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The suitability of a newly developed cell-based functional assay was tested for the detection of the activity of a range of neurotoxins and neuroactive pharmaceuticals which act by stimulation or inhibition of calcium-dependent neurotransmitter release. In this functional assay, a reporter enzyme is released concomitantly with the neurotransmitter from neurosecretory vesicles. The current study showed that the release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) can be stimulated by a carbachol-mediated activation of the Gq-coupled muscarinic-acetylcholine receptor and by the Ca2+-channel forming spider toxin α-latrotoxin. Carbachol-stimulated luciferase release was completely inhibited by the muscarinic acetylcholine receptor antagonist atropine and α-latrotoxin-mediated release by the Ca2+-chelator EGTA, demonstrating the specificity of luciferase-release stimulation. SIMA-hPOMC1-26-GLuc cells express mainly L- and N-type and to a lesser extent T-type VGCC on the mRNA and protein level. In accordance with the expression profile a depolarization-stimulated luciferase release by a high K+-buffer was effectively and dose-dependently inhibited by L-type VGCC inhibitors and to a lesser extent by N-type and T-type inhibitors. P/Q- and R-type inhibitors did not affect the K+-stimulated luciferase release. In summary, the newly established cell-based assay may represent a versatile tool to analyze the biological efficiency of a range of neurotoxins and neuroactive pharmaceuticals which mediate their activity by the modulation of calcium-dependent neurotransmitter release.
Mental health problems remain among the main generators of costs within and beyond the health care system. Psychotherapy, the tool of choice in their treatment, is qualified by social interaction, and cooperation within the therapist-patient-dyad. Research into the factors influencing therapy success to date is neither exhaustive nor conclusive. Among many others, the quality of the relationship between therapist and patient stands out regardless of the followed psychotherapy school. Emerging research points to a connection between interpersonal synchronization within the sessions and therapy outcome. Consequently, it can be considered significant for the shaping of this relationship. The framework of Embodied Cognition assumes bodily and neuronal correlates of thinking. Therefore, the present paper reviews investigations on interpersonal, non-verbal synchrony in two domains: firstly, studies on interpersonal synchrony in psychotherapy are reviewed (synchronization of movement). Secondly, findings on neurological correlates of interpersonal synchrony (assessed with EEG, fMRI, fNIRS) are summarized in a narrative manner. In addition, the question is asked whether interpersonal synchrony can be achieved voluntarily on an individual level. It is concluded that there might be mechanisms which could give more insights into therapy success, but as of yet remain uninvestigated. Further, the framework of embodied cognition applies more to the current body of evidence than classical cognitivist views. Nevertheless, deeper research into interpersonal physical and neurological processes utilizing the framework of Embodied Cognition emerges as a possible route of investigation on the road to lower drop-out rates, improved and quality-controlled therapeutic interventions, thereby significantly reducing healthcare costs.
Mental health problems remain among the main generators of costs within and beyond the health care system. Psychotherapy, the tool of choice in their treatment, is qualified by social interaction, and cooperation within the therapist-patient-dyad. Research into the factors influencing therapy success to date is neither exhaustive nor conclusive. Among many others, the quality of the relationship between therapist and patient stands out regardless of the followed psychotherapy school. Emerging research points to a connection between interpersonal synchronization within the sessions and therapy outcome. Consequently, it can be considered significant for the shaping of this relationship. The framework of Embodied Cognition assumes bodily and neuronal correlates of thinking. Therefore, the present paper reviews investigations on interpersonal, non-verbal synchrony in two domains: firstly, studies on interpersonal synchrony in psychotherapy are reviewed (synchronization of movement). Secondly, findings on neurological correlates of interpersonal synchrony (assessed with EEG, fMRI, fNIRS) are summarized in a narrative manner. In addition, the question is asked whether interpersonal synchrony can be achieved voluntarily on an individual level. It is concluded that there might be mechanisms which could give more insights into therapy success, but as of yet remain uninvestigated. Further, the framework of embodied cognition applies more to the current body of evidence than classical cognitivist views. Nevertheless, deeper research into interpersonal physical and neurological processes utilizing the framework of Embodied Cognition emerges as a possible route of investigation on the road to lower drop-out rates, improved and quality-controlled therapeutic interventions, thereby significantly reducing healthcare costs.
