Mucins are heavily glycosylated proteins, with carbohydrates comprising up to 80% of their weight. They form the primary component of mucus, a complex protective hydrogel that covers all biointerfaces in mammals. Mucins play important biological roles in our body, e.g. protection against pathogens, yet the role of the glycans is still poorly understood. The primary objective of my doctoral research was to deconstruct mucin complexity by generating well-defined, fully synthetic mucin-like glyco-hydrogels using self-assembling systems. I worked on two approaches to create supramolecular mucin mimetics capable of forming hydrogels, which serve as models to study mucus and explore relationships between composition, structure, and properties. By mimicking natural mucin structures with previously established coiled-coil peptides or self-assembling oligosaccharides as backbones, and decorating them with carbohydrates, I aimed to understand the rules governing hydrogel formation to create tuneable and responsive synthetic mucin-like hydrogels. In Chapter 2 of the thesis, I synthesized various mucin-relevant well-defined oligosaccharides with Automated Glycan Assembly (AGA). I designed a novel building block (BB) for the installation of α-GalNAc with complete stereoselectivity, aiding access to mucin core structures. I also developed chemoenzymatic synthesis strategies to access sialylated structures, expanding the scope of this work. Five synthesized structures were used by the group of Prof. Dr. Koksch to decorate a hydrogel-forming peptide, hFF03, to generate simple mucus models. Regardless of the type of carbohydrate substitution, the hydrogels maintained similar secondary structures and exhibited consistent fiber morphology. In contrast, small differences in the carbohydrate composition affected the viscoelastic behavior. In Chapter 3 I analyzed how parameters connected to the solid-support affect the AGA outcomes for three model glycan sequences. The study showed that, while loading and reaction scale did not significantly influence the AGA outcome, the chemical nature of the linker dramatically altered the isolated yields. I identified that the major determinants of AGA yields are cleavage from the solid-support and post-AGA steps. The study suggests that loading and reaction scale don't significantly affect AGA, therefore offering insights for scaling up mucin-related glycan synthesis. In Chapter 4 I focused on cellulose-based (A8) supramolecular hydrogels with tunable properties to mimic native mucus. I synthesized three XA8C analogues carrying a 3,6-methylated glucose residue (C) and a saccharide epitope (X). Furthermore, I developed a chemoenzymatic method to create a sialylated analogue, Sia6GA8C, adding complexity to the toolbox of mucus-inspired hydrogels. In this thesis, I deconstructed the complexity of mucins by developing well-defined, artificial mucin-like glyco-hydrogels through innovative self-assembling systems. The established synthetic platforms and methodologies offer a versatile toolkit for further investigations into the biological roles of mucin-type glycosylation and the development of novel therapeutic strategies.

Infektionsprävention und -kontrolle sind essentiell zur Vorbereitung auf und Bekämpfung von Pandemien. Neben dem Einfluss auf die pandemische Resilienz ist Infektionsprävention ebenso entscheidend in Bezug auf antimikrobielle Resistenzen. Infektionsprävention generell und Händehygiene im Besonderen können dazu beitragen, sowohl die Entstehung als auch die Verbreitung von Resistenzen zu verhindern. In Westafrika treffen zwei entscheidende Herausforderungen aufeinander: begrenzte finanzielle Ressourcen im Gesundheitssystem mit lückenhafter infrastruktureller Ausstattung und häufige gesundheitliche Notlagen vor allem durch infektiöse Erkrankungen. Genau in dieser Region ist es demnach entscheidend Händehygiene als Grundpfeiler der Infektionsprävention zu stärken. Die vorliegende Habilitationsschrift stellt fünf wissenschaftliche Originalarbeiten zum Thema Herausforderungen der Infektionsprävention und -kontrolle in zwei westafrikanischen Ländern vor. Die Global Health-Perspektive wird dabei mit einem Mixed-Method-Ansatz vereint um so ein tiefgreifendes Verständnis zu schaffen, das eine kontextsensible Umsetzung ermöglicht. Besonderer Fokus liegt dabei auf der lokalen Produktion von Desinfektionsmittel als hochskalierbares und resilientes System zur Überwindung von globalen Abhängigkeiten. Die vorgelegten Arbeiten zeigen, dass die Multimodale Strategie der WHO zur Verbesserung der Händehygiene zum einen lokal adaptier- und anwendbar ist und sich zum anderen als effektiv zur Verbesserung von Wissen und Compliance auf allen Ebenen der Gesundheitsversorgung sowie zu Pandemiezeiten erweist. Durch die Einbeziehung kultureller sowie systemischer Gegebenheiten kann die Multimodale Strategie der WHO zur Verbesserung der Händehygiene, als globale Gesundheitsstrategie, in den vorliegenden Arbeiten lokal, evidenzbasiert und vor allem nachhaltig umgesetzt werden. Dadurch wird sowohl auf lokaler Ebene Infektionsprävention und Resilienz gestärkt, als auch auf globaler Ebene Pandemievorsorge und -bewältigung verbessert.

