Sporadic Creutzfeldt-Jakob disease prion infection of human cerebral organoids

For the transmissible, neurogenerative family of prion diseases, few human models of infection exist and none represent structured neuronal tissue. Human cerebral organoids are self-organizing, three-dimensional brain tissues that can be grown from induced pluripotent stem cells. Organoids can model aspects of neurodegeneration in Alzheimer's Disease and Down's Syndrome, reproducing tau hyperphosphorylation and amyloid plaque pathology. To determine whether organoids could be used to reproduce human prion infection and pathogenesis, we inoculated organoids with two sporadic Creutzfeldt-Jakob Disease prion subtypes. Organoids showed uptake, followed by clearance, of the infectious inoculum. Subsequent re-emergence of prion self-seeding activity indicated de novo propagation. Organoid health assays, prion titer, prion protein electrophoretic mobility and immunohistochemistry demonstrated inoculum-specific differences. Our study shows, for the first time, that cerebral organoids can model aspects of human prion disease and thus offer a powerful system for investigating different human prion subtype pathologies and testing putative therapeutics

Comparing Redundant and Sky-model-based Interferometric Calibration: A First Look with Phase II of the MWA

© 2018. The American Astronomical Society. All rights reserved.. Interferometric arrays seeking to measure the 21 cm signal from the epoch of reionization (EOR) must contend with overwhelmingly bright emission from foreground sources. Accurate recovery of the 21 cm signal will require precise calibration of the array, and several new avenues for calibration have been pursued in recent years, including methods using redundancy in the antenna configuration. The newly upgraded Phase II of Murchison Widefield Array (MWA) is the first interferometer that has large numbers of redundant baselines while retaining good instantaneous UV coverage. This array therefore provides a unique opportunity to compare redundant calibration with sky-model-based algorithms. In this paper, we present the first results from comparing both calibration approaches with MWA Phase II observations. For redundant calibration, we use the package OMNICAL and produce sky-based calibration solutions with the analysis package Fast Holographic Deconvolution (FHD). There are three principal results: (1) We report the success of OMNICAL on observations of ORBComm satellites, showing substantial agreement between redundant visibility measurements after calibration. (2) We directly compare OMNICAL calibration solutions with those from FHD and demonstrate that these two different calibration schemes give extremely similar results. (3) We explore improved calibration by combining OMNICAL and FHD. We evaluate these combined methods using power spectrum techniques developed for EOR analysis and find evidence for marginal improvements mitigating artifacts in the power spectrum. These results are likely limited by the signal-to-noise ratio in the 6 hr of data used, but they suggest future directions for combining these two calibration schemes

Enhancing Entrepreneurship and Professionalism in Medical Informatics Instruction: A Collaborative Training Model

This report describes an innovative training program designed to foster entrepreneurship and professionalism in students interested in the field of medical informatics. The course was developed through a private–public interinstitutional collaboration involving four academic institutions, one private firm specializing in health care information management systems, and a philanthropic organization. The program challenged students to serve in multiple roles on multidisciplinary teams and develop an innovative hand-held solution for drug information retrieval. Although the course was technically and behaviorally rigorous and required extensive hands-on experience in a nontraditional learning environment, both students and faculty responded positively