Urban landscapes, whilst only accounting for a small proportion of total land surface, are now home to the majority of humanity. The functioning of soils within these systems is therefore highly influential for human wellbeing; these soils mediate flood risk, cycle nutrients, and determine whether healthy plant life can be supported. This plant life in turn brings not only aesthetic benefits to cities, but can also yield food and boost the mental wellbeing of inhabitants. These soils are also the basis of urban agriculture and provide aesthetically pleasing spaces for cultural events. This thesis examines three different aspects of soil ecology across a series of urban and peri-urban grasslands, scattered across Berlin and its neighbouring federal state, Brandenburg. Due to their varied surroundings, these sites represent a gradient of urbanization. Throughout this thesis Principal Component Analysis is used to extract axes of variation from a substantial dataset of environmental parameters, in order to make these grasslands practically comparable. The most significant axis of variation within this environmental data is consistently shown to be a selection of urban-related parameters. Examples being the degree to which soil is sealed, the proximity of roads, and the local population density. We term the axis “urbanity” and use it as a metric to score how urban a grassland is. The first aspect of these soils that we explore is their physico-chemical properties. This investigation, presented in Chapter One of this thesis, consisted of a selection of field and laboratory tests. In-situ, we used an infiltrometer to measure the infiltration rate of the soil, and ex-situ we used wet-sieving to establish the percentage of water stable aggregates within samples, and dry sieving to establish the particle sizes present. Finally, we used the molarity-of-ethanol-drop method to investigate levels of hydrophobicity present in soil samples. By using the aforementioned urbanity metric, we were able to understand how these properties were impacted by urbanization. We found that the most urban soils tended to have lower percentages of stable aggregates, larger particle sizes, and more rapid infiltration rates. In Chapter Two of this thesis, we explore the fungal colonisation levels of plant roots, again using samples taken from our study sites. By staining short sections of root, and then examining them under a microscope, it was possible to establish colonisation rates of both arbuscular mycorrhizal fungi, and non-arbuscular filamentous fungi. We also examined the degree of root-hair presence on roots. Again, we compared these parameters to the urbanity score for each site to explore how urbanization impacted root colonisation and morphology. We found that roots in the most urban soils had increased levels of colonisation by non-arbuscular filamentous fungi and higher numbers of root hairs. Finally, in Chapter Three, we use molecular techniques to explore how microbial communities changed across our study sites. We used high-throughput illumina sequencing to record the bacterial, fungal, and cercozoan communities, and then used advanced statistical techniques to investigate how the community composition and species richness of these groups shifted across our urban gradient. We also considered the distribution of some highly abundant species and identified potential urban-indicator species. We found that fungal richness was increased at the most urban sites, and that a variety of environmental variables, including urbanity, drove microbial community composition.

The conditions that individuals experience in early life, i.e. the period from conception to reproductive maturity, can have important consequences on their short and long-term performance and Darwinian fitness. In social mammals, the early-life environment can be defined in terms of ecological, maternal, social or demographic conditions. Little is known about the relative contribution of each type of environment on performance throughout life, whether multiple sources of adversity encountered early in life have a cumulative effect on performance measures, and whether particularly favourable conditions in early life may have a protective effect against the process of senescence, which corresponds to the decline in survival and reproductive probabilities with age. The purpose of this thesis was to provide a more comprehensive overview of how early-life environmental conditions can affect the behaviour (chapter 1), the short and long-term performance and fitness (chapter 2), and the senescence process (chapter 3) of spotted hyenas (Crocuta crocuta). This thesis used longitudinal data on individually known free-ranging spotted hyenas in three clans, obtained from a long-term research project in the Serengeti National Park, Tanzania. I focused specifically on females as they are philopatric and monitored from birth to death. In chapter 1, I found that the presence of migratory herds in spotted hyena clan territories increased with the amount of rainfall two months earlier, and that maternal den presence increased with the presence of migratory herds. I also found that despite the considerable increase in rainfall over the last 30 years, which has reduced the presence of migratory herds in spotted hyena clans, spotted hyenas have coped well with this climate change-induced effect, as maternal den presence has not decreased over the same period and still matched periods of high prey abundance in clan territories. The results of this first chapter thus show a high plasticity in the behavioural response of spotted hyenas to environmental variability and climate change. In chapter 2, I found that the ecological, maternal, social and demographic conditions experienced during early-life have different contributions on early growth rate, survival to adulthood, age at first reproduction (AFR), lifetime reproductive success (LRS) and longevity. I discovered, in particular, that daughters of prime-age mothers had higher growth rates, longevity and LRS than daughters of young or old mothers, that low or heavy rainfall decreased survival to adulthood and that a high number of lactating females in the clan in early life decreased growth rate, longevity and LRS. I show that cumulative adversity had a negative effect on short-term performance and LRS but that multivariate models outperformed cumulative adversity models. These results give a more complete picture of what constitutes favourable (silver-spoon) and adverse conditions for spotted hyena cubs in the Serengeti. In chapter 3, I focused on a key type of early life environment, as revealed by the results of my second chapter, maternal age at birth, to test whether daughters of prime-age mothers, who 14 benefited from a silver-spoon effect, also showed delayed senescence. Consistent with this idea, I found that silver-spooned daughters not only had higher probabilities of survival and reproduction at all ages and a longer reproductive lifespan, but also enjoyed a slower rate of reproductive senescence than daughters of young and old mothers. I also found that maternal age influenced the survival to adulthood of their grand-offspring. The results of this chapter have therefore revealed intergenerational effects of maternal age on fitness across three generations and indicate that prime-maternal age is associated with slower rates of actuarial and reproductive senescence, demonstrating that the silver-spoon effect can persist into late life. The results of my thesis provide new insights into how a wide range of factors during early life, including climatic factors such as rainfall, shape the life trajectories and performance of female spotted hyenas, including processes that occur in late life, as well as in the next generation.

