The research field of spintronics emerges as a promising solution to address the core challenges posed by charge-based electronic information processing, aiming to reduce power dissipation while delivering lasting endurance and robust read and write capabilities. Spintronic circuits have already made their mark, finding practical applications in commercially accessible magnetic random-access memories. However, to effectively compete with future complementary metal–oxide–semiconductor (CMOS) and photonic technologies, fundamental spin operations speed should ideally extend to terahertz (THz) frequencies. In this respect, an exciting discovery is a new class of highly efficient and broadband THz emitters based on magnetic heterostructures, harnessing spintronic effects at terahertz frequencies.
This work is dedicated to addressing a series of fundamental questions, for example: What is the primary driving force for spin currents in spintronic THz emitters (STEs)? How do these spin currents relate to other processes such as ultrafast demagnetization dynamics? How do spin currents propagate through different material systems? What are the maximum speeds of spin current propagation? How can the spin conductance of various materials be quantified? Finally, how can the amplitude of the THz radiation from STEs be maximized to values exceeding 1 MV/cm?
First, we compare two central phenomena in femtomagnetism: ultrafast demagnetization and ultrafast spin currents in magnetic heterostructures. Strikingly, our findings unveil that both phenomena are driven by the same force, a generalized spin voltage, i.e., the excess of magnetization relative to equilibrium. We conclude that the spin voltage is genuinely ultrafast, and the decay of the spin voltage is predominantly due to spin-flip processes inside the ferromagnet, with only a minor fraction of spins contributing to the transport. Subsequently, we explore spin current propagation in copper and MgO tunnel junctions. Our results reveal that spin currents in copper propagate at high speed, reaching the Fermi velocity vF = 1.1 nm/fs with velocity-relaxation time of of τ =4 fs, and we separate ballistic and diffusive modes of spin transport. Furthermore, we introduce the new concept of THz spin-conductance spectroscopy. We apply this method to measure the spin conductance of an MgO tunnel junction, allowing to separate different spin-transport contributions, including coherent tunneling and incoherent resonant spin tunneling mediated through MgO defects. Finally, based on these findings, we significantly improve the STE performance by optimizing the heat management and maximizing the THz outcoupling. Our proposed Si-based STE design outperforms previous glass-based STEs by a factor of six, achieving a peak electric field of 1.7 MV/cm. Eventually, Si-STEs prove to be highly effective in inducing nonlinear effects such as the THz Kerr effect in diamond or Zeeman torque in magnets. In conclusion, this work demonstrates the significant potential of terahertz spin transport that can shape the future of ultrafast circuits.
Weniger anzeigenThis thesis presents the synthesis metal complexes with a variety of fluorinated ligand systems, featuring tripodal, terpiridine and azobenzene ligands. The resulting compounds thereof show various characteristics and therefore were investigated in terms of their geometric and electronic structures by single crystal X-ray diffraction, cyclic voltammetry, superconducting quantum interference device (SQUID) magnetometry and/or (spectro- )electrochemical methods. The first part of this thesis addresses new compounds of the form [M(L)2](BF4)2 (M = cobalt(II), iron(II); L = fluorinated tripodal ligand) and the influence of fluorine specific interactions in the secondary coordination sphere on the spin state of the central metal ion. For this purpose, a combined study by single X-ray diffraction analysis and SQUID magnetometry measurements was performed to investigate the spin states of the metal centers. It could be shown, that for the ligand, which contains either a pentrafluoro-benzyl or a 4-fluorobenzyl substituents, an effect of the fluorine specific interactions was observed. The complexes bearing the pentafluorobenzyl substituents do not display the expected!⋯! interactions, but an edge-to-face interaction. However, this leads to a change of the spin state for the iron(II) complex, while the corresponding cobalt(II) complexes remain in the low spin state. For the other substituent a partial spin crossover (SCO) behavior was observed for one cobalt(II) complex, depending on the co-crystallizing solvent, while the iron(II) complex displays a complete SCO. These results were obtained by a combination of X-ray diffraction analysis, SQUID magnetometry, electron paramagnetic resonance (EPR) spectroscopy and theoretical calculations. In the second part terpyridine ligands bearing different fluorinated backbones were implemented with cobalt(II) and iron(II) and the differences within the complexes were investigated primarily by SQUID magnetometry and EPR studies. The cobalt(II) complexes, where the tpy ligands bear a long fluorinated alkyl chain, show fluorine specific interactions that have an impact on the EPR spectra. Furthermore, ruthenium(II) complexes combining a mesoionic carbene and a terpyridine ligand were employed for electrocatalytic reduction of CO2. The complexes show a high selectivity towards CO and a faradaic efficiency of 92%. The final part deals with a series of platinum(II) donor-acceptor complexes bearing different azobenzene and bridging quinone ligands. The complexes exhibit strong electrochromic behavior and were studied towards the influence of different (perfluorinated) alkyl chains on the azobenzene ligands on the electrochemical behavior. In the present thesis the impact of fluorine on different ligand systems and its influence on the physical and electrochemical properties of the resulting metal complexes are highlighted, which can be useful for estimating the properties of potential target compounds.
Weniger anzeigenCurrent genetic testing of patients performed to identify the molecular cause and potentially drive therapy decisions is predominately focused on small variation affecting coding regions due to the limitations of the underlying experimental methods. Long-read sequencing approaches have been shown to overcome these limitations allowing the detection of the entire spectrum of larger genomic alterations i.e. structural variants (SVs) with an unprecedented resolution potentially revealing previously undetected disease-causing mechanisms. In this thesis, we discuss the potential of long-read sequencing in combination with a functional annotation-based framework to identify non-coding pathogenic SVs in a cohort of limb malformation patients. In the process, we developed a pipeline that combines short- and long-read sequencing data, filters the detected SVs based on allele frequency, and applies an extensive functional annotation-based prioritization resulting in sets of candidate SVs for all involved patients. We also conduct a comprehensive comparison of callers and technologies highlighting the superior performance of long-read sequencing for SV detection and an evaluation of an automated prioritization method indicating superior performance to comparable approaches. The results of this thesis suggest the potential of performing an extended analysis of SVs as part of clinical diagnostics workflows and the relevance of non-coding functional annotation during variant prioritization.
