The Polyhedral Process Network (PPN) is a suitable parallel model of computation (MoC) used to specify embedded streaming applications in a parallel form facilitating the efficient mapping onto... Show moreThe Polyhedral Process Network (PPN) is a suitable parallel model of computation (MoC) used to specify embedded streaming applications in a parallel form facilitating the efficient mapping onto embedded parallel execution platforms. Unfortunately, specifying an application using a parallel MoC is a very difficult and highly error-prone task. To overcome the associated difficulties, we have developed the pn compiler, which derives PPN specifications from sequential static affine nested loop programs (SANLPs). However, there are many applications that have adaptive and dynamic behavior which cannot be expressed as SANLPs. In order to handle such dynamic applications, in this dissertation we address an important question: whether some of the static restrictions of the SANLPs can be relaxed while keeping the ability to perform compile-time analysis and to derive PPNs in an automated way. Achieving this will significantly extend the range of applications that can be parallelized in an automated way. By studying different dynamic applications we distinguished three relaxations to SANLP programs that would allow one to specify dynamic applications as sequential programs. These relaxations allow dynamic if-conditions, for-loops with dynamic bounds and while-loops in a program. The first relaxation has already been considered. In this dissertation, we consider the other two more difficult relaxations. Show less
Chemokines are signaling proteins that direct the migration and function of many cell types during development and responses of the immune system. The zebrafish embryo model is highly suited to... Show moreChemokines are signaling proteins that direct the migration and function of many cell types during development and responses of the immune system. The zebrafish embryo model is highly suited to investigate cell migration because of its optical transparency and availability of transgenic lines with fluorescently labeled cell types of the innate immune system. In this thesis, we analyzed the phylogenetic relationships between zebrafish and human chemokines and used Salmonella and Mycobacterium infection models to study the function of a zebrafish chemokine receptor gene, cxcr3.2, homologous to human CXCR3. Our data have demonstrated that cxcr3.2 is predominantly expressed in macrophages of the zebrafish embryo and plays an essential role in bacterial-induced macrophage migration and control of local infections. Furthermore, we used in vivo cell migration assays in wild type and cxcr3.2 mutant embryos to discover the putative ligand of the cxcr3.2 receptor. Injection of Cxcl11, an infection-inducible chemokine, resulted in the directional migration of macrophages in a cxcr3.2-dependent manner. As the first ligand-receptor pair with a proposed function in migration of zebrafish macrophages in response to bacterial infection, the identification of Cxcl11-Cxcr3.2 interaction is an important step towards understanding the chemokine signaling network underlying innate immune responses in the zebrafish model. Show less
Protein-protein interactions play an important role in all cellular processes such as signal transduction, electron transfer, gene regulation, transcription, and translation. Understanding these... Show moreProtein-protein interactions play an important role in all cellular processes such as signal transduction, electron transfer, gene regulation, transcription, and translation. Understanding these protein-protein interactions at the molecular level, is an important aim in structural biology. The protein interactions studied in this work are principally involved in the signal transduction and in electron transfer. These protein interactions belong to the family of transient dynamic interactions, meaning they associate and dissociate rapidly. The work presented in chapters two and three gives a detailed description of a study to determine the binding orientation of focal adhesion kinase derived peptide on the Src SH3 domain using paramagnetic NMR spectroscopy. The work presented in chapter four gives detailed information on the cloning, expression and purification of the focal adhesion kinase domain with the SH3 and S H2 binding sequences (32k) using a baculovirus expression system. The results of NMR characterization were presented for the complexes of different Src domains and the 32k. The work presented in the chapters five and six describes the NMR characterization of the interactions between several redox proteins. The aim of the work was to convert the transiently bound weak protein complexes into specific complexes Show less
Data mining tools often only use a single type of information. The method proposed in this thesis allows the user to insert relational information into existing data mining tools that are designed... Show moreData mining tools often only use a single type of information. The method proposed in this thesis allows the user to insert relational information into existing data mining tools that are designed for content-based information. It does so by regarding the contents of the neighborhood of an element. In this way, the content variability of elements is reduced by using the homophily in the network. Show less
