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Data stream processing systems (DSPSs) are a key enabler to integrate continuously generated data, such as sensor measurements, into enterprise applications. DSPSs allow to steadily analyze information from data streams, e.g., to monitor manufacturing processes and enable fast reactions to anomalous behavior. Moreover, DSPSs continuously filter, sample, and aggregate incoming streams of data, which reduces the data size, and thus data storage costs.
The growing volumes of generated data have increased the demand for high-performance DSPSs, leading to a higher interest in these systems and to the development of new DSPSs. While having more DSPSs is favorable for users as it allows choosing the system that satisfies their requirements the most, it also introduces the challenge of identifying the most suitable DSPS regarding current needs as well as future demands. Having a solution to this challenge is important because replacements of DSPSs require the costly re-writing of applications if no abstraction layer is used for application development. However, quantifying performance differences between DSPSs is a difficult task. Existing benchmarks fail to integrate all core functionalities of DSPSs and lack tool support, which hinders objective result comparisons. Moreover, no current benchmark covers the combination of streaming data with existing structured business data, which is particularly relevant for companies.
This thesis proposes a performance benchmark for enterprise stream processing called ESPBench. With enterprise stream processing, we refer to the combination of streaming and structured business data. Our benchmark design represents real-world scenarios and allows for an objective result comparison as well as scaling of data. The defined benchmark query set covers all core functionalities of DSPSs. The benchmark toolkit automates the entire benchmark process and provides important features, such as query result validation and a configurable data ingestion rate.
To validate ESPBench and to ease the use of the benchmark, we propose an example implementation of the ESPBench queries leveraging the Apache Beam software development kit (SDK). The Apache Beam SDK is an abstraction layer designed for developing stream processing applications that is applied in academia as well as enterprise contexts. It allows to run the defined applications on any of the supported DSPSs. The performance impact of Apache Beam is studied in this dissertation as well. The results show that there is a significant influence that differs among DSPSs and stream processing applications. For validating ESPBench, we use the example implementation of the ESPBench queries developed using the Apache Beam SDK. We benchmark the implemented queries executed on three modern DSPSs: Apache Flink, Apache Spark Streaming, and Hazelcast Jet. The results of the study prove the functioning of ESPBench and its toolkit. ESPBench is capable of quantifying performance characteristics of DSPSs and of unveiling differences among systems.
The benchmark proposed in this thesis covers all requirements to be applied in enterprise stream processing settings, and thus represents an improvement over the current state-of-the-art.
The aim of this dissertation was to conduct a larger-scale cross-linguistic empirical investigation of similarity-based interference effects in sentence comprehension.
Interference studies can offer valuable insights into the mechanisms that are involved in long-distance dependency completion.
Many studies have investigated similarity-based interference effects, showing that syntactic and semantic information are employed during long-distance dependency formation (e.g., Arnett & Wagers, 2017; Cunnings & Sturt, 2018; Van Dyke, 2007, Van Dyke & Lewis, 2003; Van Dyke & McElree, 2011). Nevertheless, there are some important open questions in the interference literature that are critical to our understanding of the constraints involved in dependency resolution.
The first research question concerns the relative timing of syntactic and semantic interference in online sentence comprehension. Only few interference studies have investigated this question, and, to date, there is not enough data to draw conclusions with regard to their time course (Van Dyke, 2007; Van Dyke & McElree, 2011).
Our first cross-linguistic study explores the relative timing of syntactic and semantic interference in two eye-tracking reading experiments that implement the study design used in Van Dyke (2007). The first experiment tests English sentences. The second, larger-sample experiment investigates the two interference types in German.
Overall, the data suggest that syntactic and semantic interference can arise simultaneously during retrieval.
The second research question concerns a special case of semantic interference: We investigate whether cue-based retrieval interference can be caused by semantically similar items which are not embedded in a syntactic structure.
This second interference study builds on a landmark study by Van Dyke & McElree (2006). The study design used in their study is unique in that it is able to pin down the source of interference as a consequence of cue overload during retrieval, when semantic retrieval cues do not uniquely match the retrieval target. Unlike most other interference studies, this design is able to rule out encoding interference as an alternative explanation. Encoding accounts postulate that it is not cue overload at the retrieval site but the erroneous encoding of similar linguistic items in memory that leads to interference (Lewandowsky et al., 2008; Oberauer & Kliegl, 2006). While Van Dyke & McElree (2006) reported cue-based retrieval interference from sentence-external distractors, the evidence for this effect was weak. A subsequent study did not show interference of this type (Van Dyke et al., 2014). Given these inconclusive findings, further research is necessary to investigate semantic cue-based retrieval interference.
The second study in this dissertation provides a larger-scale cross-linguistic investigation of cue-based retrieval interference from sentence-external items. Three larger-sample eye-tracking studies in English, German, and Russian tested cue-based interference in the online processing of filler-gap dependencies. This study further extends the previous research by investigating interference in each language under varying task demands (Logačev & Vasishth, 2016; Swets et al., 2008).
Overall, we see some very modest support for proactive cue-based retrieval interference in English. Unexpectedly, this was observed only under a low task demand. In German and Russian, there is some evidence against the interference effect. It is possible that interference is attenuated in languages with richer case marking.
In sum, the cross-linguistic experiments on the time course of syntactic and semantic interference from sentence-internal distractors support existing evidence of syntactic and semantic interference during sentence comprehension. Our data further show that both types of interference effects can arise simultaneously. Our cross-linguistic experiments investigating semantic cue-based retrieval interference from sentence-external distractors suggest that this type of interference may arise only in specific linguistic contexts.
What are the consequences of unemployment and precarious employment for individuals' health in Europe? What are the moderating factors that may offset (or increase) the health consequences of labor-market risks? How do the effects of these risks vary across different contexts, which differ in their institutional and cultural settings? Does gender, regarded as a social structure, play a role, and how? To answer these questions is the aim of my cumulative thesis. This study aims to advance our knowledge about the health consequences that unemployment and precariousness cause over the life course. In particular, I investigate how several moderating factors, such as gender, the family, and the broader cultural and institutional context, may offset or increase the impact of employment instability and insecurity on individual health.
In my first paper, 'The buffering role of the family in the relationship between job loss and self-perceived health: Longitudinal results from Europe, 2004-2011', I and my co-authors measure the causal effect of job loss on health and the role of the family and welfare states (regimes) as moderating factors. Using EU-SILC longitudinal data (2004-2011), we estimate the probability of experiencing 'bad health' following a transition to unemployment by applying linear probability models and undertake separate analyses for men and women. Firstly, we measure whether changes in the independent variable 'job loss' lead to changes in the dependent variable 'self-rated health' for men and women separately. Then, by adding into the model different interaction terms, we measure the moderating effect of the family, both in terms of emotional and economic support, and how much it varies across different welfare regimes. As an identification strategy, we first implement static fixed-effect panel models, which control for time-varying observables and indirect health selection—i.e., constant unobserved heterogeneity. Secondly, to control for reverse causality and path dependency, we implement dynamic fixed-effect panel models, adding a lagged dependent variable to the model.
We explore the role of the family by focusing on close ties within households: we consider the presence of a stable partner and his/her working status as a source of social and economic support. According to previous literature, having a partner should reduce the stress from adverse events, thanks to the symbolic and emotional dimensions that such a relationship entails, regardless of any economic benefits. Our results, however, suggest that benefits linked to the presence of a (female) partner also come from the financial stability that (s)he can provide in terms of a second income. Furthermore, we find partners' employment to be at least as important as the mere presence of the partner in reducing the negative effect of job loss on the individual's health by maintaining the household's standard of living and decreasing economic strain on the family. Our results are in line with previous research, which has highlighted that some people cope better than others with adverse life circumstances, and the support provided by the family is a crucial resource in that regard.
We also reported an important interaction between the family and the welfare state in moderating the health consequences of unemployment, showing how the compensation effect of the family varies across welfare regimes. The family plays a decisive role in cushioning the adverse consequences of labor market risks in Southern and Eastern welfare states, characterized by less developed social protection systems and –especially the Southern – high level of familialism.
The first paper also found important gender differences concerning job loss, family and welfare effects. Of particular interest is the evidence suggesting that health selection works differently for men and women, playing a more prominent role for women than for men in explaining the relationship between job loss and self-perceived health. The second paper, 'Gender roles and selection mechanisms across contexts: A comparative analysis of the relationship between unemployment, self-perceived health, and gender.' investigates more in-depth the gender differential in health driven by unemployment.
Being a highly contested issue in literature, we aim to study whether men are more penalized than women or the other way around and the mechanisms that may explain the gender difference. To do that, we rely on two theoretical arguments: the availability of alternative roles and social selection. The first argument builds on the idea that men and women may compensate for the detrimental health consequences of unemployment through the commitment to 'alternative roles,' which can provide for the resources needed to fulfill people's socially constructed needs. Notably, the availability of alternative options depends on the different positions that men and women have in society.
Further, we merge the availability of the 'alternative roles' argument with the health selection argument. We assume that health selection could be contingent on people's social position as defined by gender and, thus, explain the gender differential in the relationship between unemployment and health. Ill people might be less reluctant to fall or remain (i.e., self-select) in unemployment if they have alternative roles. In Western societies, women generally have more alternative roles than men and thus more discretion in their labor market attachment. Therefore, health selection should be stronger for them, explaining why unemployment is less menace for women than for their male counterparts.
Finally, relying on the idea of different gender regimes, we extended these arguments to comparison across contexts. For example, in contexts where being a caregiver is assumed to be women's traditional and primary roles and the primary breadwinner role is reserved to men, unemployment is less stigmatized, and taking up alternative roles is more socially accepted for women than for men (Hp.1). Accordingly, social (self)selection should be stronger for women than for men in traditional contexts, where, in the case of ill-health, the separation from work is eased by the availability of alternative roles (Hp.2).
By focusing on contexts that are representative of different gender regimes, we implement a multiple-step comparative approach. Firstly, by using EU-SILC longitudinal data (2004-2015), our analysis tests gender roles and selection mechanisms for Sweden and Italy, representing radically different gender regimes, thus providing institutional and cultural variation. Then, we limit institutional heterogeneity by focusing on Germany and comparing East- and West-Germany and older and younger cohorts—for West-Germany (SOEP data 1995-2017). Next, to assess the differential impact of unemployment for men and women, we compared (unemployed and employed) men with (unemployed and employed) women. To do so, we calculate predicted probabilities and average marginal effect from two distinct random-effects probit models. Our first step is estimating random-effects models that assess the association between unemployment and self-perceived health, controlling for observable characteristics. In the second step, our fully adjusted model controls for both direct and indirect selection. We do this using dynamic correlated random-effects (CRE) models. Further, based on the fully adjusted model, we test our hypotheses on alternative roles (Hp.1) by comparing several contexts – models are estimated separately for each context. For this hypothesis, we pool men and women and include an interaction term between unemployment and gender, which has the advantage to allow for directly testing whether gender differences in the effect of unemployment exist and are statistically significant. Finally, we test the role of selection mechanisms (Hp.2), using the KHB method to compare coefficients across nested nonlinear models. Specifically, we test the role of selection for the relationship between unemployment and health by comparing the partially-adjusted and fully-adjusted models. To allow selection mechanisms to operate differently between genders, we estimate separate models for men and women.
We found support to our first hypotheses—the context where people are embedded structures the relationship between unemployment, health, and gender. We found no gendered effect of unemployment on health in the egalitarian context of Sweden. Conversely, in the traditional context of Italy, we observed substantive and statistically significant gender differences in the effect of unemployment on bad health, with women suffering less than men. We found the same pattern for comparing East and West Germany and younger and older cohorts in West Germany.
On the contrary, our results did not support our theoretical argument on social selection. We found that in Sweden, women are more selected out of employment than men. In contrast, in Italy, health selection does not seem to be the primary mechanism behind the gender differential—Italian men and women seem to be selected out of employment to the same extent. Namely, we do not find any evidence that health selection is stronger for women in more traditional countries (Hp2), despite the fact that the institutional and the cultural context would offer them a more comprehensive range of 'alternative roles' relative to men. Moreover, our second hypothesis is also rejected in the second and third comparisons, where the cross-country heterogeneity is reduced to maximize cultural differences within the same institutional context. Further research that addresses selection into inactivity is needed to evaluate the interplay between selection and social roles across gender regimes.
While the health consequences of unemployment have been on the research agenda for a pretty long time, the interest in precarious employment—defined as the linking of the vulnerable worker to work that is characterized by uncertainty and insecurity concerning pay, the stability of the work arrangement, limited access to social benefits, and statutory protections—has emerged only later. Since the 80s, scholars from different disciplines have raised concerns about the social consequences of de-standardization of employment relationships. However, while work has become undoubtedly more precarious, very little is known about its causal effect on individual health and the role of gender as a moderator. These questions are at the core of my third paper : 'Bad job, bad health? A longitudinal analysis of the interaction between precariousness, gender and self-perceived health in Germany'. Herein, I investigate the multidimensional nature of precarious employment and its causal effect on health, particularly focusing on gender differences.
With this paper, I aim at overcoming three major shortcomings of earlier studies: The first one regards the cross-sectional nature of data that prevents the authors from ruling out unobserved heterogeneity as a mechanism for the association between precarious employment and health. Indeed, several unmeasured individual characteristics—such as cognitive abilities—may confound the relationship between precarious work and health, leading to biased results. Secondly, only a few studies have directly addressed the role of gender in shaping the relationship. Moreover, available results on the gender differential are mixed and inconsistent: some found precarious employment being more detrimental for women's health, while others found no gender differences or stronger negative association for men. Finally, previous attempts to an empirical translation of the employment precariousness (EP) concept have not always been coherent with their theoretical framework. EP is usually assumed to be a multidimensional and continuous phenomenon; it is characterized by different dimensions of insecurity that may overlap in the same job and lead to different "degrees of precariousness." However, researchers have predominantly focused on one-dimensional indicators—e.g., temporary employment, subjective job insecurity—to measure EP and study the association with health. Besides the fact that this approach partially grasps the phenomenon's complexity, the major problem is the inconsistency of evidence that it has produced. Indeed, this line of inquiry generally reveals an ambiguous picture, with some studies finding substantial adverse effects of temporary over permanent employment, while others report only minor differences.
To measure the (causal) effect of precarious work on self-rated health and its variation by gender, I focus on Germany and use four waves from SOEP data (2003, 2007, 2011, and 2015). Germany is a suitable context for my study. Indeed, since the 1980s, the labor market and welfare system have been restructured in many ways to increase the German economy's competitiveness in the global market. As a result, the (standard) employment relationship has been de-standardized: non-standard and atypical employment arrangements—i.e., part-time work, fixed-term contracts, mini-jobs, and work agencies—have increased over time while wages have lowered, even among workers with standard work. In addition, the power of unions has also fallen over the last three decades, leaving a large share of workers without collective protection. Because of this process of de-standardization, the link between wage employment and strong social rights has eroded, making workers more powerless and more vulnerable to labor market risks than in the past. EP refers to this uneven distribution of power in the employment relationship, which can be detrimental to workers' health. Indeed, by affecting individuals' access to power and other resources, EP puts precarious workers at risk of experiencing health shocks and influences their ability to gain and accumulate health advantages (Hp.1).
Further, the focus on Germany allows me to investigate my second research question on the gender differential. Germany is usually regarded as a traditionalist gender regime: a context characterized by a configuration of roles. Here, being a caregiver is assumed to be women's primary role, whereas the primary breadwinner role is reserved for men. Although many signs of progress have been made over the last decades towards a greater equalization of opportunities and more egalitarianism, the breadwinner model has barely changed towards a modified version. Thus, women usually take on the double role of workers (the so-called secondary earner) and caregivers, and men still devote most of their time to paid work activities. Moreover, the overall upward trend towards more egalitarian gender ideologies has leveled off over the last decades, moving notably towards more traditional gender ideologies.
