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Lors de l’invasion tumorale, les cellules épithéliales tumorales acquièrent des propriétésmigratoires et invasives impliquant des modifications phénotypiques importantes. Parmi ceschangements, on observe notamment une réorganisation ou une perte des complexes d’adhérenceintercellulaire et une acquisition de la capacité à dégrader la matrice extracellulaire à travers uneaugmentation d’expression des métalloprotéinases matricielles (MMPs). Dans cette étude, nous noussommes plus particulièrement intéressés aux jonctions serrées qui sont constituées de protéinestransmembranaires (occludine, claudines) liées au cytosquelette d’actine par des protéinescytoplasmiques sous-membranaires incluant les Zonula Occludens (ZO-1, -2 et -3). Parmi cesmolécules, nous avons évalué le rôle potentiel de ZO-2 dans l’acquisition de propriétés invasives parles cellules tumorales. In vivo, nous avons montré une diminution d’expression des ZOs dans lescancers broncho-pulmonaires avec une localisation cytoplasmique préférentielle. De plus, in vitro, lalocalisation des ZOs varie en fonction du potentiel invasif des cellules tumorales et leur réorganisationest corrélée à la migration cellulaire. Nous démontrons également que l’inhibition de ZO-2 augmenteles capacités invasives de cellules tumorales invasives et s’accompagne d’une augmentationd’expression des MMP-2 et -14 et du facteur de transcription ZEB-2. Ces résultats suggèrent que ZO-2, composant structural des complexes d’adhérence intercellulaire dans les cellules différenciées,pourrait jouer un rôle clé dans le processus d’invasion tumorale. Sa capacité à transiter de lamembrane au cytoplasme et/ou au noyau lui permettrait d’agir comme une molécule de signalisationen régulant la transcription de gènes. Les données obtenues démontrent un rôle anti-invasif de ZO-2. / During tumor invasion, tumor epithelial cells acquire migratory and invasive propertiesinvolving important phenotypic alterations. Among these changes, one can observe a reorganization ora loss of cell-cell adhesion complexes such as tight junctions and an increased ability to degradeextracellular matrix through an enhanced expression of matrix metalloproteinases (MMPs). Tightjunctions are composed of transmembrane proteins (occludin, claudins) linked to the actincytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family(ZO-1, -2, -3). Among these molecules, we evaluated the potential role of ZO-2 in the acquisition ofinvasive properties by tumor cells. In vivo, we showed a decrease of ZOs expression in bronchopulmonarycancers with a preferential localization in the cytoplasm. In addition, in vitro, thelocalization of ZOs varies according to invasive properties of tumor cells and their reorganization iscorrelated with cell migration. We also demonstrate that ZO-2 inhibition increases invasive capacitiesof invasive tumor cells. This was associated with an increase of MMPs (MMP-2 and -14) and thetranscription factor ZEB-2 expression. These results suggest that ZO-2, known as a structuralcomponent of cell-cell adhesion complexes in differentiated epithelial cells, could play a key role intumor invasion through its ability to shuttle from the membrane to the cytosol or nucleus, and act assignaling molecule regulating gene transcription. This study shows an anti-invasive role of ZO-2.

