The starting point for this study is that for a large part of their existence, the paintings belonging to this genre have primarily been seen as export articles without intrinsic artistic value.... Show moreThe starting point for this study is that for a large part of their existence, the paintings belonging to this genre have primarily been seen as export articles without intrinsic artistic value. This fact, and the fact that they cannot be unequivocally classified, explains why this genre has, for a long time, not received the attention it deserves. The label ‘exportware’, though, does not exclude that these paintings can also be approached as ‘art’. They have an historic, an artistic, and a material value, which, as a result of their representative and social functions, over time formed an artistic phenomenon in its own right, and a shared cultural visual repertoire with its own (Eurasian) character. In order to draw conclusions about the appreciation of the extensive and historically valuable eighteenth- and nineteenth-century Chinese export paintings in Dutch public collections, this multidisciplinary research follows the entire trajectory of this specific transcultural painting genre in sixteen museums, from the production two centuries ago to the current position. At work in this trajectory are mechanisms between people, institutions and the paintings, which increase or, indeed, diminish the appreciation of this time- and place-specific art. Show less
Cancer immunotherapy has taken up its place in oncological practice and it is likely there to stay. Although the field has come from far, much is still to learn as oncologists observe that not... Show moreCancer immunotherapy has taken up its place in oncological practice and it is likely there to stay. Although the field has come from far, much is still to learn as oncologists observe that not all patients with the same disease type respond to cancer immunotherapy, Furthermore, in some cancer types, no clinical benefit is observed at all, despite the presence of an abundant local immune infiltrate, indicating that our understanding of cancer – immune interaction is still incomplete. The overall goal of this thesis is to help address these matters in three ways. First, we have retrospectively analyzed a cohort of melanoma patients treated with ipilimumab, an anti-CTLA-4 antibody, for markers of responsiveness and review the literature to explore the limitations and curative potential of treatment strategies currently used in the clinic or under development. Second, we have developed several technology platforms that allow us to characterize and compare different types of T-cell responses that are directed against tumor-specific antigens in patient tumor material. Third, we aim to increase our understanding of the potential of cancer immunotherapy in ovarian and colorectal cancer, by analysis of the tumor-reactive compartment within these diseases. Show less
Epidural analgesia provided superior analgesia to remifentanil PCA. Women randomised to epidural analgesia with a request for pain relief are more satisfied with their analgesia than women... Show more Epidural analgesia provided superior analgesia to remifentanil PCA. Women randomised to epidural analgesia with a request for pain relief are more satisfied with their analgesia than women randomised to remifentanil PCA. Costs of epidural analgesia and remifentanil PCA are not significantly different. From an economic perspective, there is no preferential pain treatment in labouring women. Epidural analgesia is associated with a greater incidence of fever and significantly higher temperature overall. Patient controlled remifentanil has an effect on maternal SpO2 with significantly lower mean SpO2 during the labour period. This shows that respiratory complications are a serious problem associated with remifentanil and that continuous monitoring by trained personnel is obligatory. Persistent postpartum pain affects many women. Of surveyed women, 6.1% complained of significant pain related to delivery. Since this was a retrospective follow up study this results might be explained by the study design and these findings have to be evaluated by further research. Show less
The research considers structures and practices of regulatory inspections and enforcement, and particularly the relevance and effects of purported “smarter inspections” methods, e.g. risk... Show more The research considers structures and practices of regulatory inspections and enforcement, and particularly the relevance and effects of purported “smarter inspections” methods, e.g. risk-based ones, and how they compare with previously existing practices. Specifically, it considers efficiency and effectiveness of inspections in terms of achieving public welfare, and their economic impact. The first part considers the history of regulatory inspections and how specific inspection institutions started to appear from the 19th century onwards. Of particular interest is how path dependency resulted in important differences in structures and methods between different fields and countries, and how these in turn produced different effects for the public. The second part looks at existing research on the interconnected issues of regulatory compliance drivers, regulatory discretion and risk and regulation. It concludes to the importance of combining several compliance drivers to achieve better results, to the appropriateness of structuring discretion in inspections and enforcement, and to the adequacy of “risk” as an instrument to do so. The third part looks at several case studies (in particular occupational safety and health in Britain and Germany) to consider whether risk-based, ‘smart’ approaches effectively deliver better results with lower burden, and tentatively concludes to the affirmative. Show less
This thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an... Show moreThis thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an important role in COPD, and constitute a heterogeneous population with pro- (Mf1) and anti-inflammatory (Mf2) cells. This thesis evaluated YKL-40 and CD163 as markers for Mf1 and Mf2, respectively. Peripheral airways contained more CD163-positive Mf2 compared to central airways. Smoking cessation skewed the macrophage phenotype towards Mf2 in the peripheral airways, but did not influence YKL-40 levels in sputum. Whereas smoking can induce structural alterations in extracellular matrix (ECM) components in the airways, no differences in ECM components in bronchial biopsies were found between current and ex-smokers with COPD. ICS treatment attenuates lung function decline and decreases airway inflammation in a subgroup of COPD patients. However, long-term ICS treatment did not change YKL-40 levels in sputum and serum. ICS increased deposition of several ECM proteins in the airways, which was correlated with improved lung function, suggesting prevention of airway collapse. Withdrawal of ICS after long-term treatment induced a relapse in lung function decline and increased airway inflammation in bronchial biopsies and sputum, suggesting that benefits of ICS do not persist after discontinuation of ICS. Show less
This work covers two closely related topics: a theoretical study on the origins of friction and an experimental study on the growth of graphene. Both fundamental studies are focusing on the atomic... Show moreThis work covers two closely related topics: a theoretical study on the origins of friction and an experimental study on the growth of graphene. Both fundamental studies are focusing on the atomic processes involved. The study on friction treats the dissipation that takes places at one single friction contact. We show that the current explanations result in a discrepancy that we solve by evalutation of the mass involved: this mass is orders of magnitude smallar than assumed. The very small and dynamic mass at a friction contact forms an efficient channel of dissipation. This explanation allows us to understand and predict the friction behavior of surfaces at both the small and large scale. The study of graphene growth investigates the growth process of graphene at the atomic scale with a Scannning Tunneling Microscope in situ. We use our high- and, variable-temperature STM to determine the lowest nucleation temperature of graphene on Ir(111). Additionaly, individual steps that follow up each other during growth are clarified and presented. The graphene film closure is studied as well, which showed that graphene introduces internal strain in order to prevent local lattice defects. Our results are important for the improvement of the quality of graphene. Show less
In this thesis we present multiple techniques to suppress starlight in order to better directly image planets around other stars. We propose a laboratory setup to test a new focal-plane... Show more In this thesis we present multiple techniques to suppress starlight in order to better directly image planets around other stars. We propose a laboratory setup to test a new focal-plane wavefront sensing technique. We also show an optical device that suppresses starlight using liquid crystals (the vector Apodizing Phase Plate or vAPP). A broadband prototype (500-900 nm) is tested in the optical lab and its properties are determined. We suggest an simple but effective adaptation called the grating-vAPP which is insensitive to one of the common manufacturing errors (retardance offset). Two versions are tested on-sky. One narrow-band prototype at the Large Binocular Telescope that shows that the concept of the grating vAPP works. A second at Magellan/Clay that shows that we can produce a single optic with a broadband behaviour from 2 to 5 microns bandwidth that suppresses both sides of the star simultaneously. The on-sky 5 sigma contrast is 8.3 magnitudes at 2 lambda/D and 12.2 magnitudes at 3.5 lambda/D which makes this coronagraph extremely suited for imaging and characterizing planets close to nearby bright stars. Show less
We present a novel strategy to overcome this limitation and create programmable me chanical metamaterials, where the response of a single structure is determined and can be changed by the... Show more We present a novel strategy to overcome this limitation and create programmable me chanical metamaterials, where the response of a single structure is determined and can be changed by the amount of lateral confinement. Show less
