Polymodal faulting, which comprises three or more coeval fault sets, has been documented from centimeter to kilometer scale in nature. Differing from previously well-known conjugate, or bimodal, fault patterns under biaxial or plane strain, the polymodal faulting phenomenon is considered to represent triaxial deformation or strain (e.g., constriction and flattening strain). Triaxial tectonic regimes can take place variably in obliquely divergent, transcurrent, and convergent settings, allowing the coeval existence of different tectonic regimes (e.g., thrust, strike-slip, and normal faulting). The classical and widely accepted Mohr-Coulomb failure criterion can predict the orientation of conjugate fault planes parallel to (i.e., contain) the direction of the intermediate stress under plane strain, whereas polymodal fault patterns forming under triaxial deformation cannot be explained with fault orientations oblique to the direction of the intermediate principal stress (σ2). Aiming to understand the evolution, geometry, and kinematics of polymodal faults, I use 3D scaled analogue and numerical modelling to generate triaxial strain fields under variable initial and boundary conditions to decode the mechanisms and mechanics of triaxial deformation. In the first step, I primarily investigate how rheology and strain rate control deformation localization, faulting regime, and pattern in brittle‐viscous crustal‐scale models under constriction strain. I perform triaxial analog experiments by varying strain rates (or extension velocity), where distributed longitudinal extension resulting in crustal thinning is accompanied by lateral shortening. I found the structural style of faults and the degree of localization as a function of strain rate. As strain rate (ė) decreases, (1) fault patterns change from conjugate sets of strike‐slip faults (ė > 3 × 10⁻⁴ s⁻¹) to sets of parallel oblique normal faults (ė = 0.3–3 × 10⁻⁴ s⁻¹) to horst‐and‐ graben system (ė < 0.3 × 10⁻⁴ s⁻¹); (2) The strain localization increases systematically and gradually. The former change in fault pattern is interpreted to be affected by the strain rate dependency of vertical coupling between the model upper crust and upper mantle, which controls spontaneous switching of principal stress axes. The latter change in strain localization is controlled by mechanical coupling between the upper and lower crust. Furthermore, many extensional systems often experience multiple phases of deformation; however, the spatial and temporal evolution of fault networks during triaxial and biaxial strain is still poorly understood. Benefiting from the first part of the work, which identifies the change in strain conditions from constriction to plane strain over strain rate, I also use a scaled analogue model to investigate fault geometry and activity across multiple phases of triaxial (constrictional) and biaxial (plane) strain by changing extension velocity to obtain time-dependent kinematic strain conditions. Our modelling results show that (1) when shifting from plane to constrictional strain, earlier developed normal faults are completely reactivated and new conjugate sets of oblique-slip faults form during the constrictional phase; (2) when shifting from constrictional to plane strain, conjugate sets of oblique-slip faults forming during constrictional strain are randomly abandoned or reactivated. New normal faults developed during plane strain cut across and link up earlier-phase faults. Kinematic interactions of fault networks between multiphase strains are identified by observing how perturbations in stress/strain domains control the geometry of new faults and mechanical obstacles hinder fault propagation. I further explore the relationship between principal stresses and polymodal fault orientation by means of 3D scaled numerical modelling. Our models demonstrate that triaxial deformation can be accommodated by the simultaneous development of faults with different trends and partitioned into one more faulting regime. Additionally, our models can explain fault distribution with respect to the principal stress. The modelling results show good similarity with the natural prototypes at various backgrounds. In regions under a constrictional deformation field, for example, Tibet, Anatolia, and the Friulian-Venetian basin, as well as in regions under a flattening strain, for example, northern Tibet and the Barents Sea, our modelling results provide new implications for fault geometry, fault kinematics, and stress distribution. Moreover, our models with multiphase triaxial and biaxial strain can re-interpret tectonic evolution in the Aegean and Barents Seas.

Racism is a structural force that organizes daily life, shapes access to resources and opportunity, and produces cumulative impacts on health across the life course. Health disparities between racially privileged and racially marginalized groups are not due to innate genetic differences; they emerge through processes that are both chronic and systematic, rooted in long-standing structures of marginalization. Despite growing recognition of racism’s health impacts, research often treats race as a static covariate and fails to interrogate racism as a dynamic, cumulative, and upstream driver of unequal health outcomes—particularly in childhood and adolescence. Few studies examine racism as a structural force that shapes mental health trajectories over time. Even fewer integrate children’s lived experiences of racialization with epigenetic data. These gaps are especially stark in Germany, where historical legacies limit the direct study of racism’s impact on development and health. This cumulative dissertation addresses these gaps by advancing and applying a race-critical biosocial framework. While biosocial approaches are well suited to explore how social conditions shape health, they have often fallen short in addressing the structural dimensions of racism. A race-critical biosocial framework offers tools to trace how racism operates and becomes embodied, shaping children’s and adolescents’ mental health. Three peer-reviewed papers structure and guide this inquiry. Paper 1 advances a race-critical biosocial framework that integrates critical race theory, developmental science, and sociogenomics, with particular attention to Germany’s scientific and sociopolitical context. Paper 2 applies this framework in the German context through communities-based qualitative research with 29 Black families. Focus group findings highlight racism as a chronic, multisite stressor that shapes family health, children’s mental health, identity development, and coping strategies. Paper 3 extends the race-critical biosocial framework to U.S. longitudinal data (N = 4,898; DNA methylation data N = 2,039), operationalizing racism through self-identified race/ethnicity, neighborhood segregation, and skin tone. Findings show that racially marginalized children exhibit higher baseline levels of internalizing and externalizing behaviors in childhood, as well as accelerated epigenetic biological aging during adolescence, with mental health and biological aging progressing in parallel. Together, the three papers provide conceptual, qualitative, and quantitative evidence that racism is a biosocial health risk. It structures children’s environments from birth, becomes embodied through stress-related mechanisms, and contributes to early mental health disparities. The dissertation highlights the urgent need for child-centered, intersectional, and longitudinal measures of racialization in both Germany and the U.S., and calls for co-designed, communities-led biosocial research. By showing how racism “gets under the skin,” it advances a race-critical biosocial agenda for public health and developmental science.

