In society there is a constant urge to improve existing devices and the level of success is perhaps the easiest to observe in the world of electronic devices. The complexity, functionality and... Show moreIn society there is a constant urge to improve existing devices and the level of success is perhaps the easiest to observe in the world of electronic devices. The complexity, functionality and reliability of these machines has increased enormously, but it approaches its limits. A new giant step which will provide the space for further development is the concept of molecular electronics where organic molecules and their natural characteristics are used as the functional units. The research presented in this thesis is a small part of the large effort which the scientific community puts nowadays into this goal. The system under the investigation is molecular bridge where the molecule is hydrogen or CO or acetylene or benzene. We characterise junctions by point contact spectroscopy and can address different modes of oscillation by following stretching dependence of vibration energy. Show less
The main theme of this thesis is the catalytic oxidation of CO, which we have investigated on several model catalyst surfaces at atmospheric pressures and elevated temperatures with the combination... Show moreThe main theme of this thesis is the catalytic oxidation of CO, which we have investigated on several model catalyst surfaces at atmospheric pressures and elevated temperatures with the combination of Scanning Tunneling Microscopy and Mass Spectrometry.The study of CO oxidation on low-index and vicinal palladium surfaces has shown that when exposed to ambient pressures of oxygen at elevated temperature, these surfaces oxidize irrespective of their orientation. In this pressure regime the oxides were shown to have a higher reactivity than the metallic surfaces.In a certain window of partial pressure combinations of O2 and CO reaction rate oscillations were observed on Pd(100) and on its vicinal surface Pd(1.1.17). ). CO adsorption on Pt(111) was found to lead to the formation of a regular overlayer structure, identified as (√19 x √19) R23.4°-13CO. The stability of this structure under different reaction conditions was discussed. These results were further used to illustrate the importance of temperature in a catalytic system.Spectacularly high conversion rates could be achieved during CO oxidation at atmospheric pressure on metallic Pt(100) surface. Show less
Johannes Drusius (1550-1616) spent a large part of his life as professor of Oriental languages at the university of Franeker, namely from 1585 to 1616. He was a philologist whose works were... Show moreJohannes Drusius (1550-1616) spent a large part of his life as professor of Oriental languages at the university of Franeker, namely from 1585 to 1616. He was a philologist whose works were reprinted far into the seventeenth, and even in the early eighteenth century. Drusius stimulated research by Christian scholars in the northern Netherlands into Jewish writings. His scholarship in Hebrew and in Jewish works played a vital role in the development of the pedagogical ideal of humanist education with philological stamp. A prominent feature of Drusius' work is his study of Hebrew and Jewish sources for the benefit of explaining passages in the books of the Bible. This research paper constitutes an analysis of Drusius' New Testament commentaries. Chapter one offers a historical sketch of Christian Hebraist studies and in doing so gives a contextualization of Drusius' labours. Chapter two comprises a biography of Drusius. Chapter three clarifies the genre of the 'annotationes', as the contents of Drusius' commentaries consist mainly in philological notes. In chapter four are Drusius' New Testament commentaries discussed. Chapter five is devoted to the relationship between philology and divinity as Drusius saw this. Show less
De Europese aal blijkt bij uitstek een langeafstandsspecialist te zijn. Dit is gebleken uit zwemtesten in 22 zwemtunnels. Het kost schieralen slechts 40% van de vetreserves om de 5500-km naar de... Show moreDe Europese aal blijkt bij uitstek een langeafstandsspecialist te zijn. Dit is gebleken uit zwemtesten in 22 zwemtunnels. Het kost schieralen slechts 40% van de vetreserves om de 5500-km naar de paaigronden in de Sargassozee te overbruggen, mogelijk zelfs in slechts drie-en-een-halve maand. Niet alleen dienen vetten als brandstof, ze zijn ook essentieel als energievoorraad voor de toekomstige larven. Het blijkt nu dat zwemmen de afzetting van de vetten in de eitjes op gang brengt. Door te zwemmen beginnen de eicellen van, vooral oudere, alen te ontwikkelen zodat ze kunnen afpaaien zodra ze in de Sargasso zijn aangekomen. De zwemblaasparasiet beschadigt echter de zwemblaas waardoor geïnfecteerde alen minder efficiënt zwemmen en al het vet waarschijnlijk is verbruikt voordat ze de Sargasso bereiken. Een andere verstorende factor zijn de in het vet opgeloste PCB's, die al in zeer lage doses de vroege ontwikkeling van embryo's onmogelijk blijken te maken. Deze twee factoren lijken een belangrijke oorzaak te zijn in de sterke afname van de wilde populatie. Het feit dat we met zwemmen een natuurlijke 'trigger' hebben gevonden van ontwikkeling van de eicellen en dat we in staat zijn geweest schieralen in gevangenschap tot reproductie te brengen biedt hoop voor toekomstige kweek. Show less
