@phdthesis{Augustin2014,
  author    = {Augustin, Anja},
  title     = {"Norden, Suden, Osten, Wester": L{\"a}nder und Bewohner der Heidenwelt in deutschen Romanen und Epen des 12. bis 14. Jahrhunderts. Rolandslied, Herzog Ernst, Parzival, Willehalm, Reinfried von Braunschweig, Wilhelm von {\"O}sterreich},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109142},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {2 B{\"a}nde: 1. Band S.1-637; 2. Band S.638-1288},
  year      = {2014},
  abstract  = {Die vorliegende Studie untersucht die Vorstellungen von der sogenannten „Heidenwelt" in deutschen Romanen und Epen des Mittelalters - und kommt zu teilweise v{\"o}llig neuen Ergebnissen, auch zu Wolfram von Eschenbach. Die als ebenso bedrohlich wie faszinierend empfundene Welt der „Heiden" umfaßte die gesamte Welt jenseits der h{\"o}fischen Zentren des selbst noch nicht g{\"a}nzlich christianisierten Abendlandes und barg hohes Konfliktpotential. Sie begann bereits vor der Haust{\"u}r, erstreckte sich {\"u}ber den Kreuzzugsraum, den Mittleren Osten, {\"A}thiopien und Indien bis in H{\"o}llen und Himmelssph{\"a}ren. Ich vergleiche die in Romanen und Epen genannten geo- und ethnographischen und zoologischen Begriffe sowohl mit dem gelehrten Wissen von Antike und Mittelalter, darunter die Werke Plinius', Solins und Isidors, als auch mit volkst{\"u}mlichen Vorstellungen, etwa zu Wilden Leuten. Die Abhandlung bezieht sich auch auf zahlreiche weitere Werke jenseits der im Titel genannten Texte, vor allem die beliebten Alexanderromane, anhand derer das Publikum der Dichter geschult war. Weit {\"u}ber Namensregister hinausgehend zeige ich urspr{\"u}ngliche Verbindungen, also die Hintergr{\"u}nde der in den Romanen stimmig verwendeten Termini, und neue Zusammenh{\"a}nge und Entwicklungen auf. Ich beschreibe die Aufteilung des Mundus - Himmel, H{\"o}llen, Paradiese - und der Erde und bespreche Naturhistorie und ihre Verbindung zu den Mythen, philosophische Themen sowie Fragen nach Ressourcen, Handelsrouten, Reisewegen und B{\"u}ndnispolitik. Die bisher oft als m{\"a}rchenhaft angesehenen Erz{\"a}hlungen der Kreuzzugszeit erweisen sich als kluge Stellungnahmen zu den wichtigsten Diskursen der Zeit. Diese wurden nicht nur an den theologisch gebundenen christlichen Universit{\"a}ten gef{\"u}hrt - die volkssprachigen Dichter machten sie einem gr{\"o}ßeren Publikum zug{\"a}nglich, vertraten jedoch oftmals divergierende Ansichten, zuvorderst zur Einordnung und Behandlung der heidnischen Gegner: Sind es Wilde, Ungeheuer, Geister, gar Neutrale Engel, D{\"a}monen - oder doch Menschen? Neue Erkenntnisse betreffen etwa Fragen nach der Erdgestalt (Kugel oder Scheibe?), die Vorstellung vom Weltgebirge ‚Kaukasus', Ernsts Grippia und die Antipoden, den Mongolensturm und den Priesterk{\"o}nig Johannes (m{\"o}glicher Retter des Abendlandes oder gar gef{\"a}hrlicher Heide?). V{\"o}llig neu ist die Analyse, Bewertung und Einordnung von Feirefiz' ber{\"u}hmtem Triumphkatalog in „Parzival" Kap.770: Sie offenbart sich als eine geniale, die gesamte Heidenwelt in geographischer Ordnung und Kreisschluß beschreibende Aufz{\"a}hlung und Verbindung menschlicher V{\"o}lker - nicht Monstren.},
  subject      = {Mittelhochdeutsch},
  language  = {de}
}
@phdthesis{SeitzHeinrich2014,
  author    = {Seitz-Heinrich, Kerstin},
  title     = {'M{\"a}rchen' in der Werbung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107817},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Eine korpusbasierte sprachwissenschaftliche Analyse {\"u}ber die Verwendung des Wortes ‚M{\"a}rchen' sowie verschiedener M{\"a}rchenmotive, -charaktere und -requisiten in der deutschsprachigen Werbung auf Basis der M{\"a}rchen der Br{\"u}der Grimm. Ein besonderer Fokus liegt dabei auf den zahlreichen Formen von Intertextualit{\"a}t.},
  subject      = {Werbesprache},
  language  = {de}
}
@phdthesis{Xu2014,
  author    = {Xu, Jiajia},
  title     = {A high-complexity lentiviral shRNA screen identifies synthetic lethal interactions with deregulated N-Myc in neuroblastoma cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-103157},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {In contrast to c-Myc, a deregulated expression of the MYCN gene is restricted to human neuroendocrine tumours. In most cases, the excessive activity of N-Myc results from a MYCN amplification. In neuroblastoma, amplification of MYCN is a predictor of poor prognosis and resistance to therapy. The inability to target the N-Myc protein directly necessitates the search for alternative targets. This project aimed at identifying genes specifically required for growth and survival of cells that express high levels of N-Myc using high-throughput shRNA screening combined with next generation sequencing. The identification and analysis of these genes will shed light on functional interaction partners of N-Myc. We screened a shRNA library containing 18,327 shRNAs and identified 148 shRNAs, which were selectively depleted in the presence of active N-Myc. In addition, shRNAs targeting genes that are involved in p53 and ARF turnover and apoptosis were depleted in the cell population during the screen. These processes are known to affect N-Myc-mediated apoptosis. Consequently, these results biologically validated the screen. The 148 shRNAs that showed a significant synthetic lethal interaction with high levels of N-Myc expression were further analysed using the bioinformatics program DAVID. We found an enrichment of shRNAs that target genes involved in specific biological processes. For example, we validated synthetic lethal interactions for genes such as, THOC1, NUP153 and LARP7, which play an important role in the process of RNA polymerase II-mediated transcription elongation. We also validated genes that are involved in the neddylation pathway. In the screen we identified