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Water-deficits can cause lethal damage to organisms, which is rooted in cellular dehydration. Many plant species, but also other organisms have developed mechanisms to tolerate such stresses, such as the expression of LEA proteins. Many studies report on physiological protective functions of LEA proteins but lack information about their precise mechanisms on a molecular level. Most LEA proteins are intrinsically disordered in dilute solution but may adopt a distinct secondary structure upon changes in solvent conditions. Understanding the molecular mechanism of how LEA proteins contribute to the counteraction of cellular damage during water-deficits may in the long-term pave the way for breeding crops that are resistant to the effects of global warming. The objective of the work at hand is to improve the biophysical understanding of the sequencestructure-function relationship of LEA proteins as membrane stabilizers, based on the LEA_4 family of the model plant A. thaliana. This is pursued by using a combination of spectroscopic and scattering techniques, supported by bioinformatics and computational analyses. Eight out of the 18 LEA_4 proteins are experimentally assessed revealing that a coil-helix transition in response to water-deficit is a common feature, as predicted for the entire family. In addition, they all stabilize simple membrane models during a freeze/ thaw cycle. Three-dimensional structure prediction of representative members suggests that their completely folded states are represented by a sequential arrangement of alpha-helical segments connected by unstructured linkers, which is experimentally verified for the LEA_4 protein COR15A. The unstructured linker region of COR15A represents a conserved motif among its closest homologs and is, therefore, of particular interest. Facilitating a set of seven designed and investigated COR15A mutants uncovers a complex interplay of transient interactions between the amphipathic alpha-helical segments, mediated by the linker, which fine-tunes folding transitions and structural ensembles upon reduced water-availability. Finally, alpha-helicity is also induced in COR15A upon temperature decrease, which is enhanced in the presence of osmolytes. In addition, high solution osmolarity induced secondary structure is followed by oligomerization of COR15A. Interestingly, the functionality of COR15A, in terms of liposome stabilization, strongly correlates with its alpha-helix ratio in the folded state. The present work significantly improves the understanding of the sequence-structure-function relationship for LEA_4 proteins and offers novel findings on folding mechanisms and oligomerization of COR15A.
The trace elements zinc and manganese are essential for human health, especially due to their enzymatic and protein stabilizing functions. If these elements are ingested in amounts exceeding the requirements, regulatory processes for maintaining their physiological concentrations (homeostasis) can be disturbed. Those homeostatic dysregulations can cause severe health effects including the emergence of neurodegenerative disorders such as Parkinson’s disease (PD). The concentrations of essential trace elements also change during the aging process. However, the relations of cause and consequence between increased manganese and zinc uptake and its influence on the aging process and the emergence of the aging-associated PD are still rarely understood. This doctoral thesis therefore aimed to investigate the influence of a nutritive zinc and/or manganese oversupply on the metal homeostasis during the aging process. For that, the model organism Caenorhabditis elegans (C. elegans) was applied. This nematode suits well as an aging and PD model due to properties such as its short life cycle and its completely sequenced, genetically amenable genome. Different protocols for the propagation of zinc- and/or manganese-supplemented young, middle-aged and aged C. elegans were established. Therefore, wildtypes, as well as genetically modified worm strains modeling inheritable forms of parkinsonism were applied. To identify homeostatic and neurological alterations, the nematodes were investigated with different methods including the analysis of total metal contents via inductively-coupled plasma tandem mass spectrometry, a specific probe-based method for quantifying labile zinc, survival assays, gene expression analysis as well as fluorescence microscopy for the identification and quantification of dopaminergic neurodegeneration.. During aging, the levels of iron, as well as zinc and manganese increased.. Furthermore, the simultaneous oversupply with zinc and manganese increased the total zinc and manganese contents to a higher extend than the single metal supplementation. In this relation the C. elegans metallothionein 1 (MTL-1) was identified as an important regulator of metal homeostasis. The total zinc content and the concentration of labile zinc were age-dependently, but differently regulated. This elucidates the importance of distinguishing these parameters as two independent biomarkers for the zinc status. Not the metal oversupply, but aging increased the levels of dopaminergic neurodegeneration. Additionally, nearly all these results yielded differences in the aging-dependent regulation of trace element homeostasis between wildtypes and PD models. This confirms that an increased zinc and manganese intake can influence the aging process as well as parkinsonism by altering homeostasis although the underlying mechanisms need to be clarified in further studies.
Breslau has been almost entirely forgotten in the Anglophone sphere as a place of Enlightenment. Moreover, in the context of the Jewish Enlightenment, Breslau has never been discussed as a place of intercultural exchange between German-speaking Jewish, Protestant and Catholic intellectuals. The story of Moses Hirschel offers us an excellent case-study to investigate the complex reciprocal relationship between Jewish and non-Jewish enlighteners in a prosperous and influential Central European city on the cusp of the 18th century.
The characterization of exoplanets applying high-resolution transmission spectroscopy ini- tiated a new era making it possible to trace atmospheric signature at high altitudes in exoplanet atmospheres and to determine atmospheric properties which enrich our under- standing of the formation and evolution of the solar system. In contrast to what is observed in our solar system, where gaseous planets orbit at wide orbits, Jupiter type exoplanets were detected in foreign stellar systems surrounding their host stars within few days, in close orbits, the so called hot- and ultra-hot Jupiters. The most well studied ones are HD209458b and HD189733b, which are the first exoplanets where absorption is detected in their atmospheres, namely from the alkali line sodium. For hot Jupiters, the resonant alkali lines are the atmospheric species with one of the strongest absorption signatures, due to their large absorption cross-section. However, al- though the alkali lines sodium and potassium were detected in low-resolution observations for various giant exoplanets, potassium was absent in different high-resolution investiga- tions in contrast to sodium. The reason for this is quite puzzling, since both alkalis have very similar physical and chemical properties (e.g. condensation and ionization proper- ties). Obtaining high-resolution transit observations of HD189733b and HD209458b, we were able to detect potassium on HD189733b (Manuscript 1), which was the first high-resolution detection of potassium on an exoplanet. The absence of potassium on HD209458b could be reasoned by depletion processes, such as condensation or photo-ionization or high-altitude clouds. In a further study (Manuscript II), we resolved the potassium line and compared this to a previously detected sodium absorption on this planet. The comparison showed, that the potassium lines are either tracing different altitudes and temperatures compared to the sodium lines, or are depleted so that the planetary Na/K- ratio is way larger than the stellar one. A comparison of the alkali lines with synthetic line profiles showed that the sodium lines were much broader than the potassium lines, probably being induced by winds. To investigate this, the effect of zonal streaming winds on the sodium lines on Jupiter-type planets is investigated in a further study (Manuscript III), showing that such winds can significantly broaden the Na- lines and that high-resolution observations can trace such winds with different properties. Furthermore, investigating the Na-line observations for different exoplanets, I showed that the Na-line broadening follows a trend with cooler planets showing stronger line broadening and so hinting on stronger winds, matching well into theoretical predictions. Each presented manuscript depends on the re- sults published within the previous manuscript, yielding a unitary study of the exoplanet HD189733b. The investigation of the potassium absorption required to account for different effects: The telluric lines removal and the effect of center-to-limb variation (see Manuscript I), the residual Rossiter-Mc-Laughlin effect (see Manuscript II) and the broadening of spectral lines on a translucent atmospheric ring by zonal jet streams (see Manuscript III). This thesis shows that high-resolution transmission spectroscopy is a powerful tool to probe sharp alkali line absorption on giant exoplanet atmospheres and to investigate on the properties and dynamics of hot Jupiter type atmospheres.
Past and present biodiversity in northeastern Siberia inferred from sedimentary DNA metabarcoding
(2021)
The arctic-boreal treeline is a transition zone from taiga to tundra covering a vast area in Siberia. It often features large environmental gradients and reacts sensitively to changes in the environment. For example, the expansion of shrubs and a northward movement of the treeline are observable in Siberia as a response to the warming climate. The changes in vegetation across the treeline are known to influence the water chemistry in the lakes. This causes further alteration to the composition and diversity of sensitive aquatic organisms such as diatoms and macrophytes. Despite the rising awareness of the complex climate-feedback mechanisms of terrestrial plants, the understanding of their assembly rules and about responses of aquatic biomes in the surrounding treeline lakes is still limited. The goal of this thesis is to examine the previous and present biodiversity of terrestrial and freshwater biomes from the Siberian treeline ecotone, as well as their reactions to environmental changes. In particular, this thesis attempts to examine the performance of applying sedimentary DNA metabarcoding in terrestrial plants, aquatic macrophytes and diatoms, their spatial patterns along the environmental gradients and their temporal patterns throughout the climate transition from the late Pleistocene to Holocene. Sedimentary DNA metabarcoding combined with next-generation sequencing is applied as a primary tool to explore the composition and diversity of terrestrial plants, diatoms and aquatic macrophytes. The main study area is located in Chukotka of northeastern Siberia in the Arctic, a biodiversity hotspot due to its continental location and the diverse habitats of the glacial refugium. The modern diatom diversity was assessed with a specific diatom metabarcoding marker and morphological identification. Both approaches agree to a dominance of Fragilariaceae and Aulacoseiraceae, as well as on the environmental influential indicators of the diatom community. The high diversity of Fragilariaceae identified in the thermokarst lakes is found to follow the vegetation gradient along the treeline, suggesting that diatom metabarcoding can decipher relationships between diatom assemblage shifts and the relevant environmental changes. In particular, the metabarcoding approach detects diversification of fragilarioids in glacial lakes which is not visible using morphology. Sedimentary ancient DNA records indicate a vegetation mosaic of forb-dominated steppe-tundra during 28-19 ka, followed by a shift to dwarf-shrub tundra during 19-14 ka. During the most recent 14 thousand years, the vegetation consists of deciduous shrublands, then a change to boreal forest is observed. Investigations on the alpha diversity of the vegetation show that species richness is unexpectedly highest during pre-LGM, which is likely related to the extensive area that allows for more taxa. The optimum Holocene warming during 9-6 ka is not accompanied by a high richness as widely believed, but with an evenly distributed community by the fulfilment of erect shrubs. Furthermore, changes in taxonomic and phylogenetic diversity show complementary results in understanding community diversity. The composition and richness in the modern macrophytes community from Siberian Arctic and Chinese alpine are best co-influenced by July temperature and electrical conductivity.. Past macrophyte turnover during the late Pleistocene-Holocene is less noticeable in Siberia, whereas a pronounced community change from emergent to submerged plants is detected from Chinese alpine regions at about 14 ka due to increasing temperature and varying water conductivity. Finally, sedimentary DNA metabarcoding is a cost-effective and powerful proxy for ecological application, whereas completeness of the reference library, coverage and resolution of the metabarcoding marker are the major limitations of sedimentary DNA based diversity monitoring. The composition and richness in modern vegetation and macrophytes across broad spatial gradients is constrained by environmental variables, suggesting a potential usage for environmental monitoring. Diatom distributions are driven by different water variables along the treeline. Past records indicate that the shrub coverage has a noticeable influence on the assemblies of both terrestrial plants and aquatic macrophytes, though the shift in macrophyte community is relatively minor in the past 28 thousand years. In the long-term, the shrub expansion may eventually result in a genetically more diverse vegetation community but reduced species richness. When exceeding the optimal temperatures, further warming may lead to a decrease and putative loss of macrophytes and diatoms.
Investigation of Sirtuin 3 overexpression as a genetic model of fasting in hypothalamic neurons
(2021)
In modern times of evolving globalization and continuous technological developments, organizations are required to respond to ever-changing demands. Therefore, to be successful in today’s highly uncertain environments, organizations need employees to actively search for opportunities, anticipate challenges, and act ahead. In other words, employee proactivity in the workplace represents a highly valuable resource in nowadays organizations. Empirical studies conducted as part of this thesis advance the research on the outcomes of proactivity from the individual perspective. The main contribution of this thesis pertains to revealing several important individual and contextual conditions under which engaging in proactivity will have negative and positive effects on employees’ well-being and their consequent behaviours, as well as shedding light on the unique psychological mechanisms through which these effects unfold. From a practical standpoint, this research underscores the importance of creating work environments that support employees’ autonomous motivation for proactivity and urge organizations and managers to be mindful about the pressures they place on employees to be proactive at work. Besides, this thesis stimulates research efforts aimed at further extending our knowledge of when and how individual proactive behaviours at work will do more good than harm for those who enact them.