Weniger anzeigenSmall- and medium-sized enterprises (SMEs) are an important force for promoting innovation in China as they represent the bulk of China’s industrial fabric and have the most innovative vitality and potential due to entrepreneurial dynamism, organizational flexibility, and fast responsiveness. However, SMEs generally lack financial, technological, and human resources to develop innovation. Furthermore, innovation gives rise to externalities, which could reduce the incentive of SMEs to engage in innovation. Therefore, public aids are needed in support of SME innovation. In light of the variety of innovation behavior among SMEs, innovation policies should be designed to target certain SMEs and support them according to their specific characteristics. In addition, with a strong focus on formal R&D and main types of technological innovation (i.e., product and process innovation), prior research restricts a comprehensive understanding of diverse innovation activities, especially non-R&D activities, and different innovation types, especially non-technological innovation. Given the need for targeted innovation policies and the under-researched heterogeneity among innovating SMEs, this dissertation aims to deepen the understanding of SME innovation heterogeneity from a perspective of the following innovation process: innovation activities – innovation types – SME overall performance. This dissertation is organized into five chapters. Chapter 1 introduces research motivations, theoretical background, research design, and an overview of the three articles presented in Chapters 2, 3, and 4. Three empirical articles in Chapters 2, 3, and 4 constitute the core of this dissertation and they are summarized as follows. The first article in Chapter 2 empirically analyzes SME heterogeneity in innovation activities based on the input stage of the aforementioned innovation process (innovation activities – innovation types), especially by disentangling the varying effects of innovation activities on technological types of innovation. This article, focusing mainly on non-R&D sources of innovation, compares non-R&D and R&D SMEs with respect to the separate and combined effects of non-R&D activities on product and process innovation. Drawing on a database collected from 1,392 manufacturing SMEs in China, empirical result reveals heterogeneous importance of non-R&D activities to product and process innovation for non-R&D and R&D SMEs. Specifically, non-R&D SMEs rely mainly on embodied knowledge to introduce technological innovation, while R&D SMEs can access external knowledge from customers and scientific sources to develop product innovation and also from suppliers to introduce process innovation. In addition, substitutability is found between internal and external innovation strategies composed of non-R&D activities, which is limited to product innovation for non-R&D SMEs and process innovation for R&D SMEs. The second article in Chapter 3 contributes to the empirical analysis of SME heterogeneity in innovation types based on the output stage of the process (innovation types – SME overall performance), especially by exploring different combinations of innovation types and their effects on SME performance. This article investigates SMEs’ combined use of different innovation types as well as the effect of the combination of innovation types on SME performance. The empirical analysis is based on data from 1,139 Chinese manufacturing SMEs. The results of factor analysis imply a tendency of combining product, quality, and organizational innovation and the other tendency of combining efficiency and flexibility innovation. A conditional approach to supermodularity is used to test for the relationship between different types of innovation. The results show that product, quality, and organizational innovation are neither complements nor substitutes, meaning that their combination generates only additive effects on SME performance. It is also found that substitutability between efficiency and flexibility exists without organizational innovation but it disappears with organizational innovation, which suggests that simultaneous organizational innovation is required for better use of efficiency and flexibility innovation in combination. The third article in Chapter 4 synthesizes SME innovation heterogeneity through the identification of SME innovation patterns according to the inputs and outputs (i.e., innovation activities and innovation types) of the innovation process. Based on a sample of 1,127 Chinese manufacturing SMEs, this article identifies SME patterns of innovation activities and of innovation types and uses the identified innovation patterns to analyze the relationship between innovation and SME performance, contributing to a comprehensive analysis of the whole innovation process. The innovation activities associated with internal and external knowledge sourcing characterize three innovation sourcing patterns, namely internal sourcing group, low sourcing group, and open sourcing group, which differ in activeness and openness of knowledge sourcing. The innovation types involving technological and non-technological types of innovation profile three innovation introducing patterns, namely production innovators, product innovators, and multifaceted innovators, which differ in the variety of innovation types introduced. Regarding the relationship between innovation sourcing and introducing patterns, being active in innovation activities increases the likelihood of introducing various innovation types and being open is most likely to capture a variety of innovation types. The results for the relationship between innovation introducing patterns and SME performance show that production innovators combining efficiency and flexibility innovation experience decreased performance while product innovators focusing on product innovation and multifaceted innovators combining technological and non-technological innovation achieve better performance. Chapter 5 concludes by discussing the contributions to innovation research, innovation policy, and innovation management, along with the limitations of this dissertation and the directions for future research.
Weniger anzeigenDuring mammalian corticogenesis, a wide diversity of neural stem cells (NSCs) orchestrate the development and organization of the cortex. The pool of NSCs initially expands through proliferative symmetric divisions, and sequentially starts dividing asymmetrically to give rise to the diverse cell types residing within the cortical layers. Throughout this process, cortical NSCs undergo extensive modifications in their transcriptomic profile and chromatin landscape contributing to the formation of heterogeneous progenitor populations. Although much progress has been made towards understanding cell-fate specification during human corticogenesis the mechanisms responsible for the temporal lineage specification of NSCs remain largely unknown. Understanding the variability of these distinct NSC populations is key for developing an in vitro system that allows for the homogeneous and unlimited culture of the desired NSC type which is crucial for cell replacement-based therapies. Hence, one of the main aims in our lab is to identify and discern these distinct NSC types which sequentially appear during cortical development with the objective to better understand these cell stages and, eventually, being able to manipulate them in vitro. In order to address this question, my project is focused on developing a strategy to isolate the early cortical NSC population for its characterization and potential manipulation. The main approach is to identify a cell surface marker to enable the isolation of these cells from our in vitro culture by fluorescence-activated cell sorting. By profiling our hiPSC-derived cortical progenitors at different stages by means of single-cell RNA sequencing, we selected potential candidate markers that were validated using immunofluorescence and sequencing methods. In this study, we identify Protogenin (PRTG) as a novel surface marker for early human cortical NSCs that can be used to isolate this population in vitro. We provide evidence that early expression of the novel marker correlates with cortical lineage specification. Furthermore, by sorting for such marker at early stages of neural induction we can prospectively isolate three distinct cortical subpopulations, resulting in highly pure subtype-specific NSC cultures. These findings illustrate the utility of PRTG cell-surface sorting for enriching early cortical NSCs in culture and, thus, aiding to develop a more robust and homogenous differentiation protocol. Ultimately, such knowledge should facilitate the generation of highly pure stage- and region-specific NSC populations from patient-derived samples which would provide a reliable source for cell replacement and regenerative therapies.
