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NASA assembled a cross-organizational multidisciplinary “radical” project team combining a diverse set of skills including aircraft architecture modelling and optimization, advanced material science, and engineering of high performance cryogenic, thermal management and fuel cell systems components and subsystems to tackle the challenging problem of development of commercially viable mid-size aircraft that would radically transform air transportation. Our team is developing an integrated conceptual and experimental methodology to realize a medium-range hydrogen aircraft design based on fuel cells, hydrogen burning engines, advanced power management and distribution, cryogenic hydrogen storage systems, and novel thermal management systems combined with an integrated aircraft concept of operations both during the flight and at the airports. The resulting analyses suggested the aircraft architecture options, sizes and layouts for the propulsion subsystem and cryogenic liquid hydrogen (LH2) tankage to verify the weight-scaling relationships for a medium-range aircraft carrying 100-200 passengers flying 1000 - 5000 km. Hydrogen - based distributed electric propulsion and cryogenic systems were further analysed, and more detailed study identified systems goals for a viable overall system weight for missions of various lengths. The developed aircraft architecture is being optimized by total specific energy density, specific power, size and mission profiles.