In this setting, two alternative hypotheses are possible. Firstly, I assume that the negative relationship between EP and health is stronger for women than for men. This is because women are systematically more disadvantaged than men in the public and private spheres of life, having less access to formal and informal sources of power. These gender-related power asymmetries may interact with EP-related power asymmetries resulting in a stronger effect of EP on women's health than on men's health (Hp.2).
An alternative way of looking at the gender differential is to consider the interaction that precariousness might have with men's and women's gender identities. According to this view, the negative relationship between EP and health is weaker for women than for men (Hp.2a). In a society with a gendered division of labor and a strong link between masculine identities and stable and well-rewarded job—i.e., a job that confers the role of primary family provider—a male worker with precarious employment might violate the traditional male gender role. Men in precarious jobs may perceive themselves (and by others) as possessing a socially undesirable characteristic, which conflicts with the stereotypical idea of themselves as the male breadwinner. Engaging in behaviors that contradict stereotypical gender identity may decrease self-esteem and foster feelings of inferiority, helplessness, and jealousy, leading to poor health.
I develop a new indicator of EP that empirically translates a definition of EP as a multidimensional and continuous phenomenon. I assume that EP is a latent construct composed of seven dimensions of insecurity chosen according to the theory and previous empirical research: Income insecurity, social insecurity, legal insecurity, employment insecurity, working-time insecurity, representation insecurity, worker's vulnerability. The seven dimensions are proxied by eight indicators available in the four waves of the SOEP dataset. The EP composite indicator is obtained by performing a multiple correspondence analysis (MCA) on the eight indicators. This approach aims to construct a summary scale in which all dimensions contribute jointly to the measured experience of precariousness and its health impact.
Further, the relationship between EP and 'general self-perceived health' is estimated by applying ordered probit random-effects estimators and calculating average marginal effect (further AME). Then, to control for unobserved heterogeneity, I implement correlated random-effects models that add to the model the within-individual means of the time-varying independent variables. To test the significance of the gender differential, I add an interaction term between EP and gender in the fully adjusted model in the pooled sample.
My correlated random-effects models showed EP's negative and substantial 'effect' on self-perceived health for both men and women. Although nonsignificant, the evidence seems in line with previous cross-sectional literature. It supports the hypothesis that employment precariousness could be detrimental to workers' health. Further, my results showed the crucial role of unobserved heterogeneity in shaping the health consequences of precarious employment. This is particularly important as evidence accumulates, yet it is still mostly descriptive.
Moreover, my results revealed a substantial difference among men and women in the relationship between EP and health: when EP increases, the risk of experiencing poor health increases much more for men than for women. This evidence falsifies previous theory according to whom the gender differential is contingent on the structurally disadvantaged position of women in western societies. In contrast, they seem to confirm the idea that men in precarious work could experience role conflict to a larger extent than women, as their self-standard is supposed to be the stereotypical breadwinner worker with a good and well-rewarded job. Finally, results from the multiple correspondence analysis contribute to the methodological debate on precariousness, showing that a multidimensional and continuous indicator can express a latent variable of EP.
All in all, complementarities are revealed in the results of unemployment and employment precariousness, which have two implications: Policy-makers need to be aware that the total costs of unemployment and precariousness go far beyond the economic and material realm penetrating other fundamental life domains such as individual health. Moreover, they need to balance the trade-off between protecting adequately unemployed people and fostering high-quality employment in reaction to the highlighted market pressures. In this sense, the further development of a (universalistic) welfare state certainly helps mitigate the adverse health effects of unemployment and, therefore, the future costs of both individuals' health and welfare spending. In addition, the presence of a working partner is crucial for reducing the health consequences of employment instability. Therefore, policies aiming to increase female labor market participation should be promoted, especially in those contexts where the welfare state is less developed.
Moreover, my results support the significance of taking account of a gender perspective in health research. The findings of the three articles show that job loss, unemployment, and precarious employment, in general, have adverse effects on men's health but less or absent consequences for women's health. Indeed, this suggests the importance of labor and health policies that consider and further distinguish the specific needs of the male and female labor force in Europe. Nevertheless, a further implication emerges: the health consequences of employment instability and de-standardization need to be investigated in light of the gender arrangements and the transforming gender relationships in specific cultural and institutional contexts. My results indeed seem to suggest that women's health advantage may be a transitory phenomenon, contingent on the predominant gendered institutional and cultural context. As the structural difference between men's and women's position in society is eroded, egalitarianism becomes the dominant normative status, so will probably be the gender difference in the health consequences of job loss and precariousness. Therefore, while gender equality in opportunities and roles is a desirable aspect for contemporary societies and a political goal that cannot be postponed further, this thesis raises a further and maybe more crucial question: What kind of equality should be pursued to provide men and women with both good life quality and equal chances in the public and private spheres? In this sense, I believe that social and labor policies aiming to reduce gender inequality in society should focus on improving women's integration into the labor market, implementing policies targeting men, and facilitating their involvement in the private sphere of life. Equal redistribution of social roles could activate a crucial transformation of gender roles and the cultural models that sustain and still legitimate gender inequality in Western societies.
An important goal in biotechnology and (bio-) medical research is the isolation of single cells from a heterogeneous cell population. These specialised cells are of great interest for bioproduction, diagnostics, drug development, (cancer) therapy and research. To tackle emerging questions, an ever finer differentiation between target cells and non-target cells is required. This precise differentiation is a challenge for a growing number of available methods.
Since the physiological properties of the cells are closely linked to their morphology, it is beneficial to include their appearance in the sorting decision. For established methods, this represents a non addressable parameter, requiring new methods for the identification and isolation of target cells. Consequently, a variety of new flow-based methods have been developed and presented in recent years utilising 2D imaging data to identify target cells within a sample. As these methods aim for high throughput, the devices developed typically require highly complex fluid handling techniques, making them expensive while offering limited image quality.
In this work, a new continuous flow system for image-based cell sorting was developed that uses dielectrophoresis to precisely handle cells in a microchannel. Dielectrophoretic forces are exerted by inhomogeneous alternating electric fields on polarisable particles (here: cells). In the present system, the electric fields can be switched on and off precisely and quickly by a signal generator. In addition to the resulting simple and effective cell handling, the system is characterised by the outstanding quality of the image data generated and its compatibility with standard microscopes. These aspects result in low complexity, making it both affordable and user-friendly.
With the developed cell sorting system, cells could be sorted reliably and efficiently according to their cytosolic staining as well as morphological properties at different optical magnifications. The achieved purity of the target cell population was up to 95% and about 85% of the sorted cells could be recovered from the system. Good agreement was achieved between the results obtained and theoretical considerations. The achieved throughput of the system was up to 12,000 cells per hour. Cell viability studies indicated a high biocompatibility of the system.
The results presented demonstrate the potential of image-based cell sorting using dielectrophoresis. The outstanding image quality and highly precise yet gentle handling of the cells set the system apart from other technologies. This results in enormous potential for processing valuable and sensitive cell samples.
A task-based parallel elliptic solver for numerical relativity with discontinuous Galerkin methods
(2022)
Elliptic partial differential equations are ubiquitous in physics. In numerical relativity---the study of computational solutions to the Einstein field equations of general relativity---elliptic equations govern the initial data that seed every simulation of merging black holes and neutron stars. In the quest to produce detailed numerical simulations of these most cataclysmic astrophysical events in our Universe, numerical relativists resort to the vast computing power offered by current and future supercomputers. To leverage these computational resources, numerical codes for the time evolution of general-relativistic initial value problems are being developed with a renewed focus on parallelization and computational efficiency. Their capability to solve elliptic problems for accurate initial data must keep pace with the increasing detail of the simulations, but elliptic problems are traditionally hard to parallelize effectively.
In this thesis, I develop new numerical methods to solve elliptic partial differential equations on computing clusters, with a focus on initial data for orbiting black holes and neutron stars. I develop a discontinuous Galerkin scheme for a wide range of elliptic equations, and a stack of task-based parallel algorithms for their iterative solution. The resulting multigrid-Schwarz preconditioned Newton-Krylov elliptic solver proves capable of parallelizing over 200 million degrees of freedom to at least a few thousand cores, and already solves initial data for a black hole binary about ten times faster than the numerical relativity code SpEC. I also demonstrate the applicability of the new elliptic solver across physical disciplines, simulating the thermal noise in thin mirror coatings of interferometric gravitational-wave detectors to unprecedented accuracy. The elliptic solver is implemented in the new open-source SpECTRE numerical relativity code, and set up to support simulations of astrophysical scenarios for the emerging era of gravitational-wave and multimessenger astronomy.
Different lake systems might reflect different climate elements of climate changes, while the responses of lake systems are also divers, and are not completely understood so far. Therefore, a comparison of lakes in different climate zones, during the high-amplitude and abrupt climate fluctuations of the Last Glacial to Holocene transition provides an exceptional opportunity to investigate distinct natural lake system responses to different abrupt climate changes. The aim of this doctoral thesis was to reconstruct climatic and environmental fluctuations down to (sub-) annual resolution from two different lake systems during the Last Glacial-Interglacial transition (~17 and 11 ka). Lake Gościąż, situated in the temperate central Poland, developed in the Allerød after recession of the Last Glacial ice sheets. The Dead Sea is located in the Levant (eastern Mediterranean) within a steep gradient from sub-humid to hyper-arid climate, and formed in the mid-Miocene. Despite their differences in sedimentation processes, both lakes form annual laminations (varves), which are crucial for studies of abrupt climate fluctuations. This doctoral thesis was carried out within the DFG project PALEX-II (Paleohydrology and Extreme Floods from the Dead Sea ICDP Core) that investigates extreme hydro-meteorological events in the ICDP core in relation to climate changes, and ICLEA (Virtual Institute of Integrated Climate and Landscape Evolution Analyses) that intends to better the understanding of climate dynamics and landscape evolutions in north-central Europe since the Last Glacial. Further, it contributes to the Helmholtz Climate Initiative REKLIM (Regional Climate Change and Humans) Research Theme 3 “Extreme events across temporal and spatial scales” that investigates extreme events using climate data, paleo-records and model-based simulations. The three main aims were to (1) establish robust chronologies of the lakes, (2) investigate how major and abrupt climate changes affect the lake systems, and (3) to compare the responses of the two varved lakes to these hemispheric-scale climate changes.
Robust chronologies are a prerequisite for high-resolved climate and environmental reconstructions, as well as for archive comparisons. Thus, addressing the first aim, the novel chronology of Lake Gościąż was established by microscopic varve counting and Bayesian age-depth modelling in Bacon for a non-varved section, and was corroborated by independent age constrains from 137Cs activity concentration measurements, AMS radiocarbon dating and pollen analysis. The varve chronology reaches from the late Allerød until AD 2015, revealing more Holocene varves than a previous study of Lake Gościąż suggested. Varve formation throughout the complete Younger Dryas (YD) even allowed the identification of annually- to decadal-resolved leads and lags in proxy responses at the YD transitions.
The lateglacial chronology of the Dead Sea (DS) was thus far mainly based on radiocarbon and U/Th-dating. In the unique ICDP core from the deep lake centre, continuous search for cryptotephra has been carried out in lateglacial sediments between two prominent gypsum deposits – the Upper and Additional Gypsum Units (UGU and AGU, respectively). Two cryptotephras were identified with glass analyses that correlate with tephra deposits from the Süphan and Nemrut volcanoes indicating that the AGU is ~1000 years younger than previously assumed, shifting it into the YD, and the underlying varved interval into the Bølling/Allerød, contradicting previous assumptions.
Using microfacies analyses, stable isotopes and temperature reconstructions, the second aim was achieved at Lake Gościąż. The YD lake system was dynamic, characterized by higher aquatic bioproductivity, more re-suspended material and less anoxia than during the Allerød and Early Holocene, mainly influenced by stronger water circulation and catchment erosion due to stronger westerly winds and less lake sheltering. Cooling at the YD onset was ~100 years longer than the final warming, while environmental proxies lagged the onset of cooling by ~90 years, but occurred contemporaneously during the termination of the YD. Chironomid-based temperature reconstructions support recent studies indicating mild YD summer temperatures. Such a comparison of annually-resolved proxy responses to both abrupt YD transitions is rare, because most European lake archives do not preserve varves during the YD.
To accomplish the second aim at the DS, microfacies analyses were performed between the UGU (~17 ka) and Holocene onset (~11 ka) in shallow- (Masada) and deep-water (ICDP core) environments. This time interval is marked by a huge but fluctuating lake level drop and therefore the complete transition into the Holocene is only recorded in the deep-basin ICDP core. In this thesis, this transition was investigated for the first time continuously and in detail. The final two pronounced lake level drops recorded by deposition of the UGU and AGU, were interrupted by one millennium of relative depositional stability and a positive water budget as recorded by aragonite varve deposition interrupted by only a few event layers. Further, intercalation of aragonite varves between the gypsum beds of the UGU and AGU shows that these generally dry intervals were also marked by decadal- to centennial-long rises in lake level. While continuous aragonite varves indicate decadal-long stable phases, the occurrence of thicker and more frequent event layers suggests general more instability during the gypsum units. These results suggest a pattern of complex and variable hydroclimate at different time scales during the Lateglacial at the DS.
The third aim was accomplished based on the individual studies above that jointly provide an integrated picture of different lake responses to different climate elements of hemispheric-scale abrupt climate changes during the Last Glacial-Interglacial transition. In general, climatically-driven facies changes are more dramatic in the DS than at Lake Gościąż. Further, Lake Gościąż is characterized by continuous varve formation nearly throughout the complete profile, whereas the DS record is widely characterized by extreme event layers, hampering the establishment of a continuous varve chronology. The lateglacial sedimentation in Lake Gościąż is mainly influenced by westerly winds and minor by changes in catchment vegetation, whereas the DS is primarily influenced by changes in winter precipitation, which are caused by temperature variations in the Mediterranean. Interestingly, sedimentation in both archives is more stable during the Bølling/Allerød and more dynamic during the YD, even when sedimentation processes are different.
In summary, this doctoral thesis presents seasonally-resolved records from two lake archives during the Lateglacial (ca 17-11 ka) to investigate the impact of abrupt climate changes in different lake systems. New age constrains from the identification of volcanic glass shards in the lateglacial sediments of the DS allowed the first lithology-based interpretation of the YD in the DS record and its comparison to Lake Gościąż. This highlights the importance of the construction of a robust chronology, and provides a first step for synchronization of the DS with other eastern Mediterranean archives. Further, climate reconstructions from the lake sediments showed variability on different time scales in the different archives, i.e. decadal- to millennial fluctuations in the lateglacial DS, and even annual variations and sub-decadal leads and lags in proxy responses during the rapid YD transitions in Lake Gościąż. This showed the importance of a comparison of different lake archives to better understand the regional and local impacts of hemispheric-scale climate variability. An unprecedented example is demonstrated here of how different lake systems show different lake responses and also react to different climate elements of abrupt climate changes. This further highlights the importance of the understanding of the respective lake system for climate reconstructions.
