International Migration, Integration and Social Cohesion online publications
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The Cubist anatomy of the violin in the work of Georges Braque
Get PDFThis dissertation addresses the persistent use of the violin motif in Cubist art, with a focus on Georges Braque – one of the founders of Cubism. I analyse the violin in Braque’s Cubist oeuvre with respect to five musically relevant concepts: form, movement, tension, texture, and dynamic. Each of these musical concepts plays an important role in the communication with and in the interpretation of a music composition. Here, they are addressed as they apply to the Cubist violin from the visual perspective, amending the music definitions where necessary. This dissertation aims to present a close examination of the depictions of the violin in Braque’s Cubist oeuvre, currently missing from the scope of academic literature on Cubism. My research is done in the context of the social history of the instrument and of the emerging music forms and practices at the turn of the twentieth century. It relies on the concept of interart aesthetic – a notion that arises from the increasing amalgamation of various art forms at the turn of the century. Braque’s extensive experience with music and with classical instruments offer a unique perspective on representing a symphonic instrument in an avant-garde art form, while the historical context and the experimental music environment of the early twentieth century provide an ideal backdrop for a study of an instrument as versatile as the violin. This dissertation demonstrates Braque’s uniqueness among the Cubist artists, not only for his musical education, but for how he achieves coherence of art forms in his work to achieve a distinctive integration of painting and music in particular
Antiviral CRISPR-Cas strategies:Intended and unintended effects
Get PDFCombination antiretroviral therapy (cART) can effectively inhibit replication of the human immunodeficiency virus (HIV) and prevent progression to AIDS. However none of the currently available drugs inactivate the HIV DNA that is integrated on one of the chromosomes of all infected cells. As a consequence, current cART does not lead to a cure of the virus infection and HIV-infected individuals need lifelong suppressive therapy to prevent AIDS. Novel strategies are being developed that aim at the inactivation of the integrated HIV DNA in infected cells, including the use of DNA cleaving CRISPR-Cas systems. In this thesis, I describe how we investigated the possibilities and risks of such antiviral therapy by analyzing the intended and unintended CRISPR-Cas effects. We demonstrate that CRISPR-Cas treatment of HIV-infected cells can permanently inactivate the viral DNA by causing small insertions and deletions (indels) at the target sites, or by causing excision or inversion of the DNA fragment between two target sites. However, we demonstrate that such treatment also causes much larger deletions, which can include flanking cellular DNA sequences. Using a novel quantitative assay we demonstrate that CRISPR-Cas treatment of cells causes large deletions at a surprisingly high frequency, with on average one large deletion for every two indels. As large chromosomal deletions may trigger oncogenic transformation and turn the cell into a cancer cell, this high frequency poses a serious safety risk for clinical application of the CRISPR-Cas systems. Therefore, it is crucial to closely monitor for such unintended effects when applying CRISPR-Cas systems in humans, not only in antiviral approaches but also in other gene therapy applications
Controlling second coordination sphere effects in heterogeneous catalysis:A molecular approach
Get PDFA critical step towards a carbon-neutral society is minimizing the ecological footprint of the energy and chemical sectors. The speed of this transition is dependent on the development of better catalysts to lower the energy input and increase selectivity of catalytic processes, for example. Taking from all catalysis disciplines, heterogeneous, homogeneous, and biocatalysis, this dissertation focuses on implementing and understanding of second coordination sphere effects around supported single-atom catalysts.Overall, this dissertation shows the importance of controlling second coordination sphere effects in single-atom catalysis, and several strategies to achieve this are described. By synthesizing well-defined catalysts and performing detailed catalytic studies, a thorough understanding of the structure-performance relationships was provided. We hope that this motivates others to pursue in this direction focussing on the critical steps towards a carbon-neutral society
Understanding response to rituximab treatment in rheumatoid arthritis through immune fingerprinting of T and B cells
