The current classification of the Nephtheidae (Cnidaria, Octocorallia) is still based on colony morphology. In this family the Indo-Pacific genera Litophyton, Nephthea, Dendronephthya and... Show moreThe current classification of the Nephtheidae (Cnidaria, Octocorallia) is still based on colony morphology. In this family the Indo-Pacific genera Litophyton, Nephthea, Dendronephthya and Stereonephthya, and the Atlantic genus Neospongodes form a complex mix of closely related, poorly described species, which cannot be recognized using only colony morphology. Attempts with the more modern approach of comparing skeleton composition (sclerites) resulted in describing the genus Chromonephthea Ofwegen, 2005, introduced for several species previously assigned to Dendronephthya, Nephthea and Stereonephthya. In Chromonephthea 53 species were included, 34 of which were new to science. However, the true generic status of the majority of the nominal nephtheid species remained unresolved. In an attempt to clarify the phylogenetic relationships fourteen specimens have been used in molecular analyses. Two clades were supported, which were related to the shape of the sclerites present in the polyp stalks. One clade contained the specimens with characters for Stereonephthya along with a Chromonephthea specimen as a sister group. The other clade had a __true__ Nephthea and Litophyton together with the specimens that could not be placed in any particular genus using the old classification criteria. The consequences of these results for nephtheid classification are discussed. Show less
This dissertation studies trade and transport on the rivers Rhine, Waal and IJssel during the Late Middle Ages. These rivers were the main arteries connecting Holland, Flanders and Brabant on the... Show moreThis dissertation studies trade and transport on the rivers Rhine, Waal and IJssel during the Late Middle Ages. These rivers were the main arteries connecting Holland, Flanders and Brabant on the one hand with Guelders, Cleves, J_lich and Cologne on the other hand. The study tries to establish the nature and volume of river trade at three 'measuring' periods during the 14th, 15th and 16th centuries. It seeks to explain both short-term fluctuations and long-term changes in the river trade during those centuries. Short-term fluctuations were often the result of warfare or meteorological conditions and did not alter river trade structurally. Long-term changes were induced by large-scale economic developments within North-Western Europe, such as the rise of Antwerp and that of Holland and Zeeland. Merchants and skippers from territories along the rivers, such as Guelders, Oversticht and Cleves, who had found a place within the Hanseatic League from the early 14th century onwards, could not compete with their Holland neighbours. Instead they focussed on a role as full time skippers or tried to find a specialisation or niche on the large markets of Holland, Zeeland and Brabant, selling Rhine wine or lumber from the German hinterland. Show less
Synthetic peptide vaccines aiming at the induction of a protective CD8+ T-cell response against infectious or malignant diseases are widely used in the clinic but, despite their success in animal... Show moreSynthetic peptide vaccines aiming at the induction of a protective CD8+ T-cell response against infectious or malignant diseases are widely used in the clinic but, despite their success in animal models, they do not yet live up to their promise in humans. This thesis assesses the development of synthetic peptide vaccines, weighs it against the immunological concepts that have emerged, and identifies the key issues that play a role in the failure or success of a synthetic peptide vaccine. The current state-of-the-art peptide vaccine is a complete synthetic inflammatory product that is ingested by professional antigen-presenting cells and stimulates both CD4+ and CD8+ T cells. Show less
In the present thesis, a homogeneous upper middle class sample of firstborn girls and their mothers were followed from infancy (18 and 24 months) to middle childhood (89 months) using... Show moreIn the present thesis, a homogeneous upper middle class sample of firstborn girls and their mothers were followed from infancy (18 and 24 months) to middle childhood (89 months) using questionnaires and observations. The focus of the study was on three components of moral behavior, i.e. empathy, compliance and prosocial behavoir. The longitudinal development and stability of empathy and compliance from infancy to middle childhood was described, and their relation to prosocial behavior in middle childhood. Empathic concern towards mother increased from 18 to 24 months, but strongly decreased from 24 to 89 months. Empathic concern toward an unfamiliar person decreased from 18 to 89 months. Compliance increased from 18 to 89 months. Only empathy towards mother seems to be fertile ground for donating to charitable organizations like UNICEF. Also, the role of antecedent and concurrent sensitivity and attachment security in prosocial, externalizing, and internalizing behavior in middle childhood was investigated. Results showed that, controlling for concurrent influences, maternal sensitivity and attachment security in infancy predicted prosocial and externalizing behavior Show less
Caminada, C.L.J.; Haberham, A.M.; Hoogteijling, J.H.; Vording, H. 2007