Waar mensen zijn vindt nutriënten-verrijking van het water plaats. In de zomer kunnen algen hierdoor goed groeien. Dode algen en andere resten zakken naar de bodem waarna door rottingsprocessen de... Show moreWaar mensen zijn vindt nutriënten-verrijking van het water plaats. In de zomer kunnen algen hierdoor goed groeien. Dode algen en andere resten zakken naar de bodem waarna door rottingsprocessen de zuurstofconcentratie in het water sterk kan dalen. Het water wordt hierdoor onleefbaar voor vissen en andere organismen. In het Victoriameer in Afrika is het altijd zomer en grote gebieden zijn hier de laatste decennia zuurstofarm geworden. Men kan aannemen dat dit zeer slecht is voor de visstand. Toch blijken Victoriameervissen beter te kunnen overleven dan men dacht. In ons laboratorium in Leiden zagen we drie weken oude Victoriameervisjes (cichlidensoorten) zeer snel konden wennen aan zuurstofarme omstandigheden. Zij bleken zelfs met tien keer minder zuurstof (0,8 mg per liter) net zo hard te groeien als nestgenoten die onder normale omstandigheden leefden. Volwassen vissen gaan dood of overleven dit slechts tijdelijk. Jonge visjes kunnen zo goed overleven omdat zij tot 80% grotere kieuwen krijgen en continue een veel hogere ademactiviteit hebben. De aanleg van deze superkieuwen kost zoveel ruimte dat zelfs hun kop van vorm veranderde. Het bloed dat door de kieuwen stroomt bleek meer en beter zuurstof te kunnen binden terwijl een soort meerdere nieuwe typen hemoglobine bleek te produceren. Dit is een unieke eigenschap die bij andere dieren alleen optreedt bij geboorte of bijvoorbeeld transformaties van water naar land bij amfibieën. Het waterpeil in het Victoriameer was 14.000 jaar geleden extreem laag en mogelijkerwijs heeft een voorouder van deze soort deze truc destijds onder de knie gekregen die in het zuurstofarme water van nu weer van pas komt. Show less
This study of Mamluk metalwork fittings presents a hitherto largely ignored body of Mamluk metalwork objects, i.e. metal-faced doors, doorknockers, window grilles, and window shutters, and aims to... Show moreThis study of Mamluk metalwork fittings presents a hitherto largely ignored body of Mamluk metalwork objects, i.e. metal-faced doors, doorknockers, window grilles, and window shutters, and aims to trace their stylistic and technical development throughout the Mamluk period. In order to establish the uniqueness of Mamluk metalwork fittings, their relationship to pre-Mamluk metalwork traditions and to contemporary designs in other media is analysed. Moreover, the visual relationship between these metalwork artefacts and their immediate architectural context is assessed. Furthermore, attention is directed towards the various metalworking centres such as Cairo, Damascus, and Aleppo and their activities. This study is completed by a catalogue, comprehensively illustrated, comprising a description of embellished metalwork fittings predominantly found in situ in the major cities of the Mamluk realm. Show less
T cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in... Show moreT cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in particular virally induced tumors. In this thesis we aimed 1) to obtain more insight into antigen-specific T cell responses and 2) to study how antigen-specific T cell responses can be improved. For the first aim we generated new tools that by enabling the visualization of antigen-specific CD4+ and CD8+ T cells allow the study of the dynamics of antigen-specific T cell responses in time throughout an ongoing immune response (chapter 2). In addition, we developed a novel technique that enables the study of family relationships between different T cell populations. This technique for instance allows us to determine whether two different types of effector T cell populations arise from the same or different pool(s) of na_ve T cells (chapter 5). For the second aim, we analyzed whether antigen-specific T cell responses can be manipulated by providing increased costimulation in the form of constitutive triggering of CD27 (chapter 3) or by generating CD4+ T cells that are modified by the introduction of MHC class I restricted TCRs (chapter 4). Show less
