Our studies have shown MRI assessed aortic stiffness being an integrated marker of cardiac function, cerebral small vessel disease and atrophy, as well as of renal function in type1 diabetes... Show moreOur studies have shown MRI assessed aortic stiffness being an integrated marker of cardiac function, cerebral small vessel disease and atrophy, as well as of renal function in type1 diabetes mellitus patients. Aortic stiffness already in normal range is related to end-organ damage in type1 diabetes mellitus, suggesting increased organ-susceptibility for vascular alterations in diabetes mellitus. Structural changes in the brain as a manifestation of end-organ damage has shown to be clinical relevant to elderly with diabetes mellitus predicting accelerated cognitive decline. Hypertension is a major contributor to increased aortic stiffness. There is clear effect of aortic stiffness on cardiac and cerebral end-organ damage in hypertensive patients, which is different from type1 diabetes mellitus. The results of our cross-sectional studies suggest that MRI assessment of aortic pulse wave velocity could function as a marker or risk factor for generalized vascular disease and end-organ damage that might potentially be treated. Our findings may therefore have implications for cardiovascular risk stratification and optimization of therapy in diabetes mellitus and hypertensive patients beyond classical risk factors. Finally, this thesis describes the technical implementation and benefits of right coronary artery MRA at high field 7T. This is a promising step towards improved MRI detection of coronary artery disease. Show less
The Aegagropila-clade is a unique lineage of algae within the large order Cladophorales and consists of poorly known taxa that mainly occur in brackish and freshwater environments. The clade is... Show moreThe Aegagropila-clade is a unique lineage of algae within the large order Cladophorales and consists of poorly known taxa that mainly occur in brackish and freshwater environments. The clade is sister to the species-rich, primarily marine Cladophora- and Siphonocladus-lineages. Most of its members occur in narrow niches such as on the carapaces of freshwater turtles (some members of Basicladia), on freshwater snails and bivalves (monotypic Arnoldiella and several Basicladia species), on and endophytically in saltmarsh plants and mangrove pneumatophores (some members of Wittrockiella), or on marine intertidal snails (Cladophora conchopheria). Aegagropila linnaei is the best known representative of the lineage and has gained considerable scientific, cultural and economic fame due to the peculiar lake balls formed under specific conditions. The confused taxonomy of the Aegagropila-clade was clarified using methods of molecular phylogenetic inference, resulting in the re-instatement of the Pithophoraceae, descriptions of two new genera and several nomenclatural changes. Phylogenetic analyses led to an understanding of the evolution of the heterotrichous habit as an adaptation to changeable environmental conditions. In selected taxa, topics such as phylogeography and dispersal abilities, historical biogeography and glacial refugia, and ecology and declining populations were studied in detail. Show less
Evolution and Interaction are two processes in Computer Science that are used in many algorithms to create, shape, find and optimize solutions to real world problems. Evolution has been very... Show moreEvolution and Interaction are two processes in Computer Science that are used in many algorithms to create, shape, find and optimize solutions to real world problems. Evolution has been very successfully applied as a pow-erful tool to solve complex search problems in fields ranging from physics, chemistry and biology all the way to commercial application such as aircraft fuselage design and civil engineering grading plans. Defining interaction is a big part of algorithm design. Not only defining the inputs and outputs of an algorithm but for a complex algorithm the interactions inside of an al- gorithm are as important. This thesis will concentrate on where Evolution overlaps Interaction. It will show how evolution can be used to evolve in- teraction, how the interaction inside an evolutionary algorithm impacts its performance and how an evolutionary algorithm can interact with humans. By touching on these three forms of overlap this thesis tries to give insight into the world of evolution and interaction Show less
The rediscovery of the Greek-Doric temples in South-Italian Paestum caused a great stir in eighteenth-century architectural thought and turned existing ideas on classical architecture upside down.... Show moreThe rediscovery of the Greek-Doric temples in South-Italian Paestum caused a great stir in eighteenth-century architectural thought and turned existing ideas on classical architecture upside down. More than any other ancient site Paestum came to fascinate architects, artists, writers and tourists, who represented the temples in drawings, engravings, texts or publications in a complex and paradoxical way, showing the developments in architectural thought from the cautious and exploratory rediscovery of the site to a general and strong consensus about the value of the temples. The site made it possible to question many subjects that were important in architectural, aesthetic and artistic debates in England, France and Italy. I argue that this becomes understandable through the analysis of architectural experience, a major theme in the eighteenth century. In studying the experiences in situ the dissertation reconstructs Paestum’s key role in the debates, with as main issues the sublime and the picturesque, primitivism and the origins of architecture, changing ideas on cultural meaning, and classical architecture and its role and historiography. The interactions between architectural experience and architectural theory demonstrate that Paestum functioned as a focus and laboratory for the growing importance of science and history in eighteenth-century architectural thought. Show less
