Proteins represent the main target class of bioactive compounds.1 The identification of a drug’s protein target is crucial to understand drug function on a molecular level. Major progress has been achieved in both the construction of large scale screening libraries of structures with drug-like properties as well as in high-throughput methods to screen the bioactivity of those substances against a phenotype of interest. Such phenotypic screens allow to identify hit compounds that alter the disease phenotype in a desired manner.2,3 However, the following deconvolution of the mode of action (MoA) and identification of corresponding protein targets remains a key challenge in drug discovery.2,4 Here we developed a novel target identification (target-ID) approach, which combines the power of photoaffinity labeling (PAL) and quantitative affinity purification mass spectrometry (qAP-MS). This compound interaction screen on a photoactivatable cellulose membrane (CISCM) allows us to probe the interaction of many proteins with multiple compounds in parallel without compound derivatization or structure-activity relationship (SAR) studies being required. To achieve this, we equipped cellulose membranes with a diazirine PAL-probe and photoimmobilized a selection of wellstudied bioactive compounds with ultraviolet (UV) light. The resulting photocrosslinked compound cellulose array was then incubated with protein extract and specific targets were identified via quantitative affinity purification mass spectrometry. For the natural structure analogues cyclosporine A (CsA), tacrolimus (FK506) and sirolimus (rapamycin) this reliably identified known protein interactors, while the known targets of small fragment-like compounds, such as (S)-thalidomide, lenalidomide, methotrexate and metformin, could not be detected. As another limitation, the target tubulin beta (TUBB) could not be identified as a specific interactor of the pharmaceuticals vinblastine and paclitaxel. The observed results were nearly unaffected by the increase of the spacer-arm length, separating the diazirine from the cellulose surface, and by photocrosslinking the compounds isolated from the cellulose membranes with subsequent immobilization of resulting photocrosslinking products. Physisorbed CsA on diazirine-modified non-UV irradiated cellulose membranes could identify the known interactors Peptidyl-prolyl cis-trans isomerases A and F (PPIA, PPIF), whereas physisorbed CsA, sirolimus and FK506 on non-functionalized cellulose membranes could not identify any of their known protein interactors. In summary, we developed a novel compound interaction screen that can rapidly screen for drug targets in a parallel fashion without prior derivatization of the drugs. CISCM reliably identifies the targets of natural products and current limitations of our method are due to the known limitations of diazirine-based photocrosslinking strategies and affinity purification mass spectrometry.

Dem griechischen Roman und insbesondere dem frühneuzeitlichen Abenteuerroman haftet das Bild einer idealisierenden Gattung an, deren schöne und vorbildliche Heldinnen und Helden durch exotische Welten reisen und nach vielen Irrwegen ihren Liebestraum glücklich erfüllen. Die Untersuchung der spanischen 'novelas bizantinas', die an Heliodor und Achilleus Tatios modelliert sind, relativiert dieses eskapistische Genrebild. Viele der Texte spielen in einer vertrauten europäischen bis iberischen Geografie und verweisen auf die zeitgenössische Realität, in der allerdings nicht das Märchenhafte der 'romance', sondern eine Atmosphäre der Unsicherheit und Prekarität des menschlichen Schicksals herrscht: eine trostlose Wirklichkeit. Zentral für diese Neudefinition des Musters war Lope de Vegas bislang wenig beachteter Roman 'El peregrino en su patria', der zwischen Einhaltung und Herausforderung des Wahrscheinlichkeitsgebots neoaristotelischer Wirkungspoetiken den Akzent auf die Destitution des Helden legt, der unterhaltsamen Handlungsführung der 'Aithiopika' eine eigenartige Dimension ethischer Reflexion verleiht und damit das Profil einer 'novela helenizante de peregrinación' auf den Punkt bringt.

Some degree of income concentration is necessary in well-functioning market economies as it financially incentivizes individuals to work harder or take the risks of entrepreneurship. But if in- equality becomes too high, it is not only morally concerning and poses a risk to social cohesion and democratic cooperation, but carries real economic consequences. It can lead to economic instability, hinder economic growth, and jeopardize labor market functionality if the belief in up- ward mobility through work is lost. In recent decades, empirical evidence has shown a steep rise in income inequality for many industrialized countries including Germany (e.g., Chancel and Piketty 2021), elevating this topic to be among the major issues of our time.

The goal of this dissertation is to contribute to a more comprehensive understanding of labor market inequality and mobility in Germany. In particular, it is guided by the following research questions: Using different measurement approaches, how has labor market inequality and mobility evolved within generations? How has it evolved across generations? And how do current trends in inequality and mobility compare to historical trends?

Chapters 1 and 2 measure earnings growth and inequality predominantly within the same generation, a common and important way to measure labor market inequality. However, another important puzzle piece in understanding the secular evolution of inequality and its drivers is to compare work and living standards across generations. Individuals often assess their own eco- nomic progress by comparing their earnings to their parents (e.g., Goldthorpe 1987; Hochschild 2016). While the vast majority of these studies focus on relative intergenerational mobility (e.g., Chetty et al. 2014; Bratberg et al. 2017), measuring how children’s outcomes depend on parental income ranks, research has shown that people tend to think in absolute rather than in relative terms (Amiel and Cowell 1999; Ravallion et al. 2018). Therefore, Chapter 3 uses a relatively novel measure to assess intergenerational mobility: absolute income mobility. It measures the fraction of children who earn weakly more than their parents did. Chapter 4 provides a comprehensive picture of the evolution of earnings growth, inequality, and absolute mobility since 1882. This broad scope enables the historical contextualization of the other chapters’ findings.

Die Sarkopenie, das zentrale Thema dieser Arbeit, bezeichnet einen fortschreitenden und generalisierten Prozess eines zunehmenden Verlustes an Muskelmasse, Muskelkraft und muskulärer Funktion, welcher ab einem bestimmten Ausmaß auch zu negativen Folgen wie erhöhter Sturzhäufigkeit und funktionellen Einbußen führen kann. Die Sarkopenie gilt als wesentlich mit dem Alterungsprozess und den damit einhergehenden Veränderungen in der Muskulatur assoziiert. Der Schwerpunkt dieser Arbeit lag auf der Bestimmung der Prävalenz der Sarkopenie gemäß den zum Zeitpunkt der Untersuchungen empfohlenen diagnostischen Kriterien und der Analyse von Zusammenhängen zwischen Sarkopenie einerseits und möglichen Ursachen sowie auch Folgen der Sarkopenie andererseits. Ergänzt wurde dieser Schwerpunkt durch methodische Fragestellungen in Hinblick auf die diagnostischen Kriterien und Überlegungen hinsichtlich möglicher therapeutischer Optionen. In den vorgestellten Originalarbeiten konnte gezeigt werden, dass auch bei noch vergleichsweise gesunden älteren Menschen eine als relevant hoch einzuschätzende Prävalenz der Sarkopenie vorliegen kann. Es zeigte sich dabei auch, dass methodische Aspekte wie die Verwendung unterschiedlicher Parameter der Muskelmasse die Erhebung der Sarkopenieprävalenz stark beeinflussen können. Ferner waren signifikante Unterschiede zwischen zwei dieser untersuchten Parameter zu beobachten was deren Assoziation zu Pre-Frailty/Frailty und zu selbstberichteten Limitationen der physischen Performance und damit potentiellen Folgen der Sarkopenie angeht. In weiteren Analysen konnte gezeigt werden, dass ein Diabetes mellitus Typ 2 mit Sarkopenie assoziiert ist und eine niedrige Muskelmasse mit einer ausgeprägteren Insulinresistenz einherzugehen scheint, wobei hier die Kausalität aufgrund der Limitation querschnittlicher Analysen vorerst unklar bleibt. In weiteren Analysen ergaben sich zudem Hinweise, dass Störungen der thyreoidalen Funktion eine Sarkopenie begünstigen könnten. Dieser mögliche Effekt scheint sich jedoch insbesondere in Hinblick auf eine hypothyreote Stoffwechsellage in höherem Alter abzuschwächen. Ein positiver Zusammenhang zwischen der Einnahme von Angiotensin Converting Enzyme (ACE) – Hemmern und mehreren Parametern der Sarkopenie, hypothetisch möglich aufgrund potentieller protektiver Effekte von ACE-Hemmern auf die Skelettmuskulatur, fand sich nicht.