Progeroid syndromes are a heterogeneous group of rare genetic diseases characterized by a prematurely aged appearance. They are caused by pathogenic variants in various genes, including those encoding DNA repair enzymes and components of the extracellular matrix (ECM). Additionally, alterations in gene expression can also contribute to the development of these syndromes. Within the scope of this dissertation, two progeroid syndromes were characterized. First, pathogenic variants in SUPT7L were identified as the genetic cause of a new progeroid syndrome. Second, further insights into the pathomechanism of ARCL2A were obtained. One complex regulating gene expression is the transcriptional coactivator complex STAGA. Loss-of-function variants in SUPT7L, encoding a subunit of STAGA, cause a so far undescribed clinical syndrome with a progeroid appearance, developmental delay, intellectual disability and a generalized lipodystrophy. Loss of SUPT7L presumably leads to reduced stability of the entire complex, decreased expression of c-MYC- and p53-dependent genes. It also results in reduced DNA repair and subsequent accumulation of DNA damage in primary dermal fibroblasts and genome-edited HeLa cells. Moreover, evidence suggests changes of the ECM, a common feature in other progeroid syndromes such as autosomal recessive cutis laxa type 2A (ARCL2A). ARCL2A is a congenital disorder of glycosylation (CDG) characterized by connective tissue weakness and brain abnormalities. Its molecular basis are loss-of-function variants in ATP6V0A2, encoding the V0a2 subunit of the vacuolar (v)-ATPase. This subunit determines the subcellular localization of the multiprotein complex and forms the proton channel. To analyze the underlying mechanisms of ARCL2A, two mouse models were generated. A knockout (Atp6v0a2-/-) leading to absence of Atpv0a2 and a knock-in (Atp6v0a2RQ/RQ) model, carrying the p.R755Q variant, which selectively blocks proton transport. These mouse models exhibited structural aberrations of the dermis, reduced secretion of ECM proteins and altered glycosylation. However, the O-glycosylation defects appeared to be more relevant for the ARCL2A pathomechanism. Reduced O-mannosylation of ɑ-dystroglycan impairs cell-matrix interaction, leading to a secondary dystroglycanopathy involving abnormal migration of cortical neurons. Furthermore, enhanced core fucosylation in skin and murine embryonic fibroblasts (MEF) correlated with an elevated trans-Golgi pH and a delay in the intracellular vesicle transport. In both mouse models, impaired Golgi-derived acrosome formation and altered O-glycosylation lead to a globozoospermia, a previously undescribed symptom of ARCL2A. Thus, the pathomechanism of ARC2A is determined by an interplay between an elevated Golgi pH and alterations in intracellular vesicle trafficking.

Mechanosensation is a process by which nerves encode physical stimuli such as cotton swab or pinprick into electrical signals that can be understood by the nervous system. In this way, organisms can gain crucial information about the environment by means of touch sensation and avoid harmful influences thanks to nociceptive pain. But what is the molecular basis of mechanosensation, allowing this process to occur? And what happens if its functioning is disrupted? I tackle those questions in my doctoral thesis, investigating a role of newly described mechanosensitive channel and discussing tactile phenotypes in autism spectrum disorders (ASDs). This work is mostly an electrophysiological study of cutaneous mechanoreceptors, studied with the use of ex vivo mouse skin-nerve preparation. Focus is on c-fibers, small diameter unmyelinated sensory neurons, involved in relying nociceptive cues. In the first part of my doctoral project I investigate the role of Elkin1 (TMEM87a) channel in the nociceptor physiology. Results show that Elkin1-/- knockout mice exhibit lowered mechanical sensitivity when tested in behavioral assays using a hindpaw stimulation. Electron microscopy showed no structural changes in the somatosensory system of mutant animals, albeit there are changes in the physiology of sensory afferents. Extracellular recordings from single nerve fibers, made during simultaneous mechanical stimulation of receptors located in the skin, showed a changed pattern of activity in response to mechanical stimulation with faster adaptation in fibers from Elkin1-/- animals, but only when a specific protocol of stimulation was used. Furthermore, I explore the relationship of Elkin1 with Piezo2 mechanosensitive channel by studying double knockout animals. Effect of deleting both protein seem to have greater effect on dampening response to mechanical stimuli than removing any one of them separately. On the other hand, introducing human point mutation into mouse genome slightly strengthen the response. Overall, Elkin1 is a novel mechanosensory protein presumably required mostly for light touch, as changes in functioning of c-fibres point toward minor involvement in nociception. Sense of touch is also critically important for proper development. It constitutes the most primal form of communication between an infant and a parent, building foundation for more advanced social skills. Tactile-related impairments observed in toddlers pose a strong predictor of core autistic symptoms later in life and sensory processing disturbances belong to the most replicable symptoms emerging early in the diagnosis of ASDs. Modified touch perception phenotype observed in human subjects is replicated in animal models. Global knockout of 4E-BP1, the downstream effector of mTOR signalling pathway affected in some ASDs forms, was shown to be a source of mechanical hypersensitivity with enhanced nociception in mice. However, my results on the specific involvement of this phenomenon in the peripheral sensory neurons did not show any positive results. My findings, both of electrophysiological study and behavioral assessment, indicate that mechanical hypersensitivity observed in the model of 4E-BP1 deletion ca not be explained by differences in the physiology of cutaneous nociceptors.