Sunlight has many beneficial effects. However, from a biological point of view, solar UV radiation has also detrimental effects, especially at high doses of exposure. Because of its genotoxic... Show moreSunlight has many beneficial effects. However, from a biological point of view, solar UV radiation has also detrimental effects, especially at high doses of exposure. Because of its genotoxic properties, UV radiation plays an important role in the induction of skin cancer. In the last decennia, the incidence of skin cancer is rapidly increasing. This can partly be explained by an ageing population. However, the rise in skin cancer incidence appears to be primarily due to a change in human lifestyle in which sunbathing has become very popular. Our skin is continuously challenged by UV radiation, which may lead to irreversible damage. In order to withstand sustained physical, chemical and biological damage from the environment, among which UV radiation, the skin is continuously renewed. The regenerative capacity of skin is conferred by stem cells, which persist throughout the organism__s lifetime. Because of their long residency and unlimited capacity to replicate, stem cells might accumulate DNA damage and generate the multiple genetic lesions necessary for tumour development, despite efficient cellular defence mechanisms against DNA damage. Thus, stem cells may play an important role in carcinogenesis. The aim of this study is to investigate the role of stem cells in skin carcinogenesis. Show less
This study analyses the relations between Siam and the League of Nations from 1920 to 1940. It identifies Siam’s policy towards the League as a cornerstone of Siam’s foreign policy and an important... Show moreThis study analyses the relations between Siam and the League of Nations from 1920 to 1940. It identifies Siam’s policy towards the League as a cornerstone of Siam’s foreign policy and an important element of Siam’s domestic modernization during the sixth, seventh and eighth reigns of the Chakri dynasty. In doing so, the study aims at adding a key multilateral dimension to the existing historical analysis of Thai foreign relations during the first half of the twentieth century. It argues that Siam’s League membership played an important role in modernizing the country, reaffirming elite rule and regaining full sovereignty. This study concentrates on the inter-war years and traces Siam’s League membership in the most significant areas of interaction among the wide range of multilateral policy fields. It draws on extensive primary sources which have so far not been studied; the bulk of these files are located at the Thai National Archives in Bangkok and at the League of Nations Archives at the United Nations European Headquarters in Geneva. Show less
The thesis is focused on the DNA-cleaving antibiotic bleomycin that is successfully used in the chemotherapy against several types of cancer like head and neck cancer or certain lymphomas and... Show moreThe thesis is focused on the DNA-cleaving antibiotic bleomycin that is successfully used in the chemotherapy against several types of cancer like head and neck cancer or certain lymphomas and testicular cancer. Although it has been in use for more than two decades, the mechanism of its action is not known. Thus the harmful side effects are difficult to eliminate. On the other hand the process of design or improvement of pharmaceuticals is extremely complex and expensive. Therefore a new trend within drug discovery is emerging with the application of clean chemistry, by performing molecular modeling of new compounds and by running virtual tests to assess their suitability before an expensive synthesis attempt is made. In the thesis, the contribution of different computational methods into this field is discussed, emphasizing the growing role played by quantum mechanical methods. Using state-of-the-art methods, an insight into the mechanism of bleomycin action was gained. The possible reaction pathways of the active bleomycin-Fe(III)-OOH complex with the deoxyribose sugar of DNA were investigated. The simulations show that a facile decaying process involves a homolytic O-O bond cleavage with an almost simultaneous hydrogen atom abstraction. The formation of a hydrogen bond appears to be crucial for the O-O bond cleavage in the Fe(III)-OOH species. The highly selective reaction between the bleomycin drug and the genetic material comes from the selectivity of the created hydrogen bond Show less
Sunwar is a Tibeto-Burman language spoken in eastern Nepal, in the districts of Okhaldhūgā and Rāmechāp, which are situated in an area called Kirant. The languages spoken in this region, also known... Show moreSunwar is a Tibeto-Burman language spoken in eastern Nepal, in the districts of Okhaldhūgā and Rāmechāp, which are situated in an area called Kirant. The languages spoken in this region, also known as Kiranti languages. The language commonly known as Sunwar in English and as Sunuvār in Nepali, is called Koĩc by its native speakers. This description of the Sunwar language is based on data collected during twelve months of field work and contains a chapter with background information on the Sunwar language, its speakers and their culture, followed by chapters on the phonology, the indigenous writing system and the nominal and verbal morphology of Sunwar. Final chapters contain verb paradigms, glossed texts, a Sunwar-English glossary and bibliographical references. Two of the new discoveries depicted in this grammar pertain to the phonology and to the verbal morphology. Sunwar has no implosives anymore, but the language once had at least one implosive // as can be shown by a comparison of phonetic realisa¬tions of the former implosive // in different dialects. At an earlier stage, Sunwar had a biactantial agreement system typical for Kiranti languages. A comparison of the suffix conjugations of modern Sunwar with the older biactantial agreement system shows a regular relationship between the two systems. Show less
