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NASA NTRS2021

Concept of Operations for OSIRIS-REx Optical Navigation Image Planning

Optical navigation (OpNav) is a critical subsystem of the OSIRIS-REx asteroid sample return mission, which operated in the vicinity of near-Earth asteroid (101955) Bennu from August 2018 through April 2021. A substantial amount of mission resources across multiple subsystems and institutions is required to ensure that the OpNav data are successfully acquired. The KinetX OpNav team, part of the Flight Dynamics System (FDS), is responsible for performing required analysis to develop the OpNav operations plans; requesting, reviewing and verifying the plans; and ultimately using the image data for critical navigation operations. The FDS team, responsible for the mission navigation, is operated by KinetX Aerospace with management and operations support from NASA’s Goddard Space Flight Center. The Science Processing and Operations Center (SPOC), located at the University of Arizona’s Lunar and Planetary Laboratory, is responsible for generating the planning products for all science and most OpNav data. These plans are integrated into the spacecraft sequences, tested, and commanded by the Mission Support Area (MSA) at Lockheed Martin Space. To ensure mission-critical navigation image data are successfully acquired, the plan is developed through a waterfall of planning cycles over the course of 3 months prior to onboard plan execution. During the initial strategic planning for a mission phase, detailed analysis is performed by the OpNav team to conceptualize the concept of operations (ConOps) for image data collection. This phase OpNav Narrative is included along with other strategic planning documents for the key ground segment stakeholders to review and provide feedback. The detailed OpNav plans get defined in the tactical planning cycle, which spans 8 to 3 weeks before the week-long integrated sequence is executed on-board the spacecraft. During the tactical cycle, the initial OpNav Request is submitted along with the science requests, kicking off development of the science and OpNav plans. Once the initial plan is drafted, interfaces are exercised so that the plan can be reviewed and iterated, if necessary. A rigorous schedule is followed by the planning teams during the implementation cycle, spanning the last 18 days before uplink, to ensure all the necessary integration, testing, and reviewing can occur on time. The development of the OpNav planning ConOps, including responsibilities, interfaces, timelines, and procedures, took extensive collaboration across mission elements and institutions. The process was robust throughout the 137 weeks of continuous Optical Navigation Operations at Bennu, which concluded on April 9th, 2021.

Coralie D. Adam↗

DOE OSTI2023

Stabilizing the Grid and Reducing Utility Bills Through Price-Responsive Controls for Heat Pump Water Heaters

The electricity grid is facing increasing challenges in cost-effectively balancing supply and demand. These challenges are exacerbated by increased penetration of photovoltaics, which causes mid-day overproduction, and electrification of gas appliances, which increases peak-period electricity demand. Decarbonization requires shifting building loads from fossil-intensive high-cost times to renewable-intensive low-cost times while maintaining quality of service to occupants. Utilities and ISO’s are investigating new ways of incentivizing this load shifting. One promising method is the use of Highly Dynamic Prices (HDPs). HDPs feature continuously changing prices that reflect real-time grid generation and distribution costs and capacity constraints, and thus incentivize consumers to shift their loads. California’s CPUC CalFUSE proposal and Hawaii’s recent changes demonstrate that electricity tariffs are moving towards this model. For this to work however, loads must have the capability to respond to these prices. Heat pump water heaters (HPWHs) are an ideal device for this purpose because their storage tanks decouple delivery of domestic hot water from electricity consumption. The storage enables control strategies that consume midday solar power to increase the energy stored in the tank, then provide evening peak domestic hot water services using the stored energy. Berkeley Lab's CalFlexHub project is pioneering price-driven load flexibility by developing and deploying cost-minimizing controls for many flexible loads - including HPWHs - in response to HDP. Control development is based on simulations using the Flexible Heat Pump Water Heater Performance Predictor which captures the control decisions of the on-board controller in a residential, integrated HPWH . The price-responsive controls a) shift load in ways that consume additional midday solar power to help stabilize the grid and reduce overall emissions, b) ensure that occupants receive equal or better hot water delivery service, and c) minimize the operating cost for each home in the fleet. On the grid level, the resulting shift will reduce utility operating costs and emissions, and can avoid expensive system capacity expansions. The control approach is customized to each home based on typical hot water consumption patterns. HPWH controllers, whether on the device or remotely, will receive a schedule of CTA-2045-B signals or set temperature adjustments customized to the current HDP price schedule and home. Simulation results for a fleet of 148 HPWHs on a summer day in Berkeley, California show cost savings of 29% and high price electricity consumption reductions of 80%, while maintaining full quality of service.