Two-dimensional (2D) materials exhibit unique physical and chemical properties that make them promising candidates for electronic, optoelectronic, and energy-related applications. However, the limited tunability of pristine 2D materials restricts their broader practical use. This work presents a series of computational studies focused on tailoring the structural, electronic, optical, magnetic, and catalytic properties of 2D materials through functionalization and engineering strategies, including defect engineering, doping, heterostructure formation, molecular modification, and strain or pressure. The results demonstrate that these approaches effectively modulate key material properties such as band structure, charge transfer, excitonic behavior, magnetic ordering, and catalytic performance. Overall, this study provides theoretical insight and design guidelines for the rational tuning of 2D materials toward advanced device and energy applications.

This thesis focuses on the exploration of the metabolomics approach as a guided tool in the field of anti-doping by defining a workflow based on the synergy between High-Resolution Mass Spectrometry and chemometric tools.

First, the optimization of a low-energy electron ionization source to maximize the formation of molecular ion and minimize the fragmentation degree of steroid pathways, preserving the specific fragmentation pathway of the steroids considered and increasing the m/z coverage range. To this end, the effects of electron energy, emission current and source temperature on steroid fragmentation pathways were studied by performing full factorial experimental designs, using steroid reference materials chosen to cover the entire urinary steroid profile.

Second, the development and validation of systematic metabolomics workflows to reduce the time and resources required to identify direct drug metabolites for GCHRMS. To do so, the administration of 7-keto-DHEA was studied as a Proof-of-Concept to highlight the strong synergy between high-resolution mass spectrometry and chemometric tools for early detection of drug metabolites in anti-doping. A comparison of the most significant features with the spectra library validated the proposed metabolomics approach, further supported by existing data in the literature.

Third, extension of the previously proposed workflow on GCHRMS data to LCHRMS data, development and validation. The primary differences between the two workflows lie in the method validation, sample analysis processes, including preparation and acquisition, as well as in the raw data preprocessing steps. This knowledge gives the opportunity to gain insight into all possible metabolic changes, regardless of whether it is the formation of new compounds or the reduction of compounds. In contrast, the metabolite-focused approach generally reduces the scope of investigation to the formation of metabolites from the parent molecule, thus losing the response that other endogenous compounds might have as a result of its intake.

Fourth, application of the developed workflow for the investigation of the physiological and post training effects of ecdisteroid supplementation on the human serum metabolome. These outcomes elucidates the effectiveness of a metabolomics-based approach in detecting specific trends related to the intake of performance-enhancing substances that would otherwise remain undetected through traditional analytical methods or be masked by physiological changes.

The results presented in this thesis are of relevance for a more depth understanding of the complex relationships between different steroids, which may not be apparent when examining individual steroids in isolation, and in the identification of patterns or combinations of steroids that may discover new biomarkers for disease diagnosis, prognosis, or monitoring. This is a step forward in the metabolic characterization of different physio-pathological conditions that allow for the personalization of treatment strategies and optimization of individual performance outcomes. This personalized treatment enhances the value of the proposed metabolomics approach, making it beneficial not only for improving sports performance, but also in the clinical setting, where targeted supplementation can promote better health and recovery.

