Die Verkehrswende, der Umbau des Verkehrssystems hin zu einer ökologisch nachhaltigen Mobili-tät, ist ein komplexer gesellschaftlicher Transformationsprozess. Der Wandel erfordert, neben der Schaffung entsprechender politischer Rahmenbedingungen und dem Einsatz neuer Technologien, tiefgreifende Änderungen von Einstellungen und Verhaltensweisen sowie kulturell geprägter Deu-tungsmuster in der Gesellschaft. Unter welchen Bedingungen sich derartige Veränderungen auf der Ebene des Individuums und auf der Ebene sozialer Strukturen ergeben können und wie diese Ebe-nen miteinander wechselwirken, ist jedoch nicht ausreichend erforscht. Ziel dieser kumulativen Dissertation ist es, auf theoretischer sowie empirischer Basis ein agentenbasiertes Modell der Ein-stellungs- und Entscheidungsänderungen der Verkehrsmittelwahl zu schaffen. Ich beziehe mich dabei auf die kognitionswissenschaftliche Forschung zur Rolle von Emotionen bei der Informati-onsverarbeitung und Entscheidungsfindung, auf Forschungsarbeiten zu der Wirkung sozialer Ein-flüsse aus den Bereichen der Sozialpsychologie und Soziologie sowie auf die umweltpsychologische Forschung zur Segmentierung von Zielgruppen. In Studie 1 wurde anhand eines Vignettenexperiments und eines kognitiv-affektiven Modells dyadischer Kommunikation untersucht, welchen Einfluss die Verwendung emotionaler Sprache im Zuge persuasiver Kommunikation auf die Informationsverarbeitung von Menschen hat. Die Ergeb-nisse zeigen, dass die Tendenz zur motivierten Informationsverarbeitung (motivierte Kognition) durch die Valenz und den Grad der Emotionalität in der Kommunikation beeinflusst wird. Mithilfe des Modells können die beobachteten Effekte durch den Mechanismus der emotionalen Kohärenz erklärt und in ihrer Wirkung auf mentale Strukturen geschätzt werden. In Studie 2 wurden die Einstellungen und affektiven Bedeutungen einer breiten Palette von konventionellen und neueren Verkehrsmitteln untersucht. Auf Basis der affektiven Wahrnehmun-gen konnten unterschiedliche Mobilitätstypen identifiziert werden. Darüber hinaus zeigt die Studie, dass die typspezifischen affektiven Bedeutungsmuster die Bereitschaft, emissionsarme Verkehrsmit-tel zu nutzen, im hohen Maße bestimmen. In Studie 3 wurden die theoretischen und empirischen Ergebnisse aus den vorangegangenen Studien in dem agentenbasierten Modell InnoMind (Innovation diffusion driven by changing Minds) zusammengeführt. Die Simulationsszenarien zu unterschiedlichen Fördermaßnahmen von Elektromobilität verdeutlichen, dass die Wirksamkeit der Instrumente durch die zielgruppenspezifi-schen Einstellungsmuster und sozialen Interaktionen der Verkehrsteilnehmerinnen und Verkehrs-teilnehmer beeinflusst werden. In Studie 4 wurde das Modell InnoMind genutzt, um die einstellungsverändernden Effekte von Informationskampagnen zur Nutzung von Carsharing zu untersuchen. Das Vorgehen verdeutlicht die Flexibilität und Adaptivität des Simulationsansatzes. Darüber hinaus zeigt die Studie, dass die veränderte Darstellung der Mobilitätsoptionen in den Kampagnen deren Wirkung in bedeutsamen Maß beeinflussen kann. Insgesamt unterstreichen die Ergebnisse die Bedeutung affektiv-emotionaler Prozesse für die Einstellungsbildung und -änderung. Die Verarbeitung von (sozialen) Informationen unterliegt Ver-zerrungen, die zu einer Konstruktion einer konsistenten Repräsentation bestehender Überzeugun-gen und Emotionen führen. Diese auf individueller Ebene wirkenden Mechanismen haben in Wechselwirkung mit sozialen Kommunikationsprozessen und Informationsflüssen einen entschei-denden Einfluss auf die Dynamiken im Zuge gesellschaftlicher Transformationen. Das in dieser Arbeit entwickelte agentenbasierte Modell ermöglicht es, derartige komplexe In-teraktionsprozesse und Dynamiken zu analysieren. Auf der Grundlage kognitionswissenschaftlicher, sozialpsychologischer und soziologischer Theorien sowie umfassender Empirie erweitert es die bis-herige Forschung zu Meinungsdynamiken und sozialen Einflüssen mithilfe sozialer Simulationen. Zudem vermittelt das Modell handlungsrelevantes Wissen, um die Akzeptanz der Verkehrswende in der Gesellschaft zu fördern.

Phänomene der Immersion gehen häufig mit dem Wirkungsversprechen einher, Rezipierende möglichst komplett in eine Umgebung, Fiktion oder Parallelwelt einzutauchen. Insbesondere der Topos einer ‚totalen‘ Immersion suggeriert, dass Rezipierende physisch, psychisch oder emotional derart eingenommen werden, dass sie nicht nur das Vermögen verlieren, zwischen Realität und Fiktion zu unterscheiden, sondern auch, dass ihr Reflexionsvermögen zugunsten eines unmittelbaren, intensiven Erlebens eingeschränkt werde. Die vorliegende Studie zeigt am Beispiel immersiven Theaters jedoch, dass es gerade die emotionale Involvierung ist, die Prozesse der Reflexion auslöst – und eine solche, den Diskurs prägende, binäre Denkfigur die Komplexität zahlreicher Immersionsphänomene deshalb nicht angemessen erfassen kann. Vor dem Hintergrund der transdisziplinären Immersionsforschung differenziert die Studie zunächst zwischen immersiven Aufführungsdispositiven und immersivem Theater im engeren Sinn. Letzteres zeichnet sich dadurch aus, dass Zuschauer:innen nicht nur in einen multisensorischen Erfahrungsraum, sondern zugleich in eine geschlossene, gestaltete Weltversion eingelassen werden. Für die Analyse der Publikumsinvolvierung im immersiven Theater wird eine polyperspektivische Szenen- und Situationsanalyse vorgeschlagen. Diese fokussiert anhand ausgewählter Sequenzen die Relation von Aufführungsdispositiv und Zuschauer:innen im Hinblick auf konstellierte Selbst-/Weltverhältnisse. Ausgehend von der These, dass die verschiedenen Modi der Involvierung (räumlich, haptisch-taktil, olfaktorisch, figurenperspektivisch oder handlungsbezogen etc.) wirkungsästhetisch auf Vereinnahmung zielen, zeigen die Analysen, wie Zuschauer:innen z.B. von Geruchs- oder Soundwahrnehmungen derart affiziert werden können, dass es sie situativ zu einer bestimmten Re-Aktion drängt. Prozesse der Vereinnahmung werden dabei nicht nur konstitutiv reziprok gedacht, sondern in ihren vielschichtigen, hochgradig ambivalenten Wirkungen beschrieben. Über das Konzept der Vereinnahmung und die Analyse vereinnahmender Publikumsinvolvierung wird eine affekttheoretische Perspektive auf immersives Theater plausibilisiert. Die Studie nimmt damit nicht nur eine wichtige, korpusgebundene Präzisierung des umbrella-Phänomens immersive theatre vor. Sie leistet nicht zuletzt über die Integration von Zuschauer:innen-Interviews zudem eine methodische Erweiterung etablierter Strategien der Aufführungs- und Inszenierungsanalyse und zielt mit dem Konzept der Vereinnahmung auf eine Theoriebildung für Prozesse der Publikumsinvolvierung im Gegenwartstheater.

Fung Asseng (馮亞星, 1792–?) und Fung Ahok (馮亞學, 1798–1877), zwei einigermaßen gebildete Matrosen aus der chinesischen Provinz Guǎngdōng oder Canton (廣東), waren die ersten Chinesen, die sich nachweislich in Deutschland aufhielten. In den 1820er Jahren fertigten sie in Halle und Potsdam umfangreiche zweisprachige Handschriften christlichen Inhalts an, in denen sie ihre frühkantonesischen Aussprachen zahlreicher chinesischer Schriftzeichen in das lateinische Alphabet transkribierten. Gleichzeitig berichteten auch einige deutsche Autoren über ihre Sprache. Diese Schriften, die von Asseng und Ahok selbst oder ihren deutschen Mitmenschen produziert wurden und summarisch als die „deutschen Quellen“ bezeichnet werden können, gelten als aufschlussreiche Materialien für die Erforschung der frühkantonesischen Sprache. Sie werden in der vorliegenden Arbeit zum ersten Mal systematisch untersucht, und zwar aus der Perspektive der chinesischen Dialektologie, der Missionarslinguistik sowie der (deutschen) Graphematik. Dadurch können nicht nur zwei historische Varianten des Frühkantonesischen phonetisch und phonologisch rekonstruiert, sondern auch die Transkriptionsregeln herausgearbeitet werden, die im Wesentlichen unter dem Einfluss der neuhochdeutschen Orthographie entstanden sind.

