Robotic Habitat Technologies for Minimizing Crew Maintenance Requirements

NASA’s Lunar Gateway aims to be deployed later in the decade and will serve as an outpost orbiting the moon. This habitat will be utilized as a base for lunar operations as well as future missions to Mars. Unlike the International Space Station (ISS), which maintains three to six astronauts at any given time, the Lunar Gateway will be uncrewed for eleven months out of the year. Over 80% of crew time onboard the ISS is dedicated to logistics, repair, and maintenance, leaving minimal time for scientific research and experimentation. In order to maintain Gateway, robotic systems must be implemented to accomplish maintenance and operational tasks. This paper discusses our team’s proposed dexterous robotic system, which will address routine and contingency operational and maintenance tasks on Gateway. The project is experimentally-based, and split into three approaches: cataloging robotic capabilities via robot/taskboard interactions, logistics management of Cargo Transfer Bags (CTBs), and software development of an AprilTag situational development system. This research project utilizes the unique capabilities of the University of Maryland (UMD) Space Systems Laboratory (SSL), which houses various dexterous robotic manipulators, mock-ups of space habitats, and the Neutral Buoyancy Research Facility (NBRF), a 50-foot diameter, 25-foot deep water tank used to simulate microgravity conditions. By incorporating robotic systems into the architecture of the Lunar Gateway, it will allow for the lunar outpost to be continually operated and maintained while uncrewed, and will allow for astronauts, when present, to focus on maximizing scientific discoveries.NASA RASC-AL 202

ROBOTIC TECHNOLOGIES FOR MINIMIZING CREW MAINTENANCE REQUIREMENTS IN SPACE HABITATS

Gemstone Team ASTROThe International Space Station (ISS) is crewed continuously by astronauts conducting scientifc research in microgravity. However, their work is not limited to scientifc research alone; in fact, logistics, maintenance, and repair tasks on the ISS require more than 80% of available crew time, severely limiting opportunities for performing scientifc experiments and technological development. NASA is planning a new project known as Gateway (also referred to as the Lunar Orbital Platform-Gateway). This station will orbit the Moon and be uncrewed for 11 months per year. Astronauts will only be present in the outpost for a limited period of time and will not always be available for continuous repairs and maintenance, as is required for Gateway to operate. Therefore, robotic system(s) are necessary to regularly accomplish these tasks both in the absence and presence of astronauts. Throughout this project, Team ASTRO (Assessment of Space Technologies for Robotic Operations) explored the feasibility of integrating dexterous robotic systems in space habitat architectures to perform routine and contingency operational and maintenance tasks. Ultimately, this allows for astronauts, when present, to focus on exploration and scientifc discoveries. The team conducted this research through three approaches: Gateway component analog taskboard development and end e˙ector assessment, Cargo Transfer Bag (CTB) manipulation and logistics, and AprilTag situational awareness simulation development. Based on analyses and experimental results gained from this research, the team found that robotic systems are feasible alternatives for space habitat operation. Team ASTRO also determined that AprilTags can be used for optimization of the Gateway design to facilitate uncrewed operations and robotic servicing to improve crew productivity when present

scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution.

BackgroundAdeno-associated virus (AAV)-mediated gene therapies are rapidly advancing to the clinic, and AAV engineering has resulted in vectors with increased ability to deliver therapeutic genes. Although the choice of vector is critical, quantitative comparison of AAVs, especially in large animals, remains challenging.MethodsHere, we developed an efficient single-cell AAV engineering pipeline (scAAVengr) to simultaneously quantify and rank efficiency of competing AAV vectors across all cell types in the same animal.ResultsTo demonstrate proof-of-concept for the scAAVengr workflow, we quantified - with cell-type resolution - the abilities of naturally occurring and newly engineered AAVs to mediate gene expression in primate retina following intravitreal injection. A top performing variant identified using this pipeline, K912, was used to deliver SaCas9 and edit the rhodopsin gene in macaque retina, resulting in editing efficiency similar to infection rates detected by the scAAVengr workflow. scAAVengr was then used to identify top-performing AAV variants in mouse brain, heart, and liver following systemic injection.ConclusionsThese results validate scAAVengr as a powerful method for development of AAV vectors.FundingThis work was supported by funding from the Ford Foundation, NEI/NIH, Research to Prevent Blindness, Foundation Fighting Blindness, UPMC Immune Transplant and Therapy Center, and the Van Sloun fund for canine genetic research

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

© 2020 Elsevier Ltd. All rights reserved.Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.info:eu-repo/semantics/publishedVersio