The synthesis of ribosomes is one of the major tasks in actively growing bacteria, where ribosomes can make up as much as 30% of the cellular dry mass. Therefore, diverse strategies are needed to regulate the synthesis of ribosomal proteins (r-proteins) and RNAs (rRNAs) to prevent energy waste during cell growth. Expression of the E. coli rpsJ operon, which encodes 11 r-proteins, is autogenously regulated by one of its products, r-protein L4. L4 is unique as it is the only E. coli r-protein that mediates autogenous control through transcriptional attenuation. An RNA element encoded by the operon’s leader region is involved in this attenuation process. The RNA can form five hairpin structures, HA to HE, followed by two attenuation sites, ATT and ATT’. L4 attenuates rpsJ transcription by stalling RNA polymerase at ATT and ATT’ sites, a process which is strictly dependent on NusA. To understand this regulatory event at a molecular level, single-particle cryogenic electron microscopy (cryo-EM) was used to determine the structures of E. coli transcription attenuation complexes (ATTCs) in the absence and presence of transcription factors, including NusA, L4, and the universal transcription factor NusG. These structures reveal hairpin-dependent stabilization of the paused transcription complex by NusA and L4, as well as the involvement of the NusA KH1 domain and the RNA polymerase (RNAP) β’ subunit in L4 binding. NusA contributes to transcription pausing by stabilizing the RNA hairpin HE at the RNA exit channel. An additional hairpin HD, sandwiched between L4 and NusA KH1-KH2 domains, is incorporated into the ATTC when L4 binds to the complex. In vitro transcription assays using a NusA variant that lacks the KH1-KH2 domains confirmed the importance of the NusA KH1-KH2 domains in the rpsJ attenuation process. Furthermore, the roles of L4 and its interactions with hairpin HD and RNAP were demonstrated through site-directed mutagenesis of L4 and RNAP, combined with in vitro transcription assays. E. coli has also evolved a transcription anti-termination complex (rrnTAC) to efficiently synthesize rRNAs. In rrnTACs, RNAP is modified at the RNA exit channel by a complex RNA chaperone composed of the transcription factors NusA, NusB, NusG, S10, and SuhB. This multi-factor RNA chaperone facilitates the co-transcriptional folding of nascent rRNA, which is a prerequisite for subsequent processing of the primary transcript into mature rRNAs. The first step in rRNA maturation is cleavage by RNase III. Upon completion of 16S rRNA transcription, a long, double-stranded RNA (dsRNA) stem (16S stem) is formed. This stem contains the recognition motif for RNase III cleavage, which generates the pre-16S rRNA. To investigate the molecular basis of co-transcriptional rRNA folding and processing, cryo-EM was used to determine structures of rrnTACs containing variants of the 16S stem that include the RNase III cleavage motif and resemble the pre-processed transcript of pre-16S RNA. NusA and the SuhB dimer anchor the 5’ end of the 16S stem near the RNA exit channel, creating a platform for dsRNA formation in a spatially defined region. Structures of rrnTACs bound by an inactive RNase III variant were also elucidated. The dimeric RNase III engages the 16S stem on the side opposite the RNAP-associated RNA chaperone and forms direct contacts not only with the dsRNA but also with NusA and one of the SuhB subunits. These findings reveal the structural basis of co-transcriptional, long-range RNA secondary structure formation by tethering the 5’ part of the nascent RNA to a multi-factor RNA chaperone, bringing it into proximity with the emerging 3’ part to promote dsRNA formation. Together, these molecular insights into ATTCs and rrnTACs provide a better understanding of the regulatory mechanisms governing ribosome synthesis during rapid bacterial growth and may inform the development of antibiotics targeting the bacterial ribosome synthesis pathway.

In this thesis, we report on several topics related to the stability of random dynamical systems. First, we show that a mechanism known as shear-induced chaos can induce chaotic behavior, as evidenced by a positive Lyapunov exponent, in a Stuart-Landau oscillator perturbed by additive white noise. This answers a question that has been raised several times in the literature . We then study a class of stochastic differential equations that allows for stronger shear than in the Stuart-Landau oscillator. This strong shear can cause the system to no longer admit a random attractor or to even lose strong completeness, i.e., to no longer admit a global stochastic flow. We call this mechanism shear-induced blowup. Furthermore, we derive two tight conditions on the growth of the shear term, under which the system is strongly complete and admits a set attractor, respectively. Combined with information about the sign of the largest Lyapunov exponent, this allows us to conclude whether the system is strongly and/or weakly synchronizing. For this, we introduce a new set of conditions for stochastic differential equations with additive noise under which the time-1 map satisfies a stable/unstable manifold theorem. These conditions are weaker than those previously available in the literature and, in particular, can handle cases for which the stochastic differential equation is not strongly complete. The final chapter of this dissertation deals with the stability of random dynamical systems in the context of machine learning. In particular, we study an overparameterized optimization task that is commonly encountered in modern deep learning. We characterize the set of interpolation solutions that are dynamically stable under two popular learning algorithms, gradient descent and stochastic gradient descent. Dynamical stability is related to generalization and implicit bias, a topic that is still poorly understood, despite the success of machine learning. Some of the results presented in this thesis are based on joint work with Maximilian Engel and Michael Scheutzow.

Biopolymers self-assemble to generate dynamic and complex functional materials that carry out sophisticated tasks. Inspired by nature, chemists have sought to create artificial analogs that mimic biopolymer self-assembly. Unlike peptides and nucleic acids, carbohydrates are less understood at the molecular level and have rarely been employed as scaffolds to construct self-assembling materials. Consequently, the potential of carbohydrates in supramolecular chemistry remains largely untapped. The primary objective of my doctoral research was to establish structure-property correlations for oligosaccharides and apply this understanding to develop design principles for creating carbohydrate foldamers and self-assembling materials. Molecular dynamic (MD) simulations played a central role in elucidating the structure, function, and stability of both natural and artificial oligosaccharide systems. In Chapter 2 of the thesis, I demonstrated that synthetic chitin oligomers self-assemble into platelets, which then aggregate into higher-order structures. Environmental humidity significantly affects their morphologies, emphasizing water's role in shaping chitin-based architectures. Different humidity levels produced various shapes, from undefined assemblies to well-defined chiral bundles, suggesting the potential to create multiple architectures on- demand. In Chapter 3, I conducted a systematic analysis of the factors affecting the conformational stability of a synthetic glycan hairpin. The modular design of the synthetic hairpin enabled the investigation of the effect of various chemical modifications, showing that longer strands enhance conformational stability and that the turn motif's intrinsic conformational proclivity is crucial for hairpin folding. These findings challenge the perception of glycans as flexible molecules, suggesting they can be designed to adopt rigid conformations. In Chapter 4, I developed a platform to screen the conformational space of glycans. By using a novel MD-based approach, multiple turn sequences were identified that fold into the unique conformation of an anti-parallel glycan hairpin, showcasing the platform's potential. The insights gained from studying carbohydrate materials and glycan foldamers culminated in the rational design of the world's first prototype for de novo glycan design. This work provides a foundation for the future design of oligosaccharides with potential applications in material science, medicine, and catalysis.

This dissertation addresses the synthesis, structural characterization, and physicochemical investigation of novel alkali-metal sulfido- and selenido-metalates containing 3d transition metals (such as iron, cobalt, chromium, and vanadium) as well as the post-transition metal bismuth. The research focuses on the structural, electronic, magnetic, optical, dielectric, and electrochemical properties of these compounds, aiming to systematically explore the relationship between crystal structure, coordination chemistry, and functionality. The study includes materials, such as, Na2[Fe3S4], K2[Fe3S4], K2[Co3S4] and K2[Cr3S4], where varying the chalcogen content and targeted substitutions led to the formation of structural motifs, such as, square-planar and square-pyramidal coordination geometries. These geometries are rare in classical transition metal chemistry and significantly influence the observed physical properties. The materials exhibit, among other things, antiferromagnetic behavior, frequency-dependent dielectric responses, and in some cases, noteworthy ionic conductivity. Additionally, the work explores how structural features, such as, metal-site defects or specific chalcogen-metal interactions, affect functional properties like conductivity and magnetic ordering. These findings provide a deeper understanding of structure–property relationships in this class of materials and serve as a foundation for the targeted development of such compounds with potential uses in energy and information technologies. Future studies should focus on more detailed electronic and transport analyses, particularly regarding the role of defects and substitution effects. Only on this basis can possible applications, such as, cathode materials, spintronic systems, or electrochemical storage devices, be meaningfully pursued.

