Autonomous Driving (AD) has advanced significantly in recent years, yet widespread deployment remains limited. One of the most enduring challenges in Autonomous Vehicle (AV) development is planning a safe, comfortable, and efficient motion in complex, real-world environments. This thesis addresses motion planning across three distinct domains: urban shuttles, passenger vehicles, and truck-trailer systems. It contributes practical insights and novel approaches toward scalable autonomous mobility. The first part of this work presents an integrated motion planning framework for the Continental Urban Mobility Experience (CUbE) driverless shuttle. Extensive real-world testing over several years highlights the system’s robustness and underscores the importance of long-term validation in urban settings. Key innovations include a multi-layered planning stack and a data-driven motion forecasting approach that enhances interaction with human traffic participants. The second part investigates the behavior of human drivers in understructured traffic environments. Those are areas that fall between well-defined road systems and fully unstructured spaces. A novel analysis framework is introduced for mining patterns from naturalistic trajectory datasets, enabling AVs to better blend into human traffic and navigate ambiguous scenarios with improved predictability and safety. The final part of the thesis explores Deep Reinforcement Learning (DRL) for planning and controlling complex truck-trailer maneuvers. A DRL-based approach is developed and evaluated in simulated environments, demonstrating the method’s potential to handle the nonlinear dynamics of articulated vehicles. These contributions advance the field of motion planning by combining theoretical insights, system-level integration, and empirical evaluation. They offer pathways for improving AV behavior across diverse platforms and use cases, ultimately supporting the broader adoption of AD technologies.

Transform coding methods play a fundamental role in image and video coding technologies like the Versatile Video Coding (VVC) standard. Typically, the employed transforms are linear maps with strong energy compaction capabilities. Therefore, efficient quantization and entropy coding methods can be designed for transmitting and storing the transform coefficients. In recent years, there have been considerable efforts to design coding-efficient transforms from learning-based methods. As for video compression, additional bitrate savings are achieved by optimizing linear block transforms with respect to the different intra prediction modes. In contrast, end-to-end optimized image codecs have been obtained from deep-learning experiments. Learned codecs like the JPEG AI coding standard rely on using non-linear, neural networks as forward and inverse transform. Remarkably, JPEG AI is reported to have superior compression efficiency relative to conventional still image coding. Since the transforms in learned image compression are non-linear, it is not clear if rate-distortion optimization methods designed for linear blocks transforms are well-suited. Thus, this thesis studies the impact of different signal-dependent encoder optimizations on the quantization when a learned image codec is used. As a main result, an algorithm for rate-distortion optimized scalar quantization is developed which achieves bitrate savings between 1 % and 7 %. Furthermore, it has been shown that a rate-constrained vector quantizer improves the coding efficiency on a similar scale. Its design has similarities with the trellis-coded quantization stage in VVC. Thus, since rate-constrained quantization is shown to be effective when applied to non-linear transforms, different non-linear transform coding tools for block-based video compression are developed. These tools employ neural networks which are obtained from a data-driven optimization. The first tool, a non-linear coefficient prediction, uses reconstructed coefficients and the reference samples from the block boundary for predicting low-frequency coefficients. Therefore, only the difference between the predicted value and the original coefficient is quantized and coded. The second tool, a non-linear transform offset, is applied after reconstructing all coefficients and also depends on the reference samples as input. The offset is added before the synthesis transform and has been trained to improve the reconstruction quality. A combination of both methods yields coding gains between 1.0 % and 2.8 % over VVC in All-Intra configuration. Finally, non-linear transforms and intra modes are obtained from an end-to-end training method. The learned transforms do not depend on the reference samples. The training goal is to minimize the expected rate-distortion cost by using an approximation of the transform coefficients’ bitrate. The average All-intra bitrate savings of the learned transforms and intra modes are 0.9 % against VVC.

This dissertation examines Luri oral traditions in Kohgiluyeh and Boyer-Ahmad, focusing on role in shaping historical memory and identity through narratives of Alexander the Great. Using a comparative and interdisciplinary approach, it traces the evolution of Alexander’s legend across Greek, Byzantine, Syriac, and Persian sources, demonstrating that oral traditions are not passive reflections of history but active historiographical forces that preserve, reinterpret, and resist dominant narratives. By analyzing onomastics (naming practices), toponyms (place names), and gendered representations, the study examines how Luri oral traditions function as sites of cultural resistance, challenging Persian nationalist historiography. It explores how Reżā Šāh’s policies marginalized regional oral traditions, promoting the Šāhnāme while sidelining Niẓāmī’s Iskandarnāme, yet Lur oral performers continued to preserve alternative narratives, maintaining distinct historical perspectives. Through ethnographic fieldwork and an analysis of oral storytelling techniques, the study categorizes Luri oral narratives into Mas̩al (proverbs), Muqawwm (chants), Tims̩āl (literary adaptations and genealogies), Matīl (fables), and Iʿtiqāt (beliefs), demonstrating how these traditions actively shape and transmit historical meaning. The findings underscore the urgency of preserving regional oral traditions, as their erosion threatens to erase alternative historiographies and counter-histories essential to understanding Iran’s diverse historical landscape. This study contributes to oral history, historiography, and cultural memory studies, offering insights into how oral traditions function as mechanisms of historical negotiation, cultural resistance, and identity formation beyond Iran.

