Refine
Year of publication
Document Type
- Doctoral Thesis (3195) (remove)
Language
- English (3195) (remove)
Keywords
- climate change (52)
- Klimawandel (51)
- Modellierung (27)
- Nanopartikel (22)
- machine learning (22)
- Arabidopsis thaliana (17)
- Blickbewegungen (17)
- Fernerkundung (17)
- Arktis (15)
- Synchronisation (15)
Institute
- Institut für Biochemie und Biologie (746)
- Institut für Physik und Astronomie (554)
- Institut für Geowissenschaften (409)
- Institut für Chemie (348)
- Extern (146)
- Institut für Informatik und Computational Science (129)
- Institut für Mathematik (126)
- Institut für Umweltwissenschaften und Geographie (118)
- Institut für Ernährungswissenschaft (116)
- Department Linguistik (98)
Skepticism
(2022)
This dissertation offers new and original readings of three major texts in the history of Western philosophy: Descartes’s “First Meditation,” Kant’s “Transcendental Deduction,” and his “Refutation of Idealism.” The book argues that each text addresses the problem of skepticism and posits that they have a hitherto underappreciated, organic relationship to one another. The dissertation begins with an analysis of Descartes’ “First Meditation,” which I argue offers two distinct and independent skeptical arguments that differ in both aim and scope. I call these arguments the “veil of ideas” argument and the “author of my origin” argument. My reading counters the standard interpretation of the text, which sees it as offering three stages of doubt, namely the occasional fallibility of the senses, the dream hypothesis, and the evil demon hypothesis. Building on this, the central argument of the dissertation is that Kant’s “Transcendental Deduction” actually transforms and radicalizes Descartes’s Author of My Origin argument, reconceiving its meaning within the framework of Kant’s own transcendental idealist philosophy. Finally, I argue that the Refutation of Idealism offers a similarly radicalized version of Descartes’s Veil of Ideas argument, albeit translated into the framework of transcendental idealism.
The experience of premenstrual syndrome (PMS) affects up to 90% of individuals with an active menstrual cycle and involves a spectrum of aversive physiological and psychological symptoms in the days leading up to menstruation (Tschudin et al., 2010). Despite its high prevalence, the precise origins of PMS remain elusive, with influences ranging from hormonal fluctuations to cognitive, social, and cultural factors (Hunter, 2007; Matsumoto et al., 2013).
Biologically, hormonal fluctuations, particularly in gonadal steroids, are commonly believed to be implicated in PMS, with the central factor being varying susceptibilities to the fluctuations between individuals and cycles (Rapkin & Akopians, 2012). Allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite, has emerged as a potential link to PMS symptoms (Hantsoo & Epperson, 2020). ALLO is a positive allosteric modulator of the GABAA receptor, influencing inhibitory communication (Rupprecht, 2003; Andréen et al., 2006). Different susceptibility to ALLO fluctuations throughout the cycle may lead to reduced GABAergic signal transmission during the luteal phase of the menstrual cycle.
The GABAergic system's broad influence leads to a number of affected physiological systems, including a consistent reduction in vagally mediated heart rate variability (vmHRV) during the luteal phase (Schmalenberger et al., 2019). This reduction in vmHRV is more pronounced in individuals with high PMS symptoms (Baker et al., 2008; Matsumoto et al., 2007). Fear conditioning studies have shown inconsistent associations with cycle phases, suggesting a complex interplay between physiological parameters and PMS-related symptoms (Carpenter et al., 2022; Epperson et al., 2007; Milad et al., 2006).
The neurovisceral integration model posits that vmHRV reflects the capacity of the central autonomous network (CAN), which is responsible for regulatory processes on behavioral, cognitive, and autonomous levels (Thayer & Lane, 2000, 2009). Fear learning, mediated within the CAN, is suggested to be indicative of vmHRV's capacity for successful
VI
regulation (Battaglia & Thayer, 2022). Given the GABAergic mediation of central inhibitory functional connectivity in the CAN, which may be affected by ALLO fluctuations, this thesis proposes that fluctuating CAN activity in the luteal phase contributes to diverse aversive symptoms in PMS.