In this thesis, we have addressed aspects of two main arms of the adaptive immune system; the B cell and antibody arm and the T cell arm. This led to a division in the presentation of the... Show more In this thesis, we have addressed aspects of two main arms of the adaptive immune system; the B cell and antibody arm and the T cell arm. This led to a division in the presentation of the results described in this thesis into two sections. In the first section, we present the results regarding the characterization of ACPA responses, B cells and ACPA secreting plasmablasts/-cells in RA as well as autoantibody responses and their regulation by an effective anti-rheumatic drug, abatacept, in the arthritis mouse model; Collagen Induced Arthritis (CIA). The second section is compiled of results obtained from studies examining the regulatory and other aspects of CD49b+CD4+ T cells on proinflammatory responses involved in the pathogenesis of arthritis. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial membrane of the joints, culminating in destruction of cartilage and deformity of the joints if remains untreated. Infiltration of inflammatory immune cells such as B cells and T cells into the inflamed joints is a characteristic feature of RA. These immune cells are in continuous interaction with each other and create a viscous circle that sustains persistent synovitis and damage to articular cartilage. Show less
Measuring biomechanics of the knee with an acceptable degree of accuracy is difficult. When the in vivo knee joint motion is analyzed in all its six degrees-of-freedom without compromising on... Show moreMeasuring biomechanics of the knee with an acceptable degree of accuracy is difficult. When the in vivo knee joint motion is analyzed in all its six degrees-of-freedom without compromising on physiological loading conditions, the task becomes even more challenging. This thesis offers a brief overview of the development, validation and application of a non-invasive imaging methodology to capture the in vivo biomechanics of anterior cruciate ligament (ACL) deficient and posterior cruciate ligament (PCL) deficient knees. By combining dual fluoroscopy to capture the in vivo joint motion and magnetic resonance imaging to reconstruct the joint anatomy, we obtained a comprehensive insight in both tibiofemoral as well as patellofemoral kinematics and cartilage biomechanics of healthy knees under various loading conditions. These baseline measurements helped us comprehend the alterations in biomechanics seen in knees after injury of either ACL or PCL, which in turn generated clinically useful data for the improvement of our surgical reconstruction techniques. Show less
The research in this thesis was aimed at investigating the central hypothesis that susceptibility to SD determines both the susceptibility to migraine with aura and the susceptibility to... Show moreThe research in this thesis was aimed at investigating the central hypothesis that susceptibility to SD determines both the susceptibility to migraine with aura and the susceptibility to hypoxic/ischemic injury in the same direction. We envisage that factors that enhance the susceptibility to SD increase the likelihood of migraine with aura as well as ischemic stroke. To this end we assess to what extent genetic, hormonal and pharmacological modulators of SD susceptibility will influence the susceptible to ischemic injury. Thus we will unravel underlying mechanisms of SD susceptibility and susceptibility to ischemic injury. Central to this research is the use of two transgenic mouse models of migraine that carry migraine-relevant FHM1 gene mutations in voltage-gated CaV2.1 Ca2+ channels. Show less
A lack of career opportunities and long spells of temporary employment are seen as major problems in science, and are thought to decrease the attractiveness of the scientific profession. In... Show more A lack of career opportunities and long spells of temporary employment are seen as major problems in science, and are thought to decrease the attractiveness of the scientific profession. In the long run, this could hurt countries’ ability to conduct high-quality research and innovation. This dissertation examines the origin and effects of the preponderance of junior and temporary jobs in science. The research described in the dissertation shows how career prospects and employment conditions have changed in Germany since the emergence of the research university, and how publications careers of PhD graduates have changed in the United States since the 1950s. Furthermore, the dissertation describes how career prospects and employment conditions affect the job choice of recent PhD graduates. Women are more negative about career prospects and employment conditions in science and are therefore more affected by these issues when choosing a job. In addition, the dissertation describes how student status of PhD candidates limits the availability of material research infrastructure. Finally, the research in the dissertation shows that temporary employment decreases job satisfaction and affects the personal life of PhD graduates. Show less
Globally more than 200,000 people develop leprosy every year and 2-3 million people live with leprosy associated disabilities. Despite the availability of multi drug therapy, leprosy has continued... Show moreGlobally more than 200,000 people develop leprosy every year and 2-3 million people live with leprosy associated disabilities. Despite the availability of multi drug therapy, leprosy has continued affecting many individuals, including children because of the uninterrupted transmission in the population. Untreated multi bacillary cases as well as non-symptomatic M. leprae infected individuals in the population are believed to be the major sources of M. leprae infection and transmission. Leprosy reactions are also the major causes of disabilities. However, no tools are available to predict their occurrence. This thesis focuses on in vitro assessment of recombinant M. leprae proteins and synthetic peptides for their immunogenicity and specificity in populations with different genetic backgrounds by measuring cell mediated immunity and this has shown the presence of potential antigens. Further in depth analysis of the host immune responses against these unique antigens in leprosy patients, their household contacts and healthy endemic controls has led to identification of potential biomarkers with an immense importance in development of diagnostic tools for detection of M. leprae infection and early diagnosis of leprosy reactions. Currently, field friendly tests for early detection are developed at the LUMC using identified M. leprae antigens and host biomarkers with diagnostic potential. Show less