Interaction patterns between plants and flower visitors in a Mediterranean flower visitation web can be explained surprisingly well by the combination of two simple mechanisms. Firstly, the size... Show moreInteraction patterns between plants and flower visitors in a Mediterranean flower visitation web can be explained surprisingly well by the combination of two simple mechanisms. Firstly, the size threshold that the nectar tube depth of flowers puts on the tongue length of potential flower visitors; and secondly, random interactions proportional to the frequency of tube depths and tongue lengths in the local species pool. Simulation models revealed that the combination of these factors can reproduce the observed variation in the number of interaction partners, the observed asymmetry of plant - flower visitor interactions, and the degree of morphological matching between tube depth and proboscis length. The study shows also that the frequency distributions of tongue lengths and tube depths have a profound influence on the interaction patterns. The shapes of the observed trait distributions resemble ubiquitous lognormal body size distributions. Knowledge about the structure of flower visitation webs and the underlying causes is essential for understanding the evolution of plants and their pollinators. It also provides an important tool for biodiversity conservation. Show less
Aspergillus niger is a cosmopolitan fungus and its spores can be found in air and soil worldwide. This saprophyte is used in food biotechnology for the production of proteins, mainly enzymes and... Show moreAspergillus niger is a cosmopolitan fungus and its spores can be found in air and soil worldwide. This saprophyte is used in food biotechnology for the production of proteins, mainly enzymes and for the production of organic acids. In the production of proteins, several problems are encountered such as repressed gene-expression, morphologic and genetic instability and undesired metabolite accumulation. To find solutions to these problems, often mutagenesis and mitotic recombination have been used, as described in this thesis. These mutations cannot simply be recombined by crosses, as Aspergillus niger is an asexual fungus. An alternative way to recombine mutations is via the parasexual cycle, also called mitotic recombination. To obtain more information of its possibilities we studied mitotic recombination of genetic markers on chromosome III. Recently the genome sequence of A. niger has been determined and this information has been linked to the genetic map. By improving the genetic map of chromosome III we were able to study crossing-over of linked markers and found that these cross-over events occurred predominantly in a small part of the chromosome. This mitotic recombination hotspot has some interesting physical features, but it remains uncertain if and which of them is responsible for the increase in crossing-over. Show less
As part of the international presence in the Western Balkans, the European Union has adopted sanctions, brokered political agreements, launched its first-ever police and military missions and... Show moreAs part of the international presence in the Western Balkans, the European Union has adopted sanctions, brokered political agreements, launched its first-ever police and military missions and directed economic, legal and administrative reforms to eradicate the root causes of instability. Yet, despite the comprehensive nature of its involvement, the EU__s strategies have been marked by confusion, its actions by concurrent or competing mandates of other international organisations. As a result, the returns on its investments are dwindling, at a time when nation-building in the region has entered its final stages with the separation of Serbia and Montenegro, the search for bringing an end to the international governance of Bosnia-Herzegovina and a final status for Kosovo. As the Western Balkans still contain a genuine security threat, there is a real imperative now to move the region as a whole from the stage of international protectorates and weak states to the stage of accession to the euro-atlantic organisations to which they aspire. This book presents legal and political ways and means to restructure the international effort to see the defining processes through. Under the leadership of the EU, only a __tough love__ strategy based on a firm but fair application of the conditionality principle can lead to the integration of the Western Balkans into the European mainstream. Show less
Better regulation in the European Union cannot be achieved without serious attention to transposition of EU law into national legislation. As a matter of fact, EU member states breach EU law __... Show moreBetter regulation in the European Union cannot be achieved without serious attention to transposition of EU law into national legislation. As a matter of fact, EU member states breach EU law __ perpetuately. Why do member states miss deadlines when transposing EU internal market directives? What factors determine delays when transposing EU directives? How do these factors influence the timeliness of the national transposition processes? And under what conditions are transpositions of directives delayed? This study analyses the timeliness of national transposition processes across nine member states of the 2004 EU transport acquis. Based on a truly mixed-method approach __ a new quantitative data set with further insights gleaned from four controlled