The origin and evolution of galaxies are closely linked to many different physical phenomena. Among them, the most important one is the environment they reside in. Isolated and cluster member... Show moreThe origin and evolution of galaxies are closely linked to many different physical phenomena. Among them, the most important one is the environment they reside in. Isolated and cluster member galaxies indeed are affected by different forces which affect their evolution. The main concern of this thesis is to understand such forces and how they are related to galaxy evolution. Therefore, this thesis covers various topics including black hole mass calculations, the black hole mass-stellar velocity dispersion relation, the nature of AGN emission in galaxy clusters and field galaxies, a detailed investigation of X-ray and optical galaxy overdensity phenomenon, and the dynamical processes in pre-merging galaxy clusters. Show less
In this thesis, the monitoring of the immune system in balance and during active responses (by flow cytometry) plays a central role. In chapter 2.1 and 2.2, we investigated the optimal sample... Show moreIn this thesis, the monitoring of the immune system in balance and during active responses (by flow cytometry) plays a central role. In chapter 2.1 and 2.2, we investigated the optimal sample logistics for high-dimensional flow cytometry in clinical trials. In chapter 3.1-3.4, we monitored the longitidinal kinetics of circulating immune cells in humans after vaccination or bacterial challenge against Bordetella pertussis. Lastly, in chapter 4, we investigated the immune system in humans carrying a genetic variant of PLCG2 'p.P522R', which is associated with increased longevity and reduced chance of developing dementia. Show less
In condensed matter systems electron-electron interactions, negligible in everyday metals, can dramatically alter the electronic behavior of the system. Examples of such altered behavior include... Show moreIn condensed matter systems electron-electron interactions, negligible in everyday metals, can dramatically alter the electronic behavior of the system. Examples of such altered behavior include high-temperature superconductivity and modulation of the electron density. A common feature of this correlation driven behavior is the tendency of the spatial electronic structure to vary on the nanometer scale. In this thesis we explore the nanoscale variation of the electronic structure of various correlated electron systems. We use the wave-like oscillations in the electron density of states to probe fundamental properties of the system providing insights into when various experimental probes disagree with each other. Turning our attention to high-temperature superconductors we find that close to the transition between superconductor and metal a granular superconductor emerges, small nanoscale patches of superconductivity interlaces with a metallic matrix. A careful examination of the wave-like oscillations hints at the presence of spatial ordering of the electrons. Finally we study how the presence of strong interactions can alter the way electrons flow through a material such that concepts usually reserved for everyday fluids become relevant. Show less
Quantum annealing belongs to a family of quantum optimization algorithms designed to solve combinatorial optimization problems using programmable quantum hardware. In this thesis, various methods... Show moreQuantum annealing belongs to a family of quantum optimization algorithms designed to solve combinatorial optimization problems using programmable quantum hardware. In this thesis, various methods are developed and tested to understand how to formulate combinatorial optimization problems for quantum annealing. Use of both purely quantum approaches as well as hybrid quantum-classical algorithms are investigated using state-of-the-art quantum hardware. How the developed methods affect the performance of quantum hardware in practice is tested using both real-world and canonical academic problems. Show less
Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from... Show moreAcute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous elements in large arteries. The pathogenesis of atherosclerosis involves complex interactions between a wide variety of cells, including monocytes, macrophages, neutrophils, and lymphocytes. It is essential to identify novel targets for therapeutic application in order to reduce the residual atherosclerotic cardiovascular disease risk in current and future patients. Recent studies have suggested that members of the protein arginine methyltransferase (PRMT) family can potentially serve as novel therapeutic targets for atherosclerosis because of their regulatory role in inflammation and metabolism. To validate the contribution of PRMTs in the progression of atherosclerosis, in the studies presented in this thesis we have investigated the effect of inhibition of PRMT functionality on atherosclerosis susceptibility in established atherosclerotic mouse models.To address the role of PRMTs in atherosclerosis, we therefore made use of specific PRMT inhibitors, i.e. TC-E 5003 for PRMT1 inhibition, TP-064 for PRMT4 inhibition, and GSK3326595 for PRMT5 inhibition, that thus far have primarily been applied in vivo in the context of cancer treatment. Show less