This dissertation explores the context-dependent effects of tire wear particles and multiple concurrent anthropogenic stressors on soil ecosystems. In chapter 2, we address the impacts of TWPs with different delivery rates on soil physicochemical properties and microbial activities. By either adding TWPs to soils abruptly or gradually, this study showed that gradually-delivered TWPs negatively influenced the activity of carbon cycle-related enzymes, and abruptly-delivered TWPs had no significant effect. Abruptly-delivered TWPs increased the activity of nitrogen cycle-related enzymes, while gradually-delivered TWPs had no significant effect. It highlights that delivery rate of TWPs could be a key factor shaping the effects of TWPs on soil microbial activities. In chapter 3, we investigate if ageing influence the effects of TWP leachates on soil. TWPs were subjected to different ageing conditions, including mechanical-, thermal-, and UV-ageing. We found that comparing to pristine TWPs, the leachates of aged TWPs generated broader effects on soil physicochemical properties and microbial activities, and the response patterns were dependent on ageing conditions. This study suggested that ageing can alter the effects of TWP leachates on soil, and highlighted the necessity of considering ageing condition as a crucial factor when investigating the environmental effects of TWPs. In chapter 4, we explore how an increasing number of concurrent anthropogenic stressors affects plant-soil systems and the role of plant diversity in this process. Plant-soil systems with different plant diversity levels (3 vs. 9 species) were subjected to an increasing number of stressors (1, 2, 5 and 8) using random assemblages of plants and stressors from a predefined plant species pool and a stressor pool. We found not only directional changes in soil properties, functions and especially plant community composition, but also the diminishment of plant diversity effects as stressor number increased. This study broadens our insights into the ecological impacts of multifactorial environmental change and highlights the necessity of exploring the relationships between the number of anthropogenic stressors and the effect of plant diversity. Overall, this dissertation contributes to two critical areas of environmental research: the effects of TWPs on soil properties and functions, and key factors that alter these effects; how multiple anthropogenic stressors affect soil properties, functions, plant community composition, and the role of plant diversity in this process. Our work has advanced the knowledge about the ecological risks of global change, including microplastics and other anthropogenic stressors, in terrestrial ecosystems.

This dissertation systematically studied two emerging terrestrial microplastic pollutants, paint microplastics (MPs) and tire wear particles (TWPs), using innovative methodological approaches and comprehensive ecological assessments. Firstly, our research revealed a remarkably high concentration of paint MPs in urban soils, reaching up to 2.9 × 10⁷ particles per kilogram. Through chemical characterization of their polymeric constituents, we confirmed that these paint particles qualify as microplastics. This result represents the highest microplastic concentration reported in soils to date and highlights a clear vertical distribution pattern, with concentrations decreasing with increasing soil depth. Subsequent ecological evaluations demonstrated that paint MPs, especially those containing heavy metals, significantly affect soil physicochemical properties, microbial activity, and nutrient cycling. Their presence was associated with elevated soil pH and an enhancement of water-stable aggregate stability. Furthermore, the results underscored the influence of different polymeric compositions on particle size distribution and soil respiration dynamics. In addition, our research showed that soil storage conditions influence the observed ecological effects of TWPs, emphasizing the need for standardized experimental protocols to ensure comparability across studies. Moreover, the ecological effects of TWPs varied with environmental context, being modulated by soil properties and land-use intensity. These findings highlight the context-dependent nature of microplastic impacts in terrestrial ecosystems. Overall, this dissertation advances the field of terrestrial microplastic research through methodological innovation, ecological risk assessment, and the analysis of environmental modulators.

This dissertation demonstrates the interplay between perceptual and economic decision-making, two fields traditionally studied in isolation. It emphasizes how various forms of uncertainty both enable and necessitate their integration in real-world contexts. The research presented sheds light on the cognitive, computational, and psychophysiological mechanisms underlying this integration, while also exploring individual differences in adaptive behaviour.

The many tectonic plates and distinct interacting units within the Alps lead to dramatic changes in geology over a relatively small area. This poses a unique scientific challenge where understanding the evolution of the Alps and the active seismotectonics is vital to inform seismic hazard models in the highly populated greater Alpine region. Despite a long tradition of study, fundamental questions about present-day geological structure, particularly in the Eastern Alps, remain unanswered. Diverse results from separate seismological studies have often led to conflicting interpretations of the Alpine structure, and thus to dissimilar models of Alpine orogeny.

To gain a deeper understanding of the Alps, the multidisciplinary AlpArray initiative was founded. The core dataset of AlpArray was gathered with the AlpArray Seismic Network, which consisted of 628 seismic stations in the wider Alpine area. This network was supplemented by several complementary deployments; among these was the SWATH-D network, which delineates the region of the Eastern Alps that is the focus of this thesis. Thus, with a total of 168 densely spaced stations straddling Austria and Italy, SWATH-D was ideally located to investigate the Eastern Alps and provides the bulk of the seismic data that we investigate. We used three distinct methods to analyse the seismic data; the autocorrelation of ambient seismic noise, migration receiver functions, and the probabilistic inversion of surface waves and P-wave tomography.

In the field of seismic interferometry, autocorrelations can be used to extract the Green's function from ambient noise data at a single station. With this autocorrelation variation of the method, we are, in principle, able to retrieve zero-offset reflections in a stratified Earth (like cross-correlations for pairs of stations). These reflections are valuable as they do not require an active seismic source and, being zero-offset, are better constrained in space than passive earthquake-based measurements. By applying a depth-velocity stacking scheme to the autocorrelations and receiver functions together, we can resolve the ambiguity between these parameters. Their application to temporary AlpArray stations showed some success in identifying reflections from the Moho (boundary between the crust and mantle) in the (structurally simpler) Alpine foreland, thereby demonstrating that the method is also applicable for temporary seismometer deployments.