Cullin 3, which is a component of the BTB-CUL3-Rbx1 ubiquitin ligase that is involved in the turnover of Cyclin E. Depletion of cullin 3 and activation of N-Myc was found to synergistically increase Cyclin E expression to supraphysiological levels, inducing S-phase arrest and a strong DNA damage response. Together with results from a proteomics analysis of N-Myc associated proteins, our results lead us to the following hypothesis: In a neuroblastoma cell, the high levels of N-Myc result in a conflict between RNA polymerase II and the replication machinery during S-phase. The newly identified interaction partners of N- Myc are required to solve this conflict. Consequently, loss of the interaction leads to a massive DNA damage and the induction of apoptosis. In addition, inhibition or depletion of the essential components of the neddylation pathway also results in an unresolvable problem during S-phase.},
  subject      = {Neuroblastom},
  language  = {en}
}
@phdthesis{Reutelshoefer2014,
  author    = {Reutelsh{\"o}fer, Jochen},
  title     = {A Meta-Engineering Approach for Document-Centered Knowledge Acquisition},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107523},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Today knowledge base authoring for the engineering of intelligent systems is performed mainly by using tools with graphical user interfaces. An alternative human-computer interaction para- digm is the maintenance and manipulation of electronic documents, which provides several ad- vantages with respect to the social aspects of knowledge acquisition. Until today it hardly has found any attention as a method for knowledge engineering. This thesis provides a comprehensive discussion of document-centered knowledge acquisition with knowledge markup languages. There, electronic documents are edited by the knowledge authors and the executable knowledge base entities are captured by markup language expressions within the documents. The analysis of this approach reveals significant advantages as well as new challenges when compared to the use of traditional GUI-based tools. Some advantages of the approach are the low barriers for domain expert participation, the simple integration of informal descriptions, and the possibility of incremental knowledge for- malization. It therefore provides good conditions for building up a knowledge acquisition pro- cess based on the mixed-initiative strategy, being a flexible combination of direct and indirect knowledge acquisition. Further it turns out that document-centered knowledge acquisition with knowledge markup languages provides high potential for creating customized knowledge au- thoring environments, tailored to the needs of the current knowledge engineering project and its participants. The thesis derives a process model to optimally exploit this customization po- tential, evolving a project specific authoring environment by an agile process on the meta level. This meta-engineering process continuously refines the three aspects of the document space: The employed markup languages, the scope of the informal knowledge, and the structuring and organization of the documents. The evolution of the first aspect, the markup languages, plays a key role, implying the design of project specific markup languages that are easily understood by the knowledge authors and that are suitable to capture the required formal knowledge precisely. The goal of the meta-engineering process is to create a knowledge authoring environment, where structure and presentation of the domain knowledge comply well to the users' mental model of the domain. In that way, the approach can help to ease major issues of knowledge-based system development, such as high initial development costs and long-term maintenance problems. In practice, the application of the meta-engineering approach for document-centered knowl- edge acquisition poses several technical challenges that need to be coped with by appropriate tool support. In this thesis KnowWE, an extensible document-centered knowledge acquisition environment is presented. The system is designed to support the technical tasks implied by the meta-engineering approach, as for instance design and implementation of new markup lan- guages, content refactoring, and authoring support. It is used to evaluate the approach in several real-world case-studies from different domains, such as medicine or engineering for instance. We end the thesis by a summary and point out further interesting research questions consid- ering the document-centered knowledge acquisition approach.},
  subject      = {Wissenstechnik},
  language  = {en}
}
@phdthesis{Naydenova2014,
  author    = {Naydenova, Tsvetelina},
  title     = {A Study of Seebeck and Nernst effects in (Ga,Mn)As/normal semiconductor junctions},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101981},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {The discovery of the Giant Magneto Resistance (GMR) effect in 1988 by Albert Fert [Baib 88] and Peter Gr{\"u}nberg [Bina 89] led to a rapid development of the field of spintronics and progress in the information technology. Semiconductor based spintronics, which appeared later, offered a possibility to combine storage and processing in a single monolithic device. A direct result is reduced heat dissipation. The observation of the spin Seebeck effect by Ushida [Uchi 08] in 2008 launched an increased interest and encouraged research in the field of spin caloritronics. Spintronics is about the coupling of charge and spin transport. Spin caloritronics studies the interaction between heat and spin currents. In contrast to spintronics and its variety of applications, a particular spin-caloritronic device has not yet been demonstrated. However, many of the novel phenomena in spin caloritronics can be detected