Fibroblast growth differentiation factor 21 (FGF21) is known as a pivotal regulator of the glucose and lipid metabolism. As such, it is considered beneficial and has even been labelled a longevity hormone. Nevertheless, recent observational studies have shown that FGF21 is increased in higher age with possible negative effects such as loss of lean and bone mass as well as decreased survival. Hepatic FGF21 secretion can be induced by various nutritional stimuli such as starvation, high carbohydrate and fat intake as well as protein deficiency.. So far it is still unclear whether the FGF21 response to different macronutrients is altered in older age. An altered response would potentially contribute to explain the higher FGF21 concentrations found in older age. In this publication-based doctoral dissertation, a cross-sectional study as well as a dietary challenge were conducted to investigate the influence of nutrition on FGF21 concentrations and response in older age. In a cross-sectional study, FGF21 concentrations were assessed in older patients with and without cachexia anorexia syndrome anorexia syndrome compared to an older community-dwelling control group. Cachexia anorexia syndrome is a multifactorial syndrome frequently occurring in old age or in the context of an underlying disease. It is characterized by a severe involuntary weight loss, loss of appetite (anorexia) and reduced food intake, therefore representing a state of severe nutrient deficiency, in some aspects similar to starvation. The highest FGF21 concentrations were found in patients with cachexia anorexia syndrome. Moreover, FGF21 was positively correlated with weight loss and loss of appetite. In addition, cachexia anorexia syndrome itself was associated with FGF21 independent of sex, age and body mass index. As cachectic patients presumably exhibit protein malnutrition and FGF21 has been proposed a marker for protein insufficiency, the higher levels of FGF21 in patients with cachexia anorexia syndrome might be partly explained by insufficient protein intake. In order to investigate the acute response of FGF21 to different nutritional stimuli, a dietary challenge with a parallel group design was conducted. Here, healthy older (65-85 years) and younger (18-35 years) adults were randomized to one of four test meals: a dextrose drink, a high carbohydrate, high fat or high protein meal. Over the course of four hours, postprandial FGF21 concentrations (dynamics) were assessed and the FGF21 response (incremental area under the curve) to each test meal was examined.. In a sub-group of older and younger women, also the adiponectin response was investigated, as adiponectin is a known mediator of FGF21 effects on glucose and lipid metabolism. The dietary meal challenge revealed that dextrose and high carbohydrate intake result in higher FGF21 concentrations after four hours in older adults. This was partly explained by higher postprandial glucose concentrations in the old. For high fat ingestion no age differences were found. For the first time, acute FGF21 response to high protein intake was shown. Here, protein ingestion resulted in lower FGF21 concentrations in younger compared to older adults. Furthermore, sufficient protein intake, according to age-dependent recommendations, of the previous day, was associated with lower FGF21 concentrations in both age groups. The higher FGF21 response to dextrose ingestion resulted in a higher adiponectin response in older women, independent of fat mass, insulin resistance, triglyceride concentrations, inflammation and oxidative stress. Following the high fat meal, adiponectin concentrations declined in older women. Adiponectin response was not affected by meal composition in younger women. In summary, this thesis showed a positive association of FGF21 and cachexia anorexia syndrome with concomitant anorexia in older patients. Regarding the acute FGF21 response, a higher response following dextrose and carbohydrate ingestion was found in older compared with younger subjects. This might be attributed to a higher glucose response in older age. Furthermore, it was shown that the higher FGF21 response after dextrose ingestion possibly contributes to a higher adiponectin response in older women, independent of potential metabolic and inflammatory confounders. Acute protein ingestion resulted in a significant decrease in FGF21 concentrations. Moreover, protein intake of the previous day was inversely associated with fasting FGF21 concentrations. This might explain why FGF21 concentrations are higher in cachexia anorexia syndrome. These results therefore support the role of FGF21 as a sensor of protein restriction.
The Arctic environments constitute rich and dynamic ecosystems, dominated by microorganisms extremely well adapted to survive and function under severe conditions. A range of physiological adaptations allow the microbiota in these habitats to withstand low temperatures, low water and nutrient availability, high levels of UV radiation, etc. In addition, other adaptations of clear competitive nature are directed at not only surviving but thriving in these environments, by disrupting the metabolism of neighboring cells and affecting intermicrobial communication. Since Arctic microbes are bioindicators which amplify climate alterations in the environment, the Arctic region presents the opportunity to study local microbiota and carry out research about interesting, potentially virulent phenotypes that could be dispersed into other habitats around the globe as a consequence of accelerating climate change. In this context, exploration of Arctic habitats as well as descriptions of the microbes inhabiting them are abundant but microbial competitive strategies commonly associated with virulence and pathogens are rarely reported. In this project, environmental samples from the Arctic region were collected and microorganisms (bacteria and fungi) were isolated. The clinical relevance of these microorganisms was assessed by observing the following virulence markers: ability to grow at a range of temperatures, expression of antimicrobial resistance and production of hemolysins. The aim of this project is to determine the frequency and relevance of these characteristics in an effort to understand microbial adaptations in habitats threatened by climate change. The isolates obtained and described here were able to grow at a range of temperatures, in some cases more than 30 °C higher than their original isolation temperature. A considerable number of them consistently expressed compounds capable of lysing sheep and bovine erythrocytes on blood agar at different incubation temperatures. Ethanolic extracts of these bacteria were able to cause rapid and complete lysis of erythrocyte suspensions and might even be hemolytic when assayed on human blood. In silico analyses showed a variety of resistance elements, some of them novel, against natural and synthetic antimicrobial compounds. In vitro experiments against a number of antimicrobial compounds showed resistance phenotypes belonging to wild-type populations and some non-wild type which clearly denote human influence in the acquisition of antimicrobial resistance. The results of this project demonstrate the presence of virulence-associated factors expressed by microorganisms of natural, non-clinical environments. This study contains some of the first reports, to the best of our knowledge, of hemolytic microbes isolated from the Arctic region. In addition, it provides additional information about the presence and expression of intrinsic and acquired antimicrobial resistance in environmental isolates, contributing to the understanding of the evolution of relevant pathogenic species and opportunistic pathogens. Finally, this study highlights some of the potential risks associated with changes in the polar regions (habitat melting and destruction, ecosystem transition and re-colonization) as important indirect consequences of global warming and altered climatic conditions around the planet.
Simultaneously speculative and inspired by everyday experiences, this volume develops an aesthetics of metabolism that offers a new perspective on the human-environment relation, one that is processual, relational, and not dependent on conscious thought. In art installations, design prototypes, and researchcreation projects that utilize air, light, or temperature to impact subjective experience the author finds aesthetic milieus that shift our awareness to the role of different sense modalities in aesthetic experience. Metabolic and atmospheric processes allow for an aesthetics besides and beyond the usually dominant visual sense.
The incorporation of proteins in artificial materials such as membranes offers great opportunities to avail oneself the miscellaneous qualities of proteins and enzymes perfected by nature over millions of years. One possibility to leverage proteins is the modification with artificial polymers. To obtain such protein-polymer conjugates, either a polymer can be grown from the protein surface (grafting-from) or a pre-synthesized polymer attached to the protein (grafting-to). Both techniques were used to synthesize conjugates of different proteins with thermo-responsive polymers in this thesis.
First, conjugates were analyzed by protein NMR spectroscopy. Typical characterization techniques for conjugates can verify the successful conjugation and give hints on the secondary structure of the protein. However, the 3-dimensional structure, being highly important for the protein function, cannot be probed by standard techniques. NMR spectroscopy is a unique method allowing to follow even small alterations in the protein structure. A mutant of the carbohydrate binding module 3b (CBM3bN126W) was used as model protein and functionalized with poly(N-isopropylacrylamide). Analysis of conjugates prepared by grafting-to or grafting-from revealed a strong impact of conjugation type on protein folding. Whereas conjugates prepared by grafting a pre-formed polymer to the protein resulted in complete preservation of protein folding, grafting the polymer from the protein surface led to (partial) disruption of the protein structure.
Next, conjugates of bovine serum albumin (BSA) as cheap and easily accessible protein were synthesized with PNIPAm and different oligoethylene glycol (meth)acrylates. The obtained protein-polymer conjugates were analyzed by an in-line combination of size exclusion chromatography and multi-angle laser light scattering (SEC-MALS). This technique is particular advantageous to determine molar masses, as no external calibration of the system is needed. Different SEC column materials and operation conditions were tested to evaluate the applicability of this system to determine absolute molar masses and hydrodynamic properties of heterogeneous conjugates prepared by grafting-from and grafting-to. Hydrophobic and non-covalent interactions of conjugates lead to error-prone values not in accordance to expected molar masses based on conversions and extents of modifications.
As alternative to this method, conjugates were analyzed by sedimentation velocity analytical ultracentrifugation (SV-AUC) to gain insights in the hydrodynamic properties and how they change after conjugation. Within a centrifugal field, a sample moves and fractionates according to the mass, density, and shape of its individual components. Conjugates of BSA with PNIPAm were analyzed below and above the cloud point temperature of the thermo-responsive polymer component. It was identified that the polymer characteristics were transferred to the conjugate molecule which than showed a decreased ideality – defined as increased deviation from a perfect sphere model – below and increased ideality above the cloud point temperature. This effect can be attributed to an arrangement of the polymer chain pointing towards the solvent (expanded state) or snuggling around the protein surface depending on the applied temperature.
The last project dealt with the synthesis of ferric hydroxamate uptake protein component A (FhuA)-polymer conjugates as building blocks for novel membrane materials. The shape of FhuA can be described as barrel and removal of a cork domain inside the protein results in a passive channel aimed to be utilized as pores in the membrane system. The polymer matrix surrounding the membrane protein is composed of a thermo-responsive and a UV-crosslinkable part. Therefore, an external trigger for covalent immobilization of these building blocks in the membrane and switchability of the membrane between different states was incorporated. The overall performance of membranes prepared by a drying-mediated self-assembly approach was evaluated by permeability and size exclusion experiments. The obtained membranes displayed an insufficiency in interchain crosslinking and therefore a lack in performance. Furthermore, the aimed switch between a hydrophilic and hydrophobic state of the polymer matrix did not occur. Correspondingly, size exclusion experiments did not result in a retention of analytes larger than the pores defined by the dimension of the used FhuA variant.
Overall, different paths to generate protein-polymer conjugates by either grafting-from or grafting-to the protein surface were presented paving the way to the generation of new hybrid materials. Different analytical methods were utilized to describe the folding and hydrodynamic properties of conjugates providing a deeper insight in the overall characteristics of these seminal building blocks.
Halide perovskites are a class of novel photovoltaic materials that have recently attracted much attention in the photovoltaics research community due to their highly promising optoelectronic properties, including large absorption coefficients and long carrier lifetimes. The charge carrier mobility of halide perovskites is investigated in this thesis by THz spectroscopy, which is a contact-free technique that yields the intra-grain sum mobility of electrons and holes
in a thin film.
The polycrystalline halide perovskite thin films, provided from Potsdam University, show moderate mobilities in the range from 21.5 to 33.5 cm2V-1s-1. It is shown in this work that the room temperature mobility is limited by charge carrier scattering at polar optical phonons. The mobility at low temperature is likely to be limited by scattering at charged and neutral impurities at impurity concentration N=1017-1018 cm-3. Furthermore, it is shown that exciton formation
may decrease the mobility at low temperatures. Scattering at acoustic phonons can be neglected at both low and room temperatures. The analysis of mobility spectra over a broad range of temperatures for perovskites with various cation compounds shows that cations have a minor impact on charge carrier mobility.
The low-dimensional thin films of quasi-2D perovskite with different numbers of [PbI6]4−sheets (n=2-4) alternating with long organic spacer molecules were provided by S. Zhang from Potsdam University. They exhibit mobilities in the range from 3.7 to 8 cm2V-1s-1. A clear
decrease of mobility is observed with decrease in number of metal-halide sheets n, which likely arises from charge carrier confinement within metal-halide layers. Modelling the measured THz mobility with the modified Drude-Smith model yields localization length from 0.9 to 3.7 nm, which agrees well on the thicknesses of the metal-halide layers. Additionally, the mobilities are found to be dependent on the orientation of the layers. The charge carrier dynamics is also
dependent on the number of metal-halide sheets n. For the thin films with n =3-4 the dynamics is similar to the 3D MHPs. However, the thin film with n = 2 shows clearly different dynamics, where the signs of exciton formation are observed within 390 fs timeframe after
photoexcitation.
Also, the charge carrier dynamics of CsPbI3 perovskite nanocrystals was investigated, in particular the effect of post treatments on the charge carrier transport.
Precipitation forecasting has an important place in everyday life – during the day we may have tens of small talks discussing the likelihood that it will rain this evening or weekend. Should you take an umbrella for a walk? Or should you invite your friends for a barbecue? It will certainly depend on what your weather application shows.
While for years people were guided by the precipitation forecasts issued for a particular region or city several times a day, the widespread availability of weather radars allowed us to obtain forecasts at much higher spatiotemporal resolution of minutes in time and hundreds of meters in space. Hence, radar-based precipitation nowcasting, that is, very-short-range forecasting (typically up to 1–3 h), has become an essential technique, also in various professional application contexts, e.g., early warning, sewage control, or agriculture.
There are two major components comprising a system for precipitation nowcasting: radar-based precipitation estimates, and models to extrapolate that precipitation to the imminent future. While acknowledging the fundamental importance of radar-based precipitation retrieval for precipitation nowcasts, this thesis focuses only on the model development: the establishment of open and competitive benchmark models, the investigation of the potential of deep learning, and the development of procedures for nowcast errors diagnosis and isolation that can guide model development.
The present landscape of computational models for precipitation nowcasting still struggles with the availability of open software implementations that could serve as benchmarks for measuring progress. Focusing on this gap, we have developed and extensively benchmarked a stack of models based on different optical flow algorithms for the tracking step and a set of parsimonious extrapolation procedures based on image warping and advection. We demonstrate that these models provide skillful predictions comparable with or even superior to state-of-the-art operational software. We distribute the corresponding set of models as a software library, rainymotion, which is written in the Python programming language and openly available at GitHub (https://github.com/hydrogo/rainymotion). That way, the library acts as a tool for providing fast, open, and transparent solutions that could serve as a benchmark for further model development and hypothesis testing.
One of the promising directions for model development is to challenge the potential of deep learning – a subfield of machine learning that refers to artificial neural networks with deep architectures, which may consist of many computational layers. Deep learning showed promising results in many fields of computer science, such as image and speech recognition, or natural language processing, where it started to dramatically outperform reference methods.
The high benefit of using "big data" for training is among the main reasons for that. Hence, the emerging interest in deep learning in atmospheric sciences is also caused and concerted with the increasing availability of data – both observational and model-based. The large archives of weather radar data provide a solid basis for investigation of deep learning potential in precipitation nowcasting: one year of national 5-min composites for Germany comprises around 85 billion data points.
To this aim, we present RainNet, a deep convolutional neural network for radar-based precipitation nowcasting. RainNet was trained to predict continuous precipitation intensities at a lead time of 5 min, using several years of quality-controlled weather radar composites provided by the German Weather Service (DWD). That data set covers Germany with a spatial domain of 900 km x 900 km and has a resolution of 1 km in space and 5 min in time. Independent verification experiments were carried out on 11 summer precipitation events from 2016 to 2017. In these experiments, RainNet was applied recursively in order to achieve lead times of up to 1 h. In the verification experiments, trivial Eulerian persistence and a conventional model based on optical flow served as benchmarks. The latter is available in the previously developed rainymotion library.
RainNet significantly outperformed the benchmark models at all lead times up to 60 min for the routine verification metrics mean absolute error (MAE) and critical success index (CSI) at intensity thresholds of 0.125, 1, and 5 mm/h. However, rainymotion turned out to be superior in predicting the exceedance of higher intensity thresholds (here 10 and 15 mm/h). The limited ability of RainNet to predict high rainfall intensities is an undesirable property which we attribute to a high level of spatial smoothing introduced by the model. At a lead time of 5 min, an analysis of power spectral density confirmed a significant loss of spectral power at length scales of 16 km and below.