This dissertation has explored the development and application of black phosphorus (BP) nanomaterials through sustainable synthesis methods, aiming to unlock their potential in biomedicine and environmental remediation. The research focused on three interconnected goals: covalent functionalization of BP nanoflakes for biomedical applications, enhancement of mechanochemical synthesis for sustainable BP production, and application of mechanochemically derived BP-polyglycerol (BP-PG) nanomaterials in environmental remediation. In the first project of the thesis, a one-pot covalent functionalization method was successfully developed for exfoliated BP nanoflakes using an anionic ring-opening polymerization of glycidol. This innovative approach resulted in the formation of a BP-PG nanohybrid with high amphiphilicity, significantly enhancing its aqueous dispersibility and biocompatibility. The functionalized BP-PG demonstrated efficacy in near-infrared-responsive drug delivery against A549 lung carcinoma, MCF-7 breast cancer, and HeLa cervical cancer cell lines. These findings showcase the potential of BP-PG as a promising candidate for a broad range of biomedical applications, particularly in targeted drug delivery systems where hydrophilicity and biocompatibility are crucial. The second project addressed the challenges associated with the practical application of BP by optimizing mechanochemical synthesis methods. By modifying the ball-milling medium to enhance mass transfer and kinetic energy distribution, the research introduced a novel design that improved the efficiency of mechanosynthesis. This advancement not only reduced production costs and time but also significantly improved product quality due to the enhanced transfer of mass and reagents within the ball-mill chambers. The mechanochemical approach circumvented the need for high temperatures, toxic solvents, and complex purification steps, aligning with global sustainability efforts and providing a scalable method for producing high-quality BP essential for real-world applications. In the third project of the thesis, the mechanochemically synthesized covalently functionalized BP-PG nanomaterials were applied to environmental remediation, specifically in the recovery of precious metals like gold from simulated electronic waste leachate. This work marked the first successful mechanochemical polymerization of glycidol into polyglycerol via a "grafting-from" technique. The resulting BP-PG nanomaterial exhibited a uniform amorphous structure with a high surface area, advantageous for interfacial reactions such as gold-ion reduction. Remarkably, BP-PG achieved gold recovery capacities exceeding three times its own weight and efficiently converted gold ions into polymer-stabilized gold nanoparticles. This highlights the significant impact of nanohybrid architecture on interfacial properties and underscores the potential of mechanochemically derived BP-PG in environmental applications. Collectively, this dissertation contributes to expanding the understanding and utility of BP nanomaterials by developing sustainable and environmentally friendly synthesis methods that facilitate large-scale production. By enhancing the functional properties of BP through covalent functionalization, the research has led to improved biocompatibility and aqueous dispersibility, critical for biomedical applications. Demonstrating the versatility of BP-PG nanohybrids in targeted drug delivery and efficient recovery of precious metals showcases their potential in diverse fields ranging from medicine to environmental science. Furthermore, the pioneering of new mechanochemical techniques that can be applied to other materials and processes promotes innovation in green chemistry. This work paves the way for future advancements in sustainable material science, emphasizing the importance of designing synthesis strategies that are not only efficient but also environmentally responsible. In conclusion, the advancements presented in this dissertation lay a solid foundation for the practical application of polyglycerol functionalized BP nanomaterials. By addressing key challenges in synthesis and functionalization, and by demonstrating significant applications in biomedicine and environmental remediation, this research contributes valuable insights to the field of nanotechnology. Future work can build upon these findings to explore additional applications, optimize material properties, and further integrate BP nanomaterials into commercial technologies.

Die vorliegende Habilitationsschrift behandelt die Bedeutung des schweren Thoraxtraumas im Rahmen der Polytraumaversorgung. Von hospitalisierten Verletzten hat knapp ein Drittel Thoraxverletzungen, bei Polytraumatisierten mehr als die Hälfte der Betroffenen schwere Thoraxverletzungen, die bis zu 25% der traumaassoziierten Mortalität verursachen. Es konnte die Komplexität der viel diskutierten Notfallthorakotomie im Rahmen der Traumareanimation gezeigt werden, dass auf Basis von Fallkodierungen erfasste Diagnosen automatisiert in korrespondierende Verletzungsschweregrade umgerechnet werden können, eine verspätete Stabilisierung instabiler knöcherner Thoraxverletzungen mit einem geringeren Ausmaß an Outcome-Verbesserungen assoziiert ist, als es von einer frühzeitigen Intervention erwartet wäre, dass nicht nur die Anzahl der frakturierten Rippen, sondern ebenso die Länge der Segmentverletzungen die resultierende Thoraxwandinstabilität beeinflussen und dass ein traumatisches ARDS eine vergleichbare Mortalität mit anderen Ätiologien hat, wobei eine ECMO-Therapie situativ sicher einsetzbar sein kann.

The presented work depicts an in-depth approach on how to reach confident mass spectrometric analysis of metabolites of metandienone by gas chromatography. Metandienone is an anabolic androgenic steroid and a commonly used doping substance. Therefore, anti-doping testing strives to uncover its illicit intake by the detection of metandienone and its metabolites in athletes’ samples. In the following, the focus is mainly set on a reliable identification of the A-ring reduced metabolite structures 17ξ-methyl-5ξ-androstane-3ξ,17ξ-diol, 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol and 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-1,13-dien-3α-ol in human urine samples in parallel. First of all, the synthesis of reference material and its structural characterization built the basis of these investigations. It found application in a study of mass spectrometric fragmentation of 17α-methyl-5ξ-androstane-3ξ,17β-diol and various isotopologues and enabled fundamental understanding on underlying fragment ion formation in electron ionization mass spectrometry. Further assessment of the analytical method was supported by the latter investigations and allowed developing a method for confident identification of the targeted analytes. Therefore, only chromatographic separation of inter alia diastereomeric molecule structures made it possible to overcome the encountered challenges of indistinguishable mass spectrometric signals. In the end, proof of concept was provided by the application of this method to an administration study with metandienone. Not only did it lead to the confident identification of known and unknown excreted metabolite structures but also gave a deeper insight into the human metabolism of anabolic androgenic steroids. Concluding, besides the support to maintain confidence in anti-doping analysis of metandienone this work generally contributes to the field of bioanalytics by highlighting the importance of integral understanding of the analytical conditions. In general, chemosynthetic knowhow was used to obtain reported reference material and corresponding isotopologues. Applied analytical techniques consist of nuclear magnetic resonance experiments, gas chromatography coupled to unit mass spectrometry, high-resolution mass spectrometry, and tandem mass spectrometry.