This thesis is the result of several studies into the clinical and echocardiographic outcome of both open and hybrid surgical ventricular reconstruction for the treatment of ischemic cardiomyopathy... Show moreThis thesis is the result of several studies into the clinical and echocardiographic outcome of both open and hybrid surgical ventricular reconstruction for the treatment of ischemic cardiomyopathy. Additionally, predictors for a favorable outcome and important associated issues such as management and late outcome of functional mitral regurgitation and the use of LV ejection fraction as a selection criterium for indication for a implantable cardioverter defibrillator for the primary prevention ofventricular arrhythmias after surgical ventricular reconstruction were studied. In chapter 2 the early and late outcome of different types of open left ventricular reconstruction surgery by means of a meta-analysis are presented. Chapter 3 describesthe use of echocardiographic wall motion score index to predict mortality and functional results after surgical ventricular reconstruction for advanced ischemic heart failure. In chapter 4 the management of functional mitral regurgitation during left ventricular reconstruction is presented followed by a landmark analysis into the 10-year outcome of functional mitral regurgitation after left ventricular reconstruction. Chapter 5 discusses the use of the improved LV ejection fraction after SVR as an indication for a implantable cardioverter defibrillator for the primary prevention of ventricular arrhythmias after surgical ventricular reconstruction in heart failure patients. Chapter 6 discusses the early experience with a minimal-invasive hybrid transcatheter surgical ventricular reconstruction technique. First the technique of hybrid transcatheter left ventricular reconstruction is described. Followed by the preliminary results of this technique from 2 cardiac centres in the Netherland. Finally, the multicenter European results of hybrid less invasive reconstruction on clinical, functional and echocardiographic outcome are presented. Show less
This dissertation takes a technological approach to ceramic production and provides a fine-grained view of the circum-Caribbean region. It discusses the usefulness of the chaîne opératoire... Show moreThis dissertation takes a technological approach to ceramic production and provides a fine-grained view of the circum-Caribbean region. It discusses the usefulness of the chaîne opératoire methodology, together with the community of practice theory, as models to potentially explore questions related to the boundedness and cultural relations of peoples during the precolonial, colonial and postcolonial periods. Each chapter tackles diverse aspects of the manufacturing process, from the procurement of the raw materials to the forming stage and provide different cases of how methodologies need to be tailored to answer specific research questions. Geochemical and petrographic analysis combined with macro and micro-observations of the ceramic materials from different sites in Nicaragua, Haiti, Dominican Republic and Puerto Rico clarify the human-environment interactions and socio-cultural aspects of communities in precolonial times, and during the colonial and postcolonial periods. Show less
The learning of software design is known to be a difficult and challenging task for students. This dissertation studies different didactic approaches for learning software design to improve the way... Show moreThe learning of software design is known to be a difficult and challenging task for students. This dissertation studies different didactic approaches for learning software design to improve the way we teach students software design. The research in the dissertation questions whether we can assess software design skills, what guidance is needed for the improvement of students’ understanding of software design and how to motivate and engage students for learning software design. The research explores the following: an instrument for measuring software design skills based on design principles, the gamification of learning software design, revealing students’ software design strategies, the use of peer-reflection for uncovering the difficulties students have during software design tasks, the use of teaching assistants as bridge between the lecturer and the students, the automation of grading software designs with machine learning, guiding feedback by a pedagogical agent and a workshop for engaging students into the process of software development. The research contributes to the future education of software design. Show less
Dark matter is one of the biggest mysteries of the Universe. Its properties cannot be explained with the known laws of physics and elementary particles. Yet, it is the most abundant form of matter... Show moreDark matter is one of the biggest mysteries of the Universe. Its properties cannot be explained with the known laws of physics and elementary particles. Yet, it is the most abundant form of matter in the Universe.Several dark-matter theories exist, including cold dark matter (CDM), self-interacting dark matter (SIDM), and fuzzy dark matter (FDM). These theories make different predictions for the density profiles of dark-matter haloes (cuspy or cored), depending on the nature (CDM, SIDM, FDM) and properties (self-interaction strength, FDM particle mass) of dark matter. These profiles can be determined from the stellar kinematics of the galaxies hosted by the haloes. Many massive dwarf galaxies show cored profiles. However, baryonic processes such as star formation may also induce cores.In this thesis, I test CDM, SIDM, and FDM using the faintest and most dark matter–dominated galaxies, ultra-faint dwarf galaxies (UFDs), which offer a new perspective on the cusp–core problem. The stellar kinematics of UFDs should not be significantly affected by baryonic processes. I find that UFDs have no detectable cores, implying that the cores of more massive dwarf galaxies are not caused by dark-matter physics. I can also exclude the previously promising particle masses ~10^-22 eV/c^2 for FDM. Show less
Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health. Optimising antimicrobial treatment... Show moreAntimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health. Optimising antimicrobial treatment strategies in patients offers an important direction to address this challenge. In this thesis, we describe how quantitative characterisation of the drug, the pathogen, and the patients, and how these three factors interact, can help to achieve this goal. To this end, we used a combination of state-of-the-art in silico model-based approaches to analyse and integrate experimental data from in vitro models, and clinical data from healthy volunteers and patients. We developed models describing infection site drug exposure, antimicrobial resistance evolution, and host response biomarker dynamics. We explored the impact of infection on pulmonary pharmacokinetics, evolutionary-based treatment strategies, and the utility host response biomarker for treatment monitoring. The work in this thesis builds towards developing novel strategies to optimise antimicrobial treatments and showcases the importance on interdisciplinary collaborations. Show less
Water is all around us and is vital for all aspects of life. Studying the various compounds and life forms that inhabit natural waters lets us better understand the world around us.Remote sensing... Show moreWater is all around us and is vital for all aspects of life. Studying the various compounds and life forms that inhabit natural waters lets us better understand the world around us.Remote sensing enables global measurements with rapid response and high consistency. Citizen science provides new knowledge and greatly increases the scientific and social impact of research.In this thesis, we investigate several aspects of citizen science and remote sensing of water, with a focus on uncertainty and accessibility. We improve existing techniques and develop new methods to use smartphone cameras for accessible remote sensing of water. Show less
Door de verwachte toename van het aantal patiënten met verschillende chronische ziekten zullen de kosten en de complexiteit van de zorgvraag toenemen. Hierdoor kan de toegankelijkheid en... Show moreDoor de verwachte toename van het aantal patiënten met verschillende chronische ziekten zullen de kosten en de complexiteit van de zorgvraag toenemen. Hierdoor kan de toegankelijkheid en betaalbaarheid van de gezondheidszorg in het geding komen. Om de toegankelijkheid en betaalbaarheid van de gezondheidszorg te kunnen blijven waarborgen zullen we onze medische middelen zo effectief mogelijk moeten gebruiken. Dit proefschrift laat zien dat er nog steeds veel winst valt te behalen in het leveren van de juiste cardiale zorg voor de juiste patiënt op de juiste plek. Verbeteringen zijn mogelijk in eerste-, tweede- en derdelijns zorg. Wij geloven dat verticale integrale zorg het antwoord is op het managen en verdelen van de verwachte patiënten toestroom over de verschillende lijnen, en daarnaast de stijgende zorgkosten onder controle te houden. Show less
In design optimization problems, engineers typically handcraft design representations based on personal expertise, which leaves a fingerprint of the user experience in the optimization data. Thus,... Show moreIn design optimization problems, engineers typically handcraft design representations based on personal expertise, which leaves a fingerprint of the user experience in the optimization data. Thus, learning this notion of experience as transferrable design features has potential to improve the performance of similar, yet more challenging, design optimization problems. However, engineering design data are unstructured, high-dimensional and often have no canonical representation, which poses several challenges for machine learning algorithms. In this thesis, geometric deep learning techniques, in particular 3D point cloud autoencoders, are utilized to learn novel shape-generative models from engineering optimization data. Through different sets of experiments, it is shown that these autoencoders are scalable to high-dimensional engineering models and have comparable optimization performance to state-of-the-art representations. Furthermore, a novel network feature visualization technique is proposed, which provides a geometric interpretation of the knowledge stored in the network and allows one to select sub-sets of degrees of freedom to modify and optimize shapes. Due to the domain agnosticism of the autoencoders’ latent space, the learned representations are exploited in multi-task optimization problems to enable knowledge transfer between tasks and foster commonality between the optimized shapes. Finally, to improve the state of readiness of the 3D models generated by the point cloud autoencoder for engineering simulations, a novel architecture is proposed: Point2FFD. The novel architecture learns to generate 3D polygonal meshes based on input 3D point clouds and a set of existing handcrafted mesh templates parameterized with free-form deformation. Based on shape-generative and optimization experiments, it is shown that Point2FFD generates 3D models with better overall quality than state-of-the-art point cloud (variational) autoencoders and improves the quality of designs in vehicle aerodynamic optimization problems. Show less
