DNA methylation is a fundamental epigenetic modification that plays a crucial role in regulating gene expression and cell differentiation. Multiple profiling technologies have been developed to generate DNA methylation maps with varying resolutions and genome coverage. In recent years, DNA methylation-based classification of tumors has emerged as a powerful and indispensable diagnostic technique. Traditional implementations relied on methylation microarrays to establish reference datasets, and most current classifiers remain constrained to a fixed set of methylation features from specific platforms. This limitation hampers their compatibility with other platforms, particularly emerging sequencing technologies. Among these, low-coverage nanopore sequencing stands out as one of the fastest and most cost-effective options. This thesis first introduces an ad-hoc Random Forest–based approach that enables robust tumor classification using sparse methylomes obtained from low-coverage nanopore data. Building upon this, a neural network–based machine learning framework named crossNN, is presented. crossNN enables accurate tumor classification from sparse methylomes generated across different platforms, regardless of variations in epigenomic coverage or sequencing depth. It surpasses both deep learning and conventional machine learning models in accuracy and computational efficiency while maintaining interpretability. With crossNN, a pan-cancer classifier was trained and validated to distinguish more than 170 tumor entities spanning all organ systems. Overall, this work demonstrates two sequential advances in DNA methylation-based tumor classification. First low-coverage nanopore sequencing is a viable and cost-effective route for methylation-based brain tumor classification via ad-hoc Random Forest algorithm. Second, the crossNN framework extends this concept by overcoming platform-specific feature constraints and enabling cross-platform, interpretable tumor classification. These developments pave the way for scalable, explainable, and clinically applicable DNA methylation-based diagnostics.  

Neuronal function depends on the maintenance of stable activity despite environmental perturbations. Neurons engage homeostatic plasticity mechanisms to maintain their activity within a functional range while preserving information acquired through experience-dependent changes. Several diseases par- ticularly prominent in humans have been associated with homeostatic modulation of synaptic efficacy and/or membrane excitability. Such changes may contribute to disease-related dysfunction, but may also arise as a consequence of pathology. At the same time, increasing evidence suggests that homeostatic plasticity responses are highly context dependent, making it essential to understand the intricacies of these processes in human neurons. Here, using patch-clamp electrophysiology, properties of human cortical pyramidal neurons were compared before and after more than 16 h of incubation in either control artificial cerebrospinal fluid (aCSF) or a moderately depolarising aCSF, supplemented with an additional 8 mM KCl. The high-potassium treatment consistently resulted in homeostatic downregulation of intrinsic excitability, as reflected by a reduction in firing frequency across three complementary experimental paradigms. In contrast, the length of the axon initial seg- ment showed only time-dependent shortening, rather than potassium-specific structural remodelling, under the same conditions. The perturbation appeared to preserve synaptic connectivity over the in- cubation period, whereas connectivity was reduced from 12% to 6% under control conditions. There was no evidence for homeostatic synaptic scaling. Together, these findings indicate that prolonged moderate depolarisation in human cortical neurons preferentially engages intrinsic, rather than synap- tic, homeostatic mechanisms, and highlights the importance of defining the conditions under which homeostatic plasticity operates in human cortical circuits.

This thesis addresses the human metabolism of beta-receptor-active ethanolamines and the quantitative analysis of the parent drugs and their phase I and phase II metabolites in human specimens. The investigations' three key aspects are 1) the biosynthesis of reference material, 2) the development of highly sensitive bioanalytical quantitation methods using chiral and achiral chromatography coupled to tandem mass spectrometry, and 3) the final quantitation of human urine and serum samples from administration studies. The achieved milestones were: First, a biosynthesis protocol for sulfonated phase II metabolites, including salbutamol-4’-O-sulfate and propranolol sulfate, was successfully developed using genetically modified S. pombe. The protocol rendered the external addition of the expensive cofactor PAPS superfluous (Manuscript III). Subsequent upscaling of salbutamol-4’-O-sulfate biosynthesis by human SULT1A3 in S. pombe enabled production of sulfoconjugated metabolites as a reference in bioanalytical quantitation (Manuscript IV). Notably, this biosynthesis is highly enantioselective for (R)-salbutamol. Second, the successful quantitation of salbutamol-4’-O-sulfate, alongside salbutamol and formoterol, was achieved by highly sensitive HPLC-MS/MS methods for urine and serum samples in a phase I clinical trial. The study results indicate that salbutamol and formoterol tend to reach higher concentrations in the urine and serum of females (Manuscript VI). Additionally, the development of further chiral and achiral HPLC-MS/MS methods enabled research on sulfonation rates of salbutamol. In a proof-of-concept study, it was demonstrated that oral administration and administration of enantiopure levosalbutamol can be indicated by the ratio of sulfonated to parent salbutamol in urine (Manuscripts IV & V). Third, the simultaneous chiral separation of propranolol and its ring-hydroxylated phase I metabolites (4’-, 5’-, and 7’-hydroxypropranolol) was successfully achieved by SFC-MS/MS as well as by two-dimensional HPLC-MS/MS (Manuscripts I & II). Quantitative bioanalysis by chiral SFC-MS/MS faced more obstacles than quantitative bioanalysis by chiral heart-cutting 2D-HPLC-MS/MS. Attempting quantitation of all ring-hydroxylated metabolites in bioanalytical SFC-MS/MS required the examination of several sample preparation methods, including dilute-and-inject, solid-phase extraction, and liquid-liquid extraction. The challenges of fast chiral bioanalytical SFC-MS/MS quantitation are discussed, focusing on recovery, quantitative and qualitative matrix effects, and the presence of phase II metabolites. The results were obtained by employing in vitro and in vivo metabolism models. The former includes isolated recombinant human enzymes and human enzymes expressed in genetically modified fission yeasts (S. pombe). Metabolism models in S. pombe were employed as whole-cell experiments for the production of reference substance and as permeabilized yeast-cell experiments (enzyme bags) for overview incubations. In vivo experiments were conducted in human volunteers in accordance with ethical standards. The investigations required the use of HPLC coupled to a diode array detector, unit mass spectrometry, tandem mass spectrometry, and high resolution mass spectrometry. SFC was hyphenated to tandem mass spectrometry. NMR analysis was needed for the quantitation and final structure elucidation of biosynthesized salbutamol-4’-O-sulfate and was performed in cooperation with the Institute of Pharmacy in Kiel. This work demonstrates the significance of the enantioselective acquisition and quantitation of beta-receptor-active ethanolamines in human specimens and highlights the potential of targeting their metabolites, particularly sulfonated phase II metabolites. The results enhance understanding of methodological developments in therapeutic drug monitoring, forensic analysis, and anti-doping control.