In Debatten um Sexarbeit und Prostitution wird viel über »die osteuropäischen Prostituierten« diskutiert. Doch wie gestalten sich die Lebensalltage von Menschen aus osteuropäischen Ländern, die in Deutschland der Sexarbeit nachgehen? Basierend auf langfristiger ethnographischer Feldforschung in Berlin bietet Ursula Probst Antworten auf diese Frage. In Auseinandersetzung mit den Erfahrungen von Frauen und Männern aus verschiedenen Ländern des östlichen Europas zeigt sie auf, dass prekäre Lebensumstände sexarbeitender Migrant*innen Ausdruck weitreichender Marginalisierung, Sexualisierung und Rassifizierung von Osteuropäer*innen im neoliberalen Europa sind.

Recent advancements in deep learning have revolutionized method development in several scientific fields and beyond. One central application is the extraction of equilibrium structures and long- timescale kinetics from molecular dynamics simulations, i.e. the well-known sampling problem. Previous state-of-the art methods employed a multi-step handcrafted data processing pipeline resulting in Markov state models (MSM), which can be understood as an approximation of the underlying Koopman operator. However, this approach demands choosing a set of features characterizing the molecular structure, methods and their parameters for dimension reduction to collective variables and clustering, and estimation strategies for MSMs throughout the processing pipeline. As this requires specific expertise, the approach is ultimately inaccessible to a broader community. In this thesis we apply deep learning techniques to approximate the Koopman operator in an end-to-end learning framework by employing the variational approach for Markov processes (VAMP). Thereby, the framework bypasses the multi-step process and automates the pipeline while yielding a model similar to a coarse-grained MSM. We further transfer advanced techniques from the MSM field to the deep learning framework, making it possible to (i) include experimental evidence into the model estimation, (ii) enforce reversibility, and (iii) perform coarse-graining. At this stage, post-analysis tools from MSMs can be borrowed to estimate rates of relevant rare events. Finally, we extend this approach to decompose a system into its (almost) independent subsystems and simultaneously estimate dynamical models for each of them, making it much more data efficient and enabling applications to larger proteins. Although our results solely focus on protein dynamics, the application to climate, weather, and ocean currents data is an intriguing possibility with potential to yield new insights and improve predictive power in these fields.

Environmental contaminants have caused substantial population declines of many predatory species during the 20th century. Especially raptors suffered from reproductive impairments and increased mortality due to the biomagnification of persistent organic pollutants such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). These deleterious effects on raptors, in combination with adverse effects on human health, resulted in national and global bans of these substances. As a result, populations of many predator species began to recover from the 1980s onwards. Despite these advances, regulatory frameworks still have shortcomings that result in the environmental emissions of hazardous chemicals. Some of these chemical classes, like anticoagulant rodenticides (ARs), have been shown to threaten European raptor populations through secondary poisoning. ARs inhibit the synthesis of coagulation factors in the liver of vertebrates and are also used in Germany to control rodent populations. However, for other substances that are suspected of threatening raptors, such as plant protection products (PPPs) or medicinal products (MPs), only limited information is available in wildlife species.

As chemical legislations are harmonised across the member states of the European Union, monitoring the outcome of e.g. risk mitigation measures needs to be conducted at the same spatial scale. Therefore, the first part of this dissertation aimed to identify the most suitable species for pan-European biomonitoring of priority contaminants. Candidate species were shortlisted using a scoring scheme based on distribution and ecological criteria such as diet, habitat and migration (chapter 2). In contrast to other European countries, threats to birds of prey from environmental contaminants such as ARs are largely unknown in Germany. Therefore, the core topic of the dissertation dealt with the identification and characterisation of legacy and emerging chemical threats on a national scale. In the first step, the analysis focused on the livers of deceased birds as the liver allows for analyses of chemicals with different physicochemical properties (chapters 3 and 4). In the next step, blood from nestlings was analysed to increase the spatiotemporal resolution of contaminant signals (chapter 5). Chapters 3 and 5 investigated the distribution of priority substance groups such as ARs as well as selected PPPs and MPs in birds of prey of different feeding guilds. In contrast, chapter 4 focused on the identification of 2,441 legacy and emerging contaminants in white-tailed sea eagles (Haliaeetus albicilla) as an indicator species for the Baltic Sea region. For the analyses of livers (chapters 3 and 4), both liquid (LC) and gas chromatography (GC) coupled to mass spectrometry was used. In contrast, the analyses of the blood focused on more polar, non-volatile LC amendable contaminants (chapter 5).

The results of chapter 2 demonstrated that the selection of candidate species for pan-European species can be reduced to only a few species. The common buzzard (Buteo buteo) and tawny owl (Strix aluco) were the most suitable sentinel species for most of the considered contaminants due to their wide-spread distribution, large habitat niche and residency. However, other species may be better sentinels for specific monitoring schemes, such as the golden eagle (Aquila chrysaetos) for lead (Pb) or the northern goshawk (Accipiter gentilis) for studies including far northern European regions. The applied trait-based approach for identifying raptor biomonitors has proven to be robust and can be extended to other continents and contaminants.