in most spintronic devices. Moreover, thermoelectric effects might have a significant influence on spintronic device operation. This will be of particular interest for this work. Additional knowledge on the principle of coupling between heat and spin currents uncovers an alternative way to control heat dissipation and promises new device functionalities. This thesis aims to further extend the knowledge on thermoelectrics in materials with strong spin-orbit coupling, in this case the prototypical ferromagnetic semiconductor (Ga,Mn)As. The study is focused on the thermoelectric / thermomagnetic effects at the interface between a normal metal and the ferromagnetic (Ga,Mn)As. In such systems, the different interfaces provide a condition for minimal phonon drag contribution to the thermal effects. This suggests that only band contributions (a diffusion transport regime) to these effects will be measured. Chapter 2 begins with an introduction on the properties of the studied material system, and basics on thermoelectrics and spin caloritronics. The characteristic anisotropies of the (Ga,Mn)As density of states (DOS) and the corresponding magnetic properties are described. The DOS and magnetic anisotropies have an impact on the transport prop- erties of the material and that results in effects like tunneling anisotropic magnetores- istance (TAMR) [Goul 04]. Some of these effects will be used later as a reference to the results from thermoelectric / thermomagnetic measurements. The Fingerprint tech- nique [Papp 07a] is also described. The method gives an opportunity to easily study the anisotropies of materials in different device geometries. Chapter 3 continues with the experimental observation of the diffusion thermopower of (Ga,Mn)As / Si-doped GaAs tunnel junction. A device geometry for measuring the diffusion thermopower is proposed. It consists of a Si - doped GaAs heating channel with a Low Temperature (LT) GaAs / (Ga,Mn)As contact (junction) in the middle of the channel. A single Ti / Au contact is fabricated on the top of the junction. For transport characterization, the device is immersed in liquid He. A heating current technique is used to create a temperature difference by local heating of the electron system on the Si:GaAs side. An AC current at low frequency is sent through the channel and it heats the electron population in it, while the junction remains at liquid He temperature (experimentally con- firmed). A temperature difference arises between the heating channel and the (Ga,Mn)As contact. As a result, a thermal (Seebeck) voltage develops across the junction, which we call tunnelling anisotropic magneto thermopower (TAMT), similar to TAMR. TAMT is detected by means of a standard lock-in technique at double the heating current frequency (at 2f ). The Seebeck voltage is found to be linear with the temperature difference. That dependence suggests a diffusion transport regime. Lattice (phonon drag) contribution to the thermovoltage, which is usually highly nonlinear with temperature, is not observed. The value of the Seebeck coefficient of the junction at 4.2 K is estimated to be 0.5 µV/K. It is about three orders of magnitude smaller than the previously reported one [Pu 06]. Subsequently, the thermal voltage is studied in external magnetic fields. It is found that the thermopower is anisotropic with the magnetization direction. The anisotropy is explained with the anisotropies of the (Ga,Mn)As contact. Further, switching events are detected in the thermopower when the magnetic field is swept from negative to positive fields. The switchings remind of a spin valve signal and is similar to the results from previous experiments on spin injection using a (Ga,Mn)As contacts in a non-local detection scheme. That shows the importance of the thermoelectric effects and their possible contribution to the spin injection measurements. A polar plot of the collected switching fields for different magnetization angles reveals a biaxial anisotropy and resembles earlier TAMR measurements of (Ga,Mn)As tunnel junction. A simple cartoon model is introduced to describe and estimate the expected thermopower of the studied junction. The model yields a Fermi level inside of the (Ga,Mn)As valence band. Moreover, the model is found to be in good agreement with the experimental results. The Nernst effect of a (Ga,Mn)As / GaAs tunnel junction is studied in Chapter 4. A modified device geometry is introduced for this purpose. Instead of a single contact on the top of the square junction, four small contacts are fabricated to detect the Nernst signal. A temperature difference is maintained by means of a heating current technique described in Chapter 3. A magnetic field is applied parallel to the device plane. A voltage drop across two opposite contacts is detected at 2f. It appears that a simple cosine function with a parameter the angle between the magnetization and the [100] crystal direction in the (Ga,Mn)As layer manages to describe this signal which is attributed to the anomalous Nernst effect (ANE) of the ferromagnetic contact. Its symmetry is different than the Seebeck effect of the junction. For the temperature range of the thermopower measurements the ANE coefficient has a linear dependence on the temperature difference (∆T). For higher ∆T, a nonlinear dependence is observed for the coefficient. The ANE coefficient is found to be several orders of magnitude smaller than any Nernst coefficient in the literature. Both the temperature difference and the size of the ANE coefficient require further studies and analysis. Switching events are present in the measured Nernst signal when the magnetic field is swept from positive to negative values. These switchings are related to the switching fields in the ferromagnetic (Ga,Mn)As. Usually, there are two states which are present in TAMR or AMR measurements - low and high resistance. Instead of that, the Nernst signal appears to have three states - high, middle and low thermomagnetic voltage. That behaviour is governed not only by the magnetization, but also by the characteristic of the Nernst geometry. Chapter 5 summarizes the main observations of this thesis and contains ideas for future work and experiments.},