Mit dieser Studie wird ein übergeordnetes Ziel verfolgt: die theoretische und empirische Klärung der Rolle der Medien bei der Entstehung einer möglichen kollektiven nationalen und/oder regionalen Identität in Deutschland. Hintergrund der Fragestellung ist die auch 35 Jahre nach der Wiedervereinigung aktuelle Ost-West-Debatte. Ausgehend von der Annahme, dass die Bildung einer gemeinsamen kollektiven Identität in der Nachwendezeit nur unzureichend funktioniert hat, wird die besondere Rolle von Medien als Vermittlungsinstanz, vor allem der öffentlich-rechtliche Rundfunk mit seinem rechtlich-normativen Auftrag, betrachtet. Das Konzept der Medienkultur nach Hepp bildet das zentrale analytische Raster der theoretischen wie empirischen Aufbereitung der Konstruktion von kollektiver Identität in Deutschland. Vor dem Hintergrund zweier getrennter Medienkulturen in BRD und DDR bleibt offen, ob die formale Einigung und die damit einhergehende Schaffung eines gemeinsamen Kommunikationsraums auch tatsächlich zu einer neuen gemeinsamen Medienkultur geführt hat. Zur Klärung dieser Frage wird der Kreislauf der Medienkultur in ein überarbeitetes Encoding/Decoding-Modell nach Hall integriert und empirisch in ein modulares Mehrmethodendesign übersetzt. Mit drei Teilstudien wird je ein Faktor der Medienkultur empirisch untersucht: Produktion, Repräsentation und Aneignung. Auf Ebene der Produktion wird anhand von Desk Research eine strukturelle Unterrepräsentanz ostdeutscher Personen nachgewiesen. Mittels leitfadengestützten Expert:inneninterviews werden Rückschlüsse auf die Perspektiven von Akteuren aus dem Journalismus und der Journalismusausbildung zur Rolle von Medien bei der Konstruktion kollektiver Identität gezogen. Es kann gezeigt werden, dass die ungleiche Verteilung von Ressourcen und Entscheidungspositionen die Wahrscheinlichkeit erhöht, dass bestimmte Stimmen Eingang in den medialen Diskurs finden. Auf Ebene der Repräsentation wird die Konstruktion deutscher Identität im (über-)regionalen linearen öffentlich-rechtlichen Fernsehen mittels einer quantitativen Inhaltsanalyse von ARD/Das Erste, MDR und SWR untersucht. Neben einer hohen Sichtbarkeit von Deutschlandbezügen zeigen sich auch hier Asymmetrien. Ostdeutsche Bezüge sind im überregionalen Programm sowie im SWR unterrepräsentiert. Als relevant für Deutschland werden im überregionalen Programm überwiegend kontroverse Themen, im regionalen Programm vielmehr Kultur und alltägliche Lebensweltbezüge präsentiert. Identitätsanker werden regelmäßig gesetzt, vor allem durch Symbole sowie wirtschaftliche und sportliche Leistungen, während geteilte Werte und Normen oder gemeinsame Erinnerungen weniger relevant sind. Auf Ebene der Aneignung wurden Fokusgruppengespräche mit Ost- und Westdeutschen durchgeführt, um mehr über die Nutzung und Integration medialer Identitätsangebote in den jeweiligen Alltag zu erfahren. Die Befragten positionieren sich zurückhaltend, was den Einfluss der öffentlich-rechtlichen Angebote auf ihre Identitätskonstruktion angeht, implizit konnten jedoch Prägungen herausgearbeitet werden. Hinsichtlich der wahrgenommenen Repräsentation divergieren die Einschätzungen, sodass sich hier kein klares Bild zeichnen lässt. Es gibt Hinweise darauf, dass ostdeutsche Befragte eher eine Marginalisierung ihrer Perspektiven wahrnehmen. Die drei Teilstudien zusammengenommen erlauben eine Antwort auf die übergeordneten Forschungsfragen: Angebote zur Konstruktion von kollektiver Identität in Ost- und West-deutschland sind im Kreislauf der Medienkultur strukturell relevant, jedoch ungleich verteilt.