Obviously, RainNet had learned an optimal level of smoothing to produce a nowcast at 5 min lead time. In that sense, the loss of spectral power at small scales is informative, too, as it reflects the limits of predictability as a function of spatial scale. Beyond the lead time of 5 min, however, the increasing level of smoothing is a mere artifact – an analogue to numerical diffusion – that is not a property of RainNet itself but of its recursive application. In the context of early warning, the smoothing is particularly unfavorable since pronounced features of intense precipitation tend to get lost over longer lead times. Hence, we propose several options to address this issue in prospective research on model development for precipitation nowcasting, including an adjustment of the loss function for model training, model training for longer lead times, and the prediction of threshold exceedance.
The model development together with the verification experiments for both conventional and deep learning model predictions also revealed the need to better understand the source of forecast errors. Understanding the dominant sources of error in specific situations should help in guiding further model improvement. The total error of a precipitation nowcast consists of an error in the predicted location of a precipitation feature and an error in the change of precipitation intensity over lead time. So far, verification measures did not allow to isolate the location error, making it difficult to specifically improve nowcast models with regard to location prediction.
To fill this gap, we introduced a framework to directly quantify the location error. To that end, we detect and track scale-invariant precipitation features (corners) in radar images. We then consider these observed tracks as the true reference in order to evaluate the performance (or, inversely, the error) of any model that aims to predict the future location of a precipitation feature. Hence, the location error of a forecast at any lead time ahead of the forecast time corresponds to the Euclidean distance between the observed and the predicted feature location at the corresponding lead time.
Based on this framework, we carried out a benchmarking case study using one year worth of weather radar composites of the DWD. We evaluated the performance of four extrapolation models, two of which are based on the linear extrapolation of corner motion; and the remaining two are based on the Dense Inverse Search (DIS) method: motion vectors obtained from DIS are used to predict feature locations by linear and Semi-Lagrangian extrapolation.
For all competing models, the mean location error exceeds a distance of 5 km after 60 min, and 10 km after 110 min. At least 25% of all forecasts exceed an error of 5 km after 50 min, and of 10 km after 90 min. Even for the best models in our experiment, at least 5 percent of the forecasts will have a location error of more than 10 km after 45 min. When we relate such errors to application scenarios that are typically suggested for precipitation nowcasting, e.g., early warning, it becomes obvious that location errors matter: the order of magnitude of these errors is about the same as the typical extent of a convective cell. Hence, the uncertainty of precipitation nowcasts at such length scales – just as a result of locational errors – can be substantial already at lead times of less than 1 h. Being able to quantify the location error should hence guide any model development that is targeted towards its minimization. To that aim, we also consider the high potential of using deep learning architectures specific to the assimilation of sequential (track) data.
Last but not least, the thesis demonstrates the benefits of a general movement towards open science for model development in the field of precipitation nowcasting. All the presented models and frameworks are distributed as open repositories, thus enhancing transparency and reproducibility of the methodological approach. Furthermore, they are readily available to be used for further research studies, as well as for practical applications.
The prevalence of diseases associated with misfolded proteins increases with age. When cellular defense mechanisms become limited, misfolded proteins form aggregates and may also develop more stable cross-β structures ultimately forming amyloid aggregates. Amyloid aggregates are associated with neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease. The formation of amyloid deposits, their toxicity and cellular defense mechanisms have been intensively studied. However, surprisingly little is known about the effects of protein aggregates on cellular signal transduction. It is also not understood whether the presence of aggregation-prone, but still soluble proteins affect signal transduction.
In this study, the still soluble aggregation-prone HttExon1Q74 and its amyloid aggregates were used to analyze the effect of amyloid aggregates on internalization and receptor activation of G protein-coupled receptors (GPCRs), the largest protein family of mammalian cell surface receptors involved in signal transduction. The aggregated HttExon1Q74, but not its soluble form, could inhibit ligand-induced clathrin-mediated endocytosis (CME) of various GPCRs. Most likely this inhibitory effect is based on a terminal sequestration of the HSC70 chaperone to the aggregates which is necessary for CME. Using the vasopressinV1a receptor (V1aR) and the corticotropin-releasing factor receptor 1 (CRF1R) as a model, it could be shown that the presence of HttExon1Q74 aggregates and the inhibition of ligand-induced CME leads to an accumulation of desensitized receptors at the plasma membrane. In turn, this disrupts Gq-mediated Ca2+ signaling and Gs-mediated cAMP signaling of the V1aR and the CRF1R respectively. In contrast to HttExon1Q74 amyloid aggregates, soluble HttExon1Q74 as well as amorphous aggregates did not inhibit GPCR internalization and signaling demonstrating that cellular signal transduction mechanisms are specifically impaired in response to the formation of amyloid aggregates.
In addition, preliminary experiments could show that HttExon1Q74 aggregates provoke an increase in membrane expression of a protein from a structurally and functionally unrelated membrane protein family, namely the serotonin transporter SERT. As SERT is the main pharmacological target to treat depression this could shed light on this commonly occurring comorbidity in neurodegenerative diseases, in particular in early disease states.
Conceptual knowledge about objects, people and events in the world is central to human cognition, underlying core cognitive abilities such as object recognition and use, and word comprehension. Previous research indicates that concepts consist of perceptual and motor features represented in modality-specific perceptual-motor brain regions. In addition, cross-modal convergence zones integrate modality-specific features into more abstract conceptual representations.
However, several questions remain open: First, to what extent does the retrieval of perceptual-motor features depend on the concurrent task? Second, how do modality-specific and cross-modal regions interact during conceptual knowledge retrieval? Third, which brain regions are causally relevant for conceptually-guided behavior? This thesis addresses these three key issues using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in the healthy human brain.
Study 1 - an fMRI activation study - tested to what extent the retrieval of sound and action features of concepts, and the resulting engagement of auditory and somatomotor brain regions depend on the concurrent task. 40 healthy human participants performed three different tasks - lexical decision, sound judgment, and action judgment - on words with a high or low association to sounds and actions. We found that modality-specific regions selectively respond to task-relevant features: Auditory regions selectively responded to sound features during sound judgments, and somatomotor regions selectively responded to action features during action judgments. Unexpectedly, several regions (e.g. the left posterior parietal cortex; PPC) exhibited a task-dependent response to both sound and action features. We propose these regions to be "multimodal", and not "amodal", convergence zones which retain modality-specific information.
Study 2 - an fMRI connectivity study - investigated the functional interaction between modality-specific and multimodal areas during conceptual knowledge retrieval. Using the above fMRI data, we asked (1) whether modality-specific and multimodal regions are functionally coupled during sound and action feature retrieval, (2) whether their coupling depends on the task, (3) whether information flows bottom-up, top-down, or bidirectionally, and (4) whether their coupling is behaviorally relevant. We found that functional coupling between multimodal and modality-specific areas is task-dependent, bidirectional, and relevant for conceptually-guided behavior. Left PPC acted as a connectivity "switchboard" that flexibly adapted its coupling to task-relevant modality-specific nodes.
Hence, neuroimaging studies 1 and 2 suggested a key role of left PPC as a multimodal convergence zone for conceptual knowledge. However, as neuroimaging is correlational, it remained unknown whether left PPC plays a causal role as a multimodal conceptual hub. Therefore, study 3 - a TMS study - tested the causal relevance of left PPC for sound and action feature retrieval. We found that TMS over left PPC selectively impaired action judgments on low sound-low action words, as compared to sham stimulation. Computational simulations of the TMS-induced electrical field revealed that stronger stimulation of left PPC was associated with worse performance on action, but not sound, judgments. These results indicate that left PPC causally supports conceptual processing when action knowledge is task-relevant and cannot be compensated by sound knowledge. Our findings suggest that left PPC is specialized for action knowledge, challenging the view of left PPC as a multimodal conceptual hub.
Overall, our studies support "hybrid theories" which posit that conceptual processing involves both modality-specific perceptual-motor regions and cross-modal convergence zones. In our new model of the conceptual system, we propose conceptual processing to rely on a representational hierarchy from modality-specific to multimodal up to amodal brain regions. Crucially, this hierarchical system is flexible, with different regions and connections being engaged in a task-dependent fashion. Our model not only reconciles the seemingly opposing grounded cognition and amodal theories, it also incorporates task dependency of conceptually-related brain activity and connectivity, thereby resolving several current issues on the neural basis of conceptual knowledge retrieval.
This paper-based dissertation aims to contribute to the open innovation (OI) and technology management (TM) research fields by investigating their mechanisms, and potentials at the operational level. The dissertation connects the well-known concept of technology management with OI formats and applies these on specific manufacturing technologies within a clearly defined setting.
Technological breakthroughs force firms to continuously adapt and reinvent themselves. The pace of technological innovation and their impact on firms is constantly increasing due to more connected infrastructure and accessible resources (i.e. data, knowledge). Especially in the manufacturing sector it is one key element to leverage new technologies to stay competitive. These technological shifts call for new management practices.
TM supports firms with various tools to manage these shifts at different levels in the firm. It is a multifunctional and multidisciplinary field as it deals with all aspects of integrating technological issues into business decision-making and is directly relevant to a number of core business processes. Thus, it makes sense to utilize this theory and their practices as a foundation of this dissertation. However, considering the increasing complexity and number of technologies it is not sufficient anymore for firms to only rely on previous internal R&D and managerial practices. OI can expanse these practices by involving distributed innovation processes and accessing further external knowledge sources. This expansion can lead to an increasing innovation performance and thereby accelerate the time-to-market of technologies.
Research in this dissertation was based on the expectations that OI formats will support the R&D activities of manufacturing technologies on the operational level by providing access to resources, knowledge, and leading-edge technology. The dissertation represents uniqueness regarding the rich practical data sets (observations, internal documents, project reviews) drawn from a very large German high-tech firm. The researcher was embedded in an R&D unit within the operational TM department for manufacturing technologies. The analyses include 1.) an exploratory in-depth analysis of a crowdsourcing initiative to elaborate the impact on specific manufacturing technologies, 2.) a deductive approach for developing a technology evaluation score model to create a common understanding of the value of selected manufacturing technologies at the operational level, and 3.) an abductive reasoning approach in form of a longitudinal case study to derive important indicator for the in-process activities of science-based partnership university-industry collaboration format. Thereby, the dissertation contributed to research and practice 1.) linkages of TM and OI practices to assimilate technologies at the operational level, 2.) insights about the impact of CS on manufacturing technologies and a related guideline to execute CS initiatives in this specific environment 3.) introduction of manufacturing readiness levels and further criteria into the TM and OI research field to support decision-makers in the firm in gaining a common understanding of the maturity of manufacturing technologies and, 4.) context-specific important indicators for science based university-industry collaboration projects and a holistic framework to connect TM with the university-industry collaboration approach
The findings of this dissertation illustrate that OI formats can support the acceleration of time-to-market of manufacturing technologies and further improve the technical requirements of the product by leveraging external capabilities. The conclusions and implications made are intended to foster further research and improve managerial practices to evolve TM into an open collaborative context with interconnectivities between all internal and external involved technologies, individuals and organizational levels.
Anthropogenic climate change alters the hydrological cycle. While certain areas experience more intense precipitation events, others will experience droughts and increased evaporation, affecting water storage in long-term reservoirs, groundwater, snow, and glaciers. High elevation environments are especially vulnerable to climate change, which will impact the water supply for people living downstream. The Himalaya has been identified as a particularly vulnerable system, with nearly one billion people depending on the runoff in this system as their main water resource. As such, a more refined understanding of spatial and temporal changes in the water cycle in high altitude systems is essential to assess variations in water budgets under different climate change scenarios.
However, not only anthropogenic influences have an impact on the hydrological cycle, but changes to the hydrological cycle can occur over geological timescales, which are connected to the interplay between orogenic uplift and climate change. However, their temporal evolution and causes are often difficult to constrain. Using proxies that reflect hydrological changes with an increase in elevation, we can unravel the history of orogenic uplift in mountain ranges and its effect on the climate.
In this thesis, stable isotope ratios (expressed as δ2H and δ18O values) of meteoric waters and organic material are combined as tracers of atmospheric and hydrologic processes with remote sensing products to better understand water sources in the Himalayas. In addition, the record of modern climatological conditions based on the compound specific stable isotopes of leaf waxes (δ2Hwax) and brGDGTs (branched Glycerol dialkyl glycerol tetraethers) in modern soils in four Himalayan river catchments was assessed as proxies of the paleoclimate and (paleo-) elevation. Ultimately, hydrological variations over geological timescales were examined using δ13C and δ18O values of soil carbonates and bulk organic matter originating from sedimentological sections from the pre-Siwalik and Siwalik groups to track the response of vegetation and monsoon intensity and seasonality on a timescale of 20 Myr.
I find that Rayleigh distillation, with an ISM moisture source, mainly controls the isotopic composition of surface waters in the studied Himalayan catchments. An increase in d-excess in the spring, verified by remote sensing data products, shows the significant impact of runoff from snow-covered and glaciated areas on the surface water isotopic values in the timeseries.
In addition, I show that biomarker records such as brGDGTs and δ2Hwax have the potential to record (paleo-) elevation by yielding a significant correlation with the temperature and surface water δ2H values, respectively, as well as with elevation. Comparing the elevation inferred from both brGDGT and δ2Hwax, large differences were found in arid sections of the elevation transects due to an additional effect of evapotranspiration on δ2Hwax. A combined study of these proxies can improve paleoelevation estimates and provide recommendations based on the results found in this study.
Ultimately, I infer that the expansion of C4 vegetation between 20 and 1 Myr was not solely dependent on atmospheric pCO2, but also on regional changes in aridity and seasonality from to the stable isotopic signature of the two sedimentary sections in the Himalaya (east and west).
