The definition of clinical target volume (CTV) margins around gross tumor volume (GTV) for radiotherapy of esophageal cancer (EC) and many solid tumors is still a challenge hence the currently available in-vivo imaging techniques still fail to detect areas of microscopic tumor extension (MTE). Many parameters of the tumor microenvironment (TME), e.g., tumor cell proliferation, cancer stem cells, hypoxia, kinases, immune architecture and patient-specific parameters are hypothesized as inducers of MTE in esophageal cancer and other tumors. The correlation of these TME biomarkers with MTE before, during or after radiochemotherapy (RCHT) is crucial in the era of image-guided, adaptive high-precision photon or particle therapy. In this thesis, two study cohorts were used to assess some selected TME biomarkers and their predictive value on MTE for an improved CTV definition. The first study used immunohistochemistry analysis for the assessment of TME marker namely HIF-1α, Ki67, p53, CXCR4 and PD1 in a cohort of retrospectively collected formalin-fixed paraffin-embedded (FFPE) blocks of EC patients treated with either neoadjuvant radiochemotherapy plus resection (NRCHT+R) or resection alone (R). The subsequent study employing a multiplex-immunofluorescence technique assessed the expression of various markers, i.e., FAK, ILK, CD44, HIF-1α and Ki67, in a cohort of prospectively prepared FFPE resection specimens of EC patients with implantable fiducial gold markers at the proximal and distal tumor borders illustrating the GTV prior to NRCHT+R and correlated those markers to the MTE. The findings from our first study showed upregulation of HIF-1α, Ki67, p53, CXCR4 and PD1, within squamous cell carcinoma (SCC) and adenocarcinoma (AC) patients treated with R compared to those having undergone NRCHT+R. In the second study higher expression of FAK+, CD44+, HIF-1+, and Ki67+ cells in tumor-nests than in tumor-stroma of both SCC and AC patients was found, although ILK+ cells were higher in tumor stroma. In addition, MTE reaching up to 31 mm beyond the fiducial markers was found in three patients (all cT3N1) with a stronger expression of FAK+, CD44+ and ILK+ cells in tumor-nests in between the fiducial markers (former GTV) and beyond those (former CTV), even after NRCHT. In conclusion, there is thus far no evidence that the TME influences the CTV margin on an individual patient basis, hence differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not detected.

Im Rahmen der vorliegenden Arbeit wurde ein Spritzgießwerkzeug mit einem neuartigen Mehrschichtverbundheizsystem zur dynamischen Temperierung entwickelt und umgesetzt. Dabei wurde das ausgewählte Heiz‐ und Kühlsystem unter theoretischen und praktischen Gesichtspunkten betrachtet und für den variothermen Fertigungsprozess verifiziert. Aus den ersten durchgeführten praktischen Versuchen zeigte sich, dass dieses Heizsystem zur dynamischen Temperierung von Formwerkzeugen geeignet ist. Anschließend wurden mit dem realisierten Spritzgießwerkzeug Versuchskörper mit spezieller Oberflächenstrukturierung und variierenden Werkzeugwandtemperaturen angefertigt und untersucht. Ziel war es, über diese Strukturierung eine Beeinflussung der Glasfaserverteilung im Formteilrandbereich zu erreichen und die tribologischen Eigenschaften bei Kunststoff‐Kunststoff‐Gleitpaarungen hinsichtlich Reibung und Verschleiß zu verbessern. Mit einer kleinen Auswahl an Strukturen und entsprechenden thermoplastischen Polymermaterialien wurden praktische Versuche zur tribologischen Prüfung durchgeführt. / In the present work an injection mould was developed and implemented with a novel multilayer composite heating system for dynamic temperature control. Here the selected heating and cooling system was considered from a theoretical and practical point of view and verified for the variothermal manufacturing process. The first practical tests showed that this heating system is suitable for the dynamic temperature control of tools. Subsequently, with this injection mould, test specimens with a special surface structure and varying mould wall temperatures were produced and examined. The aim was to achieve through this structuring an impact on the distribution of glass fibres in the edge region of mouldings and improve the tribological properties of plastic‐plastic‐pairings in terms of friction and wear. With a small selection of structures and corresponding thermoplastic polymeric materials practical experiments for tribological testing were performed.