This dissertation examines the contested epistemological boundaries between science, culture and concepts of enchantment through a detailed analysis of J. B. Rhine’s parapsychological laboratory at Duke University and Wilhelm Reich’s experimental practices in mid-20th-century America. Rhine, transitioning from botany to psychical research, established laboratory-based studies of extrasensory perception (ESP), while Reich moved from psychoanalysis to developing his controversial theory of orgone, a purported universal life energy. Drawing on constructivist theories of science, boundary-work concepts, and theories of enchantment informed by Max Weber’s famous notion of the disenchantment of the world, I provide an in-depth analysis of their experimental methodologies, institutional contexts, and reception within scientific communities. The research demonstrates how these figures attempted to integrate enchanted elements into scientific discourse while challenging mechanistic paradigms. Through examination of archival materials, scientific publications, and media representations, I trace Rhine’s ESP experiments and Reich’s orgone research, revealing how they incorporated vitalist, Lamarckian, and spiritualist discourses into their experimental practices, creating flexible epistemological frameworks that accommodated uncertainty and enchantment. Despite their innovative approaches, both ultimately failed to establish new scientific paradigms due to methodological flaws, lack of expansive scientific networks, increasingly obsolete epistemological underpinnings, and the rigorous boundary-work of scientific thought collectives. Their enchanted practices epitomize the endpoint of enchanted sciences in America, illustrating how the epistemic borders of science became impermeable during the postwar years. The dissertation argues that while Rhine’s parapsychological research and Reich’s theories were marginalized by scientific communities, they significantly influenced popular culture and esotericism in the second half of the 20th century. By extending the historiographic focus on enchanted sciences beyond early 20th-century Europe, this project contributes to our understanding of how scientific knowledge is produced and how epistemic boundaries are negotiated and enforced.

Under the influence of neo-imperialism, Iran experienced a new form of colonial influence after World War II in the form of economic dependence, which also heralded profound cultural and political changes. In this context, Iranian intellectuals began to increasingly address questions of identity and modernity, seeking a middle ground between Western influence and Iranian traditions. This Third Space of hybrid cultural contacts and the accompanying discourses was characterised not least by complex interactions or even discursive contradictions, along whose lines of conflict identity was re-discussed. Not least, the social discourse took place in the literature of Iranian writers such as Sadeq Hedayat and Jamal Al-e Ahmad, whose works provide important insights into Iran's socio-political developments in the twentieth century. Hedayat's literature deals in particular with themes such as alienation and existential uncertainty, reflecting the cultural uprooting of broad sections of society between the pressure of modern Westernisation by the Pahlavi regime, traditional values, and the diversified discourse of intellectuals. His works illustrate the psychological and social fragmentation characteristic of the hybrid space. In a completely different way, Al-e Ahmad denounces the uncritical adoption of Western norms in his critique of “Westoxication” and calls for a revival of indigenous culture, not least from the perspective of Islam as a source of identity. In his writings, he formulates a vision of cultural hybridity that rejects both complete assimilation to the West and reactionary traditionalism. Instead, Al-e Ahmad advocated a decolonised modernity rooted in Iran's own ethical and cultural framework. Together, their works embody the debate on cultural identity within the Third Space and illustrate how Iranian intellectuals used hybrid discourses to resist neo-imperial rule and authoritarianism. Their approach challenged fixed or essentialist identities and opened up a fluid understanding of postcolonial Iranian identity.

Hydrogen produced by electrochemical water splitting is considered a promising energy carrier for future sustainable energy systems. However, the oxygen evolution reaction (OER) at the anode is the major kinetic bottleneck due to its complex multi-electron transfer mechanism. Among the various catalyst materials investigated for OER, transition-metal oxyhydroxides with bulk-phase catalytic activity have attracted considerable attention. Nevertheless, many aspects of their underlying electrochemical behavior and catalytic mechanism are still not fully clarified. In this study, cobalt-based oxyhydroxide electrocatalyst (CoCat) is employed as a model system for bulk-active catalysts for investigation of reaction kinetics. Electrochemical measurements are combined with operando spectroscopic techniques, including time-resolved X-ray absorption spectroscopy (XAS) and UV–Vis spectroscopy, in order to investigate the temporal evolution of oxidation-state changes and catalytic processes over a broad range of catalyst thicknesses and operating conditions. Additionally, electrochemical impedance spectroscopy (EIS) is employed to distinguish the characteristic timescales of double-layer charging, bulk redox transitions, and catalytic OER processes. Electric double-layer charging occurs on the microsecond timescale, followed by bulk cobalt oxidation-state transitions in the millisecond regime, whereas the catalytic OER process proceeds substantially more slowly. Correlation of time-domain measurements with impedance analysis enables assignment of equivalent circuit elements to physically meaningful electrochemical processes and provides a mechanistic interpretation of EIS parameters in terms of redox equilibration and catalytic turnover kinetics. Furthermore, temperature-dependent electrochemical measurements combined with operando XAS were performed to evaluate the activation energy parameters of the OER process and to investigate how the chemical state of the catalyst influences its catalytic activity. The analysis indicates that the Gibbs free energy of activation is determined predominantly by entropic contributions rather than solely by changes in the enthalpic energy barrier. Moreover, the results suggest that the applied potential does not directly lower the intrinsic activation barrier of the OER process, but instead controls the catalytic rate indirectly through changes in the oxidation state and population of reactive sites within the catalyst. The observed relationship between catalyst oxidation state, electrode potential, and catalytic current is described within an interaction-based framework, in which repulsive interactions between oxidized sites affect the thermodynamics of oxidation, while cooperative interactions enhance the reaction kinetics by reducing the activation energy. The temperature dependence of these interaction energies suggests a primarily entropic origin and highlights the balance between oxidation constraints and catalytic enhancement. Overall, this work establishes a comprehensive mechanistic picture, linking redox charge accumulation to changes in the chemical state of the catalyst, and ultimately to its catalytic activity, thereby providing new insight into the fundamental origin of potential- and temperature-dependent OER activity in bulk-active transition-metal oxyhydroxides.