This thesis shows that the stable isotope chemistry of surface waters can be applied as a tool to monitor the changing Himalayan water budget under projected increasing temperatures. Minimizing the uncertainties associated with the paleo-elevation reconstructions were assessed by the combination of organic proxies (δ2Hwax and brGDGTs) in Himalayan soil. Stable isotope ratios in bulk soil and soil carbonates showed the evolution of vegetation influenced by the monsoon during the late Miocene, proving that these proxies can be used to record monsoon intensity, seasonality, and the response of vegetation. In conclusion, the use of organic proxies and stable isotope chemistry in the Himalayas has proven to successfully record changes in climate with increasing elevation. The combination of δ2Hwax and brGDGTs as a new proxy provides a more refined understanding of (paleo-)elevation and the influence of climate.
Fluids in the Earth's crust can move by creating and flowing through fractures, in a process called `hydraulic fracturing’. The tip-line of such fluid-filled fractures grows at locations where stress is larger than the strength of the rock. Where the tip stress vanishes, the fracture closes and the fluid-front retreats. If stress gradients exist on the fracture's walls, induced by fluid/rock density contrasts or topographic stresses, this results in an asymmetric shape and growth of the fracture, allowing for the contained batch of fluid to propagate through the crust.
The state-of-the-art analytical and numerical methods to simulate fluid-filled fracture propagation are two-dimensional (2D). In this work I extend these to three dimensions (3D). In my analytical method, I approximate the propagating 3D fracture as a penny-shaped crack that is influenced by both an internal pressure and stress gradients. In addition, I develop a numerical method to model propagation where curved fractures can be simulated as a mesh of triangular dislocations, with the displacement of faces computed using the displacement discontinuity method. I devise a rapid technique to approximate stress intensity and use this to calculate the advance of the tip-line. My 3D models can be applied to arbitrary stresses, topographic and crack shapes, whilst retaining short computation times.
I cross-validate my analytical and numerical methods and apply them to various natural and man-made settings, to gain additional insights into the movements of hydraulic fractures such as magmatic dikes and fluid injections in rock. In particular, I calculate the `volumetric tipping point’, which once exceeded allows a fluid-filled fracture to propagate in a `self-sustaining’ manner. I discuss implications this has for hydro-fracturing in industrial operations. I also present two studies combining physical models that define fluid-filled fracture trajectories and Bayesian statistical techniques. In these studies I show that the stress history of the volcanic edifice defines the location of eruptive vents at volcanoes. Retrieval of the ratio between topographic to remote stresses allows for forecasting of probable future vent locations. Finally, I address the mechanics of 3D propagating dykes and sills in volcanic regions. I focus on Sierra Negra volcano in the Gal\'apagos islands, where in 2018, a large sill propagated with an extremely curved trajectory. Using a 3D analysis, I find that shallow horizontal intrusions are highly sensitive to topographic and buoyancy stress gradients, as well as the effects of the free surface.
The mitochondrial chaperone complex HSP60/HSP10 facilitates mitochondrial protein homeostasis by folding more than 300 mitochondrial matrix proteins. It has been shown previously that HSP60 is downregulated in brains of type 2 diabetic (T2D) mice and patients,
causing mitochondrial dysfunction and insulin resistance. As HSP60 is also decreased in peripheral tissues in T2D animals, this thesis investigated the effect of overall reduced HSP60 in the development of obesity and associated co-morbidities.
To this end, both female and male C57Bl/6N control (i.e. without further alterations in their genome, Ctrl) and heterozygous whole-body Hsp60 knock-out (Hsp60+/-) mice, which exhibit a 50 % reduction of HSP60 in all tissues, were fed a normal chow diet (NCD) or a highfat diet (HFD, 60 % calories from fat) for 16 weeks and were subjected to extensive metabolic phenotyping including indirect calorimetry, NMR spectroscopy, insulin, glucose and pyruvate tolerance tests, vena cava insulin injections, as well as histological and molecular analysis.
Interestingly, NCD feeding did not result in any striking phenotype, only a mild increase in energy expenditure in Hsp60+/- mice. Exposing mice to a HFD however revealed an increased body weight due to higher muscle mass in female Hsp60+/- mice, with a simultaneous decrease in energy expenditure. Additionally, these mice displayed decreased fasting glycemia. Opposingly, male Hsp60+/- compared to control mice showed lower body weight gain due to decreased fat mass and an increased energy expenditure, strikingly independent of lean mass. Further, only male Hsp60+/- mice display improved HOMA-IR and Matsuda
insulin sensitivity indices.
Despite the opposite phenotype in regards to body weight development, Hsp60+/- mice of both sexes show a significantly higher cell number, as well as a reduction in adipocyte size in the subcutaneous and gonadal white adipose tissue (sc/gWAT). Curiously, this adipocyte hyperplasia – usually associated with positive aspects of WAT function – is disconnected from metabolic improvements, as the gWAT of male Hsp60+/- mice shows mitochondrial dysfunction, oxidative stress, and insulin resistance. Transcriptomic analysis of gWAT shows an up
regulation of genes involved in macroautophagy. Confirmatory, expression of microtubuleassociated protein 1A/1B light chain 3B (LC3), as a protein marker of autophagy, and direct measurement of lysosomal activity is increased in the gWAT of male Hsp60+/- mice.
In summary, this thesis revealed a novel gene-nutrient interaction. The reduction of the crucial chaperone HSP60 did not have large effects in mice fed a NCD, but impacted metabolism during DIO in a sex-specific manner, where, despite opposing body weight and
body composition phenotypes, both female and male Hsp60+/- mice show signs of protection from high fat diet-induced systemic insulin resistance.
The High Energy Stereoscopic System (H.E.S.S.) is an array of five imaging atmospheric Cherenkov telescopes located in the Khomas Highland of Namibia. H.E.S.S. operates in a wide energy range from several tens of GeV to several tens of TeV, reaching the best sensitivity around 1 TeV or at lower energies. However, there are many important topics – such as the search for Galactic PeVatrons, the study of gamma-ray production scenarios for sources (hadronic vs. leptonic), EBL absorption studies – which require good sensitivity at energies above 10 TeV. This work aims at improving the sensitivity of H.E.S.S. and increasing the gamma-ray statistics at high energies. The study investigates an enlargement of the H.E.S.S. effective field of view using events with larger offset angles in the analysis. The greatest challenges in the analysis of large-offset events are a degradation of the reconstruction accuracy and a rise of the background rate as the offset angle increases. The more sophisticated direction reconstruction method (DISP) and improvements to the standard background rejection technique, which by themselves are effective ways to increase the gamma-ray statistics and improve the sensitivity of the analysis, are implemented to overcome the above-mentioned issues. As a result, the angular resolution at the preselection level is improved by 5 - 10% for events at 0.5◦ offset angle and by 20 - 30% for events at 2◦ offset angle. The background rate at large offset angles is decreased nearly to a level typical for offset angles below 2.5◦. Thereby, sensitivity improvements of 10 - 20% are achieved for the proposed analysis compared to the standard analysis at small offset angles. Developed analysis also allows for the usage of events at large offset angles up to approximately 4◦, which was not possible before. This analysis method is applied to the analysis of the Galactic plane data above 10 TeV. As a result, 40 sources out of the 78 presented in the H.E.S.S. Galactic plane survey (HGPS) are detected above 10 TeV. Among them are representatives of all source classes that are present in the HGPS catalogue; namely, binary systems, supernova remnants, pulsar wind nebulae and composite objects. The potential of the improved analysis method is demonstrated by investigating the more than 10 TeV emission for two objects: the region associated with the shell-type SNR HESS J1731−347 and the PWN candidate associated with PSR J0855−4644 that is coincident with Vela Junior (HESS J0852−463).
This thesis focuses on the study of marked Gibbs point processes, in particular presenting some results on their existence and uniqueness, with ideas and techniques drawn from different areas of statistical mechanics: the entropy method from large deviations theory, cluster expansion and the Kirkwood--Salsburg equations, the Dobrushin contraction principle and disagreement percolation.
We first present an existence result for infinite-volume marked Gibbs point processes. More precisely, we use the so-called entropy method (and large-deviation tools) to construct marked Gibbs point processes in R^d under quite general assumptions. In particular, the random marks belong to a general normed space S and are not bounded. Moreover, we allow for interaction functionals that may be unbounded and whose range is finite but random. The entropy method relies on showing that a family of finite-volume Gibbs point processes belongs to sequentially compact entropy level sets, and is therefore tight.
We then present infinite-dimensional Langevin diffusions, that we put in interaction via a Gibbsian description. In this setting, we are able to adapt the general result above to show the existence of the associated infinite-volume measure. We also study its correlation functions via cluster expansion techniques, and obtain the uniqueness of the Gibbs process for all inverse temperatures β and activities z below a certain threshold. This method relies in first showing that the correlation functions of the process satisfy a so-called Ruelle bound, and then using it to solve a fixed point problem in an appropriate Banach space. The uniqueness domain we obtain consists then of the model parameters z and β for which such a problem has exactly one solution.
Finally, we explore further the question of uniqueness of infinite-volume Gibbs point processes on R^d, in the unmarked setting. We present, in the context of repulsive interactions with a hard-core component, a novel approach to uniqueness by applying the discrete Dobrushin criterion to the continuum framework. We first fix a discretisation parameter a>0 and then study the behaviour of the uniqueness domain as a goes to 0. With this technique we are able to obtain explicit thresholds for the parameters z and β, which we then compare to existing results coming from the different methods of cluster expansion and disagreement percolation.
Throughout this thesis, we illustrate our theoretical results with various examples both from classical statistical mechanics and stochastic geometry.
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, thereby allowing mammals to maintain a constant body temperature in a cold environment. Thermogenic capacity of this tissue is due to a high mitochondrial density and expression of uncoupling protein 1 (UCP1), a unique brown adipocyte marker which dissipates the mitochondrial proton gradient to produce heat instead of ATP. BAT is actively involved in whole-body metabolic homeostasis and during aging there is a loss of classical brown adipose tissue with concomitantly reduced browning capacity of white adipose tissue. Therefore, an age-dependent decrease of BAT-related energy expenditure capacity may exacerbate the development of metabolic diseases, including obesity and type 2 diabetes mellitus. Given that direct effects of age-related changes of BAT-metabolic flux have yet to be unraveled, the aim of the current thesis is to investigate potential metabolic mechanisms involved in BAT-dysfunction during aging and to identify suitable metabolic candidates as functional biomarkers of BAT-aging. To this aim, integration of transcriptomic, metabolomic and proteomic data analyses of BAT from young and aged mice was performed, and a group of candidates with age-related changes was revealed. Metabolomic analysis showed age-dependent alterations of metabolic intermediates involved in energy, nucleotide and vitamin metabolism, with major alterations regarding the purine nucleotide pool. These data suggest a potential role of nucleotide intermediates in age-related BAT defects. In addition, the screening of transcriptomic and proteomic data sets from BAT of young and aged mice allowed identification of a 60-kDa lysophospholipase, also known as L-asparaginase (Aspg), whose expression declines during BAT-aging. Involvement of Aspg in brown adipocyte thermogenic function was subsequently analyzed at the molecular level using in vitro approaches and animal models. The findings revealed sensitivity of Aspg expression to β3-adrenergic activation via different metabolic cues, including cold exposure and treatment with β3-adrenergic agonist CL. To further examine ASPG function in BAT, an over-expression model of Aspg in a brown adipocyte cell line was established and showed that these cells were metabolically more active compared to controls, revealing increased expression of the main brown-adipocyte specific marker UCP1, as well as higher lipolysis rates. An in vitro loss-of-function model of Aspg was also functionally analyzed, revealing reduced brown adipogenic characteristics and an impaired lipolysis, thus confirming physiological relevance of Aspg in brown adipocyte function. Characterization of a transgenic mouse model with whole-body inactivation of the Aspg gene (Aspg-KO) allowed investigation of the role of ASPG under in vivo conditions, indicating a mild obesogenic phenotype, hypertrophic white adipocytes, impairment of the early thermogenic response upon cold-stimulation and dysfunctional insulin sensitivity. Taken together, these data show that ASPG may represent a new functional biomarker of BAT-aging that regulates thermogenesis and therefore a potential target for the treatment of age-related metabolic disease.
Filaments are omnipresent features in the solar chromosphere, one of the atmospheric layers of the Sun, which is located above the photosphere, the visible surface of the Sun. They are clouds of plasma reaching from the photosphere to the chromosphere, and even to the outer-most atmospheric layer, the corona. They are stabalized by the magnetic field. If the magnetic field is disturbed, filaments can erupt as coronal mass ejections (CME), releasing plasma into space, which can also hit the Earth. A special type of filaments are polar crown filaments, which form at the interface of the unipolar field of the poles and flux of opposite magnetic polarity, which was transported towards the poles. This flux transport is related to the global dynamo of the Sun and can therefore be analyzed indirectly with polar crown filaments. The main objective of this thesis is to better understand the physical properties and environment of high-latitude and polar crown filaments, which can be approached from two perspectives: (1) analyzing the large-scale properties of high-latitude and polar crown filaments with full-disk Hα observations from the Chromospheric Telescope (ChroTel) and (2) determining the relation of polar crown and high-latitude filaments from the chromosphere to the lower-lying photosphere with high-spatial resolution observations of the Vacuum Tower Telescope (VTT), which reveal the smallest details.
The Chromospheric Telescope (ChroTel) is a small 10-cm robotic telescope at Observatorio del Teide on Tenerife (Spain), which observes the entire Sun in Hα, Ca IIK, and He I 10830 Å. We present a new calibration method that includes limb-darkening correction, removal of non-uniform filter transmission, and determination of He I Doppler velocities. Chromospheric full-disk filtergrams are often obtained with Lyot filters, which may display non-uniform transmission causing large-scale intensity variations across the solar disk. Removal of a 2D symmetric limb-darkening function from full-disk images results in a flat background. However, transmission artifacts remain and are even more distinct in these contrast-enhanced images. Zernike polynomials are uniquely appropriate to fit these large-scale intensity variations of the background. The Zernike coefficients show a distinct temporal evolution for ChroTel data, which is likely related to the telescope’s alt-azimuth mount that introduces image rotation. In addition, applying this calibration to sets of seven filtergrams that cover the He I triplet facilitates determining chromospheric Doppler velocities. To validate the method, we use three datasets with varying levels of solar activity. The Doppler velocities are benchmarked with respect to co-temporal high-resolution spectroscopic data of the GREGOR Infrared Spectrograph (GRIS). Furthermore, this technique can be applied to ChroTel Hα and Ca IIK data. The calibration method for ChroTel filtergrams can be easily adapted to other full-disk data exhibiting unwanted large-scale variations. The spectral region of the He I triplet is a primary choice for high-resolution near-infrared spectropolarimetry. Here, the improved calibration of ChroTel data will provide valuable context data.