Get PDFDespite the great research advances in dissecting the mechanisms underlying rheumatoid arthritis onset and development, the exact pathophysiology of this disease remains unsolved. In the past years, the introduction of biologicals, and in particular of therapeutic monoclonal antibodies (mAb), has constituted a major breakthrough in the clinical management of the disease. Although these new drugs have proven effective, in some patients, remission or low disease activity is only partially or temporally achieved. Understanding the mechanism behind this incomplete response might lead to improved therapies and in ultimately to improved quality of life for patients. This thesis describes our efforts to elucidate the mechanisms behind response to B-cell depletion therapy using rituximab in rheumatoid arthritis. We evaluated how both direct and indirect effects can influence clinical response to the treatment. To achieve this we applied AIRR sequencing or Adaptive Immune Receptor Repertoire sequencing, which allows to identify and quantify all T- and B-cell receptors within an individual. This methodology allowed us to fingerprint and monitor ongoing immune responses in cohorts of rheumatoid arthritis patients undergoing rituximab treatment
Sovereign debt and holdout disruption:A good faith and relational contract approach
Get PDFThis thesis explores solutions to holdout creditor disruption of sovereign debt restructuring by examining a contract law theory of sovereign debt: i.e., sovereign debts as relational contracts. This thesis examines what attributes of sovereign debts that make them relational contracts and the legal consequences of sovereign debts as relational contracts. The key consequence of sovereign debt as a relational contract is the duty of good faith. The thesis considers the duty of good faith in three relational scenarios: counterparty, intercreditor, and assignment of sovereign debt obligations. For each, it explores where these duties exist, what they require of parties to sovereign debt contracts, and how holdout disruption of sovereign debt restructuring may be violative of the good faith conduct required in each case. Select precedent cases of holdout disruption of sovereign debt restructurings decided in New York courts are examined with a view to exploring how an application of the duty of good faith in each case could have successfully combated the holdout disruption and enabled the sovereign debt restructuring exercise to succeed. The enquiry on relational contract theory, the relational character of sovereign debt, the duty of good faith as an incident of relational contracts, and the possible application of the duty of good faith to combat holdout disruption, as undertaken in this thesis, is done from a comparative overview of English and New York laws, with brief comments on a plausibly even more effective application of the duty of good faith in Continental European jurisdictions
Regulering van transacties met verbonden partijen:Beperking van het risico van tunneling in rechtsvergelijkend perspectief
Get PDFAanleiding voor het onderzoek is de discussie in de Nederlandse ondernemingsrechtelijke vakliteratuur ten aanzien van de door bestuurders en commissarissen van NV’s en BV’s te hanteren procedures in geval van belangenverstrengelingsvraagstukken. De discussie speelt in het bijzonder ten aanzien van gevallen waarin sprake is van een controlerend aandeelhouder, en de belangen van minderheidsaandeelhouders in het geding zijn. In het onderzoek wordt de behoefte aan duidelijkheid ten aanzien van de toepasselijke procedures gerelateerd aan artikel 9quater van de Europese aandeelhoudersrichtlijn (Richtlijn EU 2017/828). Op grond van deze bepaling hebben de EU-lidstaten procedurevoorschriften ingevoerd voor transacties met verbonden partijen (related party transactions) bij beursgenoteerde vennootschappen. Het onderzoek betreft een Nederlandstalig rechtsvergelijkend onderzoek. In de studie zijn betrokken de achtergrond en de inhoud van artikel 9quater en in verband daarmee de regelgeving die in Nederland, Duitsland en het VK van toepassing is bij transacties met een controlerend aandeelhouder bij een beursgenoteerde vennootschap. In de analyse wordt aandacht besteed aan de toepasbaarheid van de bevindingen op kapitaalvennootschappen in besloten verhoudingen.De belangrijkste bevinding is dat bij Nederlandse kapitaalvennootschappen het risico van benadeling door transacties met verbonden partijen relatief groot is in vergelijking met de onderzochte jurisdicties, vanwege met name het gebrek aan procedurele waarborgen vooraf. Het formuleren van duidelijkere procedureregels kan bijdragen aan een betere bescherming, en lijkt mede gezien de wijze van regulering elders niet onnodig bezwaarlijk. Aan de rechtsvergelijking kan inspiratie worden ontleend voor een wijze van regulering die tegemoet komt aan de knelpunten in de lopende discussie hieromtrent
Transport and behaviour of water in oil paintings
Get PDFPreventive conservation of oil paintings is aimed at slowing down unwanted change by optimising the conditions in which the work of art is displayed or stored. To inform preventive conservation decisions, knowledge is necessary about the mechanisms responsible for detrimental chemical change in oil paintings, the rate at which change occurs and how change is influenced by the environment. Currently, only minimal quantitative data is available on the influence of the environment on chemical processes in oil paintings. To address this lack, this thesis investigates the relationship between humidity in the environment and the concentration and distribution of water inside oil paint. A computational approach is taken to calculate the transport of water through the different layers of an oil painting as a