The distinct element method (DEM) is a useful tool in rock engineering to model jointed rock masses. To simulate a jointed rock mass realistically, the main challenge is to be able to capture its complex geometry which consists of blocks with various shapes and sizes, and to model the interactions between these blocks. The main contribution of this thesis is the development of novel algorithms in the DEM to model jointed rock masses, namely rock slicing procedures for block generation, and algorithms for contact detection between polygonal blocks in 2-D or polyhedral blocks in 3-D. These algorithms make use of convex optimisation techniques, for which there exist efficient solution procedures. They do not rely on conventional vertex-edge-face hierarchical data structures and tedious housekeeping algorithms. The algorithms have been verified against analytical and numerical solutions, as well as validated against experimental results published in the literature. Among those, the results of DEM simulations were compared against the experimental model tests and numerical simulations of jointed beams carried out by Talesnick et al. (2007) and Tsesarsky & Talesnick (2007) respectively. Emphasis was placed on modelling the stiffness of the block interfaces accurately, and this was accomplished by reinterpreting the laboratory data published by the investigators. The capabilities of the numerical tools are also examined and demonstrated in areas for which the DEM has found practical application. A substantial fraction of this thesis is devoted to illustrating how these tools can assist the engineer in designing support systems; for example, designing the length and spacing of rock bolts and the lining thickness for a tunnel. Algorithms to model rock bolt and lining support were implemented for this purpose. Interesting comparisons with elastic solutions for supported openings were obtained. Further, it is shown that the relative benefit of introducing more rock bolts or thicker lining can be evaluated using the numerical tools with the aid of an interaction diagram. In the final part of this thesis, the case history of the 1963 Vaiont rock slide in Italy is studied. The 2-D analyses led to useful insights concerning the influence of the reservoir water level, the rock mass strength and deformability, and the slide surface shear stiffness. 3-D analyses were undertaken to investigate the influence of the eastern boundary of the slope, and interesting insights were obtained concerning the slope kinematics. Overall, the case study shows that the tools are capable of modelling problems with specific physical and geometrical detail in both 2-D and 3-D.

Im Zuge der kontinuierlichen Weiterentwicklung von Verarbeitungs- und Verpackungsmaschinen werden immer höhere Anforderungen an die für den Gütertransfer eingesetzte Fördertechnik gestellt. Neben der erhöhten Förderleistung sind zudem ein schmiermittelfreier Betrieb sowie eine hundertprozentige Verfügbarkeit gefordert. Durch die zunehmende Leistungssteigerung kommt es zu hohen Beanspruchungen, die bei falscher Auslegung zu mechanischem oder thermischem Versagen der Kunststoff-Bauteile im Fördersystem führen können. Während das mechanische Versagen mit den aktuellen Dimensionierungen vermieden werden kann, gibt es bezüglich des thermischen Versagens keine hinreichend genaue Auslegungsvorschrift. Die vorliegende Arbeit befasst sich mit der thermischen Analyse von Gleitketten-Fördersystemen sowie den darin eingesetzten thermoplastischen Kunststoff-Kunststoff-Gleitpaarungen. Diesbezüglich werden die Gleitkontakte eines Gleitkettenförderers und deren Belastungen analysiert. Durch Abstraktion des Kette–Schiene-Systems wird ein semi-analytisches Berechnungsmodell zur Abschätzung der Reibtemperatur entwickelt, welches mittels experimenteller Untersuchungen auf einem Tribo-Prüfstand und an einem Fördersystem verifiziert wird. Aus den Untersuchungsergebnissen konnte ein thermisches Auslegungskriterium für Kunststoff-Kunststoff-Gleitpaarungen abgeleitet werden, welches sowohl auf Gleitketten-Förderer als auch perspektivisch auf ähnliche tribologische Systeme übertragen werden kann. / In the course of the continuous enhancements of processing and packaging machines, higher demands are set on conveying technology used for transferring goods. In addition to an increased delivery rate, a lubricant-free operation as well as a hundred percent availability are claimed. Increasing performance leads to high stresses that can result to mechanical or thermal failure of plastic components in the conveying system, if incorrectly designed. While mechanical failure can be avoided with up to date dimensioning, there is no sufficiently precise dimensioning criterion in regard to thermal failure. The present thesis is concerning with the thermal analysis of sliding chain conveyor systems as well as the thermoplastic plastic-plastic sliding pairs used therein. In this regard, the sliding contacts of a sliding chain conveyor and their loads are analyzed. By abstraction of the chain–rail system, a semi-analytical model for estimating the frictional temperature is developed, which is verified by experimental studies on a tribo test bench and a conveyor system. From the study results, a thermal dimensioning criterion for plastic plastic pairings could be derived, which can be applied to sliding chain conveyor as well as perspectivly similar tribological systems.