Collective states with their fascinating optical properties occur through the coupling of dipole moments. The coupling of the dipoles leads to an overall optical response that varies strongly from the monomer. Dipole coupled systems are manifold systems with optical properties that are interesting for a variety of optoelectronic applications, solar cells, and catalytic reactions. The lattices range from atomic and molecular lattices up to plasmonic structures and can vary in their dimensionality. Depending on the approach, dipole coupled systems can easily be adapted to the relevant requirements, such as excitation energy. The first part of this work investigates collective states in one- and two-dimensional molecular lattices. These states are highly emissive, have narrow line widths as well as short radiative life times. With a microscopic real space dipole model, I show that excitations of two-dimensional molecular monolayers are robust against various forms of disorder. I realize the growth of two-dimensional monolayers with a perylene derivate and show that the collective states also exist on materials that provide a large radiative decay channel. Then I explore collective states in one-dimensional molecular aggregates, namely in molecule chains encapsulated in boron nitride nanotubes. I verify that the collective exitonic states of single- and multi-file chains show an enormous shift to lower energies that is not captured by the model of a chain of interacting dipoles. The last part of my work focuses on a different kind of dipole coupled system, namely bimetallic nanoparticle supercrystals for photocatalytic experiments. Small platinum particles that are placed in the hotspots of a gold supercrystal show an increased production of hydrogen. I investigate the layer dependent optical response of the crystal and calculate the electric fields in the hotspots which I compare with wavelength dependent catalytic experiments. In photocatalytic experiments the binary crystal shows a higher hydrogen generation rate than other top performers for formic acid dehydrogenation.

The dissertation deals with the memory of the Syrian revolution that began in 2011 in the context of the Arab Spring. It examines how leftist actors have used digital media to make visible an anarchist dimension of the revolution that has often been lost in the common narrative of a ‘complicated civil war’. At the centre of this left-wing appropriation of the Syrian revolution are the local councils, hundreds of which have sprung up across the country from the late 2011 onwards. They were conceptualized in 2011/2012 by the Syrian intellectual Omar Aziz from an anarchist perspective as forms of local self-organization against the state and political parties. The aim of the study is to reconstruct digital memory work in social media (Facebook, Twitter) and blogs in such a way that the interplay of actors, practices (archiving, circulating, claiming) and technology for the emergence of memory becomes clear. Drawing on research in the fields of social movements, cultural memory and digital media, the study contributes to theory building, differentiates existing concepts and tests new methodological approaches. The manually collected data (posts, tweets, articles from blogs and other platforms) were coded and qualitatively analyzed according each platform in order to identify different aspects of memory work: temporal dynamics, different roles of actors, interactions between platforms in the circulation and archiving of memory, etc. A backlink analysis of blogs and a qualitative content analysis of the most relevant blog articles deepen the analysis of how memory is circulated and claimed. As a result, the roles of actors were differentiated according to their skills, degree of commitment and existing (offline) networks. The findings provide a nuanced picture of how the technological ‘affordances’ of a medium play out and depend on actors and practices. The importance of blogs as temporary archives or resting points in the initial phase of memory work is emphasized, while Twitter and Facebook functioned more as circular hubs and pacemakers of a memory rhythm over nearly ten years. Alongside the question of how memory was created and cultivated, there is the question of the object of memory itself. Previous studies of the local councils have not adequately grasped how the councils functioned and have failed to recognize the links between the Syrian councils and a (left-wing) council tradition and hence their potential as an alternative to representative, statist democracy. Omar Aziz explicitly pointed to this connection by placing the Syrian revolution in the tradition of the Paris Commune of 1871, which has an iconic significance in all communist and anarchist movements and is seen as an early realization of council democracy. The analysis of claiming showed that the left reception of the Syrian revolution has also had difficulties in spelling out how the Syrian councils are related to the left council tradition. The main arguments proposed by the memory workers have relied on the ‘anarchist’ personality of Aziz, who functions as a guarantor of the anarchist credentials of the councils; on ‘mnemonic chains’ that refer to the Paris Commune; and on the emphasis on the anti-state and grassroots-democratic character of the councils. The dissertation therefore reconstructs in detail how the actual existing local councils came about and functioned while also examining the reasons for their failure. Methodically, the analysis is based on three pillars: On expert interviews, on the analysis of a website of the local council in Darayya and on studies by international NGOs. In dialogue with previous theoretical reflections on councils and drawing on key principles of anarchism, the local councils are reconstructed along four dimensions: as social sites of agency and self-organisation; as institutions of anti-state democracy; in their capacity to anticipate a new order; and as manifestations of a cooperative order. The research shows that the councils initiated a de-professionalisation of politics in favour of an expansion of agency and learning processes; that they reorganised the separation of powers in different ways; that a major achievement was the preservation of order and the restoration of everyday life; and that they promoted to some extent a new cooperative ethic. The councils’ failure to build up a ‘structural solidarity’ to ensure the provision of basic goods is identified as the major weakness which made them vulnerable to other actors’ agendas (Islamists, international NGOs, opposition in exile) and substantially undermined their independence. These findings suggest to re-consider more classical materialist objections to the assumption that councils could consolidate themselves in the long term in a purely civil or political sphere while refraining from socialization of private property. Omar Aziz’s Papers, that were written in 2011/12 from a pragmatic point of view during the turmoil of the revolution, are for the first time thoroughly analyzed, and the question is raised as to how they can be placed paradigmatically within the theory of the councils. The hitherto unrecognised theoretical potential of Aziz’s texts is revealed by reconstructing his intellectual background. Ideas such as the different everyday logics ‘authority’s time versus revolutionary time’, the ‘desire for life’ and councils as social spaces for learning and joyful experiences are identified as essential contributions to the further development of council theory.

