Model of large scale man-machine systems with an application to vessel traffic control

Mathematical models are discussed to deal with complex large-scale man-machine systems such as vessel (air, road) traffic and process control systems. Only interrelationships between subsystems are assumed. Each subsystem is controlled by a corresponding human operator (HO). Because of the interaction between subsystems, the HO has to estimate the state of all relevant subsystems and the relationships between them, based on which he can decide and react. This nonlinear filter problem is solved by means of both a linearized Kalman filter and an extended Kalman filter (in case state references are unknown and have to be estimated). The general model structure is applied to the concrete problem of vessel traffic control. In addition to the control of each ship, this involves collision avoidance between ship

In vivo modelling of Ewing sarcoma in zebrafish

Ewing sarcoma (EWS) is a disease with a high need for novel therapeutic strategies. To aid in investigating such compounds in an in vivo setting, we have developed several zebrafish model systems for EWS, which are presented in this thesis. The first is a manual xenograft model in 2-day-old zebrafish embryos, in which cell behaviour on the level of proliferation and migration has been described, as well as their interaction with the host innate immunesystem. With this model, we found that simultaneous induction of the p53 pathway and disruption of EWS-FLI1 transcriptional activity had an additive effect on the reduction of EWS malignancy in vivo. The same model was used to explore the mechanism of NOTCH-induced tumour suppression, via Sirtuin1 (SIRT1) inhibition. In addition to this manual xenograft model, we also established a high-throughput automated implantation model in blastula stage embryos. Furthermore, a flexible transgenic model has been developed, where human EWSR1-ERG expression has been placed under an UAS promoter, allowing the gene to be expressed in different tissues at different times. When this EWS-driving fusiongene was expressed neuronally, overlap in gene and protein expression was found with other EWS models, as well as a histologic similarity to EWS tumours.Research funded by Stichting Kinderen KankervrijAnimal science

Enantiomer separation using membrane systems

Many compounds applied in the agrochemical, food and pharmaceutical industry contain one or more chiral centers. The enantiomers of these compounds often have different effects on their targets. To prevent unwanted side effects or environmental burden, these compounds should rather be applied in their optically pure form. In this thesis two processes for large-scale enantiomer separations have been studied based on membrane technology: direct separation using an "intrinsic" enantioselective membrane and indirect separation in which a non-selective membrane assists an enantioselective process.For intrinsic enantioselective membranes the design criteria have been evaluated, using literature data, model calculations and experimental data. This has resulted in a categorization of these membranes into two different classes: diffusion selective membranes and sorption selective membranes.Besides intrinsic enantioselective membranes, a new stacked membrane system is developed using chiral selectors that are retained by size-selective membranes. Applying an electrical potential, selective transport of the free enantiomer will occur, thus providing separation. This separation concept is evaluated for different process conditions, showing a distinct influence of the pH. Isothermal titration calorimetry is used to compare this pH dependency of the operational selectivity and the intrinsic selector selectivity, showing no influence of the process.In the last part of this thesis a model is developed for the continuous multi-stage electrodialysis system. This model is evaluated using a 20-compartment counter-current electrodialysis stack. Model calculations have shown that using an electrodialysis stack of 250 membrane compartments allows for complete separation (99%+) for our low selective (α=1.12) model system. In conclusion, the proposed multi-stage electrodialysis separation principle, which has the advantage of making use of chiral selectors developed for existing analytical separation methods, is suitable for low selectivity (1.1-2) separations. Therefore, it provides a viable addition for the current range of large-scale enantiomer separation processe

Development of a new wheelchair for wheelchair basketball players in the Netherlands

AbstractThe aim of the development of a new basketball wheelchair was to reduce the weight of the frame, to develop a program to fit anthropometric measurements to design a custom made wheelchair and to develop high-end wheels to increase propulsion efficiency by reducing rolling resistance. The redesigning process resulted in a frame which is 30% lighter than current aluminium wheelchair frames, a program that links anthropometric data to a CAD model of wheelchairs and a new wheel. Several tests were performed to evaluate the new wheelchair. The tests showed promising results with respect to improving both technical performance combined with the athlete's performance

Ultramafic geoecology of South and Southeast Asia

Globally, ultramafic outcrops are renowned for hosting floras with high levels of endemism, including plants with specialised adaptations such as nickel or manganese hyperaccumulation. Soils derived from ultramafic regoliths are generally nutrient-deficient, have major cation imbalances, and have concomitant high concentrations of potentially phytotoxic trace elements, especially nickel. The South and Southeast Asian region has the largest surface occurrences of ultramafic regoliths in the world, but the geoecology of these outcrops is still poorly studied despite severe conservation threats. Due to the paucity of systematic plant collections in many areas and the lack of georeferenced herbarium records and databased information, it is not possible to determine the distribution of species, levels of endemism, and the species most threatened. However, site-specific studies provide insights to the ultramafic geoecology of several locations in South and Southeast Asia. The geoecology of tropical ultramafic regions differs substantially from those in temperate regions in that the vegetation at lower elevations is generally tall forest with relatively low levels of endemism. On ultramafic mountaintops, where the combined forces of edaphic and climatic factors intersect, obligate ultramafic species and hyperendemics often occur. Forest clearing, agricultural development, mining, and climate change-related stressors have contributed to rapid and unprecedented loss of ultramafic-associated habitats in the region. The geoecology of the large ultramafic outcrops of Indonesia’s Sulawesi, Obi and Halmahera, and many other smaller outcrops in South and Southeast Asia, remains largely unexplored, and should be prioritised for study and conservation