Polar crown filaments form above the polarity inversion line between the old magnetic flux of the previous cycle and the new magnetic flux of the current cycle. Studying their appearance and their properties can lead to a better understanding of the solar cycle. We use full-disk data of the ChroTel at Observatorio del Teide, Tenerife, Spain, which were taken in three different chromospheric absorption lines (Hα 6563 Å, Ca IIK 3933 Å, and He I 10830 Å), and we create synoptic maps. In addition, the spectroscopic He I data allow us to compute Doppler velocities and to create synoptic Doppler maps. ChroTel data cover the rising and decaying phase of Solar Cycle 24 on about 1000 days between 2012 and 2018. Based on these data, we automatically extract polar crown filaments with image-processing tools and study their properties. We compare contrast maps of polar crown filaments with those of quiet-Sun filaments. Furthermore, we present a super-synoptic map summarizing the entire ChroTel database. In summary, we provide statistical properties, i.e. number and location of filaments, area, and tilt angle for both the maximum and declining phase of Solar Cycle 24. This demonstrates that ChroTel provides a
promising dataset to study the solar cycle.
The cyclic behavior of polar crown filaments can be monitored by regular full-disk Hα observations. ChroTel provides such regular observations of the Sun in three chromospheric wavelengths. To analyze the cyclic behavior and the statistical properties of polar crown filaments, we have to extract the filaments from the images. Manual extraction is tedious, and extraction with morphological image processing tools produces a large number of false positive detections and the manual extraction of these takes too much time. Automatic object detection and extraction in a reliable manner allows us to process more data in a shorter time. We will present an overview of the ChroTel database and a proof of concept of a machine learning application, which allows us a unified extraction of, for example, filaments from ChroTel data.
The chromospheric Hα spectral line dominates the spectrum of the Sun and other stars. In the stellar regime, this spectral line is already used as a powerful tracer of magnetic activity. For the Sun, other tracers are typically used to monitor solar activity. Nonetheless, the Sun is observed constantly in Hα with globally distributed ground-based full-disk imagers. The aim of this study is to introduce Hα as a tracer of solar activity and compare it to other established indicators. We discuss the newly created imaging Hα excess in the perspective of possible application for modelling of stellar atmospheres. In particular, we try to determine how constant is the mean intensity of the Hα excess and number density of low-activity regions between solar maximum and minimum. Furthermore, we investigate whether the active region coverage fraction or the changing emission strength in the active regions dominates time variability in solar Hα observations. We use ChroTel observations of full-disk Hα filtergrams and morphological image processing techniques to extract the positive and negative imaging Hα excess, for bright features (plage regions) and dark absorption features (filaments and sunspots), respectively. We describe the evolution of the Hα excess during Solar Cycle 24 and compare it to other well established tracers: the relative sunspot number, the F10.7 cm radio flux, and the Mg II index. Moreover, we discuss possible applications of the Hα excess for stellar activity diagnostics and the contamination of exoplanet transmission spectra. The positive and negative Hα excess follow the behavior of the solar activity over the course of the cycle. Thereby, positive Hα excess is closely correlated to the chromospheric Mg II index. On the other hand, the negative Hα excess, created from dark features like filaments and sunspots, is introduced as a tracer of solar activity for the first time. We investigated the mean intensity distribution for active regions for solar minimum and maximum and found that the shape of both distributions is very similar but with different amplitudes. This might be related with the relatively stable coronal temperature component during the solar cycle. Furthermore, we found that the coverage fraction of Hα excess and the Hα excess of bright features are strongly correlated, which will influence modelling of stellar and exoplanet atmospheres.
High-resolution observations of polar crown and high-latitude filaments are scarce. We present a unique sample of such filaments observed in high-resolution Hα narrow-band filtergrams and broad-band images, which were obtained with a new fast camera system at the VTT. ChroTel provided full-disk context observations in Hα, Ca IIK, and He I 10830 Å. The Helioseismic and Magnetic Imager (HMI) and the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO) provided line-of-sight magnetograms and ultraviolet (UV) 1700 Å filtergrams, respectively. We study filigree in the vicinity of polar crown and high-latitude filaments and relate their locations to magnetic concentrations at the filaments’ footpoints. Bright points are a well studied phenomenon in the photosphere at low latitudes, but they were not yet studied in the quiet network close to the poles. We examine size, area, and eccentricity of bright points and find that their morphology is very similar to their counterparts at lower latitudes, but their sizes and areas are larger. Bright points at the footpoints of polar crown filaments are preferentially located at stronger magnetic flux concentrations, which are related to bright regions at the border of supergranules as observed in UV filtergrams. Examining the evolution of bright points on three consecutive days reveals that their amount increases while the filament decays, which indicates they impact the equilibrium of the cool plasma contained in filaments.
Active Galactic Nuclei (AGN) are considered to be the main powering source of active galaxies, where central Super Massive Black Holes (SMBHs), with masses between 106 and 109 M⊙ gravitationally pull the surrounding material via accre- tion. AGN phenomenon expands over a very wide range of luminosities, from the most luminous high-redshift quasars (QSOs), to the local Low-Luminosity AGN (LLAGN), with significantly weaker luminosities. While "typical" luminous AGNs distinguish themselves by their characteristical blue featureless continuum, the Broad Emission Lines (BELs) with Full Widths at Half Maximum (FWHM) in order of few thousands km s1, arising from the so-called Broad Line Region (BLR), and strong radio and/or X-ray emission, detection of LLAGNs on the other hand is quite chal- lenging due to their extremely weak emission lines, and absence of the power-law continuum. In order to fully understand AGN evolution and their duty-cycles across cosmic history, we need a proper knowledge of AGN phenomenon at all luminosi- ties and redshifts, as well as perspectives from different wavelength bands.
In this thesis I present a search for AGN signatures in central spectra of 542 local (0.005 < z < 0.03) galaxies from the Calar Alto Legacy Integral Field Area (CALIFA) survey. The adopted aperture of 3′′ × 3′′ corresponds to central ∼ 100 − 500 pc for the redshift range of CALIFA. Using the standard emission-line ratio diagnostic diagrams, we initially classified all CALIFA emission-line galaxies (526) into star- forming, LINER-like, Seyfert 2 and intermediates. We further detected signatures of the broad Hα component in 89 spectra from the sample, of which more than 60% are present in the central spectra of LINER-like galaxies. These BELs are very weak, with luminosities in range 1038 − 1041 erg s−1, but with FWHMs between 1000 km s−1 and 6000 km s−1, comparable to those of luminous high-z AGN. This result implies that type 1 AGN are in fact quite frequent in the local Universe. We also identified additional 29 Seyfert 2 galaxies using the emission-line ratio diagnostic diagrams.
Using the MBH − σ∗ correlation, we estimated black hole masses of 55 type 1 AGN from CALIFA, a sample for which we had estimates of bulge stellar velocity dispersions σ∗. We compared these masses to the ones that we estimated from the virial method and found large discrepancies. We analyzed the validity of both meth- ods for black hole mass estimation of local LLAGN, and concluded that most likely virial scaling relations can no longer be applied as a valid MBH estimator in such low-luminosity regime. These black holes accrete at very low rate, having Edding- ton ratios in range 4.1 × 10−5 − 2.4 × 10−3. Detection of BELs with such low lumi- nosities and at such low Eddington rates implies that these LLAGN are still able to form the BLR, although with probably modified structure of the central engine.
In order to obtain full picture of black hole growth across cosmic time, it is es- sential that we study them in different stages of their activity. For that purpose, we estimated the broad AGN Luminosity Function (AGNLF) of our entire type 1 AGN sample using the 1/Vmax method. The shape of AGNLF indicates an apparent flattening below luminosities LHα ∼ 1039 erg s−1. Correspondingly we estimated ac- tive Black Hole Mass Function (BHMF) and Eddington Ration Distribution Function (ERDF) for a sub-sample of type 1 AGN for which we have MBH and λ estimates. The flattening is also present in both BHMF and ERDF, around log(MBH) ∼ 7.7 and log(λ) < 3, respectively. We estimated the fraction of active SMBHs in CALIFA by comparing our active BHMF to the one of the local quiescent SMBHs. The shape of
the active fraction which decreases with increasing MBH, as well as the flattening of AGNLF, BHMF and ERDF is consistent with scenario of AGN cosmic downsizing.
To complete AGN census in the CALIFA galaxy sample, it is necessary to search for them in various wavelength bands. For the purpose of completing the census we performed cross-correlations between all 542 CALIFA galaxies and multiwavelength surveys, Swift – BAT 105 month catalogue (in hard 15 - 195 keV X-ray band), and NRAO VLA Sky Survey (NVSS, in 1.4 GHz radio domain). This added 1 new AGN candidate in X-ray, and 7 in radio wavelength band to our local LLAGN count.
It is possible to detect AGN emission signatures within 10 – 20 kpc outside of the central galactic regions. This may happen when the central AGN has recently switched off and the photoionized material is spread across the galaxy within the light-travel-time, or the photoionized material is blown away from the nucleus by outflows. In order to detect these extended AGN regions we constructed spatially resolved emission-line ratio diagnostic diagrams of all emission-line galaxies from the CALIFA, and found 1 new object that was previously not identified as AGN.
Obtaining the complete AGN census in CALIFA, with five different AGN types, showed that LLAGN contribute a significant fraction of 24% of the emission-line galaxies in the CALIFA sample. This result implies that AGN are quite common in the local Universe, and although being in very low activity stage, they contribute to large fraction of all local SMBHs. Within this thesis we approached the upper limit of AGN fraction in the local Universe and gained some deeper understanding of the LLAGN phenomenon.
Transient permeability in porous and fractured sandstones mediated by fluid-rock interactions
(2021)
Understanding the fluid transport properties of subsurface rocks is essential for a large number of geotechnical applications, such as hydrocarbon (oil/gas) exploitation, geological storage (CO2/fluids), and geothermal reservoir utilization. To date, the hydromechanically-dependent fluid flow patterns in porous media and single macroscopic rock fractures have received numerous investigations and are relatively well understood. In contrast, fluid-rock interactions, which may permanently affect rock permeability by reshaping the structure and changing connectivity of pore throats or fracture apertures, need to be further elaborated. This is of significant importance for improving the knowledge of the long-term evolution of rock transport properties and evaluating a reservoir’ sustainability. The thesis focuses on geothermal energy utilization, e.g., seasonal heat storage in aquifers and enhanced geothermal systems, where single fluid flow in porous rocks and rock fracture networks under various pressure and temperature conditions dominates.
In this experimental study, outcrop samples (i.e., Flechtinger sandstone, an illite-bearing Lower Permian rock, and Fontainebleau sandstone, consisting of pure quartz) were used for flow-through experiments under simulated hydrothermal conditions. The themes of the thesis are (1) the investigation of clay particle migration in intact Flechtinger sandstone and the coincident permeability damage upon cyclic temperature and fluid salinity variations; (2) the determination of hydro-mechanical properties of self-propping fractures in Flechtinger and Fontainebleau sandstones with different fracture features and contrasting mechanical properties; and (3) the investigation of the time-dependent fracture aperture evolution of Fontainebleau sandstone induced by fluid-rock interactions (i.e., predominantly pressure solution). Overall, the thesis aims to unravel the mechanisms of the instantaneous reduction (i.e., direct responses to thermo-hydro-mechanical-chemical (THMC) conditions) and progressively-cumulative changes (i.e., time-dependence) of rock transport properties.
Permeability of intact Flechtinger sandstone samples was measured under each constant condition, where temperature (room temperature up to 145 °C) and fluid salinity (NaCl: 0 ~ 2 mol/l) were stepwise changed. Mercury intrusion porosimetry (MIP), electron microprobe analysis (EMPA), and scanning electron microscopy (SEM) were performed to investigate the changes of local porosity, microstructures, and clay element contents before and after the experiments. The results indicate that the permeability of illite-bearing Flechtinger sandstones will be impaired by heating and exposure to low salinity pore fluids. The chemically induced permeability variations prove to be path-dependent concerning the applied succession of fluid salinity changes. The permeability decay induced by a temperature increase and a fluid salinity reduction operates by relatively independent mechanisms, i.e., thermo-mechanical and thermo-chemical effects.
Further, the hydro-mechanical investigations of single macroscopic fractures (aligned, mismatched tensile fractures, and smooth saw-cut fractures) illustrate that a relative fracture wall offset could significantly increase fracture aperture and permeability, but the degree of increase depends on fracture surface roughness. X-ray computed tomography (CT) demonstrates that the contact area ratio after the pressure cycles is inversely correlated to the fracture offset. Moreover, rock mechanical properties, determining the strength of contact asperities, are crucial so that relatively harder rock (i.e., Fontainebleau sandstone) would have a higher self-propping potential for sustainable permeability during pressurization. This implies that self-propping rough fractures with a sufficient displacement are efficient pathways for fluid flow if the rock matrix is mechanically strong.
Finally, two long-term flow-through experiments with Fontainebleau sandstone samples containing single fractures were conducted with an intermittent flow (~140 days) and continuous flow (~120 days), respectively. Permeability and fluid element concentrations were measured throughout the experiments. Permeability reduction occurred at the beginning stage when the stress was applied, while it converged at later stages, even under stressed conditions. Fluid chemistry and microstructure observations demonstrate that pressure solution governs the long-term fracture aperture deformation, with remarkable effects of the pore fluid (Si) concentration and the structure of contact grain boundaries. The retardation and the cessation of rock fracture deformation are mainly induced by the contact stress decrease due to contact area enlargement and a dissolved mass accumulation within the contact boundaries. This work implies that fracture closure under constant (pressure/stress and temperature) conditions is likely a spontaneous process, especially at the beginning stage after pressurization when the contact area is relatively small. In contrast, a contact area growth yields changes of fracture closure behavior due to the evolution of contact boundaries and concurrent changes in their diffusive properties. Fracture aperture and thus permeability will likely be sustainable in the long term if no other processes (e.g., mineral precipitations in the open void space) occur.