24 POWER TRANSMISSION AND DISTRIBUTION↗

DOE OSTI2021

Deep reinforcement learning for dynamic control of fuel injection timing in multi-pulse compression ignition engines

Conventional compression-ignition (CI) engines have long offered high thermal efficiencies and torque across a wide range of loads, but often require extensive exhaust gas treatment that decreases efficiency to meet ever-increasing emissions regulations. One strategy to decrease emissions is to split the fuel injection into a series of smaller injections. In this paper, we explore a new way of discovering optimal control strategies for the next generation of CI engines using deep reinforcement learning (DRL). We outline a DRL procedure to maximize the weighted reward of engine work while minimizing end-of-cycle NO x emissions. Through the procedure outlined in this paper, we show that the DRL agent is able to reduce NO x emissions threefold while only decreasing network by 2%. We demonstrate the use of transfer learning (TL) across hierarchies of physical models to accelerate the learning process, making this approach feasible for a range of control problems within this space. This paper presents a framework and demonstration for using DRL to design control systems in technology areas such as multi-pulse engine control where a hierarchy of models combined with multi-objective rewards are used for optimal operation.

33 ADVANCED PROPULSION SYSTEMS↗

NASA NTRS2020

In-flight Testing of the Injection of the LISA Pathfinder Test Mass into a Geodesic

LISA Pathfinder is a technology demonstrator space mission, aimed at testing key technologies for detecting gravitational waves in space. The mission is the precursor of LISA, the first space gravitational waves observatory, whose launch is scheduled for 2034. The LISA Pathfinder scientific payload includes two gravitational reference sensors (GRSs), each one containing a test mass (TM), which is the sensing body of the experiment. A mission critical task is to set each TM into a pure geodesic motion, i.e. guaranteeing an extremely low acceleration noise in the sub-Hertz frequency bandwidth. The grabbing positioning and release mechanism (GPRM), responsible for the injection of the TM into a geodesic trajectory, was widely tested on ground, with the limitations imposed by the 1-g environment. The experiments showed that the mechanism, working in its nominal conditions, is capable of releasing the TM into free-fall fulfilling the very strict constraint imposed on the TM residual velocity, in order to allow its capture on behalf of the electrostatic actuation. However, the first in-flight releases produced unexpected residual velocity components, for both the TMs. Moreover, all the residual velocity components were greater than maximum value set by the requirements. The main suspect is that unexpected contacts took place between the TM and the surroundings bodies. As a consequence, ad hoc manual release procedures had to be adopted for the few following injections performed during the nominal mission. These procedures still resulted in non compliant TM states which were captured only after impacts. However, such procedures seem not practicable for LISA, both for the limited repeatability of the system and for the unmanageable time lag of the telemetry/telecommand signals (about 4400 s). For this reason, at the end of the mission, the GPRM was deeply tested in-flight, performing a large number of releases, according to different strategies. The tests were carried out in order to understand the unexpected dynamics and limit its effects on the final injection. Some risk mitigation maneuvers have been tested aimed at minimizing the vibration of the system at the release and improving the alignment between the mechanism and the TM. However, no overall optimal release strategy to be implemented in LISA could be found, because the two GPRMs behaved differently.

LISA↗

DOE OSTI2023

Co-Simulation Model for Optimal Wind-Hydro Coordination Using Wind Farm Control Dynamics

