In the medical field, the applications of ultraviolet (UV) radiation are limited to skin or reachable sites due to its low penetration depth into biological tissue. Contrary to UV radiation, X-rays can penetrate the body with almost no attenuation, but they result in toxic side effects. Inorganic scintillators absorb X-rays and convert them into UV or visible photons and are usually used for medical imaging. We propose the use of high density inorganic nanoscale scintillators with the ability to absorb externally applied ionizing radiation directly at the site of application, e.g., inside a tumor, and to convert this ionizing radiation into UV photons in situ, enabling new biomedical applications inside the body. In this thesis, two specific new biomedical applications are discussed in detail: The first application is the use of UV-B emitting nanoscale scintillators for highly localized drugs released or activation of photoactivable therapeutics using only X-rays. The second novel approach is the use of UV-C emitting nanoscale scintillators as radiation sensitizers. However, size-reduction of inorganic scintillators, and most inorganic phosphors in general, usually result in quenching of the photoluminescence properties, defects on the surface of the particles, and a decrease of radiation hardness. Colloidal solutions of nearly monodisperse LaPO4:Gd nanocrystals (5nm) were shown to strongly emit UV radiation upon excitation with X-rays or vacuum UV radiation (160nm). The UV emission of the particles consisted mainly of a single line at 311nm. This UV-B emission of the particles was used to excite the fluorescence of laser dyes dissolved in the colloids. The emission of the dyes was also observed in the case of high dye concentrations, proving that the concept of using radiation with a high penetration depth (X-rays) to excite fluorescence emission with a low penetration depth (UV-B) wavelength is feasible. Pr-doped LuPO4 emits UV-C radiation between 225 and 280nm, where DNA shows strong absorption bands. Therefore, a systematic study of the luminescence of LuPO4:Pr was performed: Different doping concentrations, particle sizes, and excitation sources were compared. Furthermore, it was found that Pr and Nd co-doped LuPO4 results in increased UV-C emission independent of excitation source due to energy transfer. The highest UV-C emission intensity was observed for LuPO4:Pr,Nd(1%,2.5%) upon X-ray irradiation. Finally, LuPO4:Pr,Nd nanoparticles were synthesized, and the biological efficacy of the combined approach (X-rays and UV-C) was assessed using the colony formation assay. Cell culture experiments confirm increased cell death compared to X-rays alone due to the formation of UV-specific DNA damages, supporting the application of the herein synthesized particles as radiation sensitizers.

General purpose Twitter sentiment analysis is a novel field that is closely related to traditional Twitter sentiment analysis but slightly differs in some key aspects. The main difference lies in the fact that the novel approach considers the unfiltered public Twitter stream while most of the previous approaches often applied various filtering steps which are not feasible for many applications. Another goal is to yield more reliable results by only classifying a tweet as positive or negative if it distinctly consists of the respective sentiment and mark the remaining messages as uncertain. Traditional approaches are often not that strict. Within the course of this thesis it could be verified that the novel approach differs significantly from the traditional approach. Moreover, the experimental results indicated that the archetypical approaches could be transferred to the new domain but the related domain data is consistently sub par when compared to high quality in-domain data. Finally, the viability of the best classification algorithm could be qualitatively verified in a real-world setting that was also developed within the course of this thesis.