Abzug unter Beobachtung
(2022)
Mehr als vier Jahrzehnte lang beobachteten die Streitkräfte und Militärnachrichtendienste der NATO-Staaten die sowjetischen Truppen in der DDR. Hierfür übernahm in der Bundesrepublik Deutschland der Bundesnachrichtendienst (BND) die militärische Auslandsaufklärung unter Anwendung nachrichtendienstlicher Mittel und Methoden. Die Bundeswehr betrieb dagegen taktische Fernmelde- und elektronische Aufklärung und hörte vor allem den Funkverkehr der „Gruppe der sowjetischen Streitkräfte in Deutschland“ (GSSD) ab. Mit der Aufstellung einer zentralen Dienststelle für das militärische Nachrichtenwesen, dem Amt für Nachrichtenwesen der Bundeswehr, bündelte und erweiterte zugleich das Bundesministerium für Verteidigung in den 1980er Jahren seine analytischen Kapazitäten. Das Monopol des BND in der militärischen Auslandsaufklärung wurde von der Bundeswehr dadurch zunehmend infrage gestellt.
Nach der deutschen Wiedervereinigung am 3. Oktober 1990 befanden sich immer noch mehr als 300.000 sowjetische Soldaten auf deutschem Territorium. Die 1989 in Westgruppe der Truppen (WGT) umbenannte GSSD sollte – so der Zwei-plus-Vier-Vertrag – bis 1994 vollständig abziehen. Der Vertrag verbot auch den drei Westmächten, in den neuen Bundesländern militärisch tätig zu sein. Die für die Militäraufklärung bis dahin unverzichtbaren Militärverbindungsmissionen der Westmächte mussten ihre Dienste einstellen. Doch was geschah mit diesem „alliierten Erbe“? Wer übernahm auf deutscher Seite die Aufklärung der sowjetischen Truppen und wer kontrollierte den Truppenabzug?
Die Studie untersucht die Rolle von Bundeswehr und BND beim Abzug der WGT zwischen 1990 und 1994 und fragt dabei nach Kooperation und Konkurrenz zwischen Streitkräften und Nachrichtendiensten. Welche militärischen und nachrichtendienstlichen Mittel und Fähigkeiten stellte die Bundesregierung zur Bewältigung des Truppenabzugs zur Verfügung, nachdem die westlichen Militärverbindungsmissionen aufgelöst wurden? Wie veränderten sich die Anforderungen an die militärische Auslandsaufklärung des BND? Inwieweit setzten sich Konkurrenz und Kooperation von Bundeswehr und BNDbeim Truppenabzug fort? Welche Rolle spielten dabei die einstigen Westmächte? Die Arbeit versteht sich nicht nur als Beitrag zur Militärgeschichte, sondern auch zur deutschen Nachrichtendienstgeschichte.
Successful communication is often explored by people throughout their life courses. To effectively transfer one’s own information to others, people employ various linguistic tools, such as word order information, prosodic cues, and lexical choices. The exploration of these linguistic cues is known as the study of information structure (IS). Moreover, an important issue in the language acquisition of children is the investigation of how they acquire IS. This thesis seeks to improve our understanding of how children acquire different tools (i.e., prosodical cues, syntactical cues, and the focus particle only) of focus marking in a cross linguistic perspective.
In the first study, following Szendrői and her colleagues (2017)- the sentence-picture verification task- was performed to investigate whether three- to five-year-old Mandarin-speaking children as well as Mandarin-speaking adults could apply prosodic information to recognize focus in sentences. More, in the second study, not only Mandarin-speaking adults and Mandarin-speaking children but also German-speaking adults and German-speaking children were included to confirm the assumption that children could have adult-like performance in understanding sentence focus by identifying language specific cues in their mother tongue from early onwards. In this study, the same paradigm- the sentence-picture verification task- as in the first study was employed together with the eye-tracking method. Finally, in the last study, an issue of whether five-year-old Mandarin-speaking children could understand the pre-subject only sentence was carried out and again whether prosodic information would help them to better understand this kind of sentences.
The overall results seem to suggest that Mandarin-speaking children from early onwards could make use of the specific linguistic cues in their ambient language. That is, in Mandarin, a Topic-prominent and tone language, the word order information plays a more important rule than the prosodic information and even three-year-old Mandarin-speaking children could follow the word order information. More, although it seems that German-speaking children could follow the prosodic information, they did not have the adult-like performance in the object-accented condition. A feasible reason for this result is that there are more possibilities of marking focus in German, such as flexible word order, prosodic information, focus particles, and thus it would take longer time for German-speaking children to manage these linguistic tools. Another important empirical finding regarding the syntactically-marked focus in German is that it seems that the cleft construction is not a valid focus construction and this result corroborates with the previous observations (Dufter, 2009). Further, eye-tracking method did help to uncover how the parser direct their attention for recognizing focus. In the final study, it is showed that with explicit verbal context Mandarin-speaking children could understand the pre-subject only sentence and the study brought a better understanding of the acquisition of the focus particle- only with the Mandarin-speaking children.
The aim of this work is the study of silica Arrayed Waveguide Gratings (AWGs) in the context of applications in astronomy. The specific focus lies on the investigation of the feasibility and technology limits of customized silica AWG devices for high resolution near-infrared spectroscopy. In a series of theoretical and experimental studies, AWG devices of varying geometry, foot-print and spectral resolution are constructed, simulated using a combination of a numerical beam propagation method and Fraunhofer diffraction and fabricated devices are characterized with respect to transmission efficiency, spectral resolution and polarization sensitivity. The impact of effective index non-uniformities on the performance of high-resolution AWG devices is studied numerically. Characterization results of fabricated devices are used to extrapolate the technology limits of the silica platform. The important issues of waveguide birefringence and defocus aberration are discussed theoretically and addressed experimentally by selection of an appropriate aberration-minimizing anastigmatic AWG layout structure. The drawbacks of the anastigmatic AWG geometry are discussed theoretically. From the results of the experimental studies, it is concluded that fabrication-related phase errors and waveguide birefringence are the primary limiting factors for the growth of AWG spectral resolution. It is shown that, without post-processing, the spectral resolving power is phase-error-limited to R < 40, 000 and, in the case of unpolarized light, birefringence-limited to R < 30, 000 in the AWG devices presented in this work. Necessary measures, such as special waveguide geometries and post-fabrication phase error correction are proposed for future designs. The elimination of defocus aberration using an anastigmatic AWG geometry is successfully demonstrated in experiment. Finally, a novel, non-planar dispersive in-fibre waveguide structure is proposed, discussed and studied theoretically.
The Turkish language in diaspora is in process of change due to different language constellations of immigrants and the dominance of majority languages. This led to a great interest in various research areas, particularly in linguistics. Against this background, this study focuses on developmental change in the use of adverbial clause-combining constructions in Turkish-German bilingual students’ oral and written text production. It illustrates the use of non-finite constructions and some unique alternative strategies to express adverbial relations with authentic examples in Turkish and German. The findings contribute to a better understanding of how bilingual competencies vary in expressing adverbial relations depending on language contact and extra-linguistic factors.
Afropolitan Encounters
(2022)
Afropolitan Encounters: Literature and Activism in London and Berlin explores what Afropolitanism does. Mobile people of African descent use this term to address their own lived realities creatively, which often includes countering stereotypical notions of being African. Afropolitan practices are enormously heterogeneous and malleable, which constitutes its strengths and, at the same time, creates tensions.
This book traces the theoretical beginnings of Afropolitanism and moves on to explore Afropolitan practices in London and Berlin. Afropolitanism can take different forms, such as that of an identity, a political and ethical stance, a dead–end road, networks, a collective self–care practice or a strategic label. In spite of the harsh criticism, Afropolitanism is attractive for people to deal with the meanings of Africa and Africanness, questions of belonging, equal rights and opportunities.
While not a unitary project, the vast variety of Afropolitan practices provide approaches to contemporary political problems in Europe and beyond. In this book, Afropolitan practices are read against the specific context of German and British colonial histories and structures of racism, the histories of Black Europeans, and contemporary right–wing resurgence in Germany and England, respectively.
The present dissertation conducts empirical research on the relationship between urban life and its economic costs, especially for the environment. On the one hand, existing gaps in research on the influence of population density on air quality are closed and, on the other hand, innovative policy measures in the transport sector are examined that are intended to make metropolitan areas more sustainable. The focus is on air pollution, congestion and traffic accidents, which are important for general welfare issues and represent significant cost factors for urban life. They affect a significant proportion of the world's population. While 55% of the world's people already lived in cities in 2018, this share is expected to reach approximately 68% by 2050.
The four self-contained chapters of this thesis can be divided into two sections: Chapters 2 and 3 provide new causal insights into the complex interplay between urban structures and air pollution. Chapters 4 and 5 then examine policy measures to promote non-motorised transport and their influence on air quality as well as congestion and traffic accidents.
Technological progress allows for producing ever more complex predictive models on the basis of increasingly big datasets. For risk management of natural hazards, a multitude of models is needed as basis for decision-making, e.g. in the evaluation of observational data, for the prediction of hazard scenarios, or for statistical estimates of expected damage. The question arises, how modern modelling approaches like machine learning or data-mining can be meaningfully deployed in this thematic field. In addition, with respect to data availability and accessibility, the trend is towards open data. Topic of this thesis is therefore to investigate the possibilities and limitations of machine learning and open geospatial data in the field of flood risk modelling in the broad sense. As this overarching topic is broad in scope, individual relevant aspects are identified and inspected in detail.
A prominent data source in the flood context is satellite-based mapping of inundated areas, for example made openly available by the Copernicus service of the European Union. Great expectations are directed towards these products in scientific literature, both for acute support of relief forces during emergency response action, and for modelling via hydrodynamic models or for damage estimation. Therefore, a focus of this work was set on evaluating these flood masks. From the observation that the quality of these products is insufficient in forested and built-up areas, a procedure for subsequent improvement via machine learning was developed. This procedure is based on a classification algorithm that only requires training data from a particular class to be predicted, in this specific case data of flooded areas, but not of the negative class (dry areas). The application for hurricane Harvey in Houston shows the high potential of this method, which depends on the quality of the initial flood mask.
Next, it is investigated how much the predicted statistical risk from a process-based model chain is dependent on implemented physical process details. Thereby it is demonstrated what a risk study based on established models can deliver. Even for fluvial flooding, such model chains are already quite complex, though, and are hardly available for compound or cascading events comprising torrential rainfall, flash floods, and other processes. In the fourth chapter of this thesis it is therefore tested whether machine learning based on comprehensive damage data can offer a more direct path towards damage modelling, that avoids explicit conception of such a model chain. For that purpose, a state-collected dataset of damaged buildings from the severe El Niño event 2017 in Peru is used. In this context, the possibilities of data-mining for extracting process knowledge are explored as well. It can be shown that various openly available geodata sources contain useful information for flood hazard and damage modelling for complex events, e.g. satellite-based rainfall measurements, topographic and hydrographic information, mapped settlement areas, as well as indicators from spectral data. Further, insights on damaging processes are discovered, which mainly are in line with prior expectations. The maximum intensity of rainfall, for example, acts stronger in cities and steep canyons, while the sum of rain was found more informative in low-lying river catchments and forested areas. Rural areas of Peru exhibited higher vulnerability in the presented study compared to urban areas. However, the general limitations of the methods and the dependence on specific datasets and algorithms also become obvious.
In the overarching discussion, the different methods – process-based modelling, predictive machine learning, and data-mining – are evaluated with respect to the overall research questions. In the case of hazard observation it seems that a focus on novel algorithms makes sense for future research. In the subtopic of hazard modelling, especially for river floods, the improvement of physical models and the integration of process-based and statistical procedures is suggested. For damage modelling the large and representative datasets necessary for the broad application of machine learning are still lacking. Therefore, the improvement of the data basis in the field of damage is currently regarded as more important than the selection of algorithms.
Proteine sind an praktisch allen Prozessen in lebenden Zellen maßgeblich beteiligt. Auch in der Biotechnologie werden Proteine in vielfältiger Weise eingesetzt.
Ein Protein besteht aus einer Kette von Aminosäuren. Häufig lagern sich mehrere dieser Ketten zu größeren Strukturen und Funktionseinheiten, sogenannten Proteinkomplexen,
zusammen. Kürzlich wurde gezeigt, dass eine Proteinkomplexbildung bereits während der Biosynthese der Proteine (co-translational) stattfinden kann
und nicht stets erst danach (post-translational) erfolgt. Da Fehlassemblierungen von Proteinen zu Funktionsverlusten und adversen Effekten führen, ist eine präzise und verlässliche Proteinkomplexbildung sowohl für zelluläre Prozesse als auch für biotechnologische Anwendungen essenziell. Mit experimentellen Methoden lassen sich zwar u.a. die Stöchiometrie und die Struktur von Proteinkomplexen bestimmen,
jedoch bisher nicht die Dynamik der Komplexbildung auf unterschiedlichen Zeitskalen. Daher sind grundlegende Mechanismen der Proteinkomplexbildung noch nicht vollständig verstanden. Die hier vorgestellte, auf experimentellen Erkenntnissen aufbauende, computergestützte Modellierung der Proteinkomplexbildung erlaubt eine umfassende Analyse des Einflusses physikalisch-chemischer Parameter
auf den Assemblierungsprozess. Die Modelle bilden möglichst realistisch die experimentellen Systeme der Kooperationspartner (Bar-Ziv, Weizmann-Institut, Israel; Bukau und Kramer, Universität Heidelberg) ab, um damit die Assemblierung von Proteinkomplexen einerseits in einem quasi-zweidimensionalen synthetischen Expressionssystem (in vitro) und andererseits im Bakterium Escherichia coli (in vivo) untersuchen zu können. Mit Hilfe eines vereinfachten Expressionssystems, in dem die Proteine nur an die Chip-Oberfläche, aber nicht aneinander binden können, wird das theoretische Modell parametrisiert. In diesem vereinfachten in-vitro-System durchläuft die Effizienz der Komplexbildung drei Regime – ein bindedominiertes Regime, ein Mischregime und ein produktionsdominiertes Regime. Ihr Maximum erreicht die Effizienz dabei kurz nach dem Übergang vom bindedominierten ins Mischregime und fällt anschließend monoton ab. Sowohl im nicht-vereinfachten in-vitro- als auch im in-vivo-System koexistieren je zwei konkurrierende Assemblierungspfade: Im in-vitro-System erfolgt die Komplexbildung entweder spontan in wässriger Lösung (Lösungsassemblierung) oder aber in einer definierten Schrittfolge an der Chip-Oberfläche (Oberflächenassemblierung); Im in-vivo-System konkurrieren hingegen die co- und die post-translationale Komplexbildung. Es zeigt sich, dass die Dominanz der Assemblierungspfade im in-vitro-System zeitabhängig ist und u.a. durch die Limitierung und Stärke der Bindestellen auf der Chip-Oberfläche beeinflusst werden kann. Im in-vivo-System hat der räumliche Abstand zwischen den Syntheseorten der beiden Proteinkomponenten nur dann einen Einfluss auf die Komplexbildung, wenn die Untereinheiten schnell degradieren. In diesem Fall dominiert die co-translationale Assemblierung auch auf kurzen Zeitskalen deutlich, wohingegen es bei stabilen Untereinheiten zu einem Wechsel von der Dominanz der post- hin zu einer geringen Dominanz der co-translationalen Assemblierung kommt. Mit den in-silico-Modellen lässt sich neben der Dynamik u.a. auch die Lokalisierung der Komplexbildung und -bindung darstellen, was einen Vergleich der theoretischen Vorhersagen mit experimentellen Daten und somit eine Validierung der Modelle ermöglicht. Der hier präsentierte in-silico Ansatz ergänzt die experimentellen Methoden, und erlaubt so, deren Ergebnisse zu interpretieren und neue Erkenntnisse davon abzuleiten.