Awareness of escalating sustainability crises, including climate change, species extinction, and growing social injustice, evokes a wide range of emotions, often negative, in a growing number of people. Worry, anxiety, sadness, frustration, and anger are frequently reported, especially by young people. Consequently, the high relevance of emotions for effective sustainability education has long been acknowledged. At the same time, emotional competencies have received too little attention in prevailing competence models. Studies from educational practice also indicate that teachers often feel unqualified to deal with emotions. The frequent suppression of emotions that results from this can demonstrably contribute to learners feeling overwhelmed by sustainability issues and avoiding them. Against this background, this dissertation examines how human emotions, sustainability crises, and education interrelate. Specifically, it examines the questions of why emotion-sensitive sustainability education is necessary and how it could be realized. In order to answer these questions, it is first necessary to examine how emotions are addressed in the German education system. The current state of research indicates that emotions are in fact too strongly neglected, despite their high relevance for all forms of learning. A mixed-methods analysis of 422 German curricula confirms this hypothesis and shows that emotional competence (with the facets of emotion knowledge, emotion recognition, emotion expression, emotion regulation, and empathy) is insufficiently structurally anchored in the German school system (Study 1). At the same time, a latent class analysis of 3,000 young people and teachers shows how widespread feelings of hopelessness are among both educators and students (Study 2). This hopelessness, along with increasingly widespread worries, fears, and frustrations, can affect mental health. Using the same sample, multiple regression analysis shows that sustainability-related emotions are significantly stronger predictors of behavior than knowledge and attitudes and thus could be central drivers of the sustainability transformation (Study 3). A systematic review then examines the role of emotions in transformative sustainability learning and derives implications for educational practice and science. The review (n = 20) reveals that widespread negative emotions (e.g., frustration, sadness, guilt) are found particularly at the beginning of transformative learning processes. In contrast, predominantly positive emotions are found during social interactions (e.g., gratitude, fun) and when trying out new actions (e.g., satisfaction, pride). This suggests how learners’ emotionality may differ substantially depending on their learning phase and the didactics chosen (Study 4). The results of the four studies and the findings of the respective strands of research highlight an asymmetry: emotions are highly relevant when people engage with sustainability issues, but at the same time the German education system in general, and sustainability education in particular, still pays too little attention to emotions. For this reason, emotional competence is proposed as a competence concept for sustainability education. Using five competence facets and concrete examples, the usefulness of the concept for sustainability education is illustrated and general recommendations for science and practice are derived.

Neurons are highly polarized cells characterized by specific structural and functional regions. The soma, or cell body, serves as a primary site for protein synthesis, while synaptic terminals located at the ends of axons are responsible for synaptic transmission. The precise transport of presynaptic proteins from the soma to these terminals is vital for the development, maturation, and maintenance of synapses. Presynaptic precursor biogenesis is a fundamental process for synaptic function and plasticity; however, its molecular mechanisms remain incompletely understood. Our research identifies Rab2 and its effector RUND1 as key regulators of presynaptic precursor vesicle (PV) formation at the trans-Golgi network (TGN). Rab2, a small GTPase, coordinates the biogenesis, sorting, and maturation of vesicles carrying presynaptic proteins essential for synaptic vesicle (SV) recycling and active zone (AZ) organization. Loss of Rab2 results in the accumulation of synaptic material— including scaffold proteins, SV proteins, and lysosomal markers—within motoneuronal cell bodies in Drosophila larval ventral nerve cords (VNCs). This mislocalization depletes presynaptic protein levels at synaptic terminals, leading to impaired neurotransmission. Electron microscopy revealed that these aggregates likely correspond to Golgi-derived transport vesicles, suggesting that Rab2 is crucial for efficient precursor export. Our RNAi-mediated screen identified RUND1 as a critical Rab2 effector that regulates presynaptic protein sorting, maturation, and trafficking. The RUN domain of RUND1 facilitates interactions with Rab2 and other regulatory proteins, including ICA69, Trabuco, and Golgin104. ICA69, a Rab2 effector, participates in secretory vesicle biogenesis and synaptic organization, while Golgin104 (CCDC186) is implicated in vesicle tethering at the TGN. Notably, the loss of RUND1produces a phenotype reminiscent of Rab2 mutants, supporting its role in the same pathway of presynaptic precursors biogenesis. Interestingly, ultrastructural analysis of vesicles in rund1−/−mutant backgrounds revealed a striking increase in elongated and tubular structures. These vesicles exhibited two distinct populations: clear and dense-core vesicles, potentially indicating a disruption in fusion or maturation processes. The presence of these heterogeneous vesicle populations suggests that RUND1 is essential for the proper segregation and functional refinement of vesicles before their transport to synaptic terminals. Overall, our findings highlight the intricate regulation of presynaptic precursor trafficking by Rab2 and RUND1, reinforcing the importance of Golgi-associated sorting mechanisms in synaptic development and function. Disruptions in this pathway impair synaptic protein localization and neurotransmission, with potential implications for understanding synaptic disorders.