Weniger anzeigenChemical synapses are fundamental for fast and reliable synaptic transmission and proves as fundamental basis needed for cognitive functions in higher organisms as well as in humans. The ability of synapses to communicate with each other by synaptic vesicle release of neurotransmitters enables them to create a big neuronal network responsible for information relay to other parts of the body. Communication from neuron to neuron happens through release of neurotransmitter-containing synaptic vesicles from presynapse to postsynapse. Synaptic vesicles must be tethered, primed, and then fused with the presynaptic membrane to fulfil their purpose. This is orchestrated by a complex proteinaceous machinery at dedicated cytomatrix sites at the presynapse, known as active zone (AZ). These active zones are essential for synaptic vesicle release and specific scaffolding proteins are needed to assemble and maintain this complex machinery. This synaptic vesicle release machinery has been observed in Drosophila melanogaster’s glutamatergic type I terminals and can be observed as an electron-dense structure in ultrastructural images. This is not the case for the smaller type II synaptic terminals that emerge from neuromodulatory ventral unpaired median (VUM) neurons in the ventral nerve cord (VNC). These VUM neurons extend their synaptic terminals towards the peripheric larval body wall muscles of Drosophila and innervate those muscles. The synapses of these neurons are in proximity of glutamatergic type I terminal neurons and are known to act neuromodulatory on the muscle. Contrary to type I terminals, type II terminals don’t possess an electron-dense structure and the synaptic vesicle release machinery is still widely unknown. Previously it has been shown that the presynaptic active zone protein BRP is present in type I as well as in type II terminals. This thesis can confirm the presence of BRP in the neuromodulatory type II terminals via stimulated emission depletion (STED) microscopy and shows through larval locomotion analyser “IMBA” that other known type I terminal active zone proteins such as Unc13A, Unc13B and RBP are present in those neurons. The use of RNAi lines allowed for a knockdown (KD) of the tested AZ proteins, where different larval locomotive microbehaviour parameters were tested. Analysis of these data have shown that Unc13A, Unc13B and RBP KD mutants show an increased crawling speed via a decrease in “step interval”, while BRP KD mutants showed no such increase. Additionally, Unc13A and Unc13B KD mutants show an increase in lateral head movement that precedes a reorientation event, also known as head cast (HC) in Drosophila larvae. Furthermore, STED microscopy was used to check for the tested proteins in better resolution with immunohistochemical approaches , but this remained unsuccessful. STED images confirmed the presence of BRP spots in type II boutons, which were previously only seen through confocal microscopy. Overexpression and KD of BRP in octopaminergic/tyraminergic (OA/TA) neurons didn’t alter type II bouton morphology, but number of BRP spots per bouton. Additionally, this thesis inspects the possible interaction between type I and type II terminal neurons during pupal stages throughout the metamorphosis. Immunohistochemical approaches showed no obvious dependence on each other during metamorphosis for innervation target finding. In the second part of my thesis, we extended our research from our master’s thesis and started working from there. Aging is a process that remains mainly ununderstood. Few theories have been proposed, and one of them is the “free radical theory of aging and radiation chemistry” by D. Harman, suggesting the involvement of reactive oxygen species (ROS) in aging. ROS are O2-derived free radicals that are, in high amount, capable of causing several intracellular damages ultimately leading to cell death. Most of the ROS are produced in mitochondria and are within physiological levels, used for intracellular signalling. To maintain a healthy intracellular redox equilibrium, redox couples to scavenge ROS are used in the cell. One of the dominant redox couples is the tripeptide glutathione (GSH) and its oxidized form glutathione disulphide (GSSG). The distribution of GSH/GSSG in cells are around 90% in the cytoplasm, 10% in the mitochondria and a low percentage in the endoplasmic reticulum. Mitochondria are very well known as “the powerhouse of the cell” as they are the main energy producer within cells and are an organelle with their own mitochondrial DNA (mtDNA). With age, mtDNA accumulates mutations, leading to defect in the respiratory chain and ultimately resulting into cell death. To counteract an accumulation of defective mitochondria, mitochondria are transported back to the soma for degradation through mitophagy. Axonal transport declines with age and impaired mitochondrial transport are a key pathogenic change in aging associated neurodegenerative diseases. Spermidine is a polyamine that has been shown to mediate anti-aging effects through boosting autophagy and acts as an amino-butyl group donor for hypusination of the eukaryotic initiation factor 5A (eIF5A) which has been shown to be involved in spermidine-mediated protection of mitochondrial functionality. Here, we show through the use of in vivo imaging of adult fly wings, that mitochondrial transport and transport velocity were not affected with age in flies, regardless of dietary spermidine supplementation. We also showed that mitochondrial GSH/GSSG ratio was not affected with age or spermidine supplementation, through the use of an engineered green fluorescent protein (roGFP), containing a disulfide switch with different excitation maxima depending on its oxidation status. Lastly, we used the same construct investigate mitochondrial glutathione redox status to measure the effects of a deoxyhypusine synthase (DHPS) knockdown mutant on mitochondrial GSH/GSSG equilibrium. We saw no significant changes in our control groups, but a significant increase in mid-aged flies when DHPS was genetically reduced, which absent in flies with dietary spermidine supplementation.
Weniger anzeigenBianchi models are posited by the BKL picture to be essential building blocks towards an understanding of generic cosmological singularities. We study the behaviour of spatially homogeneous anisotropic vacuum spacetimes of Bianchi type VIII and IX, as they approach the big bang singularity. It is known since 2001 that generic Bianchi IX spacetimes converge towards the so-called Mixmaster attractor as time goes towards the singularity. We extend this result to the case of Bianchi VIII vacuum. The BKL picture suggests that particle horizons should form, i.e. spatially separate regions should causally decouple. We prove that this decoupling indeed occurs, for Lebesgue almost every Bianchi VIII and IX vacuum spacetime.