Due to global climate change providing food security for an increasing world population is a big challenge. Especially abiotic stressors have a strong negative effect on crop yield. To develop climate-adapted crops a comprehensive understanding of molecular alterations in the response of varying levels of environmental stresses is required. High throughput or ‘omics’ technologies can help to identify key-regulators and pathways of abiotic stress responses. In addition to obtain omics data also tools and statistical analyses need to be designed and evaluated to get reliable biological results.
To address these issues, I have conducted three different studies covering two omics technologies. In the first study, I used transcriptomic data from the two polymorphic Arabidopsis thaliana accessions, namely Col-0 and N14, to evaluate seven computational tools for their ability to map and quantify Illumina single-end reads. Between 92% and 99% of the reads were mapped against the reference sequence. The raw count distributions obtained from the different tools were highly correlated. Performing a differential gene expression analysis between plants exposed to 20 °C or 4°C (cold acclimation), a large pairwise overlap between the mappers was obtained. In the second study, I obtained transcript data from ten different Oryza sativa (rice) cultivars by PacBio Isoform sequencing that can capture full-length transcripts. De novo reference transcriptomes were reconstructed resulting in 38,900 to 54,500 high-quality isoforms per cultivar. Isoforms were collapsed to reduce sequence redundancy and evaluated, e.g. for protein completeness level (BUSCO), transcript length, and number of unique transcripts per gene loci. For the heat and drought tolerant aus cultivar N22, I identified around 650 unique and novel transcripts of which 56 were significantly differentially expressed in developing seeds during combined drought and heat stress. In the last study, I measured and analyzed the changes in metabolite profiles of eight rice cultivars exposed to high night temperature (HNT) stress and grown during the dry and wet season on the field in the Philippines. Season-specific changes in metabolite levels, as well as for agronomic parameters, were identified and metabolic pathways causing a yield decline at HNT conditions suggested.
In conclusion, the comparison of mapper performances can help plant scientists to decide on the right tool for their data. The de novo reconstruction of rice cultivars without a genome sequence provides a targeted, cost-efficient approach to identify novel genes responding to stress conditions for any organism. With the metabolomics approach for HNT stress in rice, I identified stress and season-specific metabolites which might be used as molecular markers for crop improvement in the future.
Bottom-up synthetic biology is used for the understanding of how a cell works. It is achieved through developing techniques to produce lipid-based vesicular structures as cellular mimics. The most common techniques used to produce cellular mimics or synthetic cells is through electroformation and swelling method. However, the abovementioned techniques cannot efficiently encapsulate macromolecules such as proteins, enzymes, DNA and even liposomes as synthetic organelles. This urges the need to develop new techniques that can circumvent this issue and make the artificial cell a reality where it is possible to imitate a eukaryotic cell through encapsulating macromolecules. In this thesis, the aim to construct a cell system using giant unilamellar vesicles (GUVs) to reconstitute the mitochondrial molybdenum cofactor biosynthetic pathway. This pathway is highly conserved among all life forms, and therefore is known for its biological significance in disorders induced through its malfunctioning. Furthermore, the pathway itself is a multi-step enzymatic reaction that takes place in different compartments. Initially, GTP in the mitochondrial matrix is converted to cPMP in the presence of cPMP synthase. Further, produced cPMP is transported across the membrane to the cytosol, to be converted by MPT synthase into MPT. This pathway provides a possibility to address the general challenges faced in the development of a synthetic cell, to encapsulate large biomolecules with good efficiency and greater control and to evaluate the enzymatic reactions involved in the process.
For this purpose, the emulsion-based technique was developed and optimised to allow rapid production of GUVs (~18 min) with high encapsulation efficiency (80%). This was made possible by optimizing various parameters such as density, type of oil, the impact of centrifugation speed/time, lipid concentration, pH, temperature, and emulsion droplet volume. Furthermore, the method was optimised in microtiter plates for direct experimentation and visualization after the GUV formation. Using this technique, the two steps - formation of cPMP from GTP and the formation of MPT from cPMP were encapsulated in different sets of GUVs to mimic the two compartments. Two independent fluorescence-based detection systems were established to confirm the successful encapsulation and conversion of the reactants. Alternatively, the enzymes produced using bacterial expression and measured. Following the successful encapsulation and evaluation of enzymatic reactions, cPMP transport across mitochondrial membrane has been mimicked using GUVs using a complex mitochondrial lipid composition. It was found that the cPMP interaction with the lipid bilayer results in transient pore-formation and leakage of internal contents.
Overall, it can be concluded that in this thesis a novel technique has been optimised for fast production of functional synthetic cells. The individual enzymatic steps of the Moco biosynthetic pathway have successfully implemented and quantified within these cellular mimics.
Botulinum neurotoxin (BoNT) is produced by the anaerobic bacterium Clostridium botulinum. It is one of the most potent toxins found in nature and can enter motor neurons (MN) to cleave proteins necessary for neurotransmission, resulting in flaccid paralysis. The toxin has applications in both traditional and esthetic medicine. Since BoNT activity varies between batches despite identical protein concentrations, the activity of each lot must be assessed. The gold standard method is the mouse lethality assay, in which mice are injected with a BoNT dilution series to determine the dose at which half of the animals suffer death from peripheral asphyxia. Ethical concerns surrounding the use of animals in toxicity testing necessitate the creation of alternative model systems to measure the potency of BoNT.
Prerequisites of a successful model are that it is human specific; it monitors the complete toxic pathway of BoNT; and it is highly sensitive, at least in the range of the mouse lethality assay. One model system was developed by our group, in which human SIMA neuroblastoma cells were genetically modified to express a reporter protein (GLuc), which is packaged into neurosecretory vesicles, and which, upon cellular depolarization, can be released – or inhibited by BoNT – simultaneously with neurotransmitters. This assay has great potential, but includes the inherent disadvantages that the GLuc sequence was randomly inserted into the genome and the tumor cells only have limited sensitivity and specificity to BoNT. This project aims to improve these deficits, whereby induced pluripotent stem cells (iPSCs) were genetically modified by the CRISPR/Cas9 method to insert the GLuc sequence into the AAVS1 genomic safe harbor locus, precluding genetic disruption through non-specific integrations. Furthermore, GLuc was modified to associate with signal peptides that direct to the lumen of both large dense core vesicles (LDCV), which transport neuropeptides, and synaptic vesicles (SV), which package neurotransmitters. Finally, the modified iPSCs were differentiated into motor neurons (MNs), the true physiological target of BoNT, and hypothetically the most sensitive and specific cells available for the MoN-Light BoNT assay.
iPSCs were transfected to incorporate one of three constructs to direct GLuc into LDCVs, one construct to direct GLuc into SVs, and one “no tag” GLuc control construct. The LDCV constructs fused GLuc with the signal peptides for proopiomelanocortin (hPOMC-GLuc), chromogranin-A (CgA-GLuc), and secretogranin II (SgII-GLuc), which are all proteins found in the LDCV lumen. The SV construct comprises a VAMP2-GLuc fusion sequence, exploiting the SV membrane-associated protein synaptobrevin (VAMP2). The no tag GLuc expresses GLuc non-specifically throughout the cell and was created to compare the localization of vesicle-directed GLuc.
The clones were characterized to ensure that the GLuc sequence was only incorporated into the AAVS1 safe harbor locus and that the signal peptides directed GLuc to the correct vesicles. The accurate insertion of GLuc was confirmed by PCR with primers flanking the AAVS1 safe harbor locus, capable of simultaneously amplifying wildtype and modified alleles. The PCR amplicons, along with an insert-specific amplicon from candidate clones were Sanger sequenced to confirm the correct genomic region and sequence of the inserted DNA. Off-target integrations were analyzed with the newly developed dc-qcnPCR method, whereby the insert DNA was quantified by qPCR against autosomal and sex-chromosome encoded genes. While the majority of clones had off-target inserts, at least one on-target clone was identified for each construct.
Finally, immunofluorescence was utilized to localize GLuc in the selected clones. In iPSCs, the vesicle-directed GLuc should travel through the Golgi apparatus along the neurosecretory pathway, while the no tag GLuc should not follow this pathway. Initial analyses excluded the CgA-GLuc and SgII-GLuc clones due to poor quality protein visualization. The colocalization of GLuc with the Golgi was analyzed by confocal microscopy and quantified. GLuc was strongly colocalized with the Golgi in the hPOMC-GLuc clone (r = 0.85±0.09), moderately in the VAMP2-GLuc clone (r = 0.65±0.01), and, as expected, only weakly in the no tag GLuc clone (r = 0.44±0.10). Confocal microscopy of differentiated MNs was used to analyze the colocalization of GLuc with proteins associated with LDCVs and SVs, SgII in the hPOMC-GLuc clone (r = 0.85±0.08) and synaptophysin in the VAMP2-GLuc clone (r = 0.65±0.07). GLuc was also expressed in the same cells as the MN-associated protein, Islet1.
A significant portion of GLuc was found in the correct cell type and compartment. However, in the MoN-Light BoNT assay, the hPOMC-GLuc clone could not be provoked to reliably release GLuc upon cellular depolarization. The depolarization protocol for hPOMC-GLuc must be further optimized to produce reliable and specific release of GLuc upon exposure to a stimulus. On the other hand, the VAMP2-GLuc clone could be provoked to release GLuc upon exposure to the muscarinic and nicotinic agonist carbachol. Furthermore, upon simultaneous exposure to the calcium chelator EGTA, the carbachol-provoked release of GLuc could be significantly repressed, indicating the detection of GLuc was likely associated with vesicular fusion at the presynaptic terminal. The application of the VAMP2-GLuc clone in the MoN-Light BoNT assay must still be verified, but the results thus far indicate that this clone could be appropriate for the application of BoNT toxicity assessment.
In the last decades, there was a notable progress in solving the well-known Boolean satisfiability (Sat) problem, which can be witnessed by powerful Sat solvers. One of the reasons why these solvers are so fast are structural properties of instances that are utilized by the solver’s interna. This thesis deals with the well-studied structural property treewidth, which measures the closeness of an instance to being a tree. In fact, there are many problems parameterized by treewidth that are solvable in polynomial time in the instance size when parameterized by treewidth.
In this work, we study advanced treewidth-based methods and tools for problems in knowledge representation and reasoning (KR). Thereby, we provide means to establish precise runtime results (upper bounds) for canonical problems relevant to KR. Then, we present a new type of problem reduction, which we call decomposition-guided (DG) that
allows us to precisely monitor the treewidth when reducing from one problem to another problem. This new reduction type will be the basis for a long-open lower bound result for quantified Boolean formulas and allows us to design a new methodology for establishing runtime lower bounds for problems parameterized by treewidth.
Finally, despite these lower bounds, we provide an efficient implementation of algorithms that adhere to treewidth. Our approach finds suitable abstractions of instances, which are subsequently refined in a recursive fashion, and it uses Sat solvers for solving subproblems. It turns out that our resulting solver is quite competitive for two canonical counting problems related to Sat.
There is a general consensus that diverse ecological communities are better equipped to adapt to changes in their environment, but our understanding of the mechanisms by which they do so remains incomplete. Accurately predicting how the global biodiversity crisis affects the functioning of ecosystems, and the services they provide, requires extensive knowledge about these mechanisms.
Mathematical models of food webs have been successful in uncovering many aspects of the link between diversity and ecosystem functioning in small food web modules, containing at most two adaptive trophic levels. Meaningful extrapolation of this understanding to the functioning of natural food webs remains difficult, due to the presence of complex interactions that are not always accurately captured by bitrophic descriptions of food webs. In this dissertation, we expand this approach to tritrophic food web models by including the third trophic level. Using a functional trait approach, coexistence of all species is ensured using fitness-balancing trade-offs. For example, the defense-growth trade-off implies that species may be defended against predation, but this defense comes at the cost of a lower maximal growth rate. In these food webs, the functional diversity on a given trophic level can be varied by modifying the trait differences between the species on that level.
In the first project, we find that functional diversity promotes high biomass on the top level, which, in turn, leads to a reduction in the temporal variability due to compensatory dynamical patterns governed by the top level. Next, these results are generalized by investigating the average behavior of tritrophic food webs, for wide intervals of all parameters describing species interactions in the food web. We find that the diversity on the top level is most important for determining the biomass and temporal variability of all other trophic levels, and show how biomass is only transferred efficiently to the top level when diversity is high everywhere in the food web. In the third project, we compare the response of a simple food chain against a nutrient pulse perturbation, to that of a food web with diversity on every trophic level. By joint consideration of the resistance, resilience, and elasticity, we uncover that the response is efficiently buffered when biomass on the top level is high, which is facilitated by functional diversity on every trophic level in the food web. Finally, in the fourth project, we show that even in a simple consumer-resource model without any diversity, top-down control on the intermediate level frequently causes the phase difference between the intermediate and basal level to deviate from the quarter-cycle lag rule. By adding a top predator, we show that these deviations become even more likely, and anti-phase cycles are often observed.
The combined results of these projects show how the properties of the top trophic level, including its functional diversity, have a decisive influence on the functioning of tritrophic food webs from a mechanistic perspective. Because top species are often among the most vulnerable to extinction, our results emphasize the importance of their conservation in ecosystem management and restoration strategies.
As part of our everyday life we consume breaking news and interpret it based on our own viewpoints and beliefs. We have easy access to online social networking platforms and news media websites, where we inform ourselves about current affairs and often post about our own views, such as in news comments or social media posts. The media ecosystem enables opinions and facts to travel from news sources to news readers, from news article commenters to other readers, from social network users to their followers, etc. The views of the world many of us have depend on the information we receive via online news and social media. Hence, it is essential to maintain accurate, reliable and objective online content to ensure democracy and verity on the Web. To this end, we contribute to a trustworthy media ecosystem by analyzing news and social media in the context of politics to ensure that media serves the public interest. In this thesis, we use text mining, natural language processing and machine learning techniques to reveal underlying patterns in political news articles and political discourse in social networks.