High dietary salt intake is a major risk factor for non-communicable diseases such as hypertension and associated end-organ damage. Beyond elevating blood pressure, a high salt diet (HSD) alters the gut microbiome, modulates immune responses, and contributes to tissue injury. Immune cells, particularly their modulation by microbial signals, have emerged as key players in salt-related pathologies. Although intestinal immune cells are exposed to dietary salt shortly after ingestion and are capable of migrating to peripheral organs, their role in HSD-induced organ damage remains poorly understood. This thesis explores whether, and if so, how, high salt intake affects intestinal immune cell trafficking and activation, and whether these processes contribute to systemic inflammation and salt-induced tissue damage. To tag and trace intestinal immune cell migration in vivo, transgenic mice expressing the photoconvertible Kaede protein were used. Mice underwent two 3-week phases of high salt diet (HSD), separated by a 2-week normal salt diet (NSD) washout. NSD-fed mice served as controls, and animals were pretreated with L-NAME to sensitize the vasculature. Five days after photoconversion, immune cell trafficking and activation were analyzed using flow cytometry and bulk and single-cell RNA sequencing. In parallel, microbiome profiling was performed. In separate experiments within the same model, the impact of pharmacological interventions (FTY720, antibiotics) on immune trafficking was assessed. To investigate the functional relevance of B cells, a salt-sensitive mouse model with more severe organ damage (uninephrectomy and DOCA/HSD treatment) was used in combination with anti-CD20-mediated B cell depletion. Photoconversion-based tracing revealed widespread trafficking of intestinal immune cells to peripheral organs, including the spleen and kidney, with B cells emerging as the predominant migrating population. HSD induced substantial changes in intestinal gene expression and immune cell composition, and enhanced B cell migration to peripheral organs. FTY720 treatment confirmed S1P-dependent intestinal immune cell trafficking. HSD also altered homing and retention cues in both the intestine and kidney, and enhanced migratory programs in B cells. Changes in microbiome composition under HSD, along with the impact of antibiotic treatment on immune cell trafficking, highlight microbial signals as contributors to HSD-induced migration. B cell depletion exacerbated inflammation and kidney damage, indicating a protective role of B cells. HSD induced subset-specific B cell changes, particularly among gut-originating populations, characterized by enhanced IgA expression, elevated BCR signaling, activation, and cytokine production. Notably, IL-10 was upregulated alongside pro-inflammatory cytokines, suggesting a partial induction of a regulatory B cell phenotype under HSD. In summary, HSD shapes the phenotype and function of intestinal B cells and promotes their systemic migration, thereby modulating salt-induced immune responses and organ damage. This thesis identifies gut-originating B cells as key mediators linking mucosal and systemic immunity and uncovers immune migration pathways and regulatory mechanisms relevant to salt-sensitive disease. These findings enhance our understanding of salt-responsive immunity and may guide the development of novel therapeutic strategies targeting mucosal–systemic immune interactions to mitigate salt-associated health risks.

This cumulative dissertation examines the conditions under which data use beyond the original context of collection (data reuse) becomes transparent, accountable, and auditable in regulated environments. Despite expanding regulatory frameworks such as the GDPR and the EU AI Act and a growing repertoire of privacy-preserving data-sharing approaches, valuable data frequently remain underused because access, oversight, and justificatory conditions cannot be reliably organised across heterogeneous institutions and infrastructures. The dissertation therefore treats responsible data reuse as a socio-technical governance problem in which technical enablement, institutional constraints, and documentary evidence conditions must be aligned to make reuse trustworthy and reviewable in practice. Building on a systematic literature review that consolidates privacy-preserving and access-enabling approaches while highlighting unresolved governance and implementation tensions, the dissertation develops a cumulative argument in three steps: it first diagnoses why underuse persists even where data and technical solutions exist, emphasising intrinsic data frictions and missing intermediating structures that would institutionalise workable access pathways; it then benchmarks how open repository platforms govern compliance-relevant transparency by operationalising regulation-inspired expectations as machine-auditable documentation signals, with attention to downstream reuse contexts; and it finally derives an operationalisation perspective on auditable transparency at scale by specifying minimal evidence targets and platform-level mechanisms through which governance-relevant information can become inspectable and reviewable across heterogeneous settings.

Overall, the dissertation contributes an Information Systems perspective that links data reuse to platform governance and documentation-as-governance, clarifying what it takes to move from voluntary narrative disclosure toward auditable transparency as a practical condition of responsible reuse.

Benzimidazole (BZ) resistance in Haemonchus contortus, one of the most pathogenic blood-feeding gastrointestinal nematodes of small ruminants, represents a major challenge for sustainable parasite control. Benzimidazoles are proposed to bind to the isotype-1 β-tubulin subunit, inhibit microtubule polymerization, and disrupt essential cellular processes. Single nucleotide polymorphisms (F167Y, E198A, F200Y) in the isotype-1 β-tubulin gene are considered key markers of BZ resistance. To investigate the structural basis of BZ resistance, α/β-tubulin heterodimers from H. contortus (wild-type and BZ resistant variants) were modeled in silico and their interactions with albendazole (ABZ) were analyzed. Analyses revealed that ABZ weakens critical intradimeric contacts and prevents the transition from a curved to straight α/β-tubulin heterodimer conformation, whereas these interactions remain intact in resistant variants despite ABZ binding. To assess the functional effects of BZ binding, recombinant H. contortus isotype-1 α/β-tubulin heterodimers were expressed recombinantly in Leishmania tarentolae. Although the integration of the expression cassettes were confirmed, stable transgenic cell lines could not be established. The cells ceased proliferation, showed abnormal twitching, and expressed transcripts only transiently, indicating potential cytotoxic effects on the endogenous tubulin network. In parallel, deep-amplicon sequencing was used to quantify known and novel BZ-resistance associated polymorphisms in field samples from northeastern Germany. Alongside known polymorphisms, the novel E198G polymorphism in H. contortus and the F200Stop polymorphism in Trichostrongylus colubriformis were detected, both potentially associated with BZ resistance. Overall, these results integrate structural, functional, and genetic insights into BZ resistance in H. contortus and highlight the complexity of resistance development. The results underscore the importance of continuous monitoring, innovative control strategies, and polymorphism modeling. Together, these findings support the refinement of experimental models and contribute to improved strategies for the investigation and management of benzimidazole resistance in H. contortus.