The Paradoxes of Intimacy explores the formal and narrative possibilities and limitations of writing about intimate human relationships in the second decade of the twenty-first century. In an age marked by globalization, growing social and environmental insecurities, and intensification of capitalist markets (Jeffrey Nealon), the ways we bond with each other have come under increasing scrutiny in scientific research -not least for its links to problems of alienation, solipsism, and social disintegration. Recent sociological research on intimacy has attested to a crisis in the subject describing contemporary forms of close relationships as dramatically cooling (Eva Illouz), unbinding (Zygmunt Baumann), and even eroding (Byung- Chul Han). Meanwhile, the emergence of new forms of intimate bonding, such as same-sex relationships, the #Metoo social movement’s public exposure of private harm, the rise of emotion-aware technologies, and the sentimentalization of capitalist markets have radically transformed the ways intimacies are created and experienced both in actual life and in artful practices. While the subject has been extensively studied in sociological and philosophical disciplines, it is still underexplored in literary scholarship, where intimacy is often used interchangeably with love to refer to either romantic or erotic relationships. Performing a cross-generic analysis of Rachel Cusk’s The Outline Trilogy, Margaret Atwood’s The Heart Goes Last, and Marilynne Robinson’s Lila, The Paradoxes of Intimacy argues that contemporary women’s fiction reimagines the aesthetics of intimacy by moving beyond the exhausted structures of romantic and confessional narratives. Investigating the emergent forms of literary intimacies as they are problematized and re-invented in postmillennial women’s fiction, it critically addresses the question of how literature navigates the liminal spaces of (textual and narrative) encounters and temporalities (of imagined futures and old forms) to dismantle the fictional representation of intimacy as a private matter. While literary intimacies are traditionally predicated on an individualized point of view in which the interiority of the narrator or a character is rendered through introspection, contemporary women’s fiction uses interior monologues and indirect style not to deliver psychological depth, but to reveal the sociality, artificiality, and paradoxicality of connection. In tracing these formal and thematic transformations, the dissertation contends that contemporary women’s fiction does not seek to restore intimacy or propose new modes of authentic bonding. Rather, it reflects and aestheticizes the pervasive disconnection that defines the postmillennial world. Cusk’s autofictional narratives turn intimacy into a performative repetition of stories that reveal the emptiness of self-disclosure; Atwood’s dystopian satire renders love as an apparatus of emotional and economic control; and Robinson’s Lila gestures toward a fragile fleeting alternative that neither resolves nor escapes this crisis. In this sense, The Paradoxes of Intimacy argues that intimacy in contemporary fiction becomes not a site of resolution, but a literary form of crisis and paradox -a mode that exposes the limits of relation, the failure of reciprocity, and the persistent yearning for connection in an age increasingly hostile to the intimate.

Chimeric Antigen Receptor (CAR-) T cell therapy represents one of the newest, most promising treatments for cancer. Here, the patient’s own T lymphocytes are genetically modified with a cancer-specific CAR. CAR T cell therapy has shown significant clinical success, especially for the treatment of hematologic cancers by targeting the B cell antigen CD19. Nevertheless, selective pressure on the cancer cells frequently causes suppression or complete loss of the target antigen, leading to cancer relapse with fewer treatment options. This phenomenon, known as antigen escape, renders CAR-T cells ineffective representing a major clinical challenge. Consequently, there is an urgent need for targets that are less prone to antigen escape. In this thesis, a novel type of CAR-T cells is described, employing cysteine-engineered receptors that interact with altered extracellular redox states of B cell non-Hodgkin lymphoma (B-NHL). First, the redox-reactive nanobody CB2 was used for the generation of CB2-CAR-T cells, interacting directly with B-NHL redox states via a non-canonical cysteine in the complementarity-determining region (CDR) 3. The activation and specific cytotoxicity of CB2-CAR-T cells were verified in vitro against different subtypes of B-NHL, including antigen escape models. Next, the universality of the approach was confirmed by cysteine-engineering of a non-cancer-related nanobody-CAR. A single amino acid substitution with cysteine was sufficient to redirect these CAR-T cells to specifically target B-NHL, rendering cysteine-engineered CAR-T cells (or CysCAR-T cells) a universal strategy to enable antigen-independent targeting. Additionally, it was shown that cysteine engineering of state-of-the-art CD19-CAR-T cells enables co-targeting of both CD19-positive and -negative B-NHL. No systemic toxicity associated with these bifunctional CysCD19-CAR-T cells was observed in mice. Furthermore, T cells expressing the cysteine-engineered CAR delayed tumor growth and prolonged survival of mice engrafted with CD19-positive and -negative lymphoma. These findings introduce a novel type of bifunctional CAR-T cells that simultaneously target conventional antigens and altered redox states, potentially reducing the risk of antigen escape. It was shown that those CysCAR-T cells act through an antigen-independent mechanism and that cysteine engineering can be applied to CARs of diverse specificities. Altered redox states have been described for various cancers, including breast cancer and leukemia. Hence, these results indicate a broad therapeutic scope for CysCAR-T cells in preventing antigen escape associated with conventional targets.

Current treatment options for Clostridioides difficile infections of the gut are limited by reliance on antibiotics, resulting in high recurrence and mortality. Since the secreted toxin TcdB is the source of pathogenesis, a more effective treatment route may target TcdB directly. Allosteric control of the cysteine protease domain (CPD) of TcdB offers a promising intervention point for deactivating the toxin. Here, we apply computational methods to uncover the allosteric mechanism of TcdB CPD and thereby advance the larger rational drug design project. Free energy calculations feature prominently in our toolkit. We use umbrella sampling to sample the large conformational transition of TcdB CPD and reproduce the allosteric effect on free energy surfaces. We also use free energy perturbation calculations to distinguish binding affinities among highly complex protonation states of the allosteric modulator phytate (IP6). Based on these and other computations, we construct a detailed allosteric mechanism of in the form of a switchable interaction network. This mechanism is thoroughly validated by both computations and experiments. We additionally contribute to the characterization of IP6 analogues with thiophosphate substitutions in the form of docking studies. Finally, we uncover the structural origins of the net loss of one proton on IP6–TcdB CPD complexation. Together, this computational treatment provides detailed structural and mechanistic insight on an important ligand-protein system.