The morphogen sonic hedgehog (SHH) regulates central patterning processes along the dorsoventral axis of the emerging forebrain. Secreted from the prechordal plate (PrCP), SHH targets neuroepithelial cells of the overlying forebrain organizer region in the rostral diencephalon ventral midline (RDVM), to establish and further specify ventral identity of the forebrain. Defects in this pathway result in severe developmental forebrain defects including holoprosencephaly (HPE). Besides the canonical SHH receptor patched 1 (PTCH1), several additional cell surface proteins have been identified as being essential for SHH signaling in the neuroepithelium. Jointly, they are referred to as the SHH receptorsome and include LRP2 and GAS1. Mutations in these co-receptors are the cause of familial forms of HPE and related phenotypes, such as in Donnai-Barrow syndrome (DBS), corroborating their importance for SHH-dependent forebrain development in humans. Intriguingly, the structure of SHH coreceptors is highly diverse and they show spatial and temporal differences in expression pattern, arguing for distinct functions of each receptor in SHH-dependent developmental processes. In this thesis, I used human induced pluripotent stem cell (iPSC)-based cell models to recapitulate early steps in neuroepithelial patterning and to elucidate unique roles for LRP2 and GAS1 in these processes. In the first project, I studied a unique missense mutation in LRP2 in two siblings with DBS. To do so, I differentiated patient-derived iPSCs into neural progenitor cells (NPCs) and studied the impact of this mutation on receptor handling of SHH. I demonstrated that the mutant receptor was unable to discharge its ligand SHH, leading to enhanced lysosomal degradation of the mutant receptor bound to its ligand. These studies showed that ligand-induced decay of LRP2 is responsible for the disease phenotype in this family with DBS. Additionally, the results of this study verified the molecular function of LRP2 as SHH co-receptor as it mediates endocytosis and trafficking of the morphogen in forebrain neuroepithelial cells, a process essential for SHH signal reception in this cell type. In the second project, I uncovered a novel function for GAS1 in integrating SHH and NOTCH signaling during early forebrain development. Performing comparative analyses in GAS1- deficient mice and genetically engineered GAS1 knockout (KO) iPSC-derived NPCs, I showed that loss of GAS1 impairs NOTCH-dependent facilitation of SHH signaling and results in a failure to maintain the SHH activity domain in the rostral ventral neuroepithelium. Thus, besides its known function as SHH co-receptor, GAS1 also acts as co-receptor for NOTCH1, enhancing pathway activation which, in turn, promotes maintenance of SHH signaling in the rostral ventral neuroepithelium during forebrain development.

In the context of the euro crisis, several member states of the Eurozone were forced to implement so-called Economic Adjustment Programmes. The implementation of these programmes was supervised by a troika consisting of the European Commission, the European Central Bank, and the International Monetary Fund. Fiscal adjustment was one cornerstone of the adjustment programmes. The objective of the programmes was to reduce previously soaring public deficits and to stabilise and reduce public debt in the long term. All programmes primarily aimed at cutting government spending. Increasing government revenues was to play only a secondary role. However, a look at the adjustment programmes for Ireland and Portugal shows a striking difference in the fiscal adjustment strategies. Different Irish governments pursued an adjustment strategy with a strong focus on expenditure cuts. By contrast, Portugal's adjustment strategy changed over the course of the programme and was increasingly driven by increases in revenues. How can we explain these differences? To answer this question, my dissertation provides two in-depth case studies of the adjustment programmes for Ireland and Portugal. I argue that fiscal adjustment strategies are determined by the activity of coalitions of different economic actor groups at the domestic level. These actor groups have different fiscal policy preferences. On the one hand, they differ in terms of their preferred level of redistribution and the economic risks to which they are exposed. On the other hand, sectoral actor groups have different preferences based on their prioritisation of international competitiveness and domestic demand. Actor groups with similar preferences form coalitions to influence the government’s policy-choice. Two logics determine which coalitions ultimately prevail. On the one hand, some coalitions are involved in policy-making through social pacts and other institutional arrangements. On the other hand, sectoral coalitions are influential due to their importance for economic growth. Although national coalitions have decisive influence, governments in a globalised world are constrained in their actions by international financial market actors. In Ireland, coalitions that favoured an adjustment strategy with a focus on spending cuts were more assertive. This is mainly due to the Irish growth model, which has been based on exports and foreign direct investment for more than two decades. Trade unions, which would have preferred an alternative adjustment strategy, were not able to prevail against the influential coalition of export-oriented actor groups and high-skilled workers. In Portugal, such a coalition was feasible. Here, trade unions and actor groups exposed to high economic risks were successful in preventing several attempts to cut public spending. In the face of this resistance, the government increasingly decided to resort to revenue increases. These results show, on the one hand, that domestic political processes were crucial for fiscal adjustment during the euro crisis. On the other hand, it shows that these processes differ greatly due to different national growth models and different economic dynamics.

A K_r-factor in a graph G is a collection of vertex-disjoint copies of K_r covering the vertex set of G. In this thesis, we investigate these fundamental objects in three settings that lie at the intersection of extremal and probabilistic combinatorics.

Firstly, we explore pseudorandom graphs. An n-vertex graph is said to be (p,β)-bijumbled if for any vertex sets A, B ⊆ V (G), we have e( A, B) = p| A||B| ± β√|A||B|. We prove that for any 3 ≤ r ∈ N and c > 0 there exists an ε > 0 such that any n-vertex (p, β)-bijumbled graph with n ∈ rN, δ(G) ≥ c p n and β ≤ ε p^{r −1} n, contains a K_r -factor. This implies a corresponding result for the stronger pseudorandom notion of (n, d, λ)-graphs. For the case of K_3-factors, this result resolves a conjecture of Krivelevich, Sudakov and Szabó from 2004 and it is tight due to a pseudorandom triangle-free construction of Alon. In fact, in this case even more is true: as a corollary to this result, we can conclude that the same condition of β = o( p^2n) actually guarantees that a (p, β)-bijumbled graph G contains every graph on n vertices with maximum degree at most 2.

Secondly, we explore the notion of robustness for K_3-factors. For a graph G and p ∈ [0, 1], we denote by G_p the random sparsification of G obtained by keeping each edge of G independently, with probability p. We show that there exists a C > 0 such that if p ≥ C (log n)^{1/3}n^{−2/3} and G is an n-vertex graph with n ∈ 3N and δ(G) ≥ 2n/3 , then with high probability G_p contains a K_3-factor. Both the minimum degree condition and the probability condition, up to the choice of C, are tight. Our result can be viewed as a common strengthening of the classical extremal theorem of Corrádi and Hajnal, corresponding to p = 1 in our result, and the famous probabilistic theorem of Johansson, Kahn and Vu establishing the threshold for the appearance of K_3-factors (and indeed all K_r -factors) in G (n, p), corresponding to G = K_n in our result. It also implies a first lower bound on the number of K_3-factors in graphs with minimum degree at least 2n/3, which gets close to the truth.

Lastly, we consider the setting of randomly perturbed graphs; a model introduced by Bohman, Frieze and Martin, where one starts with a dense graph and then adds random edges to it. Specifically, given any fixed 0 < α < 1 − 1/r we determine how many random edges one must add to an n-vertex graph G with δ(G) ≥ α n to ensure that, with high probability, the resulting graph contains a K_r -factor. As one increases α we demonstrate that the number of random edges required ‘jumps’ at regular intervals, and within these intervals our result is best-possible. This work therefore bridges the gap between the seminal work of Johansson, Kahn and Vu mentioned above, which resolves the purely random case, i.e., α = 0, and that of Hajnal and Szemerédi (and Corrádi and Hajnal for r = 3) showing that when α ≥ 1 − 1/r the initial graph already hosts the desired K_r -factor.