Mainstream news sources typically cover a great amount of the same news stories every day, but they often place them in a different context or report them from different perspectives. In this thesis, we are interested in how distinct and predictable newspaper journalists are, in the way they report the news, as a means to understand and identify their different political beliefs. To this end, we propose two models that classify text from news articles to their respective original news source, i.e., reported speech and also news comments. Our goal is to capture systematic quoting and commenting patterns by journalists and news commenters respectively, which can lead us to the newspaper where the quotes and comments are originally published. Predicting news sources can help us understand the potential subjective nature behind news storytelling and the magnitude of this phenomenon. Revealing this hidden knowledge can restore our trust in media by advancing transparency and diversity in the news.
Media bias can be expressed in various subtle ways in the text and it is often challenging to identify these bias manifestations correctly, even for humans. However, media experts, e.g., journalists, are a powerful resource that can help us overcome the vague definition of political media bias and they can also assist automatic learners to find the hidden bias in the text. Due to the enormous technological advances in artificial intelligence, we hypothesize that identifying political bias in the news could be achieved through the combination of sophisticated deep learning modelsxi and domain expertise. Therefore, our second contribution is a high-quality and reliable news dataset annotated by journalists for political bias and a state-of-the-art solution for this task based on curriculum learning. Our aim is to discover whether domain expertise is necessary for this task and to provide an automatic solution for this traditionally manually-solved problem. User generated content is fundamentally different from news articles, e.g., messages are shorter, they are often personal and opinionated, they refer to specific topics and persons, etc. Regarding political and socio-economic news, individuals in online communities make use of social networks to keep their peers up-to-date and to share their own views on ongoing affairs. We believe that social media is also an as powerful instrument for information flow as the news sources are, and we use its unique characteristic of rapid news coverage for two applications. We analyze Twitter messages and debate transcripts during live political presidential debates to automatically predict the topics that Twitter users discuss. Our goal is to discover the favoured topics in online communities on the dates of political events as a way to understand the political subjects of public interest. With the up-to-dateness of microblogs, an additional opportunity emerges, namely to use social media posts and leverage the real-time verity about discussed individuals to find their locations.
That is, given a person of interest that is mentioned in online discussions, we use the wisdom of the crowd to automatically track her physical locations over time. We evaluate our approach in the context of politics, i.e., we predict the locations of US politicians as a proof of concept for important use cases, such as to track people that
are national risks, e.g., warlords and wanted criminals.
The propagation of test fields, such as electromagnetic, Dirac or linearized gravity, on a fixed spacetime manifold is often studied by using the geometrical optics approximation. In the limit of infinitely high frequencies, the geometrical optics approximation provides a conceptual transition between the test field and an effective point-particle description. The corresponding point-particles, or wave rays, coincide with the geodesics of the underlying spacetime. For most astrophysical applications of interest, such as the observation of celestial bodies, gravitational lensing, or the observation of cosmic rays, the geometrical optics approximation and the effective point-particle description represent a satisfactory theoretical model. However, the geometrical optics approximation gradually breaks down as test fields of finite frequency are considered.
In this thesis, we consider the propagation of test fields on spacetime, beyond the leading-order geometrical optics approximation. By performing a covariant Wentzel-Kramers-Brillouin analysis for test fields, we show how higher-order corrections to the geometrical optics approximation can be considered. The higher-order corrections are related to the dynamics of the spin internal degree of freedom of the considered test field. We obtain an effective point-particle description, which contains spin-dependent corrections to the geodesic motion obtained using geometrical optics. This represents a covariant generalization of the well-known spin Hall effect, usually encountered in condensed matter physics and in optics. Our analysis is applied to electromagnetic and massive Dirac test fields, but it can easily be extended to other fields, such as linearized gravity. In the electromagnetic case, we present several examples where the gravitational spin Hall effect of light plays an important role. These include the propagation of polarized light rays on black hole spacetimes and cosmological spacetimes, as well as polarization-dependent effects on the shape of black hole shadows. Furthermore, we show that our effective point-particle equations for polarized light rays reproduce well-known results, such as the spin Hall effect of light in an inhomogeneous medium, and the relativistic Hall effect of polarized electromagnetic wave packets encountered in Minkowski spacetime.
As society paves its way towards device miniaturization and precision medicine, micro-scale actuation and guided transport become increasingly prominent research fields, with high potential impact in both technological and clinical contexts. In order to accomplish directed motion of micron-sized objects, as biosensors and drug-releasing microparticles, towards specific target sites, a promising strategy is the use of living cells as smart biochemically-powered carriers, building the so-called bio-hybrid systems. Inspired by leukocytes, native cells of living organisms efficiently migrating to critical targets as tumor tissue, an emerging concept is to exploit the amoeboid crawling motility of such cells as mean of transport for drug delivery applications.
In the research work described in this thesis, I synergistically applied experimental, computational and theoretical modeling approaches to investigate the behaviour and transport mechanism of a novel kind of bio-hybrid system for active transport at the micro-scale, referred to as cellular truck. This system consists of an amoeboid crawling cell, the carrier, attached to a microparticle, the cargo, which may ideally be drug-loaded for specific therapeutic treatments.
For the purposes of experimental investigation, I employed the amoeba Dictyostelium discoideum as crawling cellular carrier, being a renowned model organism for leukocyte migration and, in general, for eukaryotic cell motility. The performed experiments revealed a complex recurrent cell-cargo relative motion, together with an intermittent motility of the cellular truck as a whole. The evidence suggests the presence of cargoes on amoeboid cells to act as mechanical stimulus leading cell polarization, thus promoting cell motility and giving rise to the observed intermittent dynamics of the truck. Particularly, bursts in cytoskeletal polarity along the cell-cargo axis have been
found to occur in time with a rate dependent on cargo geometrical features, as particle diameter. Overall, the collected experimental evidence pointed out a pivotal role of cell-cargo interactions in the emergent cellular truck motion dynamics. Especially, they can determine the transport capabilities of amoeboid cells, as the cargo size significantly impacts the cytoskeletal activity and repolarization dynamics along the cell-cargo axis, the latter responsible for truck displacement and reorientation.
Furthermore, I developed a modeling framework, built upon the experimental evidence on cellular truck behaviour, that connects the relative dynamics and interactions arising at the truck scale with the actual particle transport dynamics. In fact, numerical simulations of the proposed model successfully reproduced the phenomenology of the cell-cargo system, while enabling the prediction of the transport properties of cellular trucks over larger spatial and temporal scales. The theoretical analysis provided a deeper understanding of the role of cell-cargo interaction on mass transport, unveiling in particular how the long-time transport efficiency is governed by the interplay between the persistence time of cell polarity and time scales of the relative dynamics stemming from cell-cargo interaction. Interestingly, the model predicts the existence of an optimal cargo size, enhancing the diffusivity of cellular trucks; this is in line with previous independent experimental data, which appeared rather counterintuitive and had no explanation prior to this study.
In conclusion, my research work shed light on the importance of cargo-carrier interactions in the context of crawling cell-mediated particle transport, and provides a prototypical, multifaceted framework for the analysis and modelling of such complex bio-hybrid systems and their perspective optimization.
This work develops hybrid methods of imaging spectroscopy for open pit mining and examines their feasibility compared with state-of-the-art. The material distribution within a mine face differs in the small scale and within daily assigned extraction segments. These changes can be relevant to subsequent processing steps but are not always visually identifiable prior to the extraction. Misclassifications that cause false allocations of extracted material need to be minimized in order to reduce energy-intensive material re-handling. The use of imaging spectroscopy aspires to the allocation of relevant deposit-specific materials before extraction, and allows for efficient material handling after extraction. The aim of this work is the parameterization of imaging spectroscopy for pit mining applications and the development and evaluation of a workflow for a mine face, ground- based, spectral characterization. In this work, an application-based sensor adaptation is proposed. The sensor complexity is reduced by down-sampling the spectral resolution of the system based on the samples’ spectral characteristics. This was achieved by the evaluation of existing hyperspectral outcrop analysis approaches based on laboratory sample scans from the iron quadrangle in Minas Gerais, Brazil and by the development of a spectral mine face monitoring workflow which was tested for both an operating and an inactive open pit copper mine in the Republic of Cyprus.
The workflow presented here is applied to three regional data sets: 1) Iron ore samples from Brazil, (laboratory); 2) Samples and hyperspectral mine face imagery from the copper-gold-pyrite mine Apliki, Republic of Cyprus (laboratory and mine face data); and 3) Samples and hyperspectral mine face imagery from the copper-gold-pyrite deposit Three Hills, Republic of Cyprus (laboratory and mine face data). The hyperspectral laboratory dataset of fifteen Brazilian iron ore samples was used to evaluate different analysis methods and different sensor models. Nineteen commonly used methods to analyze and map hyperspectral data were compared regarding the methods’ resulting data products and the accuracy of the mapping and the analysis computation time. Four of the evaluated methods were determined for subsequent analyses to determine the best-performing algorithms: The spectral angle mapper (SAM), a support vector machine algorithm (SVM), the binary feature fitting algorithm (BFF) and the EnMap geological mapper (EnGeoMap). Next, commercially available imaging spectroscopy sensors were evaluated for their usability in open pit mining conditions. Step-wise downsampling of the data - the reduction of the number of bands with an increase of each band’s bandwidth - was performed to investigate the possible simplification and ruggedization of a sensor without a quality fall-off of the mapping results. The impact of the atmosphere visible in the spectrum between 1300–2010nm was reduced by excluding the spectral range from the data for mapping. This tested the feasibility of the method under realistic open pit data conditions. Thirteen datasets based on the different, downsampled sensors were analyzed with the four predetermined methods. The optimum sensor for spectral mine face material distinction was determined as a VNIR-SWIR sensor with 40nm bandwidths in the VNIR and 15nm bandwidths in the SWIR spectral range and excluding the atmospherically impacted bands. The Apliki mine sample dataset was used for the application of the found optimal analyses and sensors. Thirty-six samples were analyzed geochemically and mineralogically. The sample spectra were compiled to two spectral libraries, both distinguishing between seven different geochemical-spectral clusters. The reflectance dataset was downsampled to five different sensors. The five different datasets were mapped with the SAM, BFF and SVM method achieving mapping accuracies of 85-72%, 85-76% and 57-46% respectively. One mine face scan of Apliki was used for the application of the developed workflow. The mapping results were validated against the geochemistry and mineralogy of thirty-six documented field sampling points and a zonation map of the mine face which is based on sixty-six samples and field mapping. The mine face was analyzed with SAM and BFF. The analysis maps were visualized on top of a Structure-from-Motion derived 3D model of the open pit. The mapped geological units and zones correlate well with the expected zonation of the mine face. The third set of hyperspectral imagery from Three Hills was available for applying the fully-developed workflow. Geochemical sample analyses and laboratory spectral data of fifteen different samples from the Three Hills mine, Republic of Cyprus, were used to analyse a downsampled mine face scan of the open pit. Here, areas of low, medium and high ore content were identified.
The developed workflow is successfully applied to the open pit mines Apliki and Three Hills and the spectral maps reflect the prevailing geological conditions. This work leads through the acquisition, preparation and processing of imaging spectroscopy data, the optimum choice of analysis methodology, and the utilization of simplified, robust sensors that meet the requirements of open pit mining conditions. It accentuates the importance of a site-specific and deposit-specific spectral library for the mine face analysis and underlines the need for geological and spectral analysis experts to successfully implement imaging spectroscopy in the field of open pit mining.
The aim of the doctoral project was to answer the question of whether the structural word-initial noun capitalization, as it can otherwise only be found in Luxembourgish alongside German, has a function that is advantageous for the reader. The overriding hypothesis was that an advantage is achieved by activating a syntactic category, namely the core of a noun phrase, through the parafoveal perception of the capital letters. This perception from the corner of the eye should make it possible to preprocess the following noun. As a result, sentence processing should be facilitated, which should ultimately be reflected in overall faster reading times and fixation durations.
The structure of the project includes three studies, some of which included different participant groups:
Study 1:
Study design: Semantic priming using garden-path sentences should bring out the functionality of noun capitalization for the reader
Participant groups: German natives reading German
Study 2:
Study design: same design as study 1, but in English
Participant groups:
English natives without any knowledge of German reading English
English natives who regularly read German reading English
German with high proficiency in English reading English
Study 3:
Study design:
Influence of the noun frequency on a potential preprocessing using the boundary paradigm; Study languages: German and English
Participant groups:
German natives reading German
English natives without any knowledge of German reading English
German with high proficiency in English reading English
Brief summary: The noun capitalization clearly has an impact on sentence processing in both German and English. It cannot be confirmed that this has a substantial, decisive advantage.
Compound values are not universally supported in virtual machine (VM)-based programming systems and languages. However, providing data structures with value characteristics can be beneficial. On one hand, programming systems and languages can adequately represent physical quantities with compound values and avoid inconsistencies, for example, in representation of large numbers. On the other hand, just-in-time (JIT) compilers, which are often found in VMs, can rely on the fact that compound values are immutable, which is an important property in optimizing programs. Considering this, compound values have an optimization potential that can be put to use by implementing them in VMs in a way that is efficient in memory usage and execution time. Yet, optimized compound values in VMs face certain challenges: to maintain consistency, it should not be observable by the program whether compound values are represented in an optimized way by a VM; an optimization should take into account, that the usage of compound values can exhibit certain patterns at run-time; and that necessary value-incompatible properties due to implementation restrictions should be reduced.
We propose a technique to detect and compress common patterns of compound value usage at run-time to improve memory usage and execution speed. Our approach identifies patterns of frequent compound value references and introduces abbreviated forms for them. Thus, it is possible to store multiple inter-referenced compound values in an inlined memory representation, reducing the overhead of metadata and object references. We extend our approach by a notion of limited mutability, using cells that act as barriers for our approach and provide a location for shared, mutable access with the possibility of type specialization. We devise an extension to our approach that allows us to express automatic unboxing of boxed primitive data types in terms of our initial technique. We show that our approach is versatile enough to express another optimization technique that relies on values, such as Booleans, that are unique throughout a programming system. Furthermore, we demonstrate how to re-use learned usage patterns and optimizations across program runs, thus reducing the performance impact of pattern recognition.