This dissertation contains scientific research within the realm of quantum optics, which is a branch of physics. An experimental and theoretical study is made of two-photon interference phenomena... Show moreThis dissertation contains scientific research within the realm of quantum optics, which is a branch of physics. An experimental and theoretical study is made of two-photon interference phenomena in various optical systems. Spatially entangled photon pairs are produced via the nonlinear optical process of spontaneous parametric down-conversion. These entangled photons are then passed through different optical systems to study various aspects of two-photon interference. Firstly, an experimental analysis is made of the high-dimensional entanglement that is present in the orbital angular momentum of the photons. Secondly, we present a comprehensive description of two-photon quantum interference behind a double slit. We demonstrate how to control the quantum correlations and present the first observations of complete two-photon diffraction patterns behind a double slit. Finally, we present pioneering experiments on spatially entangled two-photon states that are scattered of random media. We have observed and theoretically analyzed the structure in the random two-photon interference patterns called two-photon speckle patterns. Spatial entanglement gives two-photon speckle a much richer structure than ordinary one-photon speckle. Our experiments also demonstrate a two-photon interference phenomenon that survives averaging over different realizations of disorder. The latter results are closely related to bosonic, fermionic, and anyonic particle exchange symmetries. Show less
The software today is distributed over several processing units. At a large scale this may span over the globe via the internet, or at the micro scale, a software may be distributed on several... Show moreThe software today is distributed over several processing units. At a large scale this may span over the globe via the internet, or at the micro scale, a software may be distributed on several small processing units embedded in one device. Real-time distributed software and services need to be timely and respond to the requests in time. The Quality of Service of real time software depends on how it schedules its tasks to be executed. The state of the art in programming distributed software, like in Java, the scheduling is left to the underlying infrastructure and in particular the operating system, which is not anymore in the control of the applications. In this thesis, we introduce a software paradigm based on object orientation in which real-time concurrent objects are enabled to specify their own scheduling strategy. We developed high-level formal models for specifying distributed software based on this paradigm in which the quality of service requirements are specified as deadlines on performing and finishing tasks. At this level we developed techniques to verify that these requirements are satisfied. This research has opened the way to a new approach to modeling and analysis of a range of applications such as continuous planning in the context of logistics software in a dynamic environment as well as developing software for multi-core systems. Industrial companies (DEAL services) and research centers (the Uppsala Programming for Multicore Architectures Resrearch Center UPMARC) have already shown interest in the results of this thesis. Show less
Turner syndrome (TS) is a disorder in females that is caused by the complete or partial absence of the second sex chromosome. The main characteristics are gonadal dysgenesis and short stature, with... Show moreTurner syndrome (TS) is a disorder in females that is caused by the complete or partial absence of the second sex chromosome. The main characteristics are gonadal dysgenesis and short stature, with adult patients being on average 20 cm shorter than healthy women. Growth hormone (GH) therapy increases adult height with 5 to 12 cm and the addition of the weak androgen oxandrolone (Ox) may further increase adult height. This thesis describes the results of the first randomized, double-blind, placebo-controlled study on the question whether GH-treated girls with Turner syndrome would profit from Ox therapy, and if so, which Ox dosage should be given. It was concluded that the conventional Ox dosage (0.06 mg/kg/day) should not be used because of its limited efficacy and virilizing capacity. In contrast, the addition of Ox at a dosage of 0.03 mg/kg/day starting between the age of 8 to 15 years increases height during therapy, modestly increases adult height gain and has a fairly good safety profile, except for a small deceleration in breast development. In patients considering this deceleration less important than the increment in height gain, we therefore suggest to add Ox 0.03 mg/kg/day to GH to increase height. Show less