Greater acknowledgement of the value of assessing psychological factors and patient experiences after orthopaedic trauma may support policymaking regarding the provision of psychological therapies... Show moreGreater acknowledgement of the value of assessing psychological factors and patient experiences after orthopaedic trauma may support policymaking regarding the provision of psychological therapies as part of care. The first part focusses on factors associated with PROMs, such as pain intensity and depression, and with PREMs, such as satisfaction and communication effectiveness. The influence of psychological distress and family involvement is consistent and both minor and major trauma have a notable risk of developing symptoms of depression. In the second part of this thesis, the use of shorter and various questionnaires was evaluated for measuring patient experience to improve care. Given the mounting evidence of a common factor underlying PREMs as currently formulated, it might prove possible to measure patient experience using just a few questions, instead of measuring communication and satisfaction separately. In the last part, the use of pre-visit phone calls and software for emotion recognition was evaluated. Phone calls can replace in-person visits to establish the diagnosis and suggest treatment options. The ability to measure a patient’s mindset on the clinician’s face confirms that clinicians are registering the psychological aspects of illness, irrespective of whether they are consciously aware of them or not. Show less
Als gevolg van de grote technologische vooruitgang in de gezondheidszorg worden in toenemende mate gegevens verzameld tijdens de uitvoering van klinische onderzoeken. Het is evenwel essentieel om... Show moreAls gevolg van de grote technologische vooruitgang in de gezondheidszorg worden in toenemende mate gegevens verzameld tijdens de uitvoering van klinische onderzoeken. Het is evenwel essentieel om te beseffen dat gegevens op zich van weinig of geen waarde zijn. Ten behoeve van hun optimale bruikbaarheid dienen gegevens geanalyseerd, geïnterpreteerd en verwerkt te worden. Machine learning-strategieën kunnen hiertoe nuttige en adequate oplossingen bieden. Dit proefschrift bevat machine learning-benaderingen toegepast op verschillende klinische datasets. De klassieke gegevens bestaan uit elektrische signalen van het electrocardiogram (ecg) verkregen bijgezonde proefpersonen, de innovatieve gegevens zijn afkomstig vanmetingen in een rijsimulator, en de opkomende gegevens zijn afgeleid van dna-analyse van de micro-organismen die op de huid voorkomenvan patiënten met huidziekten. We toonden aan dat het aantal ECG’s van invloed was op de nauwkeurigheid van geschatte verlenging van het qt-interval voor alle ingezette qt-correctieformules. Met behulp van SHapley AdditiveexPlanations (shap)-waarden werd de impact van de individuele kenmerken op de voorspelling van fysiologische leeftijd van het hart bepaald. We maakten gebruik van machine learning voor een betere beoordeling van de rijprestaties van bestuurders die medicijnen gebruikten. Tot slot lieten we zien dat de belangrijkste micro-organismen voor discriminatie van seborrroische dermatitis – naast Cutibacterium en Staphylococcus – kwamen relatief weinig voor, waardoor men deze micro-organismen in standaardanalyses eenvoudig over het hoofd kan zien. Daarmee hebben we aangetoond dat machine learning kanworden toegepast op gegevens die zijn afgeleid van klinische onderzoeken om in een vroeg stadium het effect van medicijnen en andere interventies op te sporen en te evalueren. Show less
Inverse problems are problems where we want to estimate the values of certain parameters of a system given observations of the system. Such problems occur in several areas of science and... Show moreInverse problems are problems where we want to estimate the values of certain parameters of a system given observations of the system. Such problems occur in several areas of science and engineering. Inverse problems are often ill-posed, which means that the observations of the system do not uniquely define the parameters we seek to estimate, or that the solution is highly sensitive to small changes in the observation. In order to solve such problems, therefore, we need to make use of additional knowledge about the system at hand. One such prior information is given by the notion of sparsity. Sparsity refers to the knowledge that the solution to the inverse problem can be expressed as a combination of a few terms. The sparsity of a solution can be controlled explicitly or implicitly. An explicit way to induce sparsity is to minimize the number of non-zero terms in the solution. Implicit use of sparsity can be made, for e.g., by making adjustments to the algorithm used to arrive at the solution.In this thesis we studied various inverse problems that arise in different application areas, such as tomographic imaging and equation learning for biology, and showed how ideas of sparsity can be used in each case to design effective algorithms to solve such problems. Show less
