A remarkable population of short period transiting rocky exoplanets with equilibrium temperatures on the order of 2,000 K has recently been discovered. Their high temperatures make them very... Show moreA remarkable population of short period transiting rocky exoplanets with equilibrium temperatures on the order of 2,000 K has recently been discovered. Their high temperatures make them very different to the planets in our solar system. In particular, hot super-Earths are thought to have mineral atmospheres that are produced by the vaporisation of their surfaces, or large exospheres that are produced by sputtering of their exposed surfaces by intense stellar winds. Additionally, some smaller, low surface gravity hot rocky exoplanets have been found to be actively disintegrating and forming 'comet-like' dust tails that produce asymmetric transit light curves with forward scattering features. Since the gas and dust originates from the planetary surface, these planets offer the tantalising prospect of enabling us to probe the surface composition of rocky planets. The purpose of this thesis is to work towards this goal by searching for gas around hot rocky exoplanets with observational spectroscopy (Chapters 2 and 5), and by modelling the transit light curves produced by their 'comet-like' dust tails (Chapters 3 and 4). Show less
This book provides a synchronic description of the phonology, word classes, morphology, and syntax of the Cheke Holo language. Cheke Holo is an Austronesian language of the Oceanic subgroup, spoken... Show moreThis book provides a synchronic description of the phonology, word classes, morphology, and syntax of the Cheke Holo language. Cheke Holo is an Austronesian language of the Oceanic subgroup, spoken by 11,000 speakers on Santa Isabel island in the Solomon Islands. This is the first published grammar of Cheke Holo. It is based on the author’s 30 years of linguistic work carried out among Cheke Holo speakers. Like many other Oceanic languages, Cheke Holo has SVO word order, serial verbs, distinguishes alienable and inalianable possession of nouns, and reduplicates verbs to intensify or prolong the action they denote. Four types of demonstratives are attested in Cheke Holo. Basic distinctions of the demonstratives occur between specificity and number, and whether or not the noun modified is proximal or distal. The two-way distinction of past and non-past is the most useful descriptor for the Cheke Holo tense system. Several features of Cheke Holo phonology and grammar are less typical for an Oceanic language. These include its consonant clusters, the voiceless continuants, the verb nominalizations in four different phonemic environments, and the gender distinction in the third person singular pronouns. The encoding of pragmatic emphasis is a common feature of Cheke Holo grammar. Show less
In 1797 and 1798 the first steps were taken in the Netherlands towards the development of a democratic system. In 1796-1797 a written Constitution was drafted for the Batavian Republic, as the... Show moreIn 1797 and 1798 the first steps were taken in the Netherlands towards the development of a democratic system. In 1796-1797 a written Constitution was drafted for the Batavian Republic, as the Netherlands was called at the time. This Constitution was in 1797 submitted in a national referendum for a vote of the people, but it was rejected. A new draft was written and again submitted the following year. This time the Constitution was adopted. Very little is known about these referenda. Extensive archival research has been necessary in order to understand how these steps in democracy were taken. It has been possible to produce a dataset of results for 948 cities, villages and rural districts. Based on the voting results, the public support for a democratic constitution has been analyzed after a description of the voting system. The voting results are examined along two cleavages structures. First, major distinctions existed between cities and rural districts and secondly between Catholics and Protestants. As a partial explanation the religious preferences are important to understand the turnout by the two referenda. Above all, the results of the two referenda show a deeply divided society of religious minorities. Show less
Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates. One of the reasons is the lack of blood-based biomarkers that represent the interaction between... Show moreDiscovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates. One of the reasons is the lack of blood-based biomarkers that represent the interaction between the drug and the neurological systems of interest. Here we present a systems-pharmacology approach that combines a multi-biomarker approach (e.g. metabolomics) with pharmacokinetic/pharmacodynamic (PK/PD) modeling to reveal quantitative pharmacological characteristics that are relevant to dopaminergic drug action. Moreover, we set out to identify biomarkers that can be obtained from the blood as non-invasive sampling site. In the first section of this thesis the methodology is introduced in the context of translational CNS drug development. Moreover, a systematic search is performed to available biomarkers of dopaminergic drug action. Then, in the second part, the multi-biomarker PK/PD approach is applied to biomarkers from the neuroendocrine system as connection between brain and blood. In the third section, the methodology is developed using the simultaneous, time-resolved metabolomics response in brain extracellular fluid and plasma. By applying multi-biomarker PK/PD modeling we revealed quantitative pharmacological characteristics of dopaminergic drugs with regard to multiple biological processes. Moreover, we identified potential blood-based biomarkers of dopaminergic effect in the brain. Show less
