Evidence-Based Veterinary Medicine (EBVM) is a relatively new field in veterinary curricula and veterinary practice. The aim of EBVM is to base clinical decisions regarding diagnostic procedures and treatments on recent, valid, clinically relevant research data. Veterinary practitioners and clinicians should use optimal diagnostics, interventions and medications to examine and to treat their patients. Therefore, they should assess the topicality of their procedures and therapies to treat their patients as best as possible. This means clinicians need skills in observation, manual dexterity, and also other skills such as communication and empathy for patients and owners. Specifically, the EBVM concepts should be incorporated into preclinical and clinical courses. For the realization of an evidence- based patient care, it is important to know core concepts of EBVM and to be skilled in five steps: formulation of a clinical question, searching for literature, assessing the validity and applicability, the implementation into practice and finally an assessment of whether the new findings have improved clinical practice. Rather than merely transferring information, veterinary education should stimulate and motivate students and let them think critically. Frontal teaching, however, is still applied frequently in veterinary education which only rarely stimulates student interaction, besides it does not support independent thinking and critical questioning. In addition to the concept of EBVM, the critical thinking, and also the rapid development of new communication technologies has influenced veterinary education already. One helpful tool to facilitate the access to research results and thereby the implementation of Evidence-Based Medicine (EBM) is a Critically Appraised Topic (CAT). A CAT is a standardized summary of research evidence evolved around a clinical question, generated from a specific patient situation or problem. The overall objective of the conducted studies was to survey possibilities to include EBVM concepts in veterinary education. For this purpose three studies were conducted: 1\. In the first study the research question was, if fourth-year students consider in-course discussion useful and if sufficient possibilities for discussion are provided and supported by their lecturers. The majority agreed or strongly agreed that clinical topics should be discussed during class time. Frequently stated reasons were improved learning and the opportunity to look at topics from different perspectives. In conclusion, a considerable absence of and request for discussion within veterinary education was found. In light of these findings, we emphasize the need for new teaching strategies that promote independent thinking and critical questioning. That suggested the implementation of more discussion opportunities in well considered and moderated settings in veterinary teaching. 2\. The research question of the second study was to determine adoption and use of mobile devices and online services of veterinary students. According to their answers the majority used a smartphone as mobile device. The data suggested, that most students are familiar with mobile devices and the use of social media, so that new learning strategies could be developed and applied that encompass mobile online learning. These strategies could help to better address different learning types, provide sufficient interactivity and feedback. However, despite promising results reporting a positive educational effect, these perceptions need to be validated in further research. 3\. The objective of the third study was the development, the use and an evaluation of a German language database for Critically Appraised Topics (CATs). Experts of the European Board of Veterinary Specialization were asked to appraise CATs written by students. A total of 153 veterinary medicine students in their fifth year developed 21 CATs. The majority of the students stated that writing CATs is a good exercise and that it is important to train the assessment of scientific information. Nine out of 13 CATs were graded as ´good`. In conclusion veterinary medicine should in general be more responsive to the integration of recent literature and to a critical approach of information. Specifically, the development of a CAT by students is a good approach to teach the concepts of EBVM. In consideration of new technologies, the CAT-database can be used by German veterinary students and in the future by practitioners.

The three chapters of this dissertation provide new insights in modeling and estimating dynamic discrete choice models. Building on previous identification results, several new strategies are presented to estimate important aspects of dynamic decision processes. A focus lies on hyperbolic discounting and biased expectations, two elements that the vast majority of the literature on female labor supply ignores. Furthermore, the empirical analyses demonstrate that the proposed models describe behavior better than the models dominantly used in the literature. Estimations show that these elements have an economic meaning, as they increase the costs of child-related career breaks. The first chapter provides new exclusion restrictions for identifying the exponential discount factor in dynamic discrete choice models. It demonstrates how exogenous changes in restriction probabilities can be used to recover time preferences from choice data. The second chapter further extends this strategy and analytically shows the identification of hyperbolic discounting parameters within a three-period model of dynamic discrete choice. Furthermore, the chapter discusses how the identification carries over to models with more than three periods. Focusing on women's child-related career breaks, a dynamic discrete choice model of female labor supply, human capital accumulation and labor market frictions is developed. Data from the German Socio-Economic Panel is used to estimate the model, finding a present-bias of 0.77 that significantly deviates from an exponential discounting model. Interestingly, the yearly discount factor for two subsequent future periods is close to values usually assumed for exponential discounters in the literature, with a value of 0.92. This result implies that women do not tend to be myopic per se since even utilities 20 years away receive an overall weight of 0.14 in the lifetime utility. Instead, it is that instantaneous utility is valued much more than any future utility, thus providing evidence that women postpone their re-entry into the labor market, by overvaluing current leisure over future career advancements. The third chapter concentrates on another crucial aspect of dynamic choice, expectations about future states of the world. It represents one of the first analyses in the literature on female labor supply that deviates from the rational expectations hypothesis. This hypothesis assumes that individuals, on average, correctly predict future events. After presenting some suggestive evidence that economic agents systematically mispredict their future employment opportunities, I develop a structural life-cycle model of labor supply, human capital accumulation, and labor market frictions. Nesting the rational expectations framework, the model allows job offer expectations to deviate from their real probability. In this chapter, I develop an identification strategy to recover expectations within the model that allows estimating the key parameters from observed labor supply choices. Estimations provide evidence that mothers strongly overestimate their chances on the labor market since they expect the half-yearly job arrival rate to be 66% higher than the actual rate. The structural framework allows for quantifying the costs stemming from these biased beliefs. The results are striking. Overestimating future employment opportunities prolongs career breaks on average between five and eight months, depending on the length of employment protection. In total, the bias causes a reduction of lifetime earnings from employment, as measured at the first birth of a child, between 12% and 18%. Various benefits and the earnings of a potential husband mitigate some of these losses, causing consumption losses to only range from 3.1 % to 4.1 %.

Ziel: Das übergeordnete Ziel der vorliegenden Arbeit ist die Analyse der Dynamiken zwischen psychiatrischer Praxis und bildender Kunst in Brasilien von 1920 bis 1980 und die in dieser Zeit entstandenen Institutionen in ihrer Neuheit einzuordnen. Die spezifischen Ziele waren (I) zu beschreiben, mit Hilfe welcher ProtagonistInnen die Kunst als klinische Anwendung Eingang in die Psychiatrie fand, (II) aufzuzeigen, unter welchen Umständen und an welchen Orten die PatientInnen arbeiten konnten, (III) zu zeigen, wie die Kunstanwendungen in der Psychiatrie als Aspekt der Behandlung von PatientInnen dokumentiert und rezipiert wurden, (IV) gegenüberzustellen, mit welchen medizinischen, gesellschaftlichen und politischen Vorbedingungen sich die MedizinerInnen und KünstlerInnen konfrontiert sahen und (V) zu erforschen, zu welcher Institutionalisierung und Institutionskritik die neuen Dynamiken an der Grenze von Kunst und Psychiatrie geführt haben. Folgende Methoden wurden angewandt: (I) Systematische Literaturrecherche, (II) ExpertInnenbefragung und Interviews, (III) Analyse von filmischem Material. Ergebnisse: (I) drei medizinische ProtagonistInnen wurden identifiziert: Osório César, Nise da Silveira und Lula Wanderley (II) sowie drei KünstlerInnen: Alice Brill, Almir Mavignier und Lygia Clark. Nur aufgrund des gemeinsamen unberirrten Strebens der zwei Gruppen, die sich auch gegen die Repressionen der Diktatur ab den 1950er Jahren zur Wehr setzten, wurden Kunstateliers (César), Museen (Silveira) und neue Freiheiten (Wanderley) institutionalisiert. (III) Es konnten drei Dynamiken festgestellt werden, die zur Etablierung der Kunst in den Kliniken geführt haben: die Ankunft der Psychoanalyse in Brasilien, die Rezeption der Antropofagia in der Kunst und Psychiatrie und die Institutionalisierungsbestrebungen bzw. Institutionskritik. Schlussfolgerungen: Mithilfe der drei beschriebenen Dynamiken wird gezeigt, dass die entwickelten Therapiemethoden erst durch das Verwischen der Fachgrenzen zwischen MedizinerInnen und KünstlerInnen zustande kommen konnte. Die gesellschaftlichen und politischen Umbrüche in Brasilien im Laufe des 20. Jahrhunderts schufen eine neue Situation, die es – im Gegensatz zu Europa – ermöglichte, alternative Behandlungsmethoden wie die Therapie mit Kunstanwendung bereits ab 1920 zu institutionalisieren.