Basierend auf dem in dem sechsbändigen Wörterbuch Derleme Dergisi und dem zwölfbändigen Wörterbuch Derleme Sözlüğü versammelten Dialektmaterial untersucht diese Arbeit den Sprachgebrauch und Wortbestand türkeitürkischer Dialekte am Beispiel von Pflanzen- und Tierbezeichnungen in Mundarten auf dem Gebiet der Republik Türkei. Die Wortbestände der beiden Werke wurden im zweiten Viertel des 20. Jahrhunderts gesammelt und erlauben eine Untersuchung auf Basis von synchronischen Daten. Die untersuchten Pflanzen- und Tierbezeichnungen haben sich mehrheitlich als Typen, die im Oghusischen bereits vor der Sesshaftmachung der Stämme in Kleinasien verwendet wurden, als Onomatopoesie und als Lehnwörter aus Sprachen außerhalb der Türksprachen erwiesen. Die Verteilung der verschiedenen Lehnwörter liefert in diversen Fällen Hinweise auf Siedlungsräume von Sprechern dieser Sprachen oder deren Nachfahren und lässt dabei Rückschlüsse auf die historische Demografie Kleinasiens zu. In den Ergebnissen dieser Arbeit überwiegen Lehnwörter armenischen, griechischen und persischen Ursprungs. Dieses Fazit ist für sich allein nicht überraschend, nachdem diese Bevölkerungsgruppen früh mit den türkischen Stämmen Kontakt hatten. Persische Entlehnungen ins Oghusische sind bereits im 11. Jahrhundert, bevor die Besiedlung Kleinasiens durch die türkischen Stämme, belegt. Kleinasien war zu der Zeit bereits seit Jahrtausenden von griechischen und armenischen Bevölkerungen besiedelt. Diese Lehnwörter stellen frühe Entlehnungen dar. Später introduzierte Pflanzen, wie die Tomate und die Kartoffel, können sich naturgemäß allein als spätere Bildungen und Entlehnungen erweisen. Eine Übereinstimmung zwischen frühen Klassifikationsversuchen und den Verteilungen der in dieser Arbeit untersuchten Pflanzen- und Tierbezeichnungen konnte nur in wenigen Fällen nachgewiesen werden. Bei der Verteilung einiger Bezeichnungen finden wir weithin Übereinstimmungen mit Gruppen von CAFEROĞLU (1959), BANGUOĞLU ([1959] 1998) und KARAHAN (1996). Ein signifikanter Teil der untersuchten Typen von Pflanzen- und Tierbezeichnungen dokumentiert gleichwohl eine weite Verteilung über die Gruppierungen der verschiedenen Klassifikationen hinweg. Der Vergleich zwischen der Verteilung der Pflanzen- und Tierbezeichnungen und den Siedlungsräumen der neun Oghusenstämme, die als besonders bedeutsam für die Bildung der Dialekte Kleinasiens erachtet werden, kann bei der Schärfentiefe dieser Arbeit lediglich ein interpretationsfähiges Ergebnis liefern. Die breite Verstreuung der Oghusenstämme und ihre geografisch gemeinsame Präsenz in Kleinasien verbildlichen ohnehin die Schwierigkeit, Zusammenhänge zwischen ihnen und der Verteilung der Mundarten Kleinasiens herzustellen.

Infections of the lower respiratory tract represent the fifth most common cause of death worldwide. This study describes a mechanism that influences the course of pneumococcal pneumonia based on genetic determinants as well as environmental factors. Previous experiments have shown that animals deficient in IL-33 or its receptor ST2 exhibit an enhanced bacterial defense against Streptococcus pneumoniae. Initially, associations between the susceptibility to human pneumococcal pneumonia and single nucleotide polymorphisms (SNPs) in the genes coding for IL-33 and ST2 were demonstrated. Furthermore, IL-33-deficient animals were shown to produce increased amounts of IL-22, and experiments using Il33-/- Il22-/- animals as well as recombinant IL-22 revealed that enhanced IL-22 production was responsible for the increased resistance of Il33-/- mice to Streptococcus pneumoniae. Classical type 2 immune responses driven by type 2 innate lymphoid cells (ILC2s) or IL-4/IL-13 signaling cascades were not involved in the IL-33-dependent regulation, while ST2-negative ILCs, most likely representing ILC3s, were identified as the main differential producers of IL-22. Additionally, an association between bacterial defense and animal housing conditions was revealed. The IL-33-dependent negative regulation of pneumococcal pneumonia could only be reproduced in facilities with specific individual hygiene conditions. This effect was accompanied by differences in the composition of the intestinal microbiota of the animals, where increased abundance of Lactobacillus spp. correlated with a protective phenotype in Il33-/- mice. Finally, microbiota depletion and co-housing experiments resulted in equilibration of bacterial burden, while a fecal microbiota transplant was able to rescue the observed phenotype in microbiota-depleted animals. Taken together it was demonstrated, that the intestinal microbiota influences pneumococcal pneumonia. The results presented in this study enhance our understanding of the bidirectional communication between microbiota and the immune system and demonstrate that genetic as well as environmental factors infl uence the defense against Streptococcus pneumoniae.

This dissertation examines the production and transformation of knowledge in early modern Ottoman Arabia. It proposes a new historical narrative of seventeenth-century Medina by closely perusing the biography and works of Ibrahim al-Kurani (d. 1690), the most prominent Kurdish theologian, Sufi, and hadith scholar during the eleventh Islamic century, or the seventeenth century, situating this figure within broader cultural, intellectual, and political milieus in the global configuration of Islamic thought in the early modern period. This dissertation investi-gates particular routes of knowledge transmissions that took place in the post-Timurid and post-Mamluk intellectual spheres, which became the multifaceted settings of the Ottoman scholarly tradition. It argues that Kurani’s pursuit of multiple genealogies from both intellectual traditions enabled him to balance between the rational and traditional sciences, which strengthened his authority in Medina where the production, circulation, transmission, and transformation of his writings occurred through trans-imperial and transregional connections.

To examine this phenomenon, this dissertation uses a corpus of manuscripts produced and written in Arabian, Maghrebi, Indian, Ottoman, and Southeast Asian cultural contexts. It reveals the sites of connection and contestation in order to explore how Kurani’s scholarly and religious authority was formed, circulated, and contested through the views of his proponents and opponents in different geographical locations. This study demonstrates that Medinan intellectual culture in the seventeenth century was shaped by the confluence among various streams of knowledge that underpinned Ibrahim al-Kurani’s intellectual persona among Muslim elites and scholars throughout the Islamic empires. It also emphasizes the importance of textual produc-tion and transmission in comparative and transregional settings, explains the inevitability of engaging with unexplored and understudied sources from multiple cultural ecologies, and explicates an ideal case of extensive networks in the Islamicate Republic of Letters in the early modern time.

In mammals, female cells achieve dosage compensation between the sexes randomly chosing and transcriptionally silencing one of the two X chromosomes through a process known as X-chromosome inactivation (XCI). This process is initiated during early development through up-regulation of the long non-coding RNA Xist, which mediates chromosome-wide gene silencing of the future inactive chromosome (Xi) in cis. Upon completion of the XCI process Xi will maintain its silenced state in all daughter cells, which results in the genetic mosaicism of female organisms. Cell differentiation, Xist up-regulation and gene silencing are thought to be coupled at multiple levels to ensure inactivation of exactly one out of two X chromosomes.

In this thesis I performed an integrated analysis of all three processes through the analysis of allele-specific single-cell RNA-sequencing data. Specifically, I investigated the endogenous random XCI process in hybrid mouse embryonic stem cells at different time points throughout cellular differentiation developing dedicated analysis approaches that rely on the high number of polymorphisms between the two parental strains.

Putative Xist regulators were identified exploiting the inter-cellular heterogeneity of XCI onset. A large fraction of cells transiently expressed Xist on both X chromosomes which resulted in biallelic gene silencing right before being resolved to a monoallelic state, confirming a prediction of the stochastic model of XCI. The two X chromosomes showed different gene silencing dynamics, and a number of strain-specific escapees (namely, genes that escape transcriptional silencing) were identified and experimentally validated. These results suggest that genetic variation modulates the XCI process at multiple levels, providing a potential explanation for the long-known X-controlling element (Xce) effect, which leads to preferential inactivation of a specific X chromosome in inter-strain crosses.

Overall, this work provides a detailed picture of the different levels of regulation that govern both Xist up-regulation and the initiation of XCI.