Deciphering the intricate cellular interactions within the bone marrow (BM) is crucial for understanding a wide range of multifactorial diseases in immunology, regenerative medicine, and BM biology. The intricate BM microenvironment, characterized by dynamic cell trafficking, production of immune cells and self-organized remodeling, constantly shapes osteoimmunological cell functions and their metabolic adaptations. This specific microenvironment is challenging to replicate in vitro or in silico. Current intravital optical imaging techniques can investigate cells within the complex BM microenvironment but are invasive or limited in observation time, depth, hindering long term investigation of bone regeneration or specific cellular niches. This dissertation presents three novel optical imaging technologies to satisfy the critical need for long-term, minimally invasive intravital microscopy of the BM: 1) a high-energy, high-repetition-rate 3-photon (3P) laser, enabling intravital visualization of plasma cell (PC) dynamics and antibody production capacity; 2) Limbostomy, a modular microendoscope for longitudinal in vivo imaging of deep femoral BM, facilitating quantification of cellular self-organization during bone healing; and 3) FLIMB, integrating microendoscopy with NAD(P)H-dependent fluorescence lifetime imaging (FLIM), enabling label-free metabolic imaging of myeloid cells in the living BM. These methods revealed an antiproportional correlation between PC motility and antibody production capacity; the chronicity of rapid vessel sprouting and subsequent reorganization into a confined network accompanied by myeloid interactions after bone injury; and metabolic heterogeneity among myeloid cells, indicating specific metabolic patterns linked to the activation of oxidative burst and phagocytic function. These innovations provide researchers with powerful tools to study complex cellular interactions in living bone marrow, develop therapeutic strategies and monitor drug responses, for example to improve bone regeneration, combat PC dysfunction and cancer, and fundamentally understand the interplay of cellular behaviour, microenvironment and disease progression in bone marrow.

Addressing open-ended questions, the dissertation undertakes a transdisciplinary mixed-method experiment to reconstruct historical LGBT epistemic frameworks in state-socialist East Central Europe. Its aim is twofold. First, it develops new methods—combining quantitative and qualitative, evidence-based research grounded in primary sources and the critical reinterpretation of secondary sources—to recover the operations of the socialist state through an imparative (non-comparative) analytical approach. Second, it demonstrates how such decolonized perspectives enable new interpretations of queer cultural artefacts situated within socialist social, cultural, and political fields. This approach makes it possible to identify a distinctive category of LGBT artefacts within state socialism: works that were non-political, non-identitarian, and non-activist, yet profoundly queer in their epistemic and aesthetic operations. Using the uniquely transparent queer oeuvre of Soviet-Hungarian transgender artist El Kazovszkij (1948, Leningrad – 2008, Budapest) as its point of departure, the project moves between micro- and macro-levels of inquiry. Zooming in on Kazovszkij’s corpus and zooming out to the broader social and political discourses that framed and integrated it, ranging from historical political, legal and social analysis to critical hermeneutics. Grounded in art-historical inquiry, the dissertation challenges dominant Western-centric narratives of global queer history by foregrounding the specificity and complexity of state-socialist queer epistemes. It enriches non-Western histories of twentieth-century LGBT cultures and contributes to post-socialist and post-colonial studies. Through its rigorous empirical methodological experimentation, the dissertation proposes a new model for conducting research in non-Western contexts on historically ambiguous subjects - particularly in cases where empirical evidence and primary sources are opaque, uncatalogued, or difficult to access.

The nuclear periphery including the nuclear lamina is one of the main nuclear sub-compartments that facilitate the complex yet dynamic chromatin organization in eukaryotes. The concept of plant lamina is relatively recent, as true lamin homologs are absent in plants, a thorough understanding of its functionality is not fully delved into. In Arabidopsis thaliana it has been shown previously that PWO1, an interactor of Polycomb repressive complex 2 (PRC2), collaborates with the nuclear lamina protein CRWN1 to mediate gene regulation. This study has demonstrated that the SWI/SNF chromatin remodeler subunit AtBAF60 interacts with PWO1 and CRWN1 by employing protein-protein interaction studies, gene expression analysis, and nuclear phenotype measurements using confocal microscopy. Transcriptome and genome-wide analyses coupled with immunocytochemical-high resolution microscopy studies have revealed the functional interplay between the interacting partners suggesting their role in stress responses and heterochromatin organization. In a nutshell, the present study discovered a novel interrelationship between SWI/SNF chromatin remodeler complex subunit AtBAF60 with the nuclear periphery and PWO1, thereby interconnecting three major players of gene regulation and chromatin organization in A. thaliana

The history of rare diseases remains largely unexplored, as their origins, prevalence, and social perception in past societies are poorly understood. Investigating rare diseases in archaeological and prehistoric contexts requires a clear definition, yet modern epidemiological criteria cannot be applied due to preservation issues and limited sample sizes. Genetically determined rare diseases caused by spontaneous mutations can be considered relatively stable over time, while multifactorial diseases must be interpreted within their specific archaeological context. Defining rare diseases as a group increases their visibility and relevance in archaeological research. Diagnosing rare diseases in skeletal remains is challenging due to incomplete preservation and the absence of laboratory data, making awareness of rare pathological features essential to avoid missed diagnoses. Standardized documentation and transparent data sharing are necessary to enable comparative studies beyond isolated case reports. The Digital Atlas of Ancient Rare Diseases (DAARD) provides a framework for publishing cases in accordance with FAIR principles, including clear documentation of sampling and analytical methods. The study of rare diseases in bioarchaeology allows, for the first time, the investigation of their long-term morphological and genetic development. This approach offers new insights into the medical and social history of rare diseases, supports their visibility, and fosters collaboration between researchers and patient communities.