In deutschsprachigen Schulsystemen treffen aktuell die Reformansätze der Inklusion und der Bildungsstandards aufeinander, wodurch ein vielschichtiger bildungswissenschaftlicher Diskurs um deren Vereinbarkeit ausgelöst wurde. Jedoch liegt kaum Evidenz dazu vor, ob und inwiefern Lehrkräfte mit diesen aktuell bedeutsamen Reformen unterschiedliche oder gar gegensätzliche Anforderungen verbinden. Im Rahmen der vorliegenden Arbeit wurde unter Rückgriff auf sozialpsychologische und erziehungswissenschaftliche Theorien empirisch untersucht, wie sich in der Literatur diskutierte potentielle Gegensätze zwischen Inklusion und Bildungsstandards aus der Sicht von Lehrkräften darstellen. Dabei wurden Aspekte der Unterrichtsgestaltung (Studie 1) ebenso betrachtet wie Aspekte der Leistungsbeurteilung (Studie 1 und Studie 2) und Konsequenzen, die mit der Hervorhebung unterschiedlicher Beurteilungsmaßstäbe im Kontext beider Reformen für die Leistungsbeurteilung bestimmter Schülergruppen verbunden sein können (Studie 3). Die experimentell angelegte Studie 1 untersuchte auf Basis der theoretischen Unterscheidung von Sicht- und Tiefenstrukturen des Unterrichts (Oser & Baeriswyl, 2001) und der Theorie der Bezugsnormorientierung (BNO, Rheinberg, 1980) an einer Stichprobe von N = 135 Lehrkräften im Vorbereitungsdienst, inwiefern diese mit Inklusion und Bildungsstandards eine jeweils andere Unterrichtsgestaltung und Leistungsbeurteilung verbinden. Dabei wurden zwei Perspektiven der Unterrichtsbeschreibung (Selbst- und Fremdeinschätzung) kontrastiert. Die Ergebnisse zeigten, dass sich aus Lehrersicht inklusiver Unterricht von standardorientiertem Unterricht hinsichtlich der Umsetzung zentraler Merkmale von Unterrichtsqualität und hinsichtlich der darin auftretenden BNO bei der Leistungsbeurteilung unterscheidet. Berichtete Unterschiede waren zum Teil auf Einstellungen zu und Erfahrungen mit beiden Reformen sowie diesbezügliche Selbstwirksamkeitserwartungen seitens der Lehrkräfte zurückzuführen und variierten mit der Perspektive, aus der Unterricht beschrieben wurde. Davon ausgehend, dass Inklusion und Bildungsstandards unterschiedliche Bezugsnormen bei der Leistungsbeurteilung (Rheinberg, 1980) implizieren, untersuchte die experimentell angelegte Studie 2 anhand einer Stichprobe von N = 57 Lehrkräften im Vorbereitungsdienst, inwiefern eine Auseinandersetzung mit Bildungsstandards oder Inklusion in Abhängigkeit von den Einstellungen zu diesen Reformen zur Anwendung unterschiedlicher Bezugsnormen führt. Die Auseinandersetzung mit Bildungsstandards zog bei Lehrkräften mit einer positiven Einstellung zu diesen eine schwächer ausgeprägte individuelle BNO sowie tendenziell eine stärker ausgeprägte soziale BNO nach sich, während diese bei Personen mit einer negativen Einstellung zu Bildungsstandards zu einer stärker ausgeprägten individuellen BNO und tendenziell zu einer schwächer ausgeprägten sozialen BNO führte. Die Auseinandersetzung mit Inklusion beeinflusste die BNO hingegen nicht, weder bei positiver noch bei negativer Einstellung zu Inklusion. Da im Kontext beider Reformen unterschiedliche Maßstäbe der Leistungsbeurteilung hervorgehoben werden, untersuchte Studie 3 mögliche Konsequenzen der Anwendung subjektiver und objektiver Beurteilungsskalen für die Leistungsbeurteilung stereotypisierter Schülergruppen, wobei die sozialpsychologische Shifting-Standards-Theorie (z.B. Biernat, Manis & Nelson, 1991) zugrunde gelegt wurde. Die Studie gliederte sich in zwei experimentelle Vignettenstudien, wobei Teilstudie 1 (N = 115 Lehramtsstudierende) negative Stereotype gegenüber Mädchen in Mathematik fokussierte und Teilstudie 2 (N = 265 Lehramtsstudierende) negative Stereotype gegenüber türkischstämmigen Schülern in Deutsch. In beiden Teilstudien wurde jeweils das Mitglied der stereotypisierten Schülergruppe bei gleicher Leistung auf der objektiven Beurteilungsskala negativer eingeschätzt als das Mitglied der nicht stereotypisierten Schülergruppe, während sich auf der subjektiven Beurteilungsskala kein Unterschied in der Einschätzung beider Schülergruppen zeigte. Die Ergebnisse der drei Studien weisen auf bedeutsame Aspekte hin, hinsichtlich derer aus der Sicht von Lehrkräften unterschiedliche Anforderungen mit Inklusion und Bildungsstandards verbunden sein können, und tragen somit Erkenntnisse zur wahrgenommenen Vereinbarkeit beider Reformen in Bezug auf Unterrichtsgestaltung und Leistungsbeurteilung bei. Abschließend werden aus den Ergebnissen Vorschläge für die pädagogische Praxis sowie weitere Fragestellungen für die zukünftige Forschung abgeleitet.

