Cold fronts provide an environment particularly favourable for convective initiation in the mid-latitudes and can also be associated with convective hazards such as flooding, wind, hail and lightning. In this thesis, the climatology, characteristics and forcing mechanisms of cold-frontal convection are analysed by combining a radar-based cell detection and tracking dataset and an automatic front detection method applied to reanalysis data. The climatology indicates that around twice as many cells develop on cold-frontal cell days on average compared to non-cold-frontal cell days. The maximum cell frequency is found to be marginally ahead of the typical surface front location, whereas the 700 hPa front location marks the minimum cell frequency and a clear shift in regime between cells with a weakened diurnal cycle on the warm side of the 700 hPa cold front and strongly diurnally driven cells on the cold side of the 700 hPa front. Lightning strike data are analysed in Western and Central Europe and show broadly consistent results. Pre-surface-frontal cells have the largest fraction associated with mesocyclones, intense convective cores and lightning in Germany. Namely, mesocyclones were detected in around 5.0% of pre-surface-frontal cells compared to only 1.5% of non-cold-frontal cells.
To unravel the results found in the climatology, the thermodynamic environments and lifting mechanisms of convective cells are analysed by considering different variables from reanalysis data. Pre-surface-frontal cells have the highest dewpoints and convective available potential energy, which is likely a contributing factor towards the larger fraction of cells with mesocyclones, intense convective cores and lightning. Higher mid-level relative humidity than climatology was found to be particularly important to allow convective cell development on the cold-side of the 700 hPa front. While large-scale lifting is typically thought to be most relevant in the warm-sector, here its relevance is also highlighted on the cold-side of the 700 hPa front. Most cells have relatively low sunshine duration prior to development, which indicates that solar heating may not be directly relevant for the majority of cell initiation.
A more complex statistical modeling approach, incorporating one moisture, one instability, and three lifting terms, reveals a lower level of proficiency near the surface front, consistent across four distinct statistical models. Feature (predictor) importance techniques show differences in the importance of each feature depending on the front relative region. Furthermore, certain features add more skill depending on the statistical model used. Finally, a 12 feature gradient boosted model is trained to predict the probability of convective cell occurrence. The model is shown to generally represent the spatial and temporal frequency of cells around the front on new, unseen testing data.
The results in this thesis are an important step towards a deeper understanding of the drivers of cold-frontal convection depending on the region relative to the front. Furthermore, light is shed on the applications of statistical models to predict the convective cell occurrence.
Weniger anzeigenEconomic elites are powerful actors. Their influence on shaping the agenda, policy outcomes, and the public's preference has been empirically revealed. In the study of international political economy, however, these actors have not been integrated in the analysis of wealth inequality – which represents one of the most pressing problems of our time. And although we experience extreme levels of wealth inequality with ongoing consolidations of inheritance societies, the debate about a potentially powerful tool to reverse the trend – the inheritance tax – seems small and insignificant. In my PhD project I contribute to filling these research gaps in an intertwined manner by comparing Mexico and Germany. As different as Mexico and Germany are, they share an important commonality: At present, they have among the highest and nearly the same levels of wealth inequality – belonging to the most unequal democracies in the world and being rather inheritance societies than meritocracies. How have narratives and legal regulations of inheritance taxes evolved? And what are the narratives of elites towards wealth inequality and the inheritance tax? In a first step, I compare the historical development of inheritance regulations and its narratives in order to present the repertoires of narratives (RON). Once the scene is set, I present the centerpiece of my project: A narrative analysis of 38 semi-structured interviews with the economic elites, defined as CEOs, CFOs, board members, presidents and/or vice-presidents of the biggest companies in their countries. The elites' ideas, norms, and values, captured in their narratives on the topic of wealth inequality, have firstly, an explanatory power for preferences over design of public revenues, and secondly, they allow breaking through the inadequate yet extensive homogenous treatment of the group.
Weniger anzeigenThe present work studies the historical contexts of the Bactrian inscriptions of the Kušān period and attempts to extract the historical information of this epigraphic corpus by contextualising it with related sources. Following an introduction on the historical backgrounds and the problem of Kušān chronology, four main topics are studied: (1) The linguistic and literary contextualisation of the texts, (2) the titulature of the Kušān emperors in the inscriptions, (3) the religious aspects of the inscriptions and their contexts and (4) the information on the expansion and administration of the Kušān Empire which are described here as the “Imperial Strategy”. (1) shows that Bactrian was reduced to writing in the early Kušān period to facilitate its use as an imperial means of communication. This process involved individuals who spoke Greek and probably identified themselves as such. This becomes apparent from various attempts to solve problems arising from writing Bactrian in Greek script, which is phonetically unsuited for this language. An epigraphical analysis of the corpus of inscriptions further shows that by the time of Huviška, the Kušān attempted to standardise and simplify Bactrian orthography at the cost of grammatical complexity. The inscriptions contain only little material for literary analysis, but a sense of style is apparent from several passages that can be related to the inscriptions of the Achaemenid, Arsakid and Sāsānian periods. This proves that the Bactrian inscriptions of the Kušān are part of the literary history of Iran. (2) shows that the Kušān had already established a canon of imperial titles under their founder Kujula Kadphises that was only subject to marginal change afterwards. The titles are largely taken from the Bactrian tradition and originate in the Hellenistic period. The Bactrian titles were mostly translated from Greek forms current in Bactria for several centuries. A few Kušān novelties in the repository of titles are probably attributable to Chinese and Roman influence. (3) adds a study of the deities appearing on Kušān coins to explain the religious information from the inscriptions. It becomes clear that the Kušān religion appearing in epigraphic, numismatic and archaeological sources is influenced by various religious ideas in the empire, but contrary to long-standing opinions by researchers, it did not intend to portray the religious diversity of the empire. Rather, the Kušān emperors Kaniška I and Huviška assembled various groups of deities for political ideas. The Rabatak Inscription shows that such groups were also the subject of collective cults. The only known parallel to this practice in the Iranian world is possibly the cult of the Commagenean king Antiochos I. This also includes the deification of the living emperor and his predecessors, for which the epigraphic and iconographic material provides indicators that can no longer be doubted. The present work cannot, however, trace the origins of this practice. (4) first examines the expansion of the Kušān Empire from the literary and archaeological sources. An excursus of sorts then examines the long-standing claim that Kušān expansion was primarily motivated by the interest of gaining control of long-distance trade routes. Further, the related idea of a Roman influence exerted mainly through trade on the foundations of the Kušān Empire is evaluated critically. The result is that these elements have been strongly overrated by researchers and the strategy of the Kušān does not display any sort of predominant commercial interests. Roman influence on the Kušān which is mostly observable in the material culture, also seems to have only been superficial. Following these investigations, the second part of (4) is concerned with the inner structure of the Kušān Empire and its administration. The main group of sources are administrative titles from Kušān inscriptions. Titles in Bactrian inscriptions and Iranian titles in Indian inscriptions show that, apart from the top layer of the imperial court, it is hard to argue for a centralised imperial administration of the empire. It would have been expected in such a case that Bactrian administrative titles would have been spread throughout the empire during its expansion. However, the Iranian titles in Indian inscription rather seem to be part of the Achaemenid legacy there, as they can best be etymologised as Old Persian. In place of a summary, a new narrative of Kušān history has been proposed. The dissertation also includes an appendix with a catalogue of the Bactrian inscriptions of the Kušān and a glossary of these inscriptions.
