Transcriptional Profiling of Human Brain Endothelial Cells Reveals Key Properties Crucial for Predictive In Vitro Blood-Brain Barrier Models

Brain microvascular endothelial cells (BEC) constitute the blood-brain barrier (BBB) which forms a dynamic interface between the blood and the central nervous system (CNS). This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local surroundings of BEC within the neurovascular unit are presented and discussed

The Structure and Delivery of Police Use of Force Training: A German Case Study

The current study aims to investigate the current structure and delivery of police recruit training. Using a case study approach, we systematically observed a semester of police training that consisted of 30 h with a specific focus on police use of force training. Field notes and time-on-task data was analysed using an inductive approach. The results revealed, first, a lack of constructive alignment of the training modules and learning tasks within the training settings. Second, an adherence to traditional linear approaches to training resulting in high amounts of augmented instruction and feedback and a one-size-fits all approach to technical and tactical behaviour. Third, a non-efficient use of available training time with low amounts of engagement in representatively designed tasks that stimulated problem-solving processes. Based on these results we suggest that there is a need: (a) for police trainers and curriculum designers to align the objectives, practice structure and delivery of police training with the needs of police officers in the field (e.g. conflict resolution); (b) for police trainers to employ more learner-centred pedagogical approaches that account for individual action capabilities and resources, and allow for high amounts of training time with representatively designed training tasks; and (c) for senior managers of overall police training decision-makers to provide the necessary trainer education, in order to furnish trainers with the knowledge and tools to appropriately plan, deliver and reflect upon their practice in keeping with concept of constructive alignment

Educational design research

Educational design research is a genre of research in which the iterative development of solutions to practical and complex educational problems provides the setting for scientific inquiry. The solutions can be educational products, processes, programs, or policies. Educational design research not only targets solving significant problems facing educational practitioners but at the same time seeks to discover new knowledge that can inform the work of others facing similar problems. Working systematically and simultaneously toward these dual goals is perhaps the most defining feature of educational design research. This chapter seeks to clarify the nature of educational design research by distinguishing it from other types of inquiry conducted in the field of educational communications and technology. Examples of design research conducted by different researchers working in the field of educational communications and technology are described. The chapter concludes with a discussion of several important issues facing educational design researchers as they pursue future work using this innovative research approach