Weniger anzeigenWithin the body, every cell contains the same genetic blueprint, the DNA, which is wrapped around histones and densely packed in the nucleus. Given the same genome, the identity of each cell is in part defined by modifications to the histones but also the genomic sequence itself, such as DNA methylation, that define active and inactive parts of the DNA. In somatic cells, DNA methylation levels are largely bimodal, with a high genome-wide methylation average that predominantly excludes CpG islands (CGIs), features often found near gene promoters that remain free of methylation. These patterns change across the majority of human cancer types, which exhibit global loss of methylation accompanied by a gain of methylation at select CGIs. To date, bisulfite sequencing represents the gold-standard method to profile DNA methylation at single-base resolution and has been widely used to characterize and understand DNA methylation landscapes in healthy and tumor cells. This thesis presents advancements in the computational analysis of bisulfite sequencing data sets, as well as applications to large-scale studies of DNA methylation in cancer. It showcases the adaptation of a local alignment tool to enable homology search for bisulfite-converted sequences, which outperforms established semi-global alignment tools when applied to the search of metagenomic data sets. Additionally, this thesis describes the development of a new application that provides fast and simplified extraction of DNA methylation heterogeneity metrics from single reads of bisulfite sequencing data. The importance of such metrics is demonstrated in the context of two studies that focus on DNA methylation changes within primary tumors and cancer cell lines. Single-read metrics and single-cell methylome profiling show that primary tumors are mainly characterized by heterogeneous, intermediate global and CGI DNA methylation that is intrinsic to the underlying single tumor cells. In contrast, cancer cell lines mostly assume one of two different states, where global DNA methylation levels are either drastically decreased or comparable to healthy tissues, while CGIs become almost fully methylated in both scenarios. Although rarely seen in solid tumors, extremely high genome-wide methylation levels can also be observed in an exceptional primary tumor type, acute lymphoblastic leukemia, where this landscape is influenced by specific epigenetic regulators. Together, the findings of this thesis advance our ability to analyze bisulfite sequencing data sets as well as to apply these more nuanced measurements to understand DNA methylation changes during tumorigenesis and in culture.
Weniger anzeigenIm Jahr 2018 wurden 844 Augenabstriche von 785 verschiedenen Pferden bakteriologisch untersucht. Die Keimidentifizierung erfolgte neben Beurteilung der Kulturmorphologie und biochemischen Methoden mittels MALDI-TOF. Die Resistenztestung wurde im Mikrodilutionsverfahren nach den Standards des CLSI als Breakpoint-Methode durchgeführt. 8% (n=65/844) aller Augentupfer waren bakteriologisch negativ. Bei 31% (n=264/844) zeigte sich nur grampositives, bei 25% (n=207/844) ausschließlich gramnegatives Wachstum. Mischkulturen grampositiver und -negativer Keimspezies zeigten sich bei 36% (n=308/844) der Proben. Unterschiede in der Art des Keimwachstums ergaben sich im jahreszeitlichen Vergleich. Insgesamt konnten 1510 Bakterien isoliert werden. Die meisten Isolate gehörten zu den Familien der Enterobacteriaceae, Staphylococcaceae und Bacillaceae. Weiterhin kamen die Familien Streptococcaceae, Moraxellaceae und Pseudomonadaceae häufig vor. Größte Gattungen waren (in absteigender Reihenfolge): Pantoea, Staphylococcus, Bacillus, Streptococcus, Pseudomonas und Acinetobacter. Das gramnegative Keimspektrum setzt sich größtenteils aus den drei Familien Enterobacteriaceae (n=359/678), Moraxellaceae (n=141/678) und Pseudomonadaceae (n=137/678) zusammen. Weder das Alter der beprobten Pferde noch lokale antibiotische Vorbehandlung hatten einen signifikanten Einfluss auf die Nachweishäufigkeit gramnegativer Keimspezies. Auch konnten bei Schädigung der Hornhaut nicht vermehrt gramnegative Bakterien isoliert werden. Moraxella bovoculi war innerhalb der Jahresverlaufs im Herbst am häufigsten vertreten. Die klinische Relevanz der nachgewiesenen gramnegativen Bakteriengattungen muss individuell beurteilt werden.
Von 1421 Bakterienisolaten wurden Antibiogramme angefertigt. Getestet wurden die antibiotischen Wirkstoffe Oxacillin, Gentamicin, Neomycin, Kanamycin, Enrofloxacin, Tetracyclin, Florfenicol und Polymyxin. Gegenüber den gramnegativen Isolaten (n=654) zeigte sich Enrofloxacin in vitro als am wirksamsten (n= 625/654), gefolgt von Gentamicin (n=620/654) und Neomycin (n=618/654). Die meisten Isolate der grampositiven Keime waren in vitro sensibel gegenüber Florfenicol (n=713/767), Enrofloxacin (n=710/767) und Tetracyclin (n=679/767). Lokale antibiotische Vorbehandlungen hatten keinen besonderen Einfluss auf die Resistenzlage.
Das große aerobe Keimspektrum der Augenoberfläche des Pferdes und die Unterschiede in der Resistenzlage machen eine bakteriologische Untersuchung mit anschließender Antibiogrammerstellung notwendig.
Weniger anzeigenStaff training for persons handling animals intended for slaughter is necessary and its relevance is undisputed. Despite this, there is no legal basis that describes the need of repetitive training for persons with a certificate of competence in this field. Within the meat industry, there is a need for well-developed, easily understandable training materials translated in correspondingly necessary languages, containing descriptive photos and videos which provide ongoing training to the heterogeneous group of employees. Any lack of knowledge could lead to animal welfare violations by employees. Regardless of whether these violations are caused by a lack of knowledge or another cause, there must not be any handling of pigs that is in violation of animal welfare.
Through the survey and data collection of the first publication, it became clear that animal welfare training for employees is usually carried out once a year. Smaller abattoirs were comparatively less satisfied with their training concepts, materials and content. The need for descriptive videos, photos and different target languages became clear, as well as a need for adapted and specific modules depending on the area of work. The desire for practical sessions was also mentioned. It was also stated that online access or carrying out the animal welfare training online-only could be problematic.
