@phdthesis{Maas2018, author = {Maas, Daniel Peter}, title = {Currency Areas, Monetary Policy, and the Macroeconomy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168037}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Hauptgegenstand der Dissertation ist die Analyse der makro{\"o}konomischen Auswirkungen der Gr{\"u}ndung der Eurozone auf die Mitgliedsstaaten. Diese Analyse umfasst zwei Studien, die sich der Fragestellung aus verschiedenen Perspektiven n{\"a}hern. Die erste Studie unternimmt einen Vergleich der Geldpolitik von EZB und von ausgew{\"a}hlten Zentralbanken des Europ{\"a}ischen W{\"a}hrungssystems (EWS). Es wird untersucht, inwiefern sich bei makro{\"o}konomischen Nachfrage- und Angebotsschocks die systematischen Reaktionen der EZB von denen der vier wichtigsten nationalen Zentralbanken des EWS (Deutschland, Frankreich, Italien und Spanien) unterscheiden. In der zweiten Studie werden die Ursachen f{\"u}r den Aufbau interner und externer Ungleichgewichte in Spanien, d.h. auf dem Immobilienmarkt und in der Leistungsbilanz, im Vorfeld der Finanzkrise 2007/08 analysiert. Dabei wird zwischen Spanien-spezifischen und Eurozonen-spezifischen Ursachen unterschieden und deren Erkl{\"a}rungsgehalt empirisch quantifiziert. In der dritten und letzten Studie der Dissertation wird ein preistheoretisches Kreditangebotsmodell entwickelt und empirisch gesch{\"a}tzt. Als Basis f{\"u}r die empirische Sch{\"a}tzung werden Daten des Kreditmarktes f{\"u}r deutsche Unternehmen verwendet. Die methodische Vorgehensweise beinhaltet in allen Studien zeitreihen{\"o}konometrische Ans{\"a}tze wie beispielsweise (Mehrl{\"a}nder-)Vektorautoregressionen (VARs) und Zeitreihenregressionen.}, subject = {Geldpolitik}, language = {en} } @phdthesis{Confalonieri2018, author = {Confalonieri, Davide}, title = {Development and characterization of a bone marrow stem cell niche model}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163128}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Kritische Knochendefekte stellen heutzutage ein ungel{\"o}stes Problem in der klinischen Praxis dar, da die verf{\"u}gbaren prothetischen Optionen oft die mechanische Anpassung an das Gewebe nicht gew{\"a}hrleisten oder zu wichtigen immunologischen und Implantat-bedingten Komplikationen f{\"u}hren. In diesem Kontext erm{\"o}glichen Tissue Engineering-Ans{\"a}tze neue Strategien, um in vitro Zell-Material Interaktionen zu untersuchen und so die Implantatmaterialien zu optimieren. In dieser Arbeit habe ich Zell-Material Interaktionen eines neuen Kollagen-basierten Scaffolds untersucht, das langfristig als Tr{\"a}gerstruktur f{\"u}r eine zellbasierte Therapie f{\"u}r kritische Knochendefekte entwickelt werden soll. Im Rahmen der Dissertation konnte ich belegen, dass die Kollagen-basierten makropor{\"o}se Mikrocarrier f{\"u}r die Zellvermehrung humaner mesenchymaler Stammzellen (MSC) und deren osteogene Differenzierung unter GMP Bedingungen verwendet werden k{\"o}nnen. Außerdem habe ich die die Kokultur von h{\"a}matopoietischen Stammzellen des Knochenmarks und multiplen Myelomzellen funktionell charakterisiert. Ich konnte erstmals Kulturbedingungen etablieren, die die Langzeitkultur ohne die Verwendung von Zytokinen erm{\"o}glicht. Mittels dieser Kokultur konnte ich ein Knochenmarknischen-Modell etablieren und die Untersuchung der Expression von zentralen Signalkaskaden der Hom{\"o}ostase dieser Nische untersuchen. Ich konnte die Expression von zwei verschiedenen Isoformen von Osteopontin nachweisen, die in Tiermodellen nicht gefunden werden. Diese Isoformen des Osteopontins habe ich kloniert und die rekombinanten Isoformen exprimiert und ihre Rollen in der Hom{\"o}ostase der Knochenmarknische untersucht. Critical size bone defects represent nowadays an unresolved problem in the clinical practice, where the available prosthetic options often lack adequate mechanical matching to the host tissue or lead to important immunological and implant-related complications. In this context, Tissue Engineering approaches promise more effective strategies to study cell-material interactions in vitro and consequently optimize implant materials. In this work, I investigated the cell-scaffold interactions of a new collagen-based scaffold for a putative cell-based therapy for critical size defects to be developed. In the context of this thesis, I could demonstrate that the collagen-based macroporous microcarriers could be employed