Ruthenium complexes are promising prodrugs in photoactivated chemotherapy (PACT): to prevent systemic therapeutic side-effects, a non-toxic version of the drug is introduced in the body and is... Show moreRuthenium complexes are promising prodrugs in photoactivated chemotherapy (PACT): to prevent systemic therapeutic side-effects, a non-toxic version of the drug is introduced in the body and is only activated at the place of the tumor by means of visible light irradiation. However, most of these PACT compounds are only sensitive for UV or blue light, while this light does not permeate the body very well, in contrast to red or near-infrared light. To circumvent this problem, the principle of light-upconversion can be used to "upgrade" red light to blue light in a drug carrier such as a nanovesicle: the tumor is irradiated with red light, after which blue light is generated locally and used to activate the prodrug. Among the various methods of light-upconversion, triplet-triplet annihilation upconversion (TTA-UC) was selected as the most promising. In this thesis it is described that green-to-blue and red-to-blue upconverting nanovesicles were prepared. The red-to-blue upconverted light was successfully used to activate a ruthenium polypyridyl complex that was anchored to the same vesicle. Finally, the inherent oxygen-sensitivity of TTA-UC was greatly mitigated by the addition of water-soluble and biocompatible anti-oxidants. We expect that the results of this thesis will lead to exciting applications in PACT. Show less
The air transport sector including airlines, airports and providers of air navigation services have largely been State controlled. Formerly, most airlines were State owned. However, the... Show more The air transport sector including airlines, airports and providers of air navigation services have largely been State controlled. Formerly, most airlines were State owned. However, the ownership pattern of airlines has changed gradually to the majority of the airlines being privately owned as a part of globalization and liberalization of economies. These observations can be made in the case of airports too. State owned airports are being privatized in many States due to various reasons. The trend started with the privatization of British Airports Authority (BAA) owned airports in United Kingdom (UK). Europe, Asia and Latin America are now witnessing privatization of airports on a fast track basis. Australia and New Zealand have also privatized their State owned airports in the last decade. Though the models vary depending upon the economic policy of the State, the concept of privatization or private participation in airport infrastructure is gaining momentum in these States. However, the United States of America (USA) remains an exception to this trend of airport privatization. In 2006, India joined the global trend of privatization in airport infrastructure, by privatizing two State owned airports in New Delhi and Mumbai. Though the first privately owned international airport started operations in 1999 in Kochi (Cochin),1 two other privately owned airports were operationalized in Bangalore and Hyderabad only in 2008. Show less
Fluoropyrimidines are being used in the treatment of different types of cancer. The most common fluoropyrimidine is 5-flourouracil (5-FU), which is administered intravenously as a bolus or as... Show moreFluoropyrimidines are being used in the treatment of different types of cancer. The most common fluoropyrimidine is 5-flourouracil (5-FU), which is administered intravenously as a bolus or as prolonged infusion. Many tissues throughout the body express thymidine phosphorylase. Dihydropyrimidine Dehydrogenase (DPD) is involved in the degradation of endogenous pyrimidine nucleosides, but also in the degradation of fluoropyrimidines. More than 80% of the amount of 5-FU administered is catabolized primarily in the liver where DPD is abundantly expressed. DPD is encoded by the DPYD gene for which 567 coding variants are known to date, some of them being pathogenic by reducing enzyme capacity. Interindividual variability in the activity of DPD influences 5-FU pharmacokinetics and a reduced DPD activity can lead to severe toxicity and even death following administration of 5-FU or capecitabine. Knowledge regarding the clinical impact of reduced DPD activity on the pharmacokinetics and pharmacodynamics of fluoropyrimidines may be useful to dose individualize therapy. In this thesis, an in depth overview is given of methods and their potential to optimize fluoropyrimidine dosing based on individual DPD enzyme activity. Furthermore an oral uracil loading dose as probe for DPD deficiency in cancer patients treated with fluoropyrimdines for this purpose is studied. Show less