This dissertation investigates A’-dependencies where the dislocated constituent is not transformationally related to the position where it is interpreted. The analysis is carried out within the... Show moreThis dissertation investigates A’-dependencies where the dislocated constituent is not transformationally related to the position where it is interpreted. The analysis is carried out within the Principles & Parameters framework. The first two chapters address relative clauses. Based on a detailed examination of reconstruction, it is argued that German restrictive relatives should be given a Matching Analysis. Chapter three analyzes an alternative to long-distance relativization in German and Dutch where the relative pronoun is governed by the preposition von/van ‘of’ and a resumptive appears instead of a gap in the complement clause. The construction has the hallmarks of an indirect A’-dependency: The external head is interpreted inside the complement clause but cannot be transformationally related to that position. The paradox is resolved by postulating short A’-movement in the matrix clause, operator movement in the complement clause and an ellipsis operation that links the chains. Chapter four analyzes relative clauses in Zurich German. While local relativization is shown to be largely parallel to Standard German, long-distance relativization is reanalyzed in terms of Resumptive Prolepsis. This study is of interest to anyone interested in the syntax of relative clauses, reconstruction, resumption or in the syntax of Standard German, Zurich German and Dutch. Show less
In this work I consider models for survival data when the assumption of proportionality does not hold. The thesis consists of an Introduction, five papers, a Discussion and an Appendix. The... Show moreIn this work I consider models for survival data when the assumption of proportionality does not hold. The thesis consists of an Introduction, five papers, a Discussion and an Appendix. The Introduction presents technical information about the Cox model and introduces the ideas behind the extensions of the model proposed later on. In Chapter 2, reduced-rank methods for modelling non-proportional hazards are presented while Chapter 3 presents an algorithm for estimating Cox models with time varying effects of the covariates. The next Chapter deals with the gamma frailty (Burr) model and discusses alternative models with time dependent frailties. In Chapter 5 models with time varying effects of the covariates, frailty models and cure rate models are considered. The usefulness of each one of these models is discussed and their results are compared. The sixth Chapter of the thesis discusses ways of dealing with overdispersion when using generalized linear models. The Discussion is about future directions of the research presented in this thesis. Finally, there is an Appendix about the use of coxvc, a package written in R for fitting Cox models with time varying effects of the covariates. Show less
Genetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human... Show moreGenetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human reproduction. It is argued that an innate cytokine profile supportive of Th1-type T cells favors survival of infectious diseases (with longevity as the ultimate), but women with this profile are found less likely to have successful pregnancies (progeny). The probability of a normal fertility was found to increase more than 10-fold when the innate cytokine profile was characterized by high IL-10 (Th-2 cytokine) and low TNF- (Th-1 cytokine) responsiveness. The IL10 –2849 AA genotype was found to be associated with a decreased fertility and fecundity (time to pregnancy) in females, possibly due to the lower expected IL10 responsiveness. Rheumatoid arthritis (RA) is an example of a Th-1 mediated disease. It was found that the phenotype of joint destruction in RA was associated with the phenotype of reported miscarriages, suggesting common genetic risk factors for each of these two traits, possibly through the innate Th-1/Th-2 phenotype. Factor V Leiden (FVL) is a point mutation in the factor V gene generating a 7-fold increase in incidence of deep vein thrombosis. Specific advantages of the FVL mutation in early pregnancy (implantation) might balance its potentially harmful effects later in life and explain the remarkably high prevalence of this mutation in the general population. Show less