When focusing on the national monitoring of birds of prey from Germany, the results from the third chapter demonstrated that ARs pose the most severe threat among 30 PPPs and 7 MPs. Urban northern goshawks and red kites (Milvus milvus) showed ARs residues in >80% of the individuals, and concentrations frequently exceeded toxicity thresholds. The frequent detection of ARs in the northern goshawk as mainly avivorous (bird-eating) species indicates extensive food web contamination in urban areas. In contrast, the high detection rate of red kites as rodent-predating species is comparable to that in other European countries. It was shown that 38% of the mainly piscivorous (fish-eating) white-tailed sea eagles were also exposed to ARs at lower concentrations. In contrast, the purely piscivorous osprey showed no contaminant exposure. Due to the small sample size of ospreys, further studies are recommended to investigate the exposure pathway of ARs in white-tailed sea eagles. Among the MPs, ibuprofen was most frequently detected, with the highest detection rate in the livers of white-tailed sea eagles (24%). The large prescription volume and incomplete wastewater removal might be responsible for the observed exposures. Among the PPPs, only the neonicotinoid thiacloprid and the expired insecticide dimethoate (and its metabolite omethoate) were detected in two red kites each. The concentrations of dimethoate/omethoate were considered to be a result of deliberate poisoning. Together with acute AR poisoning in another red kite, deliberate poisoning is expected to threaten red kites in Germany. In addition to investigating chemical threats by three classes of priority contaminants, chapter 4 identified 85 legacy and emerging contaminants in the livers of white-tailed sea eagles. Most contaminants were MPs (including transformation products), even though they were not predicted to be persistent or bioaccumulative. Their frequent detection is expected to be influenced by the large representation of MPs among the target analytes (45%). Nevertheless, the results demonstrate that MPs enter aquatic food webs and that removal rates in wastewater treatment plants seem to be insufficient. Legacy contaminants such as DDTs and PCBs were detected in all individuals but below toxicity thresholds. Other frequently detected contaminants were per- and polyfluoroalkyl substances (PFAS), commonly known as forever chemicals. Perfluorooctanesulfonic acid (PFOS) accounted for most of the PFAS contamination (96.8% of Σ10PFAS) and showed the highest concentrations in the white-tailed sea eagles, together with DDTs and PCBs. The relatively high PFOS concentration of some individuals in the catchment area of the river Elbe indicates the presence of point pollution in northern Germany. The most frequently detected PPPs were spiroxamine (approved fungicide) and simazine (expired herbicide), which showed increasing concentrations in white-tailed sea eagles from agricultural landscapes.

The blood analysis from nestlings applied an extended LC method to chapter 3 by focusing on ARs, 90 PPPs and 7 MPs. Similar to chapter 3, red kites were particularly impacted by AR contamination (22.6%). In addition to red kites, AR residues were also detected in common buzzards (8.6%), while no residues were detected in Montagu’s harriers (Circus pygargus), white-tailed sea eagles and ospreys. The ground breeding Montagu’s harriers were sampled in cereal fields, which indicates that AR applications as PPPs do not seem to be a relevant exposure pathway in the sampling region anymore. However, the half-life of ARs in the blood is shorter than in the liver, which complicates their detection. The low half-life, in combination with the generally lower AR concentrations in white-tailed sea eagles, is expected to be responsible for non-detects in their blood. Ospreys did not show AR residues in their liver or blood, which indicates that the species is not at risk for exposure. In general, ARs residues were higher in terrestrial raptors from North-Rhine Westphalia compared to North-Eastern Germany, which was expected to be related to the increased biocidal application of ARs in regions of high population density and intensive livestock farming. The most frequently detected PPP in the blood of nestlings was the herbicide bromoxynil (14%). The median concentrations in Montagu’s harrier were similar (red kite) or lower (common buzzard) compared to the other terrestrial tree-nesting raptors. Therefore, overlaps in their dietary niche are expected to be most influential for the observed exposure rather than direct exposures in cereal fields. Similar to ARs, bromoxynil concentrations in terrestrial raptors from North-Rhine Westphalia were higher compared to North-Eastern Germany, which might be related to the intense field agriculture in the region.

In summary, the results of this dissertation demonstrate that birds of prey are exposed to a large cocktail of chemicals across different regulations. In addition to the currently approved ARs, banned persistent and bioaccumulative contaminants such as DDTs, PCBs and PFOS showed the highest concentrations. ARs have especially been shown to threaten birds of prey in urban areas and regions with intensive livestock farming. To reduce the impact of ARs on species that are particularly threatened, such as urban northern goshawks and red kites, additional sanitary measures in livestock farms and urban areas are recommended in combination with limiting the outdoor use of particularly toxic ARs. Due to the complexity of assessing toxic effects under field conditions, it is further recommended to primarily focus on persistence and bioaccumulation for protecting apex predators. This approach allows for the termination of exposures once additional information on adverse effects become apparent. In addition to persistent and bioaccumulating substances, many MPs and currently approved and expired PPPs have also been detected. These examples show that chemical exposures of apex predators are complex and do not solely rely on chemical properties. For example, the feeding ecology, the habitat uses (urban, agricultural), and the use pattern of the respective chemicals have been shown to play an important role for exposure. Based on the result of this dissertation, I recommended that monitoring data, ecological factors (e.g. feeding ecology) and the landscape context of exposures need to be better taken into account in regulatory risk assessments. Together with focusing on environmental persistence and bioaccumulation, these measures are expected to protect birds of prey and other wildlife species before adverse effects in individuals or populations manifest.

There is an intimate relationship between clothes and identity. Clothes express our ideas, values and social norms to others. Therefore, dresses can be utilized to explore and explain the identity transformation from an older to a newer socio-cultural context. This dissertation reads the shifts in Egyptian Muslim women's attitude towards modern dress and clothing style and their entanglement with gender, nationalism, faith, and socio-economic contexts starting from the 19th century from a post-colonial perspective. I rely on fashion and post-colonial theories to address three sets of questions: (i) to what extent do the shifts in socio-economic and political discourses construct gender norms and redefine the feminist quest concerning clothing choice in modern / post-colonial Egypt? (ii) Can we read fashion as a resistance strategy to Egyptian patriarchal forces and hegemonic Western secular modernity in contemporary post-colonial Egypt? (iii) How does fashion disrupt the claimed monolithic Muslim women's identity? Finally, I discuss how Leila Aboulela's literary texts deconstruct the claimed fixed relationship between modernity and its assumed emancipating values and Western dress in her texts Lyrics Alley (2010) and BirdSummons (2019). The term "clothes" is used mainly to refer to the process of veiling and unveiling as an expression of a feminist quest of Egyptian women in the public sphere.