Despite optimal medical treatment and advanced revascularization strategies, a growing number of patients suffer from severe coronary artery disease not amenable to conventional treatment... Show more Despite optimal medical treatment and advanced revascularization strategies, a growing number of patients suffer from severe coronary artery disease not amenable to conventional treatment options. Bone marrow cell injection has emerged as a new potential therapeutic option for these patients. As preclinical studies provided evidence for improvement in myocardial perfusion and function after transplantation of cells, cell therapy was introduced in the clinical setting. As initial studies demonstrated promising results, intramyocardial injection of autologous bone marrow-derived mononuclear cells emerged as a new therapeutic option for patients with severe coronary artery disease. Although studies demonstrated safety and feasibility of the approach, the overall effect of bone marrow cell treatment has shown moderately positive but variable effects. However, many questions remain whether there are certain factors, such as patient specific characteristics, that influence treatment outcome. Therefore, in the current thesis, the efficacy of bone marrow cell injection was investigated in a large refractory angina patient population with chronic myocardial ischemia to further evaluate treatment effect during short and long term follow-up. In addition, the safety and effect of autologous mesenchymal stem cells injection, a specific bone marrow-derived cell type, in patients shorty after acute myocardial infarction was evaluated. Show less
This thesis offers a description of the Bouakako Sign Language (LaSiBo, Langues des Signes de Bouakako in French), that has emerged within a community comprising a majority of hearing members.... Show moreThis thesis offers a description of the Bouakako Sign Language (LaSiBo, Langues des Signes de Bouakako in French), that has emerged within a community comprising a majority of hearing members. LaSiBo is a young language that has developed within a group of hearing-impaired community members to fulfill their communication needs, but is also used by other members of the village. The aspects studied here are firstly the formal properties of LaSiBo and inter-personal variation in sign usage; as well as semantic domains such as kinship, colors and time. The size of the community, the age of the language, the influence of the spoken language and the absence of use in education are among the factors that influence the formation of LaSiBo. The comparisons carried out in this work highlight similarities and differences not only between sign languages (used in small communities in particular) – which, however different they may be, share the same modality (visio-gestural) –, but also between languages that are in contact with each other (the Dida language and LaSiBo) but use different modality (respectively audio-oral and visio-gestural). Show less
The links between conservation and livelihood concerns remain much debated, and there is no agreement about the degree to which these concerns are linked, and how they should be tackled... Show more The links between conservation and livelihood concerns remain much debated, and there is no agreement about the degree to which these concerns are linked, and how they should be tackled together. The main objectives of this study are to uncover the local values of birds, the environment and conservation for rural people in Burkina Faso’s Sahel region, and to increase insights into interventions that aim to achieve integrated (migrant bird) conservation and sustainable development objectives in this area. By focusing on issues like local perceptions, local participation, local institutional arrangements and the role of birds, this study adds new insights to the existing literature and knowledge. The study demonstrates that both birds and the environment are valued in many ways and are strongly linked with local livelihoods. At the same time, the study shows that serious environmental problems exist, and that both local livelihoods and birds are negatively impacted. This has created conservation incentives among the local population, which is a major contributing factor for conservation organizations seeking local motivation and participation to combat environmental issues. In fact, the study provides a strong argument for the need to increase local participation, and demonstrates several ways to do so. Show less
Calypso, Identity and Social Influence, The Trinidadian Experience seeks to establish links between calypso music and the construction and maintenance of identities, and to locate the genre... Show more Calypso, Identity and Social Influence, The Trinidadian Experience seeks to establish links between calypso music and the construction and maintenance of identities, and to locate the genre as a mechanism or as part of a mechanism that has exerted on-going social influence within Trinidadian society. It chronicles the evolution of calypso music from its emergence in Trinidad, and highlights contingent institutions, peculiar traditions, and salient events that have shaped the socio-political and cultural landscape there during the Colonial and Post-Colonial periods. The study is descriptive and explorative, and follows an interdisciplinary route that integrates historical fact, socio-anthropological philosophy, psychological, musicological, and ethnomusicological thought, and notes from my own ethnographic research. It analyses a large corpus of written material, and audio/visual recordings of music performance and participation in calypso and carnival-related events by practitioners and audiences alike. Show less