Diese Dissertation soll einen Beitrag zur Weiterentwicklung der luftgestützten Verkehrslageerfassung leisten. Als Plattform dafür dient ein flugzeuggetragenes Kamerasystem, welches mit einem Inertialsystem gekoppelt ist. Vorgestellt werden hauptsächlich bildverarbeitende Algorithmen, welche an die Bildaufnahme anschließend bis hin zur Ermittlung der verkehrstechnischen Kenngrößen zum Einsatz kommen. Nach kurzer Skizzierung der verwendeten Hardware wird die Kalibrierung der Kameraeinbauwinkel durch Testflüge erläutert und auf ihre Genauigkeit hin untersucht. Es wird gezeigt, dass die Orientierungsdaten nicht die vom Hersteller angegebene Genauigkeit erreichen, was jedoch für die Verkehrslageerfassung nur von geringer Bedeutung ist. Anschließend an die Bildaufbereitung, welche die Orthobildgenerierung sowie die Eingrenzung der verkehrsaktiven Flächen beinhaltet, wird zur Ermittlung der Fahrzeugdichte ein zweistufiger Fahrzeugerkennungsalgorithmus entwickelt, welcher zunächst auf Kantenfilterbasis möglichst schnell Hypothesen erstellt. Diese werden in einer zweiten Phase durch eine Support Vector Machine überprüft, wobei ein Großteil der Fehlhypothesen verworfen wird. Die Erkennung erreicht bei guten Voraussetzungen Vollständigkeiten bis zu 90 Prozent bei sehr geringem Anteil von Fehldetektionen. Anschließend wird ein auf Singulärwertzerlegung basierender Tracking-Algorithmus verwendet, um Fahrzeughypothesen in benachbarten Bildern zu assoziieren und die mittleren Geschwindigkeiten zu ermitteln. Die erhaltenen Geschwindigkeiten unterscheiden sich um weniger als zehn km/h von den manuell erhobenen. Abschließend wird eine alternative Orientierungsmethode vorgestellt, welche auf Basis von GPS-Positionen und Bildinformationen automatisch die Fluglage ermittelt. Dies geschieht durch die Extraktion und das Matching von Straßensegmenten sowie zusätzliche Passpunktverfolgung. Die Ergebnisse weisen Genauigkeiten von etwa 0,1 bis 0,2 Grad auf. / This dissertation should make a contribution to the further development of airborne traffic detection. The used hardware is an airborne camera system combined with an inertial measurement unit for orientation determination. Mainly computer vision algorithms are presented, which are applied afterwards the image acquisition up to the determination of the most important traffic data. After a short presentation of the used hardware the calibration of the camera''s alignment angles during test flights is explained and its accuracy is analyzed. It is shown that the orientation data doesn''t reach the specified accuracy, which is fortunately less important for traffic detection. After the image preparation, which contains the ortho image generation as well as the clipping of traffic areas, a two-stage vehicle detection algorithm is implemented, which at first rapidly creates hypotheses based on edge filters. In the second stage those hypotheses are verified by a Support Vector Machine which rejects most of the False Posititves. At good conditions the detection reaches completeness rates of up to 90 percent with a low contingent of FP detections. Subsequently a tracking algorithm based on singular value decomposition is applied to associate vehicle hypotheses in adjacent images and determine the average speed. The achieved velocities differ less than ten kph from the manually obtained data. Concluding an orientation method is presented, that automatically determines the airplane''s attitude based on GPS and image information. This is realized by extraction and matching of street segments and additional tracking of ground control points. The results have accuracies of around 0.1 to 0.2 degrees.

Durch ein zunehmendes Verkehrsaufkommen wächst die Notwendigkeit den Verkehr in irgendeiner Form "intelligent" zu organisieren. In diesem Kontext sind die sogenannten Intelligent Transportation Systems (ITS) in den Fokus der Forschung gerückt. Diese Systeme zielen in der Regel auf die dynamische Optimierung der Routenwahlen von Verkehrsteilnehmern ab und sollen dadurch die Effizienz des Verkehrs verbessern. Grundsätzlich kann die Vorstellung einer optimalen Routenwahl in eine von zwei Kategorien eingeteilt werden: das Nash Gleichgewicht und die systemoptimale Routenwahl. Während Nash Gleichgewichte vergleichsweise einfach erzielt werden können-beispielsweise dadurch, dass jeder Fahrer seine Route egoistisch optimiert-ist das Erreichen des Systemoptimums ungleich schwerer. Dieses setzt nämlich voraus, dass alle Fahrer miteinander kooperieren und gemeinsam eine Lösung finden, von der die Gesamtheit als solche profitiert. In dieser Dissertation diskutieren wir das Design eines dezentralisierten ITS, welches in der Lage ist, eine systemoptimale Routenzuweisung im Straßennetzwerk zu approximieren, so dass die Fahrzeuge den price of anarchy nicht mehr in voller Höhe bezahlen müssen. Der besondere Fokus liegt hierbei auf der Anwendbarkeit des Ansatzes in realistischen Umgebungen, in denen eine Vielzahl von Schwierigkeiten zu erwarten ist. Dies beinhaltet beispielsweise eine unvollständige oder inkorrekte Sicht auf die aktuelle Verkehrssituation, das Fehlen von Wissen über Fahrzeuge, die erst in der Zukunft das Straßennetz betreten sowie ein nicht perfekter oder ressourcenlimitierter Kommunikationskanal. / The increasing amount of road traffic necessitates approaches that somehow "intelligently" organize traffic. In this context, the study of intelligent transportation systems (ITS) has been performed for some time. The goals of such systems include, e.g., is the dynamic optimization of route choices in a road network and hence the improvement of traffic conditions. There are two main methodologies how an optimization can be performed: the optimization towards a Nash equilibrium or towards a system optimum. While Nash equilibria can be easily reached, e.g., when every driver selfishly optimizes his own route, reaching the system optimum is a challenging task and requires all drivers to cooperate in an altruistic manner in favor of the system from a global perspective. In this work, we discuss the design of a decentralized ITS that is capable of approximating system optimal route choices in the network avoiding that the drivers have to pay the full price of anarchy. The focus, in this context, lies on the applicability to real life situations where a number of difficulties has to be expected, e.g., an incomplete or incorrect view on the current traffic situation, the lack of future knowledge and an imperfect or limited communication channel. Facing these challenging questions, we develop solutions to a number of research questions, that arise from the aforementioned difficulties. Before we can do so, we focus on the fundamental concepts of traffic optimization with an emphasis both on the theoretical concepts as well as their applicability in real world environments.

