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ABSTRACT As the International Space Station comes to the end of a transformative era of in-space research, NASA’s Commercial Low Earth Orbit (LEO) Destinations (CLD) Program aims to catalyze a new generation of platforms with co-investment from the private sector, preventing a potential gap in research performed in LEO, while building a robust LEO economy. In this paper, we provide insight into the CLD Program focusing on Orbital Reef, describing its operational and technical characteristics as well as new opportunities it may enable. Achieving about a third of the pressurized volume of the ISS with the launch of a single pressurized module and growing to support hundreds of Middeck Locker Equivalents (MLE) in passive and active payloads internally and externally, Orbital Reef will enable government, academic, and commercial institutions to continue and expand upon research and development (R&D) efforts currently performed on ISS. Additionally, it will enable nascent markets to establish their operations in space, by initiating new lines of research and technology development and the implementation of new ventures and visions. Using Blue Origin’s New Glenn heavy launch system, Sierra Space’s cargo and crew Dream Chaser® vehicles, and Boeing’s Starliner crew vehicle, and expertise from Amazon/Amazon Supply Chain, Arizona State University, Genesis Engineering, and Redwire, Orbital Reef is being designed to address ISS-era transportation logistics challenges. Finally, this manuscript describes some of the expected challenges from the ISS-to-CLD transition, and provides guidance on how researchers in academia and industry can shape the future of commercial destinations and work performed in LEO.

Historically, the United States has been a world leader in aerospace endeavors in both the government and commercial sectors. A key factor in aerospace leadership is continuous development of advanced technology, which is critical to U.S. ambitions in space, including a human mission to Mars. To continue to achieve progress, NASA is currently executing a series of aeronautics and space technology programs using a roadmapping process to identify technology needs and improve the management of its technology development portfolio. NASA created a set of 14 draft technology roadmaps in 2010 to guide the development of space technologies. In 2015, NASA issued a revised set of roadmaps. A significant new aspect of the update has been the effort to assess the relevance of the technologies by listing the enabling and enhancing technologies for specific design reference missions (DRMs) from the Human Exploration and Operations Mission Directorate and the Science Mission Directorate. NASA Space Technology Roadmaps and Priorities Revisited prioritizes new technologies in the 2015 roadmaps and recommends a methodology for conducting independent reviews of future updates to NASA's space technology roadmaps, which are expected to occur every 4 years.

This paper illustrates an effective application of rapid prototyping (RP) to produce a high definition polymer model of a satellite structure prior to final machining of the aluminum panels. The benefits when using this type of model in the design and assembly stages of satellite fabrication make clear that RP can and should play an important role in the design and fabrication of small satellite structures. Selective laser sintering was utilized to produce a full-scale model of a novel modular small satellite structure. This model was then used as a tool for quality control, fit check, assembly process verification, mock-up, and as a model for manufacturing tooling design. This case study illustrates that the use of RP to create a model early in the design cycle is beneficial from a cost and time perspective even when applied to a product which will be produced in a quantity of one. In addition, the merits of RP mesh well with modular designs and for applications where assembly and test tooling is required to validate the quality of a product. This paper illustrates an effective use of RP in the satellite fabrication industry. The benefits described are generally applicable to other complex systems which need design validation early in the design cycle. There are few examples of the effective application of RP to produce models, but not the final product, of a complex structure in the satellite and other industries where small lot production occurs.

A new course design methodology has been created to aid instructors at The Aerospace Institute, the education and training division of The Aerospace Corporation. This methodology’s heritage is an approach described in \"The New Professor's Handbook\" by Dr. Cliff Davidson and Dr. 1 Susan Ambrose that compares planning a course with planning a research project. For The Aerospace Institute this analogy has been modified to an analogy between course design and systems engineering, which is a concept very familiar to its instructors. This paper walks through this methodology and offers suggestions for implementation that should be useful in a variety of educational environments. Examples are provided throughout to illustrate the concepts. The Aerospace Institute was established in July 1994 to integrate key corporate educational resources toward The Aerospace Corporation vision to be the world’s leader in space technology, planning and system engineering. Since then as a part of their charter, The Aerospace Institute has been developing and offering courses for company personnel as well as the U.S. Air Force, The Aerospace Corporation’s principal customer. One dilemma The Aerospace Institute has faced is how the wealth of technical expertise that is the corporation’s major asset can be translated into courses. Also as many of these courses have started into their second and third offerings, The Aerospace Institute has realized through firsthand experience that expertise in a subject, and even exceptional presentation skills, do not necessarily result in the ability to effectively teach a subject. To address these issues a methodology that embodies an analogy between course design and system engineering has been created. This methodology’s heritage is an approach described in \"The New Professor's Handbook\" by Dr. Cliff Davidson and Dr. Susan Ambrose that compares 1 planning a course with planning a research project. For The Aerospace Institute this analogy has been modified to an analogy between course design and systems engineering, which is a concept very familiar to the various instructors involved in The Aerospace Institute. The remainder of this paper will discuss this methodology. STEPS IN PLANNING A COURSE Analogies can be a powerful method to illustrate a concept, especially when they relate something an audience knows to something it doesn’t know. The dilemma with The Aerospace 1