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.
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.
Focus on English Linguistics
(2021)
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.
Introduction
(2021)
Food intake is driven by the need for energy but also by the demand for essential nutrients such as protein. Whereas it was well known how diets high in protein mediate satiety, it remained unclear how diets low in protein induce appetite. Therefore, this thesis aims to contribute to the research area of the detection of restricted dietary protein and adaptive responses.
This thesis provides clear evidence that the liver-derived hormone fibroblast growth factor 21 (FGF21) is an endocrine signal of a dietary protein restriction, with the cellular amino acid sensor general control nonderepressible 2 (GCN2) kinase acting as an upstream regulator of FGF21 during protein restriction. In the brain, FGF21 is mediating the protein-restricted metabolic responses, e.g. increased energy expenditure, food intake, insulin sensitivity, and improved glucose homeostasis. Furthermore, endogenous FGF21 induced by dietary protein or methionine restriction is preventing the onset of type 2 diabetes in the New Zealand Obese mouse.
Overall, FGF21 plays an important role in the detection of protein restriction and macronutrient imbalance in rodents and humans, and mediates both the behavioral and metabolic responses to dietary protein restriction. This makes FGF21 a critical physiological signal of dietary protein restriction, highlighting the important but often overlooked impact of dietary protein on metabolism and eating behavior, independent of dietary energy content.
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.
Noise is ubiquitous in nature and usually results in rich dynamics in stochastic systems such as oscillatory systems, which exist in such various fields as physics, biology and complex networks. The correlation and synchronization of two or many oscillators are widely studied topics in recent years.
In this thesis, we mainly investigate two problems, i.e., the stochastic bursting phenomenon in noisy excitable systems and synchronization in a three-dimensional Kuramoto model with noise. Stochastic bursting here refers to a sequence of coherent spike train, where each spike has random number of followers due to the combined effects of both time delay and noise. Synchronization, as a universal phenomenon in nonlinear dynamical systems, is well illustrated in the Kuramoto model, a prominent model in the description of collective motion.
In the first part of this thesis, an idealized point process, valid if the characteristic timescales in the problem are well separated, is used to describe statistical properties such as the power spectral density and the interspike interval distribution. We show how the main parameters of the point process, the spontaneous excitation rate, and the probability to induce a spike during the delay action can be calculated from the solutions of a stationary and a forced Fokker-Planck equation. We extend it to the delay-coupled case and derive analytically the statistics of the spikes in each neuron, the pairwise correlations between any two neurons, and the spectrum of the total output from the network.
In the second part, we investigate the three-dimensional noisy Kuramoto model, which can be used to describe the synchronization in a swarming model with helical trajectory. In the case without natural frequency, the Kuramoto model can be connected with the Vicsek model, which is widely studied in collective motion and swarming of active matter. We analyze the linear stability of the incoherent state and derive the critical coupling strength above which the incoherent state loses stability. In the limit of no natural frequency, an exact self-consistent equation of the mean field is derived and extended straightforward to any high-dimensional case.
History of Forgetfulness
(2021)
This open access book presents a topical, comprehensive and differentiated analysis of Germany's public administration and reforms. It provides an overview on key elements of German public administration at the federal, Länder and local levels of government as well as on current reform activities of the public sector. It examines the key institutional features of German public administration; the changing relationships between public administration, society and the private sector; the administrative reforms at different levels of the federal system and numerous sectors; and new challenges and modernization approaches like digitalization, Open Government and Better Regulation. Each chapter offers a combination of descriptive information and problem-oriented analysis, presenting key topical issues in Germany which are relevant to an international readership.