One of the aims of social insurance programs is to provide a financial safety net to households when encountering adverse circumstances. However, apart from offering mere protection, a system... Show moreOne of the aims of social insurance programs is to provide a financial safety net to households when encountering adverse circumstances. However, apart from offering mere protection, a system of social insurance can also be designed with the aim to increase overall welfare. In order to make the appropriate design decisions one needs to understand how individuals react to both negative shocks, such as health and wealth shocks, and the system put in place to protect them from these shocks. To gain understanding on such behavioral effects, access to high quality microdata is crucial. This thesis contains four essays aiming to generate empirical insights to facilitate the design of social insurance program. It focusses on changes in consumption preferences in reaction to health and wealth shocks, the effectivity of complementary efforts to sickness benefits programs, and methods to construct the surveys needed to gain these empirical insights. Show less
In Luganda, the widest spoken minority language in Uganda, the word for photographs is 'ebifananyi'. However, 'ebifananyi' does not, contrary to the etymology of the word photographs, relate to... Show moreIn Luganda, the widest spoken minority language in Uganda, the word for photographs is 'ebifananyi'. However, 'ebifananyi' does not, contrary to the etymology of the word photographs, relate to light writings. 'Ebifananyi' instead means things that look like something else. 'Ebifananyi' are likenesses. My research project explores the historical context of this particular conceptualisation of photographs and its consequences for present day visual culture in Uganda. It also discusses my artistic practice as research method, which led to the digitisation of numerous historical collections of photographs. This resulted in eight books and in exhibitions that took place in Uganda and in Europe. The research was conducted in collaboration with both human and non-human actors. These actors included photographs, their owners, Ugandan picture makers and visitors to the exhibitions that were organised in Uganda and Western Europe. This methodology led to insights into differences in the production and uses of, and into meanings given to, photographs in both Ugandan and Dutch contexts. Understanding differences between ebifananyi and photographs shapes the communication about photographs between Luganda and English speakers. Reflection on the conceptualisations languages offer for objects and for sensible aspects of the surrounding world helps prevent misunderstandings in communication in general. Show less
This dissertation shows how diversity management and leadership relate to inclusiveness in public organizations and individual employee and team outcomes. Inclusiveness is about team members... Show moreThis dissertation shows how diversity management and leadership relate to inclusiveness in public organizations and individual employee and team outcomes. Inclusiveness is about team members feeling they belong to the group, while they can have their own unique identities. Inclusive leadership stimulates this by encouraging diverse team members to value, exchange, discuss and learn from their different backgrounds, perspectives and ideas. Inclusiveness in turn contributes to employees’ organizational commitment and involvement. This is particularly required in a changing society demanding of public organizations to be adaptive and responsive. Show less
This thesis aims to enhance our understanding of galaxies by testing theoretical models of galaxy formation against observations, particularly in the cases of extreme systems which have been found... Show moreThis thesis aims to enhance our understanding of galaxies by testing theoretical models of galaxy formation against observations, particularly in the cases of extreme systems which have been found to have an excess of baryonic mass in their central regions, in the form of either supermassive black holes or stellar populations, thus harbouring "monsters" in the deep. To this end we use the EAGLE project, a suite of cosmological, hydrodynamical simulations of galaxy formation and evolution that have been calibrated to reproduce the number density and sizes of galaxies in the Universe. We find that galaxies with supermassive black holes that are much more massive than expected given their stellar mass are predicted to exist and they become overmassive through early formation and/or tidal stripping from more massive galaxies. Recent evidence for excess stellar mass in the centres of high-mass, early-type galaxies has fueled claims that the stellar initial mass function (IMF) may be variable. We test the consequences of such variations in the EAGLE model by performing two additional simulations in which the IMF becomes respectively top-heavy or bottom-heavy in high-pressure environments. The strong effects of such variations are explored in terms of scaling relations between, and within, galaxies. Show less
Both prosociality in group context and morality are important aspects of social life and living together with others in society. In both situations, understanding the cognitive processes underlying... Show moreBoth prosociality in group context and morality are important aspects of social life and living together with others in society. In both situations, understanding the cognitive processes underlying the decisions is argued to be a crucial step in designing evidence-based interventions addressing not only choice outcomes, but the driving forces of the choices as well. Using fine-grained and unobtrusive measure of cognitive processes in the decision process, eye tracking is applied in the investigation of cognitive processes in this dissertation. Chapter 2 investigated active ignorance to others’ group membership. Chapter 3 presented two eye tracking studies, in which the cognitive processes of prosociality in intergroup contexts were investigated. Chapter 4 reported a study investigating the cognitive processes underlying moral decisions, speaking to the theoretical debate in moral decision making, advocating a choice discriminability perspective over the dual process theory of moral judgment. The work demonstrates the merit of further illuminating the inner workings of the “black box” of decision making, by using process-tracking techniques to gain insights about decision processes that would have been difficult to achieve when only using choices. Moreover, the work presented here makes a methodological contribution by developing a standardizable and incentivized moral dilemma task Show less