The history of the cyaphide anion and all literature known preparations are reviewed. Furthermore, new theoretical insights to the cyaphide ion are presented and complemented with additional calculations. Moreover, several novel cyaphido complexes synthesized by two innovative preparation protocols are demonstrated. The first method takes advantage of a light induced C(sp2)-C(sp) cleavage reaction in a platinum(0) coordinated arylphosphaalkyne to generate the cyaphido ligand. The second method introduces the well-known trimethylsilylphosphaalkyne as cyaphide anion transfer reagent by fluorodesilylation to build new cyaphido gold(I) complexes. Finally, the reactivity of the cyaphido complexes were investigated towards consecutive reactions on the cyaphido moiety, especially by means of [3+2] cycloaddition reactions with organic azides to yield the corresponding triazaphospholato complexes.

A way to induce structural changes in proteins is through alterations of the protonation state, a principle which is referred to as ‘protonation dynamics’. The two proteins investigated in this work, PsbO and Cph1, are both involved in processes attributed to protonation dynamics, and are studied by solution and solid-state NMR. Photosynthesis produces highly reactive compounds, whose concentrations must be strictly monitored and regulated. At the oxygen evolving centre (OEC) of photosystem II (PSII) - a multiprotein complex spanning the thylakoid membrane - the water-splitting reaction takes place and generates a high proton concentration at the proton release site. PsbO, being in close proximity to the OEC and bearing a significant number of surface carboxyl groups, is likely involved in proton storage or translocation to the lumen. This work investigates the protonation state of the surface aspartic and glutamic acid side chain carboxyl groups of the beta-barrel of PsbO to provide information about a possible proton transfer pathway. Solution NMR experiments were employed. pKa values of 21 carboxylate groups, of which 9 are aspartate and 12 glutamate residues, were determined by the application of 2D titration experiments. The determined pKa values were plotted onto the crystal structure, resulting in an uneven distribution with values below 3.5 clustered on the side of the protein facing PSII whereas values around 4.9 were located at the luminal side of PsbO. This study shows that the bilateral surface pKa distribution enables PsbO to serve as a luminal buffer and potential acceptor of protons, generated during PSII activity. Phytochromes are red and far-red light sensing photoreceptors, present in plants, fungi, and cyanobacteria that control developmental processes such as seed germination and flowering. Sedimentation NMR (sedNMR) and dynamic nuclear polarization (DNP) were combined at high field (800 MHz) to study the so-called ‘tongue’ region of the cyanobacterial phytochrome Cph1∆2, a structural element conserved in all phytochromes. This element is supposed to change its secondary structure from beta-sheet to alpha-helix upon light irradiation. We want to observe the transition in one protein by studying and comparing Cph1∆2 in the Pr and Pfr state. The application of DNP at high fields is not trivial, since enhancements decline and standard measurement conditions can lead to partial unfolding of the proteins investigated. For this reason, new buffer conditions were tested and two polarizing agents, bctol-M and M-TinyPol, were characterised. The performance of bcTol-M was convincing, showing a similar enhancement but higher stability than M-TinyPol. The combination of a selective amino acid labelling scheme and pulse sequence filtering led to reduced spectral overlap, enabling the assignment of resonances within the 58 kDa cyanobacterial phytochrome Cph1∆2 at DNP measurement conditions. By the comparison of 3D hCaNCOCa spectra, recorded on Pr and Pfr state Cph1∆2, a strong indication for structural rearrangements within the ‘tongue’ region was found.

Die öffentliche Versorgung der Bevölkerung durch Großküchen gewann im Verlauf des Ersten Weltkrieges an Bedeutung und blieb während der Nachkriegsjahre eine notwendige Maßnahme zur Linderung der Not in den Großstädten. Die vorliegende Dissertation untersucht anhand der Metropolen Wien und Berlin, ob die kriegsbedingte Massenverpflegung eine nachhaltige Veränderung der Ernährungsgewohnheiten in der Bevölkerung herbeiführte.

Auf diese Frage liefern die beiden Hauptstädte auf dem ersten Blick unterschiedliche Antworten. Während für die Wiener Kriegsküchen sowohl wachsende Besucherzahlen als auch der Fortbestand der Küchen über den Krieg hinaus festzustellen sind, wurden die Berliner Großküchen von der Bevölkerung zunehmend abgelehnt und als „Notbehelf der Kriegszeit“ zurückgewiesen. Die Studie sucht nach den Ursachen für diese unterschiedliche Entwicklung und geht davon aus, dass hierbei nicht nur die sehr viel stärker vorherrschende Not in Wien, sondern auch mehrere sich gegenseitig überlagernde organisatorisch-administrative, soziokulturelle und (sozial-)politische Faktoren eine Rolle spielten. Im Mittelpunkt der Vergleichsanalyse stehen die kommunalen Kriegsverwaltungen als Organisatoren der städtischen Küchensysteme und die mehrheitlich aus Arbeiterschaft und Mittelstand bestehende Stadtbevölkerung als Empfänger der Verpflegungsangebote. Einen weiteren Analyseschwerpunkt bilden die im starken Maße von der Sozialdemokratie beherrschten sozialpolitischen Entwicklungen ab November 1918.

An die öffentliche Verpflegung seit dem späten 19. Jahrhundert anknüpfend nimmt die Studie die Entwicklung der Massenverpflegungsaktivitäten beider Metropolen im Verlauf des Krieges in den Blick und kommt zu dem Ergebnis, dass sich das Wiener Kriegsküchenwesen im Gegensatz zur Berliner Volksspeisungsorganisation durch ein hohes Maß an kommunaler Eigenständigkeit, Entschlossenheit, Anpassungsfähigkeit und Kontinuität auszeichnete – allesamt Faktoren, die eine höhere Inanspruchnahme der Küchen begünstigten. Die vergleichsweise „effiziente“ Entwicklung der Wiener Massenversorgung wirkte sich nachhaltig auf das Verpflegungswesen der Nachkriegszeit aus. Die Sozialdemokraten, die in beiden Städten die politische Verantwortung übernahmen, betrachteten die öffentliche Massenverpflegung im Sinne des Social Engineering als ein zweckdienliches Instrument, mit dem die sozialdemokratische Rationalisierungspolitik unterstützt werden konnte. Dementsprechend betrieben die Verantwortlichen in Wien und Berlin einen großen Aufwand, um der kommunalen Massenverpflegung eine Zukunftsperspektive zu geben. Doch nur in Wien gelang es den Sozialdemokraten, die Stadtküchen zu erhalten und in ein modernes Verpflegungsunternehmen zu verwandeln. Die Studie ermittelt eine Reihe von Faktoren, die diese Entwicklung begünstigten und zeigt hierbei auf, dass die Wiener Entwicklung mit Blick auf die „moderne“ Berliner Speisehauskultur der Vorkriegszeit dennoch keine Innovation war. Schließlich kommt die Studie zu dem Ergebnis, der Erste Weltkrieg auf dem Gebiet der kollektiven Außerhausverpflegung keinen grundlegenden Wandel der Ernährungsgewohnheiten bewirkte. Angesichts der kommunalen Reformbestreben der 1920er Jahre trug er dennoch dazu bei, dass die Kollektivverpflegung einen festen Platz in der kommunalen Daseinsvorsorge einnahm.