This habilitation thesis summarizes the results of 10 scientific publications (references: paper1-10) addressing the topic "Emergence of antimicrobial resistant bacteria in and beyond companion animal medicine”. The first chapter’s intention is to introduce my research area to the reader by providing basic information on the occurrence of antimicrobial resistance (AMR) in bacteria, including general resistance mechanisms, distribution and spread in different ecological environments and the commonly applied clinical classifications relevant for the veterinary medicine field. The following section characterizes the nature of health care associated infections (HAIs) in human and veterinary medicine, including baseline similarities and differences. Subsequently, bacterial pathogens exhibiting particular antibiotic resistances are introduced. Here, a strong focus is set on AMR bacteria frequently associated with HAIs in human and veterinary medicine, which are therefore also considered as “indicator pathogens”. Since β-lactams such as penicillins and cephalosporins are known for their excellent pharmacokinetic properties which is commonly accompanied by a low toxicity for mammals, this group of active substances is of particular importance for antimicrobial treatment of bacterial infectious diseases in both humans and animals. Infections with indicator pathogens harboring resistance towards β-lactams such as Staphylococcus aureus [methicillin resistant S. aureus, (MRSA)] and Escherichia coli [Extended-Spectrum β-Lactamase (ESBL)-producing E. coli (ESBL-E. coli)] are therefore often accompanied by treatment failure. Since antibiotics belonging to this group are among the “first choices” for empirical treatment of infectious diseases, including life-threatening scenarios such as septicemia, collaborative efforts to limit spread of β-lactam resistance are currently an important goal in human- and veterinary medicine. Additional resistances towards further classes of antibiotic substances are frequently associated with MRSA and ESBL-E. coli, leading to a further reduction of therapeutic possibilities in case of infection. In the second chapter, the publications’ results are summarized into four distinct sections. First, the importance of HAI in small animal and equine medicine is illustrated by a literature review considering outbreak events reported so far. A brief historical sketch reveals that problems due to HAI in animal clinics, including cases of zoonotic transmission, have been known since at least 1961. While there have been numerous reports in the past highlighting the technical and scientific developments during the last decades in companion-animal medicine, other important fields such as hygiene management, infection control and occupational safety of employees still lack comparable achievements. The current challenges faced by companion animal clinics are described by studies evaluating the introduction rates for multi drug resistant (MDR) indicator pathogens via colonized horses in a large German university clinic. Overall, n = 341 horses representing distinct medical indications (i.e. 233 horses with "colic symptoms" and 108 with "open wounds") were sampled immediately upon hospital admission. The overall screening results showed that MRSA was detected in 3.5% of the nasal swabs and ESBL-Enterobacteriaceae in 10.3% (mainly ESBL-E. coli) of the fecal samples. Subsequent molecular typing of the isolates showed that all MRSA belonged to sequence type (ST) 398, the currently predominating MRSA lineage identified in clinical samples of horse origin in Europe. In contrast, ESBL-E. coli showed a broad heterogeneity in genomic backgrounds associated with the β-lactam resistance. However, isolates belonging to ST complexes (STC) 1250 (31.7%) and STC10 (19.5%) clearly dominated the collection. Notably, all MRSA and ESBL- E. coli isolates isolated in these studies showed additional antimicrobial resistances to a minimum of three further classes of antibiotics. For assessment of a particular AMR situation in certain bacterial pathogens and/or environments, e.g. if surveillance of AMR in a pathogen causing HAI is needed, an unambiguous species identification is mandatory. Species identification is essential for sound interpretation of antimicrobial sensitivity testing (AST) results and therefore a prerequisite to classify the resistance phenotype of the pathogen correctly. Moreover, species identification is also needed for precise interpretation of additional results gained by other molecular biological methods. A combination of bacterial genome analysis with matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF MS) allowed us to differentiate between the species Staphylococcus intermedius, S. delphini and S. pseudintermedius, which was previously a time-consuming and uncertain approach. Since methicillin resistant S. pseudintermedius (MRSP) are often associated with resistances towards several other antimicrobials, a rapid and reliable species identification using MALDI-TOF MS promotes early and targeted antimicrobial therapy in cases of infection and, if necessary, the initiation of additional hygiene measures to prevent its spread. The following results demonstrate the overwhelming importance of constant adjustments of microbiological diagnostic screening methods for identification of MDR: In 2011, a novel variant of the methicillin resistance gene (later: mecC) was described for MRSA of cattle and human origin. A study we immediately initiated identified mecC-MRSA in clinical samples from horses, dogs, cats, wild animals and rodents. Here, the “weak” expression of the resistance phenotype, now known to be a common feature of mecC-MRSA, was a challenge to classify an isolate as MRS, which was achieved after diagnostic adjustments. As described above, methicillin resistance is often associated with other resistances, e.g. towards tetracyclines, zinc and arsenic compounds. Our detailed analysis of the integration site for the methicillin resistance-mediating mobile genetic element in staphylococci was identified as a "hot spot" for recombination events: We discovered a mosaic-like genomic structure which is prone to integration of mobile resistance-mediating elements of different types. The combination of up-to-date microbiological diagnostics with classical principles of infection epidemiology allowed us to answer important questions concerning possible transmission scenarios for MDR pathogens in companion animal clinics and identify risk factors for MRSA infections in these animals. In 2012, the ability of MRSA to cause HAI in companion animals and its importance as an indicator pathogen for veterinary medicine was already known. At that time however, similar information was not available for ESBL- E. coli. To address this deficit, we retrospectively investigated several cases of serious infections caused by ESBL-E. coli in hospitalized horses in a veterinary clinic. Comparative analysis of molecular typing results obtained for 13 ESBL-E. coli together with the horses’ clinical data revealed a putative spatio-temporal relationship of the isolates, which probably reflected several transmission events between these patients. In another case-control study, we have examined the possible risk factors for wound infections caused by MRSA in horses, dogs and cats. Multivariable logistic regression identified the following variables as risk factors for MRSA infection compared to methicillin susceptible infection: (i) the number of employees working at the veterinary setting (n>10; p<0.001), (ii) antibiotic treatment prior to sampling (systemic: p=0.002; local: p=0.049, both: p=0.011) and (iii), surgical site infection (p<0.001). Spa typing revealed clonal complexes (CC) previously known for hospital-associated lineages spreading in human health-care settings in Germany (i.e. CC5 and CC22) as the dominating lineages among isolates of dog and cat origin. Equine MRSA belonged nearly exclusively to CC398, a CC previously described as a nosocomial pathogen in equine clinical settings. While performing the studies mentioned above, we considered whether transmission of relevant AMR bacteria between pets and their owners (e.g. MRS) occur outside the typical hospital environment, and further, which circumstances and human behavioral patterns might influence such events. Therefore, we investigated different aspects of the human-to-dog relationship together with MRS carriage at a dog show in 2009. We introduced a questionnaire accompanied by a screening program of the nasal swabs of dog owners (108) and their dogs (108) with respect to staphylococci. S. aureus was identified in swabs obtained from 20 (18.5%) humans and two dogs (1.8%), respectively. 15 dogs (13.9%) and six owners (5.6%) harbored S. pseudintermedius, including one MRSP. Interestingly, 68.5% of the dog owners allowed their dog(s) to rest on the sofa, 39.8% allowed their dog(s) to lay on their bed, 93.5% let them lick their hands, and 52.8% let them lick their face. A bivariate analysis of putative risk factors showed that dog owners who kept more than two dogs were significantly more likely to become colonized with S. pseudintermedius than those who kept only one or two dogs (p<0.05). The results section closes with the most recent results, which demonstrated the continuing adaptation of MDR bacteria to the companion animal hospital environment. We showed that equine MRSA-ST398 have acquired different mobile genetic elements (i.e. pathogenicity islands, phages) harboring immune-modulating factors which impede the activation of the complement system, which is among the most important defense measures of the innate immune system towards invasive S. aureus infections. The equine MRSA harbored genes encoding variants of the staphylococcal complement inhibitor protein (SKIN), known for its function in subverting the complement system in plasma of humans, cattle, pigs and horses. These results clearly demonstrated the existence of extended host (EHSG) lineages and their characteristic flexibility with respect to niche- and host-adaptation. Chapter 3’s discussion section presents the general concepts of surveillance of antibiotic consumption, HAI and antibiotic resistance in human medicine, and expands the context with respect to the results of this habilitation thesis. The importance of HAI and MDR pathogens in companion animals for human health is pointed out and current developments in this area are discussed. With regard to integrated surveillance for antibiotic resistance, antibiotic consumption and HAI, a "best practice" model featuring the One Health concept is outlined. This is followed by a discussion of prospects for small animal and horse medicine, taking into account realistic human and financial resources to establish fundamental surveillance structures. The following section summarizes the key factors for HAI prevention in veterinary clinics. In particular, technical progress (i.e. genomics/bioinformatics) in the field of molecular epidemiology has contributed to these findings, a development which is reflected in the publications presented. Finally, possible reasons for the occurrence of MDR pathogens in animal clinics are given, using horse clinics as an example. The occurrence of ESBL-E. coli and MRSA belonging to EHSG-lineages explain why further research on these MDR pathogens is necessary, especially with respect to further host- and niche-adaptation. In summary, the publications presented make it clear that research on EHSG pathogens and their importance has only just begun. New methods of molecular epidemiology currently (2020) offer completely new opportunities to study adaptive changes in bacterial genomes in large, representative studies. However, care is needed with respect to establishment of a suitable, representative isolate collection, which is of crucial importance for the validity of the studies. Integrated One Health surveillance, as outlined in this document, could reflect the current importance of MDR EHSG pathogens for human and veterinary medicine. An integrated approach would lead to a better understanding of the bacterial adaptation processes to ecological niches as a whole and reveal new, epidemiologically significant developments in a timely manner, whereas currently we can often only trace these types of developments in retrospect.

References paper1 Walther, B., K. Tedin, and A. Lübke-Becker, Multidrug-resistant opportunistic pathogens challenging veterinary infection control. Vet Microbiol, 2017. 200: p. 71-78. paper2 Walther, B., Klein, K.S., Barton, A.K., Semmler, T., Huber, C., Wolf, S.A., Tedin, K., Merle, R., Mitrach, F., Guenther, S., Lübke-Becker, A., Gehlen, H., 2018. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Acinetobacter baumannii among horses entering a veterinary teaching hospital: The contemporary "Trojan Horse". PLoS One 13, e0191873. paper3 Murugaiyan, J., Walther, B., Stamm, I., Abou-Elnaga, Y., Brüggemann-Schwarze, S., Vincze, S., Wieler, L.H., Lübke-Becker, A., Semmler, T., Roesler, U., 2014. Species differentiation within the Staphylococcus intermedius group (SIG) using a refined MALDI-TOF MS database. Species differentiation within the Staphylococcus intermedius group using a refined MALDI-TOF MS database. Clin Microbiol Infect 20(10): 1007-1015. paper4 Walther, B., Wieler, L.H., Vincze, Sz., Antão, E.-M., Brandenburg, A., Stamm, I., Kopp, P.A., Kohn, B., Semmler, T., Lübke-Becker, A., 2012b. MRSA variant in companion animals. Emerg Infect Dis 18, 2017-2020. paper5 Semmler, T., Harrison, E.M., Lübke-Becker, A., Ulrich, R. G., Wieler, L. H., Guenther, S., Stamm, I., Hanssen, A. M., Holmes, M. A., Vincze, Sz., Walther, B. 2016. A Look into the Melting Pot: The mecC-Harboring Region Is a Recombination Hot Spot in Staphylococcus stepanovicii." PLoS One 11(1): e0147150. paper6 Walther B, Lübke-Becker A, Stamm I, Gehlen H, Barton AK, Janssen T, Wieler LH, Guenther S. Suspected nosocomial infections with multidrug resistant E. coli, including extended-spectrum beta-lactamase (ESBL)-producing strains, in an equine clinic. Berl Muench Tieraerztl Wochenschr. 2014, 127(11-12):421-427. paper7 Vincze S., Brandenburg, A.G., Espelage W., Stamm I., Wieler L. H., Kopp P. A., Lübke-Becker A., Walther B., 2014. Risk factors for MRSA infection in companion animals: Results from a case-control study within Germany. Intl J Medical Microbiol 10/2014; DOI: 10.1016/j.ijmm.2014.07.007 paper8 Walther, B., Hermes, J., Cuny, C., Wieler, L.H., Vincze, S., Abou Elnaga, Y., Stamm, I., Kopp, P.A., Kohn, B., Witte, W., Jansen, A., Conraths, F.J., Semmler, T., Eckmanns, T., Lübke-Becker, A., 2012a. Sharing more than friendship--nasal colonization with coagulase-positive staphylococci (CPS) and co-habitation aspects of dogs and their owners. PLoS One 7, e35197 paper9 Walther, B., Monecke, S., Ruscher, C., Friedrich, A.W., Ehricht, R., Slickers, P., Soba, A., Wleklinski, C.G., Wieler, L.H., Lübke-Becker, A., 2009a. Comparative molecular analysis substantiates a zoonotic potential of equine Methicillin- resistant Staphylococcus aureus (MRSA). J Clin Microbiol. 47, 704-710. paper10 Walther B., Klein K.S., Barton A.K., Semmler T., Huber C., Merle R., Tedin K., Mitrach F., Lübke-Becker A., Gehlen H. Equine Methicillin-Resistant Sequence Type 398 Staphylococcus aureus (MRSA) Harbor Mobile Genetic Elements Promoting Host Adaptation. Front Microbiol 2018, 9:2516.