Mehr als 5 % der globalen Bevölkerung leiden unter beeinträchtigenden Hörstörungen mit teils dramatischen physischen, psychosozialen und ökonomischen Auswirkungen. Studien zu Folge leiden allein in Deutschland etwa 14 Millionen Menschen unter einer Hörschädigung, eine erhöhte Lärmexposition wird als eine der Hauptursachen für diese Entwicklung verantwortlich gemacht. Die vorliegende Arbeit betrachtet eigene Studien zum kurzfristigen Zeitverlauf neuronaler pathophysiologischer Prozesse in der aufsteigenden Hörbahn. Die Ergebnisse zeigen, dass bereits im akuten Stadium nach einem lärminduzierten Hörverlust degenerative Prozesse und neuroplastische Veränderungen detektiert werden können. Direkt nach einem Lärmtrauma nehmen apoptotische Prozesse in den untersuchten neuronalen Strukturen des Hirnstamms und Mittelhirns zu und es resultiert eine Verringerung der Zelldichten in den untersuchten Regionen. Innerhalb eines Zeitraums von 2 Wochen findet eine signifikante Reduktion der Zelldichten im Hörnerven und zentralen Hörsystem bis zum primären auditorischen Cortex statt, wobei cochleäre und subcortikale Areale am stärksten betroffen sind. Apoptotische Zelltodmechanismen spielen hierbei eine entscheidende Rolle. Ein wiederholtes Lärmtrauma induziert wiederum zelluläre Pathologien insbesondere in höheren Verarbeitungsstrukturen des auditorischen Systems auf thalamischer und cortikaler Ebene sowie im ventralen Nucleus cochlearis des Hirnstamms. Unsere Untersuchungen zeigen, dass ein Schalltrauma direkte Auswirkungen auf basale neuronale Strukturen der aufsteigenden Hörbahn hat und exzitatorisch-toxische Prozesse induziert, eine initiale Protektion cortikaler Areale erfolgt möglicherweise aufgrund inhibitorischer neuronaler Projektionen. Die Daten lassen den Schluss zu, dass progressive degenerative Prozesse im auditorischen System aus einer direkten Überstimulation sowie als Folge neuronaler Deprivation aufgrund von Schädigungen in der Cochlea und im auditorischen Hirnstamm resultieren. Degenerative Mechanismen in höheren Strukturen eines vorgeschädigten Hörsystems bei erneuter Lärmexposition sollten eine zunehmende Beeinträchtigung komplexer Verarbeitung akustischer Informationen zur Folge haben. Diese Prozesse werden mittels objektiver klinischer Diagnostik nicht erfasst. Die Resultate sind von hoher klinischer Relevanz, da derzeit kein evidenzbasierter Ansatz zur Therapie lärminduzierter zentralnervöser Pathologien verfügbar ist und somit präventive, sowie akute regenerative Ansätze und eine prothetische Versorgung die aktuellen Behandlungsoptionen darstellen.

Despite their seemingly simple chemical composition, many molecular liquids exhibit complex behaviors arising from their intermolecular structure: while they seem disordered on the macroscale, they feature locally ordered environments on the microscopic scale. At interfaces with other substances, the liquid's organization is altered due to chemical interactions with the opposing substance and the interfacial geometry. The local interfacial structure of liquids determines key physicochemical properties, such as wettability and surface reactivity. When a liquid is further constrained by confining it to a nanoscopic space, they undergo additional structural perturbations, leading to the emergence of unique and exotic behaviors.

Characterizing the microscopic structure of molecular liquids and relating it to their macroscopic properties stands as a central challenge in chemical physics. Among the various experimental techniques employed to study the microscopic structure of liquids, spectroscopic methods sensitive to intra- and intermolecular vibrations of molecules have proven especially successful. However, interpreting experimental spectroscopic data in terms of molecular motion and structure is still not fully understood, as the high degree of collectivity in the dynamics of molecular liquids complicates the identification of spectral features with simple molecular mechanisms.

The present thesis contributes to this field by employing molecular modeling techniques that resolve the local liquid structure and dynamics, while establishing relations between modeling results and experimental observables through concepts from statistical mechanics. We focus on liquid water, whose hydrogen bond network is paradigmatic for the complex intermolecular structure of molecular liquids, and perfluorinated hydrocarbons, a synthetic organic liquid of industrial significance, and analyze how external constraints, in the form of single interfaces and nanoconfinement, alter their molecular structure. In the bulk phase, we illustrate how signatures of the highly collective vibrational behavior in the linear absorption spectrum of perfluorinated hydrocarbons can be interpreted with the help of different molecular modeling methods and establish a method to uncover the influence of varying conformational dynamics on vibrational line shapes. We then discuss the structure of water at the interface to air and fluorinated surfaces. There, anisotropic orientation of water molecules gives rise to local electric fields and specific vibrational signatures, which we contextualize with the available experimental data. Finally, we analyze the influence of geometric confinement on the hydrogen bond network of liquid water. We propose a decomposition of linear absorption spectra to distinguish between bulk, interfacial, and confinement effects, allowing us to identify signatures of long-range collectivity in the vibrations of nanoconfined water.