for the expansion and osteogenic differentiation of human mesenchymal stromal cells (MSCs) under GMP-compliant conditions. Moreover, I functionally characterized the co-culture of bone marrow hematopoietic stem cells and multiple myeloma cells. I was for the first time able to establish culture conditions allowing their long-term culture in absence of externally supplemented cytokines. Using this co-culture, I was able to establish a bone marrow niche model to investigate the expression of key signaling pathways involved in the niche´s homeostasis. I was able to demonstrate the expression of two different isoforms of Osteopontin, that could not previously be detected in animal models. Finally, I cloned these Osteopontin isoforms, expressed recombinant versions of the isoforms, and investigated their roles in the homeostasis of the bone marrow niche.}, subject = {bone marrow niche}, language = {en} } @phdthesis{Ulbricht2018, author = {Ulbricht, Juliane}, title = {Insights into Polymer Biodegradation - Investigations on oxidative, hydrolytic and enzymatic Pathways}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158683}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The present work aims towards the investigation of polymer degradation under biologically relevant conditions. In order to assess a potential degradation of polymers of interest for biomedical applications in vivo and associated effects on living tissue, representatives of poly(2-oxazoline)s and polypeptoids as well as poly(ethylene glycol) and poly(N-vinylpyrrolidone) for reference purposes are examined regarding their stability under oxidative and hydrolytic conditions as well as towards enzymatic degradation. The polymers investigated in the framework of this thesis are generally considered to be non-biodegradable. Both poly(ethylene glycol) and poly(N-vinylpyrrolidone) are or were applied intensively in vivo provoking seriously harmful side effects like fatal blood poisoning from the oxidation of poly(ethylene glycol) chain ends or poly(N-vinylpyrrolidone) storage disease. Poly(2-alkyl-2-oxazoline)s and polypeptoids, both promising polymeric biomaterials for a wide variety of in vivo applications, are not clinically applied yet but undergo thorough investigations. However, comprising amide bonds within the backbone or the appending side chain, poly(2-alkyl-2-oxazoline)s and polypeptoids potentially offer a higher susceptibility towards (bio-)degradation. Representing the three most impactful initiators of degradation in vivo, the present study is focused on polymer deterioration by oxidative species, hydrolytic conditions and enzymes. Oxidative species are generated in a variety of processes in vivo, both on purpose and as an unintentional by-product. Previous investigations revealed the susceptibility of poly(ethylene glycol), poly(N-vinylpyrrolidone), poly(2-alkyl-2-oxazoline)s and polypeptoids to deterioration by hydroxyl radicals deriving from hydrogen peroxide and copper ions. The obtained data confirm previous results of an apparent degradation rate increasing with increasing chain length due to self-inhibitory end group effects for all investigated polymer species. Although the exact concentrations of oxidative species in vivo are very controversial, with respect to their great variety and wide distribution the investigated polymers are likely prone to oxidative deterioration to some extent, with rates, mechanisms and degradation products strongly depending on the respective reactive species, polymer structure and chain length. Like blood, most tissues of the human body benefit from a slightly alkaline pH value. Nevertheless, specific areas like the human stomach or tumor tissues possess acidic conditions potentially capable to cleave amide bonds comprised by poly(2-alkyl-2-oxazoline)s and polypeptoids. Unlike the hydrolysis of poly(2-alkyl-2-oxazoline)s resulting in side chain cleavage, the hydrolysis of polypeptoids induces backbone scission decreasing the polymer chain length tremendously and releasing, if performed exhaustively, the respective amino acids. Hydrolysis of polysarcosine is monitored by quantification of the released sarcosine via 1H-NMR spectroscopy and determination of the residual Mw via GPC. Its cyclic dimer sarcosine anhydride is formed as an intermediate product in this process via cyclization of unstable linear dimers of sarcosine. Modification and degradation of