Hypertension prevalence is still growing worldwide as well as the number of drug-therapy non-responsive patients. Therefore, improving the current and developing new therapies to control blood pressure (BP) is warranted. Growing literature points to the sympathetic nerve system as the major system controlling long-term BP homeostasis, and human hypertension is often accompanied by increased sympathetic nerve activity (SNA). The renin angiotensin system (RAS) is involved in cardiovascular control and beyond due to the broad actions of the powerful hormone angiotensin II (Ang II) produced in the circulation or within organs. The project aimed to further characterize the modulatory effects of the RAS on SNA and its impact on cardiovascular control and erythropoiesis, particularly focusing on the role of brain-borne Ang II. These questions were experimentally addressed with RAS gain and loss of function mouse models in the FVB/N background strain, and complementary experiments were performed with rats and mixed background mice. A transgenic line with brain-specific angiotensinogen (Agt) expression was validated (Agt-Tg) and used to demonstrate in vivo local brain Ang II formation. FVB/N mice cardiovascular regulation revealed predicted and surprising phenotypes. As expected FVB/N mice lacking the major Ang II receptor (AT1a-KO) presented reduced BP, and Agt-Tg displayed increased BP accompanied by increased SNA. Surprisingly, adult FVB/N mice lacking Agt (Agt-KO) were normotensive contrasting previous findings in other strains. Paradoxically, the genetic brain-rescue of Agt in Agt-KO (Agt-KO-Tg) strongly reduced BP. Using integrative physiology, we identified that the normotension in Agt-KO is driven by increased vascular tone due to exaggerated sympathetic outflow and impaired nitric oxide production which is reversed by brain Ang II in Agt-KO-Tg contrasting Agt-Tg. Agt-KO-Tg also presented better renal function compared to Agt-KO despite similar renal morphological damage. In addition, brain Ang II strongly activated renal SNA in Agt-KO-Tg, and renal denervation had minimal effect on Agt-KO and Agt-KO-Tg baseline BP. A genome-wide-association-study was employed to uncover the genetic alteration causing FVB/N Agt-KO to fail in reducing BP. For this, a mixed background (FVB/N x C57BL/6N) F2 Agt-KO line was generated. Strikingly, the phenotyping data of the F2 Agt-KO strongly indicates a single recessive allele responsible for the BP phenotype in FVB/N Agt-KO once the BP in the F2 presented a clear bimodal distribution with most mice being hypotensive. However, the association analyses demonstrated that several loci likely contribute to the phenotype in FVB/N Agt-KO. Finally, we identified one central and one peripheral mechanism of erythropoiesis regulation modulated by the RAS. In the brain, Ang II favors erythropoiesis via SNA. Agt-Tg with elevated brain Ang II displayed increased erythropoiesis that was reverted by peripheral sympathectomy, and rats with depleted brain Agt presented decreased baseline erythropoiesis. In the periphery, the experiments revealed that the RAS influences the iron homeostasis because Agt-KO mice presented microcytic anemia accompanied by reduced levels of circulating and tissue-stored iron. Altogether, the data set generated within the frame of my doctoral thesis supports local formation and function of brain Ang II. Furthermore, we provided evidence that brain Ang II is involved in differential SNA regulation to different organs impacting BP homeostasis. Finally, two unprecedented mechanisms of erythropoiesis control modulated by the RAS via SNA and iron homeostasis were revealed.

Einsatzkräfte unterscheiden sich aufgrund der Berufsselektion und dem damit zusammenhängenden Berufsstatus und Lebensalter von der Allgemeinbevölkerung. Ansonsten ist ihr „Lebensrisiko“ zur Entwicklung von psychischen Beeinträchtigungen vergleichbar – mit der Ausnahme der berufsbedingten Risiken. Da bei psychischen Störungen von Einsatzkräften keine von der Allgemeinbevölkerung unterschiedlichen Therapieverfahren eingesetzt werden müssen, bleiben zur Minimierung der diesbezüglichen beruflichen Risiken die Säulen der Einsatzvor- und -nachbereitung sowie die der De-Stigmatisierung. Um die Einsatzvor- und -nachbereitung möglichst spezifisch auf die unterschiedlichen Berufsgruppen und Geschlechter auszurichten, ist die Erfassung der verschiedenen Risikoprofile notwendig. Dieses Wissen kann dann direkt in die Maßnahmen und in die berufliche Ausbildung einfließen. Ein regelmäßiges Überprüfen der mentalen Fitness kann in diesem Segment ebenfalls helfen, Fördermöglichkeiten zu identifizieren. Da solche Ansätze jedoch maßgeblich von der Akzeptanz der Teilnehmenden abhängen, sollten sie freiwillig bleiben und den Fokus auf positive Aspekte wie Trainierbarkeit oder Resilienz richten. Zudem ist ein repetitives Screening meist nur dann sinnvoll, wenn entsprechende Trainings- und Fördermöglichkeiten zur Verfügung stehen, die unterhalb psychotherapeutischer Interventionen angesiedelt sind. Diese könnten beispielsweise im Rahmen eines betrieblichen Gesundheitsmanagements umgesetzt werden. Wenn sie eine entsprechende Bandbreite abdecken, dürfte dies auch einen positiven Einfluss auf die Perzeption dieser Angebote haben. Ein weiterer wichtiger Baustein ist die De-Stigmatisierung. Einsatzkräfte neigen aus Angst vor Stigmatisierung stärker dazu, Symptome psychischer Störungen zu verschweigen und sich nicht behandeln zu lassen. Angst vor Karrierenachteilen und der Wunsch, allein mit dem Problem fertig zu werden, sind die angegebenen Hauptgründe dafür (Wittchen et al., 2012; DePierro et al., 2021). Unter dem Ansatz „vom Helden zum Profi“ konnten Einsatzkräfte zu einer kognitiven Neubewertung gelangen und anerkennen, dass psychische Störungen genauso zu den berufsbedingten Risiken gehören wie physische Verletzungen (Wesemann et al., 2016). Häufig sind es jedoch nicht nur die Betroffenen selbst, die unter den Störungen leiden, sondern auch ihre Angehörigen. Der frühe Einbezug dieser Gruppe könnte eine Trendwende in der De-Stigmatisierung darstellen. Da die Angehörigen die Betroffenen in der Regel sehr gut kennen, bemerken sie die Veränderungen meist unmittelbar. Dieses frühe Erkennen kann aber auch zu Unsicherheiten bezüglich der eigenen Einschätzung führen. Sofern sie ein Instrument zur Beurteilung, ob diese Veränderungen noch im normalen Bereich liegen, zur Hand hätten, wäre eine gewisse Handlungssicherheit gegeben. Damit könnten sie die Betroffenen gezielter ansprechen und gemeinsam nach Lösungsmöglichkeiten suchen. Die größte Wirkung kann vermutlich erzielt werden, indem alle genannten Ansätze in einem Gesamtkonzept umgesetzt werden.