Sensory processing and sleep are essential behaviors critical for survival from animal models to humans. The presynaptic active zone (AZ) plays a central role in both processes, yet how molecular diversity at the AZ contributes to functional variability and behavioral specificity remains unclear. In the Drosophila brain, distinct nanoscopic coupling distances between Ca²⁺ channels and the priming factors Unc13A and Unc13B underlie diverse modes of short-term plasticity (STP), which are essential for sensory decoding. Unc13A drives fast phasic transmission, while Unc13B mediates adaptive dynamics such as sensory prediction error coding. However, how this balance is maintained—and spatially controlled—at individual synapses had remained unresolved. Our recent study identified a previously unrecognized AZ protein, Blobby, encoded by the Drosophila gene CG42795. Blobby is a BRP-interacting factor homologous to human TBC1D30, a large Rab GTPase-activating protein (Rab-GAP). At the developing third-instar larval neuromuscular junction (NMJ), Blobby localizes adjacent to BRP scaffold and arrives at the newly forming AZ later than BRP. Loss of Blobby in blobbyNull mutant leads to ectopic accumulation of large BRP aggregates and a reduction in evoked synaptic transmission, which is likely due to a decrease in both release probability and number of release sites.Here, in my thesis, by combining biochemistry, genetics, diverse behavioral approaches, living imaging and super resolution microscopy, I provide a comprehensive characterization of Blobby in regulating nanoscopic localization of BRP and Unc13 proteins in the adult brain, and in its critical function in odor sensation and sleep regulation. The blobbyNull mutant is surprisingly homozygous adult-viable with severely reduced Mendelian ratio and the adult flies appeared healthy at young age. However, they suffered from a strong decrease of lifespan and hypersensitivity to oxidative stress. Furthermore, the blobbyNull mutant flies exhibit a marked loss of olfactory-driven behaviors in response to both appetitive and aversive odors. By mapping through the Drosophila olfactory circuit through a targeted knockout strategy, I show that Blobby is required in the excitatory projection neurons (PN) and the mushroom body (MB) Kenyon cells (KC), but not in the olfactory receptor neurons. Importantly, at the presynapse of PN in Calyx, loss of blobby either only in PN or throughout the whole brain causes nanoscopic redistribution of Unc13B toward AZ center and increases its overall levels, without affecting the localization of the tight-coupling Unc13A. Two-photon calciumimaging at PN::KC synapses reveal that PN-specific blobby knockout resulted in a drastic reduction in odor-evoked postsynaptic calcium response. Strikingly, knocking down Unc13B in PN was sufficient to rescue the olfactory sensitivity to both blobbyNull mutant and PN-specific blobby knockout flies. These data suggest Blobby is a bona fide regulator for sensory processing, most likely through the fine-tuning of synaptic transmission in the olfactory circuit via a redistribution of Unc13B. As sleep and sensory processing are closely coupled, I further show that loss of Blobby had very limited effects on the sleep patterns. In contrast, Unc13B mutant flies exhibited a strong increase in both daytime and nighttime sleep, with shorter sleep latency and more consolidated sleep. Remarkably, the sleep phenotypes of Unc13B mutant flies were fully rescued by loss of Blobby, indicating that the interaction between Blobby and Unc13B extends from the coding of sensory information to the maintenance of sleep. In conclusion, Blobby is an essential AZ protein in tuning synaptic transmission via nanoscopic localization and balancing of Unc13 isoforms. The interactive regulatory relationship between Blobby and Unc13B in sleep and odor sensation highlights the role of synapse and synaptic plasticity in gating, filtering and integrating behavioral relevant information. By identifying novel regulators such as Blobby in regulating core AZ scaffolds and release factors, we will provide better molecular understandings in bridging nanometer-scale vesicle priming to organism-scale control of sleep and sensory behavior.

The transcription machinery in the phylum spirochetes is poorly characterized at the molecular level yet is of significant evolutionary and medical importance. Pathogenic spirochetes can easily move through the mammalian tissues, penetrate blood vessels, cross the blood-brain barrier, and cause serious diseases, such as Lyme disease, relapsing fever, and syphilis. At the same time, many non-pathogenic spirochete species exist. Spirochetal RNA polymerases (RNAPs) are naturally resistant to rifampicin (Rif), the best-known transcription inhibitor in clinical use. Spirochetes evolved independently from other bacterial phyla and are not closely related to the well-established model organisms Escherichia coli (Eco) and Bacillus subtilis (Bsu), suggesting that the regulation of transcription in spirochetes includes distinct and novel strategies. Transcription is the first step in the highly regulated process of gene expression. It is divided into three phases, initiation, elongation and termination, that determines the start and the end of the transcription unit. To initiate transcription, RNAP, together with a Sigma factor (holoenzyme), recognizes promoter motifs on the DNA template and starts RNA synthesis. Many regulatory factors are associated with RNAP during initiation and modulate its activity, including CarD, GreA and DksA. Sequence alignments identified additional or distinct domains of some of these transcription factors in spirochetes compared to most other bacteria phyla, suggesting that they may act through different molecular mechanisms. To investigate transcription mechanisms regulated by CarD, GreA, and DksA, we reconstituted initiation complexes with each initiation factor and determined their structures using cryo-electron microscopy (cryo-EM). Here, I present the cryo-EM structures of Spirochaeta africana (Sfc) RNAP open promoter complex (RPo) in the presence or absence of CarD. Sfc RNAP, together with Sfc σ 70 , binds to the promoter DNA in an open conformation in which the duplex DNA is unwounded and the transcription bubble is formed. The structures suggest that Sfc RPo is unstable and could be stabilized by Sfc CarD via binding to the upstream template DNA (tDNA) of the transcription bubble. I also present the cryo-EM structure of the Sfc RPo in complex with GreA, indicating that Sfc GreA, like Sfc CarD, can stabilize the open promoter complex. This stabilization is achieved through the CarD-like domain, confirming the role of Sfc GreA as an initiation factor. During transcription elongation, transcription factors NusG and NusA are recruited by RNAP in most operons, while LoaP comes specifically in certain operons, promoting the RNA chain extended correctly. In addition, Sfc NusA has two additional acidic disordered loops on the AR1 and AR2 domains compared to Eco NusA. To investigate the functions of Sfc NusA and LoaP, we reconstituted elongation complexes with NusG/NusA and LoaP/NusA, and determined their structures using cryo-EM. I present the cryo-EM structures of Sfc RNAP in complex with NusG/NusA and LoaP/NusA, respectively. Although Sfc NusA does not change much the conformation of RNAP in the presence of NusG, it cooperates with LoaP to push nucleic acids away from RNAP, ensuring that the correct transcription elongation factor is recruited into the appropriate operon. The structures provide essential insights into the overall architecture of Sfc RNAP, the initiation and elongation complexes, and form the basis for further functional and structural analyses of spirochete-specific transcription factors and their regulation.