Weniger anzeigenDerzeit existieren nur wenige Daten über das Auftreten verschiedener Verstöße gegen tierschutzrechtliche Normen in deutschen Schlachtbetrieben. Wissenschaftliche Literatur und offizielle Dokumente bieten lediglich eine limitierte Auswahl der Verstöße, die in der Vergangenheit aufgetreten sind. Die Datenerfassung zu eingeleiteten Maßnahmen nach Verstößen in Schlachtbetrieben ist ebenfalls sehr begrenzt. Die juristische Fachliteratur weist auf ein Vollzugsdefizit im Zusammenhang mit dem Tierschutz in deutschen Schlachtbetrieben hin. Aus diesem Grund ist das finale Ziel dieser Arbeit die Entwicklung eines Maßnahmenkatalogs, welcher sich insbesondere an amtliche Tierärzt:innen und Amtstierärztinnen richtet, aber auch an weitere Personen, die für die Tierschutzϋberwachung und den Vollzug tierschutzrechtlicher Normen an Schlachtbetrieben verantwortlich sind, wie beispielweise Tierschutzbeauftragte und Jurist:innen. Zwei wichtige Bestandteile der Entwicklung eines Maßnahmenkatalogs ist erstens die Zusammenstellung von Handlungsempfehlungen zum Gesetzesvollzug bei Verstößen gegen den Tierschutz und zweitens die retrospektive Analyse des Vorkommens unterschiedlicher Tierschutzverstöße in deutschen Schlachtbetrieben. Dabei wurden Verstöße in den folgenden fünf verschiedenen Funktionsbereichen bzw. Kategorien hinsichtlich des Schlachtprozesses berücksichtigt: (1) Anwendung verbotener Treibhilfen sowie Gewalt beim Treiben, (2) tierschutzwidrige Unterbringung und Versorgung der Tiere im Wartebereich, (3) tierschutzwidriger Umgang mit Tieren mit besonderem Betreuungsbedarf, (4) Tierschutzverstöße bei der Durchführung der Ruhigstellung, Betäubung, Nachbetäubung und Entblutung sowie (5) fehlender Sachkundenachweis. Um den aktuellen Stand der Rechtsdurchsetzung zu untersuchen, wurden fünf Schritte implementiert: 1. die Beschaffung relevanter gerichtlicher Entscheidungen, 2. die Durchführung einer anonymen Online-Umfrage unter den mit dem Vollzug tierschutzrechtlicher Normen am Schlachtbetrieb betrauten Personen, 3. halbstrukturierte Interviews mit amtlichen Tierärzt:innen, 4. ein virtuelles Kolloquium mit amtlichen Tierärzt:innen und 5. die Konsultation von Anwält:innen. Die Analyse des Auftretens unterschiedlicher Verstöße setzte sich aus zwei Hauptteilen zusammen: a) einer Auswertung der Daten, die in einer Online-Umfrage gesammelt wurden, und b) einer Analyse relevanter gerichtlicher Entscheidungen. Diese Untersuchung hat zusammengefasst, welche Maßnahmen und Strafen die Teilnehmenden einer Online-Umfrage, Teilnehmener:innen, amtliche Tierärzt:innen eines Online-Kolloquiums sowie Strafverfolgungsbehörden als angemessen erachten und welche Maßnahmen in der Vergangenheit ergriffen wurden. Rechtliche Zitate und Zusammenfassungen relevanter Gerichtsentscheidungen wurden ebenfalls aufgenommen. Dies stellt den aktuellen Stand der Rechtsdurchsetzung für verschiedene Fälle von Verstößen gegen den Tierschutz im Schlachthof dar. Die Online-Umfrage legt nahe, dass einige verantwortliche Organe nicht die erforderlichen Maßnahmen und Strafen einleiten, wie es das Gesetz vorschreibt. Möglicherweise werden weitere Schulungen benötigt, um Verstöße gegen den Tierschutz zu erkennen und die notwendigen Maßnahmen zu ergreifen. In den Jahren 2019 bis 2021 traten Verstöße am häufigsten in den folgenden Funktionsbereichen bzw. Kategorien auf: Verwendung verbotener Hilfsmittel beim Treiben; unzureichende Haltung im Wartebereich; unsachgemäße Fixierung, Betäubung und Blutung von Tieren. Den Zeitrahmen von 2019 bis 2021 betreffend wurden in den Arbeitsumgebungen von über 50% der befragten Teilnehmer fünf spezifische Verstöße in diesen Funktionsbereichen bzw. Kategorien gemeldet. Diese Arbeit legt mit zwei entscheidenden Schritten einen Grundstein für die Verbesserung des Tierschutzes in deutschen Schlachtbetrieben. Die Ergebnisse dieser wissenschaftlichen Arbeit liefern einen möglichen Hinweis auf die Notwendigkeit, die Durchsetzung tierschutzrechtlicher Normen zu verbessern. Dies muss jedoch in zukünftigen Studien validiert werden. Der fertiggestellte Maßnahmenkatalog kann zu einer konsistenteren und standardisierten Durchsetzung des deutschen Tierschutzgesetzes beitragen. Die Identifikation von Mängeln beim Schlachten kann auch als Grundlage für die Verbesserung der Schulung des amtlichen Personals dienen. In diesem Sinne könnte ein Maßnahmenkatalog dazu beitragen, die Anzahl der Verstöße gegen den Tierschutz in deutschen Schlachthöfen zu reduzieren.
Weniger anzeigenThis thesis presents the experimental investigation of different magnetic two-dimensional (2D) materials on Au(111) and on Bi2Se3. For the experimental characterization, different structural (low-temperature scanning tunneling microscopy (LT-STM) and low-energy electron diffraction (LEED)), chemical (x-ray photoelectron spectroscopy (XPS) and x-ray absorption spectroscopy (XAS)) and magnetic techniques (x-ray magnetic circular dichroism (XMCD) and magnetization curve measurements) have been used to investigate the material properties. The scope of this thesis was to investigate the properties of monolayer (ML) and multilayer samples of new two-dimensional (2D) transition metal di-halides (TMDH) magnetic materials. In 2017 the first 2D magnets were found and characterized and since then, the main focus in the area of new 2D magnetic materials has been on transition metal di-chalcogenide (TMDC) and transition metal tri-halide (TMTH). Only recently also TMDH has been added in the research field. The focus of this work is the characterization of different transition metal di-halide (TMDH) on Au(111) and Bi2Se3. The work in this thesis builds the needed fundamental background for later possible spintronic device applications. In the first and second part of the thesis, FeBr2 was grown on Au(111) and Bi2Se3 to investigate the material properties as a function of thickness and growth temperature. On Au(111), the FeBr2 ML sample shows clear differences in the magnetic properties compared to the bilayer (BL) or trilayer (TL) sample. Additionally to the change in the magnetic properties, the structural properties are changing during the transition from ML to BL. The observed hexagonal superstructure of the first layer of FeBr2 on Au(111) with a periodicity of ≈ 1 nm disappears after the second layer is grown. The origin of the superstructure is related to the strong interaction with the Au(111) surface. These kind of structural changes between the first and second layer of FeBr2 are not observed on Bi2Se3, where a long-range moiré pattern was observed. Here the magnetic properties are unaffected from ML to multilayer coverages. Only for high coverages a possible bulk transition was investigated. Therefore, during the experimental investigation we were able to determine that the strong interaction with the Au(111) substrate leads to a change in the magnetic properties of the first ML of FeBr2. This change is not observed by growing them on Bi2Se3. In the third and last part of the thesis, MnBr2 and MnCl2 have been grown on Au(111) to compare how the different halides affect the magnetic properties for different coverages on Au(111). During the characterization, a temperature-related structural change was investigated for both materials which resulted in specific rotational orientations on Au(111). Nevertheless, this temperature effect does not affect the chemical composition and oxidation state on Au(111). By comparing the magnetic properties of MnBr2 and MnCl2 on Au(111), a difference in the magnetic saturation behavior on Au(111) is observed, which could be related to the weaker interaction of Cl with Au, compared to Br with Au.