The chlorine industry is currently characterized by linear material flows arising, among others, from difficulties in handling, storage, and transport of chlorine (Cl2) and hydrogen chloride (HCl). This limits the needed rethinking of processes towards a more sustainable approach focusing on circularity and resource efficiency. Herein, the potentials of bichlorides and polychlorides as alternative chemical platforms for HCl and Cl2 were investigated to valorize industrial side streams and support a more sustainable chlorine industry. Ammonium-based poly(hydrogen chloride) chlorates, so-called bichlorides, were introduced as stable, easy to handle HCl storage systems with significantly reduced vapor pressures. Among the investigated compounds, triethylmethylammonium bichloride ([NEt3Me][Cl(HCl)n]) was identified as promising candidate, reversibly binding up to n = 2.5 equivalents of HCl under ambient conditions. Beyond storage, the bichloride can be directly used as reagent, increasing process safety by shifting, e.g., the hydrochlorination of acetylene to vinyl chloride from the gas to the liquid phase. In combination with palladium(II)chloride, a highly active and stable catalytic system was obtained as viable alternative to currently used toxic and environmentally harmful mercury(II)chloride. Furthermore, technologies of Cl2 recovery have been investigated. The bichloride enables the efficient electrochemical regeneration of Cl2 from HCl in form of the corresponding polychloride. Using a simple undivided cell setup, no parasitic side reactions were observed overcoming difficulties associated with the electrolysis of neat HCl or hydrochloric acid. Complementarily, ion exchange resins providing ammonium chloride functions have been introduced as selective adsorber materials reversibly binding Cl2 under the formation of polymer-based polychlorides. Cl2 can be efficiently recovered from tail and waste gas streams by also enabling its upcycling to base chemicals like 1,2-dichloroethane or phosgene. In this way, the further use of otherwise downgraded Cl2 can be realized as an energy- and resource-efficient alternative to current performed neutralization processes. Overall, the presented concepts demonstrate how rethinking Cl2 chemistry through circular process design could enhance safety, resource efficiency, and sustainability in the chemical industry.

Die vorliegende Dissertation untersucht die Darstellung und Bewertung des Chinesischen im deutschsprachigen wissenschaftlichen Diskurs vom 17. bis zum 19. Jahrhundert und analysiert, in welchem Sinne die Sprache innerhalb der westlichen Grammatik- und Sprachtypologietradition als ein sprachwissenschaftlicher Sonderfall („schwarzes Schaf“) wahrgenommen wurde. Im Zentrum steht die Frage, wie die strukturellen Besonderheiten des Chinesischen – insbesondere sein isolierender Sprachbau – zur Anpassung und Erweiterung bestehender grammatischer und typologischer Konzepte beitrugen.

Die Analyse zeigt, dass die Wahrnehmung einer als paradox empfundenen Konstellation – einer vergleichsweise einfachen äußeren Sprachstruktur bei zugleich anerkannten kulturellen und geistigen Leistungen Chinas – maßgeblich die theoretischen Bemühungen beeinflusste, das Chinesische nicht als form- oder grammatiklos zu klassifizieren. Diese Spannung erforderte eine Neubewertung der Einordnung des Chinesischen innerhalb der etablierten Modelle der griechisch-lateinischen Grammatik und der vergleichenden Sprachwissenschaft und begünstigte die Entwicklung nicht-morphophonologischer, zunehmend verinnerlichter Erklärungsansätze.

Die Arbeit gliedert sich in sechs Teile: Nach einer einleitenden Gegenstandsbestimmung und einem Forschungsüberblick werden die Wortartenklassifizierung der klassischen chinesischen Philologie, die philologischen Grammatiken des 18. und 19. Jahrhunderts sowie die linguistischen und sprachtypologischen Charakterisierungen des Chinesischen im 19. Jahrhundert systematisch untersucht.

Zur theoretischen Einordnung der Befunde greift die Dissertation auf Newmeyers Unterscheidung zwischen formalen und funktionalen Erklärungsansätzen zurück. In wissenschaftsgeschichtlicher Perspektive zeigt sich, dass die Beschäftigung mit dem Chinesischen wiederholt zwischen strukturell-formalen und funktional, psychologisch bzw. kognitiv begründeten Zugängen oszillierte. Anstatt die Frage nach der „Grammatiklosigkeit“ des Chinesischen dichotom zu behandeln, wird deutlich, dass die entsprechenden Debatten eine Verschiebung und Erweiterung des Grammatikbegriffs widerspiegeln. Der scheinbare Widerspruch zwischen der Negation von Grammatik und ihrer impliziten Begründung erweist sich damit als perspektivisch bedingt und als Ausdruck unterschiedlicher, historisch situierter Versuche, die sprachliche Eigenart des Chinesischen innerhalb der jeweiligen theoretischen Rahmenbedingungen zu erfassen.