Human genome has been expanded to approximately 8% by multiple waves of retroviral invasions, followed by lateral expansion, mainly in germ cells. Recent advancements provide substantial evidence that few families of Human Endogenous Retro-Viruses (HERVs) are co-opted to regulate cell-type specific physiological networks. Following up, we show that diverse modes of HERV-H activity have played a pivotal role in the evolution and development of human- specific embryogenesis including pluripotency. HERV-H provides binding sites for pluripotency transcription factors and serves as a major source for ncRNAs and chimeric transcripts in hPSCs. The interplay of host kruepel box proteins with HERV- H transcription determines the stability of human pluripotency. We updated the transcriptomic and transposcriptomic atlas of Human Preimplantation Embryogenesis (HPE) that re-define the progression of HPE at single-cell resolution. We characterize an unattended cell population in HPE that did not commit to any of the known lineages to form a stable preimplantation blastocyst. ICM being considered as reference frame for the purity of hESCs in naive/primed state conflict, we redefine ICM which adds another layer to the understanding of basic and regenerative biology. Committed and non-committed cells are distinguished by the reactivation of full-length HERVs and mutagenic retrotransposons respectively. We show that HERV-H transcripts control younger mutagenic elements with the mechanisms not known to us yet. Additionally, we also show that HERV-H expression is also prominent during fertilization and early stage of embryogenesis. We find the contrasting pattern of distinct loci of HERV-H during HPE, few of them driving the stage-specific markers that might determine the commitment of host cells to pluripotent lineages. Upon comparing the embryonic lineages and pluripotent states between primates, we decipher the probable mechanisms shaping the human-specific nature of embryogenesis. Much divergence within primate early development is owed to de-novo genes and chimeric transcripts that were remodeled by HERV-H. Moreover, HERV-H orchestrates the human-specific role in stabilizing self-renewal/pluripotency during HPE as inferred from transcriptome-wide cross-species comparison of primate pluripotent cells. Nevertheless, the HERV-H-derived regulatory network has been incorporated, and appears to be an essential feature of human pluripotency in native state. I show that HERV-H derived genes distinguishes the different pluripotent states in human embryos which plays pivotal role in the self-renewal during embryonic development and somatic reprogramming too. I show that the human pluripotency is required to maintain human-specificity in vitro to concur the native biological states with high fidelity. Finally, we show that HERV-H displays human-specific cross-talk with host-factors in distinct developmental lineages, including in-vivo and in vitro human pluripotent states. Finally our check-list of markers would be advantageous in order to sort in vitro pluripotent cells resembling in-vivo cells.

Die vorliegende Arbeit untersucht die Auswirkungen ausgewählter Reformen der Steuerbemessungsgrundlage im Bereich der Unternehmensbesteuerung. Drei Studien analysieren und evaluieren die Steuerwirkungen in Form von Belastungs-, Verteilungs- und Aufkommenswirkungen der (potentiellen) Steuerrechtsänderungen. In den Untersuchungen wird die Methode der (statischen) Mikrosimulation unter Verwendung von handelsrechtlichen Jahresabschlussdaten eingesetzt. Die erste Studie widmet sich dem implementierten EBITDA-Vortrag im Rahmen der Zinsschrankenregelung und analysiert die Steuerbelastungswirkungen auf Unternehmensebene. Die Ergebnisse zeigen, dass aus fiskalischer Sicht der EBITDA-Vortrag eine Entlastung für die Unternehmen bietet (gemessen an den Prognosen des Haushaltsausschusses). Auch aus unternehmensindividueller Sichtweise entlastet der EBITDA-Vortrag überwiegend zielgenau nach abgeleiteten Kriterien aus der Gesetzesbegründung. Unter Verwendung eines Maßstabs zur Berechnung der Steuerersparnis durch Zinsabzug (tax shield) wird allerdings deutlich, dass weitgehend die „falschen“ Unternehmen von der aktuell geltenden Zinsschranke getroffen werden. Der EBITDA-Vortrag hingegen entlastet tendenziell die „Richtigen“, kann jedoch entstandene Kollateralschäden nicht kompensieren. Die zweite Studie widmet sich zwei Reformkonzepten der zinsbereinigten Besteuerung auf Kapitalgesellschaftsebene in Deutschland unter besonderer Berücksichtigung der Verlustverrechnung und analysiert die potentiellen Steueraufkommenswirkungen. Die Ergebnisse zeigen, dass beide Ausgestaltungsalternativen zu deutlich geringeren Aufkommensverlusten führen, als bisher vom Gesetzgeber angenommen wurde, und dass vor allem auch kleine Unternehmen profitieren würden. Nahezu Aufkommensgleichheit wäre bei Grundkapitalverzinsung und Beibehaltung der Mindestbesteuerung zu erreichen. Da mit Zinsbereinigung die Verlustvortragsbestände leicht ansteigen würden, würde eine Verlustkappung die aktuelle Lage der hohen Bestände von Kapitalgesellschaften entschärfen und diese um knapp die Hälfte gegenüber dem Referenzrechtsstand reduzieren. Die dritte Studie widmet sich der Aufteilungsformel des Richtlinienvorschlags über eine gemeinsame konsolidierte Körperschaftsteuer-Bemessungsgrundlage (CCCTB) in der EU und analysiert die potentiellen Verteilungswirkungen auf Unternehmensebene. Die Studie untersucht, wie gut die CCCTB-Aufteilungsformel den „wahren“ Gewinn auf Unternehmensebene approximiert. Die Ergebnisse zeigen sehr hohe Gewinnfehlverteilungen unter dem vorgeschlagenen System des Formula Apportionment (FA). In der Hauptanalyse wird eine durchschnittliche negative (positive) Gewinnabweichung von -4,2% (6,2%) der Bilanzsumme festgestellt. Gegenüber dem durchschnittlichen Return on Assets der Stichprobe ergibt sich ein durchschnittlicher Fehler von -49,5% bzw. +74,1%. Die Analyse zeigt, dass die durch FA verursachte Abweichung nicht zufällig, sondern systematisch ist. Eine zusätzliche Analyse zeigt, dass insbesondere Verlustunternehmen unter zusätzlichen Steuerzahlungen durch FA leiden würden. Im Ergebnis schneidet die CCCTB-Aufteilungsformel im Rahmen der Studie bemerkenswert schlecht ab.

The major aims of this thesis were to describe how arbuscular mycorrhizal (AM) fungal communities vary with depth in agricultural land, and to gain insights into AM fungal community assemblage processes in subsoil. In chapter 1 I introduce basic aspects of AM fungal biology, review existing literature on the topic of this thesis and introduce the molecular methodology used in my studies. Chapter 2 and its appendices provide highthroughput sequencing evidence for the differences in AM fungal community composition in top- and subsoil, such as for the existence of phylotypes exclusively found in subsoil. As compared to topsoil, studied subsoil communities are less species rich, less even and have higher community turnover. However, they are not just a subset of topsoil communities and harbor unique taxa. In chapter 3 a top- subsoil mixing event is studied to trace the fate of subsoil phylotypes in topsoil. Here we observe the inability of these subsoil phylotypes to persist in topsoil, and interpret this as evidence for subsoil specialization in certain AM fungal taxa. Chapter 4 discusses the potential roles of subsoil AM fungi in agriculture, with a focus on sustainability and climate smart approaches. The major potential roles identified concern the access to greater nutrient and water pools, the resistance of the system to unfavorable conditions in topsoil, and the avoidance of nutrient leaching and greenhouse gas emissions. We also point out future research needs in this field. Chapter 5 puts the results of this thesis in the broader context of the literature, summarizing the conclusions 97 of previous chapters. In this chapter I also introduce ideas on AM fungal growth strategies and implications of subsoil AM fungi for the understanding of AM fungal biogeography.