Weniger anzeigenSystems biology is located at the intersection of biology, computer science, and mathematics, and is based on the translation of biological systems into math- ematical models. It aims to predict the behavior of these biological systems to improve the efficiency of time- and cost-intensive research in laboratories. In this thesis, we focus on the description and understanding of metabolic networks at steady state. These networks are mathematical models of the metabolic processes inside a cell. The stoichiometric and thermodynamic constraints that must hold in a metabolic network at steady-state define the steady-state flux cone. An im- portant concept to analyze flux cones in a mathematically and biologically meaningful way are elementary flux modes, which can be considered as mini- mal functional units of metabolic networks. In the flux cone, elementary flux modes correspond to vectors with inclusionwise minimal support. We focus on geometric aspects of flux cones of metabolic networks and elementary flux modes. The number of elementary flux modes may be very large, even for medium-sized metabolic networks. We study the facial structure and investigate the distribution of elementary flux modes among the faces of the flux cone. We observe that they are primarily contained in faces of relatively low dimension. Due to this observation, we develop a method to enumerate subsets of elementary flux modes that are contained in a specific face of the flux cone and apply this to decompositions of flux vectors. Empirically, we observed that elementary flux modes can always be written as a positive sum of exactly two others. Motivated by this, we investigate decompositions of elementary flux modes into others and discuss a conjecture that claims each EFM can always be decomposed into exactly 2 others or is not decomposable at all. Our mathematical results are illustrated on real examples and the presented data can be reproduced with a Python package we developed.
Weniger anzeigenEuropean Space Agency's (ESA's) 8th earth explorer mission, the Fluorescence Explorer (FLEX), aims to deliver the fluorescence signal emitted by terrestrial vegetation. It is planned to launch the satellite FLEX in 2025. FLEX will carry the high resolution Fluorescence imaging spectrometer (FLORIS) which has a spatial resolution of 300x300 m² and a swath width of 150 km. FLORIS will measure the complete fluorescence spectrum between 500 and 780 nm with a high spectral resolution between 0.3 and 3 nm. To disentangle the small fluorescence signal from the top-of-atmosphere (TOA) measurement, the sensor must be very sensitive and precise. Therefore, a good calibration and validation is necessary. Within this thesis, a validation strategy for FLORIS is developed by analysing pre-studies for the FLEX mission. Furthermore, an aerosol layer height retrieval is developed which can be extended to improve the atmospheric correction within the fluorescence retrieval. The Sentinel-3A and -3B tandem mission of 2018 was exploited to mimic the future tandem constellation of Sentinel-3 and FLEX. The spectral bands of the Ocean and Land Color imager (OLCI) on the Sentinel-3B satellite were shifted to a comparable band setting of FLORIS. This thesis presents a transfer function that enables the comparison of the radiance data of OLCI in FLEX configuration (OLCI-FLEX) and of OLCI in the nominal configuration. The transfer function overcomes the difference in spectral resolution by transferring information about the atmosphere and the surface from the spectral high resolution instrument to the lower resolution instrument. This information is used in a radiative transfer model to simulate OLCI-A measurement. The resulting simulated measurement at the nominal OLCI bands can be compared to the original OLCI-A measurement. The satellite-satellite comparison showed sensitivity to the known systematic measurement bias and also revealed processing errors. It was also studied how the satellite-satellite validation can be complemented by comparison of the satellite products with ground-based measurements. Ground-based instruments can be operated at low costs and with high accuracy. However, differences in spatial resolution result only in comparable signals if the surface is homogeneous. Thus, a measure for homogeneity of the surface was defined to identify the best possible ground site within a study scene by exploiting airborne measurements. The uncertainty due to differences in spatial resolution and spatial mismatch was also quantified. For the studied case, the validation uncertainty was small within the spectral range between 720 and 800 nm. The ground-based instrument should cover at least 13.5x13.5 m². The fluorescence retrieval is based on a spectral fitting method that exploits the well known structure of the oxygen absorption band at 760 nm. The depth of the absorption lines is determined by the surface pressure. Additionally, a present aerosol layer changes the depth of the lines depending on the height of the layer. Hence, the aerosol layer height is an important information for the fluorescence retrieval. A retrieval algorithm of the aerosol layer height based on OLCI measurements in the oxygen absorption band was developed. This algorithm was applied to two test cases over the ocean and for known aerosol types. The found height was comparable to results from a similar instrument, the Tropospheric Monitoring Instrument (TROPOMI). Both algorithms estimated the aerosol layer height too low compared to simultaneous measurements from an active instrument, the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). To extent the OLCI algorithm also for land cases, the surface reflectance must be well characterized and the aerosol type must be estimated. All in all, this study contributes valuable information for the development of a successful validation strategy of FLEX. This strategy should include the validation of the top of atmosphere radiance data by a comparison of FLORIS and OLCI. Especially within the oxygen absorption band at 760 nm, the application of a transfer function is necessary. Large uncertainty sources of the validation with ground-based measurements were quantified and recommendations for the choice of sites are provided. Finally, a first retrieval of the aerosol layer height from OLCI could be presented. This information can be used to improve the fluorescence retrieval.