  subject      = {Galliumarsenid},
  language  = {en}
}
@phdthesis{Fuchs2014,
  author    = {Fuchs, Kilian},
  title     = {Absolutquantifizierung der myokardialen Perfusion mit hochaufl{\"o}sender MRT bei 3 Tesla},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107015},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {In den letzten Jahren hat die myokardiale MR-Perfusionsbildgebung als nichtinvasives Verfahren zur Darstellung von funktionellen Ver{\"a}nderungen des Myokards f{\"u}r die Diagnostik der KHK zunehmend an Bedeutung gewonnen. W{\"a}hrend in den letzten 20 Jahren die kardiale MRT {\"u}berwiegend bei einer Magnetfeldst{\"a}rke von 1,5 T durchge-f{\"u}hrt wurde und dies auch immer noch wird, findet aktuell eine rasante Verbreitung von MR-Systemen h{\"o}herer Feldst{\"a}rken statt. Von der neuen Hochfeldtechnik erhofft man sich vor allem, je nach Anwendung, eine deutliche Verbesserung der Bildqualit{\"a}t mit h{\"o}herer r{\"a}umlicher und zeitlicher Aufl{\"o}sung, wodurch der diagnostische Nutzen noch weiter gesteigert werden k{\"o}nnte. In der vorliegenden Arbeit wurden mittels First-Pass-MR-Bildgebung bei einer Magnet-feldst{\"a}rke von 3 T quantitative Werte f{\"u}r die myokardiale Perfusion von 20 gesunden Probanden unter Ruhebedingungen bestimmt. Sowohl die erhobenen absoluten Perfusionswerte (0,859 ml/g/min im Mittel) als auch die Standardabweichung des mittleren MBF (0,298 ml/g/min) entsprechen den Messungen aus den fr{\"u}heren Publikationen dieser Arbeitsgruppe. In der Gesamtzusammenschau bisher ver{\"o}ffentlichter Perfusionsstudien zeigt sich eine relativ große Variabilit{\"a}t der publizierten Ruhefl{\"u}sse. Dabei liegt der absolute MBF dieser Arbeit im mittleren Wertebereich dieser Streubreite. Er l{\"a}sst sich auch mit den in PET-Studien ermittelten Ergebnissen in Einklang bringen, welche als Goldstandard zur Bestimmung der absoluten myokardialen Perfusion beim Menschen gelten. Die vorliegende Arbeit best{\"a}tigt die bereits in anderen 3 T-Studien untersuchten Vorteile der Hochfeld-MRT. Die h{\"o}here Magnetfeldst{\"a}rke erm{\"o}glicht durch das gr{\"o}ßere SNR eine signifikant bessere r{\"a}umliche Aufl{\"o}sung und besticht vor allem durch die hohe Bildqualit{\"a}t. Dies k{\"o}nnte bei der Erkennung kleiner, subendokardial gelegener Perfusionsdefekte sowie der Erstellung von transmuralen Perfusionsgradienten von Bedeutung sein und verspricht neben einer Reduktion von Partialvolumeneffekten auch eine Verminderung von „dark rim"-Artefakten. Um diese Vorteile entsprechend nutzen zu k{\"o}nnen, wird die Entwicklung von Methoden zur pixelweisen Bestimmung der absoluten Fl{\"u}sse und farblich kodierten Darstellung derselben in Form von Perfusionskarten ein weiterer Schritt in Richtung klinisch einsetzbare Diagnostik sein. Eine Voraussetzung hierf{\"u}r ist die Entwicklung einer exakten und sehr stabilen Bewegungskorrektur in weiterf{\"u}hrenden Studien. Durch den Wechsel zu einer h{\"o}heren Magnetfeldst{\"a}rke von 3 T und den sich daraus ergebenden Vorteilen kann das Potential der MR-Perfusionsbildgebung, insbesondere der Bestimmung quantitativer Perfusionswerte, im Bereich der nichtinvasiven KHK-Diagnostik zuk{\"u}nftig weiter gesteigert werden.},
  subject      = {Kernspintomographie},
  language  = {de}
}
@phdthesis{Rueppel2014,
  author    = {R{\"u}ppel, Frederike},
  title     = {Accessibility of Bilinear Interconnected Systems},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-99250},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {The subject of this thesis is the controllability of interconnected linear systems, where the interconnection parameter are the control variables. The study of accessibility and controllability of bilinear systems is closely related to their system Lie algebra. In 1976, Brockett classified all possible system Lie algebras of linear single-input, single-output (SISO) systems under time-varying output feedback. Here, Brockett's results are generalized to networks of linear systems, where time-varying output feedback is applied according to the interconnection structure of the network. First, networks of linear SISO systems are studied and it is assumed that all interconnections are independently controllable. By calculating the system Lie algebra it is shown that accessibility of the controlled network is equivalent to the strong connectedness of the underlying interconnection graph in case the network has at least three subsystems. Networks with two subsystems are not captured by these proofs. Thus, we give results for this particular case under additional assumption either on the graph structure or on the dynamics of the node systems, which are both not necessary. Additionally, the system Lie algebra is studied in case the interconnection graph is not strongly connected. Then, we show how to adapt the ideas of proof to networks of multi-input, multi-output (MIMO) systems. We generalize results for the system Lie algebra on networks of MIMO systems both under output feedback and under restricted output feedback. Moreover, the case with generalized interconnections is studied, i.e. parallel edges and linear dependencies in the interconnection controls are allowed. The new setting demands to distinguish between homogeneous and heterogeneous networks. With this new setting only sufficient conditions can be found to guarantee accessibility of the controlled network. As an example, networks with Toeplitz interconnection structure are studied.},