Thesis have quantified the total number of students from 1999 until 3th March, 2015 who graduated within the excess year after the standard length of study (SDS). During the reporting period, the total number of finished studies in SDS plus anadditional semester totalled nearly 130,000 students, in SDS plus an additional one year were then finished 117,000 studies. The total number of failed studies, which ended up in the additional extra year in period is 40,000, of which 28,000 in SDS plus one semester and 12,000 in SDS increased by one year. Direct costs of the prolonged studies were estimated at 1.1 billion Kč for 2014. Of which 200 million are sunk costs to studies that have not been completed successfully. The work also calculated the opportunity costs in terms of revenue that could have Czech Republic earned, if the student have finished in SDS and have worked which was estimated at 4.7 billion Kč including both direct and indirect taxes.

Electricity production from photovoltaic power plants has been one of the fastest growing energy industries in the last decade. Number of small power inverters working parallelly with the low voltage grid is growing. At the same time, the requirements for the correct behaviour of network inverters in the network by the distribution grid operators are also increasing. The thesis deals with creation of a workplace for testing the operational and technical requirements for micro-sources. The first part of the thesis consists of literature search of inverter demands according to the current rules for parallel production operation. The second part deals with the setting up of test procedures and automation. The last part evaluates selected tests of the functions of the inverters.

Electricity production from photovoltaic power plants has been one of the fastest growing energy industries in the last decade. Number of small power inverters working parallelly with the low voltage grid is growing. At the same time, the requirements for the correct behaviour of network inverters in the network by the distribution grid operators are also increasing. The thesis deals with creation of a workplace for testing the operational and technical requirements for micro-sources. The first part of the thesis consists of literature search of inverter demands according to the current rules for parallel production operation. The second part deals with the setting up of test procedures and automation. The last part evaluates selected tests of the functions of the inverters.

Die vorliegende Arbeit ist Teil eines Forschungsprojekts zur Entwicklung eines neuartigen Systems zur zerstörungsfreien und bildgebenden Untersuchung von Luftfracht mittels Neutronen- und Gammastrahlung. Im Rahmen dieser Arbeit wurde eine Strahlungsquelle entwickelt, die optimal auf die Anwendung angepasst ist: Ein gepulster Deuteronenstrahl wird in einer Ionenquelle erzeugt und mittels eines niederenergetischen Strahltransportsystems zum Hauptbeschleuniger geführt. Dieser besteht aus einem Radiofrequenz Quadrupol (RFQ) mit einer finalen Energie von 6 MeV. Da für die Anwendung sehr kurze Pulse der Strahlung in der Größenordnung einiger Nanosekunden unabdingbar sind, musste eine neuartige Lösung zur Pulsung des Deuteronenstrahls gefunden werden. Eine große Herausforderung bestand hierbei im Zusammenspiel der kurzen Pulsdauer und hohen Pulsladung in Kombination mit der hohen Wiederholrate. Dieses wurde erreicht, indem ein spezielles Pulsungssystem innerhalb des Strahlentransportes zwischen Ionenquelle und RFQ eingefügt wurde. Dieses System enthält neben einem strahlablenkenden auch ein strahlbündelndes Element. Der Deuteronenstrahl wird hinter dem RFQ auf ein Target geführt, welches aus Borcarbid besteht. In dieser Arbeit wird das komplette physikalische Design der Strahlungsquelle diskutiert sowie Simulationen zum Pulsungssystem bzw. dem RFQ-Beschleuniger präsentiert. Weiterhin werden Proof-of-Principle Experimente beschrieben, die mithilfe eines Prototypen-Pulsungssystems entwickelt im Rahmen dieser Arbeit und gefertigt von der RI Research Instruments GmbH an einem speziell für diesen Zweck errichteten Teststands durchgeführt wurden. Außerdem wurden mehrere Experimente sowohl an der Beschleunigeranlage der Physikalisch- Technischen Bundesanstalt (PTB) Braunschweig als auch am RFQ Beschleuniger der Nuclear Energy Corporation of South Africa (NECSA) in Pelindaba durchgeführt, um das Target zu optimieren und das erzeugte Strahlungsfeld zu charakterisieren. / This thesis is part of a research project whose goal is to develop a novel, non-destructive imaging system to be employed for air freight security. The screening will be performed employing neutron- and gamma-radiation based techniques. One of the critical issues in this project was the absence of an adequate particle source. Thus, a new type of source was developed during this work. The new source consists of four main parts: A pulsed deuteron beam is formed in an ion source (IS) and is fed, via a matching low energy beam transport system (LEBT), into the main accelerator. The latter comprises a radio frequency quadrupole (RFQ) that produces a deuteron beam with a final energy of 6 MeV. Since pulsing of this beam in the regime of several nanoseconds is mandatory for the application, a novel solution had to be found to apply the required pulsing scheme, without undershoot the required beam charge per pulse. A major challenge in doing so was the combination of pulse length, high bunch charge as well as high repetition rate. This could be achieved by adding a pulsing system in between the LEBT section and RFQ: it consists of a beam-deflection, as well as a beam-bunching element. The deuteron beam is ultimately directed to a wobbling, plasma sprayed boron carbide (B4C) target. This work focuses on an entire physical design as well as simulation work of the pulsing system and RFQ. Furthermore, proof-of-principle experiments concerning a prototype of the pulsing system developed in the framework of this thesis and manufactured by RI Research Instruments GmbH could be performed at a test bench dedicated to this project. To round up the study, the suitability of the target and target reaction was demonstrated during multiple experiments performed at Physikalisch- Technische Bundesanstalt (PTB) at Braunschweig as well as the Nuclear Energy Corporation of South Africa (NECSA) in Pelindaba.