This thesis presents the experimental characterization of a dinuclear spin-crossover (SCO) molecule and compares it to its mononuclear parent complex. For the first time, the dinuclear molecule was fabricated as a thin film using the pulsed layer injection (PLI) technique. To investigate the SCO-properties of the thin-film and bulk samples, X-ray absorption spectroscopy (XAS), far-infrared spectroscopy (FIR), and electron paramagnetic resonance (EPR) spectroscopy were employed. The scope of this thesis was to assess the feasibility of fabricating a thin film of a dinuclear SCO molecule on highly oriented pyrolytic graphite (HOPG) using PLI, while preserving its SCO capabilities, and to characterize the molecule. In the first part of the thesis, dinuclear thin film samples were fabricated using PLI, along with dropcast and bulk-powder samples of the same molecule, and characterized by XAS. The thermal and light-induced SCO characteristics were compared to those of the parent complex. The second part of the thesis investigates the vibrational and electronic structures of both SCO molecules using FIR and EPR spectroscopy. With the aid of density functional theory (DFT), individual molecular vibrations were assigned to the SCO behavior of each molecule under temperature change and light irradiation. Although the theoretical modeling of the EPR data is still ongoing, the results presented here provide initial insights into the electronic structure of both molecules under light irradiation at 10 K.

The Late Eocene to Early Oligocene transition marks a major reorganization of the Earth system characterized by substantial cooling, the emplacement of permanent Antarctic glacia- tion and fundamental changes in ocean circulation. Yet, the mechanisms driving this shift are still a matter of contention. Marine diatoms are central to this transition because their record suggests a major increase in diversity and productivity during this interval. Because modern diatoms are key agents of the biological carbon pump, evaluating their response to climatic perturbations during the Eocene/Oligocene transition is critical, not only for better understanding the nature of this transition but also for predicting plankton evolution under future climate scenarios. However, the diatom record remains underexplored and has often been limited to non-quantitative biostratigraphic compilations that overlook true diversity. Consequently, changes in diatom community composition, turnover dynamics and productivity trends during the Eocene/Oligocene transition are poorly constrained. This thesis addresses these gaps through three major contributions.

The first contribution reconstructs Southern Ocean diatom diversity and community dynamics using quantitative, species-level surveys from four sites spanning the Atlantic and Indian Ocean sectors (DSDP Site 511; ODP Sites 1090, 689, 748). This work addresses the limitations of earlier syntheses by capturing the full assemblage rather than biostratigraphic compilations. My results reveal a previously unknown dimension of Southern Ocean diatoms, indicating that Late Eocene and Early Oligocene communities were at least five times more diverse and structurally complex than previously documented. The analyses identify two intervals of substantial reorganization: one across the Middle-to-Late Eocene transition (38- 36 Ma) and a second around the Eocene/Oligocene boundary (∼34 Ma). Diversity dynamics analyses further reveal a distinct extinction event in the earliest Oligocene, at∼33 Ma, likely associated with changes in sea-surface conditions, including sea-surface cooling.

The second contribution examines Southern Ocean productivity dynamics across the same interval by separating the signals of diatoms and radiolarians. Instead of relying on bulk opal measurements alone, this work integrates group-specific abundances and accumulation rates with diversity reconstructions. The results indicate a strong rise in diatom abundance accompanied by pronounced shifts in diatom diversity structure across the Late Eocene. These coupled patterns are consistent with an ecological and productivity reorganization linked to the strengthening of circum-Antarctic current in the Late Eocene. Furthermore, this work suggests that diatom expansion, and the resulting increase in export efficiency, may have been part of the mechanistic mosaic contributing to the Late Eocene cooling, and to the threshold response at the Eocene/Oligocene boundary as Earth system shifted into an icehouse climate state. The third contribution extends the spatial scope of the thesis to the equatorial Atlantic (DSDP Site 366, NW Africa). While the first two manuscripts of this work reveal new di- mensions of the high-latitude diatom diversity and productivity responses to polar cooling, the propagation of the environmental signals into tropical systems remains critical for con- straining the extent of Eocene/Oligocene environmental change. By integrating species-level diversity with productivity data, this contribution documents a fundamental reorganization of equatorial Atlantic assemblages. A key result is a sharp community transition and extinction event at∼33.5 Ma, consistent with a threshold response to increasing thermal stratification in the tropical Atlantic. Moreover, this contribution reveals strong parallels in the timing and shape of diatom diversity profiles between the tropical Atlantic and the high southern Atlantic across the Eocene/Oligocene transition. In summary, this work extends our understanding of diatom evolution across one of the most enigmatic climatic state shifts in Earth history. Although the Eocene/Oligocene transi- tion is a recognized turning point in plankton evolution, especially for diatoms, prior evidence has often relied on diversity-incomplete biostratigraphic records. Here, by combining ex- haustive quantitative species surveys with productivity reconstructions, I provide one of the most complete views currently available of diatom diversity and productivity across both Southern Ocean and equatorial Atlantic settings. This integrated perspective refines the timing of diatom responses to environmental forcing during the Eocene/Oligocene transition. Ultimately, this study deepens our understanding of the empirical links between the geosphere and biosphere, offering critical insights into plankton ecosystem dynamics in the warmer world projected for our future.

