Sotos syndrome is a childhood overgrowth disorder which is characterised by an increased statural height and/or head circumference, characteristic facial dysmorphism and a variable level of... Show moreSotos syndrome is a childhood overgrowth disorder which is characterised by an increased statural height and/or head circumference, characteristic facial dysmorphism and a variable level of learning disability. The aim of this study was to perform a comprehensive study of Sotos syndrome and it__s molecular background. Therefore, the following three yet unresolved topics were addressed: 1. The molecular basis and mechanisms of the microdeletions in Sotos syndrome. 2. The causative molecular alterations in patients with features of Sotos syndrome but without NSD1 abnormalities. 3. The signaling pathways and downstream effectors of NSD1. Show less
Stars like our Sun are formed in large, tenuous clouds of gas and dust. As the star is formed at the centre, the remaining material collapses into a thick disk around it. The chemical composition... Show moreStars like our Sun are formed in large, tenuous clouds of gas and dust. As the star is formed at the centre, the remaining material collapses into a thick disk around it. The chemical composition of such a cloud changes dramatically during this process. Spherical models have always been used to model this chemical evolution, but they cannot properly describe the disk. This thesis presents the first model that follows the entire chemical evolution from a pre-stellar core to a circumstellar disk in two spatial dimensions. It follows material as it falls in from the cloud to the star and disk. The density, temperature and UV flux along these trajectories serve as input for a gas-phase chemical network -- including freeze-out onto and evaporation from cold dust grains. The model offers new insights into the chemical history of disks, in particular of the region where planets and comets are formed. Applications of the model include the gas/ice ratios of carbon monoxide and water (Chapter 2), the abundances of key gas-phase molecules (Chapter 3), the crystallinity of the dust (Chapter 4), the isotope-specific photodissociation of carbon monoxide (Chapter 5) and the charge balance of polycyclic aromatic hydrocarbons (PAHs; Chapter 6). Show less