The current study focused on the development of an ex vivo human skin model to investigate the added value of nanoparticle-based drug delivery systems on skin penetration and drug-mediated efficacy compared to conventional drug formulations for the topical therapy of inflammatory skin diseases. In order to induce different types and intensities of skin barrier disruption, physical and chemical means were applied on human skin explants obtained from plastic surgery. Comparative studies on structural integrity, biophysical parameters and cytokine levels were performed three times within 48 hours in two culture systems of skin. Cultures of skin maintained in tissue media preserved key skin barrier parameters and viability better than medium-free cultures in humidified chambers. The standardization of 50-times tape stripping and 4-hour sodium lauryl sulfate (5% w/v) pretreatment was reliable: transepidermal water loss values and interleukin-6 /-8 levels as examples of a wide range of affected inflammatory mediators were increased reproducibly compared to intact skin. Different structural and biological changes were induced, which are usually associated with pathological changes in diseased skin. Transepidermal water loss measurements provide a noninvasive screening tool to control and standardize skin barrier disruption ex vivo. Based on these results, time- and tissue-sparing protocols and methods for further investigations were adapted to a short-term skin culture system. Intradermal microdialysis in one experimental setup including up to nine sets for up to 24 hours enabled comparison of intact versus physically and chemically barrier-disrupted skin on the skin of one donor as well as three dexamethasone formulations (ethyl cellulose nanocarriers, nanocrystals and a conventional cream) in parallel. The application of highly sensitive detection methods, such as liquid-chromatography-tandem-mass spectrometry and Luminex R multiplex technology, provided a complex set of data on skin penetration and biological effects. The model successfully demonstrated that skin barrier disruption and the characteristic properties of the dexamethasone formulations affected drug penetration differently. Penetration rates in chemically treated skin were lower compared to tape-stripped skin. Nanocrystals quickly and effectively penetrated intact and barrier-disrupted skin. Thus, significantly higher dermal drug concentrations were achieved within six hours compared to the other formulations. The benefit of encapsulation in ethyl cellulose nanocarriers was more pronounced in intact skin. The results were largely in line with the prediction made based on in vitro release kinetics and Franz diffusion cell studies. High local cytokine levels indicated a trauma induced by probe insertion, which restricted the estimation of drug-mediated efficacy over time. Nevertheless, evidence was found that the application of nanocrystals was associated with high dermal cytokine levels, although significantly higher amounts of the anti-inflammatory drug penetrated the skin. This could point toward an irritative potential of the nanocrystals. In summary, conclusion can be drawn about drug penetration and local biological effects in intact versus barrier-disrupted skin after the application of up to three different drug formulations. Such a complex screening tool can help to characterize the added value of each individual nanoparticle-based drug delivery systems compared to conventional formulations for different pathological skin changes in order to determine the most appropriate for a particular clinical indication. To answer the questions as to whether and to which extent nanoparticles are capable of translocating across an intact skin barrier, an in situ imaging mode based on wide-field two-photon microscopy was implemented. The analysis of full-thickness samples allowed sample preparation steps to be reduced to a minimum, which mainly avoids the production of artifacts. Moreover, both interfollicular and follicular penetration were investigated in histomorphological correlation. Proof-of-concept work on fluorescently tagged nanoparticles revealed that the vast majority of nanoparticles remained in the upper Stratum corneum. However, rare events of deeper penetration were also observed in intact skin close to regions with high focal nanoparticle aggregations in the Stratum corneum and in the infundibulum of hair follicles. Total internal reflection fluorescence microscopy confirmed barrier crossing with high sensitivity. Individual nanoparticles as well as clusters of nanoparticles were detected in the Stratum corneum and within the epidermal layer directly beneath the Stratum corneum. The combination of both technologies provides highly important insights into penetration processes and pathways as well as into the barrier function of the skin, which are crucial for the development of nanoparticle-based drug delivery systems for improved topical application of drugs for inflammatory skin diseases.

Vanadium redox flow batteries (VRFBs) are amongst the most promising energy storage systems for storing renewable energies on a large scale. However, the system still has some challenges which limit its widespread application in industry. For instance, the unsatisfactory activity together with insufficient long-term stability of the state-of-the-art commercial activated carbon electrode (i.e., carbon felts) are the most known issues referenced in literature. This thesis introduces two novel solutions for the aforementioned problems: (i) fabrication of non-woven carbon nanofiber networks as alternative, efficient and stable electrodes and (ii) improving the performance of the commercial carbon felt electrodes via coating their surfaces with metal oxide nanostructures. Additionally, the hydrogen evolution reaction, a parasitic side reaction, which is believed to have detrimental impact on the performance of VRFBs, will be investigated at different operating temperatures. Non-woven polyacrylonitrile-based carbon nanofiber networks with a very high electrochemically active surface area were first produced by the scalable electrospinning approach and then directly used as an electrode in a vanadium redox flow battery. Using five sheets of polyacrylonitrile-based electrospun nanofibers achieved ~10% increase in the energy efficiency compared to the commercial carbon felt at current densities of 15 mAcm-2. Furthermore, low-cost highly active carbon-carbon composite freestanding nanofibers were produced by electrospinning a mixture of polyacrylonitrile and carbon black powder using poly acrylic acid (PAA) as binder. PAA enables the loading with higher amounts of the relatively cheap carbon black material. This results in an increase of the productivity of the electrospun carbon nanofibers at lower cost together with simultaneously enhancing the performance of the battery. Battery test results demonstrated a promising performance for the newly designed electrospun carbon fibers as negative and positive electrodes of vanadium redox flow batteries at current densities below 60 mAcm-2. The damaging role of the parasitic hydrogen evolution reaction (HER) in the negative half-cell of the vanadium redox flow battery on the performance of the commercial carbon felt electrodes was studied at different temperatures. Increasing the temperature resulted in a better catalytic performance for both the positive and negative half-cell reactions. Nevertheless, higher temperature significantly enhanced also the undesired HER at the negative side. This led to a decrease in the coulombic efficiency attributed to the higher amount of generated hydrogen causing faster fading of the overall VRFBs performance. Due II to rapid degradation of the commercial carbon felts resulting from the corrosion of their fibers. To minimize the degradation of the commercial carbon felt electrodes and therefore extend the lifetime of the battery, neodymium oxide (Nd2O3) nanoparticles were chemically deposited onto the fibers of the carbon felt by a precipitation method in non-aqueous solution. Nd2O3 modified carbon felts showed 4 times higher stability compared to the unmodified thermally activated carbon felt after 50 consecutive charge/discharge cycles. Moreover, Nd2O3 modified felts retained their original performance after exchanging the electrolyte, indicating less degradation occurred. Additionally, they could maintain their oxygen donating functionalities compared to the thermally activated commercial carbon felt.

Infektionen der unteren Atemwege zählen zu den häufigsten Todesursachen weltweit und betreffen jährlich mehr als 3 Millionen Menschen. Davon ist ein Großteil jünger als 5 oder älter als 65 Jahre alt. Der häufigste Erreger ist mit 1,5-2 Mio. Todesfällen pro Jahr S. pneumoniae. Ein grampositives, kokkoides Bakterium, das zwar allgemein gut antibiotisch behandelbar, jedoch schon lange für seine Resistenzen gegenüber u. a. β-Lactam- und Makrolidantibiotika bekannt ist. In gesunden Individuen mit einem intakten und potenten Immunsystem, die nicht ins Krankenhaus eingeliefert werden müssen, ist die Sterblichkeit mit ca. 0,1% relativ gering. Das Immunsystem verfügt offensichtlich über effektive Abwehrmechanismen. Des Weiteren sorgen kommensale Mikrobiota durch verschiedene Mechanismen dafür, dass es Pathogenen schwerfällt, sich im Wirt zu etablieren. Dies kann u. a. durch Konkurrenz um Nährstoffe, Belegung der Körpernischen oder durch die Ausschüttung von immunmodulatorischen und antibakteriellen Metaboliten geschehen. Körpereigene Immun-Abwehrproteine können durch direkte antibakterielle oder indirekte immunmodulatorische Wirkungen gegen eindringende Pathogene wirken und sorgen ebenso für ein sogenanntes gesundes Mikrobiom [67,68]. Diese Funktionen sind ebenfalls für die PGLYRP bekannt. Bislang sind jedoch keine Studien zur Wirksamkeit der PGLYRP gegenüber S. pneumoniae veröffentlicht. Um diese Lücke zu schließen wurde in dieser Arbeit der Einfluss der Proteine PGLYRP2 und PGLYRP4 auf eine S. pneumoniae-induzierte Pneumonie untersucht. Hierfür wurden WT und PGLYRP KO Mäusen transnasal infiziert und Auswirkungen auf das angeborene Immunsystem und das Mikrobiom analysiert.