We discuss uniform infinite causal triangulations (UICT) and Gibbs causal triangulations which are probabilistic models for the causal dynamical triangulations (CDT) approach to quantum gravity.... Show moreWe discuss uniform infinite causal triangulations (UICT) and Gibbs causal triangulations which are probabilistic models for the causal dynamical triangulations (CDT) approach to quantum gravity. Since there is a bijection between causal triangulations and planar rooted trees we first discuss some aspects of random trees. In particular, we describe new methods to obtain the fractal and spectral dimension for a large class of random tree ensembles which in the thermodynamic limit have the property that they posses a unique infinite spine. The results are applied to obtain the spectral dimension of generic and non-generic trees, as well as a model of randomly grown trees. In the following, we discuss in detail the relation between UICT and size-biased critical Galton-Watson processes. This relation is used to prove convergence of the joint rescaled length-area-process to a diffusion process and to derive from this the quantum Hamiltonian of CDT. In what follows, in an alternative construction to the branching process, we propose a growth process which samples sections of UICT by elementary moves in which a single triangle is added with a certain probability. This construction is used to show that the fractal dimension of UICT is almost surely 2, in an alternative derivation to the branching process picture. Furthermore, we also derive convergence results for the rescaled length-area-process of the grown triangulation to a diffusion process leading to an interesting duality relation and a mathematically rigorous derivation of the so-called peeling procedure. In the final part, we discuss Gibbs causal triangulations and using the transfer matrix formalism we show convergence of the partition function to a limiting measure. Further, we analyse the transfer matrix of the Ising model coupled to (Gibbs) causal triangulations and derive several properties of the latter Show less
Phenomenologically, cosmic inflation is a satisfying and well-tested description of the physics of the very early universe. During this epoch, the universe was dominated by high energy phenomena... Show morePhenomenologically, cosmic inflation is a satisfying and well-tested description of the physics of the very early universe. During this epoch, the universe was dominated by high energy phenomena that can only be truly understood in a quantum gravity theory such as string theory. In this thesis we show that the embedding of inflation in a string theoretic framework is very sensitive to the details of the theory. We consider both the low energy supergravity limit as well as a worldsheet set-up. Moreover, we investigate the constraints imposed by supersymmetry and conformal symmetry. Conformal symmetry is important both in the worldsheet theory as well as in a holographic description of inflation. In the latter case we investigate the imprints of conformal invariance on the (observable) statistical correlations in the cosmic microwave background radiation. Show less
In this thesis we investigate different techniques and formalisms to address complexity introduced by unbounded structures in object-oriented programs. We give a representation of a weakest... Show moreIn this thesis we investigate different techniques and formalisms to address complexity introduced by unbounded structures in object-oriented programs. We give a representation of a weakest precondition calculus for abstract object creation in dynamic logic. Based on this calculus we define symbolic execution including abstract object creation. We investigate the complex behaviour introduced by multi-threading and give a formalism based on the transformation of multi-threaded reentrant call-graphs to thread automata and the application of context free language reachability to decide deadlock freedom of such programs. We give a formalisation of the observable interface behaviour of a concurrent, object-oriented language with futures and promises. The calculus captures the core of the Creol language and allows for a comparison with the concurrency model of thread-based, object-oriented languages like Java or C#. We give a technique to detect deadlock freedom for an Actor-like subset of the Creol language. Show less
Throughout the last decades the water oxidation process has been extensively investigated. However, open questions remain on the reaction mechanism and the possible intermediates in the catalytic... Show moreThroughout the last decades the water oxidation process has been extensively investigated. However, open questions remain on the reaction mechanism and the possible intermediates in the catalytic cycle. Indeed, different catalysts can function through different reaction routes. Some of them work in a proton-coupled electron transfer (PCET) pathway, while other catalysts have a non-PCET behaviour. Some of these problems lie in the very short lifetime of intermediates, which makes it difficult to characterize them experimentally. Within this context, DFT calculations represent a very useful tool. In fact quantum-mechanical computational tools allow exploring and analyzing the possible intermediates and study and compare different reaction pathways in order to find the energetically most likely one. In the same way the thermodynamics of the catalytic cycle and the kinetics of the reaction coordinates can be analyzed. The specific aim of this thesis is the study of different catalysts and reaction pathways to find clues about the mechanism of the reaction and develop guiding principles for the design of efficient water oxidation complexes Show less
