Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

Detecting drift from event streams of unpredictable business processes

Existing business process drift detection methods do not work with event streams. As such, they are designed to detect inter-trace drifts only, i.e. drifts that occur between complete process executions (traces), as recorded in event logs. However, process drift may also occur during the execution of a process, and may impact ongoing executions. Existing methods either do not detect such intra-trace drifts, or detect them with a long delay. Moreover, they do not perform well with unpredictable processes, i.e. processes whose logs exhibit a high number of distinct executions to the total number of executions. We address these two issues by proposing a fully automated and scalable method for online detection of process drift from event streams. We perform statistical tests over distributions of behavioral relations between events, as observed in two adjacent windows of adaptive size, sliding along with the stream. An extensive evaluation on synthetic and real-life logs shows that our method is fast and accurate in the detection of typical change patterns, and performs significantly better than the state of the art.