The relevance of human-animal interactions, and the management of transport and slaughter, was confirmed by the systematic literature review and potentially training-relevant topics were identified. Mistakes in handling pigs can only be identified and corrected if they are known and recognized by staff. Appropriately prepared and repetitive training courses can help to form this recognition. Existing handouts and after publication the materials from the project "eSchulTS2" (access via https://tetfolio.fu-berlin.de/web/eschults2) are good bases for complex training and, if necessary, management adjustments.
The knowledge testing of the additional, unpublished work showed that participants answered more questions correctly as a percentage after completing the pilot modules "Handling of pigs" and "Electrical stunning". The increase in knowledge, however, varied depending on the topic and previous experience, even for individual questions. Participants with a lower level of education were more likely to have a certificate of competence and thus to work in areas relevant to animal welfare. The influence of language selection remains unclear. Romanian speaking participants had worse results than German speaking participants. We posit that the reason for the worse results in the tests is not the country of origin per se, but rather the factor of the career changing of people from other countries. An increase in knowledge was also observed among participants with a certificate of competence, which confirms the need for repetitive training for all staff.
Overall, the increase in knowledge of the participants in the pre-evaluation showed that the underlying didactic concept for the created E-learning pilot modules in the area of animal welfare training for employees of pig abattoirs is suitable. The transfer and increase in knowledge represent an added value for the protection and animal welfare of pigs intended for slaughter.
Weniger anzeigenThe emergence of a European public sphere as a shared communication space for European citizens in different countries and its importance for the democratic legitimacy of the European Union have long been subject to scholarly debate. The existence of a European public sphere is usually discussed in terms of the Europeanization of national public spheres, which includes the synchronicity of issue agendas in various countries and the degree of communicative interactions between actors from the European and the national level (vertical Europeanization) as well as in different member states (horizontal Europeanization). Over time, two key developments have contributed to increasing Europeanization of national public spheres. First, political and economic crises have served as catalysts for politicization and consequently the visibility of European issues in recent years. Second, digitalization has led to the emergence of networked public spheres as interconnection of different platforms and issue publics online. Specifically, the advent of the internet and the rise of social media platforms have fostered new communication infrastructures that allow direct communication between different actor groups and across national borders. Europeanization can thus be conceptualized as increasing density of communicative interactions between various actors in communication networks. These developments lead to a more diverse set of voices in online debates, because actors formerly dependent on journalists as gatekeepers can now directly address others online. More diverse actor constellations might in turn increase the variation of (European) issues discussed in networked public spheres, which would provide the possibility for (communicative) input to the European level from citizens and civil society actors as an important precondition for the Europeanization of networked public spheres as well as for the democratic legitimacy of the EU on the input and the output level. Problems related to the legitimacy of the EU and European institutions such as missing accountability and growing Euroscepticism have been addressed by the institutions and scholars alike. Overall, favourable context conditions regarding the communication environment on the one hand (i.e. easy direct and transnational communication) are met by unfavorable context conditions for Europeanization and democratic legitimacy (i.e. growing Euroscepticism, crises) on the other hand. Furthermore, when different actor groups can communicate directly on social media platforms, strategic decisions and communication contexts of these actor groups need to be taken into consideration. It is assumed that actors use the different communication options of social media platforms (e.g. addressing other users, sharing and forwarding contents, replying to others) for different strategic purposes. The actual outplay of communicative interactions and the resulting network structures are a result of actor-specific strategies. Consequently, an actor-centered approach to Europeanization, democratic legitimacy, as well as the salience of conflict lines is necessary when social media platforms are at the center of attention. These contemporary developments raise the question in how far networked public spheres and social media platforms with their potential for direct and transnational communication may lead to increasing Europeanization of communicative interactions and new (European) issues being discussed by diverse actors online. Specifically, this dissertation focusses on three concepts related to the scholarly debate about European public spheres and the impact of contemporary communication infrastructures and networked public spheres on these concepts. First, vertical and horizontal Europeanization are discussed against the background of changing communication environments and actor-specific communication strategies. Second, the potential of direct communication between citizens and (European) politicians as precondition for increasing democratic legitimacy of the EU is discussed. Third, the salience of Eurosceptic voices and consequent calls for newly emerging political conflict lines on the European level will be addressed. Conceptualizing communication flows in networked public spheres as communication networks with the communicating actors as nodes and communicative interactions between these actors as edges, all three concepts can be investigated using network analytical measures. To analyze Europeanization, direct communication as a precondition for democratic legitimacy as well as the salience of European level conflict lines, a combination of different methods from computational communication science (i.e. Exponential Random Graph Modelling, Structural Topic Modelling) is combined with a manual content analysis. The debate about the 2019 European Parliament elections on Twitter as discussed under the official election hashtag (#EP2019) in April and May 2019 is used as a case study for several reasons. First, European Parliament elections are times of increased importance of European actors and issues. Second, Twitter is a particularly important platform for political communication. Third, hashtag-based data sampling via Twitter’s Rest API allows to analyze the corresponding debate without prior selection of countries, issues, or actors that should be included in the analysis. The results provide optimistic outlooks for the Europeanization of networked public spheres and the inclusion of different voices in political online debates, but they also leave room for improvement when it comes to direct communication between politicians and citizens as a precondition for increasing democratic legitimacy of the EU. It also become apparent that different actor groups play different roles when it comes to the Europeanization of networked public spheres and political as well as media actors are still the most important receivers of attention in terms of incoming communicative interactions. First indicators for European level conflict lines do emerge in the network structures of the debate regarding, for example, European integration and environmental protection. However, it remains to be seen in how far these conflict lines may turn into fully-fledged cleavages in the future. The dissertation provides a detailed discussion of these results and their impact for further scholarly debates as well as practical implication for Europeanization, democratic legitimacy, and conflict lines.