Scientific practice is an activity that is data-intensive and widely supported by computerized systems, data repositories included. It is also an activity that is highly creative and, as such, can... Show moreScientific practice is an activity that is data-intensive and widely supported by computerized systems, data repositories included. It is also an activity that is highly creative and, as such, can benefit from a moment of openness, playfulness and exploration. Motivated also by recent developments in the field of Human Computer Interaction regarding play and games, this work investigates playfulness as a desirable attribute of a scientist's interaction with scientific data in repositories. Focus is on data repositories of a specific domain of science, i.e. the life sciences, and of a particular type of data, i.e. image data. Having introduced a new but relevant attribute for interfaces to scientific image repositories, i.e. playfulness, the question we ask is the following: What could playfulness with scientific images amount to and how do we design for it? Via case studies and reviews, we flesh out particular elements of play for exploration and implement artefacts, i.e. interfaces and games, that exemplify instances of playful interaction with image research material in collections. Show less
The exploitation of the unusual hydrophobic properties of diamondoid derivatives has been the primary goal of the research described in this Thesis. 1-Adamantaneacetic acid was used as a protective... Show moreThe exploitation of the unusual hydrophobic properties of diamondoid derivatives has been the primary goal of the research described in this Thesis. 1-Adamantaneacetic acid was used as a protective group in the solution-phase synthesis of (phosphorothioate) oligonucleotides. Pioneered by de Koning et al. a Solution-Phase Extraction Method (SPEM) amendable to scale-up was developed for the preparation of DNA and phosphorthioate oligonucleotide fragments. This approach utilizes extractive work-up procedures as the only tool in the isolation of oligonucleotides. Next, the design and synthesis of diamoniod decorated iminosugars as potential inhibitors of glycoside proccesing enzymes are described. Several libraries of natural iminosugars such as deoxynojirimycin and castanospermine decorated with an N-pentyloxy spacer were prepared. These iminosugar derivatives were evaluated as inhibitors of the enzymes involved in glucosylcramide metabolism, namely glucosylceramide synthase, beta-glucocerebrosidase and beta-glucosidase. Show less
Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP... Show moreNucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The yeast proteins Rad4 and Rad23 are important in NER and involved both Transcription-Coupled and Global Genome NER sub-pathways. Chapter 2 describes a novel mechanism of generegulation by the GG-NER E3 ligase. This protein complex can regulate dNTP synthesis via UV-induced Rad4 ubiquitination. In Chapter 3 we describe the effect of this histone on TC-NER at the rDNA. We find that Rad34 is only required when Histone H1 is present. In Chapter 4 we analyze the phenotype of a yeast strain containing a RAD4 mutation. The mutation affects a conserved residue that when altered in the human homolog XPC, leads to the cancer prone disorder XP. Chapter 5 is dedicated to the Rad4-Rad23 interaction that we describe in more detail. We uncovered a novel N-terminal interaction of Rad23 with Rad4 that is important for TC-NER. Finally, in Chapter 6 we reveal an unexpected UV phenotype for the commonly used wild-type yeast strain WCG4A. In this strain we identified the mutation to reside in the RAD4 gene Show less
This thesis describes the development and application of different methods for the construction of 1,2-cis glycosidic bonds, which remains one of the most challenging aspects in synthetic... Show moreThis thesis describes the development and application of different methods for the construction of 1,2-cis glycosidic bonds, which remains one of the most challenging aspects in synthetic carbohydrate chemistry. In Chapter 2 a synthesis of an orthogonally protected 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT) building block starting from D-glucosamine is outlined. Chapter 3 describes a modular approach towards the synthesis of all possible trimer repeating units of the type 1 capsular polysaccharide of Streptococcus pneumonia, Sp1. The difficulty associated with the efficient stereoselective introduction of _-galacturonic acid bonds was overcome by employing galacturonic acid-[3,6]-lactone building blocks. Chapter 4 describes a study of the reactivity and stereoselectivity of a galacturonic acid-3,6-lactone thioglycosyl donor in comparison with protected galacturonic acid and galactose donors using a series of competition experiments and condensation reactions with different thiophilic activator systems. Chapter 5a describes the application of a panel of C-6 thioether mannosyl donors, a C-6-selenoether donor and a C-6-iodide N-phenyltrifluoroacetimidate mannosyl donor in a series of condensation reactions. The applicability of one of these 1,2-cis-mannosylating agents is the subject of Chapter 5b. Upon condensation of 6-thio-6-deoxy-mannosyl donors reductive removal of the 6-thio functionality provides 1,2-cis rhamnosides. Following this methodology a backbone tetrasaccharide containing alternating _- and _-D-rhamnosides was synthesized. Show less
Lions in Waza National Park Cameroon were studied with focus on lion ecology and the human-lion conflicts due to livestock predation. The number of adult lions has declined from 40-60 in 2002 to 14... Show moreLions in Waza National Park Cameroon were studied with focus on lion ecology and the human-lion conflicts due to livestock predation. The number of adult lions has declined from 40-60 in 2002 to 14-21 in 2008, which represents a reduction of about 65% in 6 years. The human-livestock pressure on the park is enormous, 31% of photographs captured by camera traps in 2008, were of humans and livestock in the park. Retaliatory killing of lions by herders is high, as lions increasingly predate on cattle due to the strong decline of their natural prey. Lion home ranges have increased from a mean of 630 km² in 2000 to 1015 km² in 2008, extending to areas outside the park. Livestock constitutes as much as 21.6% of the diet. Characteristics of the diet and movements of the lion reflect a survival strategy of lions under highly disturbed conditions. Although the Waza lion population now seems to be most threatened, concerte d conservation efforts could save this population from local extinction. The government must greatly improve park protection through the park management authority and law enforcement, as well as providing financial and human resources for the park. Furthermore, local communities living close to the park must receive direct benefits from park revenues Show less