The studies described in this thesis focus on the feasibility of using carcinoembryonic antigen (CEA) as a target for immunotherapy of colorectal cancer and on the balance between anti-tumor... Show moreThe studies described in this thesis focus on the feasibility of using carcinoembryonic antigen (CEA) as a target for immunotherapy of colorectal cancer and on the balance between anti-tumor immunity and autoimmune pathology. The potential of CEA as a target antigen for immunotherapy of cancer is conceivably restricted by the fact that CEA is expressed in several abundant and vital tissues, including intestine and stomach, and is even routinely found in the serum of healthy individuals. We demonstrate that the CEA-specific CD4+ T-cell repertoire in CEA-tg mice is severely limited compared to wild-type mice and that this CD4+ T-cell tolerance for CEA was induced by the thymus. In addition we showed that CEA was expressed in medullary thymic epithelial cells (mTEC) in both mice and human beings. The latter suggests that the CEA-specific T-cell repertoire may also be tolerized in people. In further studies we have focussed on possibilities to overcome tolerance of CEA by reconstituting the T-cell repertoire of CEA-tg mice by adoptive transfer of the T-cell repertoire of CEA-immunized wild-type mice into tumor-bearing CEA-tg mice. Adoptive transfer in combination with immune modulation can result in efficient eradication of CEA-positive tumors. However, in order to prevent hazardous CEA-specific autoimmune reactions, the choice of the right immune modulation protocol is critical. Show less
This study surveys the theory about 'Christendom' developed by the Anglican theologian Oliver O'Donovan. The author defines 'Christendom' as a state of affairs in which the Christian faith in one... Show moreThis study surveys the theory about 'Christendom' developed by the Anglican theologian Oliver O'Donovan. The author defines 'Christendom' as a state of affairs in which the Christian faith in one way or another gives public direction to society and/or politics. The investigation is positioned within the present debate about the role of religion in Dutch society. The Anglo-Saxon Christendom debate illustrates that the discussions about the societal role of religion should not deny the theological dimension to this question. The Christendom debate of our time has been for the most part initiated by two American theologians, John Howard Yoder and Stanley Hauerwas. They take a critical view of Christendom. Besides this option there are four other positions in the Christendom debate: the Christian faith as civil religion, the liberal vision, the theocratic approach, and confessional or principled pluralism. A comparison between them and O'Donovan's theory shows out that the latter has the potential to unite what usually only exists in mutual tension and to open up a fruitful continuation of the 'Christendom' debate as well as the discussions about the role of religion in society. Show less
That art has some sort of relation to reality is an assumption underlying most of the past and the present discourse on and about art. The questions of what sort of relation, whether it is at all... Show moreThat art has some sort of relation to reality is an assumption underlying most of the past and the present discourse on and about art. The questions of what sort of relation, whether it is at all valid and specific (as opposed to science’s or philosophy’s relation to reality), however, are hardly ever addressed. In studying a relation between terms, one needs to be clear about the terms themselves: ‘Art’ is understood here in the sense of the notion that crystallized no earlier than the 18th century in Europe. That notion is, in its essential features, still valid today. ‘Reality’ tends to be understood as that what exists independently of us ‘out there’, but it can also be the inner world of feelings, perceptions and memories, which entirely depends on the individual. The former is best described by science whereas the latter is inaccessible for it. Then there is the reality of inter personal relations, like society, culture and language. The thesis examines art in relation to each of them, on the level of individual experience, on the level of social life, in historical perspective. Informed by all these different viewpoints it eventually addresses the question whether the making or the experiencing of art can lead to any knowledge.Concerning the illustrations 5, 9, 10, 11, 18, 19, 20, 21, 26, 27, 28, 34, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, and 49 of Chapter I, the illustrations 15, 17, 18, 19, 24, 25, 26, 27, 28, and 31 of Chapter II, the illistrations 20, 21, 22, 23, 27, 28, 32, 33, 42, 45, 44, 45, 46 , 47, 48, 49, and 50 of Chapter III. the illustrations 4, 5, 8, 9, and11 of chapter IV, and the reproduction of a painting by Mondriaan on the cover the author does not own the copyright, Concerning this material the author has striven to ensure that in using the illustrations all legal rights have been taken into proper account. However, parties who believe they can claim legal rights are invited to apply to Leiden University, c/- Universiteitsbibiotheek, Afd. Acquisitie, Postbus 9501, 2300 RA Leiden, or to proefschrift@library.leidenuniv.nlMet