BackgroundCardiotoxicity, characterized by severe cardiac dysfunction, is a major problem in patients treated with different classes of anticancer drugs. Development of predictable human-based... Show moreBackgroundCardiotoxicity, characterized by severe cardiac dysfunction, is a major problem in patients treated with different classes of anticancer drugs. Development of predictable human-based models and assays for drug screening are crucial for preventing potential drug-induced adverse effects. Current animal in vivo models and cell lines are not always adequate to represent human biology. Alternatively, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show great potential for disease modelling and drug-induced toxicity screenings. Fully automated high-throughput screening of drug toxicity on hiPSC-CMs by fluorescence image analysis is, however, very challenging, due to clustered cell growth patterns and strong intracellular and intercellular variation in the expression of fluorescent markers.ResultsIn this paper, we report on the development of a fully automated image analysis system for quantification of cardiotoxic phenotypes from hiPSC-CMs that are treated with various concentrations of anticancer drugs doxorubicin or crizotinib. This high-throughput system relies on single-cell segmentation by nuclear signal extraction, fuzzy C-mean clustering of cardiac α-actinin signal, and finally nuclear signal propagation. When compared to manual segmentation, it generates precision and recall scores of 0.81 and 0.93, respectively.ConclusionsOur results show that our fully automated image analysis system can reliably segment cardiomyocytes even with heterogeneous α-actinin signals. Show less
By training with virtual opponents known as computer generated forces (CGFs), trainee fighter pilots can build the experience necessary for air combat operations, at a fraction of the cost of... Show moreBy training with virtual opponents known as computer generated forces (CGFs), trainee fighter pilots can build the experience necessary for air combat operations, at a fraction of the cost of training with real aircraft. In practice however, the variety of CGFs is not as wide as it can be. This is largely due to a lack of behaviour models for the CGFs. In this thesis we investigate to what extent behaviour models for the CGFs in air combat training simulations can be automatically generated, by the use of machine learning.The domain of air combat is complex, and machine learning methods that operate within this domain must be suited to the challenges posed by the domain. Our research shows that the dynamic scripting algorithm greatly facilitates the automatic generation of air combat behaviour models, while being sufficiently flexible to be moulded into answers to the challenges. However, ensuring the validity of the newly generated behaviour models remains to be a point of attention for future research. Show less