  subject      = {Steuerbarkeit},
  language  = {en}
}
@phdthesis{Sauer2014,
  author    = {Sauer, Christoph},
  title     = {Accessing molecule-metal and hetero-molecular interfaces with direct and resonant photoelectron spectroscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107928},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {This thesis consists of two parts of original experimental work, its evaluation, and in- terpretation. Its final goal is to investigate dynamical charge transfer (CT) at a hetero- molecular interface with resonant photoelectron spectroscopy (RPES). In order to achieve this goal preliminary studies have been necessary. First two hetero-molecular inter- faces that exhibit adequate structural properties as well as an appropriate photoelec- tron spectroscopy (PES) spectrum of the valence regime have been identified. The de- sired CT analysis with RPES of these hetero-molecular systems is then conducted on the basis of the knowledge gained by previous RPES studies of homo-molecular sys- tems. The characterization of hetero-molecular films on single crystal Ag surfaces in the first part of this thesis is performed with high resolution core level PES and valence PES. The reproduction of the core level PES data with reference spectra of homo-molecular films allows me to determine which molecule is in direct contact to the Ag surface and which one is situated in higher layers (not the first one). Due to the direct correspon- dence of core level and valence PES the assignment of features in the spectra of the latter technique can be achieved with the identification of the contributions extracted from the evaluation of the data of the former technique. It is found that the systems PTCDA on one monolayer (ML) of SnPc on Ag(111) and CuPc/1 ML PTCDA/Ag(111) are stable at 300 K which means that no significant layer exchange occurs for these systems. In contrast a vertical exchange of CuPc and PTCDA molecules is observed for PTCDA de- posited on top of 1 ML CuPc/Ag(111). Up to a coverage of approximately 0.5 ML of PTCDA molecules these diffuse into the first layer, replace CuPc molecules, and con- sequently force them into higher layers. Above a coverage of approximately 0.5 ML of PTCDA molecules these are also found in higher layers. The search for a promising system for the intended RPES study then leads to an investigation of hetero-molecular films with a combination of F4TCNQ and PTCDA molecules on Ag(110) within the same approach. Depositing F4TCNQ molecules onto a 1 ML PTCDA/Ag(110) film in the herringbone phase at 300 K results in an instable hetero-organic system which un- dergoes a layer exchange. Hereby PTCDA molecules in the first layer are replaced by F4TCNQ molecules similar to the behavior of the system PTCDA/1 ML CuPc/Ag(111). Switching the order of the preparation steps leads to a stable film of PTCDA/1.0 ML F4TCNQ/Ag(110) at 300 K. Among the stable hetero-molecular films only the system CuPc/1 ML PTCDA/Ag(111) exhibits the required wetting growth of the first two layers at 300 K and a valence PES spectrum with energetically separable molecular orbital signals in the same intensity range. Thus this system is identified to be appropriate for a detailed analysis with RPES. The unexpected findings of vertical exchanges in the hetero-molecular films at 300 K motivate a study of the behavior at elevated temperatures for all systems investigated before. Therein it is revealed that annealing 1.5 ML SnPc/1 ML PTCDA/Ag(111) and 1.0 ML PTCDA/1 ML SnPc/Ag(111) to a temperature above the desorption temperature of molecules not in direct contact to the Ag(111) surface results in a 1 ML SnPc/Ag(111) film in both cases. Hence at elevated temperatures (approximately above 420 K) SnPc molecules replace PTCDA molecules in the first layer on Ag(111). At higher temper- atures (approximately above 470 K) PTCDA molecules and SnPc molecules situated above the first layer then desorb from the 1 ML SnPc/Ag(111) sample. Annealing all hetero-molecular films with CuPc and PTCDA molecules on Ag(111) to 570 K leads to a sample with CuPc and PTCDA molecules in the first and only layer. Depending on the initial CuPc coverage different ratios of both molecules are obtained. With a CuPc coverage of exactly 1 ML, or above, films with PTCDA coverages of approxi- mately 0.1-0.2 ML are produced. So at elevated temperatures CuPc molecules replace PTCDA molecules in the first layer of the system CuPc/1 ML PTCDA/Ag(111). Anal- ogously the layer exchange at 300 K for the system PTCDA/1 ML CuPc/Ag(111) is reversed at elevated temperatures. In the case of SnPc and CuPc coverages below 1 ML annealing vertical hetero-molecular systems with PTCDA on Ag(111) up to 570 K re- sults in a single layer of mixed hetero-molecular films with lateral long range order. In this way the system CuPc + PTCDA/Ag(111) is prepared and then characterized as a proper system for a detailed analysis with RPES. Additional annealing experiments of hetero-organic films consisting of F4TCNQ and PTCDA molecules on Ag(110) with an F4TCNQ coverage of 1.0 ML (and above) end in a submonolayer (sub-ML) film of F4TCNQ/Ag(110) that exhibits a contribution of amorphous carbon. Consequently, it can be concluded that at elevated temperatures part of the F4TCNQ molecules decom- pose. In the second part of this thesis homo-molecular multilayer samples and (sub-)ML films on single crystalline metal surfaces are investigated with RPES in order to enable the final RPES study of vertical and lateral hetero-molecular interface systems. First a pho- ton energy (hν) dependent intensity variation of (groups of) molecular orbital signals of exemplary multilayer films (NTCDA and coronene) is studied and explained on the basis of the local character of the electronic transitions in near edge x-ray