The development of speaking competence is widely regarded as a central aspect of second language (L2) learning. It may be questioned, however, if the currently predominant ways of conceptualising the term fully satisfy the complexity of the construct: Although there is growing recognition that language primarily constitutes a tool for communication and participation in social life, as yet it is rare for conceptualisations of speaking competence to incorporate the ability to inter-act and co-construct meaning with co-participants. Accordingly, skills allowing for the successful accomplishment of interactional tasks (such as orderly speaker change, and resolving hearing and understanding trouble) also remain largely unrepresented in language teaching and assessment. As fostering the ability to successfully use the L2 within social interaction should arguably be a main objective of language teaching, it appears pertinent to broaden the construct of speaking competence by incorporating interactional competence (IC). Despite there being a growing research interest in the conceptualisation and development of (L2) IC, much of the materials and instruments required for its teaching and assessment, and thus for fostering a broader understanding of speaking competence in the L2 classroom, still await development. This book introduces an approach to the identification of candidate criterial features for the assessment of EFL learners’ L2 repair skills. Based on a corpus of video-recorded interaction between EFL learners, and following conversation-analytic and interactional-linguistic methodology as well as drawing on basic premises of research in the framework of Conversation Analysis for Second Language Acquisition, differences between (groups of) learners in terms of their L2 repair conduct are investigated through qualitative and inductive analyses. Candidate criterial features are derived from the analysis results. This book does not only contribute to the operationalisation of L2 IC (and of L2 repair skills in particular), but also lays groundwork for the construction of assessment scales and rubrics geared towards the evaluation of EFL learners’ L2 interactional skills.
Die allergische Kontaktdermatitis ist eine immunologisch bedingte Hauterkrankung mit insbesondere in den westlichen Industrienationen hoher und weiter ansteigender Prävalenz. Es handelt sich hierbei um eine Hypersensitivitätsreaktion vom Typ IV, die sich nach Allergenkontakt durch Juckreiz, Rötung, Bläschenbildung und Abschälung der Haut äußert. Zahlreiche Xenobiotika besitzen das Potenzial, Kontaktallergien auszulösen, darunter Konservierungsstoffe, Medikamente, Duftstoffe und Chemikalien. Die wirksamste Maßnahme zur Eindämmung der Erkrankung ist die Expositionsprophylaxe, also die Vermeidung des Kontakts mit den entsprechenden Substanzen. Dies wiederum setzt die Kenntnis des jeweiligen sensibilisierenden Potenzials einer Substanz voraus, dessen Bestimmung aus diesem Grund eine hohe toxikologische Relevanz besitzt. Zu diesem Zweck existieren von der OECD veröffentlichte Testleitlinien, welche auf entsprechend validierten Testmethoden basieren. Goldstandard bei der Prüfung auf hautsensibilisierendes Potenzial war über lange Zeit der murine Lokale Lymphknotentest. Seit der 7. Änderung der EU-Kosmetikrichtlinie, welche Tierversuche für Kosmetika und deren Inhaltsstoffe untersagt, wurden vermehrt Alternativmethoden in die OECD-Testleitlinien implementiert.. Die bestehenden in vitro Methoden sind jedoch alleinstehend nur begrenzt aussagekräftig, da sie lediglich singuläre Mechanismen bei der Entstehung einer Kontaktallergie abbilden. Die Entwicklung von Testmethoden, welche mehrere dieser Schlüsselereignisse berücksichtigen, erscheint daher richtungsweisend. Einen vielversprechenden Ansatz liefert hierbei der Loose-fit coculture-based sensitisation assay (LCSA), welcher eine Kokultur aus primären Keratinozyten und PBMC darstellt. Bei der Kokultivierung von Immunzellen mit anderen Zelltypen stellt sich allerdings die Frage, inwiefern die Nutzung von Zellen derselben Spender*innen (autologe Kokultur) bzw. verschiedener Spender*innen (allogene Kokultur) einen Einfluss nimmt. Zu diesem Zweck wurden im Rahmen dieser Arbeit Hautzellen spenderspezifisch aus gezupften Haarfollikeln isoliert und der LCSA mit den generierten HFDK in autologen und allogenen Ansätzen verglichen. Zusätzlich wurde auch ein Vergleich zwischen der Nutzung von HFDK und NHK, welche aus humaner Vorhaut isoliert wurden, im LCSA durchgeführt. Dabei ergaben sich keine signifikanten Unterschiede zwischen autologen und allogenen Kokulturen bzw. zwischen der Verwendung von HFDK und NHK. Die Verwendung allogener Zellen aus anonymem Spendermaterial sowie die Nutzung von Keratinozyten aus unterschiedlichen Quellen scheint im Rahmen des LCSA problemlos möglich. Einige der getesteten Kontaktallergene, darunter DNCB und NiCl2, erwiesen sich im LCSA jedoch als problematisch und konnten nicht zufriedenstellend als sensibilisierend detektiert werden. Daher wurde eine Optimierung der Kokultur durch Verwendung ex vivo differenzierter Langerhans Zellen (MoLC) angestrebt, welche ein besseres Modell primärer epidermaler Langerhans Zellen darstellen als die dendritischen Zellen aus dem LCSA. Zusätzlich wurden weitere, den Erfolg der Kokultur beeinflussende Faktoren, wie die Art und Zusammensetzung des Mediums und die Kokultivierungsdauer, untersucht und angepasst. Das schlussendlich etablierte Kokultivierungsprotokoll führte zu einer maßgeblich verstärkten Expression von CD207 (Langerin) auf den MoLC, was auf eine wirkungsvolle Interaktion zwischen Haut- und Immunzellen in der Kokultur hindeutete. Des Weiteren konnten DNCB und NiCl2 im Gegensatz zum LCSA durch Verwendung des kostimulatorischen Moleküls CD86 sowie des Reifungsmarkers CD83 als Ausleseparameter eindeutig als Kontaktallergene identifiziert werden. Die Untersuchungen zur Kokultur von MoLC und HFDK wurden jeweils vergleichend in autologen und allogenen Ansätzen durchgeführt. Ähnlich wie beim LCSA kam es aber auch hier zu keinen signifikanten Unterschieden, weder hinsichtlich der Expression von Charakterisierungs- und Aktivierungsmarkern auf MoLC noch hinsichtlich der Zytokinsekretion in den Zellkulturüberstand. Die Hinweise aus zahlreichen Studien im Mausmodell, dass Zellen des angeborenen Immunsystems zur Erkennung von und Aktivierung durch allogene Zellen bzw. Gewebe in der Lage sind, bestätigten sich im Rahmen dieser Arbeit dementsprechend nicht. Aus diesem Grund wurden abschließend CD4+ T-Lymphozyten, die Effektorzellen des adaptiven Immunsystems, in die Kokultur aus MoLC und autologen bzw. allogenen HFDK integriert. Überraschenderweise traten auch hier keine verstärkten Aktivierungen in allogener Kokultur im Vergleich zur autologen Kokultur auf. Die Nutzung autologer Primärzellen scheint im Rahmen der hier getesteten Methoden nicht notwendig zu sein, was die Validierung von Kokulturen und deren Implementierung in die OECD-Testleitlinien erleichtern dürfte. Zuletzt wurde eine Kokultivierung primärer Haut- und Immunzellen auch im 3D-Vollhautmodell durchgeführt, wobei autologe MoLC in die Epidermisäquivalente entsprechender Modelle integriert werden sollten. Obwohl die erstellten Hautmodelle unter Verwendung autologer Haarfollikel-generierter Keratinozyten und Fibroblasten eine zufriedenstellende Differenzierung und Stratifizierung aufwiesen, gestaltete sich die Inkorporation der MoLC als problematisch und konnte im Rahmen dieser Arbeit nicht erreicht werden.
A decade ago, it became feasible to store multi-terabyte databases in main memory. These in-memory databases (IMDBs) profit from DRAM's low latency and high throughput as well as from the removal of costly abstractions used in disk-based systems, such as the buffer cache. However, as the DRAM technology approaches physical limits, scaling these databases becomes difficult. Non-volatile memory (NVM) addresses this challenge. This new type of memory is persistent, has more capacity than DRAM (4x), and does not suffer from its density-inhibiting limitations. Yet, as NVM has a higher latency (5-15x) and a lower throughput (0.35x), it cannot fully replace DRAM.
IMDBs thus need to navigate the trade-off between the two memory tiers. We present a solution to this optimization problem. Leveraging information about access frequencies and patterns, our solution utilizes NVM's additional capacity while minimizing the associated access costs. Unlike buffer cache-based implementations, our tiering abstraction does not add any costs when reading data from DRAM. As such, it can act as a drop-in replacement for existing IMDBs. Our contributions are as follows:
(1) As the foundation for our research, we present Hyrise, an open-source, columnar IMDB that we re-engineered and re-wrote from scratch. Hyrise enables realistic end-to-end benchmarks of SQL workloads and offers query performance which is competitive with other research and commercial systems. At the same time, Hyrise is easy to understand and modify as repeatedly demonstrated by its uses in research and teaching.
(2) We present a novel memory management framework for different memory and storage tiers. By encapsulating the allocation and access methods of these tiers, we enable existing data structures to be stored on different tiers with no modifications to their implementation. Besides DRAM and NVM, we also support and evaluate SSDs and have made provisions for upcoming technologies such as disaggregated memory.
(3) To identify the parts of the data that can be moved to (s)lower tiers with little performance impact, we present a tracking method that identifies access skew both in the row and column dimensions and that detects patterns within consecutive accesses. Unlike existing methods that have substantial associated costs, our access counters exhibit no identifiable overhead in standard benchmarks despite their increased accuracy.
(4) Finally, we introduce a tiering algorithm that optimizes the data placement for a given memory budget. In the TPC-H benchmark, this allows us to move 90% of the data to NVM while the throughput is reduced by only 10.8% and the query latency is increased by 11.6%. With this, we outperform approaches that ignore the workload's access skew and access patterns and increase the query latency by 20% or more.
Individually, our contributions provide novel approaches to current challenges in systems engineering and database research. Combining them allows IMDBs to scale past the limits of DRAM while continuing to profit from the benefits of in-memory computing.
Moderne Technologien befähigen die beteiligten Akteure eines Produktionsprozesses die Informationsaufnahme, Entscheidungsfindung und -ausführung selbstständig auszuführen. Hierarchische Kontrollbeziehungen werden aufgelöst und die Entscheidungsfindung auf eine Vielzahl von Akteuren verteilt. Positive Folgen sind unter anderem die Nutzung lokaler Kompetenzen und ein schnelles Handeln vor Ort ohne (zeit-)aufwändige prozessübergreifende Planungsläufe durch eine zentrale Steuerungsinstanz. Die Bewertung der Dezentralität des Prozesses hilft beim Vergleich verschiedener Steuerungsstrategien und trägt so zur Beherrschung komplexerer Produktionsprozesse bei.
Obwohl die Kommunikationsstruktur der an der Entscheidungsfindung beteiligten Akteure zunehmend an Bedeutung gewinnt, existiert keine Methode, welche diese als Grundlage für die Operationalisierung der Dezentralität verwendet. Hier setzt diese Arbeit an. Es wird ein dreistufiges Bewertungsmodell entwickelt, dass die Dezentralität eines Produktionsprozesses auf Basis der Kommunikations- und Entscheidungsstruktur der am Prozess beteiligten, autonomen Akteure ermittelt.
Aufbauend auf einer Definition von Dezentralität von Produktionsprozessen werden Anforderungen an eine Kennzahl erhoben und - auf Basis der Kommunikationsstruktur - eine die strukturelle Autonomie der Akteure bestimmenden Kenngröße der sozialen Netzwerkanalyse ermittelt. Die Notwendigkeit der zusätzlichen Berücksichtigung der Entscheidungsstruktur wird basierend auf der Möglichkeit der Integration von Entscheidungsfindung und -ausführung begründet.
Die Differenzierung beider Faktoren bildet die Grundlage für die Klassifikation der Akteure; die Multiplikation beider Werte resultiert in dem die Autonomie eines Akteurs beschreibenden Kennwert tatsächliche Autonomie, welcher das Ergebnis der ersten Stufe des Modells darstellt. Homogene Akteurswerte charakterisieren eine hohe Dezentralität des Prozessschrittes, welcher Betrachtungsobjekt der zweiten Stufe ist. Durch einen Vergleich der vorhandenen mit der maximal möglichen Dezentralität der Prozessschritte wird auf der dritten Stufe der Autonomie Index ermittelt, welcher die Dezentralität des Prozesses operationalisiert.
Das erstellte Bewertungsmodell wird anhand einer Simulationsstudie im Zentrum Industrie 4.0 validiert. Dafür wird das Modell auf zwei Simulationsexperimente - einmal mit einer zentralen und einmal mit einer dezentralen Steuerung - angewendet und die Ergebnisse verglichen. Zusätzlich wird es auf einen umfangreichen Produktionsprozess aus der Praxis angewendet.
Die Zeit um 1600 markiert eine Zäsur in der Ausbildung junger Adliger, da neben der etablierten humanistischen Ausbildung zunehmend moderne Fremdsprachen und die institutionalisierte Ausbildung standesspezifischer Inhalte wie Fechten, Tanzen und Reiten an Bedeutung gewannen. Im vorliegenden Band werden die Ausbildungsgänge der Söhne dreier südwestdeutscher Freiherren- und Grafenfamilien in der Zeit des Späthumanismus untersucht. Dabei werden standesspezifische Bildungsstrategien herausgearbeitet und familiäre sowie konfessionelle Unterschiede aufgezeigt. Die Familien der Reichsgrafen orientierten sich – soweit es ihr Budget zuließ – einerseits am Fürstenstand, andererseits waren sie bestrebt, eigene Akzente zu setzen, sei es aus standespolitischen Erwägungen oder, weil sie eigenen Traditionen verpflichtet waren. Die systematische Auswertung breiter Quellenbestände förderte dabei auch eine Fülle an Informationen zu weiteren Wissensgebieten wie etwa der Reise-, Medizin-, Musikgeschichte oder der Alltagskultur zutage.
Bio-sourced adsorbing poly(2-oxazoline)s mimicking mussel glue proteins for antifouling applications
(2022)
Nature developed countless systems for many applications. In maritime environments, several organisms established extra-ordinary mechanisms to attach to surfaces. Over the past years, the scientific interest to employ those mechanisms for coatings and long-lasting adhering materials gained significant attention.
This work describes the synthesis of bio-inspired adsorbing copoly(2-oxazoline)s for surface coatings with protein repelling effects, mimicking mussel glue proteins. From a set of methoxy substituted phenyl, benzyl, and cinnamyl acids, 2-oxazoline monomers were synthesized. All synthesized 2-oxazolines were analyzed by FT-IR spectroscopy, NMR spectroscopy, and EI mass spectrometry. With those newly synthesized 2-oxazoline monomers and 2-ethyl-2-oxazoline, kinetic studies concerning homo- and copolymerization in a microwave reactor were conducted. The success of the polymerization reactions was demonstrated by FT-IR spectroscopy, NMR spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography (SEC). The copolymerization of 2-ethyl-2-oxazoline with a selection of methoxy-substituted 2-oxazolines resulted in water-soluble copolymers. To release the adsorbing catechol and cationic units, the copoly(2-oxazoline)s were modified. The catechol units were (partially) released by a methyl aryl ether cleavage reaction. A subsequent partial acidic hydrolysis of the ethyl unit resulted in mussel glue protein-inspired catechol and cation-containing copolymers. The modified copolymers were analyzed by NMR spectroscopy, UV-VIS spectroscopy, and SEC. The catechol- and cation-containing copolymers and their precursors were examined by a Quartz Crystal Microbalance with Dissipation (QCM-D), so study the adsorption performance on gold, borosilicate, iron, and polystyrene surfaces. An exemplary study revealed that a catechol and cation-containing copoly(2-oxazoline)-coated gold surface exhibits strong protein repelling properties.