Subduction zones, where one tectonic plate slides underneath the other, host the largest earthquakes on Earth. These zones are characterized by intense earthquake activity and are responsible for 95 % of all moment releases on Earth. The shallow portion of the subduction zone interface (i.e., megathrust) generated the largest ever recorded earthquakes, such as the 1960 Valdivia earthquake in Chile, the 2004 Sumatra earthquake in Indonesia, and the 2011 Tohoku-Oki earthquake in Japan on the Earth. Unwrapping the behavior of this portion of the subduction zone, which generates the most significant earthquakes and devastating tsunamis, is a vital step forward in earthquake geoscience. Monitoring only a fraction of a single megathrust earthquake cycle and the offshore location of the source of these earthquakes are the foremost reasons for the insufficient understanding. The insufficient offshore observation and the interseismic data incompleteness led earthquake scientists to employ analog and numerical modeling approaches to unfold the linkage between short-term elastic (i.e., coseismic) and long-term permanent (i.e., several seismic cycles) deformation of the subduction zones. Revealing these relationships allows us to identify which long and short-term signals earthquake scientists should look for remotely or in the field to unwrap the subduction zone’s seismic cycle history. In this research, I investigate a simplified analog model of a subduction zone from trench to the location of volcanic arc and 240 km along strike using elastoplastic granular material and stick-slip analog material at a laboratory scale. Establishing generic seismotectonic scale models enables me to generate hundreds of megathrust seismic cycles and monitor the earthquake-related surface and cross-sectional deformation pattern at high resolution in both space and time. I attempt to demonstrate what surface deformation signals the frictional and mechanical changes on the interface generates over coseismic and early postseismic stages and interseismic intervals. Additionally, at a more extended time scale (tens to hundreds of earthquake cycles), I study what surface strain pattern in the forearc from the trench to the coastal region can be permanently preserved. This provides critical observations for earthquake geoscientists to tie forearc surface deformation to subsurface elastoplastic processes at the shallow portion of the subduction interface. I apply a geodetic slip inversion technique to analog trench-breaking and non-trench-breaking megathrust earthquakes to demonstrate how limited offshore geodetic coverage affects coseismic slip models. The slip models derived from analog earthquakes show quantitative and qualitative changes as a function of offshore coverage: 1) Shallow slip cannot be resolved if the observation coverage of the offshore segment is <50%. 2) the slip pattern of shallow event flips from landward to trenchward skewed as offshore coverage reduces to <40%. 3) In the case of no offshore coverage, the slip pattern for both event types converges to a similar unimodal pattern. Additionally, I infer 5-20% slip overestimation when the observations are above the high slipping zone during trench-breaking events versus 5-10% underestimation during non-trench-breaking events if observations are land-limited. Moreover, the moment magnitude derived for trench-breaking ruptures might be affected. Furthermore, I mimic homogenous and heterogeneous megathrust interfaces at the laboratory scale to monitor the strain relaxation on the two elastically non-identical plates by establishing analog velocity weakening and strengthening materials. I propose a sequential elastic rebound that follows the coseismic shear-stress drop in the elastic-frictional models: a fast rebound of the upper plate and the delayed and smaller rebound on the slab. The delayed rebound of the slab, along with the rapid relaxation of the upper plate after an elastic overshooting, accelerates the relocking of the megathrust. This acceleration triggers/antedates the failure of a nearby asperity and enhances the early backslip in the rupture area. The long-term frictional-elastoplastic interaction between the interface and its overlying wedge causes variable surface strain signals. I establish two coseismically compressional and extensional wedge configurations to explore the mechanical and kinematic interaction between the shallow wedge and the interface. The results demonstrate that this interaction can partition the wedge into different segments. I highlight that a more segmented upper plate represents a subduction megathrust that generates more characteristic and periodic events. Moreover, the results illustrate that different wedge segments may switch their state from compression/extension to extension/compression domains. Additionally, the strain time series of the coastal zone reveals that the strain state may remain quasi-stable over a few seismic cycles before switching to the opposite mode. These observations are key for evaluating earthquake-related morphotectonic markers (i.e., marine terraces) and short-term interseismic GPS time-series onshore (coastal region).

Die bakterielle Kontamination des männlichen Genitaltraktes und vor allem des Seminalplasmas von Bullen ist ein bekanntes Problem in der Rinderzucht. Pathogene Bakterien, die venerische Erkrankungen verursachen, wurden in den letzten Jahren intensiv untersucht. Im Gegensatz dazu ist das Wissen über kommensale Bakterien des Genitaltraktes von Bullen bislang sehr gering. Aus diesem Grund war es das Ziel dieser Studie, kommensale Bakterien aus dem bovinen männlichen Genitaltrakt zu isolieren und deren Effekt auf endometriale Epithelzellen und bovine Spermien in vitro zu untersuchen. 57 Seminalplasmaproben von 40 verschiedenen Zuchtbullen wurden untersucht. Zusätzlich wurden bei 12 geschlachteten Mastbullen Tupferproben von Penisspitze und Präputium genommen. Bakterien wurden in speziellen Nährmedien für die Anzucht von Milchsäurebakterien inkubiert. Erhaltene Isolate wurden durch eine Sequenzierung der 16S-rDNA charakterisiert. Endometriale Epithelzellen wurden bis zur zweiten Passage kultiviert und dann in Ko-Kultur mit isolierten Bakterien verbracht. Diese Ko-Kultur fand immer in drei unterschiedlichen „multiplicities of infection“ (MOI 1, 5 und 10) statt. Jeder untersuchte Bakterienstamm wurde mit Zellen von mindestens vier verschiedenen Schlachttieren kokultiviert. Eine Untersuchung der Zellviabilität via Trypanblau-Färbung wurde alle 24 Stunden über einen Zeitraum von drei Tagen durchgeführt. Zusätzlich wurden endometriale Epithelzellen für einen Zeitraum von sechs Stunden ko-kultiviert, welche alle zwei Stunden lysiert wurden. Diese Zell-Lysate dienten der Untersuchung der Chemokin-X-Ligand (CXCL) 1/-2-, CXCL3-, CXCL5-, Interleukin (IL) 6-, IL8- und Prostaglandin-Endoperoxid-Synthase 2-(PTGS2) mRNA-Expression. Dies geschah durch eine reverse Transkription und anschließender Real-time-PCR. Bovine Spermien wurden nach der Samengewinnung für bis zu 4 Stunden mit unterschiedlichen Milchsäurebakterien in dem Verdünner Triladyl kokultiviert. Nach 2 und 4 Stunden wurde via computergestützer Vitalitätsanalyse (CASA) die progressive Motilität der Spermien ermittelt. Die bakteriologische Untersuchung des Seminalplasmas von Zuchtbullen ergab bei 27 der insgesamt 54 Proben kein Nachweis von Bakterien. In 27 Proben konnten Bakterien charakterisiert werden; darunter einige Spezies der Gattungen Staphylococcus, Streptococcus und Bacillus. Allerdings konnten in vier Proben, welche von drei verschiedenen Bullen stammten, Milchsäurebakterien isoliert werden. Drei der Isolate wurden als Lactobacillus (L.) mucosae (L. mucosae 8.1, 8.2 und 31) identifiziert und ein weiteres Isolat als Leuconostoc mesenteroides. Bei den Tupferproben des Genitaltraktes von Mastbullen konnten in allen Proben Bakterien isoliert werden. Darunter war einmal Streptococcus sp. und Corynebacterium sp., während alle anderen Isolate den Milchsäurebakterien zugerechnet werden. Ein Isolat wurde als Lactococcus garviae und alle anderen als Pediococcus spp. (n = 28) oder Weissella spp. (n = 3) identifiziert. Alle vier isolierten Milchsäurebakterien aus dem Seminalplasma wurden weiterführend untersucht, während aus den Isolaten der Mastbullen nur fünf Isolate zufällig ausgesucht und weiter untersucht wurden. Einige der Isolate führten nach Ko-Kultur zu einem Zelltod der Epithelien, während andere Isolate nach 72 Stunden keine Veränderungen an endometrialen Epithelzellen bewirkten. L. mucosae 8.2, L. mucosae 31 und Leuconostoc mesenteroides führten nicht zu Veränderungen der Zell-Viabilität, während Enterococcus faecalis, Lactococcus garviae, Pediococcus acidilactici, Pediococcus pentosaceus, Weissella thailandensis und Weissella hellenica teilweise bereits nach 24 Stunden zu einem vermehrten Zelltod und zu einer verringerten Konfluenz der endometrialen Epithelzellen führten. L. mucosae 8.2, Pediococcus acidilactici, Pediococcus pentosaceus und Weissella hellenica führten nicht zu Veränderungen der mRNA-Expression der untersuchten pro-inflammatorischen Faktoren, während L. mucosae 8.1, L. mucosae 31 und Leuconostoc mesenteroides zu einer signifikanten Erhöhung der mRNA-Expression von einigen pro-inflammatorischen Faktoren führten. Die Ko-Kultur von bovinen Spermien mit Milchsäurebakterien zeigte, dass L. buchneri, isoliert aus dem bovinen Uterus, Leuconostoc mesenteroides und L. mucosae 8.1 nicht zu Veränderungen der progressiven Motilität führten. L. mucosae 8.2 und L. mucosae 31 hingegen führten bereits nach 2 Stunden zu einer geringfügigen Verringerung der progressiven Motilität boviner Spermien um maximal 5,5 %. Nach 4 Stunden wurde nur bei L. mucosae 8.2 eine Verringerung der progressiven Motilität um 4,3 % beobachtet. Abschließend lässt sich festhalten, dass kommensale Bakterien im bovinen männlichen Genitaltrakt existieren. Es wurden nur wenige Isolate aus dem Seminalplasma isoliert, während von den Schleimhäuten des Genitaltraktes aller Bullen Milchsäurebakterien kultiviert werden konnten. Der Einfluss dieser Bakterien auf das Uterusepithel und auf bovine Spermien in vitro ist speziesspezifisch sehr unterschiedlich.

Glyceraldehyde (GA) is a 3-carbon monosaccharide that is present in cells as byproduct of fructose metabolism. The phosphorylated form, glyceraldehyde-3-phosphate is a key metabolite in central carbon metabolism. Bruno Mendel and Otto Warburg proved that the application of glyceraldehyde to cancer cells inhibits glycolysis and their growth. This phenomenon was extensively studied up until the 1970's. The consensus reached was that the L-isomer of glyceraldehyde is a more effective glycolytic inhibitor than the D-isomer. However, the mechanism by which this occurred was not clarified. This thesis describes a novel mechanism by which L-GA inhibits cancer cell growth. The work describes how L-GA induces significant changes in the metabolic profile and hinders nucleotide biosynthesis. Gas chromatography–mass spectrometry and 13C-labelling was employed to measure the flow of carbon through glycolytic intermediates under L-GA treatment. The data in this thesis recapitulated previous research on the inhibitory efficacy of L-GA and D-GA. It was found that L-GA is a more potent inhibitor of glycolysis due to its targeting of NADH-dependent reactions, leading to a redox crisis in the cancer cell. Through proteomics analysis it was confirmed that redox mechanisms were modulated via L-GA. This elucidated a specific subset of proteins harbouring oxidoreductase and anti-oxidant activity. Further bioinformatic and molecular biology analysis suggested that the generation of reactive oxygen species via L-GA activates the KEAP1-NRF2 pathway, to drive the expression of anti-oxidant proteins. Analysis of nucleotide pools in L-GA treated cells depicted a remarkable and previously unreported phenotype. Nucleotide biosynthesis in neuroblastoma cells is significantly inhibited upon L-GA treatment, yet the D-isomer showed minimal inhibition. Critically, this evidence could be linked to findings in the proteome and metabolome. Through the application of the antioxidant N-acetyl-cysteine in conjunction with L-GA, inhibition was relieved. This work presents significant novel evidence for the mechanism of L-GA action in neuroblastoma cells. Specifically, a simple sugar that inhibits the growth of cancer via dysregulating the fragile homeostatic environment inherent to the nature of the cancerous cell.