By migrating receiver functions from SWATH-D stations to depth, we produced a high-resolution Moho depth map of the Eastern Alps. This was facilitated by the joint analysis of receiver function images of direct conversions and multiple reflections for both the SV (radial) and SH (transverse) components. This combination of multiples and components enabled us to map overlapping and inclined discontinuities. We observed the European Moho to be underlying the Adriatic Moho from the west up to the eastern edge of the Tauern Window. East of the Tauern Window, there is a sharp transition from underthrusting European crust to a flat and thinned crust. This thinner crust is associated with Pannonian extension tectonics and is underthrust by both European crust in the north and Adriatic crust in the south. The Adriatic lithosphere underthrusts northward below the Southern Alps and becomes steeper and deeper toward the Dinarides, where it dips towards the north-east. These observations suggest that the steep high-velocity region in the mantle below the Eastern Alps, observed in tomographic studies, is likely to be of European origin.

Probabilistic inversion with multiple geophysical observations is a natural progression from the observations that we make with receiver functions. Rather than the standard inversion for seismic velocity, we employ petrophysical constraints to directly invert for lithology and temperature within the crust in a probabilistic manner through Markov-chain Monte Carlo. The application of this method leads to a deeper understanding of the intracrustal structure, temperature, and petrophysical properties. Changes in these quantities across geological boundaries can help reconstruct tectonic history. A further significant advantage of this method is in interpretation, where the probabilities of certain lithologies being present allow for a more seamless integration of qualitative geological data and a reduction in interpretation biases compared to when only seismic velocities are presented. We show the strength of this approach by deriving the temperature, structure, and lithological probabilities for a transect of seven SWATH-D stations crossing a major tectonic fault and observe an associated change in both temperature and composition.

All three of these techniques and their application in the Alps required the simultaneous advancement and development of new seismological methods. AlpArray and its complementary seismic networks are used in conjunction with these methods to produce more complete and higher resolution images of the subsurface and to probe deeper into the properties of the crust. These advancements and associated observations contribute to answering the geological questions posed by AlpArray.

Seit Jahrhunderten reisen Muslime aus Westafrika in arabische Länder, um dort ihr Wissen über den Islam zu erweitern. Diese religiös konnotierte Bildungsreise ist unter dem Begriff ṭalab al-ʽilm bekannt. In der Arbeit wird die ṭalab al-ʽilm in ihrer historischen Entwicklung und zeitgenössischen Ausprägung am Beispiel des westafrikanischen Staates Togo seit der Unabhängigkeit 1960 betrachtet. Die Bildungsmigration erscheint dabei als eine transformative Reise, die in hohem Maße dazu beiträgt, islamische Eliten zu formen. Sie ist aber aufgrund ihrer Einbettung in zeitgenössische gesellschaftliche und politische Kontexte nie gleichförmig. Mit dem Ansatz, die Reise mit einer translokalen Perspektive zu betrachten, rücken die Akteure ins Zentrum, die reflektieren, in welcher Weise die Bildungsmigration sie selbst geprägt hat und dann wiederum in die Herkunftsgesellschaft reflektiert. Die Absolventen werden aufgrund ihrer formal erworbenen akademischen Bildungsabschlüsse wie auch aufgrund ihrer Wahrnehmung durch die Herkunftsgesellschaft, als islamische Gelehrte, ʽulamāʼ bezeichnet. Die Hauptziele der ṭalab al-ʽilm aus Togo waren lange Mekka und Medina in Saudi-Arabien und die Azhar-Universität in Ägypten. Im 20. Jahrhundert haben sich durch die Errichtung neuer Universitäten in weiteren arabischen und arabisch-afrikanischen Ländern neue Studiengelegenheiten ergeben. Die Arbeit nimmt verschiedene Generationen von Bildungsmigranten aus Togo in den Blick, die seit Anfang der 1980er Jahre aus dem arabischen Ausland zurückkehrten. In Interviews und Gesprächen reflektierten die Akteure den Verlauf ihrer Bildungsmigration, das Erleben der Gastgesellschaft und die Erfahrungen an der islamischen Bildungsinstitution, die besucht wurde. Die Bildungsmigration wird als ein translokaler Prozess betrachtet, in dem die Reisenden den Kontakt über lange Distanzen und Zeiten halten und eine transformative Auseinandersetzung mit und zwischen verschiedenen Akteuren, Institutionen und Gesellschaften passiert. Der Prozess der Rückkehr ins Heimatland und die ihn beeinflussenden Faktoren wurden mit Pierre Bourdieus Konzept von verschiedenen Formen des Kapitals analysiert. Während der Feldforschung untersuchte ich, welche Berufsfelder und Betätigungsmöglichkeiten Rückkehrern von islamisch-arabischen Universitäten im westafrikanischen Togo offenstehen. Die Rückkehrer beanspruchen Autorität in religiösen Fragen. Anhand des Prozesses der ṭalab al-ʽilm greife ich auf, welche Faktoren zur Konstitution religiöser Autorität beitragen. Rückkehrer haben seit den 1980er Jahren den islamischen Bildungssektor in Togo, wie auch in anderen westafrikanischen Ländern, ausgebaut und Reformprozesse vorangetrieben. Durch dieses Engagement entfalteten die Rückkehrer eine Wirkung darauf, wie Islam in Togo gelehrt und gelebt wird. Damit unmittelbar verknüpft ist das Ziel einer stärkeren gesellschaftlichen und politischen Teilhabe der muslimischen Community innerhalb des säkularen togolesischen Staates.

Die equine rezivierende Uveitis (ERU) gilt als eine der schwerwiegendsten Augenerkrankungen und wird als Hauptursache für Visusverlust beim Pferd beschrieben. Die Ätiologie ist bislang noch nicht vollständig geklärt. Jedoch wird die ERU, vor allem national, als Folge einer intraokularen Infektion mit Leptospira spp. angesehen. Im Rahmen der vorliegenden Arbeit wurden Proben von Pferden mit ERU sowie augengesunden Pferden einer Kontrollgruppe retrospektiv ausgewertet. Ziel dieser Arbeit war es, die Prävalenz innerhalb der Patientenpopulation der Klinik für Pferde der FU Berlin auszuwerten sowie Patienten mit Leptospiren-assoziierter Ätiologie zu identifizieren und die angewandte Diagnostik hinsichtlich ihrer Aussagekraft zu evaluieren.