Federal Administration
(2021)
The federal administration is significantly small (around 10 percent of all public employees). This speciality of the German administrative system is based on the division of responsibilities: the central (federal) level drafts and adopts most of the laws and public programmes, and the state level (together with the municipal level) implements them. The administration of the federal level comprises the ministries, subordinated agencies for special and selected operational tasks (e.g. the authorisation of drugs, information security and registration of refugees) in distinct administrative sectors (e.g. foreign service, armed forces and federal police). The capacity for preparing and monitoring government bills and statutory instruments is well developed. Moreover, the instruments and tools of coordination are exemplary compared with other countries, although the recent digital turn has been adopted less advanced than elsewhere.
This chapter describes the most prominent public management reform trajectories in German public administration over the past decades since unification. In the 1990s, the New Steering Model emerged as a German variant of the NPM. Since the mid-2000s, local governments in Germany have been subjected to a mandatory reform of their budgeting and accounting system known as the New Municipal Financial Management reforms. Both reforms have led to a substantial change in terms of internal decentralisation, customer orientation, transparency in resource use and the financial situation of administrative bodies. But the emerging reform patterns and their impacts have not replaced the dominance of a strong legalist culture with hierarchical, centralised control. However, in the course of the reforms, a citizen-customer perspective, more participation of citizens and limited application of new management instruments have been accommodated within the persisting bureaucratic system.
Over the last decades, Better Regulation has become a major reform topic at the federal and—in some cases—also at the Länder level. Although the debate about improving regulatory quality and reducing unnecessary burdens created by bureaucracy and red tape date back to the 1960s and 1970s, the introduction by law in 2006 of a new independent institutionalised body for regulatory control at the federal level of government has brought a new quality to the discourse and practice of Better Regulation in Germany. This chapter introduces the basic features of the legislative process at the federal level in Germany, addresses the issue of Better Regulation and outlines the role of the National Regulatory Control Council (Nationaler Normenkontrollrat—NKR) as a ‘watchdog’ for compliance costs, red tape and regulatory impacts.
Although German bureaucracy is typically categorised as Weberian, a clear distinction between politics and administration has never been a defining characteristic of the German political-administrative system. Many close interrelations and interactions between elected politicians and appointed civil servants can be observed at all levels of administration. Higher-ranking civil servants in Germany are used to and generally appreciate the functional politicisation of their jobs, that is their close involvement in all stages of the policy process, from policy formation, goal definition, negotiation within and outside government to the implementation and evaluation of policies. For top positions, therefore, a class of ‘political civil servants’ is a special feature of the German system, and obtaining ‘political craft’ has become an important part of the learning and job experience of higher-ranking civil servants.
German Public Administration
(2021)
The international community of public administration and administrative sciences shows a great interest in the basic features of the German administrative system. The German public administration with its formative decentralisation (called: administrative federalism) is regarded as a prime example of multilevel governance and strong local self-government. Furthermore, over the past decades, the traditional profile of the German administrative system has significantly been reshaped and remoulded through reforms, processes of modernisation and the transformation process in East Germany. Studies on the German administrative system should focus especially on
key institutional features of public administration;
changing relationships between public administration, society and the private sector;
administrative reforms at different levels of the federal system; and
new challenges and modernisation approaches, such as digitalisation, open government and better regulation.
Human resource management (HRM) reform has not been the focus of attention in Germany despite its obvious relevance for effective policy implementation. Although there is a general trend worldwide towards convergence between public and private HRM strategies and practices, management of the workforce in German public administration still remains largely traditional and bureaucratic. This chapter describes and analyses German practices regarding the central functions and elements of HRM such as planning, recruitment, training and leadership. Furthermore, it explores the importance and contribution of public service motivation, performance-related pay and diversity management in the context of German practices. The chapter concludes by highlighting some of the major paradoxes of German public HRM in light of current challenges, such as demographic change, digital transformation and organisational development capabilities.