Die komplexen Verflechtungen von architektonischer Wiederverwendung, Auflassung und Ruineninteraktionen innerhalb einer Siedlung werden archäologisch in zwei Zeitstellungen untersucht und verglichen: im Neolithikum, dem analytischen Kern der Arbeit, und ergänzend im Anthropozän. Der Terminus Ruineninteraktionen wurde gewählt, um die Wechselwirkungen zwischen Menschen und Ruinen zu verdeutlichen. Ziel ist es, Ruinen und Auflassung als integrale Bestandteile der Diversität und (Dis-) Kontinuität von Siedlungen zu verstehen, da diese Kontexte in archäologischen Interpretationen bisher unterrepräsentiert sind. Als Fallstudie wird die neolithische Siedlung Göbekli Tepe (9600–8000 calBCE) in Obermesopotamien herangezogen. Der Fundplatz ist bekannt für die großen ovalen Sondergebäude, die mit bis zu 5,5 m hohen monolithischen T-Pfeilern ausgestattet sind. Lange wurde angenommen, dass die Gebäude am Ende ihrer Nutzung intentionell verfüllt wurden (auch bezeichnet als rituelle Gebäudebestattungen). Jedoch deutet heute eine mehr auf Landschaft und Topografie fokussierte Interpretation darauf hin, dass die Verfüllungen der Steilhangarchitektur zum Großteil auf Hangrutsch zurückzuführen sind. Dieser Arbeit liegt die Ausgangshypothese zugrunde, dass Ruinen neben bewohnten Gebäuden existierten und dass die Menschen aufgrund der Affordanzen vielfältig mit ihnen interagierten. Indirekte Nachweise von Ruineninteraktionen erfolgen durch eine systematischen Kartierung von Spolien und spolienartigen Elementen in den Mauern von Sonder- und Wohngebäuden. Diese Baupraxis wird als neolithische Kulturtechnik angesprochen und deutet auf die kontinuierliche architektonische Reproduktion des Orts hin. Direkte Nachweise sind durch eine kleinteilige Untersuchung der Fundassemblagen auf den Fußböden sowie der Raumverfüllungen rekonstruierbar. Aus diesen werden Gebäudebiografien erstellt, deren Phasen in sequences of events synthetisiert werden und siedlungsinterne Vergleichbarkeit gewährleisten. Um die anthropogenen Ablagerungen kontextuell eindeutiger zu differenzieren und Aktivitätszonen auch bei Abwesenheit von Funden festzustellen, wurden Sedimentanalysen durchgeführt. Die dreiteilige Methodik (Spolienkartierung, Untersuchung von Verfüllung und Sedimentanalysen) erlaubt eine umfassende Rekonstruktion von Auflassungsprozessen und Ruineninteraktionen und kann über Göbekli Tepe hinaus in der Archäologie Anwendung finden. Dieses Potenzial wird anhand eines regionalen Vergleichs mit zwei weiteren T-Pfeiler-Siedlungen, Karahantepe und Nevalı Çori, untersucht. Neben dieser räumlichen Gegenüberstellung wird eine diachrone Perspektive durch die Einbindung des Anthropozäns geschaffen. Im Rahmen eines Surveys wurden die Ruineninteraktionen der Gegenwart – durch Landwirtschaft, Ausgrabung, Konservierung und Tourismus – am Fundplatz dokumentiert. Aufgrund dessen werden die heutigen Interaktionen mit den neolithischen Ruinen als eigener Horizont in der Biografie Göbekli Tepes angesprochen. Im Gegensatz zur Kontinuität und Transformation der Ruinen im Neolithikum stehen heute die Konservierung und Kommodifizierung von Fundplätzen im Fokus. Die Dokumentation dieser Entwicklungen zielt darauf ab, den Impact von Ausgrabungen auf archäologische Stätten sichtbar zu machen und kritisch zu hinterfragen, da die heute hinterlassene Materialität die Archäologie der Zukunft bildet.