Bats worldwide are experiencing severe declines, and a concerning percentage of bat species are considered endangered, with inadequate data for many others. This makes the application of meaningful conservation efforts challenging, as a comprehensive understanding of the behavior and habitat use of endangered species is crucial for successful conservation. The nocturnal and flying nature of bats additionally complicates observational studies. However, bats hold great potential for non-invasive acoustic monitoring as they are highly vocal and constantly emit high-frequency echolocation calls for orientation in their predominantly dark environment. While species discrimination via echolocation calls became more and more reliable over the years, similar calls evolved in some species based on habitat and prey preferences, complicating identification via echolocation calls. This is especially true within the genus Myotis. Besides calls for orientation, most species also employ a variety of social calls for communication. Social calls are far less studied than echolocation calls, especially when produced on the wing. As those calls are known to contain information about individual identity, sex, or age of the sender they should at the very least be species-specific, thus also holding great potential to be used for species identification. I aimed to study bats’ behavior and social calls during autumn swarming at a large hibernaculum in Northern Germany, the Kalkberg Cave in Bad Segeberg, whose main inhabitants are Daubenton’s bats (Myotis daubentonii) and Natterer’s bats (Myotis nattereri). Prior to hibernation, temperate zone bats gather in front of underground hibernacula (winter roosts) and participate in a behavior known as swarming. Swarming is characterized by intense flight activity and is accompanied by large amounts of both echolocation calls and social calls. Different functions of swarming are suggested, incorporating information transfer, mating, and the facilitation of gene flow between otherwise isolated colonies. The small differences between the echolocation calls of the two predominant Myotis species become further attenuated in this swarming context. To tackle that problem, in Chapter One, I tested the possibility of species identification from overlapping echolocation call sequences recorded in a crowded swarming situation. With a combination of Linear Frequency Cepstral Coefficients (LFCCs) and classic acoustic parameters, I analyzed the “soundscape” rather than single echolocation calls. This combination enabled me to detect the predominant species at the time of recording. The method has great potential to facilitate species identification and long-term monitoring in situations with more than one individual calling, e.g. on so far understudied swarming sites. By gathering information on species assemblage during autumn swarming conclusions about winter populations in hibernacula can be drawn, reducing the necessity of disruptive winter controls. Chapter Two was dedicated to further investigations of social call repertoire and function in a swarming context. I identified ten distinct call types based on differences in their spectro-temporal structure and confirmed the grouping via a discriminant function analysis. An additional analysis of the surrounding echolocation calls (as developed in Chapter One) revealed that both species potentially present at the swarming site employed social calls with large structural similarities. However, a subsequent analysis of classic acoustic parameters revealed subtle but significant differences in the structure of such calls. For a better understanding of the call function, I conducted playback experiments in the vicinity of the swarming site. I broadcasted three different call types for each species and observed an increase in bat activity (approximated as echolocation call rates) during and after the playback in three out of six scenarios, indicating that bats inspected or approached the playback site. By simultaneously taking photographs with a camera trap, I sometimes managed to identify approaching bats to species level. The results suggest that one call type is used to maintain group cohesion within the same species, while another type is used for communication between different species. The results are in line with what we already knew about the autumn swarming phenomenon and further enhance our understanding of it. The results from Chapter Two underlined the function of swarming sites for communication and in this situation, it could be possible to introduce a cue to the bats, which is subsequently connected to a suitable hibernaculum. Thus, for Chapter Three, I installed hollow hemispheres as strong echo-reflective cues at the swarming site, where bats first encountered them during swarming. Those cues are known to provide an equally strong echo over a broad range of angles which should be highly conspicuous to passing bats. To investigate whether bats subsequently prefer roosts with hollow hemispheres I installed 60 boxes (30 with and 30 without hollow hemispheres) across three study sites. To non-invasively measure bat activity I constructed a light beam system that recorded activity at boxes, and indeed, bat activity exhibited significant variation. However, I found that prior familiarity with bat boxes played a bigger role in roost occupation than the advanced echo-reflective properties did. Additionally, I developed an effective monitoring system for tracking activity rates at bat boxes. This system revealed activity at boxes weeks to months before bats or feces were detectable via traditional visual inspections. To not interfere with the animals’ natural behavior and not disturb them in their environment all investigations were made as non-invasive as possible. A reasonable combination of monitoring techniques has the potential to gain comprehensive overviews of species-specific behavior, thereby laying the basis for informed conservation decisions for endangered species. Consequently, this study enhances our understanding of bat behavior and establishes a foundation for comprehensive monitoring in the future: By integrating both soundscape analysis and social call monitoring we potentially will gain deeper insights into bat populations, including habitat usage, species assemblage, phenology, and seasonal variations.

The present study investigated the effect of a preceding, short cold treatment (4 °C, 24 h) on the resistance of Arabidopsis thaliana against hemibiotrophic Pseudomonas syringae pv. tomato (Pst) and necrotrophic Botrytis cinerea. For this aim, two different experimental cold setups were compared. In the first setup (cold pre-treatment; CT), the pathogen infection occurred directly after the cold treatment. The second experimental setup (cold priming; CP) included a memory phase between the cold treatment and the infection, whereby the impact of a priming memory on the resistance against pathogens was investigated. Arabidopsis benefited from the cold treatment and exhibited significantly increased resistance against Pst and B. cinerea. For plant defense against Pst, cold priming and cold pre-treatment led to increased resistance, while against B. cinerea only cold pretreatment resulted in transient resistance increase. To identify the immune signaling pathways responsible for the increased resistance, transcript analyses and pathogen growth experiments were conducted with Arabidopsis (Accession: Col-0) and selected mutant lines. The experiments demonstrated that cold priming-mediated resistance in Arabidopsis against virulent Pst is independent of the plant immune regulator Enhanced Disease Susceptibility 1 (EDS1) and does not alter transcript levels of pathogen-triggered Pathogenesis-related 1 (PR1), Isochorismate Synthase 1 (ICS1), FLG22-induced receptor-like Kinase 1 (FRK1), and NDR1/HIN1-like 10 (NHL10). These results, but also the observation that cold priming does not confer resistance against avirulent Pst avrRPS4 and Pst avrRPM1, indicated that cold-mediated resistance against Pst is mainly independent from effector-triggered immunity (ETI), hypersensitive response (HR), PAMPs-triggered immunity (PTI) and salicylic acid (SA) signaling. Cold pretreatment-mediated resistance against B. cinerea was also without cold signatures on the transcript levels of Pathogenesis-related 1 (PR1), Pathogenesis-related 4 (PR4), Plant Defensin 1.2a (PDF1.2a) and Phytoalexin Deficient 3 (PAD3). This suggested that cold exposure-mediated resistance against B. cinerea is independent of SA signaling, jasmonic acid (JA) signaling, and camalexin biosynthesis. Increased accumulation of reactive oxygen species (ROS) was observed in Arabidopsis leaves after the cold pre-treatment and subsequent B. cinerea infection indicating a central function of ROS in the crosstalk between the prior cold and pathogen infection. Besides other functions, ROS contribute to lignin and callose formation. Enhanced callose formation and lignification could be detected immediately after the cold exposure. In contrast, B. cinerea did not alter plant lignin amounts and pathogen-triggered callose deposition was not further affected by prior cold treatment. We extended our analyses by investigating the impact of cold-pre-treatments on the establishment of systemic aquired resistance (SAR). The induction of SAR in cold-pretreated plants was successful, but the prior cold treatments did not provide additional benefits for SAR against Pst. Interestingly, a syringe infiltration with the mock solution instead of the SAR-triggering primary Pst inoculation enhanced the susceptibility of Arabidopsis after a cold pre-treatment against Pst. The most pivotal finding of this work demonstrated that the chloroplast-localized ROS-scavenging enzymes stromal ascorbate peroxidase (sAPX) and thylakoid ascorbate peroxidase (tAPX) are essential for the wildtype-like enhanced resistance against Pst and B. cinerea after prior cold treatments. CP-mediated resistance was also confirmed in the immunocompromised null mutant enhanced disease susceptibility 1 (eds1-2) crossed with stroma ascorbate peroxidase knockout (eds1 sapx). This work, furthermore, showed that sAPX is essential for cold-induced callose formation and dispensable for pathogen-induced callose. Finally, sapx, but not thylakoid ascorbate peroxidase knockout (tapx), showed a different ROS generation pattern, with significantly more ROS being generated than in cold-treated sapx or compared to wildtype plants without cold pre-treatment. These results highlight the relevance of the chloroplast antioxidant system in cold sensing and its impact on the plant immune system.