Isochrones are an often-used, traditional instrument in traffic and town planning. For instance, isochrones might be used to analyze the optimal position of a planned public transport stop or to analyze reachability. Unfortunately, in the real world, application isochrones are rarely calculated well. Instead of using actual isochrones, planning offices evaluate the distance rn the average person walks in n minutes, shorten rn by a detour heuristic and create a circle with radius rn and center point m to approximate the n-minute isochrone. But even proper isochrones are fundamentally flawed. They either assume the walking speed for every person to be identical or guess the walking speed more pessimistic. Obviously, both methods are massively misestimating the area within an isochrone and can lead to misinformed decisions. Using one universal walking speed underestimates the area in the isochrone for some people, overestimates the area for others. Pessimistic walking times underestimate the reachable area for most people. The central flaw of the approach is the use of the expectancy value of the walking speed. The distribution of pedestrian walking speed has already been determined statistically. Thinking in distributions immediately allows more precise statements about reachability, margin of error and would benefit the understanding of modal choice. This paper aims to introduce the concept of isostochochrones, which build on top the concept of isochrones. Allowing the use of walking speed distributions and independent delay distributions at multiple points in a network allows clear margin of error statements and leads to deeper understanding of the planning situation.:Ziel der Arbeit Isostochochronen Isostochochronen ersetzen Isochronen Isostochochronen sind eine Erweiterung der Isochronen Zufallsvariablen und Mittelwerte Heuristiken müssen abgeschafft werden Relevante Planungsziele identifizieren

Um conjunto de reflexões teóricas sobre as incompatibilidades entre a Ordem Inter-nacional pós-Guerra Fria e as categorias estruturantes dos paradigmas analíticos dominantes, esta tese procura também apontar dados empíricos e listar questões a serem compreendidas por um novo modo de produção de conhecimentos em rela-ções internacionais. Ela critica tanto os paradigmas unidimensionais, principalmente os de corte liberal e leno-stalinistas, quanto os bidimensionais, de inspiração realista e racionalista, indicando que ambos formam redes conceituais baseadas numa dialé-tica dicotômica, que reduz a complexidade do internacional e do estrangeiro a um olhar e interesse nacionais. Sugere que o sistema internacional e os subsistemas regionais, como objetos de estudo, não se reduzem a suas unidades, constituindo uma terceira dimensão, ou zona cinzenta, cuja conformação, para ser compreendida depende da análise integrada dos fenômenos da guerra, das globalizações e do for-talecimento do Estado. Completando as sugestões para o debate e a formulação de conceitos interpretativos mais abrangentes, além de alguns neologismos, esta tese constrói algumas tipologias compreensivas. O autor adverte, contudo, que essas formulações têm o propósito de ilustrar a análise, não de fechar a discussão com um modelo acabado. / A set of theoretical reflections on the contradictions between the post-Cold War inter-national order and the structuring categories of the prevailing analytical paradigms, this thesis also tries to point to empirical data and list questions to be understood by a new way of producing knowledge in international relations. It criticizes both one-dimensional paradigms, mainly those in the liberal and Lenin-Stalinist model, and two-dimensional paradigms of realistic and rational inspiration, showing that both of them build conceptual networks based on the dialectics of dichotomy, which reduces the complexity of being international and foreign to a national vision and interest. The work also suggests that the international system and the regional subsystems, as objects of study, are not limited to their units, making up a third dimension, or grey zone, whose configuration can only be understood through an integrated analysis of the war phenomena, globalization and the strengthening of the State. By making suggestions for the debate and formulation of more comprehensive interpretation concepts, in addition to some neologisms, this thesis builds some broad typologies. However, the author warns that these formulations have the purpose of illustrating the analysis, not closing the debate on a finished model.