The Arab world has been profoundly affected by prolonged armed conflict, structural violence, political instability, and large-scale displacement over recent decades, leading to widespread exposure to traumatic events. Such exposure can contribute to the development of various mental disorders, including posttraumatic stress disorder (PTSD). Despite the significance, the region suffers from a dearth of comprehensive data on the prevalence, manifestation, and contributing factors of PTSD symptoms. Knowledge of scalable treatment options to support individuals with PTSD from the region remains scarce. Research suggests that interventions provided via the internet can help overcome common barriers to psychological treatment uptake on-site, such as limited accessibility and stigma. Evidence further highlights the benefits of such interventions for individuals from the Arab world; however, knowledge remains limited regarding the efficacy of brief internet-based interventions that incorporate distinct treatment components for individuals with PTSD in the region. The thesis aims to address significant knowledge gaps in the mental health landscape in the Arab world by delivering empirical insights into the prevalence and manifestation of symptoms of PTSD in populations from the region. It further aims to contribute to the advancement of accessible, low-threshold mental health services through the evaluation of two brief internet-based interventions with different treatment elements for Arabic-speaking individuals with PTSD. The thesis includes four empirical studies, each addressing a key dimension of the research aims. Study I utilized a systematic review and meta-analysis to estimate the prevalence of posttraumatic stress symptoms among populations from the Eastern Mediterranean Region. The meta-analysis of 118 eligible study samples involving 40,188 participants yielded a pooled prevalence estimate of 31%, with a prediction interval between 1% and 76% for posttraumatic stress symptoms. Significant heterogeneity was observed, but subgroup analyses could not explain it. Study II applied a latent class analysis on a large sample of 5,140 help-seeking individuals from the Arab world to uncover distinct profiles of posttraumatic stress symptoms. The results revealed that manifestation of symptoms of posttraumatic stress in this population can be characterized by five different classes: (1) a class with general high posttraumatic stress symptoms, (2) a class with high posttraumatic stress symptoms but low avoidance, (3) a class with mixed posttraumatic stress symptoms, (4) a class with high dysphoric but low re-experiencing/avoidance symptoms, and (5) a class with low posttraumatic stress symptoms. In addition to differences in the severity of posttraumatic stress symptoms, significant differences were observed in depressive symptoms, anxiety, somatic complaints, and the level of quality of life between the classes. Consistent significant predictors were gender, social support, and different trauma-related factors. Study III was a randomized controlled trial evaluating the efficacy of two brief internet-based interventions with different therapeutic foci—one centered on exposure and the other on cognitive restructuring—for Arabic-speaking populations with PTSD. Both interventions were developed based on the established Interapy protocol, and were translated and adapted for use with individuals from countries in the Arab world. In the study, 365 participants with PTSD were randomly allocated to one of three conditions: cognitive restructuring, exposure, or a waitlist control. Results revealed large within-group effects for reductions in posttraumatic stress symptoms. On average, posttraumatic stress symptom severity decreased significantly after four out of six sessions in both interventions. Significant improvements were also achieved for all other outcomes. No significant differences were found between the two interventions in terms of usage patterns (starters versus nonstarters, dropouts versus completers, and duration of treatments) or symptom change. Both interventions outperformed the waitlist control group. Those who completed one of the interventions reported high treatment satisfaction. Study IV examined whether both internet-based interventions differ in their impact on changes in trauma-related appraisals such as shame (“It is as if my insides are dirty”), self-blame (“The event happened because I was not careful enough”), fear (“Danger is always present”), anger (“I feel anger”), alienation (“I am disconnected from people”), and betrayal (“Important people let this happen to me”). Significant improvements in shame, self-blame, fear, anger, and alienation were achieved in both interventions. There was no evidence of differences between both interventions in relation to any of the specific trauma appraisals. Changes in posttraumatic stress symptom severity were significantly associated with changes in shame, self-blame, fear, anger, and alienation in both interventions. The thesis provides one of the first comprehensive and up-to-date syntheses of PTSD symptom prevalence in the region and emphasizes the substantial heterogeneity in prevalence estimates. The thesis demonstrates that PTSD symptoms manifest in diverse forms and that distinct subgroups with specific symptom profiles can be identified. These subgroups vary in terms of comorbid symptoms and can be predicted based on a range of individual characteristics. The thesis establishes the efficacy of internet-based interventions that incorporate exposure or cognitive restructuring as the main treatment component and thus highlights the potential of scalable and brief interventions for PTSD delivered via the internet in bridging gaps in care delivery for trauma-exposed populations from the Arab world.

This thesis argues that knowledge about mental health and illness developed in the Global North is exported to Indonesia, and appropriated and navigated in ways contingent on local political contexts, cultural norms, and values. I support this argument based on epistemological tools developed during the COVID-19 pandemic and 15 months of ethnographic research in Indonesia, in a series of four articles. The first article, developed in the context of the COVID-19 pandemic, shows how global knowledge flows associated with international health structures can obscure what matters most for people during a health crisis. The findings of this article (drawn on data collected from Nigeria, Guinea, Singapore, and Germany) suggest that when people are confronted with complex threats to their health and well-being, their primary concern is not about biomedical information. Non-biomedical knowledge might be just as important – if not more important – than biomedical knowledge in shaping health-seeking behaviors. In the second article, the aim was to systematically engage with knowledge emerging from Indonesia around severe mental illnesses (SMI). The review of over 100 articles suggests that research questions and topics that dominate SMI research in Indonesia are very well aligned with research agendas established in the Global North, and hence with particular notions of the mind and its ailments. Noteworthy is that this consistency with entrenched understandings of health and illness emerges despite (hyper)diverse Indonesian cultural environments. The third article illustrates how this complex web of knowledge, corresponding to biomedical notions of mental health and illness, established within international health structures, is disseminated into local communities. And how these knowledge-flows play out and influence the experiences of patients and their immediate environments. The main argument of this article is that adopting psychiatric notions of mental health decreased uncertainty and created common ground and a sense of shared experience, leading to grassroots movements for the empowerment of the mentally ill, self-help groups, and other support structures. At the same time, these processes led to an increase in uncertainty and generated a culture of blame that, at its worst, pushed patients into a world of silence. The final article turns to mental pain amid this complex knowledge landscape. This article first outlines the salient attributes of mental pain as they emerged during conversations with patients and observations of their everyday lives. These attributes partly explained the uncertainties individuals faced as part of their experiences with severe psychiatric disorders. The main argument of this article is that the interplay between mental pain and uncertainties informed certain illness behaviors, particularly tendencies toward self-isolation.

La obra analiza los enlaces históricos que permitieron a la población arabófona de México exhibir vínculos transregionales con el llamado “Medio Oriente” entre el ocaso del Imperio Otomano y el inicio del sistema de mandato europeo en Máshrek. Se argumenta que su sentido de pertenencia debe ser interpretado como un vínculo material y espiritual con su lugar de origen capaz de posicionar su presencia transnacional entre un pasado nostálgico y un proyecto de cohesión social hacia el futuro.