Cette étude présente les architectures et la dynamique sédimentaire de la pente carbonatée au nord de Little Bahama Bank (Bahamas) à partir des données de sondeur multifaisceaux, de sondeur de sédiments (Chirp) et de sismique multitraces Haute Résolution (HR) issues de la mission Carambar 1(2010). Une analyse morpho-sédimentaire de surface permet de définir les grands domaines physiographiques et les éléments architecturaux de la pente et précise la répartition spatiale des sédiments dans le contexte actuel de haut niveau marin relatif. Elle révèle une pente dominée par de la boue de périplate-forme avec différents niveaux d’induration et entaillée par des glissements et des canyons sous marins.La variabilité spatiale du transfert de boue depuis la plate-forme vers la pente, couplée à l’évolution latérale de l’intensité du courant des Antilles est à l’origine de grandes différences morphologiques d’est en ouest. Dans la partie occidentale, la pente est environ deux fois plus étendue que dans la partie orientale,elle s’apparente à un système progradant. La pente orientale, quant à elle, est marquée par des processus de bypass. En effet, cette partie est caractérisée par de nombreux canyons sous-marins se poursuivant par des sillons distributaires alimentant des zones de dépôts distales confinées. Une étude intégrée permet la caractérisation à haute résolution des glissements et des canyons et la proposition d’un modèle déformation. Ces éléments architecturaux sont initiés par des déstabilisations intra-pente et leur évolution est contrôlée par des épisodes d’érosion régressive, la sédimentation pélagique et les écoulements gravitaires boueux. Enfin, une analyse sismo-stratigraphique permet de reconstituer l’évolution tectono-sédimentaire de la pente de l’Albien à l’Actuel en lien avec le contexte géodynamique des Caraïbes, l’eustatisme et la production carbonatée sur la plate-forme. / This study focuses on the architectures and the sedimentary dynamic of a carbonate slope located on the northern part of Little Bahama Bank (Bahamas) using a dataset composed of multibeam echo sounder,subbottom profiler (Chirp) and High-Resolution (HR) multichannel seismic collected during the Carambar 1cruise (2010). A morpho-sedimentary surface analysis defines the physiographic domains and the architectural elements of the slope and investigates the spatial distribution of sediments in the context of the current sea-level highstand. It reveals a slope dominated by periplatform ooze with several levels of induration and incised by numerous slides and submarine canyons. The spatial variability of off-bank transport, combined with the lateral variability of the Antilles Current intensity, are at the origin of a morphological evolution from west to east in the study area. In the western part, the slope is around twice as large as the eastern part and can be considered as a prograding system. The eastern slope is marked by bypass processes. Indeed, numerous submarine canyons are visible on the seafloor and are connected to several shallow distributary furrows feeding confined depositional areas. An integrated study allows a high resolution characterisation of slides and submarines canyons and enables us to propose a model of formation. These architectural elements are initiated by intra-slope destabilisations and their evolution is controlled by phases of retrogressive erosion,pelagic sedimentation and muddy gravity flows. Finally, a seismo-stratigraphic analysis allow to reconstitutethe tectonic and sedimentary evolution of the slope since the Albian to the present-day by establishing a link with the geodynamic context of Caraïbes, relative sea-level changes and the carbonate production on the platform.