Obesity is characterized by excessive fat storage and is associated with various diseases like cardiovascular disease (CVD) and type 2 diabetes (DM2), thereby being a serious problem of public... Show moreObesity is characterized by excessive fat storage and is associated with various diseases like cardiovascular disease (CVD) and type 2 diabetes (DM2), thereby being a serious problem of public health. Excessive energy intake is an important cause of obesity since excess energy is primarily stored as fat. The stored fat is mobilized again during fasting in the form of fatty acids (FA). These FA are re-esterified in the liver in triglycerides (TG) that are secreted in VLDL particles to deliver FA to peripheral tissues where they can be used for energy. One of the current views of the cause of diseases related to obesity is the (mis)handling of TG derived FA. Therefore it is important to understand pathways involved in the uptake, distribution, oxidation and storage of TG. In this thesis we have evaluated the effect of different interventions on VLDL-TG metabolism to gain a better understanding of its complex regulation. For these studies we used APOE*3-Leiden (E3L) and E3L.CETP transgenic mice that have a human-like lipoprotein metabolism and respond to lipid-modifying drugs in a ways similar to humans. Show less
This thesis investigates mechanisms of adaptation to climate, and in particular temperature, in the African butterfly Bicyclus anynana. The work takes an integrated approach and brings together... Show moreThis thesis investigates mechanisms of adaptation to climate, and in particular temperature, in the African butterfly Bicyclus anynana. The work takes an integrated approach and brings together studies at the phenotypic, physiological and genetic level. By examining geographical variation among wild populations, the thesis investigates how B. anynana is adapted to geographically varying thermal conditions. The first half of the thesis is focused on phenotypic plasticity, which is a major component of adaptation to climate in B. anynana. Chapter 2 compares the plasticity response to temperature of two populations, and reveals a population-specific response for wing pattern but very small to no differences in the response of life history traits. Chapter 3 shows that a discontinuous regulatory hormone signal during development underlies the seasonal plasticity in B. anynana. In the second half of the thesis, I take a molecular genetic approach by studying geographic patterns of neutral and adaptive evolution in wild populations. Chapter 4 indicates that the B. anynana species area expanded southwards after the last ice age from glacial equatorial habitat refugia. Chapter 5 identifies clinal variation in genes coding for metabolic enzymes, indicating a putative role of these genes in thermal adaptation. Show less
Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the... Show moreStem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the research as described in this thesis was to visualize survival, proliferation, and migration of embryonic (ESC) and adult stem cells using non-invasive molecular imaging techniques in small animal models of cardiovascular diseases. The major findings can be described as follows: (1) Non-invasive bioluminescence imaging is a validated tool to monitor donor cell survival, proliferation, migration, and misbehavior; (2) ESC are a potential source for true regenerative therapy; (3) ESC form teratomas; (4) Adult stem cell survival is short-lived, but of all cells currently used in the clinic, mononuclear cells show the most prolonged survival; (5) Transplantation of mononuclear cells can preserve cardiac function in the short term after myocardial infarction in mice; (6) Compared to other measurements of murine cardiac function, Micro-CT is a superior method to assess cardiac geometry and function; and (7) Transplantation of mononuclear cells in peripheral artery disease is hampered by dismal cell survival and homing. These findings illustrate the current challenges for optimizing stem cell therapy for cardiovascular disease. Show less
The appearance of the first luminous sources in the Universe marks the beginning of the epoch of reionisation. The cosmic reionisation of hydrogen has been the last major phase transition in the... Show moreThe appearance of the first luminous sources in the Universe marks the beginning of the epoch of reionisation. The cosmic reionisation of hydrogen has been the last major phase transition in the evolution of the Universe, turning cool neutral gas into the hot, ionised plasma we observe today. Up to now, direct observations of reionisation have been impossible, most of our current knowledge therefore stems from numerical studies. However, even with current computing facilities the modelling of the reionisation epoch presents some serious challenges. Radiative transfer is perhaps the biggest challenge, due to the high dimensionality and non-locality of the problem. In this thesis the latest improvements of the SimpleX method, that was designed to overcome some of the problems related to radiative transfer, are presented. We have used this method to study the escape fraction of ionising photons from galaxies. Our results show that high-redshift dwarf galaxies can be important contributors to cosmic reionisation. In addition, we have studied the effect of the inclusion of diffuse recombination radiation in reionisation simulations on large scales, which has been neglected by recent studies. We show that diffuse recombination radiation does not have a significant influence on the reionisation process. Show less