betrekking tot de afbeeldingen 5, 9, 10, 11, 18, 19, 20, 21, 26, 27, 28, 34, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 en 49 van het hoofdstuk (I.), de afbeeldingen 15, 17, 18, 19, 24, 25, 26, 27, 28 en 31 van het hoofdstuk (II.), de afbeeldingen 20, 21, 22, 23, 27, 28, 32, 33, 42, 43, 44, 45, 46, 47, 48, 49 en 50 van het hoofdstuk (III.), de afbeeldingen 4, 5, 8, 9, 11 van het hoofdstuk (IV.), en de afbeelding van het Mondriaan schilderij op de cover bezit hij geen copyright. Met betrekking tot dit beeldmateriaal heeft de promovendus ernaar gestreefd de rechten van de illistraties volgens wettelijke bepalingen te regelen. Degenen die desondanks menen zekere rechten te kunnen doen gelden, kunnen zich wenden tot de Universiteit Leiden, p.a. Universiteitsbibliotheek, Afd. Acquisitie, Postbus 9501, 2300 RA Leiden, of bij proefschrift@library.leidenuniv.nl Show less
The metabolic syndrome is an increasing problem in our Western society. Many of the features of the metabolic syndrome, like obesity, insulin resistance, dyslipidemia, and hepatic steatosis are... Show moreThe metabolic syndrome is an increasing problem in our Western society. Many of the features of the metabolic syndrome, like obesity, insulin resistance, dyslipidemia, and hepatic steatosis are established risk factors for cardiovascular disease. Growing evidence supports the important role of body free fatty acid handling and/or body distribution of triglycerides in the pathogenesis of the metabolic syndrome-associated problems. We used several different approaches to study the development of obesity, insulin resistance, dyslipidemia, and liver steatosis. In chapter 2 we found that absence of apoC3, a natural LPL inhibitor, enhances FA uptake from plasma triglycerides in adipose tissue leading to increased susceptibility to diet-induced obesity, followed by more severe development of insulin resistance. Therefore, we have shown that regulation of body distribution of triglycerides, in a LPL-dependent process, plays an important role in obesity development. In chapter 3 we found that acute inhibition of the β-oxidation of FA indeed increases hepatic lipid content, but neither stimulates hepatic VLDL secretion nor reduces insulin sensitivity. In chapter 4 we showed that the combination of proteomics with relevant physiological parameters in a sensitive animal model, is a powerful tool, which will aid in identifying workingmechanisms of various dietary FA. In chapter 5 we found that sphingolipids protect the liver from fat and cholesterol-induced steatosis. Since sphingolipids are nutritional compounds present in several daily foods, such as milk and meat, addition of sphingolipids to the diet may decrease traditional cardiovascular risk factors, such as plasma cholesterol and triglycerides. Show less
Eating constitutes a human act that crosses the biological and symbolical, so much so, that societies have created a protocol of uses around it. Eating is tied to a system that classifies,... Show moreEating constitutes a human act that crosses the biological and symbolical, so much so, that societies have created a protocol of uses around it. Eating is tied to a system that classifies, organizes and places value not only on food, but also those who are dining in accordance with unfolding social frameworks. By understanding how communities and groups organize what they eat, we can become more aware of the social differences and tensions (in relation to gender, class, age and ethnicity among others) that exist. But above all, we can better understand how the act of eating can transform itself into a symbol that expresses and reproduces these differences. Set in Osorno, a city south of Chile, this study takes into account diverse social and symbolic aspects of cooking; analyzing how language constructs similarities and differences. The book focuses on daily eating habits, diets and dining festivities from cultural collective models (imaginaries) to the subjects’ economical and social dynamics. The author seeks to answer the question: What do you eat when you eat in Osorno? And as a guide to this investigation, it is assumed that consuming food is an action that goes beyond the necessity of nutrition, involving diverse spheres of social life. In the city of Osorno one can find an interculturality that is often times in conflict; one that realizes that cultural negotiations and dialogues where the “European”-or “white”-and the indigenous-Huilliche emerge as mechanisms to create a line that polarizes social identities. Show less