This dissertation consists of five independent chapters contributing to the field of applied economics. The first three chapters analyze workers' perceptions of the wage penalty associated with working part-time, further evaluating the labor supply implications of biased beliefs. Chapter 4 quantifies the effects of raising the normal retirement age on the career trajectories of middle-aged workers far from retirement. Chapter 5 examines the expectation management of the German government in the early phase of the COVID-19 pandemic.

Nephrologische Erkrankungen belasten unser Gesundheitssystem und Patientinnen und Patienten gleichermaßen. Leider fehlen bei den meisten dieser Erkrankungen gezielte molekulare Therapien, um das Outcome der Betroffenen zu verbessern. Die vorliegende Arbeit beschäftigt sich mit der genaueren Untersuchung der Genexpression im Nierenepithel, welches die funktionellen Grundeinheiten der Nieren konstituiert. Genexpressionsstudien in Kombination mit bioinformatischen Analysen bieten eine nützliche Grundlage für diese Forschung. Durch diese Strategie konnten wir einen neuen epithelialen Mechanismus im Sammelrohr der Niere identifizieren, der zur akuten Nierenschädigung prädisponiert. Wir konnten zeigen, dass der Transkriptionsfaktor Grainyhead-like 2 in den Epithelzellen des Sammelrohrs essenzielle Komponenten der Zell-Zell-Kontakte reguliert. Wenn diese Faktoren verloren gehen, führt dies zu einer erhöhten Durchlässigkeit des Sammelrohrs und einer Unfähigkeit der Niere, Elektrolyte und Wasser zurück zu resorbieren. Insbesondere bei reduzierter Flüssigkeitszufuhr kommt es daher häufiger zu akuter Nierenschädigung. Wir haben auch die Wirksamkeit des bekannten Pilzmedikaments Fluconazol zur Verhinderung einer akuten Nierenschädigung durch einen bisher unbekannten Mechanismus im Sammelrohr nachgewiesen. Dieses Medikament steigert die Wasserrückresorption und kann so vor akuter Nierenschädigung schützen, insbesondere bei genetischer Prädisposition für Wasserverlust. Diese Erkenntnisse werden derzeit in einer klinischen Studie weiter untersucht. Des Weiteren haben wir eine der ersten Studien zur akuten Nierenschädigung beim Menschen mit Hilfe von Einzelzellsequenzierung durchgeführt. Auch hier zeigten die renalen Epithelzellen die stärkste transkriptionelle Antwort. Wir konnten zeigen, dass der gesamte renale Tubulusapparat in die genregulatorischen Vorgänge bei der akuten Nierenschädigung involviert ist, was aus früheren Mausstudien so nicht bekannt war. Zudem identifizierten wir Zellpopulationen, die mit der Nierenschädigung assoziiert sind und vielversprechende Ziele für neue therapeutische Ansätze darstellen können. Insgesamt haben wir relevante Pathomechanismen im Zusammenhang mit der akuten Nierenschädigung aufgedeckt, ausgehend von den renalen Epithelzellen. Dabei haben Transkriptom-weite Genexpressionsdaten und darauf aufbauende bioinformatische Analysen hierbei eine zentrale Rolle gespielt. Von den neueren Plattformen zur Einzelzellsequenzierung erhoffen wir uns weitere innovative Ansätze zur Verbesserung der nephrologischen Therapie.