A research program was designed to empirically test these propositions. Study 1 investigated fear discrimination during different menstrual cycle phases and its interaction with vmHRV, revealing nuanced effects on acoustic startle response and skin conductance response. While there was heightened fear discrimination in acoustic startle responses in participants in the luteal phase, there was an interaction between menstrual cycle phase and vmHRV in skin conductance responses. In this measure, heightened fear discrimination during the luteal phase was only visible in individuals with high resting vmHRV; those with low vmHRV showed reduced fear discrimination and higher overall responses.
Despite affecting the vast majority of menstruating people, there are very limited tools available to reliably assess these symptoms in the German speaking area. Study 2 aimed at closing this gap, by translating and validating a German version of the short version of the Premenstrual Assessment Form (Allen et al., 1991), providing a reliable tool for future investigations, which closes the gap in PMS questionnaires in the German-speaking research area.
Study 3 employed a diary study paradigm to explore daily associations between vmHRV and PMS symptoms. The results showed clear simultaneous fluctuations between the two constructs with a peak in PMS and a low point in vmHRV a few days before menstruation onset. The association between vmHRV and PMS was driven by psychological PMS symptoms.
Based on the theoretical considerations regarding the neurovisceral perspective on PMS, another interesting construct to consider is attentional control, as it is closely related to functions of the CAN. Study 4 delved into attentional control and vmHRV differences between menstrual cycle phases, demonstrating an interaction between cycle phase and PMS symptoms. In a pilot, we found reduced vmHRV and attentional control during the luteal phase only in participants who reported strong PMS.
While Studies 1-4 provided evidence for the mechanisms underlying PMS, Studies 5 and 6 investigated short- and long-term intervention protocols to ameliorate PMS symptomatology. Study 5 explored the potential of heart rate variability biofeedback (HRVB) in alleviating PMS symptoms and a number of other outcome measures. In a waitlist-control design, participants underwent a 4-week smartphone-based HRVB intervention. The results revealed positive effects on PMS, with larger effect sizes on psychological symptoms, as well as on depressive symptoms, anxiety/stress and attentional control.
Finally, Study 6 examined the acute effects of HRVB on attentional control. The study found positive impact but only in highly stressed individuals.
The thesis, based on this comprehensive research program, expands our understanding of PMS as an outcome of CAN fluctuations mediated by GABAA receptor reactivity. The results largely support the model. These findings not only deepen our understanding of PMS but also offer potential avenues for therapeutic interventions. The promising results of smartphone-based HRVB training suggest a non-pharmacological approach to managing PMS symptoms, although further research is needed to confirm its efficacy.
In conclusion, this thesis illuminates the complex web of factors contributing to PMS, providing valuable insights into its etiological underpinnings and potential interventions. By elucidating the relationships between hormonal fluctuations, CAN activity, and psychological responses, this research contributes to more effective treatments for individuals grappling with the challenges of PMS. The findings hold promise for improving the quality of life for those affected by this prevalent and often debilitating condition.
Deep learning has seen widespread application in many domains, mainly for its ability to learn data representations from raw input data. Nevertheless, its success has so far been coupled with the availability of large annotated (labelled) datasets. This is a requirement that is difficult to fulfil in several domains, such as in medical imaging. Annotation costs form a barrier in extending deep learning to clinically-relevant use cases. The labels associated with medical images are scarce, since the generation of expert annotations of multimodal patient data at scale is non-trivial, expensive, and time-consuming. This substantiates the need for algorithms that learn from the increasing amounts of unlabeled data. Self-supervised representation learning algorithms offer a pertinent solution, as they allow solving real-world (downstream) deep learning tasks with fewer annotations. Self-supervised approaches leverage unlabeled samples to acquire generic features about different concepts, enabling annotation-efficient downstream task solving subsequently.
Nevertheless, medical images present multiple unique and inherent challenges for existing self-supervised learning approaches, which we seek to address in this thesis: (i) medical images are multimodal, and their multiple modalities are heterogeneous in nature and imbalanced in quantities, e.g. MRI and CT; (ii) medical scans are multi-dimensional, often in 3D instead of 2D; (iii) disease patterns in medical scans are numerous and their incidence exhibits a long-tail distribution, so it is oftentimes essential to fuse knowledge from different data modalities, e.g. genomics or clinical data, to capture disease traits more comprehensively; (iv) Medical scans usually exhibit more uniform color density distributions, e.g. in dental X-Rays, than natural images. Our proposed self-supervised methods meet these challenges, besides significantly reducing the amounts of required annotations.