Bezogen auf die Klinikpopulation wurden 1,8 % (n = 143/8086) der vorstellig gewordenen Pferde im Zeitraum von Februar 2015 bis einschließlich Dezember 2021 mit ERU diagnostiziert. 4- bis 7-jährige Pferde waren signifikant häufiger an ERU erkrankt als Pferde anderer Altersklassen. Weiterhin waren Islandpferde (n = 13/365; 3,6 %) sowie Pferde der Rassen mit möglicher homozygoten LP-Mutation („Tigerschecken“; n = 12/88; 13,6 %) signifikant überrepräsentiert. Der Anteil der deutschen Warmblutpferde mit ERU war, innerhalb der Klinikpopulation, nicht signifikant erhöht (n = 55/3644; 1,5 %). Bei 53/80 Patienten (66,3 %) mit ERU wurde mittels Berechnung des Goldmann-Witmer-Koeffizienten sowie PCR eine intraokulare Infektion mit Leptospira spp. nachgewiesen. Es gilt anzumerken, dass ein GWC ≥ 3 bei 53/80 Pferden (66,3 %) vorlag, während ein positives PCR-Ergebnis bei 16/80 Pferden (20,0 %) ermittelt wurde. Dabei wurde bei allen Pferden mit positivem PCR-Ergebnis ein GWC ≥ 3 ermittelt. Ein bei 42/80 Pferden zusätzlich durchgeführter ELISA detektierte keine intraokulare Leptospireninfektion, die nicht bereits mittels Berechnung des GWC und/oder PCR diagnostiziert wurde. Verglichen mit dem GWC, erwies sich die Berechnung des C-Values mit einer Sensitivität von 70,7 % (C ≥ 4) und 81,2 % (C ≥ 2) sowie die Bestimmung eines Antikörpertiters mittels MAT bei einem Grenzwert ≥ 1:100 (im Serum Sensitivität 70,4 %; im Kammerwasser Sensitivität 83,7 %) als nicht geeignet zur Diagnostik intraokularer Infektionen mit Leptospira spp. ERU-Patienten mit Leptospirenbeteiligung waren signifikant jünger als Pferde mit nicht-Leptospiren-assoziierter Genese. Obgleich eine intraokulare Infektion mit Leptospira spp. seltener bei Tigerschecken, verglichen mit Pferden anderer Rasse, diagnostiziert wurde, konnte in der vorliegenden Studie kein signifikanter Zusammenhang zwischen einer intraokularer Leptospireninfektion sowie Rasse und Geschlecht der an ERU erkrankten Patienten verzeichnet werden. Im Rahmen dieser Studie wurden Kammerwasser- und Serumproben von Pferden mit ERU als auch augengesunden Pferden biochemisch auf Harnstoff-, Totalprotein-, Albumin- und Bilirubingehalt untersucht und die Ergebnisse der verschiedenen Gruppen miteinander verglichen. Dabei wurde für Pferde mit ERU ein signifikant höherer Harnstoff-, Protein- sowie Albumingehalt im Kammerwasser ermittelt, verglichen mit den Pferden der Kontrollgruppe (p = 0,04; p < 0,001; p < 0,001). Sowohl der Protein- als auch Albumingehalt waren bei Pferden mit Leptospiren-assoziierter Genese signifikant höher gegenüber den entsprechenden Werten derer mit nicht Leptospiren-assoziierter ERU. Wenngleich zwischen Patienten- und Kontrollgruppe kein signifikanter Unterschied hinsichtlich des Bilirubingehaltes nachgewiesen wurde, so war dieser bei Pferden mit Leptospiren-assoziierter ERU, verglichen mit jenen Patienten mit nicht Leptospiren-assoziierter ERU, signifikant erhöht (p = 0,04). Der Vergleich der Serumproben erbrachte für keinen der analysierten Parameter einen signifikanten Unterschied zwischen den jeweiligen Gruppen. Weiterhin wurden Kammerwasserproben von Pferden mit ERU und augengesunden Pferden der Kontrollgruppe refraktometrisch untersucht. Dabei wurde eine signifikante Erhöhung des spezifischen Gewichts (p < 0,001), des Brechungsindex (p < 0,001) sowie des Proteingehaltes (p = 0,001) bei Patienten mit ERU verglichen mit den Pferden der Kontrollgruppe ermittelt. Der Vergleich innerhalb der Gruppe der Pferde mit ERU, unterteilt in Pferde mit Leptospirenassoziierter ERU und ERU anderer Genese, erbrachte hingegen keine signifikanten Unterschiede. Insgesamt verdeutlichen die marginalen Unterschiede bei der Refraktion des Kammerwassers zwischen Pferdeaugen mit Leptospiren-assoziierter ERU und nicht Leptospiren-assoziierter ERU die Komplexität der Diagnosestellung und die Notwendigkeit einer umfassenden Betrachtung verschiedener diagnostischer Parameter in der Veterinärmedizin. Die Erkenntnis, dass sowohl die biochemische Analyse als auch die Refraktometrie des Kammerwassers möglicherweise nicht ausreichen, um eine präzise Diagnose der Leptospiren-assoziierten ERU bei Pferden zu stellen, hat direkte Auswirkungen auf die klinische Praxis. Es erfordert weitere Forschung, um andere diagnostische Parameter zu identifizieren oder zu entwickeln, die spezifischer auf die Ätiologie dieser Augenerkrankung hinweisen.

Basierend auf den Ergebnissen der vorliegenden Arbeit, ist, neben einer vollständigen Anamnese und klinischen Untersuchung zur Diagnosestellung einer ERU nach den Leitlinien des ACVO/ECVO, die Labordiagnostik zur Ermittlung des GWC zu empfehlen. Bei einem GWC < 3 ist, in Abhängigkeit des Signalements des betroffenen Patienten, weitere Diagnostik (z.B. Glaskörperdiagnostik, sowie PCR, ELISA, Betrachtung der vorkommenden Immunglobulinisotypen) einzuleiten.

1. Systematisation of the existing data (catalogue of the archaeological sites and findings) Comprehensive data from Georgia is available and includes published, as well as unpublished, sites. For findings from Azerbaijan, Armenia and Turkey existing publications have been used.

2. Classification of the archaeological sites Trialeti Culture is represented by two kinds of archaeological sites: graves and settlements. Graves are divided in two groups: burial mound graves and flat graves. Burial mound graves are divided into five types according to their characteristics. The following questions have been raised: “Which burial type is related to which topographical environment?”, and “Is there any link between burial type and grave goods?” Study has shown that there is a connection between topography and burial type. Burial mounds with below ground burial chambers are observed only on the high mountain plateau’s of Trialeti and Zurtaketi. Burial mounds with above ground burial chambers are found in similar locations. It is presumed that both burial types are associated with the privileged society of Trialeti culture. Significant archaeological findings are related with these grave types; amongst them various precious metal artifacts. On the contrary, burial mounds with pits can be found in all regions; in river valleys, at low level elevations, as well as on high mountain plateau‘s. Catacomb burials and flat graves are usually present at lower elevations - typically below 1050 m. However, there are exceptions in Armenia. Burial mounds with stone constructed burial chambers are mainly observed on high mountain plateaus.