case studies and a concluding fuzzy set analysis - this study shows that the European Union has a serious transposition problem. Almost 70 percent of all national legal measures transposing the transport acquis cause problems, either because they are transposed too late, risking the opening of an infringement proceeding, or because they are too early (gold-plating), risking warping effects on the regulatory environment for business and citizens in the EU alike. Furthermore, this book provides some progress regarding the conditions under which transposition performance of member states could be improved. Seven potential European and national drivers and constrainers for timely transposition can be identified with different effects on the lengths of transposition delays. Distinguishing between three outcomes of transposition process (on time, short and long delay) it is the specific features of European directives that account for short term delays, whereas serious time lags of more than six months are a result of domestic factors. Furthermore, the timing of general elections in a member state and policy sector-related crises retard or rather accelerate national transposition processes just as political priority represents a significant necessary condition for timeliness. Show less
The focus of this thesis is on the dynamics and functions of saprotrophic soil fungi during conversion from an arable land into a natural ecosystem (heathland) and to asses their effects on soil... Show moreThe focus of this thesis is on the dynamics and functions of saprotrophic soil fungi during conversion from an arable land into a natural ecosystem (heathland) and to asses their effects on soil ecosystem processes. Chapter 2 describes that fungal biomass in abandoned arable land is not increasing for at least 3 decades to the level of a natural ecosystem. Opportunistic fungi showed to be responsible for the decomposition processes, and these fungi are stimulated by large sizes of nitrogen-rich substrate buried in soil (Chapter 4& 5). Chapter 3 presents that no large amounts of phosphorus seem to leach into deeper soil layers after land abandonment. In Chapter 6 it is shown that the establishment of Calluna vulgaris in a recently abandoned arable land can be due to a fast colonization of Calluna immediately after abandonment and the reduction of microbial nitrogen mineralization, in combination with the colonization of Calluna roots by ericoid mycorrhizal fungi. In Chapter 7 it is concluded that an increase in fungal biomass in ex-arable soils can be of interest for soil ecosystem restoration and this may be triggered by the introduction of large particles of recalcitrant organic matter together with sufficient fungal biomass. Show less
The results presented in this thesis provide new information on the role of the p53.S389A point mutation in chemical-induced tumorigenesis. After DNA damage, p53 protein levels increase due to... Show moreThe results presented in this thesis provide new information on the role of the p53.S389A point mutation in chemical-induced tumorigenesis. After DNA damage, p53 protein levels increase due to several post-translational activation processes. Phosphorylation of p53.S389 seems to be partly required for optimal induction of these p53 protein levels. Next, target genes are either induced or repressed, and phosphorylation of p53.S389 seems essential for an optimal p53-related transcriptional response both endogenously (especially repressed genes) as well as after the induction of DNA damage. Than as a read-out system for the activation of different genes, several cellular responses (apoptosis, cell cycle arrest etc.) can be observed, which again seems partly dependent on p53.S389 phosphorylation. When these processes are adversely affected due to inadequate functioning of p53, like is the case in p53.S389A mutant mice, this might lead to increased risks of developing tumors. Indeed, two chronic carcinogenicity experiments revealed an increased sensitivity of the p53.S389A mutant mice for tumor development upon exposure to DNA damaging agents. In conclusion, knowledge about the in vivo relationship between DNA damage induction, regulation of p53 activity (in terms of cell cycle control and/or apoptosis), DNA repair (NER) and the development of cancer was obtained. Show less
The objective of the investigations described in this thesis was to characterize the in vivo pharmacological and PK-PD properties of buprenorphine relative to fentanyl with respect to: 1) kinetics... Show moreThe objective of the investigations described in this thesis was to characterize the in vivo pharmacological and PK-PD properties of buprenorphine relative to fentanyl with respect to: 1) kinetics of onset and offset of the pharmacological effects at the mu-opioid receptor, 2) selectivity of action (antinociception versus respiratory depression), 3) the interspecies extrapolation of the PK-PD correlation of the antinociceptive and respiratory depressant effect, 4) the role of active metabolites, 5) kinetics of antagonism of the respiratory depressant effect. Preclinical investigations were performed to develop and validate mechanism-based PK-PD models for the effects of opioids on antinociception and respiration. These PK-PD models were subsequently applied to characterize the effects of buprenorphine and fentanyl in humans. It was shown that the developed PK-PD model can be used to predict the efficacy and safety outcome of opioids in animals. Furthermore, the PK-PD model had excellent properties to enable animal-to-human extrapolation of the efficacy and safety outcome. Show less