We show in a best-case prototype that the implementation of our approach is feasible and can also be applied to general purpose programming systems, namely implementations of the Racket language and Squeak/Smalltalk. In several micro-benchmarks, we found that our approach can effectively reduce memory consumption and improve execution speed.
Modern knowledge bases contain and organize knowledge from many different topic areas. Apart from specific entity information, they also store information about their relationships amongst each other. Combining this information results in a knowledge graph that can be particularly helpful in cases where relationships are of central importance. Among other applications, modern risk assessment in the financial sector can benefit from the inherent network structure of such knowledge graphs by assessing the consequences and risks of certain events, such as corporate insolvencies or fraudulent behavior, based on the underlying network structure. As public knowledge bases often do not contain the necessary information for the analysis of such scenarios, the need arises to create and maintain dedicated domain-specific knowledge bases.
This thesis investigates the process of creating domain-specific knowledge bases from structured and unstructured data sources. In particular, it addresses the topics of named entity recognition (NER), duplicate detection, and knowledge validation, which represent essential steps in the construction of knowledge bases.
As such, we present a novel method for duplicate detection based on a Siamese neural network that is able to learn a dataset-specific similarity measure which is used to identify duplicates. Using the specialized network architecture, we design and implement a knowledge transfer between two deduplication networks, which leads to significant performance improvements and a reduction of required training data.
Furthermore, we propose a named entity recognition approach that is able to identify company names by integrating external knowledge in the form of dictionaries into the training process of a conditional random field classifier. In this context, we study the effects of different dictionaries on the performance of the NER classifier. We show that both the inclusion of domain knowledge as well as the generation and use of alias names results in significant performance improvements.
For the validation of knowledge represented in a knowledge base, we introduce Colt, a framework for knowledge validation based on the interactive quality assessment of logical rules. In its most expressive implementation, we combine Gaussian processes with neural networks to create Colt-GP, an interactive algorithm for learning rule models. Unlike other approaches, Colt-GP uses knowledge graph embeddings and user feedback to cope with data quality issues of knowledge bases. The learned rule model can be used to conditionally apply a rule and assess its quality.
Finally, we present CurEx, a prototypical system for building domain-specific knowledge bases from structured and unstructured data sources. Its modular design is based on scalable technologies, which, in addition to processing large datasets, ensures that the modules can be easily exchanged or extended. CurEx offers multiple user interfaces, each tailored to the individual needs of a specific user group and is fully compatible with the Colt framework, which can be used as part of the system.
We conduct a wide range of experiments with different datasets to determine the strengths and weaknesses of the proposed methods. To ensure the validity of our results, we compare the proposed methods with competing approaches.
Polymeric semiconductors are strong contenders for replacing traditional inorganic semiconductors in electronic applications requiring low power, low cost and flexibility, such as biosensors, flexible solar cells and electronic displays. Molecular doping has the potential to enable this revolution by improving the conductivity and charge transport properties of this class of materials. Despite decades of research in this field, gaps in our understanding of the nature of dopant–polymer interactions has resulted in limited commercialization of this technology. This work aims at providing a deeper insight into the underlying mechanisms of molecular p-doping of semiconducting polymers in the solution and solid-state, and thereby bring the scientific community closer to realizing the dream of making organic semiconductors commonplace in the electronics industry. The role of 1) dopant size/shape, 2) polymer chain aggregation and 3) charge delocalization on the doping mechanism and efficiency is addressed using optical (UV-Vis-NIR) and electron paramagnetic resonance (EPR) spectroscopies. By conducting a comprehensive study of the nature and concentration of the doping-induced species in solutions of the polymer poly(3-hexylthiophene) (P3HT) with 3 different dopants, we identify the unique optical signatures of the delocalized polaron, localized polaron and charge-transfer complex, and report their extinction coefficient values. Furthermore, with X-ray diffraction, atomic force microscopy and electrical conductivity measurements, we study the impact of processing technique and doping mechanism on the morphology and thereby, charge transport through the doped films.
This work demonstrates that the doping mechanism and type of doping-induced species formed are strongly influenced by the polymer backbone arrangement rather than dopant shape/size. The ability of the polymer chain to aggregate is found to be crucial for efficient charge transfer (ionization) and polaron delocalization. At the same time, our results suggest that the high ionization efficiency of a dopant–polymer system in solution may subsequently hinder efficient charge transport in the solid-state due to the reduction in the fraction of tie chains, which enable charges to move efficiently between aggregated domains in the films. This study demonstrates the complex multifaceted nature of polymer doping while providing important hints for the future design of dopant-host systems and film fabrication techniques.
The objective of this book is to provide ICAO, States, competent authorities and aerodrome operators with a comprehensive overview of legal challenges related to international aerodrome planning. Answers to derived legal questions as well as recommendations thereafter shall help to enhance regulatory systems and to establish a safer aerodrome environment worldwide. Compliant aerodrome planning has an immense impact on the safety of passengers, personnel, aircraft – and of course the airport. Achieving a high safety standard is crucial, as many incidents and accidents in aviation happen at or in the vicinity of airports. Currently, more than 40% of the ICAO Member States do not fully comply with international legal requirements for aerodrome planning. Representatives of ICAO and States, as well as aerodrome and authority personnel, will understand why compliance with the different legal facets of aerodrome planning is challenging and learn how shortcomings can be solved.
Negotiations between buyers and suppliers directly influence a company’s costs, revenue, and consequently its profits. The outcome of these negotiations relies heavily on the companies’ as well as the negotiators’ power position. Across three empirical articles the author demonstrates how the own power position can first be identified as well as improved and subsequently used to maximize profits in negotiations between sellers and buyers. In the first paper the sources underlying buyer and supplier power are identified and weighted. The results of the first paper show the impact of each single sources on the buyer and supplier power. The number of suppliers available for one product is by far the most important source of power for both sides. The results indicate that a higher number of suppliers leads to a better power position of the buyer and simultaneously to an inferior power position of a single supplier. The second paper aims to examine the impact of the number of suppliers on the outcome of buyer-seller-negotiations thereby considering the innovation level of the products purchased. The results of the second study which are based on real negotiation data from a German car manufacturer indicate that the number of available suppliers has a stronger impact on the negotiation outcome for innovative than for functional, less innovative products. The third paper analyzes how the ability to take the counterpart’s perspective (perspective taking ability) influences the negotiation outcome. This relationship is examined for different power positions. The results indicate that a negotiator’s high perspective taking ability leads to a more unfavorable negotiation outcome compared to low perspective taking ability. Simultaneously, high perspective taking ability causes a more positive perception of the conducted negotiation than low perspective taking ability. This contradictory effect of perspective taking ability bears the risk for buyers and suppliers to assess an unfavorable outcome as positive. Finally, the results of the papers are summarized and discussed. The dissertation concludes with implications for practice, limitations of the work, and approaches for future research.
Angular momentum is a particularly sensitive probe into stellar evolution because it changes significantly over the main sequence life of a star. In this thesis, I focus on young main sequence stars of which some feature a rapid evolution in their rotation rates. This transition from fast to slow rotation is inadequately explored observationally and this work aims to provide insights into the properties and time scales but also investigates stellar rotation in young open clusters in general.
I focus on the two open clusters NGC 2516 and NGC 3532 which are ~150 Myr (zero-age main sequence age) and ~300 Myr old, respectively. From 42 d-long time series photometry obtained at the Cerro Tololo Inter-American Observatory, I determine stellar rotation periods in both clusters. With accompanying low resolution spectroscopy, I measure radial velocities and chromospheric emission for NGC 3532, the former to establish a clean membership and the latter to probe the rotation-activity connection.
The rotation period distribution derived for NGC 2516 is identical to that of four other coeval open clusters, including the Pleiades, which shows the universality of stellar rotation at the zero-age main sequence. Among the similarities (with the Pleiades) the "extended slow rotator sequence" is a new, universal, yet sparse, feature in the colour-period diagrams of open clusters. From a membership study, I find NGC 3532 to be one of the richest nearby open clusters with 660 confirmed radial velocity members and to be slightly sub-solar in metallicity. The stellar rotation periods for NGC 3532 are the first published for a 300 Myr-old open cluster, a key age to understand the transition from fast to slow rotation. The fast rotators at this age have significantly evolved beyond what is observed in NGC 2516 which allows to estimate the spin-down timescale and to explore the issues that angular momentum models have in describing this transition. The transitional sequence is also clearly identified in a colour-activity diagram of stars in NGC 3532. The synergies of the chromospheric activity and the rotation periods allow to understand the colour-activity-rotation connection for NGC 3532 in unprecedented detail and to estimate additional rotation periods for members of NGC 3532, including stars on the "extended slow rotator sequence".
In conclusion, this thesis probes the transition from fast to slow rotation but has also more general implications for the angular momentum evolution of young open clusters.
The scapula plays a significant role in efficient shoulder movement. Thus, alterations from typical scapular motion during upper limb movements are thought to be associated with shoulder pathologies. However, a clear understanding of the relationship is not yet obtained.. Scapular alterations may only represent physiological variability as their occurrence can appear equally as frequent in individuals with and without shoulder disorders. Evaluation of scapular motion during increased load might be a beneficial approach to detect clinically relevant alterations. However, functional motion adaptations in response to maximum effort upper extremity loading has not been established yet. Therefore, the overall purpose of this research project was to give further insight in physiological adaptations of scapular kinematics and their underlying scapular muscle activity in response to high demanding shoulder movements in healthy asymptomatic individuals. Prior to the investigation of the effect of various load situation, the reproducibility of scapular kinematics and scapular muscle activity were evaluated under maximum effort arm movements. Healthy asymptomatic adults performed unloaded and maximal loaded concentric and eccentric isokinetic shoulder flexion and extension movements in the scapular plane while scapular kinematics and scapular muscle activity were simultaneously assessed. A 3D motion capture system (infra-red cameras & reflective markers) was utilized to track scapular and humerus motion in relation to the thorax. 3D scapular position angles were given for arm raising and lowering between humerus positions of 20° and 120° flexion. To further characterize the scapular pattern, the scapular motion extent and scapulohumeral rhythm (ratio of scapular and humerus motion extent) were determined. Muscle activity of the upper and lower trapezius and the serratus anterior were assessed with surface electromyography. Amplitudes were calculated for the whole ROM and four equidistant movement phases. Reliability was characterized by overall moderate to good reproducibility across the load conditions. Irrespective of applied load, scapular kinematics followed a motion pattern of continuous upward rotation, posterior tilt and external rotation during arm elevation and a continuous downward rotation, anterior tilt and internal rotation during arm lowering. However, kinematics were altered between maximal loaded and unloaded conditions showing increased upward rotation, reduced posterior tilt and external rotation. Further, the scapulohumeral rhythm was decreased and scapular motion extent increased under maximal loaded movements. Muscle activity during maximum effort were of greater magnitude and differed in their pattern in comparison to the continuous increase and decrease of activity during unloaded shoulder flexion and extension. Relationships between scapular kinematics and their underlying scapular muscle activity could only be identified for a few isolated combinations, whereas the majority showed no associations. Scapular kinematics and scapular muscle activity pattern alter according to the applied load. Alterations between the load conditions comply in magnitude and partially in direction with differences seen between symptomatic and asymptomatic individuals. Even though long-term effects of identified adaptations in response to maximum load are so far unclear, deviations from typical scapular motion or muscle activation should not per se be seen as indicators of shoulder impairment. However, evaluation of alterations in scapular motion and activation in response to maximum effort may have the potential to identify individuals that are unable to cope with increased upper limb demands. Findings further challenge the understanding of scapular motion and stabilization by the trapezius and serratus anterior muscles, as clear relationships between the underlying scapular muscle activity and scapular kinematics were neither observed during unloaded nor maximal loaded shoulder movements.
The development of type 2 diabetes (T2D) is driven by genetic as well as life style factors. However, even genetically identical female NZO mice on a high-fat diet show a broad variation in T2D onset. The main objective of this study was to elucidate and investigate early epigenetic determinants of type 2 diabetes. Prior to other experiments, early fat content of the liver (<55.2 HU) in combination with blood glucose concentrations (>8.8 mM) were evaluated as best predictors of diabetes in NZO females. Then, DNA methylome and transcriptome were profiled to identify molecular pathophysiological changes in the liver before diabetes onset. The major finding of this thesis is that alterations in the hepatic DNA methylome precede diabetes onset. Of particular interest were 702 differentially methylated regions (DMRs), of which 506 DMRs had genic localization. These inter-individual DMRs were enriched by fivefold in the KEGG pathway type 2 diabetes mellitus, independent of the level of gene expression, demonstrating an epigenetic predisposition toward diabetes. Interestingly, among the list of hepatic DMRs, eleven DMRs were associated with known imprinted genes in the mouse genome. Thereby, six DMRs (Nap1l5, Mest, Plagl1, Gnas, Grb10 and Slc38a4) localized to imprinting control regions, including five iDMRs that exhibited hypermethylation in livers of diabetes-prone mice. This suggests that gain of DNA methylation in multiple loci of the paternal alleles has unfavourable metabolic consequences for the offspring. Further, the comparative liver transcriptome analysis demonstrated differences in expression levels of 1492 genes related to metabolically relevant pathways, such as citrate cycle and fatty acid metabolism. The integration of hepatic transcriptome and DNA methylome indicated that 449 differentially expressed genes were potentially regulated by DNA methylation, including genes implicated in insulin signaling. In addition, liver transcriptomic profiling of diabetes-resistant and diabetes-prone mice revealed a potential transcriptional dysregulation of 17 hepatokines, in particular Hamp. The hepatic expression of Hamp was decreased by 52% in diabetes-prone mice, on account of an increase in DNA methylation of promoter CpG-118. Hence, HAMP protein levels were lower in mice prone to develop diabetes, which correlated to higher liver triglyceride levels.. In sum, the identified DNA methylation changes appear to collectively favor the initiation and progression of diabetes in female NZO mice. In near future, epigenetic biomarkers are likely to contribute to improved diagnosis for T2D.