The growing share of Variable Renewable Energy sources (VRES) in power systems presents challenges for regula- tors, grid operators and energy producers. The VRES’ operation has limited flexibility in their operations, as they are highly dependent on ambient environments. To address these challenges, decision-makers must consider multiple objectives, among these are revenue, power system services and mechanical load on wind turbines. Coordinated operation of power plants and different wind farm control strategies are examples of measures that can benefit these objectives. This study proposes a Multi-Objective Linear Programming (MOLP) model to simulate the optimum operation of wind and hydropower plants that share limited transmission capacity. Further, wind farm control dynamics are included to obtain realistic output power and accumulated damage. From this, a case study based on a relevant location in Norway is presented to analyze the improved effect of wind- hydro coordination and wind farm control in achieving the objectives of accumulated wind turbine damage and total revenue of the hybrid power system. In addition, the study considers the potential advantages of adding a variable-speed pump to the hydropower plant. The results demonstrate that by considering multiple objectives in the optimization, one may achieve better overall performance of the objectives. By utilizing the flexibility of hydro storage, the decision maker may adjust to obtain the most desired outcome. Moreover, the added flexibility of utilizing a pump for hydro storage shows great improvements for the combined revenue of the power plants and reduced curtailment of the wind farm. However, less impact is observed from using a variable speed pump compared to a fixed speed pump.

13 HYDRO ENERGY↗

DOE OSTI2015

SU-E-J-273: Skin Temperature Recovery Rate as a Potential Predictor for Radiation-Induced Skin Reactions

Purpose: To assess the potential of dynamic infrared imaging to evaluate early skin reactions during radiation therapy in cancer patients. Methods: Thermal images were captured by our home-built system consisting of two flash lamps and an infrared (IR) camera. The surface temperature of the skin was first raised by ∼ 6 °C from ∼1 ms short flashes; the camera then captured a series of IR images for 10 seconds. For each image series, a basal temperature was recorded for 0.5 seconds before flash was triggered. The temperature gradients (ε) were calculated between a reference point (immediately after the flash) and at a time point of 2sec, 4sec and 9sec after that. A 1.0 cm region of interest (ROI) on the skin was drawn; the mean and standard deviations of the ROIs were calculated. The standard ε values for normal human skins were evaluated by imaging 3 healthy subjects with different skin colors. All of them were imaged on 3 separate days for consistency checks. Results: The temperature gradient, which is the temperature recovery rate, depends on the thermal properties of underlying tissue, i.e. thermal conductivity. The average ε for three volunteers averaged over 3 measurements were 0.64±0.1, 0.72±0.2 and 0.80±0.3 at 2sec, 4sec and 9sec respectively. The standard deviations were within 1.5%–3.2%. One of the volunteers had a prior small skin burn on the left wrist and the ε values for the burned site were around 9% (at 4sec) and 13% (at 9sec) lower than that from the nearby normal skin. Conclusion: The temperature gradients from the healthy subjects were reproducible within 1.5%–3.2 % and that from a burned skin showed a significant difference (9%–13%) from the normal skin. We have an IRB approved protocol to image head and neck patients scheduled for radiation therapy.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2000