We evaluate our self-supervised methods on a wide array of medical imaging applications and tasks. Our experimental results demonstrate the obtained gains in both annotation-efficiency and performance; our proposed methods outperform many approaches from related literature. Additionally, in case of fusion with genetic modalities, our methods also allow for cross-modal interpretability. In this thesis, not only we show that self-supervised learning is capable of mitigating manual annotation costs, but also our proposed solutions demonstrate how to better utilize it in the medical imaging domain. Progress in self-supervised learning has the potential to extend deep learning algorithms application to clinical scenarios.
Arctic climate change is marked by intensified warming compared to global trends and a significant reduction in Arctic sea ice which can intricately influence mid-latitude atmospheric circulation through tropo- and stratospheric pathways. Achieving accurate simulations of current and future climate demands a realistic representation of Arctic climate processes in numerical climate models, which remains challenging.
Model deficiencies in replicating observed Arctic climate processes often arise due to inadequacies in representing turbulent boundary layer interactions that determine the interactions between the atmosphere, sea ice, and ocean. Many current climate models rely on parameterizations developed for mid-latitude conditions to handle Arctic turbulent boundary layer processes.
This thesis focuses on modified representation of the Arctic atmospheric processes and understanding their resulting impact on large-scale mid-latitude atmospheric circulation within climate models. The improved turbulence parameterizations, recently developed based on Arctic measurements, were implemented in the global atmospheric circulation model ECHAM6. This involved modifying the stability functions over sea ice and ocean for stable stratification and changing the roughness length over sea ice for all stratification conditions. Comprehensive analyses are conducted to assess the impacts of these modifications on ECHAM6's simulations of the Arctic boundary layer, overall atmospheric circulation, and the dynamical pathways between the Arctic and mid-latitudes.
Through a step-wise implementation of the mentioned parameterizations into ECHAM6, a series of sensitivity experiments revealed that the combined impacts of the reduced roughness length and the modified stability functions are non-linear. Nevertheless, it is evident that both modifications consistently lead to a general decrease in the heat transfer coefficient, being in close agreement with the observations.
Additionally, compared to the reference observations, the ECHAM6 model falls short in accurately representing unstable and strongly stable conditions.
The less frequent occurrence of strong stability restricts the influence of the modified stability functions by reducing the affected sample size. However, when focusing solely on the specific instances of a strongly stable atmosphere, the sensible heat flux approaches near-zero values, which is in line with the observations. Models employing commonly used surface turbulence parameterizations were shown to have difficulties replicating the near-zero sensible heat flux in strongly stable stratification.
I also found that these limited changes in surface layer turbulence parameterizations have a statistically significant impact on the temperature and wind patterns across multiple pressure levels, including the stratosphere, in both the Arctic and mid-latitudes. These significant signals vary in strength, extent, and direction depending on the specific month or year, indicating a strong reliance on the background state.
Furthermore, this research investigates how the modified surface turbulence parameterizations may influence the response of both stratospheric and tropospheric circulation to Arctic sea ice loss.
The most suitable parameterizations for accurately representing Arctic boundary layer turbulence were identified from the sensitivity experiments. Subsequently, the model's response to sea ice loss is evaluated through extended ECHAM6 simulations with different prescribed sea ice conditions.
The simulation with adjusted surface turbulence parameterizations better reproduced the observed Arctic tropospheric warming in vertical extent, demonstrating improved alignment with the reanalysis data. Additionally, unlike the control experiments, this simulation successfully reproduced specific circulation patterns linked to the stratospheric pathway for Arctic-mid-latitude linkages. Specifically, an increased occurrence of the Scandinavian-Ural blocking regime (negative phase of the North Atlantic Oscillation) in early (late) winter is observed. Overall, it can be inferred that improving turbulence parameterizations at the surface layer can improve the ECHAM6's response to sea ice loss.
The wide distribution of location-acquisition technologies means that large volumes of spatio-temporal data are continuously being accumulated. Positioning systems such as GPS enable the tracking of various moving objects' trajectories, which are usually represented by a chronologically ordered sequence of observed locations. The analysis of movement patterns based on detailed positional information creates opportunities for applications that can improve business decisions and processes in a broad spectrum of industries (e.g., transportation, traffic control, or medicine). Due to the large data volumes generated in these applications, the cost-efficient storage of spatio-temporal data is desirable, especially when in-memory database systems are used to achieve interactive performance requirements.