Carbohydrates are found in every living organism, where they are responsible for numerous, essential biological functions and processes. Synthetic polymers with pendant saccharides, called glycopolymers, mimic natural glycoconjugates in their special properties and functions. Employing such biomimetics furthers the understanding and controlling of biological processes. Hence, glycopolymers are valuable and interesting for applications in the medical and biological field. However, the synthesis of carbohydrate-based materials can be very challenging. In this thesis, the synthesis of biofunctional glycopolymers is presented, with the focus on aqueous-based, protecting group free and short synthesis routes to further advance in the field of glycopolymer synthesis.
A practical and versatile precursor for glycopolymers are glycosylamines. To maintain biofunctionality of the saccharides after their amination, regioselective functionalization was performed. This frequently performed synthesis was optimized for different sugars. The optimization was facilitated using a design of experiment (DoE) approach to enable a reduced number of necessary experiments and efficient procedure. Here, the utility of using DoE for optimizing the synthesis of glycosylamines is discussed.
The glycosylamines were converted to glycomonomers which were then polymerized to yield biofunctional glycopolymers. Here, the glycopolymers were aimed to be applicable as layer-by-layer (LbL) thin film coatings for drug delivery systems. To enable the LbL technique, complimentary glycopolymer electrolytes were synthesized by polymerization of the glycomonomers and subsequent modification or by post-polymerization modification. For drug delivery, liposomes were embedded into the glycopolymer coating as potential cargo carriers. The stability as well as the integrity of the glycopolymer layers and liposomes were investigated at physiological pH range.
Different glycopolymers were also synthesized to be applicable as anti-adhesion therapeutics by providing advanced architectures with multivalent presentations of saccharides, which can inhibit the binding of pathogene lectins. Here, the synthesis of glycopolymer hydrogel particles based on biocompatible poly(N-isopropylacrylamide) (NiPAm) was established using the free-radical precipitation polymerization technique. The influence of synthesis parameters on the sugar content in the gels and on the hydrogel morphology is discussed. The accessibility of the saccharides to model lectins and their enhanced, multivalent interaction were investigated.
At the end of this work, the synthesis strategies for the glycopolymers are generally discussed as well as their potential application in medicine.
Cardiovascular diseases are the main cause of death worldwide, and their prevalence is expected to rise in the coming years. Polymer-based artificial replacements have been widely used for the treatment of cardiovascular diseases. Coagulation and thrombus formation on the interfaces between the materials and the human physiological environment are key issues leading to the failure of the medical device in clinical implantation. The surface properties of the materials have a strong influence on the protein adsorption and can direct the blood cell adhesion behavior on the interfaces. Furthermore, implant-associated infections will be induced by bacterial adhesion and subsequent biofilm formation at the implantation site. Thus, it is important to improve the hemocompatibility of an implant by altering the surface properties. One of the effective strategies is surface passivation to achieve protein/cell repelling ability to reduce the risk of thrombosis.
This thesis consists of synthesis, functionalization, sterilization, and biological evaluation of bulk poly(glycerol glycidyl ether) (polyGGE), which is a highly crosslinked polyether-based polymer synthesized by cationic ring-opening polymerization. PolyGGE is hypothesized to be able to resist plasma protein adsorption and bacterial adhesion due to analogous chemical structure as polyethylene glycol and hyperbranched polyglycerol. Hydroxyl end groups of polyGGE provide possibilities to be functionalized with sulfates to mimic the anti-thrombogenic function of the endothelial glycocalyx.
PolyGGE was synthesized by polymerization of the commercially available monomer glycerol glycidyl ether, which was characterized as a mixture of mono-, di- and tri-glycidyl ether. Cationic ring opening-polymerization of this monomer was carried out by ultraviolet (UV) initiation of the photo-initiator diphenyliodonium hexafluorophosphate. With the increased UV curing time, more epoxides in the side chains of the monomers participated in chemical crosslinking, resulting in an increase of Young’s modulus, while the value of elongation at break of polyGGE first increased due to the propagation of the polymer chains then decreased with the increase of crosslinking density. Eventually, the chain propagation can be effectively terminated by potassium hydroxide aqueous solution. PolyGGE exhibited different tensile properties in hydrated conditions at body temperature compared to the values in the dry state at room temperature. Both Young’s modulus and values of elongation at break were remarkably reduced when tested in water at 37 °C, which was above the glass transition temperature of polyGGE. At physiological conditions, entanglements of the ployGGE networks unfolded and the free volume of networks were replaced by water molecules as softener, which increased the mobility of the polymer chains, resulting in a lower Young’s modulus.
Protein adsorption analysis was performed on polyGGE films with 30 min UV curing using an enzyme-linked immunosorbent assay. PolyGGE could effectively prevent the adsorption of human plasma fibrinogen, albumin, and fibronectin at the interface of human plasma and polyGGE films. The protein resistance of polyGGE was comparable to the negative controls: the hemocompatible polydimethylsiloxane (PDMS), showing its potential as a coating material for cardiovascular implants. Moreover, antimicrobial tests of bacterial activity using isothermal microcalorimetry and the microscopic image of direct bacteria culturing demonstrated that polyGGE could directly interfere biofilm formation and growth of both Gram-negative and antibiotic-resistant Gram-positive bacteria, indicating the potential application of polyGGE for combating the risk of hospital-acquired infections and preventing drug-resistant superbug spreading.
To investigate its cell compatibility, polyGGE films were extracted by different solvents (ethanol, chloroform, acetone) and cell culture medium. Indirect cytotoxicity tests showed extracted polyGGE films still had toxic effects on L929 fibroblast cells. High-performance liquid chromatography/electrospray ionization mass spectrometry revealed the occurrence of organochlorine-containing compounds released during the polymer-cell culture medium interaction. A constant level of those organochlorine-containing compounds was confirmed from GGE monomer by a specific peak of C-Cl stretching in infrared spectra of GGE. This is assumed to be the main reason causing the increased cell membrane permeability and decreased metabolic activity, leading to cell death. Attempts as changing solvents were made to remove toxic substances, however, the release of these small molecules seems to be sluggish. The densely crosslinked polyGGE networks can possibly contribute to the trapping of organochlorine-containing compounds. These results provide valuable information for exploring the potentially toxic substances, leaching from polyGGE networks, and propose a feasible strategy for minimizing the cytotoxicity via reducing their crosslinking density.
Sulfamic acid/ N-Methyl-2-pyrrolidone (NMP) were selected as the reagents for the sulfation of polyGGE surfaces. Fourier transform attenuated total reflection infrared spectroscopy (ATR-FT-IR) was used to monitor the functionalization kinetics and the results confirmed the successful sulfate grafting on the surface of polyGGE with the covalent bond -C-O-S-. X-ray photoelectron spectroscopy was used to determine the element composition on the surface and the cross-section of the functionalized polyGGE and sulfation within 15 min guarantees the sulfation only takes place on the surface while not occurring in the bulk of the polymer. The concentration of grafted sulfates increased with the increasing reaction time. The hydrophilicity of the surface of polyGGE was highly increased due to the increase of negatively charged end groups. Three sterilization techniques including autoclaving, gamma irradiation, and ethylene oxide (EtO) sterilization were used for polyGGE sulfates. Results from ATR-FT-IR and Toluidine Blue O quantitative assay demonstrated the total loss of the sulfates after autoclave sterilization, which was also confirmed by the increased water contact angle. Little influence on the concentration of sulfates was found for gamma-irradiated and autoclaving sterilized polyGGE sulfates. To investigate the thermal influence on polyGGE sulfates, one strategy was to use poly(hydroxyethyl acrylate) sulfates (PHEAS) for modeling. The thermogravimetric analysis profile of PHEAS demonstrated that sulfates are not thermally stable independent of the substrate materials and decomposition of sulfates occurs at around 100 °C. Although gamma irradiation also showed little negative effect on the sulfate content, the color change in the polyGGE sulfates indicates chemical or physical change might occur in the polymer. EtO sterilization was validated as the most suitable sterilization technique to maintain the chemical structure of polyGGE sulfates.
In conclusion, the conducted work proved that bulk polyGGE can be used as an antifouling coating material and shows its antimicrobial potential. Sulfates functionalization can be effectively realized using sulfamic acid/NMP. EtO sterilization is the most suitable sterilization technique for grafted sulfates. Besides, this thesis also offers a good strategy for the analysis of toxic leachable substances using suitable physicochemical characterization techniques. Future work will focus on minimizing/eliminating the release of toxic substances via reducing the crosslinking density. Another interesting aspect is to study whether grafted sulfates can meet the need for anti-thrombogenicity.
Synthetische Transkriptionsfaktoren bestehen wie natürliche Transkriptionsfaktoren aus einer DNA-Bindedomäne, die sich spezifisch an die Bindestellensequenz vor dem Ziel-Gen anlagert, und einer Aktivierungsdomäne, die die Transkriptionsmaschinerie rekrutiert, sodass das Zielgen exprimiert wird. Der Unterschied zu den natürlichen Transkriptionsfaktoren ist, sowohl dass die DNA-Bindedomäne als auch die Aktivierungsdomäne wirtsfremd sein können und dadurch künstliche Stoffwechselwege im Wirt, größtenteils chemisch, induziert werden können. Optogenetische synthetische Transkriptionsfaktoren, die hier entwickelt wurden, gehen einen Schritt weiter. Dabei ist die DNA-Bindedomäne nicht mehr an die Aktivierungsdomäne, sondern mit dem Blaulicht-Photorezeptor CRY2 gekoppelt. Die Aktivierungsdomäne wurde mit dem Interaktionspartner CIB1 fusioniert. Unter Blaulichtbestrahlung dimerisieren CRY2 und CIB1 und damit einhergehend die beiden Domänen, sodass ein funktionsfähiger Transkriptionsfaktor entsteht. Dieses System wurde in die Saccharomyces cerevisiae genomisch integriert. Verifiziert wurde das konstruierte System mit Hilfe des Reporters yEGFP, welcher durchflusszytometrisch detektiert werden konnte. Es konnte gezeigt werden, dass die yEGFP Expression variabel gestaltet werden kann, indem unterschiedlich lange Blaulichtimpulse ausgesendet wurden, die DNA-Bindedomäne, die Aktivierungsdomäne oder die Anzahl der Bindestellen, an dem sich die DNA-Bindedomäne anlagert, verändert wurden. Um das System für industrielle Anwendungen attraktiv zu gestalten, wurde das System vom Deepwell-Maßstab auf Photobioreaktor-Maßstab hochskaliert. Außerdem erwies sich das Blaulichtsystem sowohl im Laborstamm YPH500 als auch im industriell oft verwendeten Hefestamm CEN.PK als funktional. Des Weiteren konnte ein industrierelevante Protein ebenso mit Hilfe des verifizierten Systems exprimiert werden. Schlussendlich konnte in dieser Arbeit das etablierte Blaulicht-System erfolgreich mit einem Rotlichtsystem kombiniert werden, was zuvor noch nicht beschrieben wurde.
The index theorem for elliptic operators on a closed Riemannian manifold by Atiyah and Singer has many applications in analysis, geometry and topology, but it is not suitable for a generalization to a Lorentzian setting.
In the case where a boundary is present Atiyah, Patodi and Singer provide an index theorem for compact Riemannian manifolds by introducing non-local boundary conditions obtained via the spectral decomposition of an induced boundary operator, so called APS boundary conditions. Bär and Strohmaier prove a Lorentzian version of this index theorem for the Dirac operator on a manifold with boundary by utilizing results from APS and the characterization of the spectral flow by Phillips. In their case the Lorentzian manifold is assumed to be globally hyperbolic and spatially compact, and the induced boundary operator is given by the Riemannian Dirac operator on a spacelike Cauchy hypersurface. Their results show that imposing APS boundary conditions for these boundary operator will yield a Fredholm operator with a smooth kernel and its index can be calculated by a formula similar to the Riemannian case.
Back in the Riemannian setting, Bär and Ballmann provide an analysis of the most general kind of boundary conditions that can be imposed on a first order elliptic differential operator that will still yield regularity for solutions as well as Fredholm property for the resulting operator. These boundary conditions can be thought of as deformations to the graph of a suitable operator mapping APS boundary conditions to their orthogonal complement.
This thesis aims at applying the boundary conditions found by Bär and Ballmann to a Lorentzian setting to understand more general types of boundary conditions for the Dirac operator, conserving Fredholm property as well as providing regularity results and relative index formulas for the resulting operators. As it turns out, there are some differences in applying these graph-type boundary conditions to the Lorentzian Dirac operator when compared to the Riemannian setting. It will be shown that in contrast to the Riemannian case, going from a Fredholm boundary condition to its orthogonal complement works out fine in the Lorentzian setting. On the other hand, in order to deduce Fredholm property and regularity of solutions for graph-type boundary conditions, additional assumptions for the deformation maps need to be made.
The thesis is organized as follows. In chapter 1 basic facts about Lorentzian and Riemannian spin manifolds, their spinor bundles and the Dirac operator are listed. These will serve as a foundation to define the setting and prove the results of later chapters.
Chapter 2 defines the general notion of boundary conditions for the Dirac operator used in this thesis and introduces the APS boundary conditions as well as their graph type deformations. Also the role of the wave evolution operator in finding Fredholm boundary conditions is analyzed and these boundary conditions are connected to notion of Fredholm pairs in a given Hilbert space.
Chapter 3 focuses on the principal symbol calculation of the wave evolution operator and the results are used to proof Fredholm property as well as regularity of solutions for suitable graph-type boundary conditions. Also sufficient conditions are derived for (pseudo-)local boundary conditions imposed on the Dirac operator to yield a Fredholm operator with a smooth solution space.
In the last chapter 4, a few examples of boundary conditions are calculated applying the results of previous chapters. Restricting to special geometries and/or boundary conditions, results can be obtained that are not covered by the more general statements, and it is shown that so-called transmission conditions behave very differently than in the Riemannian setting.
Plant metabolism is the main process of converting assimilated carbon to different crucial compounds for plant growth and therefore crop yield, which makes it an important research topic. Although major advances in understanding genetic principles contributing to metabolism and yield have been made, little is known about the genetics responsible for trait variation or canalization although the concepts have been known for a long time. In light of a growing global population and progressing climate change, understanding canalization of metabolism and yield seems ever-more important to ensure food security. Our group has recently found canalization metabolite quantitative trait loci (cmQTL) for tomato fruit metabolism, showing that the concept of canalization applies on metabolism. In this work two approaches to investigate plant metabolic canalization and one approach to investigate yield canalization are presented.
In the first project, primary and secondary metabolic data from Arabidopsis thaliana and Phaseolus vulgaris leaf material, obtained from plants grown under different conditions was used to calculate cross-environment coefficient of variations or fold-changes of metabolite levels per genotype and used as input for genome wide association studies. While primary metabolites have lower CV across conditions and show few and mostly weak associations to genomic regions, secondary metabolites have higher CV and show more, strong metabolite to genome associations. As candidate genes, both potential regulatory genes as well as metabolic genes, can be found, albeit most metabolic genes are rarely directly related to the target metabolites, suggesting a role for both potential regulatory mechanisms as well as metabolic network structure for canalization of metabolism.
In the second project, candidate genes of the Solanum lycopersicum cmQTL mapping are selected and CRISPR/Cas9-mediated gene-edited tomato lines are created, to validate the genes role in canalization of metabolism. Obtained mutants appeared to either have strong aberrant developmental phenotypes or appear wild type-like. One phenotypically inconspicuous mutant of a pantothenate kinase, selected as candidate for malic acid canalization shows a significant increase of CV across different watering conditions. Another such mutant of a protein putatively involved in amino acid transport, selected as candidate for phenylalanine canalization shows a similar tendency to increased CV without statistical significance. This potential role of two genes involved in metabolism supports the hypothesis of structural relevance of metabolism for its own stability.