Weniger anzeigenThis dissertation consists of four chapters which study how external events influence attitudes, preferences, perceptions, and identities of migrants and natives in different settings. The first chapter examines the effects of the European Refugee Crisis between 2014 and 2015 on the ethnic identity of already resident migrants in Germany. Thereby, I exploit the quasi-experimental setting in Germany, by which refugees are allocated to different counties by state authorities without being able to choose their locations themselves. Doing so, I find that higher shares of refugees in a county increased migrants’ attachment to their home countries, but not their perceived belonging to Germany. Further analyses uncover strong heterogeneities with respect to country of origin and suggest that concerns about xenophobia, experiences of discrimination, and the consumption of foreign media contributed to these effects. Lastly, I find that changes in ethnic identity coincide with the political polarization of migrants. The second chapter looks at the effects of far-right protests in Germany on natives’ attitudes toward migration nationwide. More specifically, we test whether protesters are able to raise support for their concerns, or whether they are perceived as a threat by the public. To do so, we perform a regression discontinuity design approach to estimate short-term effects on natives’ worries about xenophobia and concerns about immigration. Results indicate that protesters were seen as a threat as worries about xenophobia increased while concerns about immigration remained flat after demonstrations took place. Further analyses indicate that media coverage was essential in driving results and that effects were highly dependent on people’s preexisting political views, suggesting that protests had polarizing effects. In the third chapter, we study how unemployment impacts bitterness, which describes a feeling of not having achieved what one deserves compared to others. After finding consistently positive effects using pooled OLS and fixed effects regressions, we identify the causal effect of unemployment on bitterness by exploiting variation from plant closures and firm layoffs in Germany. Combining matching based on entropy balancing with difference-in-differences estimation, we show that unemployment leads to a substantial and significant increase in bitterness. Further analyses uncover evidence that the experience of job loss, the state of being unemployed, and the duration of unemployment contribute separately to overall effects. Lastly, we find some evidence that effects persist over time. In Chapter 4, we analyze how changes in legal status affect perceived discrimination of migrants in Germany. Hereby, we follow two distinct approaches. First, studying the direct impact of naturalization, we estimate a fixed effects model. As this method cannot fully account for all potential sources of endogeneity, we thereafter exploit exogenous variation in residency requirements due to two citizenship reforms in Germany. Overall, we find that while naturalization does appear to reduce perceptions of discrimination overall, these effects are limited to men and immigrants from Eastern European countries. Extending the analysis, we exploit exogenous variation from EU enlargement to show that citizens from countries that became part of the EU experienced a significant reduction in discrimination compared to non-EU immigrants.
Weniger anzeigenThe term Internet use disorders (IUD) covers addictive behaviors related to the use of Internet applications and contents such as online computer games, social networks, online pornography and shopping platforms. Research findings have demonstrated that IUD lead to significant psychological, societal and social impairments. Based on scientific evidence and clinical requirements, Internet Gaming Disorder (IGD) has been included in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11). The formal recognition of IGD as a disorder due to behavioral addiction has been highlighted as an achievement regarding the nosological classification and the development of treatment approaches. In addition to IGD, other IUD appear to be of comparable clinical relevance considering their addictive potential and the aversive consequences. Scientific research on interventions for IUD is still at an early stage and further studies are required. Although, systematic reviews and meta-analyses suggest that Cognitive Behavioral Therapy (CBT) may be an effective treatment approach for IUD. Even though the availability of specific interventions for the treatment of IUD is steadily increasing, access barriers and a low utilization of outpatient services lead to shortages of sufficient health care. Digital interventions have the potential to facilitate access to healthcare services and to address treatment barriers.
Based on the current state of research, digital interventions for IUD were investigated in the cumulative dissertation. The research project was embedded in the online short-term therapy of the randomized controlled trial Stepped Care Approach for Problematic Internet use Treatment (SCAPIT; German: Stepped Care Ansatz zur Versorgung Internetbezogener Störungen, SCAVIS). The first study synthesized the systematic evidence for treatment interventions for IUD in order to critically appraise the quality of reporting according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. The evaluation of systematic reviews and meta-analyses of interventions for IUD revealed considerable heterogeneity in terms of classification of addictive Internet behaviors and treatment approaches. In addition, a lack of studies on IUD manifestations other than IGD was highlighted. The assessment of the quality of reporting indicated deviations from the PRISMA guidelines in terms of missing information on the methodological and scientific approach. The second study was conducted as part of the scientific monitoring of the pilot phase of the online short-term therapy. Baseline data collected from the pilot sample were analyzed to provide preliminary information on clinical characteristics of treatment recipients. A descriptive analysis of sociodemographic data, psychopathological and individual variables was performed and correlations with symptoms of IUD were analyzed. Results of the study revealed that comorbid psychopathologies were associated with INS. The majority of participants reported at least one comorbid mental disorder at the time of inclusion in the online short-term therapy, while affective disorders were most prevalent. In the third study effects of psychopathological symptoms and impairments of functioning on symptom severity of IUD and the duration of Internet use was examined in the sample of patients. Based on a dichotomous classification of the symptom severity of IUD, differences among participants presenting moderate compared to severe addictive Internet behavior were analyzed. Besides psychosocial impairments, depressive, social phobic and somatoform symptoms were assessed. Results of the regression analyses confirmed that psychopathological symptoms and impairments of functioning had a significant effect on symptoms of IUD. Participants with severe addictive Internet behavior exhibited significantly higher psychopathological strains compared to patients with moderate addictive Internet behavior.
In summary, findings of the three studies contribute to the scientific evidence base of digital interventions for IUD. Results of the first study highlight that the current evidence on treatment interventions for IUD is limited by considerable heterogeneity and shortcomings in reporting. Further studies are urgently required to investigate digital treatment approaches. Findings of the second study underline the relevance of studies on certain manifestations of IUD and confirm that those affected commonly exhibit additional psychopathologies in clinical setting. Further, results of the third study imply opportunities for the expansion of the health care system by considering digital interventions as a promising way to minimize access barriers, and to provide evidence-based treatments for those affected. Additional research studies with high methodological quality should be conducted to confirm the findings and to promote the evidence base for digital interventions for the treatment of IUD.
Weniger anzeigenRegardless of our birthplace, culture or language, the body plays a central role in our experiences. In order to understand language learning, it is thus crucial to consider not only aspects of language, but also to understand the interconnections between the brain, body and social interaction. Despite the fundamental role of gestures in human communication and classroom instruction, their impact on second language (L2) learning is poorly understood and has rarely been studied in naturalistic instructional settings like schools. Drawing on methods from psycholinguistics, English language teaching and ethnography, this thesis examines the social and cognitive processes that underlie gesture-based L2 learning. In particular, the present work focuses on codified gestures as a teaching tool to support L2 fluency as well as spatial term and grammatical morpheme learning in diverse classrooms. The first study found that learners with lower initial fluency benefited more from morpheme-level gestures, while those with higher fluency improved more with sentence-level gestures plus access to a written text. The second study did not replicate findings from experiment one, but rather showed that with the same comparison, gestures at the morpheme level led to better spatial term comprehension for all learners. In a third study, subjects were asked to complete word fragments in phrases containing the plural and possessive {-s} in gesture form. Compared with the single-gesture condition, fragment completion response time after training was found to be faster in the condition with two distinct gestures for plural and possessive {-s}. Notably, the gestures in the two gesture condition in study three were the same as those used in the gesture per morpheme condition in study one and two. Overall, it was demonstrated that learners in this age group benefit from instructional gestures, where one gesture represents a sentence, word, or morpheme. In the case of gestures at the level of morphology, gestures also help learners to internalize and apply L2 grammar. As a learning tool, gestures bring together our social, physical, and mental experiences. These findings add to the growing literature examining gestures in naturalistic contexts and provide plausible reasons for greater inclusion in L2 instruction in diverse teaching settings.