PGLYRP2 KO Mäuse zeigten gegenüber den WT Mäusen eine Verschlechterung des klinischen Verlaufs der Pneumokokken-induzierten Pneumonie. Insbesondere wiesen sie mehr Bakterien in Milz und tendenziell auch im Blut 48 hpi auf. Interessanterweise weist das PGLYRP2 keinen direkten, antibakteriellen Effekt gegenüber S. pneumoniae auf und es konnten ebenfalls keine Veränderungen des Darmmikrobioms festgestellt werden. Vielmehr wurden die Effekte durch eine Verringerung an proinflammatorischen Zytokinen und folglich einer geringeren Rekrutierung an PMN in die Lunge der PGLYRP2-KO Mäuse verursacht. Infolgedessen zeigten die PGLYRP2-KO Tiere einen beschleunigten Krankheitsverlauf. Im Gegensatz zu den PGLYRP2-KO Mäusen, wiesen die PGLYRP4-KO Mäuse einen verbesserten klinischen Verlauf gegenüber WT Mäusen auf. Diese Verbesserung war mit einer signifikant geringeren Bakterienlast sowohl in den Lungen, als auch im Blut der infizierten Tiere verbunden. Die bessere Eliminierung der Pneumokokken in PGLYRP4-KO gegenüber WT Mäusen wurde von einer stärkeren inflammatorischen Immunantwort, mit einer Infiltration von PMN, T und B Zellen in die Lunge, sowie einer stärkeren Aktivierung von PMN durch lösliche Faktoren von AEC ausgelöst. Zusätzlich wurde eine stärkere alveoläre Barriere festgestellt, die eine Dissemination der Bakterien in die Peripherie vermutlich reduziert. Des Weiteren konnte gezeigt werden, dass die PGLYRP4-KO Mäuse über ein vermehrt proinflammatorisches Mikrobiom im Darm verfügen. Durch Übertragung dieser Mikrobiota auf keimfreie WT Mäuse konnte belegt werden, dass die Veränderungen im Mikrobiom keine Folge des proinflammatorischen Phänotyps, sondern ursächlich für den Schutz der PGLYRP4 KO Mäuse vor einer Pneumokokken-induzierten Pneumonie sind. Zusammenfassend konnte der Einfluss von zwei PGLYRP auf die S. pneumoniae-induzierte Pneumonie belegt werden. Dabei nimmt PGLYRP2 in diesem Modell eine proinflammatorische Rolle und PGLYRP4 eine anti-inflammatorische und Mikrobiom-modulierende Rolle ein. Fortführende Arbeiten könnten, durch die Aufklärung der genauen Mechanismen und beteiligten Bakterien, möglicherweise neue Behandlungsstrategien für Infektionserkrankungen, insbesondere der Pneumonie, ermöglichen.

Foodborne diseases induced by viruses involving plant-derived food such as berries are increasingly recognized as threat for public health. For example, a large human norovirus (hNV) gastroenteritis outbreak involving >10,000 diseased people occurred in Germany in 2012, which was traced back to contaminated frozen strawberries. To increase food safety for consumers, three areas were identified, which should be addressed in this thesis. First, different previously described virus extraction methods in combination with quantitative real time PCR (RT-qPCR) were compared using frozen strawberries artificially contaminated with hNV and the recovery rates (RRs) were calculated. Out of five published protocols, the method according to ISO/TS15216-2 revealed the best RRs. Further improvement of RRs from 2.83±2.92% to 15.28±9.73% was achieved by an additional RNA purification using Sephacryl®-based columns. The optimized protocol showed significantly better hNV detection rates by testing of berries originally involved in gastroenteritis outbreaks in 2012 and 2016. Second, novel methods for virus quantification and broad pathogen identification were tested on strawberries from the outbreak in 2012: Digital PCR (dPCR) and Next Generation Sequencing (NGS). A quantification of the hNV genomes using RT-dPCR confirmed a very low mean virus amount in the berries (185 RNA copies/25g), which was similar to the independently assessed RT-qPCR result (257 RNA copies/25g). By NGS, about 29 mio sequence reads were generated and analyzed by RIEMS 4.0 software. They mainly showed homologies to sequences from the plant matrix and from the bacterial flora. The most abundant virus sequences originated from plant-specific viruses. Two virus reads showed homologies to hNV identical to those derived from gastroenteritis patients and a strawberry sample obtained during the outbreak. Third, the thermal inactivation kinetics of hNV in strawberry puree was assessed. Due to the lack of a reliable system for hNV infectivity assessment, capsid integrity assays using RNase treatment prior to detection of protected viral RNA were applied. In addition, murine norovirus (mNV) and Tulane virus (TV) served as surrogates and were analyzed by plaque assay and RT-qPCR. Infectious mNV and TV were completely inactivated (>7 log10 reductions) after treatment at 80°C for 8 sec. However, in comparison to hNV, TV showed a markedly lower stability in capsid integrity assays. A predictive model generated from the data, which covers reduction of hNV capsid-protected RNA between 50-80°C, suggests that temperatures under 70°C are not reliable for inactivation. About 3.5 log10 reductions are achieved by heating at 80°C for 8 sec. In conclusion, methods for detection, identification and characterization of hNV in berries could be improved. The generated heat inactivation model may help developing efficient heat treatment strategies to prevent hNV infection due to consumption of berries in the future.

Infectious diseases still remain one of the main causes of death across the globe. Despite huge advances in clinical diagnostics, establishing a clear etiology remains impossible in a proportion of cases. Since the emergence of next generation sequencing (NGS), a multitude of new research fields based on this technology have evolved. Especially its application in metagenomics – denoting the research on genomic material taken directly from its environment – has led to a rapid development of new applications. Metagenomic NGS has proven to be a promising tool in the field of pathogen related research and diagnostics. In this thesis, I present different approaches for the detection of known and the discovery of unknown pathogens from NGS data. These contributions subdivide into three newly developed methods and one publication on a real-world use case of methodology we developed and data analysis based on it. First, I present LiveKraken, a real-time read classification tool based on the core algorithm of Kraken. LiveKraken uses streams of raw data from Illumina sequencers to classify reads taxonomically. This way, we are able to produce results identical to those of Kraken the moment the sequencer finishes. We are furthermore able to provide comparable results in early stages of a sequencing run, allowing saving up to a week of sequencing time. While the number of classified reads grows over time, false classifications appear in negligible numbers and proportions of identified taxa are only affected to a minor extent. In the second project, we designed and implemented PathoLive, a real-time diagnostics pipeline which allows the detection of pathogens from clinical samples before the sequencing procedure is finished. We adapted the core algorithm of HiLive, a real-time read mapper, and enhanced its accuracy for our use case. Furthermore, probably irrelevant sequences automatically marked. The results are visualized in an interactive taxonomic tree that provides an intuitive overview and detailed metrics regarding the relevance of each identified pathogen. Testing PathoLive on the sequencing of a real plasma sample spiked with viruses, we could prove that we ranked the results more accurately throughout the complete sequencing run than any other tested tool did at the end of the sequencing run. With PathoLive, we shift the focus of NGS-based diagnostics from read quantification towards a more meaningful assessment of results in unprecedented turnaround time. The third project aims at the detection of novel pathogens from NGS data. We developed RAMBO-K, a tool which allows rapid and sensitive removal of unwanted host sequences from NGS datasets. RAMBO-K is faster than any tool we tested, while showing a consistently high sensitivity and specificity across different datasets. RAMBO-K rapidly and reliably separates reads from different species. It is suitable as a straightforward standard solution for workflows dealing with mixed datasets. In the fourth project, we used RAMBO-K as well as several other data analyses to discover Berlin squirrelpox virus, a deviant new poxvirus establishing a new genus of poxviridae. Near Berlin, Germany, several juvenile red squirrels (Sciurus vulgaris) were found with moist, crusty skin lesions. Histology, electron microscopy, and cell culture isolation revealed an orthopoxvirus-like infection. After standard workflows yielded no significant results, poxviral reads were assigned using RAMBO-K, enabling the assembly of the genome of the novel virus. With these projects, we established three new application-related methods each of which closes different research gaps. Taken together, we enhance the available repertoire of NGS-based pathogen related research tools and alleviate and fasten a variety of research projects.