Nozomi Cis-Lunar Phase Orbit Determination

Japan's Institute of Space and Astronautical Science (ISAS) launched Nozomi, its first mission to the planet Mars using the newly developed M-V launch vehicle on July 3, 1998. Scientific objectives of the mission are to study the structure and dynamics of the Martian upper atmosphere and its interaction with the solar wind. Nozomi is a cooperative mission between ISAS and the National Aeronautics and Space Administration (NASA). The NASA contribution includes navigation and tracking services provided by the Jet Propulsion Laboratory (JPL). The spacecraft also serves as an engineering demonstration of basic technology for planetary exploration. One of the new technologies was a unique trajectory, developed by ISAS, which used solar gravitational perturbations at the weak stability boundary as an aid to achieve an Earth-Mars transfer orbit. This trajectory saves approximately 120 m/s of Delta V compared to direct hyperbolic insertion and is considered an enabling technology for the mission. Nozomi was the first spacecraft to employ this trajectory and provided on-orbit validation of the technique. The trajectory was achieved by initially placing the spacecraft in a highly elliptical cis-lunar phasing orbit. Six maneuvers were performed during this period to correct injection errors and target an outbound lunar swingby in September 1998. The gravity assist from the lunar swingby raised apogee to the vicinity of the weak stability boundary. After three more targeting maneuvers, Nozomi performed an inbound lunar swingby followed immediately by a powered Earth swingby in late December 1998. A 420 m/s Trans Mars Insertion (TMI) burn at the final Earth periapsis was intended to place the spacecraft on a heliocentric trajectory leading to Mars orbit insertion in October 1999. Orbit determination for Nozomi is performed in parallel by both ISAS and the Multi-Mission Navigation (MMNAV) group at JPL. This was an advantage for the mission because each group would generate solutions based on data collected from their respective tracking networks. Spacecraft events, such as sequence uplinks and maneuvers, were generally scheduled during passes at the Usuda tracking station in Japan. As a result, maneuver design and reconstruction was derived from MMNAV solutions based on JPL tracking data obtained immediately prior to or following maneuvers. Data was also exchanged between ISAS and MMNAV so orbit determination could be performed on joint data sets in support of critical targeting late in the cis-lunar phase. In this paper, information regarding the MMNAV orbit determination effort for the first six months of the mission is presented. The spacecraft trajectory is characterized first, followed by a discussion of the orbit determination estimation procedure and models. Results from selected orbit solutions are presented and compared against reconstructed trajectories. One area of emphasis in this paper is orbit determination in the vicinity of the weak stability boundary. Precise navigation was necessary to target the second lunar swingby and the powered Earth swingby. Delivery accuracy of 150 m was required for these critical encounters, but a number of factors contributed to the general degradation of orbit determination accuracy. This included the fact that the spacecraft was at apogee, at a range of 1.7 million km and moving at less than I km/sec perpendicular to the line of sight. Nozomi was also close to zero degrees declination where there are known limitations on orbit determination performance. Finally, S-band tracking data was acquired through the Nozomi backup low gain antenna. This antenna is offset from the axis of this spin stabilized spacecraft and superimposed large signatures in the Doppler and range data. These difficulties were overcome by combining long data arcs, spanning several maneuvers, with a high fidelity solar pressure model. The model included a physically accurate representation of the spacecraft structure and a high time resolution orientation model. Observation modeling included the removal of the spin induced Doppler bias, spin signature and per pass correction of range calibration errors applied for data leading up to critical events. As a result, all orbit determination goals were met. A second area of emphasis in this paper is the JPL tracking and orbit determination effort in support of the TMI maneuver. TMI occurred out of contact with ground stations and the JPL Goldstone tracking complex had the first pass following the bum. As a result, MMNAV had the responsibility to make a rapid assessment of the maneuver performance. MMNAV made the determination that a 100 m/s under bum had occurred and promptly informed ISAS via voice lines. ISAS immediately began preparations for a correction maneuver (TMIc), which had to be performed during the next Usuda pass. The near real time assessment by MMNAV provided accurate antenna frequency and pointing updates for the spacecraft acquisition at Usuda and the close coordination between the two agencies enabled the design and successful execution of the TMc maneuver. Propellant consumption during the correction burn dictated that the mission be redesigned. ISAS developed a new plan which adds 3 full solar orbits, two Earth swingbys and one lunar swingby with arrival at Mars in January 2004. The final Mars orbit will still enable the mission to achieve all of its science objectives.

Ryne, Mark↗

NASA NTRS2011

Wireless Sensor Networks for Developmental and Flight Instrumentation

Wireless sensor networks (WSN) based on the IEEE 802.15.4 Personal Area Network and ZigBee Pro 2007 standards are finding increasing use in home automation and smart energy markets providing a framework for interoperable software. The Wireless Connections in Space Project, funded by the NASA Engineering and Safety Center, is developing technology, metrics and requirements for next-generation spacecraft avionics incorporating wireless data transport. The team from Stennis Space Center and Mobitrum Corporation, working under a NASA SBIR grant, has developed techniques for embedding plug-and-play software into ZigBee WSN prototypes implementing the IEEE 1451 Transducer Electronic Datasheet (TEDS) standard. The TEDS provides meta-information regarding sensors such as serial number, calibration curve and operational status. Incorporation of TEDS into wireless sensors leads directly to building application level software that can recognize sensors at run-time, dynamically instantiating sensors as they are added or removed. The Ames Research Center team has been experimenting with this technology building demonstration prototypes for on-board health monitoring. Innovations in technology, software and process can lead to dramatic improvements for managing sensor systems applied to Developmental and Flight Instrumentation (DFI) aboard aerospace vehicles. A brief overview of the plug-and-play ZigBee WSN technology is presented along with specific targets for application within the aerospace DFI market. The software architecture for the sensor nodes incorporating the TEDS information is described along with the functions of the Network Capable Gateway processor which bridges 802.15.4 PAN to the TCP/IP network. Client application software connects to the Gateway and is used to display TEDS information and real-time sensor data values updated every few seconds, incorporating error detection and logging to help measure performance and reliability in relevant target environments. Test results from our prototype WSN running the Mobitrum software system are summarized and the implications to the scalability and reliability for DFI applications are discussed. Our demonstration system, incorporating sensors for life support system and structural health monitoring is described along with test results obtained by running the demonstration prototype in relevant environments such as the Wireless Habitat Testbed at Johnson Space Center in Houston. An operations concept for improved sensor process flow from design to flight test is outlined specific to the areas of Environmental Control and Life Support System performance characterization and structural health monitoring of human-rated spacecraft. This operations concept will be used to highlight the areas where WSN technology, particularly plug-and-play software based on IEEE 1451, can improve the current process, resulting in significant reductions in the technical effort, overall cost and schedule for providing DFI capability for future spacecraft. RELEASED -