This work aims to develop superhydrophobic surfaces from supramolecular xerogels with low molecular weight gelators (LMWGs). LMWGs are small organic compounds that have a strong preference to form gels in a suitable solvent. To achieve a xerogel coating, one can drop-cast the gel onto substrates such as glass cover slips, allowing it to dry under ambient condition. The LMWGs used in this work are based on a trans-1,2-diamidocyclohexane core, equipped with two equilateral perfluorinated side chains (CFn, where n represents the number of the carbon atoms on each chain). The amide groups on the core facilitate strong intermolecular hydrogen bondings and lead the way to supramolecular self-assembly, while the perfluorinated side chains contribute to the intrinsic low surface energy of the materials. Both parts are essential for the formation of the superhydrophobic xerogel coating.

The first part of this work focuses on investigating the effect of the side-chain length on the resulting xerogel coating. Eight LMWGs, from CF3 to CF10, are included in the investigation. The xerogel coatings were examined from three different scales. In the nanoscale, surface x-ray diffraction (sXRD) reveals the difference in the structural properties of the resulting supramolecular aggregates. Scanning electron microscopy (SEM) and optical microscopy were used to reveal the morphologies of the aggregates in the microscale. As for the macroscopic scale, the coatings were tested for their hydrophobicity and durability towards water flushing. In addition to the standard contact angle measurements and gravimetric studies, an image processing script coined Morphology evolution analysis (MEA) was devised to investigate the change of the coating after intensive flushing. This method evaluates the durability by assessing the change in the relative thickness of the coating through pixel intensity. The first part of this work concludes that the length of the perfluorinated side chains has a significant impact on the resulting xerogel, as certain LMWGs provide xerogel coatings with better properties in terms of both hydrophobicity and durability.

To broaden the applicability of the xerogel coating, it is crucial to overcome the intrinsic mechanical fragility of the xerogels. Therefore, the second part of this work focuses on the preparation of the more mechanically-durable hydrophobic coatings from the combination of supramolecular xerogels and polymers. CF7 was selected as the concept LMWG, while two monomers, methyl methacrylate (MMA) and trifluoroethyl methacrylate (TFEMA), were chosen as the candidates for the polymer component. Extensive screening was done to find the optimised fabrication condition for a robust hydrophobic supramolecular-polymer co-assembly. The co-assemblies were investigated with SEM and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for the structure of the aggregates and the uniformity of the coating, respectively. The iterability and durability of the co-assemblies are again tested with water flushing. A sclerometer was employed in addition to test the scratch resistance of the co-assemblies. Practical implementations including metal corrosion protection and oil-repellency were also carried out. In conclusion, xerogel-based hydrophobic and oleophobic coatings with significantly improved scratch-resistance are achieved by fixating the supramolecular network with a polymer matrix.

T. gondii is a zoonotic protozoon that can infect virtually all warm-blooded species on all continents. The parasite has a complex population structure, including countries and continents dominated by only a few clonal lineages, while T. gondii populations in South America are highly diverse. The genetic diversity described in Central and South America is associated with higher virulence and more severe cases of toxoplasmosis in humans, making it important to detect the introduction of such genotypes into Europe. This work focused on genotyping of T. gondii in Europe where the clonal lineage type II is predominant. The predominance of T. gondii type II in Europe was described in the past as part of global studies on population genetics of T. gondii, but there were no studies that focused exclusively on Europe. Therefore, the available genotyping information on European T. gondii was summarized in a review and the distribution of circulating strains in Europe was mapped, revealing that there was little or no information available for some countries. Moreover, it was recognized that the application of genotyping methods was not consistent between different laboratories. A frequently used genotyping method for T. gondii is based on MS markers. It represents the current reference standard for genotyping and fingerprinting. To reach consistency in T. gondii MS typing, a ring trial among five European laboratories was organized and the results were published together with guidelines for a harmonized application of MS typing. On this basis, MS typing results may become more comparable in the future, which is necessary to combine larger data sets on T. gondii genotypes originating from different studies. Guidelines for MS typing may also encourage more laboratories in Europe to use the MS method, which may help to fill the identified gaps in genotyping data. MS typing and WGS analysis revealed genetic variability within T. gondii type II. To explore this further, an NGS-based typing method with a high typing resolution among T. gondii type II strains was established. This new Ion AmpliSeq method appears to be suitable to improve the understanding of transmission pathways of T. gondii, to trace infection sources in outbreaks or to detect recombination and the introduction of genotypes to new areas. Furthermore, the harmonized MS method was applied in a study for genotyping of T. gondii DNA extracted from tissue samples of red squirrels (Sciurus vulgaris) found dead in the Netherlands. This study identified genetic clusters based on the MS typing results, but without obvious regional association. In future studies, cluster analyses can be performed with large, combined datasets using the harmonized MS typing method or Ion AmpliSeq typing to obtain further insights into the population structure of T. gondii in Europe.

Background: It was recently reported that periportal fibrosis in mice did affect the expression of CYP proteins, a set of pericentrally located drug-metabolizing enzymes. This observation suggests an interplay between zonated morphological disorders and metabolic zonation, a potentially clinically relevant finding. Therefore, we raised the hypothesis that periportal steatosis in mice may affect zonated drug metabolism parameters. Cross-species variation has not yet been systematically explored with respect to hepatic lobular geometry and CYP expression as needed for clinical translation. We hypothesized that lobular geometry as an anatomical feature is species-independent, whereas CYP zonal expression as a functional parameter is species-dependent. Method: We performed a detailed drug metabolism study in mice with periportal steatosis induced by feeding a high-fat methionine-choline reduced diet applied over two, respectively, four weeks. Drug metabolism was assessed in terms of the spatial distribution of drug-metabolizing CYP enzymes, CYP activity, and a pharmacokinetic study. For the cross-species analysis, we involved four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry to quantify lobular geometry and zonated expression of key cytochrome P450 (CYP) enzymes. Results: Periportal steatosis did not alter the pericentral expression pattern of the CYP enzymes. However, the activity of selected CYPs was related to the type and severity of steatosis. Caffeine elimination was accelerated by microvesicular steatosis, whereas midazolam elimination was delayed in macrovesicular steatosis. Using the newly developed automated image analysis pipeline, we observed that hepatic lobular geometry is rather robust, whereas zonated expression shows species-specific features, with mice being most similar to humans. Conclusion: In this thesis, we demonstrated that periportal pathology such as steatosis could affect certain features of hepatic drug metabolism, a metabolic process taking place in the pericentral region. We demonstrated the robustness of lobular geometry in four different species and described the impact of the given species on the spatial distribution of CYP proteins in normal livers. Perspective: Our planned future studies include assessing species-specific features of steatosis, including heterogeneity, and their implications for the spatial distribution of CYP expression. Based on this data, we want to perform a translational study using human samples to confirm the impact of periportal and pericentral steatosis on distinct parameters of drug metabolism.