Weniger anzeigenSince its launch in 2012, Wikidata has grown to become the largest open knowledge base (KB), containing more than 100 million data items and over 6 million registered users. Wikidata serves as the structured data backbone of Wikipedia, addressing data inconsistencies, and adhering to the motto of “serving anyone anywhere in the world,” a vision realized through the diversity of knowledge. Despite being a collaboratively contributed platform, the Wikidata community heavily relies on bots, automated accounts with batch, and speedy editing rights, for a majority of edits. As Wikidata approaches its first decade, the question arises: How close is Wikidata to achieving its vision of becoming a global KB and how diverse is it in serving the global population? This dissertation investigates the current status of Wikidata’s diversity, the role of bot interventions on diversity, and how bots can be leveraged to improve diversity within the context of Wikidata. The methodologies used in this study are mapping study and content analysis, which led to the development of three datasets: 1) Wikidata Research Articles Dataset, covering the literature on Wikidata from its first decade of existence sourced from online databases to inspect its current status; 2) Wikidata Requests-for-Permissions Dataset, based on the pages requesting bot rights on the Wikidata website to explore bots from a community perspective; and 3) Wikidata Revision History Dataset, compiled from the edit history of Wikidata to investigate bot editing behavior and its impact on diversity, all of which are freely available online. The insights gained from the mapping study reveal the growing popularity of Wikidata in the research community and its various application areas, indicative of its progress toward the ultimate goal of reaching the global community. However, there is currently no research addressing the topic of diversity in Wikidata, which could shed light on its capacity to serve a diverse global population. To address this gap, this dissertation proposes a diversity measurement concept that defines diversity in a KB context in terms of variety, balance, and disparity and is capable of assessing diversity in a KB from two main angles: user and data. The application of this concept on the domains and classes of the Wikidata Revision History Dataset exposes imbalanced content distribution across Wikidata domains, which indicates low data diversity in Wikidata domains. Further analysis discloses that bots have been active since the inception of Wikidata, and the community embraces their involvement in content editing tasks, often importing data from Wikipedia, which shows a low diversity of sources in bot edits. Bots and human users engage in similar editing tasks but exhibit distinct editing patterns. The findings of this thesis confirm that bots possess the potential to influence diversity within Wikidata by contributing substantial amounts of data to specific classes and domains, leading to an imbalance. However, this potential can also be harnessed to enhance coverage in classes with limited content and restore balance, thus improving diversity. Hence, this study proposes to enhance diversity through automation and demonstrate the practical implementation of the recommendations using a specific use case. In essence, this research enhances our understanding of diversity in relation to a KB, elucidates the influence of automation on data diversity, and sheds light on diversity improvement within a KB context through the usage of automation.
Weniger anzeigenMore and more diseases have been found to be strongly correlated with disturbances in the microbiome constitution, e.g., obesity, diabetes, and even some types of cancer. Advances in high-throughput omics technologies have made it possible to directly analyze the human microbiome and its impact on human health and physiology. Microbial composition is usually observed over long periods of time and the interactions between their members are explored. Numerous studies have used microbiome data to accurately differentiate disease states and understand the differences in microbiome profiles between healthy and ill individuals. However, most of them mainly focus on various statistical approaches, omitting microbe-microbe interactions among a large number of microbiome species that, in principle, drive microbiome dynamics. Constructing and analyzing time-evolving graphs is needed to understand how microbial ecosystems respond to a range of distinct perturbations, such as antibiotic exposure, diseases, or other general dynamic properties. This becomes especially challenging due to dozens of complex interactions among microbes and metastable dynamics.
The key to addressing this challenge lies in representing time-evolving graphs constructed from microbiome data as fixed-length, low-dimensional feature vectors that preserve the original dynamics. Therefore, we propose two unsupervised approaches that map the time-evolving graph constructed from microbiome data into a low-dimensional space where the initial dynamic, such as the number of metastable states and their locations, is preserved. The first method relies on the spectral analysis of transfer operators, such as the Perron--Frobenius or Koopman operator, and graph kernels. These components enable us to extract topological information such as complex interactions of species from the time-evolving graph and take into account the dynamic changes in the human microbiome composition. Further, we study how deep learning techniques can contribute to the study of a complex network of microbial species. The method consists of two key components: 1) the Transformer, the state-of-the-art architecture used in the sequential data, that learns both structural patterns of the time-evolving graph and temporal changes of the microbiome system and 2) contrastive learning that allows the model to learn the low-dimensional representation while maintaining metastability in a low-dimensional space.
Finally, this thesis will address an important challenge in microbiome data, specifically identifying which species or interactions of species are responsible for or affected by the changes that the microbiome undergoes from one state (healthy) to another state (diseased or antibiotic exposure). Using interpretability techniques of deep learning models, which, at the outset, have been used as methods to prove the trustworthiness of a deep learning model, we can extract structural information of the time-evolving graph pertaining to particular metastable states.
Weniger anzeigenDer "Masterstudiengang für das Lehramt an Integrierten Sekundarschulen und Gymnasien mit dem Profil Quereinstieg" (Q-Master) stellt einen alternativen Weg in das Lehramt dar. Es ist wenig darüber bekannt, ob ein solcher Qualifikationsweg in adäquater Weise auf die beruflichen Herausforderungen vorbereitet.
Mit der vorliegenden Arbeit wurde die Ausprägung und Entwicklung fachspezifischer professioneller Kompetenzen der Studierenden des Q-Masterstudiengangs (N=14) im Fach Physik längsschnittlich erhoben und mit den Studierenden des regulären Lehramtsmasterstudiengangs (N=30) verglichen. Ergänzend wurden Interviews zu den motivationalen Eingangsbedingungen der Q-Masterstudierenden sowie Aspekten der individuellen Nutzung der Lernangebote des Lehramtstudiums durchgeführt.
Als Ergebnis zeigt sich ein großer Zuwachs des fachdidaktischen Wissens der Q-Masterstudierenden im Verlauf des Q-Masterstudiums. Im Vergleich zu den regulären Lehramtsmasterstudieren werden keine Unterschiede in der Kompetenzausprägung und -entwicklung nachgewiesen. Die motivationalen Eingangsbedingungen der Q-Masterstudierenden scheinen günstig für die professionelle Entwicklung zu sein und die Lerngelegenheiten des Studiums werden als überwiegend nützlich erlebt. Damit scheint der Modellstudiengang geeignet zu sein, um einen qualitätsgesicherten Wechsel in das Lehramt innerhalb eines überschaubaren Zeitraums zu ermöglichen.
