In this thesis we have studied the influence of emotion on learning. We have used computational modelling techniques to do so, more specifically, the reinforcement learning paradigm. Emotion is... Show moreIn this thesis we have studied the influence of emotion on learning. We have used computational modelling techniques to do so, more specifically, the reinforcement learning paradigm. Emotion is modelled as artificial affect, a measure that denotes the positiveness versus negativeness of a situation to an artificial agent in a reinforcement learning setting. We have done a range of different experiments to study the effect of affect on learning, including the effect on learning if affect is used to control the exploration behaviour of the agent and the effect on learning when affect is communicated by a human (though real-time analysis of that human__s facial expressions) to a simulated robot. We conclude that affect is a useful concept to consider in adaptive agents that learn based on reinforcement learning and that in some cases affect can indeed help the learning process. Further, affective modelling in this way can help understand the psychological processes that underlie influences of affect on cognition. Finally, we have developed a formal notation for a specific type of emotion theory, i.e., cognitive appraisal theory. Show less
This thesis describes the design and realization of a small-cantilever AFM, and the application of this instrument to the measurement of hydrophobic forces between nanoscopic surfaces.
This thesis describes the formation and physical properties of atomic chains consisting of metal atoms and incorporated small molecules. Small molecules like oxygen and hydrogen modify the... Show moreThis thesis describes the formation and physical properties of atomic chains consisting of metal atoms and incorporated small molecules. Small molecules like oxygen and hydrogen modify the electrical and mechanical properties of these wires, resulting in new one-dimensional conductors. Show less
The aim of the studies described in this thesis was the functional analysis of JA-responsive transcription factors in Arabidopsis with an emphasis on the interaction with the promoters of their... Show moreThe aim of the studies described in this thesis was the functional analysis of JA-responsive transcription factors in Arabidopsis with an emphasis on the interaction with the promoters of their target genes. In short, the following new results were obtained. The promoter of the PDF1.2 gene contains at least two functionally equivalent GCC boxes instead of one as reported earlier (Brown et al., 2003). The JA biosynthesis genes AOC1 and AOC2 are direct target genes of ORA47, corroborating the notion that ORA47 controls JA biosynthesis via regulation of the biosynthesis genes (Pr_, 2006). JA controls ORA59 activity by promoting the nuclear localization and stabilization of the protein. JA-responsive nuclear localization is independent of the jasmonate receptor COI11, indicating the existence of an alternative jasmonate receptor. The JRE from the ORCA3 promoter is active in Arabidopsis and its activity is controlled by the bHLH transcription factor AtMYC2, suggesting that a related bHLH protein controls ORCA3 gene expression in Catharanthus. Show less
The general aim of the work described in this thesis is to help explain the variation in ageing by using the life history framework of B. anynana. Each chapter focuses on a different aspect of the... Show moreThe general aim of the work described in this thesis is to help explain the variation in ageing by using the life history framework of B. anynana. Each chapter focuses on a different aspect of the life history, together giving a complete picture of the origins of variation in ageing in this species. A central theme to every chapter is the relative influence of genes, the environment, and how they related to plasticity. A summarising discussion of all chapters, and a perspective on how the ideas in this thesis will contribute to ageing research in the future is also included. Show less
Starburst galaxies undergo a phase of vigorous star formation. In these galaxies, gas is turned into stars at such a high rate, that the reservoir of available gas is quickly emptied. Numerous... Show moreStarburst galaxies undergo a phase of vigorous star formation. In these galaxies, gas is turned into stars at such a high rate, that the reservoir of available gas is quickly emptied. Numerous massive, bright star clusters are created from the giant molecular clouds. They form an ideal laboratory for the study of rapid star formation. In this thesis, a detailed study of active star-forming regions in the starburst galaxies NGC 4038/4039 and M83 is presented. Sincethe stars are hidden from view by large quantities of dust, we observe them at infrared wavelengths. We address the properties of the newly formed star clusters and the surrounding interstellar matter. Show less
In developmental biology, the expression of genes is studied to understand development, phenotypes and to construct models to understand disease. In this thesis, we explore and validate biological... Show moreIn developmental biology, the expression of genes is studied to understand development, phenotypes and to construct models to understand disease. In this thesis, we explore and validate biological as well as computerized tools, to address research questions in developmental biology. Based on these techniques, we developed a workflow to generate a large number of 3D spatio-temporal patterns of gene expression. Though several techniques for gene expression analysis are available, most spatial gene expression data are only in 2D. In order to study gene expression and differentiation of structures during development at the same time, both spatial 3D information, and temporal data are essential. These spatio-temporal patterns of gene expression have to be generated. To that end, we have developed a workflow based on fluorescent in situ hybridization (FISH) (ZebraFISH;), confocal laser scanning microscopy (CLSM) and subsequent three-dimensional modeling with, in our case, TDR-3Dbase software- resulting in a large amount of 3D spatio-temporal patterns of gene expression, obtained in a straightforward and non-destructive manner. In the work described in this thesis, we applied the workflow to 30 genes in 5 developmental processes. 3D modeling and data mining software are used to analyse gene expression patterns in zebrafish embryos and across species Show less
