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
Colorectal cancer (CRC) is the second leading cause of cancer death in the Netherlands and the fourth worldwide. Matrix metalloproteinases (MMPs) are involved in the process of colorectal cancer... Show moreColorectal cancer (CRC) is the second leading cause of cancer death in the Netherlands and the fourth worldwide. Matrix metalloproteinases (MMPs) are involved in the process of colorectal cancer development and progression. MMPs are capable of degrading the extracellular matrix components of the intestinal basement membrane and facilitate invasion into the deeper layers of the bowel wall, lymph nodes and/or blood vessels. Furthermore, they are implicated in several processes in the microenvironment of colorectal cancer, like angiogenesis, cell death and inflammation. In this thesis, the focus is on the clinical impact of matrix metalloproteinases (MMPs) in the different stages of colorectal cancer development and metastasis. MMP-7, -8 and -9 were shown to be involved in the early stages of colorectal cancer development, whereas MMP-2 levels were only increased in cancer tissue but not in precancerous lesions. Furthermore, MMP-2, MMP-7 and MMP-9 were identified as predictors of outcome in patients with colorectal carcinoma, both at genetic (SNP) and protein level. The increased knowledge of the role of MMPs in the various stages of CRC might contribute to further development of specific anti-MMP therapies in the future. Show less
This thesis reports three studies examining how electronic storybooks contribute to young children’s literacy development. Study 1 shows that ‘reading’ e-books facilitates 4- to 6-year-olds’... Show moreThis thesis reports three studies examining how electronic storybooks contribute to young children’s literacy development. Study 1 shows that ‘reading’ e-books facilitates 4- to 6-year-olds’ vocabulary development and story comprehension. Video books including motion pictures and sounds/music were more effective than versions with merely static illustrations, in particular for learning new vocabulary. Interactive video books including extra-textual word meaning explanations were the best alternative to stimulate word learning. In Study 2, two methods of extra-textual vocabulary instruction were compared. Results showed that instructional formats that require children to invest more effort are more effective than formats that require less effort: multiple-choice questions were more beneficial than providing definitions. In addition to these effects in normative groups, Study 3 showed that independent e-book ‘reading’ is effective in children with severe language impairments (SLI) as well. However, background music and sounds embedded in video books interfered with word learning: e-books were only effective when the audio included the narration only. In sum, this thesis shows that media-specific design features such as video and interactivity may make ‘independent e-book reading’ a valuable tool to promote early language and literacy development. 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
Central in the representation of eroticism between brother and sister, classical theme in litterature and film, stands the incest prohibition as source of tension between similarity and difference.... Show moreCentral in the representation of eroticism between brother and sister, classical theme in litterature and film, stands the incest prohibition as source of tension between similarity and difference. Brother and sister share the same genes and because of this they belong together and go different paths. Until halfway through the twentieth century this theme possessed an absolute, because transcendental dimension. The incest prohibition was given from (a) god. However, in our secularized world this is no longer the case. Within this context this study explores the vision on similarity and difference, the two meaning-producing principles of our culture. More and more, formerly still irrefutable contradictions as ratio versus imagination, black versus white or man versus woman count as gradual differences. In de ban van het incestverbod shows this development on the basis of four paradigmatic texts – Debrot, Mijn zuster de negerin; Campert, Het satijnen hart; Van Woerden, Utramarijn – and Grimm, a film of Alex Van Warmerdam. Show less
This thesis is dedicated to the study of random walks in dynamic random environments. These are models for the motion of a tracer particle in a disordered medium, which is called a static random... Show moreThis thesis is dedicated to the study of random walks in dynamic random environments. These are models for the motion of a tracer particle in a disordered medium, which is called a static random environment if it stays constant in time, or dynamic otherwise. The evolution of the random walk is defined by assigning to it random jump rates which depend locally on the random environment. Such models belong to the greater area of \emph{disordered systems}, and have been studied extensively since the early seventies in the physics and mathematics literature. The goal is to understand the scaling properties, as time goes to infinity, of the path of the random walk. Several results are available in the literature for dynamic random environments which are uniformly elliptic and have uniform and fast enough mixing in space-time. However, very little is known when either of these conditions fail. In this thesis, we study examples of such situations, namely, non-elliptic cases in Chapter 2, a dynamic random environment with fast but non-uniform mixing in Chapter 4, and a dynamic random environment with both slow and non-uniform mixing in Chapters 3 and 5. Show less
This study examines a strategic partnership in the areas of peace and security between the EU and Africa. The EU has been strengthening its institutional ties with African organisations since 2000,... Show moreThis study examines a strategic partnership in the areas of peace and security between the EU and Africa. The EU has been strengthening its institutional ties with African organisations since 2000, with security relations with Africa a priority on the EU’s agenda following the 9/11 attacks on the United States of America. The study shows the driving forces behind the establishment of the partnership, arguing that the EU’s economic interests have played a significant role in its development. In addition, new global threats and challenges, such as immigration issues, climate change, international terrorism, conflicts, and the emerging global actors in Africa have affected the EU’s current foreign and security policy towards Africa. Norms and ideas also contribute to the emergence of the notion of strategic security partnership, but to a lesser extent. Drawing on literature, the method of process-tracing, and p rimary, secondary and tertiary sources, this dissertation opens up previously unexplored aspects of security relations between the two continents. Against the historical background of colonialism and recent moves to continental confederation and globalism, it seeks to determine why the EU has consolidated its institutional relations with African organisations. 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