Weniger anzeigenThe present research was inspired by the chance encounter of an important dissonance between the Basic Principles and Guidelines on the Right to a Remedy and Reparation for Victims of Gross Violations of International Human Rights Law and Serious Violations of International Humanitarian Law and Uganda’s nascent transitional justice policy. The latter foresaw reparations for all victims of Uganda’s civil wars while the former stated that customary international law merely encouraged but did not oblige States to repair victims of non-State actors, the victims of others. Was Uganda’s policy gratuitous? Or has public international law evolved beyond the economy of the Basic Principles and Guidelines? It is the purpose of the present text to answer these questions. The thesis is divided into three substantive chapters that are preceded by an Introduction and tied together by a brief Conclusion.
The Introduction articulates the hypothesis and highlights that if correct, i.e., if there exists a rule of public international law obliging States to repair victims not their own, there exist two candidates for the content of that rule. The candidates are explored in Chapters 1 and 2. Before turning to them, the Introduction demonstrates that avenues typically proposed today are insufficient juxtaposed with the aim of making reparations a reality for victims of non-State actors. It thereby underlines that the hypothesis is not just thought-provoking but also of immense practical value.
Chapter 1 first investigates the nature of the States’ obligation to protect economic, social and cultural rights, and concludes that the existing consensus as it is contained in the Basic Principles and Guidelines is that the obligation is a qualified obligation of result. It then examines the historical origins of the rule, demonstrates why it is inappropriate to apply it to the situation at hand and proposes that the obligation to protect be understood as an unqualified obligation of result instead, meaning that the State would find itself in a position of wrongfulness at the exact moment a non-State actor committed a violation. This would ipso facto create the State’s secondary obligation to repair. Lacking a conventional articulation to that effect, such a rule would have to exist in the sphere of customary international law.
Chapter 2 takes under the magnifying glass the International Covenant on Economic, Social and Cultural Rights and explores the potential of the obligation of progressive realisation, the prohibition against discrimination and studies the work of the Committee on Economic, Social and Cultural Rights, substantiating the argument that the obligation to repair could be understood as a primary obligation.
What we do not yet know at this point in the thesis is whether either proposition corresponds to the States’ understanding of the law. Chapter 3 therefore examines a dozen countries that have experienced a non-international armed conflict in their more or less recent past. It looks at their practice in regard to reparations, paying particular attention to whether States discriminate between victims of the State and those not of the State. As far as it can be discerned, it also analyses their understanding of public international law.
The Conclusion suggests an affirmation of the hypothesis.
Weniger anzeigenRepresenting molecules in a computer-interpretable way plays a crucial role in enabling the application of computational method to the field of chemistry and pharmaceutical drug development in particular. Recently, there has been a surge of interest in using machine learning to predict molecular properties such as the binding affinity to protein targets of interest or to generate molecular structures with desirable properties. However, as chemical entities are challenging to represent in an expressive and computer-interpretable way, much work in the field of cheminformatics has concerned itself with defining clever feature extractors, which encode the chemical graph structure in a uniform, fixed-sized, numerical manner. Recently Deep Neural Networks have shown great success in learning to extract meaningful features directly from raw data representations, outperforming hand-crafted feature extraction protocols and revolutionizing fields such as image analysis or natural language processing. Deep Neural Networks have also been directly applied on raw data representations of molecules such as their structural graph. However, the capabilities of this method in pharmaceutical drug development are usually limited by the scarcity of labeled data as their collection usually involves running expensive wet lab experiments. Unsupervised Learning, on the other hand, is a powerful machine learning strategy that enables the training of Deep Neural Networks without the need of labeled training data. In this thesis we discuss how Unsupervised Learning can be used to train powerful feature extractors on unlabeled chemical structures. We propose for different input representations of molecules (such as line notations, graphs and point clouds) novel methods to extract expressive representations. We show how those representations can efficiently be used as input for downstream molecular property prediction models or to generate novel molecules with desirable properties. Moreover, we discuss how certain symmetries of molecular representations are crucial to respect (e.g. permutation invariance of molecular graphs or rotation and translation invariance of molecular conformations) and develop novel methods particularly designed to extract invariant representations.
Weniger anzeigenBacteria mostly prefer to live as biofilms on surfaces rather than in flowing environments. However, biofilms are mostly unwanted by humans and preventing possibilities besides biocides and antibiotics are urgently needed. One strategy is to prevent the bacteria directly from attaching to the substrate. This study aims to investigate the effect of nano- and microstructures on bacterial attachment and pursues two approaches whether such surfaces reduce bacterial attachment under flow conditions. The first approach involves ZnO nanorods to design surfaces with varying topographies in the nano- and micrometer range, while the second uses 3D printed microstructures to induce microflows that repel bacteria from the surface. The tailored substrates were integrated into a specially developed flow chamber and exposed to a flowing suspension of P. fluorescens under in-situ conditions. Additionally, the attached bacteria were subjected to higher shear forces by increased flow velocities. For evaluation, the attached bacteria were imaged using fluorescence microscopy and automated counted on a single-cell level. The cell counts were compared between different substrates and a control surface to assess the effectiveness of the surfaces in preventing bacterial attachment. Lower cell numbers indicated a surface that better prevented bacterial attachment. However, it was found that none of the investigated surfaces reduced the attachment of P. fluorescens. These findings and additionally made observations have the potential to alter the current perspective of the believed capability of nano and microstructures for preventing microbial attachment. Remarkably, it was found that although accompanying computational fluid dynamic simulations predicted uniform flows in the channels, anomalies in the flows occurred, resulting in uneven distribution of the bacteria. Furthermore, P. fluorescens revealed the ability to attach to any surface studied and rapidly establish irreversible attachment there. Thus, this study also suggests using those microorganism types that perform best in attachment for benchmarking surfaces that are intended to have a bacteria-repellent effect in the future. During the project, a method for a lipopolysaccharide encapsulated polystyrene (LPS-PS) microparticle system was developed as a further approach. The easy-to-use method was developed to mimic bacteria for attachment studies. A variety of analytical techniques were used to detect the LPS on the polystyrene microparticles. Among others, a procedure for labeling the particles for fluorescence microscopy is presented. The data from the analyses offers a reference for future applications of the LPS-PS microparticles, whose use goes far beyond bacterial attachment studies; they are attractive for vaccine research and serological tests.