Weniger anzeigenStreulicht-Nahfeldmikroskopie (s-SNOM) ist eine vielseitige Methode zur Strukturaufklärung, die nicht der Beugungsbegrenzung unterliegt. Somit gelingt, unabhängig von der Wellenlänge der verwendeten Strahlung, die Abbildung von Strukturen auf der Nanometerebene durch die Detektion von Streulicht einer Probe, die sich im optischen Nahfeld einer Sonde befindet. Durch die Verwendung von breitbandigem Licht in Kombination mit einem Michelson-Interferometer können Infrarotspektren von einzelnen Strukturen, die kleiner als 20 nm sind, aufgenommen werden. Die in der vorliegenden Arbeit verwendete Strahlungsquelle für breitbandige IR-Strahlung ist der Elektronenspeicherring Metrology Light Source (MLS) der Physikalisch-Technischen Bundesanstalt (PTB) in Berlin-Adlershof. Es wird Synchrotronstrahlung aus dessen Infrarotstrahlrohr verwendet und als Nahfeldsonde wird die Spitze eines Rasterkraftmikroskops verwendet. Es wird die Entwicklung eines neuen Betriebsmodus‘ für den Speicherring beschrieben, der zur Anpassung der Synchrotronstrahlung an das Mikroskop dient, womit die Empfindlichkeit der nano-FTIRSpektroskopie gesteigert werden kann. Um die langen Messzeiten bei der Aufnahme eines hyperspektralen Datensatzes zu verkürzen, wird die Technik des Compressed Sensing auf s-SNOM angewendet und deren Machbarkeit für eine SiC-Probe untersucht. Es wird die Verwendung einer neuartigen Messmethode beschrieben, bei der die Detektion auf dem thermoelektrischen Effekt beruht. Somit kann auf den ansonsten bei s-SNOM verwendeten, halbleiterbasierten (und mit flüssigem Stickstoff gekühlten) Detektor im Fernfeld der Probe verzichtet werden. Schließlich wird am Beispiel von drei Probensystemen gezeigt, wie Polaritonen ausgenutzt werden können, um die Empfindlichkeit von s-SNOM-basierten Spektroskopiemessungen zu steigern. Beim 2D-Material MoS2 können durch die Kopplung an Phononen des Substrats SiO2 Plasmonen spektroskopisch nachgewiesen werden, die ansonsten nicht zugänglich wären. Beim Probensystem der funktionalisierten Metalloxide SrTiO3/LaAlO3 kann an der Grenzfläche der beiden Perowskite durch den Einfluss der Dicke des Deckmaterials auf die Anwesenheit eines 2D-Elektronengases geschlossen werden. Auf einer Phospholipid-Monolage, welche auf Graphen aufgebracht wurde, kann mittels einer als Plasmonen-Interferometrie bezeichneten Methode eine Kontrastverstärkung erzielt werden. Hierdurch ist es wiederum möglich, Domänenstrukturen des Phospholipids abzubilden, die mittels einfacher Nahfeldmikroskopie nicht zugänglich wären.
Weniger anzeigenThis work explores the potential of supercritical fluid chromatography for the analysis of peptide drugs. The regulatory aspects of peptides are more complex and challenging than for small drug molecules. The same applies to the analytical characterization of peptides. After technical innovations and the introduction of a new instrument generation, supercritical fluid chromatography nowadays is a suitable alternative to reversed-phase chromatography, which is considered the gold standard in peptide analysis. However, the scientific data on the analysis of peptides with supercritical fluid chromatography is limited. In the first part of this thesis, supercritical fluid chromatography is used to develop a method to separate the variety of cyclic and linear peptides characteristic for tyrothricin. A software-based design of experiments approach is utilized to optimize an analytical method that provides superior separation of cyclic peptides compared to the reversed-phase separation. Even isomeric peptide pairs are efficiently separated. Subsequently, the potential of a binary mixture of methanol and acetonitrile combined with additives as the modifier for the separations of other cyclic peptides is investigated. The proportion of the mixture is optimized to improve the resolution and control the elution order of the analytes. Paired with an aromatic stationary phase, this chromatographic parameter offers an effective method optimization opportunity. This knowledge is furthermore extended to larger and more hydrophilic peptides in the following experiment. A single method for the purity analysis of human insulin and six analogs is optimized. A crown ether is also investigated as a promising additive to control the elution order of the insulins in dependence to its concentration. In the last study, the applicability of an established chromatographic modeling software for the in-silico optimization of peptide separations in supercritical fluid chromatography is demonstrated. Optimizing a binary mixture of methanol and acetonitrile serves as an effective parameter of the model. Using such software tools offers enormous time savings and, at the same time, meets the current requirements for analytical method development according to the quality by design concept. These already published studies are finally put into the context of the life cycle concept of analytical methods that will soon be demanded by the ICH Q14 guideline "Analytical procedure development". Existing knowledge, in the form of scientific publications, is employed as the basis for a general risk assessment applicable to peptide separations with supercritical fluid chromatography. From this, a generic method development strategy is derived and presented. This way, the current state of science and technology is taken into account to define an efficient workflow. This is particularly relevant in early pharmaceutical development phases, from where only a small fraction of initial drug candidates reaches market maturity. At the same time, this approach enhances the drug knowledge in early development phases and ultimately serves patient safety. The present work makes an important contribution to demonstrating the potential of supercritical fluid chromatography for the analysis of peptide drugs. It serves as a concise example of how supercritical fluid chromatography can be interpreted as a new technique in the ICH Q14 guideline setting. The approach presented can be easily applied to any other analytical technique or analyte class.
Weniger anzeigenArctic amplification is the phenomenon of accelerated warming of the Arctic polar regions in the context of climate change induced by anthropogenic greenhouse gas emissions. A number of recent cold episodes in midlatitudes in winter have raised the question of whether the Arctic amplification has led to the observed midlatitude cooling. The proposed mechanism of this Arctic-midlatitude linkage involves a stratospheric pathway. Accordingly, the horizontal temperature gradients are decreasing due to the enhanced polar warming at the surface. Consequently, the superjacent winds are weakened which results in slower and more meandering polar jet streams. The enhanced planetary waves propagate into the stratosphere, where they induce strong circulation anomalies, referred to as sudden stratospheric warmings (SSWs). These strong disturbances of the stratospheric polar vortex can potentially exert a downward influence on the troposphere, favouring local cold air outbreaks. Investigating this stratospheric pathway in a climate model requires an accurate representation of the middle atmosphere. Therefore, a comprehensive evaluation using the climate-chemistry model ECHAM/MESSy Atmospheric Chemistry (EMAC) was conducted in this thesis, with the additional aim of examining the impact of ozone chemistry on the stratospheric processes. The suggested steps of the stratospheric pathway were examined using a set of transient simulations and timeslice experiments. Although the Arctic amplification signal continued to rise, no cooling trend or cessation of warming was found in the transient simulations. In contrast, the frequency of SSWs has increased significantly under the influence of climate change. This increase could be attributed to a larger planetary wave input from the troposphere. The primary area of enhanced planetary wave propagation was identified as the Northern Pacific and the region spanning the North Atlantic and Europe. Moreover, the number of events corresponding to strong wave input into the stratosphere increased significantly in a warmer climate. The behaviour of the jet streams was evaluated using a jet detection scheme to determine the exact jet positions. The Eurasian region exhibited an increased occurrence of polar jets, showing a wavier path as well. In contrast, the western hemisphere was characterised by a reduced polar jet frequency. A straightforward connection between the wavier jets and temperature gradients in the lower troposphere was not established in this study. While the modifications in the lower layers imply reduced baroclinic instability and fewer atmospheric waves, an enhanced wave generation became evident in the upper troposphere. However, these anomalies coincide with changes in the static stability and in subtropical temperature changes. The release of additional waves into the stratosphere appears to be related to these upper-tropospheric anomalies. The findings of this thesis suggest that the step linking temperature gradients to upper-tropospheric wave propagation requires further clarification. This is critical for validating the stratospheric pathway. Moreover, an evaluation of the downward influence of SSWs was conducted. Despite more frequent SSWs in a warmer climate, no tendency towards more extreme cold events was found in the most affected regions. While significant cooling anomalies still existed after the SSW events, the temperature anomalies are considerably lower. Finally, the representation of ozone chemistry in the model was determined to have an insignificant impact on the results of the stratospheric pathway.
