Abbe diffraction limit using Structured Illumination Microscopy (SIM). This produces 3D volumetric image data with lateral resolution near 100nm and axial resolution of about 200nm. In the second part of this thesis I show first results achieved using the OMX microscope. Chromosome dynamics was analyzed using various newly developed image analysis algorithms. Sub-second motion was observed for in situ Drosophila X-chromosomes tagged with GFP-MSL3. Parts of the chromosome can be traced within the nucleus and time-series data shows its folding and unfolding as a function of time. Chromosome structure was imaged using SIM on formaldehyde fixed primary embryonic cultures stained with DAPI. Features of the sub-structure with sizes around 100-200nm were apparent. Many chromosomes show an outer layer along the chromatin axis appearing persistently denser in DNA than the central core. Polytene chromosomes were imaged using SIM. Band patterns are visible in much more detail than in conventional deconvolution microscopy and longitudinal fibers known only from electron microscopy were visible.

Large display environments (LDEs) are interactive physical workspaces featuring one or more static large displays as well as rich interaction capabilities, and are meant to visualize and manipulate very large datasets. Research about mid-air interactions in such environments has emerged over the past decade, and a number of interaction techniques are now available for most elementary tasks such as pointing, navigating and command selection. However these techniques are often designed and evaluated separately on specific platforms and for specific use-cases or operationalizations, which makes it hard to choose, compare and combine them.In this dissertation I propose a framework and a set of guidelines for analyzing and combining the input and output channels available in LDEs. I analyze the characteristics of LDEs in terms of (1) visual output and how it affects usability and collaboration and (2) input channels and how to combine them in rich sets of mid-air interaction techniques. These analyses lead to four design requirements intended to ensure that a set of interaction techniques can be used (i) at a distance, (ii) together with other interaction techniques and (iii) when collaborating with other users. In accordance with these requirements, I designed and evaluated a set of mid-air interaction techniques for panning and zooming, for invoking commands while pointing and for performing difficult pointing tasks with limited input requirements. For the latter I also developed two methods, one for calibrating high-precision techniques with two levels of precision and one for tuning velocity-based transfer functions. Finally, I introduce two higher-level design considerations for combining interaction techniques in input-constrained environments. Designers should take into account (1) the trade-off between minimizing limb usage and performing actions in parallel that affects overall performance, and (2) the decision and adaptation costs incurred by changing the resolution function of a pointing technique during a pointing task.

Les environnements à grands écrans (Large Display Environments, LDE) sont des espaces de travail interactifs contenant un ou plusieurs grands écrans fixes et divers dispositifs d'entrée ayant pour but de permettre la visualisation et la manipulation de très grands jeux de données. La recherche s'est de plus en plus intéressée à ces environnements durant ces dix dernières années, et il existe d'ores-et-déjà un certain nombre de techniques d'interaction correspondant à la plupart des tâches élémentaires comme le pointage, la navigation et la sélection de commandes. Cependant, ces techniques sont souvent conçues et évaluées séparément, dans des environnements et des cas d'utilisations spécifiques. Il est donc difficile de les comparer et de les combiner.Dans ce manuscrit, je propose un ensemble de guides pour l'analyse et la combinaison des canaux d'entrée et de sortie disponibles dans les LDEs. Je présente d'abord une étude de leurs caractéristiques selon deux axes: (1) le retour visuel, et la manière dont il affecte l'utilisabilité des techniques d'interaction et la collaboration co-localisée, et (2) les canaux d'entrée, et comment les combiner en d'efficaces ensembles de techniques d'interaction. Grâce à ces analyses, j'ai développé quatre pré-requis de conception destinés à assurer que des techniques d'interaction peuvent être utilisées (i) à distance, (ii) en même temps que d'autres techniques et (iii) avec d'autres utilisateurs. Suivant ces pré-requis, j'ai conçu et évalué un ensemble de techniques de navigation, d'invocation de commandes tout en pointant, et de pointage haute-précision avec des moyens d'entrée limités. J'ai également développé deux méthodes de calibration de techniques de pointage, l'une spécifique aux techniques ayant deux niveaux de précision et l'autre adaptée aux fonctions d'accélération. En conclusion, j'introduis deux considérations de plus haut niveau sur la combinaison de techniques d'interaction dans des environnements aux canaux d'entrée limités : (1) il existe un compromis entre le fait de minimiser l'utilisation des membres de l'utilisateur et celui d'effectuer des actions en parallèle qui affecte les performances de l'ensemble ; (2) changer la fonction de transfert d'une technique de pointage durant son utilisation peut avoir un effet négatif sur les performances. / Large display environments (LDEs) are interactive physical workspaces featuring one or more static large displays as well as rich interaction capabilities, and are meant to visualize and manipulate very large datasets. Research about mid-air interactions in such environments has emerged over the past decade, and a number of interaction techniques are now available for most elementary tasks such as pointing, navigating and command selection. However these techniques are often designed and evaluated separately on specific platforms and for specific use-cases or operationalizations, which makes it hard to choose, compare and combine them.In this dissertation I propose a framework and a set of guidelines for analyzing and combining the input and output channels available in LDEs. I analyze the characteristics of LDEs in terms of (1) visual output and how it affects usability and collaboration and (2) input channels and how to combine them in rich sets of mid-air interaction techniques. These analyses lead to four design requirements intended to ensure that a set of interaction techniques can be used (i) at a distance, (ii) together with other interaction techniques and (iii) when collaborating with other users. In accordance with these requirements, I designed and evaluated a set of mid-air interaction techniques for panning and zooming, for invoking commands while pointing and for performing difficult pointing tasks with limited input requirements. For the latter I also developed two methods, one for calibrating high-precision techniques with two levels of precision and one for tuning velocity-based transfer functions. Finally, I introduce two higher-level design considerations for combining interaction techniques in input-constrained environments. Designers should take into account (1) the trade-off between minimizing limb usage and performing actions in parallel that affects overall performance, and (2) the decision and adaptation costs incurred by changing the resolution function of a pointing technique during a pointing task.

