Als een bestuursorgaan een maximum stelt aan het aantal vergunningen, ontheffingen of concessies dat verleend kan worden of het beschikbare subsidiebedrag beperkt, is sprake van een schaars besluit... Show moreAls een bestuursorgaan een maximum stelt aan het aantal vergunningen, ontheffingen of concessies dat verleend kan worden of het beschikbare subsidiebedrag beperkt, is sprake van een schaars besluit. Door een dergelijk plafond kan de situatie ontstaan dat er meer aanvragers zijn dan beschikbare besluiten. Hoe moeten deze besluiten in dat geval worden verdeeld? Welke rechtsnormen moeten bij de verdeling in acht worden genomen? Centraal in dit onderzoek staat één van de rechtsnormen die bij de verdeling van schaarse besluiten in acht moet worden genomen: de transparantieverplichting. Door bepaalde transparantievereisten in acht te nemen, stellen bestuursorganen alle potentieel geïnteresseerde partijen in staat om een aanvraag voor een schaars besluit in te dienen. De transparantieverplichting draagt hiermee bij aan de gelijke behandeling van de aanvragers. In dit boek wordt onderzocht in hoeverre de transparantieverplichting bij de verdeling van schaarse rechten in het bestuursrecht in acht zou moeten worden genomen. De belangrijkste conclusie van het onderzoek is dat de transparantieverplichting een toegevoegde waarde heeft voor het Nederlandse bestuursrecht, gelet op de gewenste gelijke behandeling van geïnteresseerde partijen bij de verdeling van schaarse besluiten. Daarom zou de transparantieverplichting als onderdeel van het gelijkheidsbeginsel bij schaarse besluitvorming in acht moeten worden genomen. Show less
The availability of single-molecule fluorescence detection techniques has brought about a breakthrough in the optical studies of biomolecular properties and functions by enabling the study of... Show moreThe availability of single-molecule fluorescence detection techniques has brought about a breakthrough in the optical studies of biomolecular properties and functions by enabling the study of molecules one at a time. In this thesis, single-molecule detection is used to obtain detailed information of electron transfer reactions at the interface of a copper protein and a gold electrode. The approach is based on Förster resonance energy transfer (FRET) in a suitably labeled redox protein, where a site-specifically attached, fluorescent dye-label (the donor) and the redox center (the acceptor, with a characteristic absorption spectrum) form a FRET pair. The FRET efficiency depends on the overlap integral of emission and absorption bands of the donor and acceptor, respectively. Thus, changes in the absorbance upon reduction or oxidation of the protein can be monitored via changes in the fluorescence intensity of the covalently attached label. Fluorescence detection provides a much enhanced sensitivity compared to absorbance measurements, down to the single-molecule level. In the present work, azurin was labeled with Cy5, the latter forming the donor in a FRET pair with the Cu redox center of the protein, acting as the acceptor. In the work described in this thesis, it was shown that fluorescence-detected electrochemistry and chemical control of the redox state-changes of a metalloprotein provide excellent methods to explore the kinetic and thermodynamic mechanisms of redox proteins at the single-molecule level. Especially, fluorescence detected electrochemistry may be used for further investigation of protein‐electrode or protein-protein interactions. The methods can be easily applied to many other redox proteins or enzymes, and have potential for applications in fluorescence‐based biosensors and molecular electronics. Show less
This thesis describes the use of MRI contrast agents and vessel wall parameters to image different stages of atherosclerosis. Chapter 2 summerizes different MRI contrast agents targeted towards... Show moreThis thesis describes the use of MRI contrast agents and vessel wall parameters to image different stages of atherosclerosis. Chapter 2 summerizes different MRI contrast agents targeted towards vulnerable plaques that have been presented in literature. Chapter 3 illustrates accumulation of paramagnetic micelles and liposomes in atherosclerosis, yet have complex kinetics when followed over time. In chapter 4 the use of self-gated MRI was validated to detect contrast agent accumulation in atherosclerotic plaques and assess the vessel wall compliance. The potential of both techniques to monitor plaque progression and anti-atherosclerotic therapy was assessed. In chapter 5 we developed a scavenger receptor-A1 targeted USPIO to detect vulnerable lesions. Chapter 6 describes the application of VCAM-1 targeted USPIO. Imaging at different time points, allows to discriminate early plaques from advanced lesions and can be used to monitor treatment response in ApoE-/- mice. In Chapter 7 an E-selectin targeted USPIO was validated. This USPIO allowed discrimination of lesions rich in macrophages from early lesions. In Chapter 8 we developed a micelle encapsulating rosiglitazone. Targeted delivery to the plaque lead to an anti-atheroscle rotic response without cardiac side-effects. Finally in Chapter 9 the potentials and pitfalls of histological validation of MRI contrast agents are illustrated. Show less
