Membrane tubes are ubiquitous within cells. They have a diameter of approximately 50 nanometers, and are formed when a sufficiently large localized force is exerted on a membrane. Important... Show moreMembrane tubes are ubiquitous within cells. They have a diameter of approximately 50 nanometers, and are formed when a sufficiently large localized force is exerted on a membrane. Important generators of this force are the motor proteins that can move along cytoskeletal filaments. We studied membrane tube formation by motor proteins from giant vesicles in an in vitro reconstituted system, and showed that motor proteins can dynamically associate to form clusters that work together. In addition, the physical parameters that determine the force required to form tubes were examined, and it was found that the force barrier for tube formation increases with the area the pulling force is exerted on. Finally, some first results are presented on the competition between motor proteins of opposite directionality. Our findings suggest regulatory mechanisms that may be used for the intracellular spatial organization of membranes. Show less
Schistosomiasis (Bilharzia) is a tropical parasitic disease caused by schistosomes. At present more than 200 million people are infected by these parasites. If the infection is left untreated, the... Show moreSchistosomiasis (Bilharzia) is a tropical parasitic disease caused by schistosomes. At present more than 200 million people are infected by these parasites. If the infection is left untreated, the parasites can survive within the body for 5 years or more. The parasite has developed r escape mechanisms to escape the immune response of its host. The production by the parasite of heavily glycosylated proteins and lipids is thought to play an important role in this. One important carbohydrate structure expressed in all stages is the trisaccharide Lewis X (Le^x). By measuring the interaction with mono-, di-, and trimeric Lex of antibodies both in vitro and in vivo it has become clear that the humoral immune response to the various oligomeric forms of Le^x is different. This can now be taken into account in further studies in which the humoral and cellular immunogenicity of Le^x is investigated. Next, the elucidation of the crystal structure of a monoclonal antibody in complex with Le^x has led to a better insight in protein-carbohydrage interactions on the molecular level. This new knowledge can be used for further improvement of diagnostic techniques for schistosomiasis, and also for a better understanding of this and other diseases in which Le^x plays a role (e.g. cancer). Show less
Besides the features of a class-based object-oriented language, Java integrates concurrency via its thread classes, allowing for a multithreaded flow of control. The concurrency model includes... Show moreBesides the features of a class-based object-oriented language, Java integrates concurrency via its thread classes, allowing for a multithreaded flow of control. The concurrency model includes shared-variable concurrency via instance variables, coordination via reentrant synchronization monitors, synchronous message passing, and dynamic thread creation. To reason about safety properties of multithreaded Java programs, we introduce a tool-supported assertional proof method for JavaMT ("Multi-Threaded Java"), a small sublanguage of Java, covering the mentioned concurrency issues as well as the object-based core of Java. The verification method is formulated in terms of proof-outlines, where the assertions are layered into local ones specifying the behavior of a single instance, and global ones taking care of the connections between objects. We establish the soundness and the completeness of the proof system. From an annotated program, a number of verification conditions are generated and handed over to the interactive theorem prover PVS. Show less
The thesis is based on a decade of research in Cameroon, with several rounds of interviews at all stages of the rattan production chain, from the forest to the consumer. One of the findings was... Show moreThe thesis is based on a decade of research in Cameroon, with several rounds of interviews at all stages of the rattan production chain, from the forest to the consumer. One of the findings was that this chain is relatively short: few middlemen on the product flow producer-workshop-customer. Rattan is not produced on plantations but cut in relatively intact forests close to villages and then transported to town. It is transformed into furniture, utilities or artwork in very small workshops, with very simple tools. There is little innovation in design, hardly any marketing effort and virtually no export. Income from rattan and number of jobs created is modest, though the impact on some individuals is distinctly positive. This contrasts with the situation in The Philippines, where the rattan sector is well d eveloped and creates much employment and foreign exchange. In the Philippines, however, exploitation has been unsustainable, and the sector has to face serious shortages and problems related to import of unprocessed rattan. The ecological impact of rattan cutting in Cameroon is currently not alarming, due to the weaknesses of the sector, but care should be taken to prevent resource scarcity. Little evidence was found of the hypothesized contribution of this non-timber forest product to halt deforestation, both in Cameroon and in The Philippines. The thesis ends with recommendations on the sustainable development of the rattan sector. Show less
There are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain.... Show moreThere are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain. However, treatment is difficult since many drugs cannot reach the brain in sufficient quantities due to the existence of the blood-brain barrier (BBB). This barrier is situated at the interface of blood and brain and its primary function is to maintain the homeostasis of the brain. The research described in this thesis was initiated to meet the challenge of drug delivery across the BBB. The focus was to explore the possibilities for drug delivery to the brain via the transferrin receptor (TfR). Although drug delivery to the brain via the TfR is not selective, it is effective. A mechanistic approach was chosen in which the binding and association of Tf, Tf-drug conjugates and Tf-tagged liposomes by BCEC in vitro was determined. The efficiency of delivery depends mainly on the size of the cargo: a 40 kDa protein does not affect the association of Tf by the TfR, while a liposomal drug carrier (100 nm in diameter) affects both the association and the intracellular routing. Show less
The ecological compensation principle was introduced in the Dutch Structural Scheme for the Rural Areas (1993). The principle aims to enhance the input of natural conservation interests in... Show moreThe ecological compensation principle was introduced in the Dutch Structural Scheme for the Rural Areas (1993). The principle aims to enhance the input of natural conservation interests in decision-making on large development projects and to counterbalance the adverse impacts of such projects when implemented. The thesis describes the process of implementing the ecological compensation principle within the Directorate-General of Public Works and Water Management (Rijkswaterstaat) as initiator of highway projects. Additionally, it has developed a theoretical and practical framework for ecological compensation. Ecological compensation and related issues have been investigated in the different stages of planning, decision-making and realisation of highway projects. The thesis' leading element is the incentive-based character of compensating for impacts according to the Structural Scheme. This implies the parties involved are obliged to reach agreement on finding and realising compensation sites. Besides some specific conditions, there is still no legislation that facilitates the initiatiors' acquisition of lands for compensation purposes. Show less