Multidimensionale Aspekte wie Komorbiditäten, Lebensqualität, Ernährungszustand sowie anästhesiologische, perioperative und chirurgische Daten waren Bestandteil unserer bisherigen Forschungsarbeit. Der Ernährungszustand und die funktionelle Lebensqualität stellten sich als die wichtigsten Risikofaktoren für die erhöhte Morbidität und Mortalität heraus. In unseren Arbeiten konnten wir zeigen, dass neben dem FIGO-Stadium und dem ECOG-Status der präoperative Ernährungsstatus, einschließlich BMI und Phasenwinkel in der Bioimpedanzmessung, wichtige Indikatoren für schwere postoperative Komplikationen sind. Lebensqualität mit eingeschränkter körperlichen Funktion, Symptome wie Übelkeit und Erbrechen und reduzierte kognitive Funktion zeigten sich ebenfalls als signifikante Prädiktoren für schwere postoperative Komplikationen. Außerdem haben wir versucht die Gebrechlichkeit der Patientinnen evident zu quantifizieren und mögliche verbundene Risiken zu erkennen. Zur Quantifizierung der Gebrechlichkeit haben wir zwei neue Modelle, das physikalische phänotypische Modell und das kumulative Defizitmodell bei unseren Patientinnen untersucht. Den Frailty Index haben wir modifiziert für unsere gynäkologischen Patientinnen und konnten zeigen, dass gebrechliche Patientinnen mit einem Frailty Index> 0,26 5-fach höheres Risiko für schwere postoperative Komplikationen hatten. Das physikalische Phänotyp Model nach Fried zeigte hingegen keine signifikante Korrelation mit den schweren postoperativen Komplikationen in unserer Kohorte.

Die Herausforderung besteht darin, ein zuverlässiges und praktisches Vorhersagemodell für schwere postoperative Komplikationen zu entwickeln, das eine umfassende präoperative Beurteilung mit einem mehrdimensionalen Ansatz für die Patientin umfasst.

Die methylierungsbasierte Klassifikation von Hirntumoren hat zu einer tiefgreifenden Veränderung unserer Betrachtungsweise neuropathologischer Tumoren geführt, die sich auch in der kommenden, neuen WHO Klassifikation in Form integrierter, molekularer Diagnosen niederschlägt. Der Paradigmenwechsel durch neue molekulare Methoden hat sich jedoch auch essentiell auf den Arbeitsalltag und die Routineabläufe in neuropathologischen Instituten ausgewirkt, ebenso wie auf die Art der Befundung, das Selbstverständnis als Diagnostiker und die Ausbildung junger Neuropathologen. Die Arbeit zeigt anhand ausgewählter, konkreter Beispiele wie sich wissenschaftliche Fragestellungen und Herangehensweisen, aber auch Verständnis und Implementierung von Ergebnissen vor, während und nach der epigenetischen Revolution im Bereich der Hirntumordiagnostik verändert haben. Während vor Einführung der Methylierungsanalysen histologisch definierte Hirntumorentitäten Ausgangpunkt für explorative, genetische Untersuchungen waren, wie dies in der ersten Arbeit anhand der papillären Kraniopharyngeome und in der zweiten Arbeit anhand der solitär fibrösen Tumoren und Hämangioperizytomen gezeigt wird, repräsentiert die dritte Arbeit einen diagnostischen Meilenstein in der Hirntumordiagnostik und weist auf das transformierende Potential einer morphologie-unabhängigen, auf epigenetischen Signaturen beruhenden und durch bioinformatische Analysen erst nutzbaren Klassifikation von ZNS Tumoren für die Routinediagnostik und Forschung hin. Die vierte Arbeit zeigt am Beispiel der ZNS Paragangliome, wie sich durch die Anwendung der epigenetischen Analysen neue, molekular definierte Entitäten abgrenzen lassen. In der fünften Arbeit wird am Beispiel ependymaler Tumoren mit dem epigenetischen Profil der Methylierungsklasse „Subependymom, posterior fossa“ gezeigt, dass sich innerhalb einer nun epigenetisch definierter Tumorentität molekulare Risikogruppen identifizieren lassen, die charakteristische, genetische Veränderungen aufweisen, deren routinemäßige Bestimmung möglicherweise zu einer verbesserten Patienten-Stratifizierung in zukünftigen Studien beitragen könnte.

Die restaurative Proktokolektomie mit Ileumpouchanlage gilt als Goldstandard in der operativen Therapie der Colitis ulcerosa. Das Verfahren wurde 1978 durch Parks und Nicholls erstbeschrieben und hat seitdem eine kontinuierliche Weiterentwicklung erfahren. Es wird heutzutage überwiegend mehrzeitig und minimalinvasiv durchgeführt. Dennoch entstehen, insbesondere im Hinblick auf die stetige Weiterentwicklung der medikamentösen Therapiemaßnahmen, immer wieder neue Herausforderungen an die Umsetzung und weitere Optimierung der chirurgischen Maßnahmen. Eine Heilung der Erkrankung ist zum aktuellen Zeitpunkt noch immer lediglich der Chirurgie zuzuschreiben. Da die immunsuppressive Therapie jedoch im Vordergrund der Behandlung von Colitis ulcerosa PatientInnen steht, muss deren Einfluss auf die Entscheidung zu einem operativen Vorgehen untersucht werden. Steht die Indikation zur Operation fest, muss noch zwischen zwei- oder dreizeitigem Verfahren entschieden werden. Hierbei sollte neben dem Allgemein- und Ernährungszustand der PatientInnen, die präoperative Immunsuppression beachtet werden. Es konnte gezeigt werden, dass das dreizeitige Vorgehen bei ausgeprägter präoperativer Immunsuppression über einen längeren Zeitabschnitt deutliche Vorzüge hinsichtlich einer kürzeren Liegedauer, einer kürzeren Intensivzeit und der geringeren Rate an Majorkomplikationen im Hinblick auf die Indexoperation Pouchanlage aufweist und daher bei PatientInnen mit Colitis Ulcerosa und einer hohen Rate an Immunsuppression als Verfahren der Wahl gewählt werden sollte. Diese Aspekte finden in den nationalen und internationalen Leitlinien bereits Anwendung. Ferner wurde im Rahmen der zunehmend an Bedeutung gewinnenden Minimalisierung des Zugangsweges von Operationstechniken deren Effekte auf die restaurative Proktokolektomie untersucht. Sowohl die komplette bergeinzisionslose als auch die klassische laparoskopische Proktokolektomie stellten in der vorliegenden Arbeit sichere Operationstechniken für PatientInnen mit chronisch entzündlichen Darmerkrankungen dar und sollten daher durchgeführt werden, wenn entsprechende Expertise vorhanden ist. Neben besseren kosmetischen Ergebnissen scheint sich durch eine weitere Minimierung des Zugangstraumas ein potenzieller Vorteil hinsichtlich reduzierter Wundinfektionen, insbesondere bei den häufig immunsupprimierten PatientInnen, zu ergeben. In einem weiteren Untersuchungsansatz sollte die Lebensqualität der PatientInnen nach einem mehrzeitigen Operationsverfahren, was einen zusätzlichen Krankenhausaufenthalt und eine weitere Operation beinhaltet, untersucht werden. Es konnte gezeigt werden, dass die restaurative Proktokolektomie zu einer verbesserten Lebensqualität, die sogar mit der Normalbevölkerung vergleichbar ist, führt. Die Lebensqualität wird dabei weder kurz- noch langfristig durch die Wahl für ein zwei- oder dreizeitiges Verfahren beeinflusst. Die Indikation für ein mehrzeitiges Verfahren sollte daher an die Schwere der Grunderkrankung, den Ernährungszustand der PatientInnen und dem Ausmaß der Immunsuppression zum Zeitpunkt der Operation angepasst werden. Sie sollte nicht von der Angst vor Komplikationen oder einer reduzierten Lebensqualität durch eine zusätzliche Operation beim mehrzeitigen Verfahren beeinflusst werden. Ferner sollte der optimale Zeitpunkt zur Operation untersucht werden. Oft kommt es zu einer Verzögerung einer nötigen Operation, entweder aus Sorge der PatientInnen vor eventuellen Komplikationen oder aufgrund zurückhaltender Überweisung der PatientInnen in einer chirurgischen Klinik. Der Operationszeitpunkt ist somit sehr variabel und abhängig vom Rat der betreuenden ÄrztInnen und der Präferenzen der PatientInnen. Ein Drittel der PatientInnen in der vorliegenden Untersuchung fand, dass ihre Operation früher hätte durchgeführt werden sollen. Bei einer therapierefraktären Erkrankung ist die Beratung zu einer frühen elektiven Operation patientInnenzentriert und in Übereinstimmung mit der Entscheidung der PatientInnen. Frühe interdisziplinäre Diskussionen durch ein auf chronisch entzündliche Darmerkrankungen spezialisiertes Team können Komplikationen reduzieren, Therapiekosten und Nebenwirkungen der immunsuppressiven Medikamente reduzieren. Trotz der über die Jahrzehnte gesammelten umfangreichen Erfahrung in der operativen Behandlung der Colitis ulcerosa gibt es immer wieder Fälle, in denen die Ileumpouchanlage frustran verläuft. In der vorliegenden Arbeit konnten mehrere unabhängige Risikofaktoren für eine frustrane IPAA identifiziert werden. Eine Verkürzung der Mesenterialwurzel bildet den technischen Hauptgrund für eine fehlgeschlagene IPAA ab. Die Optimierung der präoperativen Bedingungen, wie eine Reduktion des Übergewichts, Entzündung und immunsuppressive Medikation, kann dazu beitragen, die Rate der PatientInnen mit erfolgreicher ileoanaler Pouchkonstruktion zu erhöhen.