This thesis addresses the regulation of TRPM7 channels by receptor-mediated signals and the effects of the ensuing ionic signals on the cytoskeleton. Several signaling pathways were investigated... Show moreThis thesis addresses the regulation of TRPM7 channels by receptor-mediated signals and the effects of the ensuing ionic signals on the cytoskeleton. Several signaling pathways were investigated that activate TRPM7 channel opening. Stimulation of PLC-activating receptors opens TRPM7 channels, leading to influx of extracellular Ca2+. The results contrast markedly with a report by Runnels et al. who showed inhibition of TRPM7, rather than activation by PLC. To explain this discrepancy, we explored the differences in PIP2-mediated regulation of TRPM7 measured in perforated-patch and whole-cell configuration after intracellular Mg2+ depletion. This leads us to propose that the effects of PLC activation on TRPM7 currents as detected in whole cells can best be viewed as ‘accelerated rundown’ rather than as bona fide signal transduction. Agonist-induced TRPM7 activation and subsequent Ca2+ influx affects the cytoskeleton by phosphorylation of the myosin II heavy chain to promote cytoskeletal relaxation and the conversion of focal adhesions to podosomes. Ca2+ influx appears crucial for the in vivo function of the TRPM7-kinase by triggering the association between the kinase and its substrate. A second effect of receptor-mediated Ca2+ influx can affect the cytoskeleton by translocating Rac in a PKC-dependent manner to the plasma-membrane, where it induces extensive membrane ruffling. Show less
The main topic of the book is the nature of inner aspect of the Verb Phrase, and the relation between the decompositional and the quantificational approaches to this problem. Decompositional... Show moreThe main topic of the book is the nature of inner aspect of the Verb Phrase, and the relation between the decompositional and the quantificational approaches to this problem. Decompositional approaches analyze eventualities into simpler components, organized by some kind of structure. In this view, an eventuality is telic if, in decomposition, it can be shown to involve a result component (also referred to as the culmination or termination component, or as the telos). Quantificational approaches see telicity as a property of the predicate of an eventuality, usually described as boundedness, lack of the subinterval property, or a specified quantity. The major advantage of the decompositional approaches is that they directly match the syntax-semantics interface of the VP with the conceptual image of an eventuality. Quantificational approaches blur the picture in this respect, because they involve effects like distributive readings, which are not a typical interpretational component of the VP domain. On the other hand, the major advantage of the quantificational approaches is that they assign similar or identical properties to (the predicates of) eventualities and nominal expressions. This enables them to capture the phenomenon of incremental themes (participants that appear to measure out the eventuality in which they take part), by relating the predicates of eventualities and those of their arguments. The dissertation presents a new approach, which not only combines the two approaches above, but also shows how they are directly mutually related, and how some quantificational properties can be derived from the domain of decomposition. Show less
The female cones of hop (Humulus lupulus L.) are added to beer, providing taste and flavour and contributing to the stability of foam. The main constituents of hop related to these properties are... Show moreThe female cones of hop (Humulus lupulus L.) are added to beer, providing taste and flavour and contributing to the stability of foam. The main constituents of hop related to these properties are generically known as alpha-acids. During the brewing process, these acids are isomerized, resulting in the formation of three pairs of trans-/cis-iso-alpha–acids. The aim of this thesis project was to develop a method for the analysis (Chapter 2 and 7) as well as the purification of iso-alpha-acids (Chapter 3-5). Moreover, the stability of iso-α-acids need to be improved (Chapter 6) since these compounds degrade easily in the light and in the presence of oxygen. We have shown that β-CD is effective to separate cis-isomers from trans-isomers and at the same time increases the stability of the complexed compounds. The pure individual iso-alpha-acids can now be produced from pure alpha-acids, obtained from a CPC separation, followed by isomerization and beta-CD separation of the two isomers. These compounds can be used as reference standard for analytical purposes to replace the DCHA-salts of trans-iso-alpha-acids. It also opens the possibility to use pure iso-alpha-acids in brewery research. An HPLC system using these pure individual iso-alpha-acids as calibration standard was developed as well. The application of 2D J resolved NMR has been developed and seems promising to detect a wide range of compounds in beer. Show less