Die Implementierung von Systemen zur Überwachung der Vitalparameter von Patient:innen auf der ITS konnte die Patientensicherheit in der Intensivmedizin signifikant erhöhen. Seit Ende der 1960er Jahre stellt das Monitoring neben der klinischen Untersuchung von Patient:innen auf der ITS einen wesentlichen Bestandteil der intensivmedizinischen Versorgung dar und ist seit 2005 in diversen Leitlinien aufgenommen worden. Trotz innovativer Fortschritte im Bereich der Medizin, Informatik und Signalverarbeitung konnten neuere Ansätze jedoch nur unzureichend in die klinische Routine translatiert werden. Diese Habilitationsschrift fokussiert sich daher darauf, welche Aspekte des aktuellen Patientenmonitorings aus Sicht der Nutzer:innen auf der ITS sicherheitsrelevante Defizite aufweisen und wie die Patientensicherheit durch Umsetzung spezifischer Maßnahmen erhöht werden kann. Im Rahmen einer qualitativen Interviewstudie und einer quantitativen Befragung mittels Online-Fragebogen (Originalarbeit 1 und 2) konnte der Status quo des Patientenmonitorings evaluiert werden. Hierbei zeigten sich fünf relevante Angriffspunkte für eine Erhöhung der Patientensicherheit: Reduktion der falsch positiven Alarme, Implementierung eines krankenhausweiten Alarmmanagement-Standards, Einführung von kabellosen Sensoren, Einführung von KI-augmentierten klinischen Entscheidungssystemen mit einer hohen Benutzerfreundlichkeit und Interoperabilität sowie die Erhöhung der digitalen Kompetenz des Personals. Aufbauend auf den Ergebnissen aus den ersten beiden Arbeiten wurde in Orginalarbeit 3 ein datengestützter Ansatz des Alarmmanagements entwickelt, mit dem die Alarmlast auf einer ITS anhand einer deskriptiven Alarmdatenanalyse quantifiziert und somit die Wirkung von Interventionen gemessen werden kann. Die publizierte Do-it-yourself-Anleitung kann von technisch versierten Pflegekräften und Ärzt:innen genutzt werden und bietet die Grundlage für ein zielgerichtetes und fokussiertes Alarmmanagement. In Originalarbeit 1 wurde durch das ITS-Personal eine hohe Benutzerfreundlichkeit von Patientenmonitoringgeräten als essenziell eingestuft. Daran orientierend wurde in Originalarbeit 4 durch die partizipative Einbeziehung der Nutzer:innen im Rahmen eines Human-centered-Design (HCD)-Ansatzes ein Think-Aloud-Protokoll angewendet und damit die Benutzerfreundlichkeit einer Softwareoberfläche eines Patientenfernüberwachungssystems signifikant verbessert. Der Einsatz von HCD-Methoden vor der Implementierung technischer Geräte auf der ITS könnte sicherstellen, dass diese Geräte effiziente und effektive Arbeitsabläufe unterstützen und keine Hindernisse darstellen. Dieser sicherheitsrelevante Aspekt wurde ebenfalls in den entwickelten Leitfaden für die Implementierung von digitalen Technologien in die intensivmedizinische Routine (Originalarbeit 5) mit aufgenommen. Hierbei wurde ein hybrider qualitativer Ansatz mit induktiven und deduktiven Elementen verfolgt und die bestehenden Strukturen des Consolidated Framework for Implementation Research (CFIR) und der Expert Recommendations for Implementing Change (ERIC) genutzt. Der entwickelte Leitfaden sollte Implementierungsvorhaben auf der ITS unterstützen und könnte perspektivisch auf den Bereich der Normalstation adaptiert werden. Zusammenfassend ist festzustellen, dass durch die vorliegenden Arbeiten diverse sicherheitsrelevante Aspekte des Patientenmonitorings aus Sicht der Nutzenden identifiziert wurden und die entwickelten Maßnahmen in den Bereichen Alarmmanagement, Benutzerfreundlichkeit und Implementierungswissenschaft maßgeblich zu einer höheren Patientensicherheit in der Krankenversorgung beitragen können. Entscheidend für die Weiterentwicklung der datengetriebenen personalisierten Medizin ist das Patientenmonitoring, sodass diese Erkenntnisse darüber hinaus die digitale Transformation des Gesundheitswesens vorantreiben können.

Human pluripotent stem cells (hPSCs), which include human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), infinitely self-renew, and can differentiate into any cell type on the human body [1–3]. hESCs are derived from early human embryos and became widely used to study the molecular pathways specific to human embryogenesis [1, 4–8]. Considering the ethical challenge in using embryo-derived cells and the possible immune rejection, hiPSCs are currently more common for regenerative therapies [3, 9–11]. hiPSCs are reprogrammed from a somatic cell line of a patient, genetically modified, and then differentiated to the desired lineage to transplant them back to the patient. hiPSCs are the future of personalized medicine, but not every hiPSC line can differentiate to every given cell type, as a result of cell heterogeneity. To reduce this heterogeneity, a naïve cell state might be a solution [3]. Whereas cultured hPSCs reside in a primed state, the cells of pre-implantation embryos resemble naïve pluripotency [12–16]. By adjusting culture conditions, it is possible to support hPSCs in a naïve state, similar in gene expression signature to early embryos [4, 5, 17–19]. The similarity is reflected as well in transcripts of some of the L1, Alu, and SVA retroelements (REs) [5]. These REs are phylogenetically young and still active human transposons, which might be detrimental for the integrity of the genome [20–27]. Our research group had previously derived the different types of naïve cells, resembling the later stages of pre-implantation development and highly expressing human endogenous retrovirus H (HERVH) [6]. HERVH is a phylogenetically older endogenous retrovirus, which was transposing following New- and Old-World monkey separation [28–30]. Now, HERVH can’t mobilize, but its transcripts were shown to support pluripotency in later stages of human embryogenesis, reprogramming, and in cultured primed hPSCs [6, 7, 31, 32]. Here I show that HERVH controls the transposition of young REs. In HERVH-depleted hESCs, L1 transposition increases, which is measured by two transposition assays. The active L1 elements drive the transposition of non-autonomous REs, resulting in the accumulation of de novo Alus and SVAs integrations, shown by whole-genome sequencing of cells undergoing stable HERVH knock-down. A subgroup of HERVH has the potential to control L1 transposition. These HERVHlin loci contain lin motif, two tandem LIN28A binding sites [33]. HERVHlin is supposedly evolutionary younger than the other HERVH. There are around 100 of HERVHlin sequences in the human, chimp, and gorilla genomes, while less exist in orangutans, and none in other primates. Based on the analysis of the previously published CLIP-seq data [33] and performed RIP-qPCRs, the lin motif allows LIN28A to bind HERVHlin more efficiently than other HERVH transcripts. LIN28A is known to inhibit the maturation of let-7 microRNA [34–37], which in turn controls the transposition of L1 [38]. HERVHlin sponging LIN28A to allow let-7-mediated inhibition of L1 might be the molecular mechanism of HERVH-controlled transposition of young REs. The supporting experiment shows that a let-7 independent L1-ORFeus reporter does not change the transposition activity in HERVH-depleted cells. HERVHlin embedded itself in a previously conservative pluripotency-specific LIN28A-let-7 pathway to protect the genome of hESCs from the mutagenic activity of REs. This is an example of a new evolutionary event where the selfish transposon HERVH evolved to compete with other transposable elements, which could be harmful to the host.