Weniger anzeigenIn the skin sensitization assessment, the in vivo method, specifically the Local Lymph Node Assay (LLNA), is regarded as the gold standard. However, to adhere to the 3R principle (Reduction, Refinement, Replacement), which advocates for the Reduction, Refinement, and Replacement of animal testing, and to enhance the ethical standards of risk assessment, a greater number of in vitro and in silico testing methods have been developed. While these in vitro and in silico methods offer a higher throughput and a more ethical approach to risk assessment, they each come with their own set of limitations. For instance, most in vitro tests can only be used for a single readout. On the other hand, in silico methods lack physiological and biological feedback. The adverse outcome pathway (AOP) for skin sensitization, as defined by the Organization for Economic Cooperation and Development (OECD) guidelines, involves four key events, which are protein binding (Key Event 1 – KE1), keratinocyte activation (Key Event 2 – KE 2), dendritic cell activation (Key Event 3 – KE 3), and T-lymphocyte activation (Key Event 4 – KE 4) (OECD, 2014). While animal-based assays are reasonably accurate, their skin is physiologically different than human skin. Therefore, this thesis aimed to develop the ‘ImmuSkin-MT’, a 3D-human skin model with immune cells, designed to address the limitations inherent in in vitro skin sensitization assays. The thesis began with 2D co-culture of keratinocytes and immune cells, which have shown to fall short in detecting a skin sensitizer. In parallel to the development of the 2D co-culture assay, the advantages of the autologous in comparison to the allogenic 2D co-culture were investigated. The results indicated that within the donor pool used, allogenic 2D co-culture did not lead to an alloreactive response in the cells. Therefore, whether autologous or allogenic cell pairings were used in the co-culture, they had no impact on the development of the assay. Later, the project progressed and the 'ImmuSkin-MT', created from human hair follicle-derived keratinocytes (HFDK), fibroblasts (HFDF), and immune cells were developed. monocyte-derived Langerhans cells (MoLC) and CD4+ naïve T-lymphocytes were integrated into the reconstructed human skin models (RHS). ImmuSkin-MT were topically exposed to various substances, including non-sensitizers and contact sensitizers. Using the MoLC activation and the stimulation index (SI) of T-lymphocytes, results demonstrate the effectiveness of ImmuSkin-MT in replicating KE 3 and 4 of skin sensitization in response to the skin sensitizers. This model presents a promising alternative to animal testing for contact sensitizers, contributing to more ethical and precise skin sensitization assessment techniques. In conclusion, ImmuSkin-MT represents a significant advancement in skin sensitization assessment by capturing multiple key events simultaneously. The project's findings have the potential to optimize skin sensitization testing methods, providing more accurate, reliable, and ethical alternatives to traditional animal-based assays.
Weniger anzeigenEndogenous retroviruses (ERVs) are repetitive elements that constitute around 10 percent of mammalian genomes. ERVs need to be kept transcriptionally silenced during development and ERV upregulation is linked to loss of pluripotency and mouse embryonic lethality. Precise mechanistic understanding of this process remains incomplete. To investigate effects of ERV derepression, I utilized degradation tag (dTAG) system to acutely deplete endogenous levels of TRIM28, a heterochromatin protein that recruits silencing machinery to ERVs in mouse embryonic stem cells (mESCs). Nascent transcriptome sequencing indicated TRIM28 depletion induces acute transcriptomic changes: upregulation of ERVs and other targets of TRIM28-mediated repression and simultaneous downregulation of key pluripotency super enhancers (SEs) and associated genes. High-resolution microscopy data indicated ERV derepression reduces association of SEs with RNA polymerase II (RNAPII) and Mediator (MED1), the key components of transcriptional condensates. In turn, derepressed ERVs associated with RNAPII and MED1, indicating transcriptional condensate components are redistributed upon TRIM28 depletion. Presence of transcriptional machinery at derepressed ERV loci upregulated nearby genes, including Cthrc1. Ectopic overexpression of pluripotency factors enriched at SEs prevented the reduction in transcriptional condensate association with SEs. ERV knockdown rescued transcriptional condensate localization indicating RNAs produced at ERV play an important in transcriptional condensate redistribution. Evidence presented here shows derepressed ERVs have the capacity to ‘hijack’ transcriptional condensates from key pluripotency genes upon TRIM28 degradation. This may be the molecular mechanism contributing to embryonic lethality associated with ERV derepression in TRIM28 knockout mice.
Weniger anzeigenWe live in a structured world, where objects rarely exist in isolation but are often surrounded by similar environments. When objects consistently co-occur with certain objects and scene contexts, our neural systems can implicitly extract and learn such regularities in real-world environments. Predictive processing theories propose that our brains can use learned statistical regularities to predict the structure of incoming sensory input across space and time during visual processing. The predictions may allow us to efficiently recognize objects and understand scenes, thus forming coherent visual experiences in natural vision. In this dissertation, we conducted three studies to explore how our brains use real-world structures to create coherent visual experiences using neuroimaging techniques (EEG & fMRI) and multivariate pattern analyses (MVPA). Study 1 investigated how scene context affects object processing across time by recording EEG signals while participants viewed semantically consistent or inconsistent objects within scenes. The results reveal that semantically consistent scenes facilitate object representations, but this facilitation is task-dependent rather than automatic. In Study 2, we investigated how cortical feedback mediates the integration of visual information across space by manipulating the spatiotemporal coherence of naturalistic video stimuli shown in both visual hemifields. By analytically combining EEG and fMRI data, we demonstrated that spatial integration of naturalistic visual inputs is mediated by cortical feedback in alpha dynamics that fully traverse the visual hierarchy. In Study 3, we further investigated what level of spatiotemporal coherence is needed to trigger such integration-related alpha dynamics. The findings suggest that integration-related alpha dynamics have some flexibility so that they can accommodate information from videos belonging to the same basic-level category. Together, the dissertation provides multimodal evidence demonstrating that contextual information facilitates object perception and scene integration, highlighting the critical role of predictions related to real-world regularities in constructing coherent visual experiences.