Voltage gated potassium channels (Kv) play a key role in the nervous system- not only due to their involvement in the action potential. Vertebrates express four subtypes, which are termed Kv1, Kv2, Kv3 and Kv4, respectively. Tsha3 is a Kv1 channel which was originally isolated from brain tissue of rainbow trout (Oncorhynchus mykiss). This channel possesses an unique amino terminus and a characteristic amino acid sequence in the T1 domain, which is engaged in the oligomerization of Kv α-subunits and is thus involved into the segregation of subfamilies. The two major goals of this thesis were the structural and functional characterization of the N-terminal cytosolic domain of Tsha3 as well as the invention of a system to gain data about the functional dynamics of full length Kv channels. Molecular biological techniques were used to isolate mRNA from trout brains, to transcribe it into cDNA and clone it into vectors. DNA from such plasmids was ligated into expression vectors for heterologous expression in E. coli, P. pastoris and Sf21 cells, with concomitant fusion of marker proteins (GFP or DsRed) or tags (6 x HisTag or StrepTagII) due to the individual experiment. Protein was overexpressed in E. coli and affinity purified to analyze separated domains with biochemical (SDS-PAGE and Western Blot, Pull-Down-Assay or Dot-Blot-Assay) or biophysical (CD-spectroscopy, EPR spectroscopy) efforts. The P. pastoris system to express Tsha1 was established, to generate a system for future EPR-measurements of whole Kv channels. Heterologous expression of Kv1α (Tsha3 and Tsha1) and the core domain of Kvβ in Sf21 cells was performed to analyze the subcellular distribution of the respective subunits via fluorescence microscope and via subcellular fractionation of cell lysates with downstream biochemical analyses (SDS-PAGE and Western Blot). Furthermore the gating of diverse fusion constructs of Tsha3 in co-expressions and the gating of diverse cystein substitution mutants of Tsha1 were measured via path-clamp recordings in whole cell modus. The structural analyses of the N-terminal cytosolic domain (NCD) of Tsha3 revealed that the 128 amino acid containing part before the T1-domain (Tsha3-NT) can be structurally divided into three parts of different structure and mobility. The most outward part possesses a very high mobility and is putatively unfolded as random coil. This section is expected to express no tertiary contacts. The middle part of Tsha3-NT is structured in α-helices and β-sheets and thus slightly immobile. This folded part is also assumed to build no tertiary structure and to be exposed into the cytosol. The third, which is directly neighboring the T1 domain, has the most restricted mobility of Tsha3-NT. It consists predominantly of α-helices and exhibits a tertiary structure, putatively with the T1 domain. Tsha3-NCD self-tetramerizes and oligomerizes with Tsha1, although mutations exist in Tsha3 in conserved amino acids, which were reported to function in subfamily specific hetero-tetramerization. Thus it is proven, that Tsha3 takes part in the segregation into the Kv1 subfamily. Furthermore, Tsha3 interacts with the core domain of Kvβ2 although there are also mutations in the reported consensus sequence for interaction. Association of Kvβ2 in co-expression studies directs Tsha3-DsRed fusion constructs from internal vesicular structures into the cell membrane. But the fusion with DsRed is leading to a loss of function of Tsha3 which cannot be rescued by co-expression of the chaperone Kvβ2. But- without fusion of marker proteins- Tsha3 was identified as an outward rectifier in a cooperative Bachelor Thesis. These structural data lead to the assumption, that Tsha3-NT exhibits lateral interactions and especially the helical but mobile middle part of the N-terminus can play such a role. Due to the localization next to the membrane, interactions with membrane proteins- putatively with protein cascades are possible. Although Tsha3-NT contains no reported interaction domains for protein-protein interactions, follow-up experiments should be performed to shed light on this interesting question. Tsha1 C30S C31S C180S C224A C239S C389S C424S C476S is a complete cysteine free mutant, which was identified as a functional voltage-gated potassium channel. It was expressed in and purified from eukaryotic cells (P. pastoris) and therefore it can be assumed to be properly folded and modified. After a slight optimization of the features of expression, this system can be used to reconstitute Tsha1 channels into liposomes and use them for Freeze Quench EPR to gain structural information about a Kv1 channel in the open as well as in the closed state. This is the first report of the establishment of a full length Kv for studies of structure and functional dynamics experiments.

In Wissenschaft und Praxis herrscht Einigkeit über die Notwendigkeit der Unterstützung von Dienstleistungen durch mobile Informationssysteme (IS). Der primäre Untersuchungsgegenstand der vorliegenden Dissertation ist die Gestaltung eines mobilen IS zur Unterstützung produktbegleitender Dienstleistungen. Innovativ an der im Rahmen dieses Promotionsverfahrens entwickelten Lösung ist die Verwendung der neu auf dem Markt erschienenen Smart Glasses, die u. a. dadurch, dass sie freihändig bedient werden können, einen Mehrwert zur Unterstützung während der Dienstleistungserbringung bieten. Ziel der Arbeit ist die Entwicklung von Gestaltungswissen zum Design, zur Implementierung und zur Evaluation mobiler Informationssysteme. Die Bearbeitung der Zielsetzung beinhaltet (1) die multi-methodische Analyse zentraler Anforderungen an das IS in Form der zu deckenden Informationsbedarfe der Leistungserbringer und der zu implementierenden Anwendungsfälle. (2) Die fachlichen Anforderungen adressierend, wird das Design, die Implementierung und die Evaluation des mobilen Informationssystems selbst durchgeführt. Hierzu werden zusätzlich technische Funktionalitäten der Smart Glasses erfasst. (3) Aus der Analyse, dem Design und der Evaluation des mobilen Informationssystems wird anschließend methodisches Gestaltungswissen abgeleitet. (4) Abschließend erfolgt die Anwendung des Gestaltungswissens innerhalb weiterer Dienstleistungssektoren (Logistikdienstleistungen, Gesundheitsdienstleistungen). Hierbei werden ein Smart Glasses-basiertes IS für die Unterstützung von Logistikdienstleistungen und eine Smartphone-Applikation zur Unterstützung von Gesundheitsdienstleistungen für das Entwicklungsland Papua-Neuguinea konzipiert. Die vorliegende Dissertation leistet einen Beitrag zum Service Systems Engineering als Teildisziplin der Wirtschaftsinformatik. Sie füllt die Forschungslücke zu evidenzbasiertem Gestaltungswissen in der Disziplin, indem durch einen gestaltungsorientierten Ansatz sowohl mobile Informationssysteme selbst, als auch methodische Erkenntnisse generiert werden.