Seafood is considered as an important food source which contains high nutritional values via e.g. proteins, vitamins and minerals. Therefore, seafood production and consumption has increased worldwide in recent decades. Despite the nutrient benefits, consumption of seafood containing human pathogens might pose a potential risk of foodborne illness. Pathogenic bacteria, viruses, parasites, chemicals, heavy metals and natural toxins have been found in seafood. Among different bacterial pathogens detectable in seafood, Vibrio spp. are the most commonly associated with human infections. Another public health hazard related to seafood is the rapid increase of antimicrobial resistance among zoonotic pathogens in aquatic population. The spread of antimicrobial resistant bacteria, especially ESBL/AmpC-producing Enterobacteriaceae to human through the food chain has been reported and become a major concern of public health because of increasing in the number and severity of infections, as well as the frequency of treatment failure. In this thesis, three studies were conducted with the objectives (i) to determine the prevalence of Vibrio spp., (ii) to determine the prevalence, to investigate the quantitative load, and to characterize ESBL/AmpC-producing Enterobacteriaceae in retail seafood in Berlin, Germany, and (iii) to investigate the effect of HHP on the inactivation of Vibrio spp. in pure culture as well as mussel homogenates. The seafood investigation results demonstrate a high prevalence of Vibrio spp. in retail seafood with 55% (95% CI: 47.2% - 62.8%), and positive samples were detected in all types of seafood investigated. V. alginolyticus was the most prevalent species (35.6%), followed by V. parahaemolyticus (27.5%), V. cholerae (6.3%) and V. vulnificus (0.6%). The storage conditions seemed to influence the prevalence of Vibrio spp. Among chilled samples, the prevalence of Vibrio spp. in unpacked samples was significantly higher than in packed samples (P = 0.006). Whereas, among packed samples, no significant difference in the prevalence of Vibrio spp. between chilled or frozen conditions was observed (P = 1). None of the V. cholerae and V. parahaemolyticus isolates carried virulence genes. However, this should not be neglected because of previous findings on pathogenic strains lacking these virulence markers. In parallel with detection of Vibrio spp., the presence of ESBL/AmpC-producing Enterobacteriaceae in retail seafood was also investigated. The obtained data reveal that ESBL/AmpC-producing Enterobacteriaceae were detected in 21.3% of seafood samples (95% CI: 14.8% - 27.7%). Of the positive samples, 91.2% contained an ESBL/AmpC-producing Enterobacteriaceae load of < 100 CFU/g (lower detection limit), whereas 8.8% contained counts of 100 to 1,000 CFU/g. K. pneumoniae and E. coli were the two predominant species among the 45 isolates. β-lactamase genes were detected in 39 isolates, of which 33 isolates carried ESBL/AmpC β-lactamase genes with the majority of isolates harbouring blaCTX-M (27.3%), blaCMY (21.2%) and blaDHA (21.2%) genes. The obtained results from HHP experiment indicate the efficacy of HHP inactivating Vibrio spp. in both pure culture and mussel homogenates. Significant increases in reductions of Vibrio spp. were observed when pressure levels increased in combination with longer processing times. The reduction levels were significant different among the respective Vibrio spp., and V. vulnificus was the most susceptible species to HHP. To achieve a > 5-log reduction in mussel homogenates, treatment at 350-450 MPa for ≥ 1 min at 25ºC for V. alginolyticus, V. cholerae and V. vulnificus, or 250 MPa for ≥ 3 min for V. vulnificus are required, while pressure levels of 350 MPa for ≥ 3 min or 450 MPa for ≥ 1 min should be applied for V. parahaemolyticus. Our research highlights the hazard potential of seafood containing both Vibrio spp. and ESBL/AmpC-producing Enterobacteriaceae in Germany. Further investigations along the seafood chain should be carried out to clarify the contamination route of Vibrio spp. and ESBL/AmpC-producing Enterobacteriaceae as well as the transmission of resistance genes among these bacteria. Additionally, application of effective post-harvesting methods like HHP is recommended to reduce the contamination level of Vibrio spp. in seafood and finally to ensure the food safety for human consumption.

Forest ecosystems persist over thousands of years. The prevailing paradigm describes how a tight nutrient re-utilisation loop (recycling) from organic matter stored in the forest floor into trees ensures forest ecosystem nutrition. However, these nutrients are constantly lost by drainage during storage on the forest floor. This nutrient loss must be balanced on the long-term, because otherwise ecosystems would run into a deficit of mineral nutrients. In supply-limited weathering regimes, which are often found in non-eroding, well-drained settings, chemical weathering has run to completion and the nutrient loss from the forest floor is counterbalanced by external atmospheric wet and dry deposition. In kinetically limited weathering regimes, which are often found in eroding, temperate settings, the regolith (comprising soil, saprolite and weathered rock) still contains mineral nutrients, as mineral dissolution kinetics are slower than the advection of minerals from deep, unweathered rock to the Earth’s surface. At the surface, minerals and plant litter are removed by erosion. The mechanisms by which forest ecosystem nutrition is maintained in the face of these losses is the topic of this thesis. I explore the role of the deeper regolith and the mechanisms and fluxes by which this deep reservoir serves to sustain ecosystems over the long-term. I use geochemical mass balances and innovative metal isotope proxies to derive fluxes and sources from rock weathering into forest trees in montane, eroding and temperate forest ecosystems. How montane, temperate forest ecosystems are nourished was explored at two study sites in the Schwarzwald (site CON) and the Bayerischer Wald (site MIT). Both sites are underlain by paragneiss of contrasting mineralogy, mantled by Cambisols developed on periglacial slope deposits and covered by Fagus sylvatica and Picea abies. At both sites I quantified nutrient availability, nutrient accessibility, fluxes of nutrient supply by chemical weathering, and nutrient uptake by forest trees. The regolith at site CON experienced substantially more nutrient loss through chemical weathering than at site MIT. Nevertheless, nutrient uptake fluxes from forest trees are virtually identical at both sites. Considering a forest ecosystem in a mass balance comprising a shallow `organic nutrient cycle´ and a belowground `geogenic nutrient pathway´ shows that the nutrient inventory in the forest floor is of finite size that lasts only for decades, because persistent nutrient loss through plant litter drainage and erosion occurs from the forest floor. This permanent nutrient loss is balanced by fluxes from a reservoir consisting of the biologically available fraction (water-soluble and easily exchangeable fractions for the metal elements, and exchangeable and calcium-bound phosphorus fractions for phosphorus) from the upper regolith (<3 m), and even more significantly from the deep regolith (>3 m). This reservoir of nutrients ensures forest ecosystem nutrition over millennia, because it can replace the nutrient loss from the forest floor and is continually replenished through chemical weathering. Supply from this deep reservoir is linked to the organic nutrient cycle which is regulated by uptake into forest trees through the adjustment of the number of nutrient re-utilisation cycles from plant litter depending on nutrient supply fluxes. Thus, uniform uptake of mineral nutrients emerges despite large differences in their release through rock weathering. With this new concept in mind I constrained the uptake depth of the most plant-essential mineral nutrient phosphorus (P). While biologically accessible P forms, namely exchangeable P, are negligible throughout the regolith, the Ca-bound P, biologically available as 〖"PO" 〗_"4" ^"3-" through mineral dissolution, increases with depth and dominates in the lower part of the regolith and in unweathered rock. To test whether this deep P and other mineral nutrients from this depth are utilised by trees, I applied isotopic tracing methods. To track the depth of nutrient uptake radiogenic Strontium (Sr), namely the ^"87"Sr/^"86"Sr ratio, an established isotope proxy for source tracing was used together with the first application of the meteoric cosmogenic Beryllium (Be) isotope system, namely ^"10"Be_"meteoric"/^"9"Be_"stable". From the agreement in these isotope ratios between plant tissue and the forest floor´s biologically accessible fraction I demonstrate that these elements, and by inference also P and other mineral nutrients, are turned over between the forest floor and trees. I also show that these elements initially originate from the lower part of the regolith. Because this depth lies beyond reported rooting depths of the prevalent tree species it is speculated that nutrient uplift occurs through a combination of root-mycorrhiza symbiosis, dimorphic root systems and capillary rise of pore water. Nutrient export after rock weathering was explored in the montane, temperate forest ecosystems of the Southern Sierra Critical Zone Observatory, California, underlain by granodiorite bedrock, mantled by Entisols and Inceptisols and covered mainly by Pinus ponderosa. Magnesium (Mg) stable isotopes are sensitive indicators of Mg utilisation by biota. Mg utilisation takes place from up to 6 m depth, as evidenced by the light Mg isotopic composition of the easily exchangeable fraction. It was further found that trees, in particular wood, are isotopically heavy, whereas stream water is isotopically light. Converting this difference into a mass balance shows that 50-100 % of the Mg released by chemical weathering is utilised by trees. From the comparison between the river dissolved fluxes of other plant-essential and plant-beneficial elements (K, Ca, P and Si) with their weathering release fluxes a deficit is found in the river dissolved fluxes that is attributed to nutrient uptake by forest trees. Thus, either the mineral nutrients are accumulating today in re-growing forest biomass after clear cutting, or they are exported in plant litter and coarse woody debris, rather than appearing in drainage. The two major outcomes of this thesis are that the permanent nutrient loss at the Earth surface by plant litter drainage and erosion is balanced by nutrient uptake from the deep regolith, and that erosion and weathering are coupled through nutrient uptake at depth and erosion of these nutrients in plant debris at the surface.