To efficiently utilize the available DRAM capacities, modern database systems support various tuning possibilities to reduce the memory footprint (e.g., data compression) or increase performance (e.g., additional indexes structures). By considering horizontal data partitioning, we can independently apply different tuning options on a fine-grained level. However, the selection of cost and performance-balancing configurations is challenging, due to the vast number of possible setups consisting of mutually dependent individual decisions.
In this thesis, we introduce multiple approaches to improve spatio-temporal data management by automatically optimizing diverse tuning options for the application-specific access patterns and data characteristics. Our contributions are as follows:
(1) We introduce a novel approach to determine fine-grained table configurations for spatio-temporal workloads. Our linear programming (LP) approach jointly optimizes the (i) data compression, (ii) ordering, (iii) indexing, and (iv) tiering. We propose different models which address cost dependencies at different levels of accuracy to compute optimized tuning configurations for a given workload, memory budgets, and data characteristics. To yield maintainable and robust configurations, we further extend our LP-based approach to incorporate reconfiguration costs as well as optimizations for multiple potential workload scenarios.
(2) To optimize the storage layout of timestamps in columnar databases, we present a heuristic approach for the workload-driven combined selection of a data layout and compression scheme. By considering attribute decomposition strategies, we are able to apply application-specific optimizations that reduce the memory footprint and improve performance.
(3) We introduce an approach that leverages past trajectory data to improve the dispatch processes of transportation network companies. Based on location probabilities, we developed risk-averse dispatch strategies that reduce critical delays.
(4) Finally, we used the use case of a transportation network company to evaluate our database optimizations on a real-world dataset. We demonstrate that workload-driven fine-grained optimizations allow us to reduce the memory footprint (up to 71% by equal performance) or increase the performance (up to 90% by equal memory size) compared to established rule-based heuristics.
Individually, our contributions provide novel approaches to the current challenges in spatio-temporal data mining and database research. Combining them allows in-memory databases to store and process spatio-temporal data more cost-efficiently.
This thesis presents an attempt to use source code synthesised from Coq formalisations of device drivers for existing (micro)kernel operating systems, with a particular focus on the Linux Kernel.
In the first part, the technical background and related work are described. The focus is here on the possible approaches to synthesising certified software with Coq, namely the extraction to functional languages using the Coq extraction plugin and the extraction to Clight code using the CertiCoq plugin. It is noted that the implementation of CertiCoq is verified, whereas this is not the case for the Coq extraction plugin. Consequently, there is a correctness guarantee for the generated Clight code which does not hold for the code being generated by the Coq extraction plugin. Furthermore, the differences between user space and kernel space software are discussed in relation to Linux device drivers. It is elaborated that it is not possible to generate working Linux kernel module components using the Coq extraction plugin without significant modifications. In contrast, it is possible to produce working user space drivers both with the Coq extraction plugin and CertiCoq. The subsequent parts describe the main contributions of the thesis.
In the second part, it is demonstrated how to extend the Coq extraction plugin to synthesise foreign function calls between the functional language OCaml and the imperative language C. This approach has the potential to improve the type-safety of user space drivers. Furthermore, it is shown that the code being synthesised by CertiCoq cannot be used in kernel space without modifications to the necessary runtime. Consequently, the necessary modifications to the runtimes of CertiCoq and VeriFFI are introduced, resulting in the runtimes becoming compatible components of a Linux kernel module. Furthermore, justifications for the transformations are provided and possible further extensions to both plugins and solutions to failing garbage collection calls in kernel space are discussed.
The third part presents a proof of concept device driver for the Linux Kernel. To achieve this, the event handler of the original PC Speaker driver is partially formalised in Coq. Furthermore, some relevant formal properties of the formalised functionality are discussed. Subsequently, a kernel module is defined, utilising the modified variants of CertiCoq and VeriFFI to compile a working device driver. It is furthermore shown that it is possible to compile the synthesised code with CompCert, thereby extending the guarantee of correctness to the assembly layer. This is followed by a performance evaluation that compares a naive formalisation of the PC speaker functionality with the original PC Speaker driver pointing out the weaknesses in the formalisation and possible improvements. The part closes with a summary of the results, their implications and open questions being raised.