absorption fine structure (NEXAFS) spectroscopy in combination with the real space probability den- sity of the contributing molecular orbitals. This simple approach is found to be able to correctly describe relative intensity variations by orders of magnitude while it fails for hν dependent relative intensity changes in the same order of magnitude. After that the hν dependent line-shape evolution of an energetically separated molecular orbital signal of a CuPc multilayer is discussed in relation to small molecules in the gas phase and explained with an effect of electron vibration coupling. Through a comparison of the hν dependent line-shape evolution of the highest occupied molecular orbital (HOMO) of a CuPc with a SnPc multilayer the molecule specific character of this effect is identified. Then the same effect with either two (or more) electronic transitions or multiple coupling vibrational modes is observed for a coronene multilayer. Thereafter the influence of the adsorption on metal surfaces on this effect is studied and discussed with special emphasis on a possible contribution by features which are related to dynamical interface CT. For a sub-ML of SnPc/Au(111) no variation with respect to a SnPc multilayer film is detected while for a sub-ML of CuPc/Au(111) less intensity is distributed into the high binding energy (EB) part of the HOMO signal with respect to the corresponding multilayer film. In the RPES data of a sub-ML of coronene/Ag(111) a resonance specific variation of the hν dependent line-shape evolution of the HOMO signal is found by the revelation of a change of this effect with respect to the coronene multilayer data in only one of the two NEXAFS resonances. All these findings are consistently explained within one effect and a common set of parameters, namely all quantities that characterize the potential energy surfaces involved in the RPES process. Through that an alternative explanation that re- lies on dynamical CT can be excluded which influences the following CT analysis with RPES. Three criteria for such an analysis of dynamical interface CT with RPES are identified. In the system coronene on Ag(111) a low EB feature is related to metal-molecule inter- face CT through the assignment of a particular final state and hence named CT state. In the EB region of the frontier molecular orbital signals of the molecule-metal inter- face systems with a signal from the lowest unoccupied molecular orbital (LUMO) in direct valence PES a broad line-shape is measured in RPES. This finding is related to interface CT by a possible explanation that emerges through the comparison to the line- shape of the CT state. The constant kinetic energy (EK ) features detected for several molecule-metal interfaces constitute the third criterion for a CT analysis with RPES. For the molecule-metal interface systems without a LUMO signal in direct valence PES the energy of these features can be calculated with the assignment of the responsible decay channel in combination with explicitly given simplifying assumptions. Through that the involvement of metal-molecule interface CT in the generation of these constant EK fea- tures is demonstrated. The RPES data of the lateral and the vertical hetero-molecular interface, identified in the first part, is then scanned for these three CT criteria. Thereby neither for the lateral hetero-molecular system CuPc + PTCDA/Ag(111) nor for the verti- cal hetero-molecular system CuPc/1 ML PTCDA/Ag(111) dynamical hetero-molecular interface CT can be confirmed. In the former system the molecule-metal interface in- teraction is found to dominate the physics of the system in RPES while in the latter system no hints for a significant hybridization at the CuPc-PTCDA interface can be revealed},
  subject      = {Organisches Molek{\"u}l},
  language  = {en}
}
@phdthesis{Sumski2014,
  author    = {Sumski, Anna Magdalena},
  title     = {Adenosinrezeptoren auf Zervix-, Uterus- und Mammakarzinomzellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-99332},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Adenosinrezeptoren werden auf nahezu allen K{\"o}rperzellen exprimiert und {\"u}bernehmen dort vielf{\"a}ltige und wichtige Funktionen. Auch auf diversen Tumorzelllinien konnten bereits Adenosinrezeptoren nachgewiesen und - je nach Subtyp - mit Pro- oder Anti-tumor-Effekten in Zusammenhang gebracht werden. In dieser Arbeit wurden Geb{\"a}rmutterhalskrebszellen sowie endometriale und triple-negative Brustkrebszellen auf Expression und m{\"o}gliche Funktionen von Adenosinrezep-toren untersucht. Da spezifische Antik{\"o}rper bis heute nicht verf{\"u}gbar sind, wurde ein pharmakologischer Ansatz mit subtypspezifischen Agonisten und Antagonisten gew{\"a}hlt. In Radioliganden-Bindungsassays, konnte nachgewiesen werden, dass sich auf der Zer-vixkarzinom-Zelllinie SiHa und der Brustkrebs-Zelllinie HCC1806 Adenosinrezeptoren des Subtyps A1 befinden. Die endometrialen Krebszelllinien Ishikawa und HEC-1-A exprimieren Rezeptoren vom Subtyp A1 und A2A. A3-Adenosinrezeptoren wurden auf keiner der untersuchten Zelllinien gefunden. Der Nachweis von A2B-Rezeptoren kann mit dem Radioliganden-Bindungsassay nicht erbracht werden, da bislang kein Radioligand bekannt ist, der eine ausreichende Affini-t{\"a}t besitzt, um diesen Subtyp zweifelsfrei nachweisen zu k{\"o}nnen. Obwohl die Mehrheit der untersuchten Zelllinien Adenosinrezeptoren exprimiert, konnte ein signifikanter Effekt auf die Adenylatcyclase bei Stimulation der auf den Zellen vorhandenen Adenosinrezeptoren nur bei den HEC-1-A-Zellen festgestellt werden. Auch auf funktionelle A2B-Rezeptoren fand sich im Adenylatcyclaseassy kein Hinweis. Im durchgef{\"u}hrten Kristallviolettassay zeigte sich ein proapoptotischer Effekt auf Ishi-kawa- und HEC-1-A-Zellen bei hohen Adenosin-Konzentrationen (100 µM). Die im