Lyme borreliosis (LB) is caused by spirochetes that are part of the Borrelia burgdorferi sensu lato (s.l.) complex group. The most prevalent manifestation of LB is characterized by a red, migrating... Show moreLyme borreliosis (LB) is caused by spirochetes that are part of the Borrelia burgdorferi sensu lato (s.l.) complex group. The most prevalent manifestation of LB is characterized by a red, migrating skin lesion, also known as erythema migrans. If left untreated, then B. burgdorferi s.l. can disseminate through the body and infect other body parts such as the joints, the nervous system (Lyme neuroborreliosis (LNB)), the heart and/or other parts of the skin, although for the majority of cases LB resolves without treatment. The diagnosis of LB is based on the presence of clinical symptoms and, for most Lyme manifestations, should be supported by laboratory tests. The most widely used laboratory test is based on the detection of Borrelia-specific antibodies. The utility of antibody detection to support the diagnosis of LB, however, is hampered by a low sensitivity of antibody detection early in the infection, and the persistence of antibodies after a cleared infection. The research conducted in this thesis focused on the humoral and the cellular immune response to investigate whether LB diagnostics can be improved. As clear case-definitions are available for active LNB, well-defined patients with LNB were used as a proxy for patients with active LB.The research in this thesis has provided more insight into the added value and the pitfalls of laboratory tests for the diagnosis of LNB. It shows that the interferon-gamma enzyme-linked immunospot assay cannot be used for the diagnosis of LNB. Furthermore, it demonstrates the added value of elevated levels of the B-cell chemokine (C-X-C motif) ligand 13 in the cerebrospinal fluid for the diagnosis of LNB and that more research is necessary to investigate if an international reference standard can be established. Additionally, the research in this thesis underlines that a thorough validation of serological tests is important before its use in diagnostics and it illustrates that antibiotic treatment of an infection with B. burgdorferi s.l. is associated with discordant serological test results. The most important finding of the research conducted in this thesis; however, is the proposal of a diagnostic algorithm for LNB diagnostics. Such an algorithm should include tests that consider both the humoral as well as the cellular immune response as both may contribute to the diagnosis of LNB. By covering different aspects of the immune system, a concrete and feasible tool is provided that can better discriminate between an active and a previous infection with B. burgdorferi s.l., which and this will improve LNB diagnostics. Show less
The external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore... Show moreThe external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore encounter microbiota at the exposure interface. Many antimicrobial substances have been found to disturb beneficial interactions between microbiota and the host, thereby impairing host health. Nanomaterials exhibit nanoscale properties that could affect host health in two additional, understudied, microbiota-dependent ways. Firstly, owing to their large surface area, adsorption interactions between nanomaterials, microbial metabolites and microbes could alter the identity and colloidal stability of nanomaterials, and may influence the dispersal of microbes. Secondly, the immuno-modulatory effects of microbiota could affect the sensitivity of hosts to immunotoxic nanomaterials. In this dissertation, we use a combination of computational techniques and zebrafish larvae experiments to unravel and quantify these interactions. We predict the affinity of microbial metabolites to carbon and metal nanomaterials, and show that titanium dioxide nanoparticles can affect the dispersal of microbes through aquatic ecosystems, and across different life stages of oviparous animals. Additionally, we provide insight into microbiota-dependent signaling pathways that affect the sensitivity of zebrafish larvae to particle-specific, immunotoxic effects of silver nanoparticles. Altogether, these results contribute to mechanistic pathways for microbiota-inclusive nanomaterial safety assessment. Show less
In the young and healthy shoulder, cranially directed forces during abduction are counteracted by co-contraction of the rotator cuff muscles. In this way, it is prevented that the humerus moves... Show moreIn the young and healthy shoulder, cranially directed forces during abduction are counteracted by co-contraction of the rotator cuff muscles. In this way, it is prevented that the humerus moves cranially towards the acromion, thus entrapping subacromial tissues. During ageing however, shoulder tissues are subject to marked degeneration, which particularly concerns the rotator cuff muscles. This may have two consequences. First, due to reduced contribution of the upper parts of the rotator cuff to the abduction movement, the deltoid has to compensate, which results in a more cranially, instead of mediocranially directed force. Second, reduced stabilising force by the rotator cuff may jeopardise counteraction of cranial deltoid forces. These changes could lead to cranialisation of the humerus with painful compression of subacromial tissues, as observed in patients with Subacromial Pain Syndrome (SAPS). Previous studies have shown that by co-contraction of arm adductors, humeral-head depression may be accomplished, for the purpose of unloading subacromial tissues. In this thesis, we investigated the role of adductor co-contraction in the ageing asymptomatic population and in patients with SAPS. This has resulted in eight scientific publications with which the fundaments for evidence-based therapy in SAPS have been built, with as cornerstone training of adductor co-contraction. Show less