Weniger anzeigenAprès l’énonciation en 1993 de conditions d’adhésion à l’Union européenne (UE), la politique d’élargissement à l’Est a été qualifiée d’asymétrique et unilatérale. A la suite de la réforme de 1997, la littérature a identifié l’introduction d’un nouveau mode de gouvernance. Qu’en est-il exactement ? Les éléments empiriques réunis entre 2000 et 2004 nous ont permis de formuler l’hypothèse selon laquelle l’UE a transféré une méthode de gouvernance interne fondée sur l’interaction – la méthode ouverte de coordination (MOC) – pour résoudre les difficultés rencontrées au niveau externe. Lors des élargissements précédents, la Communauté européenne s’est toujours inspirée des modes d’intégration interne – intergouvernementalisme, régulation économique, méthode communautaire – pour dépasser ses contradictions. Ainsi, dans quelle mesure la conditionnalité de l’adhésion à l’UE a-t-elle représenté à partir de 1997 un cadre d’apprentissages et de socialisation mutuelle entre acteurs de l’élargissement ? L’approche constructiviste par les cadres normatif et d’action nous a permis de déconstruire trois vertus de la gouvernance par les connaissances : la cohérence et la légitimité interne de la politique d’élargissement sont restées inaccomplies ; dans les pays candidats, la mise en oeuvre des réformes est restée limitée par les héritages du passé ; enfin, les mécanismes d’apprentissages et de socialisation mutuelle ont certes ouvert des possibilités de définition communes des cadres cognitif et d’action des politiques internes et externes à l’UE. Néanmoins, la convergence sur des valeurs partagées n’empêche pas l’existence de tensions internes relatives au sens à donner à l’Europe à Vingt-Cinq.
Weniger anzeigenPredicting the behavior of foldamer assemblies with all-α-peptides in higher-ordered arrangements remains a challenge. However, there is a strong interest and need to develop a deeper and more thorough knowledge to access foldamer designs that undergo interactions with natural peptide motifs. In this dissertation, the endeavors of investigating higher-ordered interactions between foldamers and all-α-peptides were continued in a well-defined tetrameric coiled-coil model system. First, two Cys/Phe-motifs identified in previous work as complementary binding partners of an α/β/γ-chimera were compared using CD-spectroscopy and cryogenic transmission electron microscopy (cryo-TEM). Systematic substitutions were performed on cysteine and analyzed by CD-spectroscopy to determine differences between the two different Cys/Phe-motif-containing complementary sequences in the formation of helical bundles with the α/β/γ-chimeric sequence. High-resolution structural data were obtained using a variety of analytical methods to investigate the favored side chain packing in the higher-ordered helical fold. The analytical techniques applied are NMR spectroscopy, vibrational sum-frequency generation (SFG) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and X-ray crystallography. In the course of this thesis, the thiol region was examined for the first time by vibrational SFG-spectroscopy at the air/water interface for shifts due to H-bonding. In addition, the first crystal structure of a heterotypic coiled-coil assembly of an α/β/γ-chimera with an all-α-peptide was generated, providing the first high-resolution packing information of the heterotypic helical bundle in a solid state. Another part of this work deals with the construction of a library of chimeric peptides with iterative substitutions that increase the number of β/γ-modules. These chimeras were then evaluated for stability when complemented with corresponding all- α-peptide sequences involving the Cys/Phe-motifs. This investigation revealed a restriction of intermolecular interactions sensitive to a variation in the number of backbone residues. Finally, a β/γ-peptide consisting of five β/γ-modules was analyzed for structural features by CD-spectroscopy.
Weniger anzeigenIn the arid and semi-arid region in northern Namibia, there are three main catchment areas the Kunene, the Kavango, and the Cuvelai-Etosha Basin (CEB). The Kunene and the Kavango Rivers are perennial and provide the northwestern and northeastern regions with water. In central northern Namibia, the transboundary CEB consists of an ephemeral and endorheic drainage system with channels and depressions, known as the Iishana system. High temperatures, high evaporation rates, and low rainfall increase the risk of polluting these waters. Groundwater resources near the surface are heavily salinized and can hardly serve as an adequate water source. Deeper groundwater reservoirs are difficult to access. The high population density in the Iishana system area increases the demand upon the surface waters. The geomorphology and surface hydrology of the Iishana system favors very slow surface runoff and low infiltration rates. An extreme change in dry and rainy seasons results in an erratic freshwater supply, which can decrease water quantity and water quality and is thus a major challenge. Since there were no data on the quality of the surface waters in this area, the state of the ecosystem and the health risk for the population are completely unclear; therefore, the regional surface waters were examined to determine their suitability as potable water. The aim is to better understand the hydrological systems in northern Namibia. In four field campaigns between 2017 and 2021, the surface waters, suspended solids, and sediments of the three systems (Kunene, Kavango, and CEB) and the local water supply system, the Calueque-Oshakati Canal, were sampled at more than 30 sites. Relevant hydrochemical parameters were analyzed, microplastics were investigated, and bioassays were conducted to gain insights into the status of aquatic ecosystems and the ecological impacts of pollutants. Spatial differences in the water quality relative to the decreasing precipitation gradient from east to west were noticed. Furthermore, metals such as aluminum and iron accumulate around the densely populated region in the eastern part of the study area. These waters were more polluted during the drought events in 2018 and 2019 than in 2017. Microplastics were found in different quantities, in particular PE and PP fragments. Three different trophic levels (algae, daphnia, and zebrafish embryos) were tested for acute toxicity. Mechanism-specific effects, such as estrogenicity (YES), cytochrome potential (micro-EROD), and mutagenicity (AMES) were investigated using in vitro assays. Acute toxicity could be detected for all three systems; in particular, the fish embryos showed several effects. Estrogenic and mutagenic effects were identified for several sampling sites. The different methodological approaches facilitate a holistic monitoring. This work is the first study to provide a comprehensive statement on water quality. The ecosystems of the Iishana, the Kunene, and Kavango Rivers are severely stressed and differ significantly. They show several signs of anthropogenic pollution that can affect human health. The use of water as potable water is not possible without prior treatment. Further investigation of the exact influencing factors, such as pesticides, is necessary to find suitable treatment measures for water use.
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