The research investigates the main characteristics of harmonizing the copyright laws of post-Soviet non-EU states with European copyright law. The interrelation between these two components - European copyright law, on one hand, and the copyright laws of the post-Soviet non-EU states, on the other, is the main subject of the study. In this research both of these components, as well as their interrelation, are examined with critical perspective. Georgia is selected as typical example of a post-Soviet country aspiring towards European integration but which is not a member of the EU. Since Georgia shares certain similarities with other post-Soviet non-EU states, the copyright laws of Armenia, Azerbaijan, Moldova, Russia and Ukraine are also examined in this context. The final part of the research presents certain proposals for further implementation of EU copyright legislation into those of the post-Soviet non-EU states. All of these practical proposals are based on the theoretical observations and hypotheses elaborated so far, and are oriented to contribute to the process of harmonizing European copyright law with those of the post-Soviet non-EU states.

An der Grenzschicht zwischen einer festen Oberfläche und der umgebenden Luft wachsende subaerische Biofilme (SAB) zeichnen sich durch eine erhöhte Toleranz gegenüber extremen Umweltbedingungen und dem Eintrag von Bioziden aus. Dieser Schutz vor äußeren Umwelteinflüssen wird vornehmlich durch den Beitrag von extrazellulären polymeren Substanzen (EPS) und Pigmenten, wie Melanin und Carotinoiden, vieler unterschiedlicher Organismen gewährleistet. Deren Synthese wird wiederum durch intrazelluläre Botenstoffe reguliert. Das Cyanobakterium Nostoc punctiforme und der mikrokoloniale Pilz Knufia petricola, als Partner eines etablierten SAB-Modells und Vertreter zweier typischer Organismengruppen in SAB, wurden genutzt, um Botenstoffe und Pigmente genetisch zu manipulieren und die Biofilmmatrix dieser Mutanten strukturell zu untersuchen. In dieser Arbeit konnten erstmals die EPS beider Organismen extrahiert und die Struktur der extrazellulären Polysaccharide beschrieben werden. Daneben wurden die extrazellulären Polysaccharide von K. petricola Wildtyp mit denen verschiedener Pigmentmutanten verglichen. Das Fehlen des Schutzpigmentes Melanin führte zu einer ausgeprägteren extrazellulären Matrix in den Biofilmen. Gleichzeitig änderte sich die Struktur der extrazellulären Polysaccharide. Während der Wildtyp zu ~80% ein α-Glucan und zu ~20% ein α/β-Galaktomannan sekretierte, war der Anteil des Galaktomannans bei den Melaninmutanten erhöht. Das Ausschalten der Carotinoid-Synthese hatte jedoch keinen Einfluss auf die Beschaffenheit der extrazellulären Polysaccharide. Ein deutlich komplexeres extrazelluläres Polysaccharid aus acht verschiedenen Monosaccharid-Einheiten bildete N. punctiforme. Durch die Überproduktion des bakteriellen sekundären Botenstoffes c-di-GMP konnte zudem ein grundlegender Einfluss auf die Reaktion des Cyanobakteriums gegenüber externen Signalen und die damit verbundene Zelldifferenzierung gezeigt werden. Ein artifiziell erhöhtes c-di-GMP-Level in den Zellen führte zur Ausbildung eines sessilen Lebensstils durch Hemmung der Differenzierung motiler Hormogonien und vermehrte Produktion von EPS. Die Struktur der extrazellulären Polysaccharide wurde dadurch nicht verändert. Neben der strukturellen Analyse konnten die Veränderungen der extrazellulären Matrix beider Organismen zusätzlich durch mikroskopische Methoden visualisiert werden. Beide Organismen steuern komplexe Polymere, deren Produktion maßgeblich mit intrazellulären Faktoren verknüpft ist, zu der extrazellulären Matrix des Modellbiofilms bei.

Dieses Dissertationsprojekt analysiert und stellt die Problematik der literarischen Nachahmung bei Isidore Ducasse, Comte de Lautréamont vor. Der Fokus dieser Arbeit liegt im dichterischen Werk von Comte de Lautrémont, das als außergewöhnlicher Fall der neueren französischen Literatur gilt. Die Problematik seiner individuellen und einzigartigen literarischen Imitatio stellt hierbei den Gegenstand meiner Untersuchungen. Ausgehend von der These „[der] Möglichkeit der anderen Literatur“ als charakteristisches Merkmal in den „Les Chants des Maldoror“ und den „Poésies“, die einen besonderen Platz in der Literaturgeschichte als antiromantisches Werk im Ausklang der romantischen Epoche und als Einleitung zur Postmoderne einnehmen, wird diese Dissertation den nicht gelungener Vorschlag einer alternativen literarischen Strategie, die sich im Weiteren nicht etabliert hat, erforschen.

Within the scope of this cumulative thesis, four aspects behind oxo-functionalized graphene (oxo-G) and thereout derived graphene (G) were examined: the mechanism behind the formation of oxo-G out of several types of graphite, the control of the size distribution of thus obtained oxo-G nanoparticles, the cell-toxicity of oxo-G and its performance to act as a carrier system for the DNA transport into cells, and finally methods to functionalize oxo-G and G to produce novel materials. This thesis could elucidate unknown material properties and possible application of this outstanding class of carbon based 2D materials in the means of a divers set of analytical tools.