bio(macro)molecules is an essential part of human metabolism. Polymers bearing amide bonds and showing a great similarity to natural occurring and widely distributed polypeptides, like poly(2-alkyl-2-oxazoline)s and polypeptoids, bear the potential of an enzymatic biodegradability by (more or less specific) peptidases. Just like the acidic hydrolysis described previously, peptidase activity would result in the cleavage of polymer amide bonds. The aim of the present thesis was to evaluate the stability of poly(2-alkyl-2-oxazoline)s and polypeptoids as well as poly(ethylene glycol) for the sake of reference under circumstances resembling in vivo conditions as closely as possible. Initial experiments focused on the degradation of dye-labeled upon incubation with homogenates of freshly harvested rat liver and kidney. However, although the obtained results are promising for the most part, they are considered rather unreliable and non-reproducible for various reasons. More conclusive data are attained from the incubation of non-labeled polymers in freshly laid chicken eggs. While no evidence for an enzymatic digestion of poly(ethylene glycol) in chicken egg white is found and deterioration of poly(2-methyl-2-oxazoline) upon incubation apparently derives from non-enzymatic hydrolysis, incubated polysarcosine samples reveal distinct elugram patterns depending on the respective C- and N-terminal end groups indicating both exopeptidase and endopeptidase activity. It has to be kept in mind though, that an enzymatic digestibility of polysarcosine does not necessarily imply the digestion of polypeptoids bearing longer side chains by peptidases as well, which should be investigated in further studies.}, subject = {Biologischer Abbau}, language = {en} } @phdthesis{Dejure2018, author = {Dejure, Francesca Romana}, title = {Investigation of the role of MYC as a stress responsive protein}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158587}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The transcription factor MYC is deregulated in over 70\% of all human tumors and, in its oncogenic form, plays a major role in the cancer metabolic reprogramming, promoting the uptake of nutrients in order to sustain the biosynthetic needs of cancer cells. The research presented in this work aimed to understand if MYC itself is regulated by nutrient availability, focusing on the two major fuels of cancer cells: glucose and glutamine. Initial observations showed that endogenous MYC protein levels strongly depend on the availability of glutamine, but not of glucose. Subsequent analysis highlighted that the mechanism which accounts for the glutamine-mediated regulation of MYC is dependent on the 3´-untranslated region (3´-UTR) of MYC. Enhanced glutamine utilization by tumors has been shown to be directly linked to MYC oncogenic activity and MYC-dependent apoptosis has been observed under glutamine starvation. Such effect has been described in experimental systems which are mainly based on the use of MYC transgenes that do not contain the 3´-UTR. It was observed in the present study that cells are able to survive under glutamine starvation, which leads to cell cycle arrest and not apoptosis, as previously reported. However, enforced expression of a MYC transgene, which lacks the 3´-UTR, strongly increases the percentage of apoptotic cells upon starvation. Evaluation of glutamine-derived metabolites allowed to identify adenosine nucleotides as the specific stimulus responsible for the glutamine-mediated regulation of MYC, in a 3´-UTR-dependent way. Finally, glutamine-dependent MYC-mediated effects on RNA Polymerase II (RNAPII) function were evaluated, since MYC is involved in different steps of global transcriptional regulation. A global loss of RNAPII recruitment at the transcriptional start site results upon glutamine withdrawal. Such effect is overcome by enforced MYC expression under the same condition. This study shows that the 3´UTR of MYC acts as metabolic sensor and that MYC globally regulates the RNAPII function according to the availability of glutamine. The observations presented in this work underline the importance of considering stress-induced mechanisms impinging on the 3´UTR of MYC.