Weniger anzeigenAls eine bisher noch wenig für fremd- und zweitsprachliche Kontexte erarbeitete soziale Kategorie werden in der vorliegenden Arbeit „Zugehörigkeiten“ als lohnender Zugang für den Sprach-, Kultur- und Literaturunterricht vorgeschlagen. Am Beispiel brasilianischer Germanistikstudierender zeigt die Studie, wie die erworbene Zugehörigkeit zur deutschen Sprachgemeinschaft und die bestehende Zugehörigkeit zu Brasilien als fruchtbar und motivierend für fremdsprachliche Lehr-Lern-Prozesse genutzt werden können. Dafür wurde ein Vernetzungsmodell konzipiert, das einzelne Verdichtungspunkte deutsch-brasilianischer Literaturen betrachtet und sie nicht in Bezug auf Nationalphilologien, sondern im Kontext zueinander sieht. Konzeptionell wurde für das Modul die Perspektive einer doppelten Zugehörigkeitsorientierung entwickelt und deren unterrichtliche Ausarbeitung empirisch begleitet: So teilt sich das Konzept in eine subjektorientierte Zugehörigkeitsorientierung, die sich an den Zugehörigkeitskontexten der Teilnehmer*innen in Lehr- und Lernarrangements orientiert und in eine epistemische Zugehörigkeitsorientierung, die die Teilnehmer*innen anleitet, die Zugehörigkeiten von anderen verstärkt wahrzunehmen und die sich somit auf die soziale Verfasstheit unserer Gesellschaften richtet.
Weniger anzeigenResistive random-access memory (RRAM), one of the next-generation non-volatile memory technologies, offers scalability, enhanced performance, and lower power consumption compared to traditional memories, making it a promising solution for future memory architectures. In this work, we study different types of polycrystalline RMnO3 (R = Y, Er) thin films-based RRAM devices. This research starts with the synthesis and characterization of polycrystalline YMnO3 and ErMnO3 thin films with mixed hexagonal and orthorhombic phases. Films are prepared with radio frequency sputtering at room temperature and post-deposition annealing. The orthorhombic phase cannot always be discriminated by X-ray diffraction, as there is an overlap with the peaks of the hexagonal phase and its low volume fraction and the nano-sized grains lead to undetectable peaks. Employing a set of correlative spectroscopy and microscopy techniques, we develop a method to unambiguously identify the presence of the orthorhombic phase, locate it, and quantify it. Subsequently, we investigate different types of memristive devices using polycrystalline thin films with the presence of both hexagonal and orthorhombic phases. First, electrochemical metallization (ECM) memristive devices based on YMnO3 with Al active electrode are studied. These devices exhibit bipolar resistive switching with high ROFF/RON ratios (~ 104), low Set/Reset voltages (VSet ~ 1.7 V and VReset ~ -0.36 V), and good retention. The resistive switching mechanism is ascribed to the formation and rupture of an Al filament along oxygen-deficient boundaries between hexagonal and orthorhombic phases. These localized nanochannels for Al3+ migration effectively remove the randomness of the Al filament formation in the electrolyte. Second, we investigate bipolar resistive switching in Pt/ErMnO3/Ti/Au devices. They exhibit high ROFF/RON ratios (~ 105) and ultra-low resistances (~ 10 ohm) in the low resistance state (RON). The resistive switching is the result of the formation and rupture of an oxygen-vacancy-based conductive filament, which likely occurs either in the orthorhombic phase or at the boundary between the two polymorphs. An increased fraction of the orthorhombic phase strongly reduces the operating voltage in devices (down to VSet ~ -2.07 V) and the variability of VSet. The presence of hexagonal phase prevents large leakage currents in the devices, which otherwise would not show switching behavior. Finally, we present the first demonstration of electroforming-free threshold switching devices with ErMnO3. Pt/ErMnO3/Pt devices exhibit repeatable unipolar threshold switching with a memory window of 0.7 V, characterized by a S-shape current-controlled negative differential resistance (NDR). The devices show a high endurance up to 104 sweeps. We successfully model the threshold switching using Joule-heating-enhanced 3D Poole-Frenkel conduction mechanism. The conducting orthorhombic phase plays a key role in enabling the self-heating mechanism while the hexagonal phase prevents too large electrical and thermal conductivities. Adjusting the conductivity of o-ErMnO3 and engineering the two crystalline phase fractions are key knobs for tuning the threshold switching characteristics. The oscillatory behavior of the NDR devices is demonstrated. This new type of NDR devices based on two polymorphs with different electronic and thermal properties present advantages for tunability of the memory window compared to known NDR devices such as those based on an insulator-to-metal transition (e.g. VO2) or based on the formation of a filament (e.g. NbOx). In all studied devices, the coexistence of the hexagonal and orthorhombic phases of RMnO3 (R = Y, Er) provides unique functionalities. The possibility to engineer these two phases both in conductivity and content through synthesis, provide original routes to design new memristive devices and optimize their properties.
Weniger anzeigenDiese Arbeit untersucht die im Dīwān luġāt at-Turk des Maḥmūd al-Kāšġarī aus dem 11. Jh. n. Chr. verstreuten Angaben zur Sprache der Qïfǰāq mit dem Ziel, die Beziehungen dieser frühesten bekannten kiptschakischen Wörter einschließlich ihrer Lautgestalt zu historischen Vorgänger- und Nachfolgersprachen und bestimmten Sprachregionen der gesamten Turcia herauszuarbeiten und sie so in einen sprachhistorischen Kontext zu stellen. Dazu wurden sämtliche Varietäteneinträge des 637 Manuskriptseiten umfassenden Dīwān luġāt at-Turk neu verzettelt und der so gebildete Auszug des Wortmaterials der Qïfǰāq in alphabetischer Reihenfolge in der Art eines Meta-Wörterbuches aufbereitet. Nach Klärung der Textüberlieferung, Wortherkunft, Wortbildung, Lautstruktur und Bedeutungsspannweite wurde eine Belegsammlung erstellt, die das betreffende Wort in der Gesamtheit seiner Erscheinungsformen in möglichst zahlreichen alttürkischen, mitteltürkischen und neutürkischen Sprachen und Varietäten registriert und die Überlieferungs- und wo möglich Entlehnungswege der spezifisch kiptschakischen Elemente nachzuverfolgen versucht. Im Auswertungsteil wurden die Ergebnisse dieser Nachverfolgung zusammengeführt und verglichen. Besonderes Augenmerk lag darüberhinaus auf der textkritischen Aufarbeitung der Stellen, auf der Rolle des Kopisten und besonders späterer Kommentatoren, auf der Frage nach der Verlässlichkeit der Angaben Maḥmūd al-Kāšġarīs auf dem Hintergrund der so erarbeiteten Daten und auf seinen Angaben zur Verbreitung bestimmter Merkmale im Kiptschakischen zugleich mit anderen Varietäten des 11. Jhs., insbesondere in den Ogusischen Sprachen. Die Nachverfolgung, Lokalisierung und Bewertung charakteristischer sich während der gesamten historischen Zeit ausbreitender Lautwandelerscheinungen erfolgte in einer ergänzenden Untersuchung. Das so gewonnene Bild wurde in einen durch muslimische Geschichtsquellen des 10. bis 12. Jhs. und