Intrusive memories are a core symptom of posttraumatic stress disorder (PTSD), a mental disorder with a high risk for chronic progression, psychological and physical comorbidities and socio-functional impairments. Despite extensive research, the mechanisms underlying the development of PTSD following trauma exposure remain insufficiently understood. There is increasing evidence that neuroendocrine stress systems, such as the hypothalamic-pituitary- adrenal (HPA) axis and the noradrenergic system, play a role in the formation of intrusive memories. Beyond that, the oxytocin system, known for its involvement in stress regulation and social behavior, has emerged as a promising candidate for PTSD prevention research. However, findings regarding its effects on memory and stress remain inconclusive and appear to depend on individual and contextual factors. Oxytocin’s effects seem to be closely intertwined with endocrine stress system activity, suggesting that variations in physiological stress states may shape its impact. The use of oral contraceptives (OCs), which alter endocrine functioning, is gaining recognition as a relevant, yet underexplored, factor in both oxytocin-related and PTSD research. The primary aim of this dissertation is to investigate whether and how exogenous oxytocin influences the formation of intrusive (involuntary) memories after a trauma paradigm in healthy women. A secondary aim is to examine the moderating role of neuroendocrine stress markers, genetic factors, and OC use on oxytocin’s effects. In addition, the dissertation explores oxytocin’s influence on voluntary trauma-related memory. To address these questions, four experimental studies using a validated trauma film paradigm in healthy women were conducted. Study I examined whether the administration of oxytocin after trauma exposure—during the consolidation phase—affects the development of intrusive memories. Study II investigated the effects of oxytocin administration before trauma exposure, mainly targeting the memory acquisition phase. In both studies, potential moderating effects of individual differences in cortisol (as an indicator of HPA axis activity), salivary alpha-amylase (sAA; as a marker of noradrenergic activity), heart rate variability (HRV; reflecting autonomic nervous system regulation), and genetic variations on the oxytocin effect were explored. Study III investigated whether the use of OCs impacts oxytocin’s effects on the development of intrusive memories and whether OCs independently influence the development of intrusive memories. Study IV examined whether oxytocin administration before or after trauma exposure influences voluntary recognition memory for trauma-related content. The main findings are as follows: Oxytocin did not exert a general dampening effect on intrusive memories. Rather, its impact was modulated by timing and individual physiological profiles. While the administration of oxytocin after a trauma paradigm (Study I) did not influence the subsequent development of intrusive memories, the administration of oxytocin before a trauma paradigm (Study II) increased intrusive memories in the aftermath. This effect was influenced by baseline cortisol, HRV, and genetic variation, including polygenic risk scores for PTSD and the single nucleotide polymorphism rs53576 in the oxytocin receptor gene. OC use did not affect the impact of oxytocin on intrusive memories. However, participants using OCs showed a blunted decline in intrusive memories after the trauma film compared to naturally cycling women (Study III). Voluntary recognition memory was unaffected by oxytocin administration, whether given before or after the trauma film (Study IV). In conclusion, the trauma film paradigm enabled a controlled investigation of processes that cannot be studied during real-life trauma exposure. This dissertation provides novel insights into the role of oxytocin in trauma-related memory formation and underscores the importance of accounting for neuroendocrine and genetic moderators (i.e., cortisol, HRV and genetic variations) when examining oxytocin in the context of PTSD. Notably, the findings suggest that oxytocin administration prior to trauma exposure may be contraindicated, as it was associated with an increase in intrusive memories, particularly in individuals with certain physiological profiles. In contrast, no effects were observed for oxytocin administration after trauma exposure; however, this absence of effect may be attributable to methodological factors, such as timing, dosage, or the nature of the trauma analogue. By integrating the biological moderators assessed in this dissertation into existing models of PTSD, the findings offer promising directions for the development of targeted, individualized prevention strategies. Although not the primary focus of this dissertation, the results also point to OC use as a biologically relevant variable that may influence trauma-related memory processes and should therefore be considered in both future research and clinical practice.

Ausgangspunkt dieser Arbeit ist der Staat als (Völker-)Rechtssubjekt, als Akteur und als Adressat der Aufarbeitung staatlicher Unrechtsvergangenheit, fokussiert auf das Verhältnis Staat–Individuum. Zentrale Frage ist, ob es rechtliche Pflichten des Staates zur Aufarbeitung staatlichen Unrechts gegenüber dem Individuum gibt und ob daraus ein durchsetzbares Individualrecht auf Aufarbeitung resultiert. Die Untersuchung richtet sich nach derzeitigen geltendem Recht Vietnams und prüft, ob sich aus einer fortbestehenden oder neu geprägten Rechtsordnung eine rechtliche Pflicht zur Aufarbeitung ableiten lässt, insbesondere im Kontext eines Systems, das sich als sozialistischer Rechtsstaat bezeichnet.

Claudins are considered the backbone of the tight junctions (TJ), sealing the gap between two adjacent cells and preventing the passage of solutes across epithelia. Interestingly, claudin-2 (Cldn2) forms channels at the TJ that allow the paracellular passage of cations and water. This protein is co-expressed in some epithelia, e.g., proximal nephron and small intestine, along with the barrier formers claudin-3 (Cldn3) and claudin-1 (Cldn1). However, the impact that the interaction of these claudins may have on the properties of Cldn2 channels is unclear.

Therefore, the aim of this dissertation was to determine whether co-expression of Cldn2 with Cldn3 or Cldn1 affects the ion and water permeability of Cldn2 channels. To achieve this goal, two knockout cell models (MDCK C7/Cldn3KO and MDCK II/quinKO) were used to express Cldn2 and co-express Cldn2/Cldn3. Additionally, Cldn2/Cln1 was co-expressed in MDCK II/quinKO cells. After characterizing the different cell lines by Western blot and different microscopy techniques (confocal, STED, and freeze-fracture electron), different electrophysiological assays were performed to evaluate the functions of Cldn2 channels in cell monolayers. The results of these experiments showed that co-expression of Cldn2/Cldn3 in both cell models, and co-expression of Cldn2/Cldn1 in MDCK II/quinKO cells reduced the absolute ion permeability of Cldn2 channels without altering their charge- or size-selectivity or ion dehydration patterns. However, co-expression of Cldn2/Cldn3 did not affect water flux in MDCK C7/Cldn3KO cells.

These findings suggest that Cldn2 channel properties are regulated by hetero-oligomerization of Cldn2 and either Cldn3 or Cldn1, forming claudin-intermixed channels that are permeable to water but not cations. These hybrid channels may coexist in the TJ meshwork with homo-oligomeric Cldn2 channels, which is supported by the results of this study and complementary experiments demonstrating Cldn2-Cldn3 trans– and Cldn2-Cldn1 cis-interactions.