The prevalence of musculoskeletal complaints in professional musicians is higher compared to the general population (Odds ratio 2.3): point prevalences in the literature range between 9% and 68%;... Show moreThe prevalence of musculoskeletal complaints in professional musicians is higher compared to the general population (Odds ratio 2.3): point prevalences in the literature range between 9% and 68%; year prevalences range between 41% and 93%. Female gender is the most important risk factor. Also among amateur musicians musculoskeletal complaints are frequent, the year prevalence of playing-related is 68%. Female gender, a sudden increase in playing time and playing a string instrument were the main risk factors. Among professional musicians with musculoskeletal complaints, the impact of these complaints on daily functioning is appreciated as more severe, compared non-musicians with musculoskeletal complaints. Also, healthcare usage is higher among musicians with these complaints. Musicians with complaints report worse illness perceptions compared to non-musicians with musculoskeletal complaints. In the last part of this thesis biomechanical aspects of violin playing are evaluated: Violinists with complaints show more activity of the superficial neck and shoulder muscles while playing the instrument, which is hypothesized to be the result of co-contraction. From a biomechanical point of view, playing without a shoulder rest, or with a shoulder rest with minimal height seems favourable, the latter being subjectively most comfortable by the violinists. Show less
Including modelling as part of software development appears to have various benefits. Why then is it that not all companies use software modelling? One of the main reasons is that it requires up... Show moreIncluding modelling as part of software development appears to have various benefits. Why then is it that not all companies use software modelling? One of the main reasons is that it requires up-front investments. From an economic point of view, any type of investment must be justified in terms of how much payback there will be at a later stage. This being the case, in the context of software projects, investment in modelling should be justified by benefits, such as improved productivity and improved product quality, which can be seen later during software development or maintenance. When such benefits are not tangible or foreseeable, modelling becomes a practice without clear added value for the system being developed. The problem, therefore, is how we can investigate and prove whether or not modelling, or some specific characteristics of modelling, provide any benefits during software development and maintenance. As long as this question remains unanswered, it will be difficult to motivate and justify modelling activities in real software projects. This thesis therefore contributes to partially answering these open questions by focusing the empirical research on the benefits of using UML modelling during software maintenance. Show less
Obesity, type 2 diabetes and cardiovascular diseases are major public health problems. South Asians are specifically at risk for the development of (cardio)metabolic diseases, due to a... Show moreObesity, type 2 diabetes and cardiovascular diseases are major public health problems. South Asians are specifically at risk for the development of (cardio)metabolic diseases, due to a combination of known and unknown risk factors. Since effective long-term treatment strategies are currently lacking, the search for additional risk factors and development of targeted treatment strategies to combat these (cardio)metabolic diseases is warranted. An attractive approach seems to be activation of energy-combusting brown adipose tissue (BAT), which can result in increased energy expenditure and improvement in glucose and lipid metabolism. In this thesis, we aimed to address two key objectives: 1) unravelling the underlying mechanisms that could explain the increased predisposition for metabolic disease in the South Asian population, and 2) identifying novel pharmacological strategies that activate BAT and increase energy expenditure in risk populations, including South Asians and individuals with overweight and prediabetes. The studies described in this thesis have highlighted some novel factors, such as endocannabinoids and angiopoitein-like-protein-4, that might in part explain to unbeneficial metabolic phenotype of South Asians. In addition, novel potential therapeutic strategies were identified to combat metabolic disease, such as treatment with a β3-adrenergic receptor agonist and a dipeptidyl-peptidase-4 inhibitor. Show less
This thesis discusses the discovery potential of Intensity Frontier experiments. As a particular examples of such experiment the SHiP and MATHUSLA experiments where taken. The reach of these... Show moreThis thesis discusses the discovery potential of Intensity Frontier experiments. As a particular examples of such experiment the SHiP and MATHUSLA experiments where taken. The reach of these experiments was studied for the number of specific model of the Beyond Standard Model physics, namely neutrino Minimal Standard Model, Higgs-like scalar, axion-like particles and light dark matter. Show less
This thesis assessed methods to identify possible hazards to patient safety of new surgical instruments in minimally invasive surgery, before their introduction in daily clinical practice. Using a... Show moreThis thesis assessed methods to identify possible hazards to patient safety of new surgical instruments in minimally invasive surgery, before their introduction in daily clinical practice. Using a newly developed uterine manipulator and uterine power morcellators as a template, the concepts of a clinically driven approach and a prospective risk inventory were explored. Show less