In the third project, a mutant for a putative disulfide isomerase, important for thylakoid biogenesis, is characterized by a multi-omics approach. The mutant was characterized previously in a yield stability screening and showed a variegated leaf phenotype, ranging from green leaves with wild type levels of chlorophyll over differently patterned variegated to completely white leaves almost completely devoid of photosynthetic pigments. White mutant leaves show wild type transcript levels of photosystem assembly factors, with the exception of ELIP and DEG orthologs indicating a stagnation at an etioplast to chloroplast transition state. Green mutant leaves show an upregulation of these assembly factors, possibly acting as overcompensation for partially defective disulfide isomerase, which seems sufficient for proper chloroplast development as confirmed by a wild type-like proteome. Likely as a result of this phenotype, a general stress response, a shift to a sink-like tissue and abnormal thylakoid membranes, strongly alter the metabolic profile of white mutant leaves. As the severity and pattern of variegation varies from plant to plant and may be effected by external factors, the effect on yield instability, may be a cause of a decanalized ability to fully exploit the whole leaf surface area for photosynthetic activity.
Digital transformation (DT) has not only been a major challenge in recent years, it is also supposed to continue to enormously impact our society and economy in the forthcoming decade. On the one hand, digital technologies have emerged, diffusing and determining our private and professional lives. On the other hand, digital platforms have leveraged the potentials of digital technologies to provide new business models. These dynamics have a massive effect on individuals, companies, and entire ecosystems. Digital technologies and platforms have changed the way persons consume or interact with each other. Moreover, they offer companies new opportunities to conduct their business in terms of value creation (e.g., business processes), value proposition (e.g., business models), or customer interaction (e.g., communication channels), i.e., the three dimensions of DT. However, they also can become a threat for a company's competitiveness or even survival. Eventually, the emergence, diffusion, and employment of digital technologies and platforms bear the potential to transform entire markets and ecosystems.
Against this background, IS research has explored and theorized the phenomena in the context of DT in the past decade, but not to its full extent. This is not surprising, given the complexity and pervasiveness of DT, which still requires far more research to further understand DT with its interdependencies in its entirety and in greater detail, particularly through the IS perspective at the confluence of technology, economy, and society. Consequently, the IS research discipline has determined and emphasized several relevant research gaps for exploring and understanding DT, including empirical data, theories as well as knowledge of the dynamic and transformative capabilities of digital technologies and platforms for both organizations and entire industries.
Hence, this thesis aims to address these research gaps on the IS research agenda and consists of two streams. The first stream of this thesis includes four papers that investigate the impact of digital technologies on organizations. In particular, these papers study the effects of new technologies on firms (paper II.1) and their innovative capabilities (II.2), the nature and characteristics of data-driven business models (II.3), and current developments in research and practice regarding on-demand healthcare (II.4). Consequently, the papers provide novel insights on the dynamic capabilities of digital technologies along the three dimensions of DT. Furthermore, they offer companies some opportunities to systematically explore, employ, and evaluate digital technologies to modify or redesign their organizations or business models.
The second stream comprises three papers that explore and theorize the impact of digital platforms on traditional companies, markets, and the economy and society at large. At this, paper III.1 examines the implications for the business of traditional insurance companies through the emergence and diffusion of multi-sided platforms, particularly in terms of value creation, value proposition, and customer interaction. Paper III.2 approaches the platform impact more holistically and investigates how the ongoing digital transformation and "platformization" in healthcare lastingly transform value creation in the healthcare market. Paper III.3 moves on from the level of single businesses or markets to the regulatory problems that result from the platform economy for economy and society, and proposes appropriate regulatory approaches for addressing these problems. Hence, these papers bring new insights on the table about the transformative capabilities of digital platforms for incumbent companies in particular and entire ecosystems in general.
Altogether, this thesis contributes to the understanding of the impact of DT on organizations and markets through the conduction of multiple-case study analyses that are systematically reflected with the current state of the art in research. On this empirical basis, the thesis also provides conceptual models, taxonomies, and frameworks that help describing, explaining, or predicting the impact of digital technologies and digital platforms on companies, markets and the economy or society at large from an interdisciplinary viewpoint.
Characterization of the role of stress - responsive NAC transcription factors ANAC055 and ATAF1
(2022)
Over the past decades, there has been a growing interest in ‘extreme events’ owing to the increasing threats that climate-related extremes such as floods, heatwaves, droughts, etc., pose to society. While extreme events have diverse definitions across various disciplines, ranging from earth science to neuroscience, they are characterized mainly as dynamic occurrences within a limited time frame that impedes the normal functioning of a system. Although extreme events are rare in occurrence, it has been found in various hydro-meteorological and physiological time series (e.g., river flows, temperatures, heartbeat intervals) that they may exhibit recurrent behavior, i.e., do not end the lifetime of the system. The aim of this thesis to develop some
sophisticated methods to study various properties of extreme events.
One of the main challenges in analyzing such extreme event-like time series is that they have large temporal gaps due to the paucity of the number of observations of extreme events. As a result, existing time series analysis tools are usually not helpful to decode the underlying
information. I use the edit distance (ED) method to analyze extreme event-like time series in their unaltered form. ED is a specific distance metric, mainly designed to measure the similarity/dissimilarity between point process-like data. I combine ED with recurrence plot techniques to identify the recurrence property of flood events in the Mississippi River in the United States. I also use recurrence quantification analysis to show the deterministic properties
and serial dependency in flood events.
After that, I use this non-linear similarity measure (ED) to compute the pairwise dependency in extreme precipitation event series. I incorporate the similarity measure within the framework of complex network theory to study the collective behavior of climate extremes. Under this architecture, the nodes are defined by the spatial grid points of the given spatio-temporal climate dataset. Each node is associated with a time series corresponding to the temporal evolution
of the climate observation at that grid point. Finally, the network links are functions of the pairwise statistical interdependence between the nodes. Various network measures, such as degree, betweenness centrality, clustering coefficient, etc., can be used to quantify the network’s topology. We apply the methodology mentioned above to study the spatio-temporal coherence pattern of extreme rainfall events in the United States and the Ganga River basin, which reveals its relation to various climate processes and the orography of the region.
The identification of precursors associated with the occurrence of extreme events in the near future is extremely important to prepare the masses for an upcoming disaster and mitigate the potential risks associated with such events. Under this motivation, I propose an in-data prediction recipe for predicting the data structures that typically occur prior to extreme events using the Echo state network, a type of Recurrent Neural Network which is a part of the reservoir
computing framework. However, unlike previous works that identify precursory structures in the same variable in which extreme events are manifested (active variable), I try to predict these structures by using data from another dynamic variable (passive variable) which does not show large excursions from the nominal condition but carries imprints of these extreme events. Furthermore, my results demonstrate that the quality of prediction depends on the magnitude
of events, i.e., the higher the magnitude of the extreme, the better is its predictability skill. I show quantitatively that this is because the input signals collectively form a more coherent pattern for an extreme event of higher magnitude, which enhances the efficiency of the machine to predict the forthcoming extreme events.
It is well-known that individuals with aphasia (IWA) have difficulties understanding sentences that involve non-adjacent dependencies, such as object relative clauses or passives (Caplan, Baker, & Dehaut, 1985; Caramazza & Zurif, 1976). A large body of research supports the view that IWA’s grammatical system is intact, and that comprehension difficulties in aphasia are caused by a processing deficit, such as a delay in lexical access and/or in syntactic structure building (e.g., Burkhardt, Piñango, & Wong, 2003; Caplan, Michaud, & Hufford, 2015; Caplan, Waters, DeDe, Michaud, & Reddy, 2007; Ferrill, Love, Walenski, & Shapiro, 2012; Hanne, Burchert, De Bleser, & Vasishth, 2015; Love, Swinney, Walenski, & Zurif, 2008). The main goal of this dissertation is to computationally investigate the processing sources of comprehension impairments in sentence processing in aphasia.
In this work, prominent theories of processing deficits coming from the aphasia literature are implemented within two cognitive models of sentence processing –the activation-based model (Lewis & Vasishth, 2005) and the direct-access model (McEl- ree, 2000)–. These models are two different expressions of the cue-based retrieval theory (Lewis, Vasishth, & Van Dyke, 2006), which posits that sentence processing is the result of a series of iterative retrievals from memory. These two models have been widely used to account for sentence processing in unimpaired populations in multiple languages and linguistic constructions, sometimes interchangeably (Parker, Shvarts- man, & Van Dyke, 2017). However, Nicenboim and Vasishth (2018) showed that when both models are implemented in the same framework and fitted to the same data, the models yield different results, because the models assume different data- generating processes. Specifically, the models hold different assumptions regarding the retrieval latencies. The second goal of this dissertation is to compare these two models of cue-based retrieval, using data from individuals with aphasia and control participants. We seek to answer the following question: Which retrieval mechanism is more likely to mediate sentence comprehension?
We model 4 subsets of existing data: Relative clauses in English and German; and control structures and pronoun resolution in German. The online data come from either self-paced listening experiments, or visual-world eye-tracking experiments. The offline data come from a complementary sentence-picture matching task performed at the end of the trial in both types of experiments. The two competing models of retrieval are implemented in the Bayesian framework, following Nicenboim and Vasishth (2018). In addition, we present a modified version of the direct-acess model that – we argue – is more suitable for individuals with aphasia.
This dissertation presents a systematic approach to implement and test verbally- stated theories of comprehension deficits in aphasia within cognitive models of sen- tence processing. The conclusions drawn from this work are that (a) the original direct-access model (as implemented here) cannot account for the full pattern of data from individuals with aphasia because it cannot account for slow misinterpretations; and (b) an activation-based model of retrieval can account for sentence comprehension deficits in individuals with aphasia by assuming a delay in syntactic structure building, and noise in the processing system. The overall pattern of results support an activation-based mechanism of memory retrieval, in which a combination of processing deficits, namely slow syntax and intermittent deficiencies, cause comprehension difficulties in individuals with aphasia.
Localisation of deformation is a ubiquitous feature in continental rift dynamics and observed across drastically different time and length scales. This thesis comprises one experimental and two numerical modelling studies investigating strain localisation in (1) a ductile shear zone induced by a material heterogeneity and (2) in an active continental rift setting. The studies are related by the fact that the weakening mechanisms on the crystallographic and grain size scale enable bulk rock weakening, which fundamentally enables the formation of shear zones, continental rifts and hence plate tectonics. Aiming to investigate the controlling mechanisms on initiation and evolution of a shear zone, the torsion experiments of the experimental study were conducted in a Patterson type apparatus with strong Carrara marble cylinders with a weak, planar Solnhofen limestone inclusion. Using state-of-the-art numerical modelling software, the torsion experiments were simulated to answer questions regarding localisation procedure like stress distribution or the impact of rheological weakening. 2D numerical models were also employed to integrate geophysical and geological data to explain characteristic tectonic evolution of the Southern and Central Kenya Rift. Key elements of the numerical tools are a randomized initial strain distribution and the usage of strain softening. During the torsion experiments, deformation begins to localise at the limestone inclusion tips in a process zone, which propagates into the marble matrix with increasing deformation until a ductile shear zone is established. Minor indicators for coexisting brittle deformation are found close to the inclusion tip and presumed to slightly facilitate strain localisation besides the dominant ductile deformation processes. The 2D numerical model of the torsion experiment successfully predicts local stress concentration and strain rate amplification ahead of the inclusion in first order agreement with the experimental results. A simple linear parametrization of strain weaking enables high accuracy reproduction of phenomenological aspects of the observed weakening. The torsion experiments suggest that loading conditions do not affect strain localisation during high temperature deformation of multiphase material with high viscosity contrasts. A numerical simulation can provide a way of analysing the process zone evolution virtually and extend the examinable frame. Furthermore, the nested structure and anastomosing shape of an ultramylonite band was mimicked with an additional second softening step. Rheological weakening is necessary to establish a shear zone in a strong matrix around a weak inclusion and for ultramylonite formation.
Such strain weakening laws are also incorporated into the numerical models of the
Southern and Central Kenya Rift that capture the characteristic tectonic evolution. A three-stage early rift evolution is suggested that starts with (1) the accommodation of strain by a single border fault and flexure of the hanging-wall crust, after which (2) faulting in the hanging-wall and the basin centre increases before (3) the early-stage asymmetry is lost and basinward localisation of deformation occurs. Along-strike variability of rifts can be produced by modifying the initial random noise distribution. In summary, the three studies address selected aspects of the broad range of mechanisms and processes that fundamentally enable the deformation of rock and govern the localisation patterns across the scales. In addition to the aforementioned results, the first and second manuscripts combined, demonstrate a procedure to find new or improve on existing numerical formulations for specific rheologies and their dynamic weakening. These formulations are essential in addressing rock deformation from the grain to the global scale. As within the third study of this thesis, where geodynamic controls on the evolution of a rift were examined and acquired by the integration of geological and geophysical data into a numerical model.
This thesis is analyzing multiple coordination challenges which arise with the digital transformation of public administration in federal systems, illustrated by four case studies in Germany. I make various observations within a multi-level system and provide an in-depth analysis. Theoretical explanations from both federalism research and neo-institutionalism are utilized to explain the findings of the empirical driven work. The four articles evince a holistic picture of the German case and elucidate its role as a digital government laggard. Their foci range from macro, over meso to micro level of public administration, differentiating between the governance and the tool dimension of digital government.
The first article shows how multi-level negotiations lead to expensive but eventually satisfying solutions for the involved actors, creating a subtle balance between centralization and decentralization. The second article identifies legal, technical, and organizational barriers for cross-organizational service provision, highlighting the importance of inter-organizational and inter-disciplinary exchange and both a common language and trust. Institutional change and its effects on the micro level, on citizens and the employees in local one-stop shops, mark the focus of the third article, bridging the gap between reforms and the administrative reality on the local level. The fourth article looks at the citizens’ perspective on digital government reforms, their expectations, use and satisfaction. In this vein, this thesis provides a detailed account of the importance of understanding the digital divide and therefore the necessity of reaching out to different recipients of digital government reforms. I draw conclusions from the factors identified as causes for Germany’s shortcomings for other federal systems where feasible and derive reform potential therefrom. This allows to gain a new perspective on digital government and its coordination challenges in federal contexts.
Core-shell upconversion nanoparticles - investigation of dopant intermixing and surface modification
(2022)
Frequency upconversion nanoparticles (UCNPs) are inorganic nanocrystals capable to up-convert incident photons of the near-infrared electromagnetic spectrum (NIR) into higher energy photons. These photons are re-emitted in the range of the visible (Vis) and even ultraviolet (UV) light. The frequency upconversion process (UC) is realized with nanocrystals doped with trivalent lanthanoid ions (Ln(III)). The Ln(III) ions provide the electronic (excited) states forming a ladder-like electronic structure for the Ln(III) electrons in the nanocrystals. The absorption of at least two low energy photons by the nanoparticle and the subsequent energy transfer to one Ln(III) ion leads to the promotion of one Ln(III) electron into higher excited electronic states. One high energy photon will be emitted during the radiative relaxation of the electron in the excited state back into the electronic ground state of the Ln(III) ion. The excited state electron is the result of the previous absorption of at least two low energy photons.