Het post 9/11 terrorisme en de daarmee gepaard gaande war on terror hebben de roep om veiligheid binnen het politieke en het maatschappelijk debat over veiligheid doen aanwakkeren. Hierbij dreigt... Show moreHet post 9/11 terrorisme en de daarmee gepaard gaande war on terror hebben de roep om veiligheid binnen het politieke en het maatschappelijk debat over veiligheid doen aanwakkeren. Hierbij dreigt het gevaar dat de (individuele) rechtsbescherming tegen de overheid, soms uit het oog dreigt te worden verloren. Het is aan de (straf)wetgever de verschillende bij nieuwe wet- en regelgeving de verschillende in het geding zijnde belangen continu voor ogen te houden en, indien er keuzes gemaakt moeten worden, deze verschillende belangen weloverwogen en consciëntieus tegen elkaar af te zetten. In dit onderzoek wordt aan de hand van een analyse van de totstandkoming van antiterrorismewetgeving inzicht gegeven in de wijze waarop maatschappelijke veranderingen in sociale structuren en culturele gevoeligheden, alsook veranderingen en ontwikkelingen in de politieke context, hun doorwerking hebben gevonden op deze lastige taak van de (straf)wetgever. Hierbij wordt eveneens stilgestaan bij de invloed van de (straf)rechtswetenschap. Een bezinning op de totstandkoming van de antiterrorismewetgeving en de belangenafweging door de wetgeving daarbij biedt inzicht in de legitimiteit en noodzakelijkheid, maar ook in de kwaliteit, van de desbetreffende wetgeving. Op basis van het onderzoek zijn uiteenlopende bevindingen geformuleerd die niet alleen de (straf)wetgever betreffen, maar eveneens ‘de’ politiek en ‘de’ strafrechtswetenschap. Show less
The concepts, policies, laws and practices regarding community-based forest management have changed over time. However, their objective is constant, namely to fight forest destruction and poverty... Show moreThe concepts, policies, laws and practices regarding community-based forest management have changed over time. However, their objective is constant, namely to fight forest destruction and poverty and to resolve conflicts regarding forest tenure. Securing community forest tenure is a way for achieving this objective. Forest tenure security, however, requires more than legalisation of community property rights by state law. It results from an interplay between state and/or community normative systems, actual practices and actors’ perceptions. Legalisation of rights by state institutions is only one facet of security, more specifically legal security of forest tenure that will be determined by the rights’ robustness, proper duration and strong legal protection. The security of community forest tenure will be also achieved through the ability of social norms to secure the rights of ordinary people. In addition, the consistent enforcement of the rules or norms by the officials or local authorities is necessary and the behaviour of these officials and local authorities must be in line with the interests and perception of the majority of community members. Last but not least, efforts of securing communities’ rights must take into consideration the specific history of land tenure and conflicts. Show less
This thesis focuses on the quantification of hypothalamus-pituitary-adrenal (HPA) axis activation in healthy volunteers by applying pharmacological function tests with distinct pharmacodynamic (PD)... Show moreThis thesis focuses on the quantification of hypothalamus-pituitary-adrenal (HPA) axis activation in healthy volunteers by applying pharmacological function tests with distinct pharmacodynamic (PD) mechanisms. Its main objective is to contribute to the validation of different function tests for the two most well-characterized HPA axis activation routes. To realize this objective, different experiments were executed in which specific principles that have been proposed to optimize the reliability of pharmacological function tests were observed. Human corticotrophin-releasing hormone (corticorelin - hCRH) and the direct serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) were applied for the corticotrophinergic (CRH-mediated) route while the synthetic analogue of arginine-vasopresin (AVP) desmopressin (dDAVP)and the D2 receptor antagonist metoclopramide were used for the vasopressinergic (AVP-mediated) pathway. Additionally, the application of these function tests was expected to contribute to a better understanding of the respective contributions of the corticotrophinergic and vasopressinergic pathways to HPA axis activation in health. Finally, an extra dimension was added to the validation process by applying proton magnetic resonance spectroscopy (MRS)to measure changes in hypothalamic metabolites during pharmacological stimulation. Show less
In this thesis we provide a unit testing approach for multi-purposes object-oriented programming languages in the style of Java and C#. Our approach includes the definition of a test... Show moreIn this thesis we provide a unit testing approach for multi-purposes object-oriented programming languages in the style of Java and C#. Our approach includes the definition of a test specification language which results from extending the programming language with new designated specification constructs. This way, the software developer does not need to learn a completely new language. At the same time, adding new constructs allows to increase the abstraction of the language regarding the specification of interaction-based tests. In order to execute a specified test, programming language code is automatically generated from a test specification. Our testing approach is presented in terms of a formal framework. On the one hand, this enables us to identify and analyze the requirements on the design of the specification language in a formal way. On the other hand, on the formal basis we can, likewise, give a formal definition of the code generation algorithm which, in turn, allows us to formally prove its correctness. Finally, we provide a correctness proof regarding the code generation algorithm. Show less