'Prior tempore iure' (eerder in tijd, sterker in recht). Deze Romeinsrechtelijke vuistregel wordt van oudsher gehanteerd voor de oplossing van conflicten tussen verschillende pandrechten die op... Show more'Prior tempore iure' (eerder in tijd, sterker in recht). Deze Romeinsrechtelijke vuistregel wordt van oudsher gehanteerd voor de oplossing van conflicten tussen verschillende pandrechten die op dezelfde zaak zijn gevestigd. De volgorde van de totstandkoming van de zekerheidsrechten bepaalt aldus welke pandhouder zich als eerste op de executieopbrengst mag verhalen. Naar hedendaags burgerlijk recht strekt het toepassingsbereik van de zogenoemde prioriteitsregel zich uit tot het goederenrecht in het algemeen. In dit boek worden eerst de herkomst en de ontwikkeling van de prioriteitsregel geschetst. Daarna wordt zijn toepassing in het perspectief van het Duits en Franse recht geplaatst om vervolgens aandacht te besteden aan zijn toepassing in het Nederlandse vermogensrecht. Show less
Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood. Other risk factors... Show moreCardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood. Other risk factors contributing to cardiovascular disease can develop in individuals which are overweight. The clinical consequences of being overweight are clustered in the medical term: metabolic syndrome. Included in the metabolic syndrome are high blood pressure, dyslipidemia and glucose intolerance. At present, most cardiovascular disease patients are treated with statins which lower blood cholesterol levels. However, this treatment is not as effective in all patients and can cause some adverse drug reactions. Therefore, it is essential that novel therapeutic targets for the treatment of cardiovascular disease are identified. In this thesis, potential novel therapeutic targets in cardiovascular disease and metabolic syndrome are validated. In total, three potential targets were investigated: proteoglycan 4, protein arginine methyltransferase 3 and stabilin 1. Our studies showed the involvement of two of these targets in the development of cardiovascular disease and metabolic syndrome. Moreover, our results stress (1) that cardiovascular disease and metabolic syndrome are complex, multifactorial diseases with overlapping mechanisms and (2) that integration of research into both diseases can benefit therapeutic target identification and validation. Show less
In this thesis I review the history of oxygen application for cluster headache; I describe a retrospective and subsequently a prospective cross-sectional correlation study on predictors of the... Show moreIn this thesis I review the history of oxygen application for cluster headache; I describe a retrospective and subsequently a prospective cross-sectional correlation study on predictors of the effect of oxygen in cluster headache; I define and describe the rebound phenomenon; and I describe the results and potential prophylactic effect of the nociception specific blink reflex in cluster headache. Show less
We used the corneal immunosuppressive environment to test the possibility of inserting a Fish Scale-Derived Collagen Matrix in a corneal pocket, and the excellent results and lack of primary... Show moreWe used the corneal immunosuppressive environment to test the possibility of inserting a Fish Scale-Derived Collagen Matrix in a corneal pocket, and the excellent results and lack of primary and secondary immune responses led to a clinical trial, which is currently underway. The immunosuppressive environment of the eye allows the growth of malignant melanocytes which leads to the formation of uveal melanoma. The association between increased numbers of macrophages and lymphocytes in uveal melanoma and an increased development of uveal melanoma metastases suggest an influence of pro-angiogenic macrophages, The relation between loss of BAP1 expression and a very bad prognosis and the influx of leukocytes into the primary tumor, suggests that BAP1 functions as a regulator of inflammation. Further research will focus on the role of BAP1 in the regulation of inflammation in the uveal melanoma microenvironment. Show less
In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy. These... Show moreIn this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy. These mice carry conditional alleles of Cdh1, which result in the inactivation of the cell-adhesion molecule E-cadherin when Cre-recombinase is expressed. As mice with mammary-specific inactivation of E-cadherin alone were not prone to develop mammary tumors, they were used to investigate the contribution of additional genetic mutations to the development of ILCs using different genetic approaches. Firstly, we used non-germline modeling to study the role of PI3K-AKT signaling in the development of ILCs by performing intraductal injections of high-titer lentiviruses. Secondly, we employed a Sleeping Beauty (SB)-based insertional mutagenesis screen in conditional Cdh1 knockout mice to identify novel genes and pathways involved in the development of ILCs. We show that active transposon mutagenesis drives ILC formation and analysis of common insertion sites in SB-induced tumors identified a mutually exclusive group of four genes, of which three are frequently aberrated in human ILCs. Lastly, we used active mobilization of transposons in transplanted mouse ILCs to identify genes involved in acquiring resistance to the FGFR inhibitor AZD4547. Show less
The scope of this thesis spanned several issues in the measurement and evaluation of OD. The screening, assessment, and treatment effect for OD have been covered,with a special emphasis on... Show moreThe scope of this thesis spanned several issues in the measurement and evaluation of OD. The screening, assessment, and treatment effect for OD have been covered,with a special emphasis on patient self-evaluation. Show less