Spacecraft design has gone from maximizing performance under technology constraints to minimizing cost under performance constraints. This is characteristic of the “faster, better, cheaper” movement that has emerged within NASA. Currently spacecraft are “optimized” manually through a tool-assisted evaluation of a limited set of design alternatives. With this approach there is no guarantee that a systems-level focus will be taken and “feasibility” rather than “optimality” is commonly all that is achieved. To improve spacecraft design in the “faster, better, cheaper” era, a new approach using multidisciplinary design optimization (MDO) is proposed. Using MDO methods brings structure to conceptual spacecraft design by casting a spacecraft design problem into an optimization framework. Then, through the construction of a model that captures design and cost, this approach facilitates a quicker and more straightforward option synthesis. The final step is to automatically search the design space. As computer processor speed continues to increase, enumeration of all combinations, while not elegant, is one method that is straightforward to perform. As an alternative to enumeration, genetic algorithms are used and find solutions by reviewing fewer possible solutions with some limitations. Both methods increase the likelihood of finding an optimal design, or at least the most promising area of the design space. This spacecraft design methodology using MDO is demonstrated on three examples. A retrospective test for validation is performed using the Near Earth Asteroid Rendezvous (NEAR) spacecraft design. For the second example, the premise that aerobraking was needed to minimize mission cost and was mission enabling for the Mars Global Surveyor (MGS) mission is challenged. While one might expect no feasible design space for an MGS without aerobraking mission, a counterintuitive result is discovered. Several design options that don't use aerobraking are feasible and cost effective. The third example is an original commercial lunar mission entitled Eagle-eye. This example shows how an MDO approach is applied to an original mission with a larger feasible design space. It also incorporates a simplified business case analysis.

Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.

The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis. The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05). Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota.

Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions.MethodsThe colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents.Results Helicobacter bilis–colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P < 0.05), whereas ASF360/361-positive bacteria were decreased (P < 0.05) versus controls. Adherent biofilms in colitic mice were most often (P < 0.05) composed of total bacteria, ASF457, and H. bilis. Total numbers of ASF519 and H. bilis bacteria were positively correlated (P = 0.03, r = 0.39 and P < 0.0001, r = 0.73), and total numbers of ASF360/361 bacteria were negatively correlated (P = 0.003, r = −0.53) to histopathologic score. Differences in cecal abundance of ASF members were not observed.ConclusionsAltered community structure with murine colitis is characterized by distinct ASF bacteria that interact with the colonic mucosa, by formation of an isolating interlaced layer, by attachment, or by invasion, and this interaction is differentially expressed over time.

Complex environmental factors influence the distribution of species within lotic systems. This is especially apparent for amphibian species that have a multi-year larval stage. Pre-metamorphic Coastal Tailed Frogs (Ascaphus truei) are found in fast-flowing headwater streams for up to four years. Although there is considerable opportunity for the spatial redistribution of larval frogs, there is relatively little known of the habitat ecology of the various growth stages. We compared the abundance of larvae near the northern extent of the species range to a collection of environmental factors hypothesized to influence population density. We also assessed spatial segregation at various developmental stages where relatively short summers and cool climates result in a long residence for larvae. The top ranked model for larvae abundance included covariates representing the wetted width and wetted depth of the stream. Capture rates decreased in a nonlinear fashion as wetted width increased, and rates increased in streams wider than 6 m. Capture rates nonlinearly increased when stream depth exceeded 20 cm. Older larvae were associated with greater slopes than younger larvae. Our results suggest little evidence for a relationship between elevation and cohort distribution. We recommend considering micro-scale influences on the presence and movement patterns of Coastal Tailed Frog larvae within streams.

The objective of the Coastal and Inland Flooding Observation and Warning (CI-FLOW) project is to prototype new hydrometeorologic techniques to address a critical NOAA service gap: routine total water level predictions for tidally influenced watersheds. Since February 2000, the project has focused on developing a coupled modeling system to accurately account for water at all locations in a coastal watershed by exchanging data between atmospheric, hydrologic, and hydrodynamic models. These simulations account for the quantity of water associated with waves, tides, storm surge, rivers, and rainfall, including interactions at the tidal/surge interface. Within this project, CI-FLOW addresses the following goals: i) apply advanced weather and oceanographic monitoring and prediction techniques to the coastal environment; ii) prototype an automated hydrometeorologic data collection and prediction system; iii) facilitate interdisciplinary and multiorganizational collaborations; and iv) enhance techniques and technologies that improve actionable hydrologic/hydrodynamic information to reduce the impacts of coastal flooding. Results are presented for Hurricane Isabel (2003), Hurricane Earl (2010), and Tropical Storm Nicole (2010) for the Tar–Pamlico and Neuse River basins of North Carolina. This area was chosen, in part, because of the tremendous damage inflicted by Hurricanes Dennis and Floyd (1999). The vision is to transition CI-FLOW research findings and technologies to other U.S. coastal watersheds.