The objective of the project described in this thesis was to study the complex induction of extracellular proteases in the filamentous fungus Aspergillus niger using information gathered with... Show moreThe objective of the project described in this thesis was to study the complex induction of extracellular proteases in the filamentous fungus Aspergillus niger using information gathered with functional genomics technologies. A special emphasis is given to the requirements for performing a successful systems biology study and addressing the challenges met in analyzing the large, information-rich data sets generated with functional genomics technologies. The role that protease activity plays in strain and process development of A. niger and other aspergilli is reviewed. The influence of several environmental factors on the production of extracellular proteases of A. niger in controlled batch cultivations was studied. Samples generated in this study were used for analysis with different functional genomics technologies. With a shotgun proteomics approach the A. niger secretome under different experimental conditions was determined. Furthermore, the effect of different quantitative phenotypes related to protease or glucoamylase activity on the information content of a metabolomics data set was investigated. Finally, the clustering of co-expressed genes is described. First, a set of conserved genes was used to construct gene co-expression networks. Subsequently, all protein-coding A. niger genes, including hypothetical and poorly conserved genes, were integrated into the co-expression analysis. Show less
Dit proefschrift bestaat uit twee delen: een monografie (verschenen in 2005) en een essay. De monografie vormt eerst en vooral een bronnenboek: zij bevat een biografie van de kunstenaar, geeft een... Show moreDit proefschrift bestaat uit twee delen: een monografie (verschenen in 2005) en een essay. De monografie vormt eerst en vooral een bronnenboek: zij bevat een biografie van de kunstenaar, geeft een beeld van de context waarin Jessurun de Mesquita leefde, zijn werk ontstond en werd ontvangen, en beschrijft de diverse facetten van zijn oeuvre, zowel afzonderlijk als in relatie tot elkaar. Het tweede deel van de monografie bestaat uit een grondig gedocumenteerde oeuvrecatalogus van de grafiek, waarmee een vrijwel volledig beeld van De Mesquita's veelomvattende grafische oeuvre is gegeven. De gegevens die in de monografie bijeengebracht zijn, vormen de basis voor een essay waarin de tweespalt die zich aftekent in zijn oeuvre tot uitgangspunt wordt genomen. De ene groep omvat portretten en uitbeeldingen van exotische dieren, planten en bloemen. De tweede groep werken bestaat uit bizarre, vaak humoristische, soms grimmige fantasievoorstellingen die onder de noemer sensitivistische verbeeldingen bekend zijn geworden. Aan de hand van een confrontatie van beide groepen is de vraag naar de intentie van deze werken onderzocht: wat beoogde De Mesquita met deze werken? Show less
Wat bepaalt de kwaliteit van gehechtheid? In een grootschalig onderzoek, Generation R, zijn de stresshuishouding en enkele kandidaatgenen van de kinderen onderzocht, en het gedrag van de ouder. De... Show moreWat bepaalt de kwaliteit van gehechtheid? In een grootschalig onderzoek, Generation R, zijn de stresshuishouding en enkele kandidaatgenen van de kinderen onderzocht, en het gedrag van de ouder. De gehechtheidsrelatie is de relatie tussen een kind en een ouder (of andere stabiele verzorger) die in het eerste levensjaar wordt opgebouwd. Veilig gehechte kinderen gebruiken hun ouder als veilige haven van waar ze de omgeving verkennen. Onveilig gehechte kinderen hebben hier moeite mee; zij kunnen niet de juiste balans vinden tussen contact met de ouder en het verkennen van de omgeving. Dit onderzoek laat zien dat onveilig gehechte kinderen heftiger op stress reageren dan veilig gehechte kinderen. Wanneer er sprake was van depressie in het leven van de moeder, leidt dit tot een verdere toename van stress bij de onveilig gehechte kinderen. Hetzelfde gold voor onveilig gehechte kinderen met een risico-gen dat verantwoordelijk is voor een minder goede stressregulatie. Verder vonden we dat sensitief opvoedgedrag van moeder leidde tot meer veilige gehechtheid, maar alleen wanneer het kind een bepaalde variant van een gen droeg dat van belang is bij het omgaan met stress. De resultaten laten de kwetsbaarheid en stressgevoeligheid van onveilig gehechte kinderen zien. Daarnaast kunnen we op basis van de huidige resultaten zeggen dat insensitief opvoedgedrag, depressie van moeder en genetische risico’s een rol spelen bij onveilige gehechtheid. De ontwikkeling van gehechtheid is complex, en het resultaat van het samenspel tussen biologische aspecten en de opvoedingsomgeving. Daarop moet toekomstig onderzoek dan ook gericht zijn. Show less