Cancer is a leading cause of death worldwide and the second leading cause of death in Germany. The primary goal of cancer therapy is to reduce mortality and improve patient survival. However, the choice of therapy is heavily influenced by the patient’s prognosis, highlighting the importance of cancer survival prediction as a means to quantify the patient’s risk and estimate prognosis. This dissertation presents a cancer survival prediction approach that uses XGBoost tree ensemble learning and is based on gene expression data of 25 different cancer types from The Cancer Genome Atlas (TCGA). We evaluate two versions of this approach, one trained on each cancer type separately and the other trained on pan-cancer data comprising all 25 cancer types, and find that the pan-cancer approach yields improved performance over the single-cancer approach. Furthermore, we evaluate the pan-cancer approach on additional molecular data types, including mutations, copy number variations, and protein expression data, and identify gene expression as the most informative data type. To assess the biological plausibility of the gene expression-based pan-cancer survival prediction approach, we apply network propagation to gene weights derived from the survival prediction model and infer a pan-cancer survival network comprising 103 genes. These 103 genes are most significantly enriched for the tumor microenvironment, which has been associated with cancer progression, metastasis, and response to therapy, validating the biological plausibility of our survival prediction approach. Furthermore, we explore the potential of transfer learning for cancer survival prediction. To this end, we pre-train neural networks for cancer survival prediction, but also for related tasks such as tissue type and age prediction. We then transfer the learned knowledge to cancer survival prediction on independent datasets from TCGA, as well as substantially smaller cancer studies. We find that transfer learning can indeed improve cancer survival prediction, although the benefit of transfer learning may depend on the size and characteristics of the datasets used.

Combining organic molecules with inorganic substrates, especially two-dimensional materials such as transition-metal dichalcogenides (TMDCs), is a wide field with much interest and many possibilities. Finding the right combination to achieve a purposeful union with desired properties requires a detailed examination of the fundamental processes that occur in these hybrid systems. Scanning tunnelling microscopy (STM) and spectroscopy (STS) are ideal tools for investigating these hybrid systems, as they allow us to employ their powerful capabilities of local spatial resolution on the atomic scale, resulting in direct access to the local electronic structure. The locality of electronic effects is a crucial piece of information in reaching a full understanding of the various mechanisms at play. In this thesis, we utilise STM and STS to investigate three different hybrid systems under three different aspects: In the first part, we create and explore the system of trifluoromethyl-terphenyl-thiol (CF3-3P-SH) molecules on Au(111) and MoS2/Au(111) and the various adsorption properties. We compare physisorption on both surfaces of Au(111) and MoS2/Au(111), and chemisorption, facilitated by successfully anchoring the CF3-3P-S(H) molecules to purposefully created S-vacancies in the MoS2 monolayer. The anchoring molecules are identified by their rotation around one of their terminations. We observe two different species of anchored molecules that differ only in their electronic structure: the majority shows nothing around the Fermi energy, whereas a small percentage exhibits a peak at zero bias which we assign to a Kondo resonance. This chemisorption process is disentangled at the atomic level by combining experiment and theory in collaboration. Detailed analysis of the stability of the hybrid system, ab-initio molecular dynamics simulations and DFT calculations confirm that two different molecular species are involved: intact CF3-3P-SH and dehydrogenated CF3-3P-S. Both show electronic states inside the bandgap of MoS2 which crucially differ in their occupation. Secondly, we further explore the capabilities of MoS2 as a decoupling layer that enhances the lifetime of molecular states inside its bandgap. Using the model system of single vanadyl-naphthalo-cyanine (VONc) molecules adsorbed on MoS2/Au(111), we study the electronic states of this molecule in detail. We identify the observable in-gap states and analyse the local variations in the electronic structure which are determined to be caused by the tip-perturbation potential as well as vibration-induced effects such as vibration-assisted tunnelling. In the last part, we investigate the capabilities of bulk 2H-MoTe2 as a substrate for STM, identifying and exploring its inherent n-type semiconductor characteristics and the importance of choosing suitable molecular adsorbates such as tetrathiofulvalene (TTF) molecules which show signs of charge transfer with the substrate. Various naturally occurring defects of MoTe2, showing strong states in the bandgap of MoTe2, are observed as well. These states are imaged spatially using dI/dV maps.