The UC process is very interesting in the biological/medical context. Biological samples (like organic tissue, blood, urine, and stool) absorb high-energy photons (UV and blue light) more strongly than low-energy photons (red and NIR light). Thanks to a naturally occurring optical window, NIR light can penetrate deeper than UV light into biological samples. Hence, UCNPs in bio-samples can be excited by NIR light. This possibility opens a pathway for in vitro as well as in vivo applications, like optical imaging by cell labeling or staining of specific organic tissue. Furthermore, early detection and diagnosis of diseases by predictive and diagnostic biomarkers can be realized with bio-recognition elements being labeled to the UCNPs. Additionally, "theranostic" becomes possible, in which the identification and the treatment of a disease are tackled simultaneously.
For this to succeed, certain parameters for the UCNPs must be met: high upconversion efficiency, high photoluminescence quantum yield, dispersibility, and dispersion stability in aqueous media, as well as availability of functional groups to introduce fast and easy bio-recognition elements. The UCNPs used in this work were prepared with a solvothermal decomposition synthesis yielding in particles with NaYF4 or NaGdF4 as host lattice. They have been doped with the Ln(III) ions Yb3+ and Er3+, which is only one possible upconversion pair. Their upconversion efficiency and photoluminescence quantum yield were improved by adding a passivating shell to reduce surface quenching.
However, the brightness of core-shell UCNPs stays behind the expectations compared to their bulk material (being at least μm-sized particles). The core-shell structures are not clearly separated from each other, which is a topic in literature. Instead, there is a transition layer between the core and the shell structure, which relates to the migration of the dopants within the host lattice during the synthesis. The ion migration has been examined by time-resolved laser spectroscopy and the interlanthanoid resonance energy transfer (LRET) in the two different host lattices from above. The results are
presented in two publications, which dealt with core-shell-shell structured nanoparticles. The core is doped with the LRET-acceptor (either Nd3+ or Pr3+). The intermediate shell serves as an insulation shell of pure host lattice material, whose shell thickness has been varied within one set of samples having the same composition, so that the spatial separation of LRET-acceptor and -donor changes. The outer shell with the same host lattice is doped with the LRET-donor (Eu3+). The effect of the increasing insulation shell thickness is significant, although the LRET cannot be suppressed completely.
Next to the Ln(III) migration within a host lattice, various phase transfer reactions were investigated in order to subsequently perform surface modifications for bioapplications. One result out of this research has been published using a promising ligand, that equips the UCNP with bio-modifiable groups and has good potential for bio-medical applications. This particular ligand mimics natural occurring mechanisms of mussel protein adhesion and of blood coagulation, which is why the UCNPs are encapsulated very effectively. At the same time, bio-functional groups are introduced. In a proof-of-concept, the encapsulated UCNP has been coupled successfully with a dye (which is representative for a biomarker) and the system’s photoluminescence properties have been investigated.
The motivation for this work was the question of reliability and robustness of seismic tomography. The problem is that many earth models exist which can describe the underlying ground motion records equally well. Most algorithms for reconstructing earth models provide a solution, but rarely quantify their variability. If there is no way to verify the imaged structures, an interpretation is hardly reliable. The initial idea was to explore the space of equivalent earth models using Bayesian inference. However, it quickly became apparent that the rigorous quantification of tomographic uncertainties could not be accomplished within the scope of a dissertation.
In order to maintain the fundamental concept of statistical inference, less complex problems from the geosciences are treated instead. This dissertation aims to anchor Bayesian inference more deeply in the geosciences and to transfer knowledge from applied mathematics. The underlying idea is to use well-known methods and techniques from statistics to quantify the uncertainties of inverse problems in the geosciences. This work is divided into three parts:
Part I introduces the necessary mathematics and should be understood as a kind of toolbox. With a physical application in mind, this section provides a compact summary of all methods and techniques used. The introduction of Bayesian inference makes the beginning. Then, as a special case, the focus is on regression with Gaussian processes under linear transformations. The chapters on the derivation of covariance functions and the approximation of non-linearities are discussed in more detail.
Part II presents two proof of concept studies in the field of seismology. The aim is to present the conceptual application of the introduced methods and techniques with moderate complexity. The example about traveltime tomography applies the approximation of non-linear relationships. The derivation of a covariance function using the wave equation is shown in the example of a damped vibrating string. With these two synthetic applications, a consistent concept for the quantification of modeling uncertainties has been developed.
Part III presents the reconstruction of the Earth's archeomagnetic field. This application uses the whole toolbox presented in Part I and is correspondingly complex. The modeling of the past 1000 years is based on real data and reliably quantifies the spatial modeling uncertainties. The statistical model presented is widely used and is under active development.
The three applications mentioned are intentionally kept flexible to allow transferability to similar problems. The entire work focuses on the non-uniqueness of inverse problems in the geosciences. It is intended to be of relevance to those interested in the concepts of Bayesian inference.
The geomagnetic main field is vital for live on Earth, as it shields our habitat against the solar wind and cosmic rays. It is generated by the geodynamo in the Earth’s outer core and has a rich dynamic on various timescales. Global models of the field are used to study the interaction of the field and incoming charged particles, but also to infer core dynamics and to feed numerical simulations of the geodynamo. Modern satellite missions, such as the SWARM or the CHAMP mission, support high resolution reconstructions of the global field. From the 19 th century on, a global network of magnetic observatories has been established. It is growing ever since and global models can be constructed from the data it provides. Geomagnetic field models that extend further back in time rely on indirect observations of the field, i.e. thermoremanent records such as burnt clay or volcanic rocks and sediment records from lakes and seas. These indirect records come with (partially very large) uncertainties, introduced by the complex measurement methods and the dating procedure.
Focusing on thermoremanent records only, the aim of this thesis is the development of a new modeling strategy for the global geomagnetic field during the Holocene, which takes the uncertainties into account and produces realistic estimates of the reliability of the model. This aim is approached by first considering snapshot models, in order to address the irregular spatial distribution of the records and the non-linear relation of the indirect observations to the field itself. In a Bayesian setting, a modeling algorithm based on Gaussian process regression is developed and applied to binned data. The modeling algorithm is then extended to the temporal domain and expanded to incorporate dating uncertainties. Finally, the algorithm is sequentialized to deal with numerical challenges arising from the size of the Holocene dataset.
The central result of this thesis, including all of the aspects mentioned, is a new global geomagnetic field model. It covers the whole Holocene, back until 12000 BCE, and we call it ArchKalmag14k. When considering the uncertainties that are produced together with the model, it is evident that before 6000 BCE the thermoremanent database is not sufficient to support global models. For times more recent, ArchKalmag14k can be used to analyze features of the field under consideration of posterior uncertainties. The algorithm for generating ArchKalmag14k can be applied to different datasets and is provided to the community as an open source python package.
The complex hierarchical structure of bone undergoes a lifelong remodeling process, where it adapts to mechanical needs. Hereby, bone resorption by osteoclasts and bone formation by osteoblasts have to be balanced to sustain a healthy and stable organ. Osteocytes orchestrate this interplay by sensing mechanical strains and translating them into biochemical signals. The osteocytes are located in lacunae and are connected to one another and other bone cells via cell processes through small channels, the canaliculi. Lacunae and canaliculi form a network (LCN) of extracellular spaces that is able to transport ions and enables cell-to-cell communication. Osteocytes might also contribute to mineral homeostasis by direct interactions with the surrounding matrix. If the LCN is acting as a transport system, this should be reflected in the mineralization pattern. The central hypothesis of this thesis is that osteocytes are actively changing their material environment. Characterization methods of material science are used to achieve the aim of detecting traces of this interaction between osteocytes and the extracellular matrix. First, healthy murine bones were characterized. The properties analyzed were then compared with three murine model systems: 1) a loading model, where a bone of the mouse was loaded during its life time; 2) a healing model, where a bone of the mouse was cut to induce a healing response; and 3) a disease model, where the Fbn1 gene is dysfunctional causing defects in the formation of the extracellular tissue.
The measurement strategy included routines that make it possible to analyze the organization of the LCN and the material components (i.e., the organic collagen matrix and the mineral particles) in the same bone volumes and compare the spatial distribution of different data sets. The three-dimensional network architecture of the LCN is visualized by confocal laser scanning microscopy (CLSM) after rhodamine staining and is then subsequently quantified. The calcium content is determined via quantitative backscattered electron imaging (qBEI), while small- and wide-angle X-ray scattering (SAXS and WAXS) are employed to determine the thickness and length of local mineral particles.
First, tibiae cortices of healthy mice were characterized to investigate how changes in LCN architecture can be attributed to interactions of osteocytes with the surrounding bone matrix. The tibial mid-shaft cross-sections showed two main regions, consisting of a band with unordered LCN surrounded by a region with ordered LCN. The unordered region is a remnant of early bone formation and exhibited short and thin mineral particles. The surrounding, more aligned bone showed ordered and dense LCN as well as thicker and longer mineral particles. The calcium content was unchanged between the two regions.
In the mouse loading model, the left tibia underwent two weeks of mechanical stimulation, which results in increased bone formation and decreased resorption in skeletally mature mice. Here the specific research question addressed was how do bone material characteristics change at (re)modeling sites? The new bone formed in response to mechanical stimulation showed similar properties in terms of the mineral particles, like the ordered calcium region but lower calcium content compared to the right, non-loaded control bone of the same mice. There was a clear, recognizable border between mature and newly formed bone. Nevertheless, some canaliculi went through this border connecting the LCN of mature and newly formed bone.
Additionally, the question should be answered whether the LCN topology and the bone matrix material properties adapt to loading. Although, mechanically stimulated bones did not show differences in calcium content compared to controls, different correlations were found between the local LCN density and the local Ca content depending on whether the bone was loaded or not. These results suggest that the LCN may serve as a mineral reservoir.
For the healing model, the femurs of mice underwent an osteotomy, stabilized with an external fixator and were allowed to heal for 21 days. Thus, the spatial variations in the LCN topology with mineral properties within different tissue types and their interfaces, namely calcified cartilage, bony callus and cortex, could be simultaneously visualized and compared in this model. All tissue types showed structural differences across multiple length scales. Calcium content increased and became more homogeneous from calcified cartilage to bony callus to lamellar cortical bone. The degree of LCN organization increased as well, while the lacunae became smaller, as did the lacunar density between these different tissue types that make up the callus. In the calcified cartilage, the mineral particles were short and thin. The newly formed callus exhibited thicker mineral particles, which still had a low degree of orientation. While most of the callus had a woven-like structure, it also served as a scaffold for more lamellar tissue at the edges. The lamelar bone callus showed thinner mineral particles, but a higher degree of alignment in both, mineral particles and the LCN. The cortex showed the highest values for mineral length, thickness and degree of orientation. At the same time, the lacunae number density was 34% lower and the lacunar volume 40% smaller compared to bony callus. The transition zone between cortical and callus regions showed a continuous convergence of bone mineral properties and lacunae shape. Although only a few canaliculi connected callus and the cortical region, this indicates that communication between osteocytes of both tissues should be possible. The presented correlations between LCN architecture and mineral properties across tissue types may suggest that osteocytes have an active role in mineralization processes of healing.
A mouse model for the disease marfan syndrome, which includes a genetic defect in the fibrillin-1 gene, was investigated. In humans, Marfan syndrome is characterized by a range of clinical symptoms such as long bone overgrowth, loose joints, reduced bone mineral density, compromised bone microarchitecture, and increased fracture rates. Thus, fibrillin-1 seems to play a role in the skeletal homeostasis. Therefore, the present work studied how marfan syndrome alters LCN architecture and the surrounding bone matrix. The mice with marfan syndrome showed longer tibiae than their healthy littermates from an age of seven weeks onwards. In contrast, the cortical development appeared retarded, which was observed across all measured characteristics, i. e. lower endocortical bone formation, looser and less organized lacuno-canalicular network, less collagen orientation, thinner and shorter mineral particles.
In each of the three model systems, this study found that changes in the LCN architecture spatially correlated with bone matrix material parameters. While not knowing the exact mechanism, these results provide indications that osteocytes can actively manipulate a mineral reservoir located around the canaliculi to make a quickly accessible contribution to mineral homeostasis. However, this interaction is most likely not one-sided, but could be understood as an interplay between osteocytes and extra-cellular matrix, since the bone matrix contains biochemical signaling molecules (e.g. non-collagenous proteins) that can change osteocyte behavior. Bone (re)modeling can therefore not only be understood as a method for removing defects or adapting to external mechanical stimuli, but also for increasing the efficiency of possible osteocyte-mineral interactions during bone homeostasis. With these findings, it seems reasonable to consider osteocytes as a target for drug development related to bone diseases that cause changes in bone composition and mechanical properties. It will most likely require the combined effort of materials scientists, cell biologists, and molecular biologists to gain a deeper understanding of how bone cells respond to their material environment.
Cosmic rays (CRs) are a ubiquitous and an important component of astrophysical environments such as the interstellar medium (ISM) and intracluster medium (ICM). Their plasma physical interactions with electromagnetic fields strongly influence their transport properties. Effective models which incorporate the microphysics of CR transport are needed to study the effects of CRs on their surrounding macrophysical media. Developing such models is challenging because of the conceptional, length-scale, and time-scale separation between the microscales of plasma physics and the macroscales of the environment. Hydrodynamical theories of CR transport achieve this by capturing the evolution of CR population in terms of statistical moments. In the well-established one-moment hydrodynamical model for CR transport, the dynamics of the entire CR population are described by a single statistical quantity such as the commonly used CR energy density. In this work, I develop a new hydrodynamical two-moment theory for CR transport that expands the well-established hydrodynamical model by including the CR energy flux as a second independent hydrodynamical quantity. I detail how this model accounts for the interaction between CRs and gyroresonant Alfvén waves. The small-scale magnetic fields associated with these Alfvén waves scatter CRs which fundamentally alters CR transport along large-scale magnetic field lines. This leads to the effects of CR streaming and diffusion which are both captured within the presented hydrodynamical theory. I use an Eddington-like approximation to close the hydrodynamical equations and investigate the accuracy of this closure-relation by comparing it to high-order approximations of CR transport. In addition, I develop a finite-volume scheme for the new hydrodynamical model and adapt it to the moving-mesh code Arepo. This scheme is applied using a simulation of a CR-driven galactic wind. I investigate how CRs launch the wind and perform a statistical analysis of CR transport properties inside the simulated circumgalactic medium (CGM). I show that the new hydrodynamical model can be used to explain the morphological appearance of a particular type of radio filamentary structures found inside the central molecular zone (CMZ). I argue that these harp-like features are synchrotron-radiating CRs which are injected into braided magnetic field lines by a point-like source such as a stellar wind of a massive star or a pulsar. Lastly, I present the finite-volume code Blinc that uses adaptive mesh refinement (AMR) techniques to perform simulations of radiation and magnetohydrodynamics (MHD). The mesh of Blinc is block-structured and represented in computer memory using a graph-based approach. I describe the implementation of the mesh graph and how a diffusion process is employed to achieve load balancing in parallel computing environments. Various test problems are used to verify the accuracy and robustness of the employed numerical algorithms.