3. Classification of archaeological findings Archaeological findings are classified according to the material they are made of. They are then divided by kinds, types and versions. Kinds of clay vessels differ from each other by proportion index (height correlation to rim diameter). The following question has been raised: “Which archaeological findings are related to which grave type?” Data obtained from burial mounds with below ground burial chambers is incomplete, as grave goods have frequently been robbed out during past times. To a lesser extent, the same situation exists for burial mounds with above ground burial chambers. But, for the latter more data is available as famous artifacts of Trialeti culture have been found in these graves. Comparatively speaking, more information is available for burial mounds with burial pits. Most recovered ceramics are large in size (pitchers, jars). Smaller size pottery, such as plates and cups, are relatively less in quantity. The majority of metal weapons originate from these burials. In contrast, catacomb burials contain mostly small size pottery, rather than pitchers and large jars. These graves also contain a small number of metal and stone artefacts. In burial mounds with below ground stone burial chambers, pitchers are found in large numbers, followed by bowls and plates and small numbers of jars and cups. In flat graves, the majority of recovered artifacts comprise of pitchers, followed by almost similar quantities of bowls, plates, jars and cups. According to the above observations, it can be deduced that each specific grave type has its own distinct range of grave goods.

4. Regional division Observations have been made on all burial types as well as on the territorial distribution of recovered archaeological findings. Some regional differences have been observed but, according to available data, there is insufficient evidence to clearly distinguish them as a local version of the Trialeti Culture. On the fringes of the Trialeti Culture (East, North-East and South) foreign influence is noticeable due to contact with neighboring cultures.

5. Chronology a) Seriation. Computer seriation was used to study data from fourteen burial mounds in the Trialeti region. Two different chronological groups were determined. Other monuments of Trialeti culture can be compared and reviewed simultaneously with these two groups. b) Comparative chronology. Based on the results of seriation, information from other regions and new C14 dates, it can be concluded that: in Trialeti Culture two different chronological groups are determined. In addition, there are fifteen burial mounds (according to E. Gogadze - I Group) with a very small quantity of grave goods. In the scientific literature, this group of burials is thought to be older, but according to the available evidence it is difficult to conclusively prove this. C14 dates are not available for these burials and archaeological findings are small in quantity. Seriation shows that this group of burials is placed at the end of the seriation table, thus demonstrating that they are older. However, there is insufficient evidence to separate this group. Fourth stage of the Middle Bronze Age is also discussed. The majority of burials from this group should be the same age as the late burial mounds of Trialeti. In our work we have tried to determine characteristic features for both chronological groups and based on these divide the monuments of Trialeti culture into two groups;- Burial mounds of Trialeti number IX, VIII, V, VI, XVII, XVIII, XVI, XXIX and Tetri Kvebi 1, 3, Mravaltskali 12, Gokhebi, Lilo 1, Artashavan 5, Karashamb belong to an early group. Burial mounds of Trialeti XV, I, VII, Akhchia 1, 3, Dalis Mta 12, Kirovakan, Lori Berd 77 and flat graves of Samtavro and Kvasatala cemeteries belong to a later group.

c) Absolute Chronology C14 analysis was performed on six animal bones originating from sites of Trialeti Culture. Four bones correspond to an early group of seriation and its absolute ate is 2134 – 1910 BC. Two bones correspond with youth group of seriation 1878 – 1695 BC.

6. Inter-regional connection Aegean. In Trialetti Culture there are several artefacts which have analogous in the Bronze Age Aegean region. But the same analogies are also present in other regions. Despite this, Trialeti and Aegean artefacts are different from a chronological point of view. Based on this, it is unlikely that a direct link between these two regions at the end of 3rd millennium and beginning of 2nd millennium BC can be established. Most probably, contact between these two regions could have been instigated through a third region. a) Mesopotamia. There is an argument to suggest contact between Trialeti culture and Southern Mesopotamia, but here too, it is difficult to confirm the exact origin of the imported artefacts. Presumably, there were cultural influences. Beginning of Trialeti culture chronologically corresponds with the 3rd Dynasty of Ur (2112 – 2004 BC). During this period, Mesopotamia was involved in intense trade contact with the near east. It is reasonable to assume that contact had also been established with the south Caucasus. b) Other regions. Questions regarding whether the south Caucasus was connected to Karum Kanesh trade system at the beginning of 2nd millennium BC, cannot be answered at this stage, due to insufficient evidence

Fluorinated compounds are ubiquitous in modern society and effective strategies for their synthesis are needed on both laboratory and industrial scales. Electrochemical fluorination on nickel anode immersed in anhydrous HF (Simons process) was first reported in the middle of the last century and has been applied ever since on an industrial scale. Despite that, its mechanism is not yet fully understood. This thesis explores the structure and reactivity of nickel fluorides in the context of the Simons process by first-principles calculations. It is divided into two main parts; part A deals with the unknown structures of nickel fluorides formed on the nickel anode in the Simons process and part B delves into the reactivity and the fluorination process itself. All the investigations were done by means of periodic density functional theory (DFT). \\ In part A two of the experimentally synthesised binary nickel fluorides with unknown crystal structures were investigated, NiF4 and Ni2F5. Both of them were proposed to be involved in the Simons process. Furthermore, a previously not calculated mixed valent Ni(II)Ni(IV) polymorph of NiF3 was calculated. In collaboration with the experimental in situ XANES study of the nickel anode subjected to Simons-type conditions, the first direct proof of higher-valent nickel centres on the anode was reported. \\ From a previous first-principles study of NiF2 and its surfaces, a suitable surface, the twice oxidised NiF2 (001) surface, was identified to study fluorination reactions in part B. This surface is stabilised by the external potential applied in the Simons process and features nickel in higher oxidation state together with an [F2]^- unit readily available to aid fluorination. Three of the smallest carbon-containing molecules were chosen to model the fluorination. Methane as the smallest hydrocarbon, carbon monoxide as the smallest molecule containing a carbon oxygen bond, and ethene as the smallest hydrocarbon containing a carbon double bond. The adsorption of these three molecules on the surface was modelled together with the co-adsorption of one HF molecule for CH4 and one or two HF molecules for CO. The results were able to reproduce most of the experimentally observed products. These are the first theoretical studies of fluorination in the Simons process and pave the way for further investigations aimed at understanding electrochemical fluorination on the nickel anode.