The formation of complex organic molecules that consist of more than four atoms in space is one of the main questions in the field of astrochemistry and star formation. Although the exact formation... Show moreThe formation of complex organic molecules that consist of more than four atoms in space is one of the main questions in the field of astrochemistry and star formation. Although the exact formation mechanisms are not yet known, they are expected to form in thin ice layers on the surfaces of small interstellar dust grains through successive addition of H, C, N or O atoms to CO (carbon monoxide). In this thesis the formation of these molecules is studied in two different ways: simulation of interstellar ices analogues in the laboratory and observations of the same molecules after evaporation toward star forming regions. The laboratory experiments are high and ultra high vacuum setups in which ices of e.g. CO, CO2, HCOOH and CH3CHO are frozen out on an inert surface. The spectroscopy and the thermal behavior of pure and layered ices have been studied. Furthermore, the ices have been bombarded with H-atoms to test reactions schemes relevant for astronomical environments. In the second part of this thesis the same molecules have been observed with the single dish submillimeter telescopes the __James Clerk Maxwell Telescope__ at Hawaii and the Institut de Radioastronomie Millim_trique in Spain toward a sample star forming regions as well as with interferometer the SubMillimeter Array at Hawaii toward two sources. The relative abundances of molecules in different star forming regions measured with the single dish telescopes as well as the spatial extent of the emission detected with the interferometer has been used to determine the chemical relations between complex organics that have also been studied in the laboratory. Show less
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
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
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
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
In this thesis we study the dust around solar-type young stars. In particular, we focus on one specific species of dust, namely the Polycyclic Aromatic Hydrocarbons (PAHs), a family of large... Show moreIn this thesis we study the dust around solar-type young stars. In particular, we focus on one specific species of dust, namely the Polycyclic Aromatic Hydrocarbons (PAHs), a family of large molecules, or small grains, that are widely observed in nearby star-forming regions. We address the following questions. What happens to PAHs in the embedded phase of a forming star? Are PAHs present in low-mass young star systems? Does the PAH emission originate from the envelope or from the disk? What do they tell us about disk structure and evolution and grain growth? What can we say about the evolution of PAHs during star formation and their typical size? We present mid-infrared spectroscopy and imaging surveys combined with 3D radiative transfer models to constrain the presence and location of PAH emission toward embedded young stellar objects and circumstellar disks around young solar-type stars. PAHs are detected toward a small fraction (11-14%) of young solar-type stars with disks and toward a minority of embedded objects (<3%), with derived abundances of 10-100 times lower than standard interstellar values. A new class of disks with weak mid-IR continuum emission and very strong PAH features is found. Show less
Gold nanoparticles are spherical clusters of gold atoms, with diameters typically between 1 and 100 nanometers. The applications of these particles are rather diverse, from optical labels for... Show moreGold nanoparticles are spherical clusters of gold atoms, with diameters typically between 1 and 100 nanometers. The applications of these particles are rather diverse, from optical labels for biological experiments to data carrier for optical data storage. The goal of my project was to develop new methods to study the physical properties of single gold nanoparticles on ultra-short timescales. Exciation with a short laser pulse brings a nanoparticle out of equilibrium, which makes it vibrate with a period that depends on the particle diameter and the speed of sound in gold. The vibrational period of a gold nanoparticle with a diameter of 60 nanometer is 20 picoseconds. This acoustic vibration has been detected by us for the first time for single particles. The main advantage of single-particle studies over bulk detection of these particles lies in the fact that all particles in an ensemble vibrate at slightly different frequencies, which causes increased damping due to dephasing. The damping of the vibrations of single particles only depends on the elastic coupling between the particle and its environment, which offers the possibility of using these particles as mechanical nanosensors. Show less
Photosynthetic reaction centers (RCs) from plants, heliobacteria and green sulphur bacteria has been investigated with photochemically induced dynamic nuclear polarization (photo-CIDNP) MAS NMR. In... Show morePhotosynthetic reaction centers (RCs) from plants, heliobacteria and green sulphur bacteria has been investigated with photochemically induced dynamic nuclear polarization (photo-CIDNP) MAS NMR. In photosystem (PS) I of spinach, all signals appear negative which is proposed by a predominance of the three spin mixing (TSM) over the differential decay (DD) mechanism. There are contrasting magnetic-field dependence of photo-CIDNP of PSI and PSII. For PSII the optimal NMR enhancement factor of ~5000 is observed at 4.7 T, while the strongest light-induced signals of PSI are at 9.4 T. The simulations indicate that difference between bacterial RCs and plant PS I can be due to an increase of the exchange coupling between the donor and acceptor radicals. In the RCs of Chlorobium tepidum the spectra appear negative and can be tentatively assigned to two bacterio chlorophyll a molecules of the donor. The spectral pattern obtained from membrane fragments of Heliobacillus mobilis at 4.7 T, appear to be both positive and negative, which is similar to the pattern observed in the RCs of plant PSII and RCs of Rhodobacter sphaeroides R-26. However, unlike the other RCs, in this system, at 17.6 T, the positive signals undergo a sign change and appear negative. Show less