Auf gesellschaftlicher Ebene spielt Bildung in Deutschland eine wichtige Rolle bei der Reproduktion kultureller Normen und Werte. Aber auch auf individueller Ebene fördert sie die soziale Teilhabe und die Identitätsentwicklung. Trotz des Prinzips der Chancengleichheit bleibt der Bildungserfolg in Deutschland nach wie vor stark von der sozialen Herkunft und somit vom familiären Kontext abhängig. In dieser Dissertation wird das Zusammenspiel verschiedener Aspekte des familiären Zusammenlebens und ihr Einfl uss auf die Bildung von Kindern untersucht. Die Analysen basieren auf Daten der Startkohorte 3 (SC3) des Nationalen Bildungspanels (NEPS) sowie des Beziehungs- und Familienpanels (pairfam). Im Fokus stehen Kinder, die mindestens die vierte und höchstens die zehnte Klasse besuchen. Die Ergebnisse zeigen, dass die Qualität der innerfamiliären Beziehungen eine Rolle für die Bildung dieser Kinder spielt. In der deutschen Forschung fand dieses Thema bislang wenig Beachtung, ebenso wie die Einbeziehung der Wahrnehmung und Perspektive der Kinder auf die Familie. Untersucht wird insbesondere, wie Veränderungen innerhalb der Familie - sowohl hinsichtlich ihrer Form als auch der Beziehungsqualität - die Mathematikleistungen und Bildungsaspirationen von Kindern beeinflussen. Ein besonderer Fokus liegt dabei auf dem Vergleich zwischen Kindern, die mit beiden leiblichen Elternteilen in einem Haushalt aufwachsen, und solchen, die dies nicht tun. Die Erkenntnisse dieser Dissertation unterstreichen die zentrale Bedeutung familiärer Beziehungsdynamiken für Bildungsprozesse und betonen, wie wichtig es ist, die Perspektiven und Bedürfnisse der Kinder stärker in den Mittelpunkt zu stellen. Es zeigt sich, dass eine umfassende Förderung, die sowohl emotionale als auch materielle Unterstützung umfasst, unerlässlich ist, um negative Einflüsse auf schulische Leistungen, insbesondere in instabilen Familienverhältnissen, zu vermeiden. Die Ergebnisse bieten wertvolle Impulse für die Familien- und Bildungspolitik und verdeutlichen die Notwendigkeit ganzheitlicher Unterstützungsangebote, die allen Kindern gleiche Bildungs- und Entwicklungschancen ermöglichen, unabhängig von ihrer familiären Situation. Dabei ist es von zentraler Bedeutung, Programme zu entwickeln, die die emotionalen, sozialen und akademischen Bedürfnisse der Kinder gleichermaßen berücksichtigen.

The overall objectives of this thesis were (1) to evaluate different methods of serum collection for the detection of FTPI via refractometry in neonatal calves, (2) to evaluate a pyroelectric infrared monitoring system assessing movement of preweaned calves, and (3) to assess temperature preferences for heated calf hutches during winter in newborn dairy calves.

The on-farm monitoring of FTPI to optimize colostrum management is an integral part of heifer rearing. Therefore, the objective of the first study was to compare 4 different methods of serum collection to assess failed transfer of passive immunity (FTPI) in dairy calves. We hypothesized that centrifuged serum, filtered serum and clotted serum at room temperature, and clotted serum at refrigerator temperature measured with Brix refractometry would highly correlate with IgG concentration assessed by radial immunodiffusion (RID; gold standard) in centrifuged serum. Blood samples were collected from 321 newborn dairy calves. In centrifuged serum, serum clotted at room temperature, serum clotted at refrigerator temperature, and filtered serum, total solids (TS) in % Brix, and IgG concentrations measured with RID were highly correlated. Regarding the refractometry results among the different serum types, the TS of clotted and filtered serum showed high correlation coefficients compared with the TS results of centrifuged serum. Filtered serum was slightly less accurate. All serum types are valid methods to detect an FTPI in dairy calves, if the specific Brix thresholds for each serum type are considered. Nevertheless, serum clotted at refrigerator temperature should not be the preferred method to avoid the risk of hemolysis.

Sensor technology is becoming more and more popular in calf rearing, and could provide important information about health and performance in the future. The objective of this study was to correlate movement assessed by a pyroelectric infrared sensor system (IMS) in preweaned dairy calves with lying and standing time assessed by a 3D accelerometer considering the temperature-humidity index (THI). A total of 35 dairy calves (1–7 d of age) were enrolled in the study and 20 calves were included in the final analyses. Number of movements per hour measured by the IMS was compared with data obtained with a validated 3D accelerometer. The Pearson correlation coefficient between both standing and lying time and the number of movements was r = 0.85 and r = −0.85, respectively. The Pearson correlation coefficients were only slightly influenced by THI. Our data show that the number of movements of dairy calves measured by IMS were highly correlated with the chosen gold standard reference method. High THI slightly affects the measurement accuracy of IMS. Newborn calves face challenges adapting from the warm uterine environment to cold ambient temperatures, often experiencing cold stress. Therefore, the objective of the third study was to assess the preferred inside hutch temperature of dairy calves in their first week after birth during Central European winter and to compare lying behavior in heated and non-heated hutches. Calves spent 90% of their time inside a hutch, irrespective of the number of heat lamps switched on. No preference for a specific inside hutch temperature existed. There was, however, a tendency for the location of the hutches closest to the control calf. Lying behavior did not differ between preference and control phase, but decreased marginally with increasing age. These findings could indicate that there is a need of shelter for calves in winter, but without a preference for a certain inside hutch temperature under the prevailing conditions of deep straw bedding, highly sufficient milk supply and an ambient temperature of 5.4 ± 3.3°C.

Overall, the results of this thesis show that (1) there are different valuable methods to harvest serum for the detection of FTPI in newborn dairy calves, even without centrifugation, (2) there is a high correlation between the assessment of movement with an IMS and the lying and standing times assessed with a 3D accelerometer data logger, and (3) there is no preference for a certain inside hutch temperature in mild winters, but a preference for social contact. All three studies provide results that can contribute to concrete decision-making and practical application for good calf health monitoring