Ce travail présente une analyse de la dynamique sédimentaire du système turbiditique actuel de l’Ogooué (Golfe de Guinée), secteur encore très peu exploré à l’heure actuelle. Il se base sur l’interprétation de données géo-acoustiques (sondeur multifaisceaux et sismique chirp), sédimentologiques (carottes küllenberg et interface) et courantométriques issues de campagnes océanographiques réalisées par le SHOM. L’analyse morpho-bathymétrique détaillée a révélé la diversité des structures morphologiques le long de la marge. Ces observations, associées aux données sédimentaires et courantométriques ont permis de préciser les différents processus de dépôt. La configuration du plateau continental, dont la largeur se réduit fortement vers le Nord va entraîner une variabilité des transferts sédimentaires en profondeur le long du système turbiditique de l’Ogooué. La très faible extension du plateau continental à l’extrémité de l’île Mandji et l’action de la dérive littorale favorisent une sédimentation gravitaire active sous la forme d’écoulements turbiditiques dans le canyon du Cap Lopez ou de glissements sous-marins. Grâce à la comparaison de données bathymétriques à différentes échelles de temps, il a été possible de documenter à très haute résolution les mécanismes d’initiation et de développement d’instabilités ainsi que les processus sédimentaires à l’origine du développement des méandres. En plus des apports détritiques, les écoulements gravitaires initiés dans ce secteur vont également transporter de grandes quantités de matière organique. / This work presents an analysis of the sedimentary dynamic in the Ogooué turbidite system (Gulf of Guinea), previously poorly studied. It is based upon the interpretation of geo-acoustic (multibeam bathymetry and imagery, seismic chirp), sedimentological (Küllenberg and interface cores) and current-meter data recovered during oceanographic cruises conducted by the SHOM. The detailed morpho-bathymetric analysis reveals the diversity of morphological structures along the margin. These observations, combined with current meter and sedimentological data allowed us to determine various depositional processes. The decreasing width of the continental shelf toward the North involves a variability of sediment transfer along the Ogooué turbidite system. The very small extension of the continental shelf at the extremity of the Mandji Island and the action of longshore drift promote active gravitary sedimentation dominated by turbiditic flows in the Cap Lopez canyon or submarine slides.By comparing bathymetric data at different time scales, we document the mechanisms responsible for the initiation and development of instabilities and the sedimentary processes related to meander growth. In addition to detrital fraction, the gravity flows initiated in this area also carry large amounts of organic matter.

With cancer being one of the leading causes of death globally, and with oral cancers being among the most common types of cancer, it is of interest to conduct large-scale oral cancer screening among the general population. Deep Learning can be used to make this possible despite the medical expertise required for early detection of oral cancers. A bottleneck of Deep Learning is the large amount of data required to train a good model. This project investigates two topics: certainty calibration, which aims to make a machine learning model produce more reliable predictions, and Active Learning, which aims to reduce the amount of data that needs to be labeled for Deep Learning to be effective. In the investigation of certainty calibration, five different methods are compared, and the best method is found to be Dirichlet calibration. The Active Learning investigation studies a single method, Cost-Effective Active Learning, but it is found to produce poor results with the given experiment setting. These two topics inspire the further development of the cytological annotation tool CytoBrowser, which is designed with oral cancer data labeling in mind. The proposedevolution integrates into the existing tool a Deep Learning-assisted annotation workflow that supports multiple users.

This master’s thesis introduces a slide bearing analysis using the MBS software tool of FEV Virtual Engine, including real surface topography based on 3D roughness measurements. The first half of the thesis gives a brief overview about gasoline combustion engines, slide bearing usage in engines, slide bearing construction and about essential approaches for the characterization of elasto-hydrodynamic behavior. In the second half, the process of model building, rough surface measurement and preparation of analyses are described. At the end of this thesis, the results of the analyses are shown and discussed.

The diploma thesis deals with the analysis of surface texture parameters during pistol production. The aim of the diploma thesis was to formulate requirements for pistol quality, to analyze the existing production process of the chosen pistol component, to analyze the texture of the functional surface after selected technological operations with a proposal for correction of the manufacturing process and recommendations for practice. The work includes mapping the life cycle of the pistol with a focus on the technological procedure of processing the main part of the pistol - the slide of the pistol. The surface texture of surface texture is also described, depending on the measurement of the defined area. Based on 250 measured and evaluated surface texture parameters, recommendations for correction of the manufacturing process and recommendations for the design and development of the pistol were formulated.

Main subject of this work is design of childrens playgroung elements. In this work there is also presented analysis of existent theme. I have designed a few variations, from which I chose the best solution. This solution I worked out in technical, aesthetic and ergonomical aspects. Designed elements match current requirements of safety standards.