Cell division is a process fundamental to life. While the genetic material is duplicated in mitosis, the division and separation of cellular organelles, cytoplasm, and surrounding membrane during cytokinesis is just as important. Cytokinesis is initiated during mitotic anaphase, by factors translocating to the midzone of the mitotic microtubule central spindle. It begins with the assembly of a contractile furrow at the division plane, which ingresses inwards to separate the two daughter cells. The central spindle transforms into the intercellular bridge, an extremely dense microtubule bundle connecting the dividing cells. In its center lies the midbody, an organelle discovered by W. Flemming in 1891, which stabilizes the intercellular bridge. In the last step of cytokinesis, the intercellular bridge is severed during abscission, marking the physical separation of the daughter cells. The main players that execute the ingression of the cleavage furrow, the formation of the midbody in the intercellular bridge, and finally the abscission of the dividing cells, have long been identified. However, the temporal progression of their nanoscale organization and redistribution during cytokinesis remains unclear, as cytokinesis is a complex three-dimensional process exerted at various speeds. While ingression of the cleavage furrow is relatively fast, the final remodeling of the intercellular bridge before abscission can take hours depending on the cell type. Additionally, remodeling has to be studied in three spatial dimensions, which is difficult to achieve at high spatiotemporal resolution, especially below the diffraction limit of light. In this thesis, I describe the development of a pipeline for the assembly of a multidimensional atlas of mammalian cytokinesis. I combined fast volumetric imaging using lattice light-sheet microscopy and super-resolution expansion microscopy (ExM) to assemble a multiplexed dynamic representation of several cytokinetic stakeholders. I prove that ExM is an ideal tool to study the organization of the protein-dense midbody region in cytokinesis, while providing increased resolution and allowing multiplexing of targets. Furthermore, I use computational modeling of cytokinesis based on the septin and microtubule cytoskeleton as markers to register and correlate multiple cytokinetic factors along a pseudotime axis. Pseudotemporal modeling of the static ExM data allows the generation of a dynamic and sequential representation of cytokinesis. With the increased resolution of ExM, I discovered a new stage of late cytokinesis, termed the septin manchette stage. I show the importance of this stage for remodeling of the intercellular bridge before abscission, based on key cytokinetic factors, such as the centralspindlin complex, actomyosin, and the endosomal sorting complex required for transport (ESCRT)-machinery. Finally, by correlating all information, I assemble an atlas of cytokinesis, providing unprecedented three-dimensional, dynamic and contextual insights into mammalian cytokinesis at high-resolution and in pseudotime.

Ribosomes are essential macromolecular machines responsible for protein synthesis in both humans and bacteria, governing the viability of cells across the superkingdoms. Comprising intricate assemblies of ribosomal RNA and ribosomal proteins, ribosomes form through a coordinated, stepwise maturation process involving numerous assembly factors. Eukaryotic ribosome assembly is inherently more complex due to the increased size of the ribosome and the requirement for transport across the nucleolar membrane, a process in which ATPases play a critical role. In both prokaryotes and eukaryotes, ribosomes comprise a small and a large subunit; the large subunit is designated 50S in bacteria and 60S in eukaryotes. The bacterial ribosome is a well-validated target for antibiotic development. Existing antibiotics primarily act by inhibiting the function of the mature ribosome. However, resistance mechanisms have now evolved against all classes currently in clinical use. In the face of rapid emergence of resistance mechanisms to antibiotics, and a dearth of novel antibiotic classes being produced, there is a great unmet clinical need for novel antibiotic classes and structures. Cancer remains a leading cause of mortality worldwide, accounting for a substantial proportion of global deaths and representing a major public health burden. Cancer cells rely on ribosomal maturation for their proliferation and survival, and a long history of evidence implicates eukaryotic ribosomal dysregulation in tumor progression along with cancer cell proliferation and treatment resistance. Indeed, a number of current cancer therapeutics have retrospectively been found to impair ribosome biogenesis. The human ATPase MIDASIN (MDN1) crucial to 60S ribosomal assembly, is overexpressed in breast cancer and implicated in hormonal cancer therapy resistance. This work leverages recently published atomistic models of key ribosomal assembly intermediates and factors. One characterizes a set of assembly intermediate structures along the bacterial 50S subunit assembly pathway, and the other depicts a crucial interaction between two human 60S assembly factors. These structural insights provide the foundation for computer-aided drug design campaigns that aim to develop a novel antibiotic and a new anticancer therapeutic, respectively, by selectively disrupting species-specific ribosomal assembly pathways. Cryo-Electron Microscopy models of the 50S ribosomal subunit in various stages of its assembly provide unprecedented insight into the molecular mechanisms governing bacterial ribosomal assembly, highlighting opportunities for therapeutic intervention. The bacterial ribosomal protein bL17 has been identified as a promising pharmacological target via both genetic knockout experiments and computational investigations. Previous work has already identified a series of potential bL17 binding compounds. Anticancer strategies targeting human ribosomal assembly have remained underexplored, in part due to the complexity of eukaryotic ribosome biogenesis, which is not yet fully understood. The potential of MDN1 as a pharmacological target to disrupt ribosomal assembly and thereby limit cell viability has been demonstrated in yeast. While MDN1 has been shown to play an essential role in ribosome biogenesis in human cells, its potential as a pharmacological target for anticancer therapy remains unvalidated, and no ligands have been specifically developed against human MDN1. The determination of an X-ray structure of human MDN1 in complex with its ribosomal binding partner, NLE1, represents a significant advance, providing mechanistic insight and a structural framework for rational drug design. This work begins with the biophysical characterization of the binding of an initial hit compound, A14, to bL17, and determination of the in vivo inhibitory effect of A14 on E. coli cell growth. These experimental data informed the computational characterization of the A14 binding mode to bL17 via static and dynamic methods. Ligand-based analysis of A14 enabled its computational derivatization into a subsequent compound series, termed the C series. Of these, compound C07 showed an inhibitory effect on E. coli 50S subunit assembly in vitro. In silico molecular modeling of the putative binding mode of C07 within the predicted binding site of bL17 enabled the generation of a preliminary structure-activity-relationship model characterizing the potential contribution of compound moieties and bL17 protein residues to bL17 affinity and 50S assembly inhibition. This structure-activity-relationship model further guided the computational generation of the D series of compounds. Thus, iterative cycles of ligand-based optimization guided by the results of experimental validation ultimately yielded a series of antibiotic scaffold candidates. In parallel, the X-ray crystallographic model capturing the interaction between the two human ribosomal assembly factors MDN1 and NLE1 provided a template for design of inhibitors targeting this protein-protein interaction. The unliganded surface of the MDN1 MIDAS domain was analyzed via static and dynamic structure-based methods to generate a structure-based 3D pharmacophore for use in virtual screening. The resulting hit compounds were characterized extensively via in vitro and in vivo methods. The results show that compound R06 is capable of inhibiting the MDN1-NLE1 interaction in vitro, leading to 60S assembly defects and cancer cell lethality in vivo. The putative binding mode of R06 was characterized via molecular modeling, to generate a hypothesis on the molecular basis of its demonstrated activity.