Schulleitungen nehmen eine zentrale Rolle bei der Weiterentwicklung der schulischen Qualität ein. Hierfür existieren Hinweise empirischer Untersuchungen, die Schulleitungen attestieren, dass ihr berufliches Handeln im direkten Zusammenhang mit Strukturen und Prozessen der schulischen Arbeit und mit Merkmalen auf Ebene der Lehrkräfte steht (z.B. Berufszufriedenheit, professionelle Weiterentwicklung; Kim & Lee, 2020; Liu, Keeley, Sui & Sang, 2021). Über diese Zusammenhänge steht das Führungshandeln von Schulleitungen in einer indirekten Beziehung mit der Qualität des Unterrichts sowie mit den Leistungen von Schüler*innen (z.B. Grissom, Egalite & Lindsay, 2021; Özdemir, Gün & Yirmibes, 2021; Pietsch, Lücken, Thonke, Klitsche & Musekamp, 2016). Im Rahmen der schulischen Entwicklung tragen Schulleitungen wesentlich dazu bei, die Entwicklungsbedarfe der Schule zu identifizieren, konkrete Zielstellungen zu definieren sowie entsprechende Maßnahmen zur Erreichung dieser Ziele zu planen, zu implementieren und zu evaluieren (vgl. Dalin, Rolff & Buchen, 1998). In all diese Prozesse können Schulleitungen weitere Mitglieder ihres Leitungsteams sowie Lehrkräfte involvieren und ihnen somit indirekt Führungsverantwortung übertragen (Heck & Hallinger, 2010). Auch aus normativer Perspektive nehmen Schulleitungen eine wichtige Funktion für die schulische Qualität ein. So verfügen sie neben Aufgaben der Administration und Verwaltung der Schule auch zunehmend über die Verantwortung, die schulische Qualität weiterzuentwickeln (Schratz, Wiesner, Kemethofer, George, Rauscher, Krenn & Huber, 2016). In Anbetracht der hohen Relevanz schulischen Führungshandelns für die Schulentwicklung, müssen Schulleitungen über die Kompetenzen zur Ausübung entsprechender Tätigkeiten verfügen. Diese können sie im Zuge einer vorbereitenden Ausbildung sowie durch Angebote der berufsbegleitenden Fort- und Weiterbildung erwerben. Die vorliegende Dissertation schließt an bestehende Forschungsarbeiten an und untersucht mithilfe von insgesamt vier Teilstudien, (1) über welche Aufgaben Schulleitungen hinsichtlich der Schulentwicklung verfügen, (2) wie ihr Handeln mit der Kooperation von Lehrkräften zusammenhängt, (3) wie sie die Zusammenarbeit von Lehrkräften im Rahmen der Schulentwicklung fördern können und (4) wie Schulleitungen auf Tätigkeiten der Schulentwicklung im Rahmen einer Fortbildung vorbereitet werden können. Insgesamt unterstreichen die vier Teilstudien in vielfältiger Weise die Relevanz von Schulleitungen und ihrem beruflichen Handeln für Strukturen und Prozesse der Schulentwicklung. Die Befunde können zeigen, inwiefern Schulleitungen über Aufgaben im Bereich der Schulentwicklung verfügen, wir ihr Handeln mit der Partizipation und Zusammenarbeit und von Lehrkräften im Rahmen der Schulentwicklung zusammenhängt und wie Schulleitungen auf Tätigkeiten der Schulentwicklung im Kontext von Fortbildungen vorbereitet werden können. Diesen Befunden sollte in Zukunft Rechnung getragen werden, indem Schulleitungen einerseits mehr Zeiten und Möglichkeiten für Tätigkeiten der Schulentwicklung eingeräumt werden. Anderseits betonen die Befunde die hohe Relevanz grundständig ausgebildeter Schulleitungen, um die Qualität der schulischen Arbeit längerfristig und eigenverantwortlich weiterentwickeln zu können. Dies sollte im Rahmen der Aus- und Fortbildung von Schulleitungen berücksichtigt werden.
Die vorliegende Arbeit vertritt die These, dass Hegels Wissenschaft der Logik mit einer Konzeption von Absolutheit Ernst zu machen versucht, nach der es kein Außerhalb des Absoluten geben kann. Dies macht sich bereits im Anfang der Logik bemerkbar: Wenn es nichts außerhalb des Absoluten geben kann, dann darf auch der Anfang nicht außerhalb des Absoluten sein. Folglich kann der Anfang nur mit dem Absoluten gemacht werden. Das Setzen des Anfangs als absolut ist aber gleichzeitig ein Testen des Anfangs auf seine Absolutheit. Diese Prüfung kann der Anfang nicht bestehen. Denn es liegt im Wesen eines Anfangs, nur Anfang und nicht das Ganze und somit nicht das Absolute zu sein. Der Anfang ist am weitesten davon entfernt, das Ganze zu sein, und muss folglich als das Nicht-Absoluteste innerhalb der Logik betrachtet werden. Also ist er beides: Er ist ein Anfang mit dem Absoluten und er ist ein Anfang mit dem Nicht-Absolutesten. Die Logik widerspricht sich bereits in ihrem Anfang. Von diesem Widerspruch muss sie sich befreien. Diese Befreiung treibt den Gang vom Anfang fort. Dies erzeugt den Fortgang der Logik. Die anfängliche Bestimmung hebt sich auf und geht in ihre Folgebestimmung über. Die Folgebestimmung wird ihrerseits absolut gesetzt, kann dieser Setzung aber ebenfalls nicht gerecht werden und hebt sich in ihre Folgebestimmung auf. Eine jede Bestimmung, die auf den Anfang folgt, durchläuft diese Bewegung des Absolutsetzens, Daran-Scheiterns und Sich-Aufhebens, bis – ganz am Ende der Logik – ebendiese Bewegung als dasjenige erkannt wird, was allein vermögend ist, dem Anspruch auf Absolutheit zu genügen. Denn wenn eine jede Bestimmung dieser Bewegung unterworfen ist, dann gibt es kein Außerhalb zu dieser Bewegung. Und also muss sie das gesuchte Absolute sein.
Auf ihrem Weg hin zur wahren Bedeutung des Absoluten kehrt die Logik immer wieder in die Bestimmung ihres Anfangs zurück, um Voraussetzungen einzuholen, die in Zusammenhang mit ihrem Anfang gemacht werden mussten. Für das Einholen dieser Voraussetzungen werden folgende Textstellen von Interesse sein: der Übergang in die Wesenslogik, der Übergang in die Begriffslogik und das Schlusskapitel. Denn auch zuallerletzt, in ihrem Ende kehrt die Logik in ihren Anfang zurück. Entsprechend kann mit Hegel gesagt werden: Das Erste ist auch das Letzte und das Letzte ist auch das Erste.
Die Studie analysiert das brandenburgisch-preußische Gesandtschaftszeremoniell um 1700. Der Untersuchungszeitraum, von 1648 bis 1740, umfasst die Regentschaft dreier Hohenzollern, veranschaulicht vorhandene Kontinuitäten und erläutert den Einfluss einzelner Personen auf das Zeremoniell. Zugleich wird die Entwicklung des Gesandtschaftszeremoniells an sich über einen längeren Zeitraum verfolgt. Hier offenbart sich, die Vorgänge am und das Vorgehen des Berliner Hofes muten geradezu exemplarisch an. Die Hohenzollern waren Vertreter der allgemein vorherrschenden zeremoniellen Konjunkturen. In der vorliegenden Arbeit werden wiederkehrende Muster und Mechanismen des Gesandtschaftszeremoniells, sei es das Aufeinderbeziehen von Forderungen, der beständige Vergleich mit den übrigen Mächten oder die Darstellung von Abhängigkeiten, aufgezeigt. Es wird analysiert, welche Elemente einander bedingten, wie diese zusammenwirkten und welche Bestandteile häufig zu Diskussionen führten.
Das Image der Päpste
(2022)
Wie jede öffentlichkeitssuchende Institution oder Person legen auch die katholische Kirche und ihre Päpste großen Wert auf das eigene Image. Dabei weicht die intendierte Selbstdarstellung oftmals von der medialen Wahrnehmung ab oder steht ihr sogar diametral entgegen. Ganz gleich ob Pius XII. als „Hitlers Papst“, Johannes XXIII. als „Revoluzzer“ oder Paul VI. als „Antipillenpapst“ – es existieren eine Fülle von außen zugetragener printmedialer Papst-Images, deren Entstehung, Verlauf und Brüche es in diesem Buch mithilfe einer mediensemiotischen, textbasierten Methodik auszumachen und nachzuzeichnen gilt.
Das kolonisierte Heiligtum
(2022)
Während der Zeit des historischen Kolonialismus wurden in Völkerkundemuseen komplexe Formen rassistischer und religiöser Diskriminierung institutionalisiert, z.B. in den dort gültigen Ästhetik- und Kunstbegriffen. Viele der heutigen Museumsangestellten erklären sich deswegen zu Reformen bereit. Doch können sie sich tatsächlich vom Kolonialismus trennen? Ist eine Dekolonisation ethnologischer Museen mit kolonialer Beute je abschließend möglich? Am Beispiel umstrittener Heiligtümer lebender Kulturen untersucht Christoph Balzar das Verfahren der Musealisierung durch die Linse der Diskriminierungskritik. Im Fokus stehen dabei die Sammlungen der »Staatlichen Museen zu Berlin«.
Dass das Wohlergehen künftig lebender Individuen moralische Berücksichtigung verdient, ist unbestritten. Sowohl im Rahmen des öffentlichen Diskurses als auch in der akademischen Umwelt- oder Zukunftsethik wird diese Ansicht vertreten.Durch das Problem der Nicht-Identität wird sie jedoch auf empfindliche Weise in Frage gestellt: Wie kann eine Handlung wie die Verschwendung begrenzt verfügbarer Ressourcen falsch sein, wenn die faktisch davon betroffenen künftig lebenden Individuen nur durch sie in die Existenz gelangen konnten? Gilt dann nicht, dass diese Handlung für niemanden schlecht ist und keine Schädigung darstellt? Dieses Buch verfolgt das Ziel zu verdeutlichen, wie das moralische Unrecht, das künftig lebende Individuen durch Handlungen gegenwärtig lebender Akteur:innen erfahren – trotz des Faktums der Nicht-Identität – mithilfe eines nicht-personenbezogenen Prinzips identifiziert und das Problem der Nicht-Identität somit gelöst werden kann.
Das Totenfürsorgerecht
(2022)
Die vorliegende Untersuchung befasst sich mit den allgegenwärtigen Fragen, welches rechtliche Schicksal der menschliche Körper nach dem Tod nimmt, ob der Leichnam vererbt wird und wer in welchem Umfang über ihn bestimmen darf. Die Autorin gelangt zu dem Ergebnis, dass das Totenfürsorgerecht als wesentlicher Bestandteil des - im Grundgesetz als Staatszielbestimmung zu verankernden - sog. postmortalen Persönlichkeitsschutzes auf die Wahrung der Pietät ziele und zuvörderst dem Willen des Verstorbenen verpflichtet sei. Bei unbekanntem Verstorbenenwillen dürfe der Totenfürsorgeberechtigte aber in einigen wenigen Bereichen auch eigene Entscheidungen über den ihm anvertrauten Leichnam treffen. Der Umgang mit dem Leichnam lasse sich bislang keinem bekannten Rechtsinstitut zuordnen und stelle Gewohnheitsrecht dar. Gegenwärtig herrsche Rechtsunsicherheit. Zur Behebung des gesetzgeberischen Defizits schlägt die Autorin ein Bundesgesetz vor und unterbreitet hierfür einen Gesetzesvorschlag.
Das vergessene Gedenken
(2022)
Seit Aufstellung der Bundeswehr 1955 verloren über 3300 Soldaten und Soldatinnen ihr Leben im Dienst. Nur eine kleine Minderheit von ihnen fiel während des Kampfeinsatzes in Afghanistan. Die weitaus meisten Soldaten starben bei Unfällen. Ihnen hat die Bundeswehr lange das öffentliche Gedenken verweigert.
Erst mit Beginn des Afghanistan-Einsatzes 2002 setzte letztlich ein Umdenken ein, das in der Einweihung des Berliner Ehrenmales der Bundeswehr 2009 seinen vorläufigen Höhepunkt findet. Seitdem gedenkt die Bundeswehr offiziell und öffentlich ihrer toten Soldaten.
Aber warum verweigerte die Bundeswehr ihren Toten so lange ein öffentlich sichtbares und dauerhaftes Gedenken?
Julia Katharina Nordmann beleuchtet die komplexen Ursachen für diesen Umgang der Bundeswehr mit ihren Toten. Und sie rekonstruiert den langen und mühsamen Prozess, der zur Ausbildung einer Gedenkkultur geführt hat. Einer Gedenkkultur, die heute in vielfältiger Weise die Toten der Bundeswehr würdigt.
Der Gefährdungsschaden
(2022)
Das Konzept des Gefährdungsschadens gehört seit mindestens 130 Jahren zum festen strafrechtlichen Repertoire. Allerdings ist bis heute nicht eindeutig geklärt, wo die Grenze zwischen vermögensrelevanten und -irrelevanten Gefährdungen verläuft. Im Gegensatz zu den bisherigen sachverhalts- und deliktsbezogenen Fallgruppen bildet Melanie Epe daher zehn induktiv-dogmatische Fallgruppen auf Basis aller in der Standardliteratur publizierten 382 Entscheidungen des Reichsgerichts, des BGH und der Obergerichte. Die Leistungsfähigkeit der Fallgruppen ist, dass diese die Figur des Gefährdungsschadens in der Praxis greifbarer machen. Denn es wird an dogmatische, wirtschaftliche Besonderheiten für die Begründung des Gefährdungsschadens angeknüpft.
In der fortwährenden Diskussion zur Familienbesteuerung bewertet der Autor vor dem Hintergrund des deutschen Verfassungsrechts die geltenden Regelungen und mögliche Reformmodelle rechtlich, steuerpolitisch und ökonomisch. Unter dem besonderen Blickwinkel eines seit mehr als 20 Jahren tätigen Steuerberaters kann der Autor die Wirkung des Splittingtarifs und deren Alternativen ökonomisch gut durchdringen.
Die Ehe und Familie stehen unter dem besonderen Schutz der deutschen staatlichen Ordnung. Diese Schutzpflicht aus Art. 6 Abs. 1 GG geht deutlich über ein Abwehrrecht hinaus. Sie gebietet es, die Ehe zu schützen, ihr einen grundsätzlich unantastbaren Kernbereich privater Lebensführung zu gewähren und innerfamiliär staatlicherseits keine bestimmte innereheliche Arbeits- und Aufgabenverteilung vorzuschreiben.
Die Ehe wird häufig als „Keimzelle“ jeglicher menschlichen Gesellschaft bezeichnet. Das erscheint folgerichtig und historisch bedeutsam. Im heutigen Zeitalter jedoch ist sie mehr oder weniger eine Erwerbs-, Konsum- und Verantwortungsgemeinschaft. Insofern stellt sich vornehmlich die Frage nach einer genügenden Rechtfertigung für die Gewährung eines Splittingtarifs.
Ausgangspunkt der umfassenden systematischen Darstellung ist die historischen Entwicklung in Deutschland und den angrenzenden Staaten; insbesondere der heutigen Europäischen Union. Denn in anderen Staaten werden bereits unterschiedliche Modelle wie beispielsweise die Einzel- oder Familienbesteuerung angewendet.
Verfassungsrechtlich hat der Gesetzgeber Veränderungen der gesellschaftlichen Rahmenbedingungen in und für die Familie in seine gesetzgeberischen Entscheidungen zwingend einzubeziehen. Es stellt sich demnach die Frage, ob beispielsweise seit der Entscheidung des Bundesverfassungsgerichts zum Ehegattensplitting im Jahr 1957 relevante Veränderungen eingetreten sind, die eine Änderung der Familienbesteuerung rechtfertigen oder gar erfordern. Die zwischenzeitliche Anerkennung von Lebenspartnerschaften und die Ehe für alle sind Ausdruck einer solchen Veränderung. Sie implizieren die bereits eingetretenen Veränderungen der Lebensverhältnisse. Daher ist die politische Diskussion für eine Veränderung nachvollziehbar. Ob jedoch Alternativen vorzugswürdig sind, wird ausführlich dargestellt.