In this thesis, patterning methods to fabricate various functional particle patterns on substrates were developed, with the main aim of modifying the properties and functions of the substrates. Two classes of model substrates were selected; topographically patterned and smooth substrates. For the first model system, i.e., topographically patterned substrates, replication molding was used to topographically pattern substrates of different materials. The topographically patterned substrates, including TiO2, block-copolymer substrates (PS-b-P2VP and PS-b-P4VP), and microrings (TiO2 and Au), were then used to assemble silica (SiO2) microparticles for functional applications. By the assembly of microparticles on topographically patterned substrates, the wettability of the former could be reversibly switched from hydrophobic to hydrophilic. Moreover, a platform for the preparation of Janus particles by orthogonal functionalization of the top and bottom sides of microparticles assembled on topographically patterned substrates was developed. Clusters of superparamagnetic nanoparticles were stamped on the second class of model substrates, i.e., smooth silanized silicon substrates. A capillary stamping approach combined with an external permanent magnetic field or electromagnets was realized to print magnetic nanoparticle-based inks. In this way, ordered arrays of clusters of magnetic nanoparticles were produced.

Adaptability and flexibility are some of the most important human characteristics. Learning based on new experiences enables adaptation by changing the structural connectivity of the brain through plasticity mechanisms. But the human brain can also adapt to new tasks and situations in a matter of milliseconds by dynamic coordination of functional activation. To understand how this flexibility can be achieved in the computations performed by neural networks, we have to understand how the relatively fixed structural backbone interacts with the functional dynamics. In this thesis, I will analyze these interactions between the structural network connectivity and functional activations and their dynamic interactions on different levels of abstraction and spatial and temporal scales. One of the big questions in neuroscience is how functional interactions in the brain can adapt instantly to different tasks while the brain structure remains almost static. To improve our knowledge of the neural mechanisms involved, I will first analyze how dynamics in functional brain activations can be simulated based on the structural brain connectivity obtained with diffusion tensor imaging. In particular, I will show that a dynamic model of functional connectivity in the human cortex is more predictive of empirically measured functional connectivity than a stationary model of functional dynamics. More specifically, the simulations of a coupled oscillator model predict 54\% of the variance in the empirically measured EEG functional connectivity. Hypotheses of temporal coding have been proposed for the computational role of these dynamic oscillatory interactions on fast timescales. These oscillatory interactions play a role in the dynamic coordination between brain areas as well as between cortical columns or individual cells. Here I will extend neural network models, which learn unsupervised from statistics of natural stimuli, with phase variables that allow temporal coding in distributed representations. The analysis shows that synchronization of these phase variables provides a useful mechanism for binding of activated neurons, contextual coding, and figure ground segregation. Importantly, these results could also provide new insights for improvements of deep learning methods for machine learning tasks. The dynamic coordination in neural networks has also large influences on behavior and cognition. In a behavioral experiment, we analyzed multisensory integration between a native and an augmented sense. The participants were blindfolded and had to estimate their rotation angle based on their native vestibular input and the augmented information. Our results show that subjects alternate in the use between these modalities, indicating that subjects dynamically coordinate the information transfer of the involved brain regions. Dynamic coordination is also highly relevant for the consolidation and retrieval of associative memories. In this regard, I investigated the beneficial effects of sleep for memory consolidation in an electroencephalography (EEG) study. Importantly, the results demonstrate that sleep leads to reduced event-related theta and gamma power in the cortical EEG during the retrieval of associative memories, which could indicate the consolidation of information from hippocampal to neocortical networks. This highlights that cognitive flexibility comprises both dynamic organization on fast timescales and structural changes on slow timescales. Overall, the computational and empirical experiments demonstrate how the brain evolved to a system that can flexibly adapt to any situation in a matter of milliseconds. This flexibility in information processing is enabled by an effective interplay between the structure of the neural network, the functional activations, and the dynamic interactions on fast time scales.