In this thesis two subjects are treated. The first one is the poisoning of hydrogen dissociation on Pt(533) by CO. It was found that decorating the step edges of Pt(533) by CO does not only block... Show moreIn this thesis two subjects are treated. The first one is the poisoning of hydrogen dissociation on Pt(533) by CO. It was found that decorating the step edges of Pt(533) by CO does not only block the indirect dissociation mechanism and the direct dissociation at step edges but also introduces an additional barrier for dissociation at the terraces. The second area contains a description of how a cylindrical Ni single crystal is employed in dissociation dynamics measurements. The analysis of the circumference by LEED is explained. Results for hydrogen dissociation are shown. They are analyzed by means of a model introduced for hydrogen dissociation on stepped Pt surfaces with (111) terraces and (100) steps. Show less
Adverse drug reactions are problematic for both society and pharmaceutical industry. The costs are high in severe cases: for pharmaceutical companies due to the loss of income if a drug needs to be... Show moreAdverse drug reactions are problematic for both society and pharmaceutical industry. The costs are high in severe cases: for pharmaceutical companies due to the loss of income if a drug needs to be removed from the market; for society due to the extra healthcare that is required to treat the affected individuals. Liver damage upon drug intake is the most common type of adverse drug reaction and reason for drug withdrawal. What makes the liver such a vulnerable target is its role as the main drug-metabolizing organ and its large amount of stationary immune cells. This results in frequent exposure to drug metabolite-induced and inflammatory stress. In this thesis I have investigated the role of the signaling induced by the pro-inflammatory cytokine TNF_ in the exacerbation of drug-induced liver injury using an in vitro liver cell model. Using this model and methods such as high content imaging, gene array analysis and functional genomics we have gotten closer to understanding the molecular mechanisms of liver injury. This knowledge can be used to design novel tests for the drug-industry to assess the toxicity of novel drug candidates as well as to pin-point potentially susceptible individuals. Show less
This doctoral dissertation describes a series of empirical investigations into representation, dissemination and coordination of software architecture design in the context of global software... Show moreThis doctoral dissertation describes a series of empirical investigations into representation, dissemination and coordination of software architecture design in the context of global software development. A particular focus is placed on model-centric and model-driven software development. Show less
A study of the effect of chloride and sulfate anions, as well as of SPS molecules on Cu electrodeposition is presented in this thesis. The deposition process was analyzed by means of a home-built... Show moreA study of the effect of chloride and sulfate anions, as well as of SPS molecules on Cu electrodeposition is presented in this thesis. The deposition process was analyzed by means of a home-built fast electrochemical STM in situ after and during deposition. Show less
The soil is a thriving ecosystem, composed of both living and non-living matter with a multitude of interactions between them. It is considered as the most diverse microbial habitat on earth. Soil... Show moreThe soil is a thriving ecosystem, composed of both living and non-living matter with a multitude of interactions between them. It is considered as the most diverse microbial habitat on earth. Soil microorganisms perform important functions in recycling nutrients. They act as nutrient scavengers, obtaining nutrition from dead, decaying matter of plants and animals. Actinomycetes (including Streptomyces) are a large group of filamentous bacteria and may account even 30% of the total microorganisms in the soil rhizosphere, depending on nutrient availability (Barreto et al., 2008; Kennedy, 1999).They are able to utilize broad range of naturally occurring polymers, including starch, cellulose, chitin and xylan. A sufficiency of utilisable organic material promotes the vegetative growth of these bacteria, thereby delaying morphological development and associated antibiotic production. My thesis focuses on understanding the molecular mechanisms by which Streptomyces link nutrient availability with antibiotic production and development. Show less
In this thesis the evolutionary background, function and localization of the domesticated transposase DAYSLEEPER are described. We found that DAYSLEEPER-like genes can be found in angiosperms, but... Show moreIn this thesis the evolutionary background, function and localization of the domesticated transposase DAYSLEEPER are described. We found that DAYSLEEPER-like genes can be found in angiosperms, but not in lower plants. We also found that DAYSLEEPER interacts with several proteins and is probably involved in regulating protein degradation through involvement in ubiquitin-mediated protein degradation. Show less