Obstetrics has been plagued by challenges in clinical care, not only historically, but also up to this day. With a combined approach, using technology as a tool, a holistic approach to problem solving, adopting concepts from other fields of science and, along with new educational training concepts for medical professionals, we can meet some of the challenges of classic obstetric problems with new innovative thinking and solutions. By focusing on developing synergistic strategies throughout the antenatal, intrapartum, and postpartum periods of pregnancy, targeting specific perinatal pathologies and complications, we can improve maternal and neonatal outcomes. With this concept in mind and by aiming solutions to specific patient populations and obstetric scenarios, a reduction in the incidence of complications can be realized in the short and long term. Specific targets include the following; (i) improving the management of twin pregnancies with the leading twin in breech position through the use of external cephalic version (ECV) and with the new concept of stimulating fetal primitive reflexes under sonographic control, (ii) identifying the uterine anomalies that are present in breech pregnancies at term which would benefit from delivery planning and follow up care in the short and long term, (iii) using ultrasound intrapartum to improve the safety of rotational deliveries in the second stage of labor thereby avoiding late secondary cesarean section (CS) and improving maternal outcomes, (iv) applying the mathematical concept of vector forces to facilitate improved umbilical cord traction by retained placenta delivery and thereby reducing postpartum bleeding risk and complications leading to invasive surgical measures, and finally (v) the use of high-fidelity simulation training to improve the recognition of common mistakes made by health care professionals in the management of postpartum hemorrhage so that the risk of complications and maternal mortality is reduced. There is no other time in life when a woman or a baby is at greater risk of death or significant morbidity than at and around the time of birth. Since the beginning of recorded history, this has been documented and despite the advances in care and interventions to improve outcomes, it continues, even though to a certain extent reduced, to remain a continuous challenge.

Epithelien bilden die Grenzschicht unseres Körpers und schützen die inneren Organe. Sie fungieren als physikalische Barrieren, die durch die Proteine der Tight Junction (TJ) zusammengehalten werden. Das gastrointestinale Epithel adulter Säugetiere erhält die Integrität der Darmmukosa durch eine hohe Zellumsatzrate. Eine dynamische Regulation der Barrierefunktion führt zu unterschiedlichen Transport- und Barriereeigenschaften, welche u.a. Schutz vor mechanischen Schäden und pathogenen Mikroorganismen bieten. Eine Störung der epithelialen Darmbarriere kann molekular durch Veränderungen der TJ-Proteine, wie Claudine analysiert und klinisch an Symptomen wie Diarrhö erkannt werden. Der anaerobe Sporenbildner Clostridioides difficile (C. difficile) ist der häufigste Auslöser von Antibiotika- assoziierten und nosokomialen Durchfallerkrankungen (C. difficile Infektion, CDI). Die Symptome der CDI sind vielfältig und schwere Verläufe werden durch hypervirulente Stämme begünstigt. Die akute Phase von CDI hängt von toxinogenen Proteinen ab, die von C. difficile produziert werden. Als Hauptvirulenzfaktoren gelten die Rho-glykosylierenden C. difficile Toxine A (TcdA) und B (TcdB), bei denen es sich um große Toxine handelt, die eindeutig mit Diarrhö und Kolitis in Verbindung gebracht werden. Es fehlen jedoch noch funktionelle Studien zur Störung der intestinalen epithelialen Barrierefunktion durch die Clostridientoxine, sowie eine molekulare Charakterisierung der Zusammensetzung der TJ-Proteine in Darmzellmodellen von CDI-Patienten. In der vorliegenden Arbeit wurde deshalb der Einfluss von TcdA und TcdB auf TJ-Proteine und die daraus resultierende Störung der Darmbarriere mit Hilfe eines neu etablierten Kolonorganoid-Monolayermodells (organoid-derived monolayer, ODM) untersucht, um den Pathomechanismus von C. difficile näher zu beleuchten und patientenorientiert Therapien zu entwickeln. Beide Toxine lösen in sublethalen Konzentrationen eine Barriereschädigung in unserem neuartigen Modell aus, indem der TER in den ODMs reduziert und die parazelluläre Permeabilität von 332 Da Fluorescein und 4 kDa Fluorescein-Isothiocyanat-Dextran erhöht wurde. Zusätzlich wurde die Expression und Lokalisation von TJ-Proteinen durch die Toxinexposition beeinflusst, wodurch sowohl der pore pathway als auch die parazelluläre Leckage beeinflusst wurden. Diese Expressions- und Lokalisationsänderung der TJ-Proteine wurde mittels Western Blot-Analyse quantifiziert und mit konfokaler Laser-Scanning Mikroskopie visualisiert. Des Weiteren wurde die beobachtete Barrierestörung über die TJ vermittelt, da alle eingesetzten Toxinkonzentrationen keinen Zelltod durch Nekrose auslösen. Als letzten entscheidenden Mechanismus im Hinblick auf die Clostridientoxin-induzierte Störung der Barrierefunktion konnte eine aus der Toxin-Interaktion resultierende Zusammenfassung VIII Immunantwort des Epithels gezeigt werden, die wiederum die epitheliale Barriere schwächen kann und somit den Teufelskreis des Leaky Gut-Phänomens mit weiterem Antigeneinstrom hervorrufen kann. Die Zytokinfreisetzung aus den Epithelzellen wurde mittels einer Durchflusszytometrie-Analyse gemessen. RNA-Sequenzierungsdaten der mit Toxin behandelten Kolonepithelzellen der HT-29/B6-Zelllinie, die mit der Ingenuity Pathway Analysis (IPA)-Software analysiert wurden, bestätigten Barriere-relevante Zytokine als aktivierte Upstream Regulatoren, welche auch eine zentrale Rolle in der Progression von CDI spielen (Gene, die auch in CDI-Patienten hochreguliert sind). Mit diesem neuartigen Organoidmodell war es möglich definierte Wirkungen von TcdA und TcdB auf die TJ-Proteine aufzuzeigen. In zukünftigen Studien kann dieses Modell auch verwendet werden, um ein Co-Kultur-Modell mit Immunzellen zu etablieren, sodass zum einen mögliche immunologische Aspekte des Leaky Gut-Konzepts für die Chronifizierung der Kolitis charakterisiert werden. Zum anderen können Barriere-fördernde Substanzen zur patientenorientierten Therapie bei CDI gescreent und identifiziert werden.