This survey describes the different facets of South African settler primitivism and the interactions of its protagonists, who moved between the poles of European modernism and local traditional cultures. Marked by great ambivalences, they oscillated between transnational and national approaches to an art production that appropriated indigenous landscapes, peoples and their visual cultures in order to indigenise white settlers to the South African land. A focus is set on the women artists Irma Stern and Maggie Laubser, who were key to the development of South African modernism.

Chronische Schmerzen sind ein wesentliches globales Gesundheitsproblem, welches eine hohe sozioökonomische Belastung auf der Ebene der Individuen, der Gesellschaften und der Institutionen mit sich bringt. Die vorliegende Habilitationsschrift thematisiert die Evaluation nichtpharmakologischer Interventionen aus der Integrativen Medizin und Digitalen Gesundheit bei chronischen Schmerzen. Hierzu wurden randomisierte kontrollierte Studien zu klassischen komplementärmedizinischen Verfahren wie Tuina oder Akupunktur durchgeführt oder zu diesen Verfahren in Kombination mit modernen digitalen Technologien. Eine Wirksamkeit konnte nur zum Teil gezeigt werden. Die per Smartphone-App durchgeführte Selbstakupressur führte bei jungen Frauen zu einer Verringerung der Menstruationsschmerzen im Vergleich zur Normalversorgung. Die Wirkung nahm mit der Zeit zu, und die Therapieadhärenz war gut. Im Gegensatz dazu konnte die Studien-App, die Verfahren aus dem Bereich der Mind-Body-Medizin integrierte, chronische Nackenschmerzen nicht wirksam reduzieren. Die Therapieadhärenz war weniger gut. Unsere aktuelle und noch laufende Studie zu Menstruationsschmerzen zeigte, dass Betroffene auch ohne direkten Kontakt zu Gesundheitsexperten und allein über einen App-Store erreicht werden können und diese die App dann auch nutzen. Im Setting einer Hochschulambulanz zeigte sich eine zusätzliche Behandlung mit sechs Tuina-Sitzungen über drei Wochen bei Patienten mit chronischen Nackenschmerzen als wirksam, sicher und relativ kosteneffektiv im Vergleich zu einer Patientengruppe mit chronischen Nackenschmerzen ohne zusätzliche Intervention. Eine im ambulanten Setting einer Allgemeinarztpraxis durchgeführte individualisierte Akupunktur zeigte sich einer standardisierten Akupunktur bei chronischen Kreuzschmerzen nicht überlegen. Die Studie weist darauf hin, dass eine Vereinfachung der Akupunkturbehandlung und dadurch ein möglicherweise breiterer Einsatz denkbar wären. Als wesentliche Schlussfolgerungen der vorliegenden Arbeit lassen sich ziehen, dass nichtpharmakologische Interventionen der Integrativen Medizin und Digitalen Gesundheit einen wichtigen Beitrag zur Behandlung chronischer Schmerzerkrankungen leisten könnten. Insbesondere die Kombination klassischer komplementärmedizinischer Verfahren und Digitaler Anwendungen scheint lohnend. Weitere Forschung zu Mechanismen, Wirksamkeit, Kosteneffektivität und optimalen Anwendungsszenarios ist notwendig. Die Grundlagen für evidenzbasiertes Arbeiten scheinen jedoch gelegt.

In der vorliegenden Arbeit wurden innovative Einsatzmöglichkeiten der Computertomographie (CT) in der Diagnostik von Pathologien der Bandscheibe in den Bereichen traumatischer, infektiöser und degenerativer spinaler Veränderungen untersucht. Im Rahmen traumatischer Verletzungen der Wirbelsäule wurde das CT-morphologische Auftreten eines Fraktur-assoziierten Vakuumphänomens in der Bandscheibe als möglicher Indikator für eine Bandscheibenbeteiligung untersucht, wobei eine Assoziation mit Berstungsfrakturen festgestellt wurde. Gleichzeitig konnte der Nachweis gelingen, dass das Vorhandensein einer Gasansammlung in der Bandscheibe im Gegensatz zur bisherigen Annahme kein Ausschlusskriterium für das Vorhandensein einer spinalen Infektion darstellt. Im Bereich degenerativer spinaler Veränderungen wurden dagegen Kollagen-sensitive Rekonstruktionen basierend auf der Dual-Energy Computertomographie (DECT) hinsichtlich der Darstellung der Bandscheibenmorphologie untersucht. Im nächsten Schritt erfolgte dann die Analyse ihrer Machbarkeit hinsichtlich der Darstellung lumbaler Bandscheibenpathologien sowie Stenosen der Foramina intervertebralia. Die diskutierten Arbeiten zeigen, dass die CT als diagnostisches Mittel wesentlich zu der Beurteilung von Pathologien der Bandscheibe in den untersuchten Bereichen beiträgt, verdeutlichen aber gleichzeitig, dass die Untersuchung mittels einer einzelnen bildgebenden Modalität alleinig in vielen Fällen keine vollumfassende Diagnostik zur Festlegung des therapeutischen Vorgehens erlaubt.