Over the last few decades, western archaeology increasingly abandoned its __ivory tower__ in order to investigate, negotiate and develop its position and role in global society. The way in which we... Show moreOver the last few decades, western archaeology increasingly abandoned its __ivory tower__ in order to investigate, negotiate and develop its position and role in global society. The way in which we deal with other peoples views in the interpretation of archaeological materials, the way in which we integrate our narratives and practices with other heritage demands, and the way in which we deal with power differences in both these processes; all are challenging issues when undertaking archaeological research projects abroad. Sjoerd van der Linde brings forward an ethnographic and discursive analysis of two archaeological projects by the Faculty of Archaeology of Leiden University - notably the Deir Alla Joint Archaeological Project in the Hashemite Kingdom of Jordan and the Santa Barbara Project in Cura_ao. Focusing on the ways and extents to which these projects are influenced by different policy and funding programs, and investigating the operational systems, social relationships and dominating values and discourses that determine project outcomes, he explores how archaeological research projects abroad work in their social context. Van der Linde offers a critical reflection upon the role and responsibility of archaeologists in relation to the values and demands of other actors in society. 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
A life-like human arm decorated with lace sleeves, holding an eyelid on a string, fragments of skin swivelling in a phial with a twig, a shiny silvery liver, a dog with a cleft palate, a human ear... Show moreA life-like human arm decorated with lace sleeves, holding an eyelid on a string, fragments of skin swivelling in a phial with a twig, a shiny silvery liver, a dog with a cleft palate, a human ear with a tiny pox mark, foetuses decorated with colourful beads. At first sight, it seems an odd collection of specimens. Yet they are all part of the eighteenth century Leiden anatomical collections, made by Leiden anatomists and their acquaintances and acquired by Leiden University afterwards.A lot has been written about the anatomists and their discoveries, but very little is known about these preparations. That is odd, as it are the preparations themselves that evoke so many questions: why these body parts, plants, animals? Why these decorations and combinations? Why did their makers conceive them? Why were they acquired by the university? It is also worrying that we know so little about these preparations, as they are steadily deteriorating - no matter how great the curatorial efforts made.This Ph.D. thesis uses the materiality of the anatomical preparations as the starting point to answer the questions they evoke, combining material and contextual analysis. The author argues that aesthesis, an epistemic culture that included a tacit quest for beauty and perfection rooted in sensory experience and intertwined with the rise of the new field of aesthetics, was defining for the way the eighteenth-century Leiden anatomists made and used their preparations. The knowledge embedded in the materiality of these historical objects is essential for making informed decisions about their preservation and display, now and in the future. Show less
The thesis starts with a high-level introduction into cryptography and quantum mechanics. Chapter 2 gives a theoretical foundation by introducing probability theory, information theory, functional... Show moreThe thesis starts with a high-level introduction into cryptography and quantum mechanics. Chapter 2 gives a theoretical foundation by introducing probability theory, information theory, functional analysis, quantum mechanics and quantum information theory. Chapter 3, 4 and 5 are editions of work published earlier. In Chapter 3, we present a quantum-information-theoretic tool to analyze random sampling in a quantum setting. In particular, we present two new rigorous security proofs that make use of our new sampling tool: one for BB84 quantum key distribution, and one for a quantum reduction from oblivious transfer (OT) to bit commitment. Chapter 4 studies the problem of message authentication from a weak key (which is a key that is not uniformly random, e.g., a password) in a new scenario. In this scenario, the weak key is a one-time session key that is derived from a public source of randomness with the help of a long-term key (e.g., a password). We propose a new four-round protocol for message authentication from a weak (session) key. In Chapter 5 we present a new entropic uncertainty relation and furthermore we consider the task of password-based identification. We devise a new quantum identification protocol that is secure in two security models simultaneously. Show less
The current health care system is severely challenged by for instance rising costs, fewer new blockbuster drugs and increasing numbers of hospitalizations due to side effects. Especially in the... Show moreThe current health care system is severely challenged by for instance rising costs, fewer new blockbuster drugs and increasing numbers of hospitalizations due to side effects. Especially in the area of chronic diseases the current disease fighting strategy is failing and a more personalized medicine approach is needed. In this thesis new sub-types of rheumatoid arthritis are characterized with metabolomics analysis and symptoms patterns. The sub-types are based on diagnostic knowledge from Chinese medicine. The two sub-types of RA patients were found to have differences in apoptosis regulation of T-cells and differences in urine acylcarnitine levels. A questionnaire was designed to distinguish the two sub-types and to evaluate symptom patterns of arthritis patients. In the future the response to treatment of these sub-types of patients can be studied and specific treatment can be targeted to these sub-types. 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