The last part lists all used sources, separated into scientific literature, documentations or reference manuals and artifacts, i.e. source code.
The plant cell wall plays several crucial roles during plant development with its integrity acting as key signalling component for growth regulation during biotic and abiotic stresses. Cellulose microfibrils, the principal load-bearing components is the major component of the primary cell wall, whose synthesis is mediated by microtubule-associated CELLULOSE SYNTHASE (CESA) COMPLEXES (CSC). Previous studies have shown that CSC interacting proteins COMPANION OF CELLULOSE SYNTHASE (CC) facilitate sustained cellulose synthesis during salt stress by promoting repolymerization of cortical microtubules. However, our understanding of cellulose synthesis during salt stress remains incomplete.
In this study, a pull-down of CC1 protein led to the identification of a novel interactor, termed LEA-like. Phylogenetic analysis revealed that LEA-like belongs to the LATE EMBRYOGENESIS ABUNDANT (LEA) protein family, specifically to the LEA_2 subgroup, showing a close relationship with the CC proteins. Roots of the double mutants lea-like and its closest homolog emb3135 exhibited hypersensitivity when grown on cellulose synthesis inhibitors. Further analysis of higher-order mutants of lea-like, emb3135, and cesa6 demonstrated a genetic interaction between them indicating a significant role in cellulose synthesis.
Live-cell imaging revealed that both LEA-like and EMB3135 migrated with the CSC at the plasma membrane along microtubule tracks in control and oryzalin-treated conditions which destabilize microtubules, suggesting a tight interaction. Investigation of fluorescently labeled lines of different domains of the LEA-like protein revealed that the N-terminal cytosolic domain of LEA-like colocalizes with microtubules, suggesting a physical association between the two.
Considering the established role of LEA proteins in abiotic stress tolerance, we performed phenotypic analysis of the mutant under various stresses. Growth of double mutants of lea-like and emb3135 on NaCl containing media resulted in swelling of root cell indicating a putative role in salt stress tolerance. Supportive of this the quadruple mutant, lacking LEA-like, EMB3135, CC1, and CC2 proteins, exhibited a severe root growth defect on NaCl media compared to control conditions. Live-cell imaging revealed that under salt stress, the LEA-like protein forms aggregates in the plasma membrane.
In conclusion, this study has unveiled two novel interactors of the CSC that act with the CC proteins that regulate plant growth in response to salt stress providing new insights into the intricate regulation of cellulose synthesis, particularly under such conditions.
Leaves exhibit cells with varying degrees of shape complexity along the proximodistal axis. Heterogeneities in growth directions within individual cells bring about such complexity in cell shape. Highly complex and interconnected gene regulatory networks and signaling pathways have been identified to govern these processes. In addition, the organization of cytoskeletal networks and cell wall mechanical properties greatly influences the regulation of cell shape. Research has shown that microtubules are involved in regulating cellulose deposition and direc-tion of cell growth. However, comprehensive analysis of the regulation of the actin cytoskele-ton in cell shape regulation has not been well studied.
This thesis provides evidence that actin regulates aspects of cell growth, division, and direction-al expansion that impacts morphogenesis of developing leaves. The jigsaw puzzle piece mor-phology of epidermal pavement cells further serves as an ideal system to investigate the com-plex process of morphogenetic processes occurring at the cellular level. Here we have em-ployed live cell based imaging studies to track the development of pavement cells in actin com-promised conditions. Genetic perturbation of two predominantly expressed vegetative actin genes ACTIN2 and ACTIN7 results in delayed emergence of the cellular protrusions in pave-ment cells. Perturbation of actin also impacted the organization of microtubule in these cells that is known to promote emergence of cellular protrusions. Further, live-cell imaging of actin or-ganization revealed a correlation with cell shape, suggesting that actin plays a role in influencing pavement cell morphogenesis.
In addition, disruption of actin leads to an increase in cell size along the leaf midrib, with cells being highly anisotropic due to reduced cell division. The reduction of cell division further im-pacted the morphology of the entire leaf, with the mutant leaves being more curved. These re-sults suggests that actin plays a pivotal role in regulating morphogenesis at the cellular and tis-sue scales thereby providing valuable insights into the role of the actin cytoskeleton in plant morphogenesis.