Entzündlich-rheumatische Gelenkerkrankungen stellen hohe Anforderungen an die bildgebende Diagnostik, da sie sowohl akute Entzündungsprozesse als auch chronisch-strukturelle Veränderungen erfassen müssen. Die multiparametrische Dual-Energy CT bietet hierbei neue Möglichkeiten, entzündliche Aktivität, Gewebecharakteristika und biomechanische Veränderungen in einem Untersuchungsgang zu erfassen. Im Rahmen dieser Habilitationsschrift wird die Einsatzfähigkeit der multiparametrischen Dual-Energy CT und deren Beitrag zur differenzierten Arthritisdiagnostik untersucht. Mehrere Studien vergleichen kontrastmittelgestützte Dual-Energy CT-Techniken (CT-Subtraktion, Iodine Maps) mit MRT und Ultraschall als Referenzstandard. Dabei zeigt sich eine hohe diagnostische Genauigkeit bei der Detektion von Synovialitis und Tenosynovialitis, wobei die CT-Subtraktion am besten mit dem Ultraschall korreliert. Virtuell monochromatische Subtraktionen zeigen keinen zusätzlichen Vorteil. Ergänzend wird das Potenzial suszeptibilitätsgewichteter MRT-Sequenzen (SWI) zur Erosionsdetektion sowie der Einsatz der 4D-CT zur Analyse dynamischer Handgelenkspathologien evaluiert. Darüber hinaus werden die Möglichkeiten der Dual-Energy CT zur nichtinvasiven Quantifizierung der Kollagendichte in Bändern sowie der Einfluss iodhaltiger Kontrastmittel auf die Harnsäuredetektion untersucht. Die Ergebnisse dieser Habilitationsschrift leisten einen wesentlichen Beitrag zur Etablierung der multiparametrischen Dual-Energy CT in der Arthritisdiagnostik. Als präzise und vielseitige Weiterentwicklung der CT-Bildgebung ermöglicht sie bei Patient:innen mit entzündlich-rheumatischen Gelenkerkrankungen eine differenzierte Beurteilung entzündlicher und struktureller Veränderungen. Fortschritte in der Strahlenreduktion fördern zudem eine zunehmend breitere Anwendung in der klinischen Praxis.

This PhD thesis investigates Hodge structures on a particular class of complex algebraic varieties known as character varieties. Our objective is to integrate a powerful result stemming from motivic integration and the proofs of the Weil conjectures, with classical representation-theoretic point-counting techniques. In this work, we develop a hybrid approach combining arithmetic and geometric methods to compute the Deligne-Hodge polynomials of SL2 (C)- character varieties associated with the fundamental group of a circle bundle - referred to as a Seifert group - over an orbifold with a single ramified point. Additionally, using an orbifold version of the non-abelian Hodge correspondence, we derive certain topological properties of the moduli space of trace-free Higgs bundles, with fixed determinant, over the same base orbifold.

Histone deacetylase 7 (HDAC7), a member of the class IIa HDAC, is the predominant HDAC expressed in CD8+ T cells. Loss of Hdac7 impairs CD8+ T cells survival and functionality, leading to heightened apoptosis, increased exhaustion, and impaired anti-tumor activity both in vitro and in vivo. However, the molecular mechanisms underlying these phenotypic alterations in Hdac7ko CD8+ T cells have not been fully elucidated.

In this study, we demonstrated that HDAC7 undergoes activation-induced nuclear export in CD8+ T cells, suggesting a dynamic regulatory mechanism in response to stimulation. We further identified the extrinsic apoptotic pathway as a primary contributor to the increased cell death observed in Hdac7ko CD8+ T cells. Mitochondrial dysfunction, evidenced by altered mitochondrial membrane potential, was also detected. Transcriptional profiling using bulk RNA-sequencing, validated by RT-qPCR, revealed differential expression of genes associated with cellular metabolism, including components of the mTOR and c-Myc signaling pathways, as well as several amino acid transporters such as Slc1a4, Slc1a5, Slc7a1, Slc7a5. The upregulation of glutamine transporters in Hdac7ko CD8+ T cells was accompanied by enhanced glutamine uptake, suggesting a shift in metabolic programming. Additionally, transcriptional analysis indicated a tendency for Hdac7ko CD8+ T cells to adopt a terminally exhausted phenotype, a state typically associated with reduced responsiveness to immune checkpoint blockade therapies.

Collectively, these findings identify Hdac7 as a critical regulator of CD8+ T cell fate and metabolic fitness, shaping their capacity for anti-tumor responses. This work advances our understanding of Hdac7’s role in adaptive immunity, underscores potential adverse consequences of non-selective HDAC inhibition, and highlights the need for developing HDAC inhibitors with greater target specificity as therapeutic agents.

The quantum Hall effect is a fundamental phenomenon in condensed matter physics, characterized by a quantized Hall resistance and zero longitudinal resistance in two-dimensional conductors under a high perpendicular magnetic field. This effect is important for both metrology and fundamental physics, while its microscopic nature is still a subject of controversial discussions.

The textbook explanation of the quantum Hall effect is the Landauer-Büttiker picture, which explains it assuming scattering-free current in compressible one-dimensional edge channels and an insulating bulk state. The screening theory, which accounts for the Coulomb interaction between the charge carriers, challenges this model and predicts that the current flows inside incompressible strips. While the incompressible strips are narrow edge channels near the low magnetic field side of a quantized Hall plateau, they widen as the magnetic field is increased and cover the bulk region of the Hall bar near the high magnetic field end of the plateau. Scanning probe experiments, which measure the Hall potential distribution, support the screening theory and conflict with the Landauer-Büttiker picture.

In this thesis, using a Hall bar with an additional contact in its center, we show direct experimental evidence for scattering-free bulk transport, in agreement with the screening theory. Simultaneously, multiterminal current measurements and model calculations reveal that the current flow is chiral for the quantized Hall resistance plateaus. In contrast, between plateaus, our measurements agree with the Drude model, which predicts a homogeneous current density distribution given a uniform mobility and carrier density. Furthermore, experiments on a sample featuring two overlapping metallic gates demonstrate the possibility of tuning quantized Hall plateaus by adjusting the confinement potential of the two-dimensional electron system in the Hall bar.

Our findings not only demonstrate the importance of Coulomb interactions between charge carriers for the quantum Hall effect but also deepen our understanding of the nature of the current distribution in the quantized Hall regime while opening new possibilities for controlling and manipulating quantized Hall states.