Women diagnosed with a sexual dysfunction often suffer from marked distress and interpersonal difficulty that arise from unwanted, persistent or recurrent low sexual desire (hypoactive sexual... Show moreWomen diagnosed with a sexual dysfunction often suffer from marked distress and interpersonal difficulty that arise from unwanted, persistent or recurrent low sexual desire (hypoactive sexual desire disorder, HSDD). An imbalance of excitatory and inhibitory neurotransmitters has been proposed to underlie certain forms of HSDD. Serotonin (5-HT) is a key neurotransmitter involved in female sexual inhibition. Animal studies that apply 5-HT receptor subtype specific ligands permit mechanistic examination of 5-HT mediated effects on sexual behavior. The aim of this thesis was to investigate the serotonergic regulation of female sexual behavior in the common marmoset (Callithrix jacchus), a nonhuman primate that is characterized by a pairmate social setting comparable to humans. The experimental agents employed in the study were (1) flibanserin, a 5-HT1A agonist, 5-HT2A antagonist and putative pharmacotherapeutic treatment for HSDD in women, and (2) 8-OH-DPAT, a prototype 5-HT1A agonist. Neuroendocrine, PET imaging and genetic experiments were conducted to explore hormonal, brain activity and gene expression patterns that underlie female sexual behavior. While flibanserin, administered daily to the female for several weeks, enhanced the male pairmate’s sexual interest and increased pro-social interactions between pairmates, 8-OH-DPAT reduced female sexual receptivity and increased aggressive interactions between pairmates. HPA responses to restraint stress were enhanced after both flibanserin and 8-OH-DPAT. Furthermore, 8-OH-DPAT treated females showed reduced glucose uptake to the medial occipital cortex that correlated with sexual rejection behavior, while gene transcription of the serotonin transporter in the dorsal raphé nucleus, and of oxytocin in the medial preoptic area of the hypothalamus, was increased. Gene cluster analysis of microarray data indicated brain region-specific alterations in neural development, neurotransmission and energy production after 8-OH-DPAT. The results presented in this thesis demonstrate that pair-bond quality between partners and sexual behavior are closely linked and suggest that oxytocin may be the pivot of serotonergic regulation of female sexual behavior, pair-bond and pharmacotherapy of HSDD. Show less
In dit proefschrift heeft Suurland vanuit een rechtstheoretisch en politiek filosofisch kader uitvoerig onderzoek gedaan naar de volgende vragen: •Welke overeenkomsten en verschillen kunnen er... Show moreIn dit proefschrift heeft Suurland vanuit een rechtstheoretisch en politiek filosofisch kader uitvoerig onderzoek gedaan naar de volgende vragen: •Welke overeenkomsten en verschillen kunnen er worden gevonden tussen de politieke, economische, sociale en filosofische achtergronden en de praktische implicaties van het Nazisme, Stalinisme en het Islamisme? •Voor wie is het Islamisme eigenlijk de grootste bedreiging? Voor Moslims of niet-Moslims? •Wat kunnen beleidsmakers en wetgevers, zowel in de niet-Islamitische als Islamitische wereld, leren van de geschiedenis van het Nazisme en Stalinisme als het gaat om het gevaar dat het Islamisme vormt voor hun samenlevingen? •Wat kunnen zij er van leren om dit gevaar te neutraliseren? •Welke plek neemt het Islamisme eigenlijk in binnen het groter kader van het politieke en rechts theoretische denken in de geschiedenis van de Islamitische wereld? •Zijn er wellicht rechtstheoretische methoden van exegese die een alternatief kunnen bieden voor het Islamistisch discours? Show less
Schuman’s Europe: His frame of reference provides an insight into the way European unification was envisioned by its founding father Robert Schuman. The thesis makes clear why Schuman can be... Show moreSchuman’s Europe: His frame of reference provides an insight into the way European unification was envisioned by its founding father Robert Schuman. The thesis makes clear why Schuman can be considered the main architect of European unification because of his thoughts, his personality, his religious background as a practicing catholic and his origins from the region of Alsace-Lorraine. A comparison with several contemporary thinkers shows the uniqueness of Schuman’s thoughts regarding European unification. It explains that Schuman considered the European spiritual and cultural heritage to be the raison d’être of European unification and that this implies effective solidarity beyond frontiers. Schuman’s aim for European unification was peace and security, which should be achieved by political unification through economic integration at the service of the citizen and be consistent with the moral order based in Christianity. Schuman’s method of integration was one of small steps, taking into account the human psyche. He therefore believed that the process of unification would take several generations. According to Schuman the national interests needed to be safeguarded as much as possible, unless they go against the common European interests. Show less
This book is about the politics of nature conservation in late New Order and early Reformasi Indonesia. It approaches the subject through discourse analysis. Understanding politics as a struggle... Show moreThis book is about the politics of nature conservation in late New Order and early Reformasi Indonesia. It approaches the subject through discourse analysis. Understanding politics as a struggle for discourse hegemony it analyses both processes of policy- and lawmaking in Jakarta and of implementation in national parks, and their outcomes, and addresses a number of questions: Which discourses have dominated conservation policies and laws throughout history? How did Ministers, members of Parliament, state officials, NGOs and residents of national parks try to decide debates on conservation in their advantage? Which unwritten rules helped or constrained them in this effort? How did the struggle for discourse hegemony affect policy and law, policy- and lawmaking and implementation? Based on rich empirical case material the book argues that a multitude of discourses have come to co-exist which enabled actors to use arguments strategically, and that various actors have succeeded to mobilise discourses enabling them to participate in the debate without obligations. The results of this study go beyond participating in the debate on what element of sustainable development to focus on but link the policy debate to the debate on governance and rule of law. By addressing the policy discourse and the discourses structuring policy- and lawmaking and implementation, the study wants to contribute not only to the field of nature conservation but also to the field of Indonesian law and governance in general Show less