BrdU-Assay gemessene Proliferationsrate hingegen {\"a}nderte sich nach Vorbehandlung mit Adenosin nicht. Das metabolisch stabilere NECA (in Kombination mit ADA) hatte im Kristallviolettassay einen st{\"a}rkeren Einfluss auf die Apoptoserate der jeweiligen Zelllinie als Adenosin und auch im BrdU-Assay sank die Menge an inkorporiertem BrdU. Ein Synergismus zwischen Stimulation von Adenosinrezeptoren und diversen Todesliganden bzw. Chemotherapeutika konnte nicht nachgewiesen werden. Freies extrazellul{\"a}res Adenosin kann auch aus dem Abbau von ATP generiert werden, wenn Zellen die Ektonukleotidasen CD39 und CD73 exprimieren. Aufgrund der im-munsuppressiven Wirkung von Adenosin k{\"o}nnen diese Enzyme T-Zell- und NK-Zellantworten im Mikromilieu von Tumoren hemmen. Die durchflusszytometrische Analyse von HEC-1-A- und Ishikawa-Zellen zeigte zwar, dass die Expression von CD39 und CD73 nach Stimulation der Adenosinrezeptoren unver{\"a}ndert blieb. Die Ex-pression von Enzymen, l{\"a}sst aber vermuten, dass die Zellen in vivo von Adenosin profi-tieren k{\"o}nnten. Angesichts der in vitro Daten, die allenfalls einen wachstumshemmen-den Effekt von Adenosin zeigten, k{\"o}nnte die vorrangige Wirkung von Adenosin im Tumormikromilieu tats{\"a}chlich auf der Inhibition von Immunantworten beruhen. M{\"o}g-licherweise w{\"u}rden die Rezeptoren dann in erster Linie als Sensoren dienen. Weitere Forschungsarbeit wird helfen, die Rolle der Adenosinrezeptoren im Tumorge-schehen vollst{\"a}ndig zu verstehen und m{\"o}glicherweise f{\"u}r die Krebstherapie nutzbar zu machen.},
  subject      = {Adenosinrezeptor},
  language  = {de}
}
@phdthesis{Wittmann2014,
  author    = {Wittmann, Katharina},
  title     = {Adipose Tissue Engineering - Development of Volume-Stable 3-Dimensional Constructs and Approaches Towards Effective Vascularization},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-107196},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Adipose tissue defects and related pathologies still represent major challenges in reconstructive surgery. Based on to the paradigm 'replace with alike', adipose tissue is considered the ideal substitute material for damaged soft tissue [1-3]. Yet the transfer of autologous fat, particularly larger volumes, is confined by deficient and unpredictable long term results, as well as considerable operative morbidity at the donor and recipient site [4-6], calling for innovative treatment options to improve patient care. With the aim to achieve complete regeneration of soft tissue defects, adipose tissue engineering holds great promise to provide functional, biologically active adipose tissue equivalents. Here, especially long-term maintenance of volume and shape, as well as sufficient vascularization of engineered adipose tissue represent critical and unresolved challenges [7-9]. For adipose tissue engineering approaches to be successful, it is thus essential to generate constructs that retain their initial volume in vivo, as well as to ensure their rapid vascularization to support cell survival and differentiation for full tissue regeneration [9,10]. Therefore, it was the ultimate goal of this thesis to develop volume-stable 3D adipose tissue constructs and to identify applicable strategies for sufficient vascularization of engineered constructs. The feasibility of the investigated approaches was verified by translation from in vitro to in vivo as a critical step for the advancement of potential regenerative therapies. For the development of volume-stable constructs, the combination of two biomaterials with complementary properties was successfully implemented. In contrast to previous approaches in the field using mainly non-degradable solid structures for mechanical protection of developing adipose tissue [11-13], the combination of a cell-instructive hydrogel component with a biodegradable porous support structure of adequate texture was shown advantageous for the generation of volume-stable adipose tissue. Specifically, stable fibrin hydrogels previously developed in our group [14] served as cell carrier and supported the adipogenic development of adipose-derived stem cells (ASCs) as reflected by lipid accumulation and leptin secretion. Stable fibrin gels were thereby shown to be equally supportive of adipogenesis compared to commercial TissuCol hydrogels in vitro. Using ASCs as a safe source of autologous cells [15,16] added substantial practicability to the approach. To enhance the mechanical strength of the engineered constructs, porous biodegradable poly(ε caprolactone)-based polyurethane (PU) scaffolds were introduced as support structures and shown to exhibit adequately sized pores to host adipocytes as well as interconnectivity to allow coherent tissue formation and vascularization. Low wettability and impaired cell attachment indicated that PU scaffolds alone were insufficient in retaining cells within the pores, yet cytocompatibility and differentiation of ASCs were adequately demonstrated, rendering the PU scaffolds suitable as support structures for the generation of stable fibrin/PU composite constructs (Chapter 3). Volume-stable adipose tissue constructs were generated by seeding the pre-established stable fibrin/PU composites with ASCs. Investigation of size and weight in vitro revealed that composite constructs featured enhanced stability relative to stable fibrin gels alone. Comparing stable fibrin gels and TissuCol as hydrogel components, it was found that TissuCol gels were less resilient to degradation and contraction. Composite constructs were fully characterized, showing good cell viability of ASCs and strong adipogenic development as indicated by functional analysis via histological Oil Red O staining of lipid vacuoles, qRT-PCR analysis of prominent adipogenic markers (PPARγ, C/EBPα, GLUT4, aP2) and quantification of leptin