Die vorliegende Dissertationsschrift untersucht das Phänomen der Kirchenumgestaltungen in Italien. In systematischer Form erfasst sie die Tatsache, dass die Innenräume italienischer Kirchen nach ihrer Ersteinrichtung immer wieder zum Gegenstand umfassender Umgestaltungskampagnen geworden sind. In diesem Zuge legt die Schrift zunächst eine Theorie und Methodologie der Kircheninnenraumforschung vor. Hauptthemen bilden dabei die räumliche Disposition, die zumeist künstlerische Ausgestaltung der Oberflächen der Raumhülle und der Einrichtungsgegenstände sowie das Phänomen der Umgestaltung eines vorbestehenden Kirchbaus. Anschließend erfolgt eine exemplarische Untersuchung der Kirche S. Pietro in Perugia, die die gesamte Fortdauer ihrer ca. 1000 Jahre andauernden Existenz hinweg erfasst. Zu jeder der in S. Pietro erfolgten Umgestaltungskampagnen (je nach Zählung sind es ungefähr sechs bis acht) sowie zur Ursprungsgestalt der Kirche und zum Phänomen der späteren Fiktion einer noch in das Frühchristentum zurückreichenden Existenz werden außerdem auf breitester Ebene Vergleichsuntersuchungen mit anderen Bauten und der Entwicklung der Kircheninnenräume in unterschiedlichsten mittel- und norditalienischen Regionen vorgelegt. Die vorliegende Schrift liefert damit auch einen ersten Überblick über die Kircheninnenraumgeschichte in Italien. Von zentraler Bedeutung ist dabei auch das Phänomen der frühwissenschaftlichen Beschäftigung mit italienischer Kirchen- und Heiligengeschichte. Publikationen wie Ferdinando Ughellis „Italia Sacra“ und die lokale Guidenliteratur haben nämlich sowohl weitere (Um-)Gestaltungen von Kircheninnenräumen mitbestimmt als auch die moderne Forschung nachhaltig beeinflusst. So werden auch heute noch immer wieder fehlerhafte Datierungen und Rekonstruktionen tradiert, die die frühmodernen Forschung seit dem 17. Jahrhundert als vermeintlich gesicherte Wahrheiten etabliert hat. Einen weiteren Schwerpunkt der Arbeit bildet die Erforschung der Baugesetzgebung und der überregionalen Netzwerkbildung der Cassinensischen Kongregation, der neben S. Pietro in Perugia lange Zeit fast sämtliche weitere Benediktinerklöster Italiens angehört haben. Außerdem liefert die Arbeit neue Erkenntnisse zur Ursprungsgestalt bzw. zu späteren Umgestaltungen der berühmten ehemaligen Altarbilder von S. Pietro, also von Meo da Sienas ursprünglich doppelseitigem Dorsale im Frankfurter Städel und von Pietro Peruginos Himmelfahrtsaltar. Zusätzlich legt die vorliegende Schrift umfassende Editionen sowohl zu mittelalterlichen Quellen als auch zu Schriften der frühmodernen Forschung vor, die der Wissenschaft bisher nur schwer oder sogar nur in handschriftlicher Form in einem einzigen Archiv zugänglich waren. Schließlich wird in einem eigenen Doppelband ein sehr umfangreicher Bildteil vorgelegt, der nicht nur den Kircheninnenraum von S. Pietro im Detail vorstellt. Vielmehr gibt er auch einen Überblick über die romanische Architektur in Umbrien und zu Kirchenumgestaltungen im 16. und 17. Jahrhundert in Mittel- und Norditalien. Da in diesem Zuge viele, teils auch sehr prominente Kircheninnenräume und ihre Ausstattung erstmals umfassend und in Farbe dokumentiert werden, können die Bildbände auch als Ausgangspunkt zu weiteren Untersuchungen der Kircheninnenraumforschung dienen.

In silico neuroscience is an emerging research paradigm consisting in the generation of large amounts of in silico neural responses using encoding models, followed by the experimentation on these in silico data. The in silico generation of neural responses is resource-efficient, saving enormous amounts of time and money, and therefore greatly speeds up research. This dissertation consists of my three doctoral studies, each contributing to the paradigm of in silico neuroscience in an idiosyncratic way, with a focus on human vision. In Study 1, I collected and released THINGS EEG2, a large-scale visual neural dataset (LSVND) of EEG responses of 10 subject to 16,740 naturalistic images. I showed that this large amount of data allows to train accurate encoding models of neural responses to images–including end-to-end encoding models based on randomly initialized deep learning architectures–indicating the suitability of this EEG dataset for in silico neuroscience. In Study 2, I used the paradigm of in silico neuroscience to develop relational neural control (RNC), a neural control algorithm to move from an atomistic understanding of visual cortical areas (i.e., “What does each area represent?”) to a network-level understanding (i.e. “What is the relationship between representations in different areas?”). Crucially, I then validated the in silico discoveries on in vivo fMRI responses recorded from independent subjects, thus revealing how visual areas jointly represent the world as an interconnected network, and showcasing the power of in silico neuroscience. In Study 3, I contributed to the improvement of the out-of-distribution (OOD) prediction accuracy of encoding models by releasing NSD-synthetic, the OOD companion dataset of the Natural Scenes Dataset (NSD)–the most popular LSVND of human fMRI responses to naturalistic images. I showed that encoding models trained on NSD generalize in-distribution (ID) and, to a lower extent, OOD on NSD-synthetic. Furthermore, these OOD tests revealed differences between encoding models that were not detected ID. Thus, NSD-synthetic provides unique insight for the development of more robust encoding models that better generalize OOD, in turn increasing the reliability of in silico neuroscience findings. Together, my vision for the future of the paradigm of in silico neuroscience is that richer LSVNDs including OOD components will promote encoding models that more accurately predict in silico neural responses, leading to an increase of in silico experimentation that will ultimately result in faster scientific development.

We develop and apply generalized Langevin equations (GLEs) for modeling non-Markovian dynamics in discrete time-series data. Emphasizing both theoretical and computational aspects, we investigate how memory effects, non-Gaussian noise, and coupling between multi-dimensional reaction coordinates shape the dynamics of stochastic observables. Through diverse examples from synthetic, simulated, and experimental data, we show that the GLE framework offers a versatile and practical tool for data-driven modeling and prediction of complex dynamics, and establish it as a physically grounded and efficient framework for time-series analysis across molecular, environmental, and financial systems.