The goal of this thesis is to study charge transport phenomena in organic materials. This is done optically by means of single-moleculespectroscopy in a field-effect transistor based on a molecular... Show moreThe goal of this thesis is to study charge transport phenomena in organic materials. This is done optically by means of single-moleculespectroscopy in a field-effect transistor based on a molecular crystal.We present (in Chapter 2) a fundamental requirement for single-moleculespectroscopy concerning the energy levels of the guest molecule withrespect to the ones of the host molecule. Following this constraint, westudy (in Chapters 3 and 4) the photophysics of a new system forhigh-resolution spectroscopy at cryogenic temperatures, which consistsof dibenzoterrylene molecules inserted in a crystal of anthracene. Wethen characterise (in Chapter 5) the electrical properties of theanthracene field-effect transistor with 'conventional' methods. In Chapter 6, wefinally use the influence of an electric field on the spectroscopicproperties of fluorescent molecules to investigate locally the chargecarrier transport phenomena in a crystal of anthracene.The goal of this thesis is to study charge transport phenomena inorganic materials. This is done optically by means of single-moleculespectroscopy in a field-effect transistor based on a molecular crystal.We present (in Chapter 2) a fundamental requirement for single-moleculespectroscopy concerning the energy levels of the guest molecule withrespect to the ones of the host molecule. Following this constraint, westudy (in Chapters 3 and 4) the photophysics of a new system forhigh-resolution spectroscopy at cryogenic temperatures, which consistsof dibenzoterrylene molecules inserted in a crystal of anthracene. Wethen characterise (in Chapter 5) the electrical properties of theanthracene field-effect transistor with 'conventional' methods. In Chapter 6, wefinally use the influence of an electric field on the spectroscopicproperties of fluorescent molecules to investigate locally the chargecarrier transport phenomena in a crystal of anthracene.The goal of this thesis is to study charge transport phenomena inorganic materials. This is done optically by means of single-moleculespectroscopy in a field-effect transistor based on a molecular crystal.We present (in Chapter 2) a fundamental requirement for single-moleculespectroscopy concerning the energy levels of the guest molecule withrespect to the ones of the host molecule. Following this constraint, westudy (in Chapters 3 and 4) the photophysics of a new system forhigh-resolution spectroscopy at cryogenic temperatures, which consistsof dibenzoterrylene molecules inserted in a crystal of anthracene. Wethen characterise (in Chapter 5) the electrical properties of theanthracene field-effect transistor with 'conventional' methods. In Chapter 6, wefinally use the influence of an electric field on the spectroscopicproperties of fluorescent molecules to investigate locally the chargecarrier transport phenomena in a crystal of anthracene. Show less
From its origin at the center of a star to the edge, through the surrounding gas and dust in the distant galaxy, through the intergalactic medium, traveling billions of light years only to be... Show moreFrom its origin at the center of a star to the edge, through the surrounding gas and dust in the distant galaxy, through the intergalactic medium, traveling billions of light years only to be reflected by a mirror and captured by a detector; the little amount of light observed from galaxies in the early universe contains a wealth of historic information. This thesis concentrates on translating the luminosities and colors of distant galaxies to physical properties such as distance, mass, age of the stellar population, and dust content. Analyzing deep optical and infrared observations of distant (redshift z~2.5) galaxies, we learn that massive galaxies have on average redder colors than less massive galaxies, although simulations show that mass underestimates of star-forming galaxies are possible. Roughly half of the red galaxies at high redshift owe their color to an old, quiescent stellar population. The other half is still actively star-forming, but obscured by large columns of dust. The abundance of star-forming and quiescent galaxies is consistent with a model that assigns a key role to collisions between gas-rich disk galaxies involving quasar activity, and leaving red spheroids as remnants. However, this model does not reproduce the colors of dusty red galaxies. Show less
Atherosclerosis is a progressive disease of the large arteries characterized by lipid deposition, inflammation, cell death and fibrosis and it is the major cause of death in the Western world. In... Show moreAtherosclerosis is a progressive disease of the large arteries characterized by lipid deposition, inflammation, cell death and fibrosis and it is the major cause of death in the Western world. In this thesis new and experimental therapies against atherosclerosis are designed and tested. New targets for these therapies were identified by using a mouse model for atherosclerosis, the LDL receptor deficient mouse. We used micro-arrays to compare gene expression from mice with atherosclerosis to control mice and the following targets, all related to leukocyte migration and activation, were identified; CCR5, CXCR3, CD99, IL-16, OX-40 and CD127. Vaccines against CD99, IL-16 and CD127 were designed and tested. Specific antagonists of CCR5 and CXCR3 were used to block these molecules and a specific antibody against OX40 ligand was tested in LDL receptor deficient mice. The effects of these treatment strategies are described in the chapters of this thesis. In conclusion, modulation of leukocyte activation and migration provides an attractive possibility for future drug design in the field of atherosclerosis. Show less