Nosokomiale Infektionen und die damit einhergehende Problematik der Besiedlung von Patienten mit multiresistenten Erregern (MRE) stellt immer mehr eine ernst zu nehmende Herausforderung sowohl in der Human- als auch in der Veterinärmedizin dar. Gerade in Pferdekliniken haben NI in den letzten Jahren zugenommen, weshalb ein Hygienemanagement zur Prävention von Wundinfektionen eine immer größere Bedeutung bekommt. Pferdekliniken stellen hierbei aufgrund der tierartspezifischen Anforderungen eine besondere Herausforderung dar, während Kleintierkliniken viele Erkenntnisse aus der Humanmedizin übertragen können. Besonders im Zusammenhang mit Wundinfektionen beim Pferd treten die klassischen opportunistischen und zoonotischen Pathogene wie z.B. Methicillin-resistente Staphylococcus aureus (MRSA) und Extended Spectrum Beta-Laktamase (ESBL-) produzierende Entereobacteriaceae auf. Vor diesem Hintergrund war es Ziel dieser Arbeit, ein multimodales Hygienemanagement im Zusammenhang mit SOPs zu entwickeln, welches in der Pferdeklinik eine wirksame und umsetzbare Anwendung finden kann und somit zu einer Reduzierung von Wundinfektionen beitragen soll. In dieser Studie wurde bei insgesamt 341 equinen Patienten in den Jahren 2014 und 2015 ein Eingangsscreening mittels nasaler Tupferproben und Kotproben für eine mikrobiologische Untersuchung durchgeführt und ein Status quo der mitgebrachten Keimflora ermittelt. Eingeschlossen wurden alle Patienten die mit der Indikation Kolik (n = 233) oder mit einer offenen Verletzung (n = 108) in der Klinik für Pferde, Allgemeine Chirurgie und Radiologie der Freien Universität Berlin vorstellig wurden. Zusätzlich erfolgte bei allen Verletzungen im Rahmen des Screenings eine Probennahme aus dem Zentrum der Wunde. Das Studiendesign untergliederte sich in drei verschiedene Abschnitte: Untersuchungszeitraum A im Jahr 2014, einer darauffolgenden Intervention und damit verbunden die Einführung der im Untersuchungszeitraum A entwickelten neuen Hygienemaßnahmen in Form von SOPs und anschließend Untersuchungszeitraum B im Jahr 2015. Der Fokus der SOPs für die Intervention wurde dabei auf die Verbesserung der Händehygiene-Compliance gelegt und der Verbrauch an Desinfektionsmitteln in den Untersuchungszeiträumen A und B ermittelt. Zusätzlich wurde in beiden Untersuchungszeiträumen eine aktive Surveillance von postoperativen Wundinfektionen durchgeführt und alle detektierten Infektionen einer mikrobiologischen Folgeuntersuchung unterzogen. Dadurch konnte die Infektionsrate und Belastung mit multiresistenten Erregern (MRE) in den Untersuchungszeiträumen A und B miteinander verglichen werden. Einbezogen wurden zusätzlich verschiedenen Risikofaktoren auf das Erlangen einer Wundinfektion wie die Aufenthaltsdauer, der chirurgische Eingriff und die Inzisionslänge, eine Vorbehandlung mit Antibiotika sowie Alter und Gewicht. Die Auswertungen des Eingangsscreenings zeigten, dass 3,5 % der Patienten bereits mit MRSA bei Einlieferung in die Klinik belastet waren und 10,7 % positiv auf ESBL-produzierende Enterobacteriaceae getestet wurden. Die Abstriche der Wunden zeigten eine Keimbelastung von 3,7 % mit MRSA, 1,9 % mit ESBL-produzierenden Enterobacteriaceaen und 0,9 % mit Acinetobacter baumanii (A. baumanii) bei Aufnahme in die Klinik. Im Rahmen der Studie wurden mehrere Faktoren identifiziert, die das Wundinfektionsrisiko im signifikanten Maße beeinflussten. Die Aufenthaltsdauer erhöhte sich um das Doppelte bei Patienten mit einer Wundinfektion (p = 0,001), ein chirurgischer Eingriff beeinflusste signifikant das Erlangen einer Infektion (p < 0,005) und wies damit verbunden ein 33,7-fach erhöhtes Wundinfektionsrisiko auf. Auch die stationäre Behandlung einerseits (p < 0,005) und die Vorbehandlung mit Antibiotika vor der Kliniküberweisung (p = 0,002) andererseits beeinflussten das Wundinfektionsrisiko. Zudem konnten das Alter (p = 0,006) und das Gewicht (p = 0,0037) als Risikofaktoren ermittelt werden. Insgesamt konnten 42 Infektionen in den Untersuchungszeiträumen A und B detektiert werden, wovon 69 % mit mindestens einem MRE besiedelt waren. Durch die Einführung des zielgerichteten Hygienemanagements und der dazugehörigen SOPs konnte eine deutliche Senkung von Wundinfektionen erzielt werden (p = 0,033). Bei der Indikation Kolik, von denen 48 Patienten einer Laparotomie unterzogen wurden, erlagen im Untersuchungszeitraum A 30 % der Patienten einer Wundinfektion, im Untersuchungszeitraum B nur noch 17,9 %. Bei der Indikation der Verletzungen entwickelten im Untersuchungszeitraum A 31,7 % der Patienten eine Wundinfektion und nur 25 % im Untersuchungszeitraum B. Dies entsprach einer Gesamtabnahme der Infektionsrate um 8,9 % in US B nach Intervention. Zudem sank die Gesamtzahl an MRE in den Folgeuntersuchungen der Wundinfektionen um 9,5 %. Die Haupterkenntnis aus diesen Daten war, dass zielgerichtete Maßnahmen, v.a. die Steigerung der Händehygiene-Compliance, einen großen Einfluss auf die Risikominimierung von Wundinfektionen haben mussten, der Verbrauch an Desinfektionsmitteln stieg in dieser Studie im Untersuchungszeitraum B um 190 % an.

Die Bestimmung der aeroben mesophilen Gesamtkeimzahl auf Schlachttierkörpern eignet sich im Speziellen zur Beurteilung der Prozesshygiene am Ende der Schweineschlachtkette. Für diese mikrobiologische Schlachttierkörperuntersuchung stehen verschiedene destruktive und nicht-destruktive Techniken zur Verfügung, welche unterschiedliche Vor- und Nachteile aufweisen. Die Agarkontakt-Methode, bei der der Nähragar für eine quantitative Keimzahlbestimmung homogenisiert wird, basiert auf der Anwendung von Agarkontaktplatten. Die Probenahmetechnik mittels Agarkontaktplatten ist für die Untersuchung von Gegenständen nach DIN EN ISO 18593:2018 genormt und besitzt den entscheidenden Vorteil einer schnellen und praktikabel durchführbaren Beprobung.

Um die Aussagekraft der Ergebnisse der Agarkontakt-Methode für die Anwendung auf Schweineschlachttierkörperoberflächen bewerten zu können, wurde in einer Methodenvergleichsuntersuchung die Agarkontakt-Methode mit dem nach DIN EN ISO 17604:2015-12 genormten Nass-Trocken-Tupferverfahren in Bezug auf den Nachweis der aeroben mesophilen Gesamtkeimzahl verglichen. Dazu wurden beide Methoden in einem experimentellen Ansatz mit inokulierten Schweinehautteilstücken und in einem konventionellen Schlachtbetrieb auf Schweineschlachttierkörpern untersucht. Es ergab sich für beide Teilversuche eine statistisch signifikante Äquivalenz zwischen den beiden nicht-destruktiven Beprobungsmethoden. Der Feldversuch im Schlachtbetrieb ergab Oberflächenkeimzahlen des Schlachtkörpers, welche vereinzelt an oder unter der minimalen Nachweisgrenze für die Agarkontakt-Methode lagen. Insgesamt war die Ermittlung einer geringen Anzahl an Oberflächenkeimen mit der Agarkontakt-Methode weniger zuverlässig als mit dem Nass-Trocken-Tupferverfahren. Allerdings wurde die Vergleichbarkeit der Ergebnisse beider Methoden bei hohen Oberflächenkeimzahlen ermittelt. Insbesondere ermöglicht diese praktikable und tiergerechte Methode die mikrobiologische Untersuchung von lebenden Schlachtschweinen und Schlachttierkörpern an mehreren Schlachtprozessstufen, ohne den Arbeitsablauf unterbrechen oder die Methode wechseln zu müssen.

Die Agarkontakt-Methode realisierte eine longitudinale Studie in einem industriellen Schlachtbetrieb mit moderner Schlachttechnologie zur Bestimmung der Oberflächenkeimzahl und Salmonellen von Schlachtschweinen, beginnend im Wartestall bis zur Prozessstufe vor der Kühllagerung. Die Untersuchung ergab einen mit zahlreichen Studien vergleichbaren Verlauf der Gesamtkeimzahl über den gesamten Schlachtprozess. Zudem konnten die Berieselung im Wartestall sowie die Betäubung und Entblutung als Stufen mit einem möglichen Risiko der Kreuzkontamination identifiziert werden. Es konnte gezeigt werden, dass die Agarkontakt-Methode einen wichtigen Beitrag zur Ermittlung von systemischen und individuellen Defiziten im Schweineschlachtprozess und von kontaminierten Schlachtschweinpartien im Rahmen einer zusätzlichen betriebsspezifischen Schlachtprozessanalyse leisten kann. Die mit dieser einfachen Probenahmetechnik erhobenen Gesamtkeimzahlen und Salmonellen auf Schweinehautoberflächen können ein sinnvolles und praktikables Mittel zur ergänzenden Einschätzung und Optimierung der Schlachthygiene sein.

The overall objectives of this thesis were 1) to compare the effect of an additional prostaglandin F2α (PGF2α) treatment and an increased dosage of PGF2α on d 7 during an Ovsynch protocol with an untreated control group, regarding luteolysis and reproductive performance; 2) to determine the effect of progesterone (P4) supplementation by means of a P4 releasing intravaginal device (PRID) insert for 8 days during an Ovsynch protocol on pregnancy per artificial insemination (P/AI) and pregnancy loss; 3) to evaluate vaginal discharge at device removal on fertility, and 4) to evaluate the diagnostic performance of transrectal ultrasound to detect a functional corpus luteum (CL) based on circulating P4 levels.