In this thesis, ultra-thin films of MnxAu1−x have been studied structurally and magnetically. We prepared the thin films with electron-beam evaporators in ultrahigh vacuum (UHV). The growth of the films was monitored by medium-energy electron diffraction (MEED). The films’ structures were investigated by means of low-energy electron diffraction (LEED) and scanning tunneling microscopy (STM), and the chemical composition was checked by Auger electron spectroscopy (AES). The magnetic property of the antiferromagnetic (AFM) films in contact with FM films was studied by longitudinal magneto-optic Kerr effect (L-MOKE), X-ray magnetic circular dichroism (XMCD), and X-ray resonant magnetic reflectivity (XRMR) spectroscopy at L2,3 absorption edge. AFM Mn2Au might be very significant for future spin-electronic applications. We studied MnxAu1−x films in detail to investigate their structure for a variety of thicknesses on Cu(001) and Ag(001) single crystals. First, we studied Au/Mn/Co on Cu(001) to define the growth rate for Au, Mn, and Co using MEED. The vertical interlayer distances for Co on Cu(001) and Mn on Co/Cu(001) and surface topography of Au on Mn/Co/Cu(001) were investigated by LEED-I(V) (00 spot intensity was recorded vs. electron beam energy) and STM, respectively. After that, we studied from sub-ML (surface coverage of less than one monolayer) to more than 1ML of MnxAu1−x on Cu(001) structurally by LEED and STM. We observed a c(2×2) superstructure for coverages between 0.5 and 1ML of MnxAu1−x on Cu(001). MnxAu1−x revealed MEED oscillations during growth on Cu(001), but no LEED patterns could be observed for thicker films (> 1 ML). For studying the magnetic properties of AFM MnxAu1−x on Cu(001), we grew Co on top, then we employed MOKE after zero-field cooling as well as after field cooling. We observed coercivity changes with temperature, however, we did not observe any exchange bias. Finally, we studied Mn and MnxAu1−x growth on Ag(001) to define the growth rate and structure of the resulting films. Fe growth on Ag(001) was also studied structurally. We deduced vertical interlayer distances for single-layer and bilayer films (Fe, MnxAu1−x) on Ag(001) from a kinematic analysis of LEED-I(V) curves because both show LEED patterns. The MnxAu1−x showed MEED oscillations during growth on Ag(001). Fe/MnxAu1−x bilayers on Ag(001) were studied magnetically by MOKE.We did not observe any significant change in coercivity to confirm the antiferromagnetism of the MnxAu1−x films.

Diese kumulative Habilitationsschrift befasst sich mit den Herausforderungen der Lebertransplantation in Deutschland im letzten Jahrzehnt. Hierbei soll besonders deutlich werden, dass multifaktoriell bedingt ein Mangel an adäquaten Spenderorganen vorherrscht und die Transplantation grenzwertiger Organe mit individuellen Problemen behaftet ist. Experimentelle Ansätze zur Organevaluierung durch ex vivo Maschinenperfusion im Kleintiermodell können dabei helfen, in Zukunft Strukturen für eine verbesserte Transplantationslogistik zu schaffen. Zudem soll hervorgehoben werden, dass bei Kindern, auch durch die vermehrte Leberlebendspende, die Ergebnisse einem nicht so starken Wandel unterliegen und vielmehr individuelle Herausforderungen im Vordergrund stehen.

Traditionally, patients have been regarded as passive recipients of healthcare interventions. However, the growing demand for inclusion and representation of patients as stakeholders has led to a paradigm shift. The mantra "Nothing About Us Without Us" emphasizes the need for people living with chronic conditions to be involved in the development of services, products, policies, and educational resources.

A primary example of patient-led innovation democratization in healthcare is the #WeAreNotWaiting movement, spearheaded by people with diabetes and their loved ones who transform their existing medical devices into "do-it-yourself" or "open-source" artificial pancreas systems. These systems enable automated, closed-loop insulin delivery based on available medical devices. Unlike commercially developed systems, code and documentation needed to create open-source systems are freely and openly shared by the #WeAreNotWaiting community and used at the user's own risk. Leveraging predictive control algorithms, these systems adjust insulin dosing based on predicted glycemic trends. Despite lacking regulatory approval, open-source automated insulin delivery systems have gained widespread popularity and are being used by thousands of individuals worldwide.

This thesis provides a comprehensive overview of open-source automated insulin delivery systems, elucidating their clinical and quality of life benefits for users. It presents novel evidence of the real-world effectiveness of these systems, offering insights into the lived experiences of users and their families. Moreover, the feasibility of implementing open-science infrastructures for sharing real-world data is explored. An international consensus statement is also provided, offering guidance to healthcare professionals and other key stakeholders. Additionally, this thesis addresses the issues of health disparities and barriers to access related to diabetes treatments and technology, both on a global scale and within specific countries. Further, the ethical and legal dilemmas associated with open-source automated insulin delivery systems and the significance of addressing the digital divide in access to modern treatments are being discussed, as well as potential advancements in artificial intelligence and diabetes technology.

User-led initiatives such as #WeAreNotWaiting and the technological innovations emerging from them hold promise for enhancing healthcare. However, concerted efforts are necessary to ensure universal accessibility and suitability for all patients.

Die Hochpräzisionsbestrahlung mittels stereotaktischer Radiochirurgie (SRS), fraktionierter stereotaktischer Radiotherapie (FSRT) und Körperstereotaxie (SBRT) stellt heutzutage eine unverzichtbare Therapiemodalität in der modernen Onkologie dar. Im Kontext dieser Habilitation wurden die klinischen bzw. radioonkologischen Ergebnisse der Stereotaxie für Foramen magnum Meningeome, intramedulläre Metastasen, Nebennierenmetastasen, spinale Ependymome und Prostatakarzinomlokalrezidive analysiert. Darüber hinaus erfolgte eine erstmalige Betrachtung der gyroskopischen Radiochirurgie (GRS). Die dargestellten Arbeiten und Daten zeigen, dass die Stereotaxie auch im Rahmen seltener Indikationen und Tumorlokalisationen meist effektiv und sicher eingesetzt werden kann. Durch weitere Fortschritte auf dem Gebiet der funktionellen und nicht-funktionellen Bildgebung, adaptiven Strahlentherapie sowie der molekularpathologischen Diagnostik und biologischen Charakterisierung von Tumoren wird sich zusätzliches Potenzial zur Therapieoptimierung ergeben. Darüber hinaus wird es Aufgabe zukünftiger radioonkologischer Forschung sein, die Patientenselektion für die SRS, FSRT und SBRT weiter zu verfeinern und die Stereotaxie sinnvoll in den Kontext multimodaler Therapiekonzepte zu implementieren. Hierfür werden eine standardisierte und prospektive Datenerhebung und Evaluation von zentraler Bedeutung sein. Weiterhin sind technische Innovationen – wie bei der GRS oder Magnetresonanztomographie-gestützten Linearbeschleunigern ersichtlich – von großer Relevanz, um die Verfügbarkeit, Effektivität und Sicherheit der Hochpräzisionsbestrahlung weiter voranzutreiben.