Mein Dissertationsprojekt verfolgt das Ziel, die sprachlichen Ausdrucksmöglichkeiten für Emotionen und andere innere Zustände und das diesen Ausdrucksmöglichkeiten zugrundeliegende Verständnis von Emotionen und inneren Zuständen bei einem seltenen genetischen Syndrom, dem Williams-Syndrom (WS), umfassend zu erforschen. Dafür werden 15 Kinder und Jugendliche mit WS und eine Vergleichsgruppe aus 30 Kindern und Jugendlichen mit einem unauffälligen Entwicklungsverlauf anhand verschiedener Tests untersucht. Der Ausdruck von Emotionen und inneren Zuständen war in der bisherigen WS-Forschung kein expliziter Untersuchungsgegenstand und ist daher nur unvollständig erschlossen. Weiterhin herrscht aufgrund der bisher primär neuro- psychologisch orientierten Forschungspraxis bezüglich des WS eine statische Sichtweise auf das Syndrom vor, die die Entwicklungsspezifik dieser Erkrankung weitgehend außer Acht lässt. In dieser Arbeit wird deshalb versucht, die vielfältigen sprachlichen und sprachbegleitenden Ausdrucksmöglichkeiten für Emotionen und mentale Zustände beim WS zu erforschen und dabei einen größeren Entwicklungszeitraum in den Blick zu nehmen, nämlich den Zeitraum vom Schuleintritt bis zum Jugendalter. Diese Forschungsperspektive erlaubt nicht nur die Beantwortung der Frage, welche spezifischen Ausdrucksmöglichkeiten für Emotionen bei WS zu finden sind, sondern auch der Frage, ab welchem Entwicklungsgrad diese Mittel erstmals auftreten und wie sie sich im Weiteren entwickeln. Diese Forschungsperspektive ist besonders spannend, da inhomogene Leistungen im sprachlichen, sozialen, emotionalen und kognitiven Bereich für das Syndrom typisch sind, welche in keiner eindeutigen Relation zum allgemeinen kognitiven Entwicklungsstand der Betroffenen stehen. Diese Stärken und Schwächen betreffen beispielsweise den Bereich des sozial-emotionalen Verhaltens, das durch eine offene, distanzlose und einnehmende Persönlichkeit einerseits, andererseits jedoch durch bedeutende Probleme im Aufbau und der Aufrechterhaltung von Freundschaften zu Gleichaltrigen und teilweise durch depressive und aggressive Tendenzen gekennzeichnet ist. Die genaue Analyse des sprachlichen Ausdrucks von Emotionen und deren Verständnis ist vor diesem Hintergrund von besonderem Interesse. Mit der Studie soll also die Frage beantwortet werden, in welchem Verhältnis das Verständnis mentaler Vorgänge und Emotionen und die Produktion sprachlicher Äußerungen, die diese reflektieren, zueinander stehen. Spezifische Leistungsmuster können gegebenenfalls mit den genetischen Charakteristika der Erkrankung in Zusammenhang gebracht werden. Die Ergebnisse der Studie zeigen deutliche Beeinträchtigungen im nonverbal-kognitiven Bereich bei allen Probanden mit WS und moderate Schwierigkeiten hinsichtlich der sprachsystematischen Kompetenzen. Bezüglich der Emotionsverarbeitung zeigen sich sowohl bei der Interpretation emotionaler Gesichtsausdrücke als auch der von Körperhaltungen Einschränkungen, die jedoch weniger stark ausgeprägt sind, als das Entwicklungsniveau der Probanden vermuten ließe. Im Verstehen von Emotionswörtern und in der Interpretation wütender Gesichtsausdrücke erreichen die WS-Probanden sogar das Niveau altersgleicher Kontrollprobanden. Die höhere kognitive Leistung des Aufbaus einer sogenannten Theorie des Geistes entwickelt sich bei den untersuchten Kindern und Jugendlichen mit WS zwar verzögert, nicht aber verlangsamt. Im Kontrast zu den genannten Befunden stehen die Ergebnisse der narrativen Untersuchung der Probanden. Hier zeigte sich eine verstärkte Verwendung vieler die Geschichten ausschmückender Mittel, wie zum Beispiel die Verwendung von Lautmalereien, des Nachahmens bestimmter Handlungsaspekte und die Verwendung von Ausrufen in der direkten Rede. Selbst wenn der mentale Entwicklungsstand der untersuchten WS-Probanden berücksichtigt wird, finden sich noch Vorteile gegenüber den jüngeren nach mentalem Alter gematchten Kontrollkindern. Dies ist unter anderem der Fall für die Länge der erzählten Geschichten, für Verben, die emotionale Zustände der Akteure der Geschichten widerspiegeln und für Verkleinerungsformen. Eine besondere Schwäche fand sich bezgüglich der inhaltlichen Ausgestaltung der Erzählungen bei WS. Die Geschichten wurden also in beeindruckender Weise ausgeschmückt, wenngleich die inhaltlich bedeutsamen Aspekte der Erzählung oft nicht ausreichend verbalisiert wurden. Die Befunde werden vor dem Hintergrund der vorhandenen Forschungsliteratur diskutiert.

The North Anatolian Fault Zone (NAFZ) in the Sea of Marmara, Turkey, is likely to host a major earthquake (magnitude M > 7) in the coming decades. This exposes one of Europe’s largest metropolitan areas, Istanbul, to substantial risk. The thesis at hand contributes to the description of the seismotectonic setting in the area, a prerequisite for a comprehensive seismic hazard assessment.

As the extended water body in the area has inhibited continuous seismic near-fault recordings, this long term study covering a decade of seismic activity (2006–2016) aggregates different land based, permanent seismic networks for joint analysis including the two largest, national seismic networks. With such optimized azimuthal coverage and a consistent waveform-processing scheme, a refined earthquake catalogue with 6812 hypocentre locations is obtained. The development and regional adjustment of the involved automatized timing (picking) and iterative inversion of seismic P- and S-wave onsets are explained in detail. Newly calculated moment magnitudes indicate completeness down to Mc = 2.1. As part of this thesis, the new catalogue serves as input for a search of highly similar earthquakes (repeaters) and a segmented investigation of the stress field where waveform cross-correlation and direct inversion of first-motion polarities are the employed methods, respectively.

The earthquake distribution distinguishes the northern branch of the NAFZ as the more active fault strand and spares several aseismic patches there. The latter are interpreted as locked fault segments where their contours are further sharpened by a catalogue of 4407 relatively relocated earthquakes. Repeating earthquakes in the western half of the Sea of Marmara indicate that the fault segments there accommodate the far-field deformation by partial creep. For the same fault segment the stress-field inversion indicates a normal faulting regime.

Adjacent, in the east and west offshore the Ganos Mountains and the Princes’ Islands, respectively, it is framed by strike-slip regimes. This spatial variation of the orientation of the largest and intermediate principal stresses as well as most of the newly calculated single focal mechanisms are in agreement with large scale transtension. It is found for other seismically active areas off the northern fault branch too and it is characterized by a least compressive principal stress that has almost constant N35°E trend on average and a subhorizontal plunge.

The transtensional setting with a combination of normal and strike-slip stress regimes implies that both faulting types could be involved during the expected major earthquake. Its nucleation seems more likely within locked fault patches and less likely at segments displaying creep. As the latter are situated on the farer end of the fault zone, the hazard from a rupture directed towards Istanbul is relaxed.