Wie können sich Menschen in einer zunehmend diversen und stratifizierten Gesellschaft begegnen? Franziska Seise adressiert aus einer Perspektive der Psychologischen Anthropologie die Herausforderungen und (Un-)Möglichkeiten in Patenschaften mit geflüchteten Kindern. Dabei verknüpft sie das ambivalente gesellschaftliche Klima eines restriktiven Migrationsregimes mit der prekären Engagementlandschaft Deutschlands sowie den Anstrengungen, die sich entlang divergierender Erwartungen, Erziehungsideale und Verhaltensmaximen entfalten können. Als ungewöhnliche Beziehungskonstellation erfordern Patenschaften eine besondere Form der Affektbewältigung, die kontinuierlich der gemeinsamen Reflexion bedarf.

This thesis explores the further development and application of ultrafast soft Xray absorption spectroscopy (XAS) at the nitrogen K-edge to resolve fundamental molecular dynamics in both the gas and liquid phases. A laboratory-based high-order harmonic generation (HHG) source, driven by infrared pulses (centered around 1800 nm) produced by a Ti:Sa laser amplifier coupled with an optical parametric amplifier, was used to produce broadband soft X-ray pulses covering the energy range between 250 eV and 450 eV. The capabilities of this table-top setup for accessing ultrafast structural changes in molecules were first demonstrated by investigating the photodissociation and early conical intersection dynamics of gaseous nitrogen dioxide following single-photon excitation. The result highlights the sensitivity of transient X-ray absorption spectroscopy in probing the wave packet motion near the conical intersection. The research was further extended to the condensed phase using a novel liquid flat-jet system to study the charge transfer process of the metal-organic complex iron[II] 2,2’-bipyridine in the solution phase. By probing at the nitrogen K-edge, this work provides the first femtosecond-resolved observation of the ligand’s local electronic environment during metal-to-ligand charge transfer (MLCT). The results uniquely benchmark the MLCT state signature both spectrally and temporally, offering new insights into the involved intermediate states that govern the efficiency of charge separation in transition metal complexes.

Die Dissertation untersucht die Werkhandlungen von Franz Erhard Walther mit einem Schwerpunkt auf den 1960er Jahren und entwickelt erstmals eine systematische Analyse ihrer choreografischen Organisation. Ausgangspunkt ist die Beobachtung, dass die Werkhandlungen zwar seit Jahrzehnten als zentraler Bestandteil von Walthers Œuvre rezipiert werden, ihre konkreten Bewegungsabläufe bislang jedoch nicht in ihren choreografischen Logiken untersucht wurden. Die Arbeit fragt danach, wie sich Objekt und Bewegung, Werk und Handlung, innerhalb der Werkhandlungen zueinander verhalten und was dies für die Publikumsbeteiligung bedeutet. Methodisch greift die Untersuchung auf den Choreografiebegriff zurück, verstanden als räumlich-zeitliche Organisation von Bewegungen auch jenseits von Tanz. Dieser Ansatz ermöglicht eine interdisziplinäre Perspektive zwischen Kunst- und Tanzwissenschaften und erlaubt es, Walthers Werkhandlungen sowohl formal zu analysieren als auch historisch zu kontextualisieren.

Fungicides and human antimicrobials play a crucial role in controlling diseases in agriculture and medicine but are often assessed as individual chemicals, ignoring real-world pollutant mixtures. This study examines their effects, alone and in combination with other pollutants, on soil microbes and functions.

We first assessed the growth responses of 31 fungal species from a nature-protected grassland area in Brandenburg, Germany to two fungicides with different modes of action. The study highlights the risk posed to soil fungi by fungicide contamination of non-target areas, particularly those neighboring croplands. The sensitivity of fungi co-occurring in the same soil varied significantly at the phylum level, with Basidiomycota being the most affected. Contrary to expectations, slow-growing fungi were not more tolerant to fungicides; rather, phylogenetic relationships better explained species-specific responses.

From this core set of fungi, we selected representative species belonging to three major phyla (Ascomycota, Mucoromycota and Basidiomycota). We examined how common fungicide application strategies aimed at delaying fungicide resistance influenced soil functions under varying fungal diversity. The study shows that repeated applications of individual fungicides had distinct inhibitory effects, but the strongest negative impact was observed when both fungicides were simultaneously applied. This emphasizes the negative side effects of the established and recommended practice to combat pathogen resistance. Contrary to our expectation, higher fungal diversity did not significantly enhance soil function under fungicide stress, suggesting that diversity alone offers limited support in maintaining soil processes.

We also explored the combined effects of pharmaceuticals used during the COVID-19 pandemic and microplastics from FFP2 masks on soil processes. We incorporated null models to analyze potential interactions among these pollutants. We found that combined treatments had a more pronounced impact on soil respiration and Fluorescein Diacetate (FDA) hydrolysis compared to the individual treatments. Pharmaceutical-microplastic mixtures intensified negative effects, highlighting the potential risks of pandemic-related waste. Moreover, elevated concentrations of pharmaceuticals in soil may intensify interactions, whether synergistic or antagonistic. Our findings emphasize the complex interactions between antimicrobials and other environmental pollutants, demonstrating that their combined effects can be more severe than those of individual compounds. This research underscores the need for holistic environmental risk assessments, aligning with the One Health approach.