The design and synthesis of novel heterodinuclear complexes combining a DNA-cleaving agent and a DNA-targeting moiety

Cancer is a leading cause of death worldwide. Nowadays, the treatment of cancer by chemotherapy can consist of a combination of antitumor drugs. Nevertheless, chemotherapy is accompanied by serious side effects and intrinsic and acquired resistance to the drugs. This thesis describes the design and synthesis of novel potential antitumor drugs that combine two different mechanisms of action. One of the two active units is derived from cisplatin, which cured Lance Armstrong?s testicular cancer. This platinum compound is known to induce a distortion of the DNA helix upon binding, resulting in the death of the cancer cells. The second active moiety is based on Cu(3-Clip-Phen), which is a highly active nuclease agent. In other words, the platinum moiety act as an antitumor drug and as an anchor to DNA, while the copper unit cleaves the DNA strand in the close proximity of the platinum-DNA adducts. The two active units have been covalently coupled with a (in)flexible bridge aiming at a synergistic action of the two drugs. The cleaving activity of some of the complexes is higher compared to Cu(3-Clip-Phen). Moreover, three of the new complexes have been found to show equivalent or higher cytotoxicities compared to cisplatin or Cu(3-Clip-Phen).UBL - phd migration 201

Seasonal and site-specific variation in vapour and aerosol phase PAHs over Flanders (Belgium) and their relation with anthropogenic activities

Peer reviewe

TOWARDS FULLY AUTOMATED DIGITAL ALIBIS WITH SOCIAL INTERACTION

Digital traces found on local hard drives as a result of online activities have become very valuable in reconstructing events in digital forensic investigations. This paper demonstrates that forged alibis can be created for online activities and social interactions. In particular, a novel, automated framework is presented that uses social interactions to create false digital alibis. The framework simulates user activity and supports communications via email as well as instant messaging using a chatbot. The framework is evaluated by extracting forensic artifacts and comparing them with the results obtained from a human user study

Patient-Reported Adverse Events of Radiopharmaceuticals:Development and Validation of a Questionnaire

Introduction Radiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient's perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals. Objective The aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals. Methods Based on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events. Results Questions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association. Conclusion After validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research

New insights in dermatophyte research

Dermatophyte research has renewed interest because of changing human floras with changing socioeconomic conditions, and because of severe chronic infections in patients with congenital immune disorders. Main taxonomic traits at the generic level have changed considerably, and now fine-tuning at the species level with state-of-the-art technology has become urgent. Research on virulence factors focuses on secreted proteases now has support in genome data. It is speculated that most protease families are used for degrading hard keratin during nitrogen recycling in the environment, while others, such as Sub6 may have emerged as a result of ancestral gene duplication, and are likely to have specific roles during infection. Virulence may differ between mating partners of the same species and concepts of zoo- and anthropophily may require revision in some recently redefined species. Many of these questions benefit from international cooperation and exchange of materials. The aim of the ISHAM Working Group Dermatophytes aims to stimulate and coordinate international networking on these fungi

Interfacial tension and nucleation in mixtures of colloids and long ideal polymer coils

Mixtures of ideal polymers with hard spheres whose diameters are smaller than the radius of gyration of the polymer, exhibit extensive immiscibility. The interfacial tension between demixed phases of these mixtures is estimated, as is the barrier to nucleation. The barrier is found to scale linearly with the radius of the polymer, causing it to become large for large polymers. Thus for large polymers nucleation is suppressed and phase separation proceeds via spinodal decomposition, as it does in polymer blends.Comment: 4 pages (v2 includes discussion of the scaling of the interfacial tension along the coexistence curve and its relation to the Ginzburg criterion

Low Effective Dispersal of Asexual Genotypes in Heterogeneous Landscapes by the Endemic Pathogen Penicillium marneffei

Long-distance dispersal in microbial eukaryotes has been shown to result in the establishment of populations on continental and global scales. Such “ubiquitous dispersal” has been claimed to be a general feature of microbial eukaryotes, homogenising populations over large scales. However, the unprecedented sampling of opportunistic infectious pathogens created by the global AIDS pandemic has revealed that a number of important species exhibit geographic endemicity despite long-distance migration via aerially dispersed spores. One mechanism that might tend to drive such endemicity in the face of aerial dispersal is the evolution of niche-adapted genotypes when sexual reproduction is rare. Dispersal of such asexual physiological “species” will be restricted when natural habitats are heterogeneous, as a consequence of reduced adaptive variation. Using the HIV-associated endemic fungus Penicillium marneffei as our model, we measured the distribution of genetic variation over a variety of spatial scales in two host species, humans and bamboo rats. Our results show that, despite widespread aerial dispersal, isolates of P. marneffei show extensive spatial genetic structure in both host species at local and country-wide scales. We show that the evolution of the P. marneffei genome is overwhelmingly clonal, and that this is perhaps the most asexual fungus yet found. We show that clusters of genotypes are specific to discrete ecological zones and argue that asexuality has led to the evolution of niche-adapted genotypes, and is driving endemicity, by reducing this pathogen's potential to diversify in nature