Les symétries géométriques jouent un rôle important dans la compréhension de la stabilité de tout système physique. En structure nucléaire, elles sont reliées à la forme du champ moyen utilisé pour décrire les propriétés des noyaux atomiques. Dans le cadre de cette thèse, nous avons utilisé les prédictions obtenues avec l'aide du Hamiltonien du champ moyen nucléaire avec le potentiel de Woods-Saxon Universel pour étudier les effets des symétries dites de « Haut-Rang ». Ces symétries ponctuelles mènent à des dégénérescences des états nucléaires d’ordre 4. Il est prédit que la symétrie tétraédrique influence la stabilité des noyaux proches des nombres magiques tétraédriques [Z,N]=[32,40,56,64,70,90-94,136]. Nous avons sélectionné la région des Terres-Rares proche du noyau doublement magique tétraédrique 154Gd pour notre étude. Dans cette région, il existe des structures de parité négative qui sont mal comprises. Or la symétrie tétraédrique, en tant que déformation octupolaire non-axiale, brise la symétrie par réflexion et doit produire des états de parité négative. Après une étude systématique des propriétés expérimentales des noyaux de la région, nous avons sélectionné le 156Gd comme objet de notre étude des modes d’excitation octupolaire. Nous avons utilisé les probabilités réduites de transition gamma pour discerner ces différents modes. Pour atteindre cet objectif, nous avons réalisé trois expériences de spectroscopie gamma à l’ILL de Grenoble avec les détecteurs EXILL et GAMS afin de mesurer les durées de vie et les intensités des transitions gamma des états candidats. L'analyse de nos résultats montre que notamment la forme tétraédrique aide à comprendre les probabilités des transitions dipolaires. Ce résultat ouvre de nouvelles perspectives expérimentales et théoriques. / Geometrical symmetries play an important role in the understanding of all physical systems. In nuclear structure they are linked to the shape of the mean-field used to describe the atomic nuclei properties. In the framework of this thesis, we have used the predictions obtained with the help of the nuclear mean-field Hamiltonian with the Universal Woods-Saxon potential to study the effects of the so-called “High-Rank” symmetries. These point-group symmetries lead to a nuclear state degeneracy of the order of 4. It is predicted that the tetrahedral symmetry affects the stability of nuclei close to the tetrahedral magic numbers [Z,N]=[32,40,56,64,70,90-94,136]. We have selected the Rare-Earth region close to the tetrahedral doubly magic nucleus 154Gd for our study. In this region, there exists negative parity structures poorly understood. Yet the tetrahedral symmetry, as related to a non-axial octupole deformation, breaks the reflection symmetry and leads to the negative parity states. Following a systematics of experimental properties of the nuclei in this region, we have selected 156Gd as the object of our study for the octupole excitation modes. We have used the reduced transitions probabilities to discriminate between these modes. To achieve this goal, we have performed three gamma spectroscopy experiments at the ILL in Grenoble with the EXILL and GAMS detectors to measure the lifetimes and the gamma transition intensities from the candidate states. The analysis of our results shows that including the tetrahedral shape helps to understand the dipole transition probabilities. This result will open new experimental and theoretical perspectives.