Intraokulare Entzündungen sind die dritthäufigste Erblindungsursache im mittleren Alter, darunter fällt die schwerwiegende und funktionell relevante Uveitis posterior, u.a. White-dot-Syndrome (WDS). WDS, übersetzt „Weißfleckenkrankheiten“ umfasst eine Gruppe von Erkrankungen mit charakteristischen entzündlichen Veränderungen der Netzhaut (Retina), des retinalen Pigmentepithels (RPE) und der Aderhaut (Choroidea). In dieser Habilitationsschrift sind die Schwerpunkte auf zwei Erkrankungen, die Birdshot-Retinochoroiditis und die punktförmige innere Choroidopathie gelegt.

Glycans are among the fundamental building blocks of life on Earth, essential to all known living organisms. They play key roles in a variety of biological processes, and contribute significantly to the extraordinary molecular and functional diversity of cells. As the importance of glycans has gradually been recognized, earning them the well-deserved attention of the scientific community, the lack of a high-throughput, de novo sequencing method has become a major obstacle in glycosciences, preventing the field from reaching its full potential. Although the invention of soft ionization methods gave enormous impetus for mass spectrometry-based glycan analysis, conventional fragmentation techniques often fail to distinguish isomeric carbohydrates or provide unambiguous structural assignment.

With the prospect of overcoming these limitations, this thesis aims to expand the mass spectrometry-based toolbox for glycan analysis and go beyond simply weighing sugars. Through the combination of mass spectrometry with orthogonal methods suitable to study ions transferred into the gas phase, we try to reveal further information about the species underlying the peaks in mass spectra. Coupling mass spectrometry to ion mobility spectrometry – a technique that harnesses electric forces for separating ions in gaseous media – results in a powerful method that provides information not only on the mass and charge, but also on the size and shape of ions. Using the concept of theoretical plates and plate heights, we develop a detailed analytical model that describes three main aspects of ion mobility separations: zone broadening, resolution, and peak capacity. The plate-height model for ion mobility separations was conceived in analogy to existing models of chromatography. As such, it enables the direct comparison of ion mobility spectrometry with other zonal separation methods, and may help to integrate this technique into the unified language of separation science. While our work is mainly theoretical and focuses on the technique rather than on specific molecules, the utility of the plate-height model to aid glycan analysis in everyday practice is demonstrated through a systematic study on fluorescently labeled oligosaccharides.

Santiago Ramón y Cajal warned young investigators against becoming obsessed with theories and instruments to an unhealthy extent, forgetting about nature in natural sciences. To avoid these pitfalls, the second part of this thesis focuses on the most important element of glycomics: the sugars themselves. In particular, we study the structure of glycosaminoglycans, a well-recognizable class of complex carbohydrates with a linear sequence and highly acidic character. As their biosynthesis is not entirely deterministic, the structure of glycosaminoglycans also exhibits random features. Moreover, sulfation of the disaccharide building blocks at various positions, together with potential epimerization of certain residues, lead to a multitude of isomeric sequences. To decipher this complexity, we studied mass-selected glycosaminoglycan ions with infrared action spectroscopy in the cryogenic environment of superfluid He droplets. The recorded infrared spectra revealed details about the structure of deprotonated oligosaccharides that could not have been attained by simple mass measurements, such as the localization of charges or differences in intramolecular hydrogen bonding patterns. In addition, diagnostic spectral features allowed for the unambiguous distinction of glycosaminoglycan stereoisomers with minute structural differences. Finally, the surprisingly strong structure–spectrum correlations observed in the vibrational fingerprints of these ions have potential implications for de novo sequence assignment, providing motivation for future spectroscopic experiments on glycosaminoglycans.

Even some 50 years after the ban of DDT in Europe and North America, DDT and its metabolites are still posing a severe problem due to the environmental persistence. According to the Stockholm Convention DDT is one of the “Dirty Dozen”, supposed to be phasing out in 2020. Industrial production sites and their surroundings still exhibit a high risk of contamination in recent years. During the mid-1990´s a survey of different aquatic ecosystems revealed background information about the degree of contamination in North-East (NE) Germany, including the Arkona Basin in the Baltic Sea. The applied analytical approach provided basic data on trace metals and organic contaminants such as PCDD/F´s, PAH´s, PCB´s, DDX and HCH´s. The optimising of the analytical tool and extension to include non-extractable residues into the assessment led in combination with a non-target screening approach to the identification of the point source (Berlin-Chemie) at the Teltow Canal. Recent research activities have focused on this area contaminated by the effluents from this point source. Surface sediments, sediment cores, surface and ground water samples were extensively analysed and identified more than 30 different metabolites of DDT, among other pesticides and various industrial compounds. As a result, in the 1990´s about 135,000 m-3 of contaminated sediment (approximately 180,000 t) were removed by dredging. The remaining sediment has been investigated with regard to the contamination state. Due to the improved water solubility of DDA through the polar carboxyl group, it is one of the best water-soluble DDT metabolites. The assessment of the maximum contamination potential in relation to DDX (in particular DDA and its precursor metabolites) was considered. Furthermore, the incorporation of metabolites into sediment was investigated by applying a five-step degradation procedure. Free available (Extractable Fraction) as well as easily (Easily Releasable) and hardly available fractions of DDA and precursor metabolites were obtained and a maximum of 48 kg in the EF fraction (32 - 82 kg) and 1,360 kg in the ER fraction (11 – 4,010 kg) were estimated by application of a trapezoid model. Calculation using a column model resulted in 278 kg in the EF fraction (214 - 354 kg) and 9,800 kg in the ER fraction (250 - 29,000 kg). In both cases the mean values are applied and the variation is high, resulting in a very rough calculation. The comprehensive analysis scheme provides information on free accessible and potentially metabolised precursors also in the non-extractable residues (NER). This allows a quantitative assessment of the DDA contamination potential derived from DDT residues in the canal sediments close to the source. The remobilisation of sedimentary DDA under dynamic conditions such as dredging or shipping activities has been investigated. Hence, a high remobilisation and release potential of DDA was observed. The vast majority of the available DDA content has been released immediately resulting in a direct contamination potential for the aquatic environment. Several precursor metabolites of DDA, e.g. DDD and DDMS, extractable from the sediment organic matter (SOM), revealed a high potential for a long-term formation of DDA, especially in the easily releasable fraction (via hydrolysis) with a mean concentration of up to 11,000 μg g-1 dry sediment. The resulting DDA-contamination potential represents a significant contamination risk for the groundwater from a downstream waterworks area and by remobilisation into the whole ecosystem and adjacent rivers. The application of the presented methods provides a tool for a quantitative assessment of the long-term release potential of DDA and similar compounds under different scenarios by a comprehensive analysis of contaminated sediments (and soils). This approach can be transferred to contaminants that are also characterised by a complex metabolism accompanied by NER-formation and, in combination with toxicological data and bioavailability tests, represents a more advanced and detailed evaluation approach. This thesis should demonstrate the necessity to investigate not only extractable residues of sedimentary contamination but to consider the incorporation of contaminants and metabolites in particulate matter as well. Non-extractable residues in sediments can represent a long-term contamination potential for the environment. In most studies, the remobilisation of NER and their transformation reactions were widely neglected. In addition, released compounds can be transported to distant locations due to sorption on particles and colloids. The transport of released sedimentary compounds to the aquatic environment is neglected in literature as well. An analytical approach resulting from the experience of the work is presented, where a distinction is made between the water phase and various particulate phases, including humic substances. The applied degradation scheme is integrated in the scheme. These separate extracts can be used for bioassays. Differences in the analytical approaches and degradation techniques lead to further scientific questions about the formation of NER and the constituents involved. Combined analytical approaches with classes of SOM components (such as lipids, humic substances) are possible and the kinetics and dynamics of the NER formation and release process can be studied. Natural attenuation is underway. To complete the evaluation potential of the instrument, desorption and bio-accumulation experiments can provide insights into the actual and potential contamination by the accumulated sediments. Comparable contamination data were obtained in comparison to previous studies, indicating a still high contamination level and, by calculating the maximum contamination range, a continuous release potential into the water phase and the canal ecosystem. Besides natural particulate sorbents such as humic substances and natural organic matter, synthetic polymers and plastic particles are an additional particulate sorbent in aquatic ecosystems. Plastic is a general term for a class of materials that is composed of different types of (synthetic) polymers. Such materials own beside the polymer often different additives at a low content, which optimise or adjust the properties during processing and application. Plastic particles including micro plastic are widely detected in the environment today. Micro contaminants, especially very persistent organic compounds, are also detected in large parts in the (aquatic) environment resulting in many recent papers, dealing with interactions between organic contaminants and (micro) plastic particles in the environment, hypothesizing the function of plastic particles as a vector for bio-magnification, resulting in negative ecosystem effects. In the present work such interactions between polymers (polyethylene (LD-PE) and hard polyvinyl chloride (H-PVC) and organic, persistent compounds (here: DDT, methoxychlor and dicofol) were investigated. A new and innovative experimental approach based on a static system similar to a burial in deeper sediment layers was investigated. With the presented sorption test, it was possible to demonstrate the adsorption/incorporation of contaminants into the two polymers. The recovery of the three target compounds ranged between 2.0 - 2.4 % of the initial concentration for PE and 0.2 – 1.9 % for PVC, respectively. Differences between the two polymers are addressed. In the sorption experiments all the target compounds were detected in alignment with their hydrophobicity, resulting in a relative order of DDT > DMDT > Dicofol. In the desorption experiments, diffusion of the contaminants out of a contaminated sediment on the polymers could be verified. In maximum 22 μg Ʃ DDX (DDD/DDE/DBP and DDMS) could be desorbed within one month in the PE-experiment. Relative to published data of the International Pellet Watch project (IPW) 180-460 ng Ʃ DDX/g PE-polymer were analysed. These are in the range of other more contaminated sites, except for a few very highly sites. Differences in polymers are analysed and explained mainly by the glassy transition temperature with subsequent flexibility at room temperature. All three aspects differentiating LD-PE and H-PVC in polymer structure, polarity and properties, free volume and contaminant behaviour are obvious. The rapid formation of a biofilm on the polymer surface limits the sorption capacity, even with highly contaminated material and compared to pellets and fragments. The ATR-FTIR analysis of the surface layers of the 3-month containers led to the identification of a water-rich surface layer consisting of hydroxy and aromatic structures. The differences between the two plastic polymers meet expectations, based upon the different glass transition temperatures (Tg). The new experimental desorption approach shows an easy to handle alternative means for sorption and desorption experiments with (plastic) polymers as well as kinetic experiments. The limited capacity of pure polymers is demonstrated in the sorption experiments, including antagonistic effects due to differences in hydrophobicity. These complex issues are routinely not addressed in simple kinetic lab-experiments with a single substance approach. The rapid formation of diffusion barriers at the polymer surface limits the sorption capacity, even for the highly contaminated material, demonstrating a more realistic approach for naturally contaminated systems with a huge number of different compounds and possible antagonistic effects on sorption. The very low sorption capacity means that the possibility of remediation by plastic polymer material is very low and, together with the natural organic matrix, it has no function as a transport vehicle in natural ecosystems. Further investigations are urgently needed to verify the postulated effect as a vector. A monitoring programme is strongly recommended, especially in the heavily contaminated area near the point source, considering the use of the Johannisthal waterworks as a protective well for the incoming bank filtrate from the Teltow Canal. The analysis of micro plastic in the Teltow Canal ecosystem is currently underway and the relative proportion of anthropogenic contaminants in these analyses can provide information about the relative proportion of micro plastic as a transport vehicle.