In the first study, the aim was to compare the effect of two PGF2α treatments 24 h apart (25 mg of dinoprost at d 7 and 8) and the treatment of a double PGF2α dose (50 mg of dinoprost at d 7) with a control group (25 mg of dinoprost at d 7) during a 7-d Ovsynch protocol with inclusion of a PRID device for 8 days on luteal regression and P/AI in lactating Holstein cows. Furthermore, we wanted to evaluate the potential impact of vaginal discharge caused be the P4 insert on fertility and whether serum P4 levels correspond with ultrasound CL diagnostic.

The experiment was conducted on a single commercial farm in Northeast Germany. A total of 1,056 cows were randomly assigned within parity to receive 1 of 3 Ovsynch protocols on a weekly basis: 1) a control group in which cows received an Ovsynch protocol with a single PGF2α treatment (control: d 0, 100 μg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 μg of GnRH), 2) an Ovsynch protocol with a double dose of PGF2α (DoubleDose: d 0, 100 μg of GnRH + PRID; d 7, 50 mg of dinoprost; d 8, PRID removal; d 9, 100 μg of GnRH) and 3) an Ovsynch protocol with an additional PGF2α treatment 24 h after the first one (2PGF: d 0, 100 μg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, 25 mg of dinoprost and PRID removal; d 9, 100 μg of GnRH). All cows received a PRID from d 0 until removal on d 8, on which vaginal discharge was evaluated and scored [vaginal score (VS) 0 = no debris, VS 1 = small flecks of purulent debris, VS 2 = abundant amount of purulent debris]. To facilitate first post partum timed AI (TAI), the farm used a Presynch-Ovsynch protocol (PGF2α, 14 d later PGF2α, 12 d later start of an Ovsynch protocol). All cows were inseminated approximately 16 h after the second GnRH treatment (G2) of the Ovsynch protocol. Ovarian ultrasonography was performed on d 0 (G1) to determine abence or presence of a CL and its size. Blood samples were collected on d 0, 7 and 9 in order to asses P4 concentrations. Pregnancy diagnosis was performed using transrectal ultrasound d 38 ± 3 after AI and reconfirmed d 80 ± 7.

Treatment affected P4 concentration at G2. Mean P4 concentrations at G2 differed (P = 0.037) among treatments (control 0.35 ± 0.02 ng/mL; DoubleDose 0.29 ± 0.02 ng/mL; 2PGF 0.30 ± 0.02 ng/mL) and were lower for 2PGF cows (P = 0.043) and DoubleDose cows (P = 0.023) compared with cows in the control group. There was an interaction between treatment and CL at G1 (P = 0.087). Cows without a CL at initiation of the protocol had decreased (P = 0.014) P4 concentrations when treated with a double dose of PGF2α and tended (P = 0.062) to have a decreased P4 concentration at G2 when receiving 2 consecutive treatments 24 h apart. Proportion of cows with luteolysis differed among treatments (P = 0.025; control 84.8%; DoubleDose 91%; 2PGF 92.6%) considering only cows with P4 concentrations above 1.0 ng/mL (indicative of presence of a CL) at first PGF2α (863/1011) and 0.5 ng/mL at G2 (indicative of complete luteolysis).

Cows that received an additional treatment 24 h apart had greater P/AI (46.5%) compared with DoubleDose cows (37.7%; P = 0.045), but did not differ compared with cows in the control group (40.3%; P = 0.144). Considering luteal status at G1, cows within the 2PGF group had greater (47.9%; P = 0.043) P/AI when compared with DoubleDose cows (32.7%), but did not differ compared with control cows (36.1%; P = 0.109) when no CL was present at protocol initiation. The overall accuracy was 87.2% to identify a functional CL using transrectal ultrasound at the beginning of the protocol. The area under the curve (AUC) was 0.901 and can be considered highly accurate. The optimum cutoff was a 20-mm diameter of the CL.

Vaginal discharge score had a significant association (P = 0.001) with P4 concentrations at the first PGF2α treatment. Cows assigned to a VS of 2 had greater (4.3 ± 0.2 ng/mL) serum P4 levels than cows assigned to score 0 (3.0 ± 0.3 ng/mL; P = 0.001) and 1 (3.7 ± 0.1 ng/mL; P = 0.002). Progesterone concentration at d 7 was greater (P = 0.027) for cows assigned to VS 1 compared with cows assigned to VS 0. Vaginal discharge score at PRID removal tended to have an association with P/AI at d 38 after AI (P = 0.072). Pregnancy per AI did not differ (P = 0.459) among cows scored with a VS of 0 and 1 [36.5% (25/69); 41.3% (320/780)], but was significantly greater [49.7% (102/207)] for cows having a VS of 2 compared with VS 1 (P = 0.039), and tended to be greater compared with VS 0 (P = 0.066).

Outcomes from this study demonstrate that both PGF2α modifications can increase luteolysis in P4 supplemented Ovsynch protocols compared with a standard PGF2α treatment on d 7 of the protocol. Interestingly, only cows receiving an additional PGF2α treatment had a numerical increase in P/AI (6.2 %), especially in cows without a CL at G1 (11.8 %), whereas an increased dose of PGF2α did not lead to any improvement in reproductive performance. Vaginal discharge at d 8 of the protocol, after PRID removal, was associated with higher P4 concentrations at d 7 and greater P/AI. Ultrasound can be deemed as a valuable tool for CL detection.

The second study aimed to elucidate the effect of P4 supplemention for 8 days, by means of a PRID insert, during an Ovsynch protocol on P/AI and pregnancy loss compared with a standard 7-d Ovsynch protocol.

A total of 716 lactating Holstein cows from one commercial dairy farm in Northeast Germany were enrolled in this study. The treatment group was part of the aforementioned study and received an 8-d P4-based Ovsynch protocol (PRIDsynch: d 0, 100 μg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 μg of GnRH), whereas the control group received a standard 7-d Ovsynch protocol as part of the farms reproductive schedule (control: d 0, 100 μg of GnRH; d 7, 500 μg of cloprostenol; d 9, 100 μg of GnRH). All cows were inseminated approximately 16 h after G2. Pregnancy diagnosis was performed by transrectal ultrasound examination d 38 ± 3 after AI and reconfirmed d 80 ± 7. Pregnancy loss included cows that experienced pregnancy loss from d 38 to 80.

Results from this study demonstrate the overall beneficial effect of an elongated P4, 8 d supplementation with a PRID insert in an Ovsynch protocol on reproductive performance. Pregnancy per AI was significantly increased in PRIDsynch cows [P = 0.014; 38.9 % (115/360)] compared with untreated control cows [31.7 % (115/360)] on d 38 ± 3 after AI. However, pregnancy loss was not affected by treatment [P = 0.279; control: 8.8 (10/113) vs. PRIDsynch: 6.2 (9/146)].

Overall, this thesis shows that 1) the proportion of cows with complete luteal regression near TAI was increased by both PGF2α modifications, but only the second treatment 24 h apart resulted in greater P/AI compared with the increased PGF2α dose and a numerical increase in P/AI compared with control cows, especially in cows lacking a CL at protocol initiation, 2) the addition of a PRID from d 0 until removal on d 8 of the TAI protocol increased reproductive performance but did not influence pregnancy loss, 3) vaginal discharge caused by P4 inserts has no negative impact on fertility and 4) ovarian ultrasound examinations are suitable for detection of a functional CL. Taken together, these results have a potential to improve reproductive performance on dairy farms using TAI protocols.