result of fluctuations in environmental humidity. The parameters for the diffusion model are estimated based on data from literature and water sorption experiments. The model is applied to gain a better understanding of the effect of wax-resin linings on the water transport behaviour of paintings. At the molecular level, the distribution of water in the oil paint polymer network is investigated using infrared spectrsoscopy and differential scanning calorimetry. Furthermore, a case study of water-based chemical deterioration in a 17th-century oil painting places this research in context of the complexity and material heterogeneity of historical paintings. In the last chapter, a suite of non-invasive imaging techniques is employed to monitor chemical and physical change in paintings, an essential step towards effective preventive conservation of oil paintings
The secrecy and science of Cold War atoms in the Netherlands and Norway
Get PDFThis study focuses on a unique nuclear collaboration between the Netherlands and Norway in the early Cold War, with special attention to the role of secrecy. A small joint research reactor was completed in Norway in July 1951. In addition, a small device to enrich uranium—a "calutron"—was realized in the summer of 1953 in Amsterdam. In those years America pursued a strict policy of secrecy and control of nuclear materials such as uranium. It was not until December 1953 that US President Eisenhower announced a relaxation of this policy; the "Atoms for Peace" program. The realization of these capabilities under a regime of maximum restrictions provides an ideal case for studying knowledge limitation and the relationship between science and secrecy. How did scientists and state officials deal with secrecy? How and why did the boundaries of secrecy shift over time? Three decisive factors can be identified for secret knowledge and technology to move: possession of special nuclear materials such as heavy water or uranium, scientists with a strong international network, and political will to support nuclear development. Norwegian and some Dutch assistance extended to third countries in the period up to 1960. Finally, secrecy was important in the joint project in a specific way: it enabled the production of scientific disinformation as a Cold War weapon. Openness and secrecy alternated to reflect changing power relations within Cold War science. As this history shows, secrecy is a convenient historiographical instrument to reveal such essential historical patterns
Dopaminergic control of food choice preference and tVTA influence on learned helplessness
Get PDFThis thesis investigated a rodent model of Parkinson’s disease, with a bilateral lesion of the substantia nigra, for the presence of motor and non-motor symptoms, with the latter covering aspects related to food intake, pain, and depression. We showed that a co-lesion of the tail of the ventral tegmental area (tVTA) is sufficient to reverse these parkinsonian-like symptoms. We next studied the influence of the dopaminergic system on food choice by selectively destroying dopamine neurons and their terminals and testing the animals with a free-choice high-fat high-sugar diet. We reported an increase in fat intake with the loss of dopaminergic transmission, or the blockade of D1 receptors, in the rostral part of the lateral nucleus accumbens. Finally, we showed an increased excitatory synaptic transmission in the tVTA associated with the development of learned helplessness in rats. Overall, this work has thus contributed to the progress of our knowledge of central dopaminergic systems’ influence on behavior, affecting motor skills, pain, food intake, and mood
Photocatalysis for applications in living cells
Get PDFBioorthogonal catalysis has emerged as a potent tool for introducing new-to-nature reactions in living organisms, facilitating diverse biological applications such as fluorescence imaging, drug synthesis and protein labeling. While transition metal catalysts have been employed for catalyzing reactions in living cells, achieving precise control over reactions remains a challenge. Photocatalysis provides a controllable approach to catalyzing reactions in both temporal and spatial dimensions within living organisms, constituting a burgeoning research field. However, this approach faces numerous challenges, including the development of new photocatalytic reactions that operate under physiological conditions, implementing photocatalysis for targeting cancer cells, and utilizing red or near-infrared (NIR) light for catalysis. In response to these challenges, our research involves designing diverse transition metal catalysts to enable efficient and controlled catalysis targeting cancer cells, thereby holding promise for potential disease treatment.The central focus in this thesis is on photocatalysis in living cells. We comprehensively explore the expansion of novel photocatalytic reactions to physiological conditions, targeting photocatalysis in cancer cells and the utilization of long-wavelength red light and NIR light photocatalysis. The research described in this thesis contributes to the development of efficient, targeted and controllable catalytic systems, which provides tools to deepen our understanding of biological processes and contributing to the treatment of disease