This work analyzes geomorphological devolatilization features on the atmosphereless asteroid Vesta. In particular, it predominantly analyzes the features associated with the crater Marcia, as those add up to more than 96% on the whole body and are the only ones occurring within the ejecta of a crater. These features are called Pitted Impact Deposits, or short PIDs, and they have been previously identified on Mars, Vesta and the dwarf planet Ceres. PIDs are characterized by closely spaced pits that occur as locally confined clusters of several kilometers length. The individual pits can overlap and often share boundaries. They lack raised rims as would be typical of an impact crater and are polygonal to circular in shape. Furthermore, they show distinct spectral characteristics like higher reflectance at 750 nm and more intense pyroxene absorptions near 0.9 and 1.9 µm. It is evident through previous studies that PIDs formed via degassing or devolatilization of parts of the ejecta, yet the detailed mechanism behind remained debated. Additionally to the previously known dominance of pyroxene-rich HED-like material on Vesta (HED: howardite, eucrite, diogenite meteorites), many studies have reported on the existence of OH-bearing material and the so-called ‘dark material’ which has been proposed to originate from influx of carbonaceous chondrite material. The identified OH is likely bound within the crystal structure of phyllosilicates (that are commonly found in carbonaceous chondrites) and is able to leave the crystal structure when heated. All remote observations shown here were obtained by NASA’s Dawn mission. The presented analysis show that the formation of PIDs is controlled by the proportion of an ejecta deposit’s volume to surface area, or depth. Many PIDs are located in small craters or at steep topographic slopes that existed prior to the Marcia impact or to the time of PID formation. This enables the estimation of the pre-existing topography and therefore of the shape and extent of the post-impact ejecta deposit. The accumulation of ejecta at these sites leads to a slower cooling of the ejecta deposit, a larger volume not exposed to the space environment and an extended possibility for volatiles to escape from its host mineral. The depth of the ejecta deposit appears to control the shape and extent of the developing devolatilization vents and therefore, of the individual pits themselves. The proportion of volatiles within the whole ejecta is estimated here to be less than 2 wt% and the proportion of lost volatiles at the PIDs’ sites to ~1 wt%. This shows that particularly elevated volatile contents are not needed to form PIDs. PIDs are always part of a larger impact deposit not featuring a pitted surface. This suggest that the original material of both deposit parts were identical or very similar. The spectral changes of the PIDs with respect to their immediate surroundings are not consistent with variations in grain size, roughness or glass content. One possibility of creating similar spectral characteristics is the removal of darkening agents. At high temperatures, organic material (which are commonly dark) can decompose, as do other components of carbonaceous chondrites. Tochilinite for example is a major constituent in the carbonaceous chondrite Murchison and decomposes already at 400 °C. However, the mere removal of dark components cannot explain all aspects of spectral characteristics shown for PIDs, i.e. the ratio of pyroxene band strength to reflectance at 750 nm with respect to other more typical regions on Vesta. This thesis furthermore presents laboratory experiments in order to explain the PIDs’ spectral characteristics. Both terrestrial and meteoritic materials were used. These were assembled to adequately represent the Vestan regolith. The experiments involving the heating of these analog materials show that hematite formed due to oxidation and therefore, a strong reddening of the visible spectral slope of the samples was observed. This is not observed on Vesta, yet might be explained. First, the ejecta deposit on Vesta is likely very heterogeneous, as has been shown by previous studies. This can lead to a smaller and slower extent of these oxidation processes. Second, the estimated devolatilization duration is in the range of hours to days, possibly inhibiting the onset of hematite formation or the incapability of remote spectrometers to record the small amounts that might have already formed. Third, the processes of space weathering of hematite over geological timescales are not well-known, which could additionally play a role. In combination with existing literature, the laboratory experiments presented here show that an oxidizing environment together with higher temperatures (≥400 °C, well below the minerals’ melting point) can result in similar spectral characteristics, i.e. higher reflectance and pyroxene band strength, as shown for PIDs. The underlying process could involve the migration of Fe2+ to the grain surfaces, where it increases the relative iron abundance that electromagnetic energy (i.e., light) encounters first which in turn intensifies the pyroxene absorption. Many studies have observed similar processes where Fe2+ is converted to Fe3+ and forms hematite (Fe2O3) or other iron (hydr-)oxides. An alternative explanation also includes the migration of Fe2+, yet to its preferred crystallographic M2 site, where it likewise would intensify the pyroxene absorption. Original pyroxene crystals might have been disordered regarding their cation distribution, whereas the temperature increase would enable the cations to migrate to their preferred position. This work shows that oxidation processes can occur on planetary bodies thought to be dry. The surficial contamination with carbonaceous chondrite material enables this process, which might be relevant to future space missions and could influence the search for organic matter.

Visible-light is a powerful “reagent” for sustainable synthetic organic chemistry. In particular, the combination of photo- and nickel catalysis (metallaphotocatalysis) has emerged as a valuable strategy for carbon–carbon and carbon–heteroatom cross-couplings. This research field is dominated by expensive homogeneous noble metal complexes that can only convert a small portion of visible light (<500 nm) into chemical energy. The highenergy photons that excite the photocatalyst can result in unwanted side reactions and the homogenous nature of these does not allow for straightforward catalyst recycling. Heterogeneous semiconductors that absorb visible light are a promising sustainable alternative to noble metal photocatalysts (Chapter 2). Their potential for metallaphotocatalytic C–N cross-couplings was demonstrated (Chapter 3). This transformation suffers from deactivation of the nickel catalyst using homogeneous photocatalysts. The broad absorption range (up to 700 nm) of an organic, heterogeneous carbon nitride photocatalyst (CN‐OA‐m) allows controlling the rate of the bond-forming step by carefully selecting the wavelength thereby preventing catalyst deactivation. This is not only crucial for the reproducibility of such reactions, but also expands the scope to substrates that were previously unsuitable. The redox potential of a carbon nitride photocatalyst can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials (Chapter 4). This was the key to design photo‐chemo‐enzymatic cascades that enable the synthesis of (S)‐ or (R)‐ 1-phenylethan-1-ol from ethylbenzene by choosing the irradiation wavelength and the enzyme co-catalyst. In contrast to common photocatalysts that can be only excited using short wavelengths, abundant organic dyes absorb broadly across the entire visible-light spectrum. Inspired by dye-sensitized solar cells, the short-lived excited singlet states of such dyes were harnessed for light-mediated cross-coupling reactions (Chapter 5). Immobilization of a nickel catalyst on dye-sensitized titanium dioxide results in a material that catalyzes carbon–heteroatom and carbon–carbon bond formations. The modular approach of dye-sensitized metallaphotocatalysts (DSMPs) accesses the entire visible light spectrum and allows tackling selectivity issues resulting from low-wavelengths strategically. The concept overcomes current limitations of metallaphotocatalysis by unlocking the potential of dyes that were previously unsuitable. However, recycling studies suffered from a gradual decrease of the yield due to leaching of the nickel catalyst and the dye from the surface of TiO2. This was rationalized by the weak interaction between carboxylic acid anchoring groups and titanium dioxide. Therefore, recyclable, bifunctional materials for metallaphotocatalytic C–S cross-couplings were developed (Chapter 6). Key to the success was the permanent immobilization through phosphonic acid anchor groups. The optimized catalyst harvests a broad range of the visible light spectrum and requires a nickel loading of only ~0.1 mol%. Another robust alternative to organic dyes that does not suffer from photobleaching was realized, by immobilizing carbon dots on titanium dioxid (Chapter 7). The potential of these sustainable materials was demonstrated for various carbon–heteroatom cross-couplings.