moderne Untersuchungen an historischem Genmaterial aufgebauten Rahmen eingeordnet. Hier wurde auch versucht, Bezüge zu aus der Geschichtsschreibung bekannten mittelalterlichen Völkerbewegungen herzustellen. Als Arbeitsgrundlage dienten neben dem einzigen erhaltenen Autographen des Dīwān luġāt at-Turk, gelesen nach dem Faksimile von 1990, die Edition des Werks von Dankoff und Kelly (Maḥmūd al-Kāšγarī, Compendium of the Turkic dialects, drei Bände, 1982 bis 1985) und zahlreiche Wörterbücher der alttürkischen, mitteltürkischen und neutürkischen Sprachen, darunter auch historische Wörterbücher, außerdem eine Auswahl an mitteltürkischen literarischen Quellen, Editionen islamischer Geschichtsschreiber und moderne Sekundärliteratur, u.a. zu Geschichte, Klimageschichte und historischer DNA Eurasiens. Als Ergebnis des sprachwissenschaftlichen Teils der Arbeit mit ihrer Untersuchung der von Maḥmūd al-Kāšγarī als kiptschakisch bezeichneten Formen nebst aller anderen Varianten in ihrer zeitlichen und lokalen Verbreitung ergaben sich 68 Wortstammbäume. Diese Wortstammbäume wurden ihrerseits ggf. unter Berücksichtigung interner Kategorien des Dīwān luġāt at-Turk wie Verbreitung in mehreren Türksprachenvarietäten des 11. Jhs. hinsichtlich des Vor- und Weiterlebens der als Kiptschakisch gekennzeichneten Varianten zusammengeführt und ausgewertet und die Ergebnisse ggf. in Gruppen nach Art des Merkmals sortiert und einzeln besprochen. Für einzelne Wörter ergaben sich im Zuge der Aufarbeitung Beiträge zur Lehnwortforschung und Etymologie. Insgesamt konnte die Zweiteilung der kiptschakischen Siedlungsgebiete, wie sie auf der Karte des Dīwān luġāt at-Turk gezeigt ist, durch das Textmaterial bestätigt werden, es ergaben sich jeweils leicht unterschiedliche Bezüge zum West- und Ostalttürkischen. Für das 11. Jh. waren entsprechend charakteristische Sprachvarietätengruppierungen feststellbar. Hier zeichnete sich schwach eine Aufteilung in ein nordtürkisches und ein südtürkisches Sprachareal ab, das allerdings nicht mit dem im Text des Dīwān luġāt at-Turk vorgestellten Nord- und Südriegel der Türkstämme deckungsgleich ist – diese Anordnung im Dīwān luġāt at-Turk stellt eine Momentaufnahme der Wanderbewegungen diverser Türkvölker nach Westen dar. In den Kapiteln zum Erhalt des kiptschakischen Wortmaterials des Dīwān luġāt at-Turk in den mittel- und neutürkischen Sprachen ergaben sich vereinzelt Einblicke in die Entstehungsgeschichte der zeitgenössischen Familie der Kiptschaksprachen. Hierbei waren Überlegungen zu Lautsystemverschiebungen für die Auswertung unerlässlich. Für das 11. Jh. wurde dahingehend eine grobe Dreiteilung der türkischen Sprachgemeinschaft rekonstruiert und diese für die Folgejahrhunderte in ihrer weiteren Entwicklung nachverfolgt. Auch die Vertretung der türkischen Klusile im Altuigurischen von Xinjiang und die Häufigkeit von Frikativen in der Aralo-kaspischen Region spielen in diesem Rahmen eine Rolle. Zwei Kapitel zur Bewertung der Fähigkeiten und Leistungen des Autors Maḥmūd al-Kāšġarī, eines ohne und eines mit Einbeziehung der Ergebnisse der Wortstammbäume, liefern ein mehrschichtiges Profil des Autors und seiner Leistungen. Ein Ergebnis der textkritischen Arbeit ist die versuchte Identifikation des bisher namentlich unbekannten aktivsten nachträglichen Kommentators und Glossenschreibers des Dīwān luġāt at-Turk, "the later hand", mit Aḥmad Ḫaṭīb Dārayyā und damit die Datierung wichtiger Glossen. Schließlich wurde eine Auswertung der muslimischen Quellen zur Geschichte der Kiptschaken mit einer Sichtung historischen genetischen Materials kombiniert und über die aus der sprachwissenschaftlichen Untersuchung gewonnenen Daten geblendet. Im Ergebnis ergaben sich Vermutungen zum Ablauf des mehrphasigen Wanderungsgeschehens der Kiptschaken, Kimäk und Yemäk unter Beteiligung von Bevölkerungsgruppen östlicher (darunter C-Y15550 und C-F12970 unter C-M86) und westlicher (darunter R1b-M73) Herkunft.
Weniger anzeigenTight junctions (TJs) seal the paracellular space between epithelial and endothelial cells, and are essential for tissue compartmentalization and barrier formation. The backbone of the TJ is formed by a group of transmembrane proteins, called claudins. Claudins polymerize into strands and meshes through cis- and trans-interactions, and are expressed in different combinations, based on the needs of the respective tissue. The large protein family can be divided into pore- and barrier-formers claudins, with the former being selectively permeable to ions or water. Structural insight in claudin polymerization is limited; models have been created, but only of a few homopolymers. Recent studies have found only half of the claudin family to form homopolymers, whereas co-expression can promote polymerization of certain claudins. This thesis thus focuses on regulation of claudin polymerization. In the first part of the thesis, intrinsic regulation was examined by a comparison of claudin-3 and claudin-4. These proteins have high sequence homology, yet only claudin-3 polymerizes by itself in fibroblasts. With sequence alignment and molecular dynamics simulations, we predicted a motif in the second extracellular segment key to stable trans-interaction and polymerization. We mutated the two residues in claudin-4 into their claudin-3 equivalents and found that they promote polymerization in fibroblasts. Moreover, the mutated claudin-4 could (partially) rescue TJ localization, as well as the formation of a TJ barrier with ruffled morphology in TJ-deficient epithelial cells. Extrinsic regulation of claudin polymerization, specifically how co-expression of claudins can influence polymerization, was investigated next. Our focus was on claudin-16 and claudin-19, that form a cation-permeable copolymer in the thick ascending limb (TAL) of the kidney. Mutations in either protein cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, emphasizing their essential role in kidney Ca2+ transport. We also investigated claudin-14, that can block this cation-pore upon its hypercalcemia-induced expression, and is associated with kidney stone formation. It is known that non-polymerizing claudin-16 integrates into the claudin-19 meshwork, but how this is affected by claudin-14 is still poorly understood. Super-resolution microscopy in fibroblasts revealed that claudin-14 can replace claudin-16 in a strand-specific manner. We further validated this in epithelial cells with endogenous claudin-16 and in the TAL of hypercalcemic mice. Claudin-14 expression by transduction in epithelial cells, and in response to hypercalcemia in the mice, again led to claudin-16 replacement. Overall, we have identified a motif that intrinsically regulates claudin polymerization and have shown that claudin-14 replaces claudin-16 to regulate Ca2+ transport in the kidney. These insights form a basis to understand and manipulate claudin polymerization, for instance to improve drug delivery or to prevent pathogen entry. More directly, the knowledge of the claudin-14 regulatory mechanism can be used to develop treatments for kidney stones and other pathologies involving hypercalciuria.
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