}, subject = {Myc}, language = {en} } @phdthesis{Lutz2018, author = {Lutz, Peter}, title = {Surface and Interface Electronic Structure in Ferroelectric BaTiO\(_3\)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159057}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Transition metal oxides (TMO) represent a highly interesting material class as they exhibit a variety of different emergent phenomena including multiferroicity and superconductivity. These effects result from a significant interplay of charge, spin and orbital degrees of freedom within the correlated d-electrons. Oxygen vacancies (OV) at the surface of certain d0 TMO release free charge carriers and prompt the formation of a two-dimensional electron gas (2DEG). Barium titanate (BaTiO3) is a prototypical and promising d0 TMO. It displays ferroelectricity at room temperature and features several structural phase transitions, from cubic over tetragonal (at room temperature) and orthorhombic to rhombohedral. The spontaneous electric polarization in BaTiO3 can be used to manipulate the physical properties of adjacent materials, e.g. in thin films. Although the macroscopic properties of BaTiO3 are studied in great detail, the microscopic electronic structure at the surface and interface of BaTiO3 is not sufficiently understood yet due to the complex interplay of correlation within the d states, oxygen vacancies at the surface, ferroelectricity in the bulk and the structural phase transitions in BaTiO3. This thesis investigates the electronic structure of different BaTiO3 systems by means of angle-resolved photoelectron spectroscopy (ARPES). The valence band of BaTiO3 single crystals is systematically characterized and compared to theoretical band structure calculations. A finite p-d hybridization of titanium and oxygen states was inferred at the high binding energy side of the valence band. In BaTiO3 thin films, the occurrence of spectral weight near the Fermi level could be linked to a certain amount of OV at the surface which effectively dopes the host system. By a systematic study of the metallic surface states as a function of temperature and partial oxygen pressure, a model was established which reflects the depletion and accumulation of charge carriers at the surface of BaTiO3. An instability at T ~ 285K assumes a volatile behavior of these surface states. The ferroelectricity in BaTiO3 allows a control of the electronic structure at the interface of BaTiO3-based heterostructures. Therefore, the interface electronic structure of Bi/BaTiO3 was studied with respect to the strongly spin-orit coupled states in Bi by also including a thickness dependent characterization. The ARPES results, indeed, confirm the presence of Rashba spin-split electronic states in the bulk band gap of the ferroelectric substrate. By varying the film thickness in Bi/BaTiO3, it was able to modify the energy position and the Fermi vector of the spin-split states. This observation is associated with the appearance of an interface state which was observed for very low film thickness. Both spectral findings suggest a significant coupling between the Bi films and BaTiO3.}, subject = {Bariumtitanat}, language = {en} } @phdthesis{Schoetz2018, author = {Sch{\"o}tz, Matthias}, title = {Convergent Star Products and Abstract O*-Algebras}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174355}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Diese Dissertation behandelt ein Problem aus der Deformationsquantisierung: Nachdem man die Quantisierung eines klassischen Systems konstruiert hat, w{\"u}rde man gerne ihre mathematischen Eigenschaften verstehen (sowohl die des klassischen Systems als auch die des Quantensystems). Falls beide Systeme durch *-Algebren {\"u}ber dem K{\"o}rper der komplexen Zahlen beschrieben werden, bedeutet dies dass man die Eigenschaften bestimmter *-Algebren verstehen muss: Welche Darstellungen gibt es? Was sind deren Eigenschaften? Wie k{\"o}nnen die Zust{\"a}nde in diesen Darstellungen beschrieben werden? Wie kann das Spektrum der Observablen beschrieben werden? Um eine hinreichend allgemeine Behandlung dieser Fragen zu erm{\"o}glichen, wird das Konzept von abstrakten O*-Algebren entwickelt. Dies sind im Wesentlichen *-Algebren zusammen mit einem Kegel positiver linearer Funktionale darauf (z.B. die stetigen positiven linearen Funktionale wenn man mit einer *-Algebra startet, die mit einer gutartigen Topologie versehen ist). Im Anschluss daran wird dieser Ansatz dann auf zwei Beispiele aus der Deformationsquantisierung angewandt, die im Detail untersucht werden.}, subject = {Deformationsquantisierung}, language = {en} }