We begin by outlining the theoretical basis of the GLE via the projection operator formalism and present numerical techniques for extracting parameters from discrete data, suitable for analyzing systems in and out of equilibrium. In the molecular dynamics setting, we apply these methods to dihedral transitions in butane using molecular dynamics (MD) trajectories to compare various GLE formulations. Incorporating non-Gaussian noise improves predictions of mean first-passage times, surpassing Gaussian-based Markovian embeddings. For multi-dimensional systems, we develop GLE models for the coupled dynamics of the dihedral angles of pentane, revealing strong off-diagonal friction from intramolecular interactions. These models capture cross-displacement statistics and reaction kinetics in MD data.

For real-world applications, convolution filtering decomposes time-series data, and we fit a GLE model to the fast-fluctuating component. This reveals long-range memory in daily weather data, while financial assets exhibit rapid decay, consistent with the efficient-market hypothesis. GLE-based forecasting rivals the performance of state-of-the-art methods like recurrent neural networks while being more computationally efficient and offering physically interpretable insights.

As part of time-series analysis, we explore the microscopic origins of memory friction $\Gamma(t)$. We begin by the computation of static friction coefficients from MD simulations and introduce an integration-based method that accurately estimates friction and separates electrostatic and Lennard-Jones contributions to diffusivity in water. Next, we examine frequency-dependent friction spectra for water and methane in bulk water. Water spectra align with hydrodynamic theory for a diffusing sphere in a viscous medium, enabling feature attribution of $\Gamma(t)$, while methane reveals deviations that can be rationalized by the concept of a viscoelastic hydration shell. We extend these findings to polymeric hydrogels, where a generalized Stokes-Einstein relation considering an interfacial adsorption shell accounts for differences between viscosities from experimental macro- and microrheology data.

A reverse genetics system (RGS) for iridovirus frog virus 3 (FV3, Ranavirus rana1), one of the key members in Megaviricetes class, was successfully developed using transformation- associated recombination (TAR) cloning in yeast Saccharomyces cerevisiae. This method enabled the construction of BAC-YAC constructs containing the full-length FV3 genome, from which infectious virus could be rescued. One of the constructed clones - FV3-S3Ar - retained key phenotypic and functional characteristics of the parental FV3, demonstrating the integrity of the construct. To evaluate the established RGS applicability, a recombinant virus was generated by replacing ORF64R with an enhanced green fluorescent protein (EGFP), constructing a reporter virus FV3-Δ64R-EGFP. The resulting reporter virus showed stable replication and persistent EGFP expression over several passages. This confirmed the platform’s suitability for targeted gene manipulation and the viability of the system. An alternative rescue method using the heterologous fish ranavirus Largemouth bass virus virus (LMBV, Ranavirus micropterus1) as a helper virus was developed and validated. This approach proved effective for virus rescue and may provide a safer and more straightforward option compared to the use of a traditional UV-irradiated helper virus. Overall, this system offers a reliable and flexible tool for the genetic mutagenesis of FV3 and paves the way for future investigations into viral gene function, pathogenicity, and potential vaccine development.

Feed management decisions play an essential role in reducing greenhouse gas (GHG) and nitrogen (N) emissions from ruminant farming systems. However, evaluating the downstream effects of diet on emissions in dairy production is challenging. This is due to the complex interplay among interconnected components such as animals, housing, manure storage, and soil. Consequently, a comprehensive assessment that considers both direct and indirect GHG and N emissions and accounts for the underlying processes and drivers of carbon (C) and nitrogen within the system is necessary. Static emission factors (EFs) and empirical models often fail to capture the spatial and temporal variability of these systems. This limits their utility for site-specific assessments and targeted mitigation strategies. This thesis addresses this problematic by applying PB modelling approaches that simulate the underlying biogeochemical processes driving emissions, thereby offering a more dynamic and comprehensive perspective. The research begins with a comprehensive review (the first Paper) of modelling the influence of feed management on GHG and N emissions in cattle farming systems. It contrasts statistical and empirical models, with mechanistic PB models. The former are useful for inventory applications, whilst the latter capture dynamic interactions between feed composition, microbial fermentation, and downstream emissions. This review establishes the scientific rationale for integrating PB approaches into whole-farm emission assessments. By identifying the limitations of simpler methods, it sets the stage for a more sophisticated modelling approach. Building on this foundation, the second paper introduces an innovative PB modelling framework. This framework creates links across the manure management chain. It integrates the Dutch Tier 3 model for animal emissions with the Manure-(DNDC) model for manure storage and a soil biogeochemistry model. This study evaluates the downstream impact of dietary factors on whole-farm emissions. The methodology was rigorously applied to two contrasting dairy systems: a confined system in Germany and a pasture-based system in New Zealand. The differences in production systems between them demonstrated significant differences in C and N emission. This highlights the critical role of feeding and manure management practices in shaping the environmental footprint. This application showed the framework's adaptability and its capacity to reveal system-specific dynamics. The third paper further advances the research by comparing the dynamic PB Tier 3 modelling approach with IPCC Tier 1 and Tier 2 methods. This comparative analysis showed substantial differences between PB Tier 3 dynamic EFs and IPCC Tier 1 and 2 EFs. This reveals that PB models can capture interannual and system-specific GHG emission variability more accurately, leading to more precise and adaptable emission estimates. The housing component of the Manure-DNDC model was validated against field measurements, confirming its effectiveness in simulating ammonia and methane barn emissions, a key source of uncertainty in GHG assessments. This validation underscores the reliability of the PB approach for capturing complex emission processes that generic EFs may overlook. Collectively, these studies demonstrate that integrating PB models into whole-farm emission assessments enables a more nuanced understanding. It shows how feeding and manure management practices impact GHG and N emissions. These models offer a more wholistic and accurate picture of on-farm emissions by simulating the underlying processes and considering the interactions between different farm components. This integrated modelling approach has significant implications. It can help develop of targeted mitigation strategies and improve the C accounting in the context of Carbon-farming and monitoring, reporting and verification (MRV) in agricultural systems. It can also inform future policies aimed at reducing the environmental footprint of cattle farming. The PB models represent a step towards more precise and adaptable tools for researchers and policymakers. They facilitate evidence-based decision-making in sustainable agriculture and pave the way for more environmentally responsible livestock production.