secretion. In a pilot study in vivo, investigating the suitability of the constructs for transplantation, stable fibrin/PU composites provided with a vascular pedicle gave rise to areas of well-vascularized adipose tissue, contrasted by insufficient capillary formation and adipogenesis in constructs implanted without pedicle. The biomaterial combination of stable fibrin gels and porous biodegradable PU scaffolds was thereby shown highly suitable for the generation of volume-stable adipose tissue constructs in vivo, and in addition, the effectiveness of immediate vascularization upon implantation to support adipose tissue formation was demonstrated (Chapter 4). Further pursuing the objective to investigate adequate vascularization strategies for engineered adipose tissue, hypoxic preconditioning was conducted as a possible approach for in vitro prevascularization. In 2D culture experiments, analysis on the cellular level illustrated that the adipogenic potential of ASCs was reduced under hypoxic conditions when applied in the differentiation phase, irrespective of the oxygen tension encountered by the cells during expansion. Hypoxic treatment of ASCs in 3D constructs prepared from stable fibrin gels similarly resulted in reduced adipogenesis, whereas endothelial CD31 expression as well as enhanced leptin and vascular endothelial growth factor (VEGF) secretion indicated that hypoxic treatment indeed resulted in a pro-angiogenic response of ASCs. Especially the observed profound regulation of leptin production by hypoxia and the dual role of leptin as adipokine and angiogenic modulator were considered an interesting connection advocating further study. Having confirmed the hypothesis that hypoxia may generate a pro-angiogenic milieu inside ASC-seeded constructs, faster vessel ingrowth and improved vascularization as well as an enhanced tolerance of hypoxia-treated ASCs towards ischemic conditions upon implanatation may be expected, but remain to be verified in rodent models in vivo (Chapter 5). Having previously been utilized for bone and cartilage engineering [17-19], as well as for revascularization and wound healing applications [20-22], stromal-vascular fraction (SVF) cells were investigated as a novel cell source for adipose tissue engineering. Providing cells with adipogenic differentiation as well as vascularization potential, the SVF was applied with the specific aim to promote adipogenesis and vascularization in engineered constructs in vivo. With only basic in vitro investigations by Lin et al. addressing the SVF for adipose repair to date [23], the present work thoroughly investigated SVF cells for adipose tissue construct generation in vitro, and in particular, pioneered the application of these cells for adipose tissue engineering in vivo. Initial in vitro experiments compared SVF- and ASC-seeded stable fibrin constructs in different medium compositions employing preadipocyte (PGM-2) and endothelial cell culture medium (EGM-2). It was found that a 1:1 mixture of PGM-2 and EGM-2, as previously established for co-culture models of adipogenesis [24], efficiently maintained cells with adipogenic and endothelial potential in SVF-seeded constructs in short and long-term culture setups. Observations on the cellular level were supported by analysis of mRNA expression of characteristic adipogenic and endothelial markers. In preparation of the evaluation of SVF-seeded constructs under in vivo conditions, a whole mount staining (WMS) method, facilitating the 3D visualization of adipocytes and blood vessels, was successfully established and optimized using native adipose tissue as template (Chapter 6). In a subcutaneous nude mouse model, SVF cells were, for the first time in vivo, elucidated for their potential to support the functional assembly of vascularized adipose tissue. Investigating the effect of adipogenic precultivation of SVF-seeded stable fibrin constructs in vitro prior to implantation on the in vivo outcome, hormonal induction was shown beneficial in terms of adipocyte development, whereas a strong vascularization potential was observed when no adipogenic inducers were added. Via histological analysis, it was proven that the developed structures were of human origin and derived from the implanted cells. Applying SVF cells without precultivation in vitro but comparing two different fibrin carriers, namely stable fibrin and TissuCol gels, revealed that TissuCol profoundly supported adipose formation by SVF cells in vivo. This was contrasted by only minor SVF cell development and a strong reduction of cell numbers in stable fibrin gels implanted without precultivation. Histomorphometric analysis of adipocytes and capillary structures was conducted to verify the qualitative results, concluding that particularly SVF cells in TissuCol were highly suited for adipose regeneration in vivo. Employing the established WMS technique, the close interaction of mature adipocytes and blood vessels in TissuCol constructs was impressively shown and via species-specific human vimentin staining, the expected strong involvement of implanted SVF cells in the formation of coherent adipose tissue was confirmed (Chapter 7). With the development of biodegradable volume-stable adipose tissue constructs, the application of ASCs and SVF cells as two promising cell sources for functional adipose regeneration, as well as the thorough evaluation of strategies for construct vascularization in vitro and in vivo, this thesis provides valuable solutions to current challenges in adipose tissue engineering. The presented findings further open up new perspectives for innovative treatments to cure soft tissue defects and serve as a basis for directed approaches towards the generation of clinically applicable soft tissue substitutes.},
  subject      = {Tissue Engineering},
  language  = {en}
}