Alena, Richard↗

NASA NTRSDate not supplied

Electrostatic Regolith Interaction Experiment (ERIE) Electrometer Initial Flight Results

The Electrostatic Regolith Interaction Experiment (ERIE) is a suborbital flight payload studying electrostatically charged dust particle dynamics under microgravity, jointly developed by University of Central Florida (UCF) and NASA Kennedy Space Center (KSC). ERIE combines components from two systems, the COLLisions Into Dust Experiment (COLLIDE) from UCF and the Wheel Electrostatic Spectrometer (WES) from NASA KSC, to advance understanding of charged grain behavior on low gravity bodies such as the Moon and asteroids. ERIE slides a door containing an electrometer system monitoring various insulating disks across the surface of a regolith simulant bed. The experiment is activated when the payload enters the microgravity potion of the flight. The grains in the simulant bed tribocharge via agitation during launch as well as through frictional interactions with the door and its protruding insulators. As the retention door retracts, particles are allowed to loft into an open volume, achieving motion due to electrostatic repulsion. The electrometer system measures the charge transfer between the granular material and the insulators. As the charged grains exit the bed, they travel through an applied electric field and a camera observes the kinematics of the individual grains whose trajectories are determined by their net charges. The design of the ERIE electrometer instrument and initial results from the first flight was presented at the 2021 AGU Fall Meeting under P55E-2002. Shortly after microgravity was achieved and the retaining door began to open, the rate of charge acquisition measured by the electrometer increased, indicating the insulators were accumulating triboelectric charge. Charged grains were observed in the video data to traverse across the external electric field and become deflected from a linear path due to their charges. Pairs of grains were also observed to orbit one another as expected from two oppositely charged bodies in proximity to one another. Improvements to the design of the instrument and preliminary results obtained from the second flight scheduled for Q3 2022 will be presented at this meeting.

Electrostatics↗

NASA NTRSDate not supplied

Electrostatic Regolith Interaction Experiment (ERIE) Electrometer Initial Flight Results

Electrostatics↗

DOE OSTI2020

Demand Driven Cycamore Archetypes

Future nuclear fuel cycle options may present advantages over today’s once-through fuel cycle. Nuclear fuel cycle simulation tools assess the performance of those fuel cycles as well as the dynamics of long-term technology transitions. In many nuclear fuel cycle simulation tools, it has historically been the responsibility of the user to manually define facility deployment schemes and all facility parameters. While this is straightforward in simple fuel cycles, transitions from one fuel cycle to another can be more complex. In particular, deployment schemes for supportive fuel cycle facilities beyond the reactor become complex if the analyst desires to avoid gaps in the nuclear fuel and power supply chain during those transition scenarios. As nuclear fuel cycle analysis approaches questions regarding the feasibility and performance of the deployment schemes and technology choices during technology transition, automation of this historically manual process is necessary. The main objective of this work was to develop and demonstrate Cyclus automation capabilities toward key nuclear fuel cycle transition scenarios. While deploying reactors to meet power demand is trivial, and existed in the earliest versions of CYCLUS, automated, predictive deployment and decommissioning of other facilities is more complex. These include mining, milling, enrichment, fuel fabrication, reprocessing, and others. For example, a balanced closed fuel cycle may require ensuring that there is enough fast reactor fuel for their operation and may drive deployment of a fleet of light water reactors. This concern comprises the main challenge that drove the project effort. The Demand-Driven Cycamore Archetype project (NEUP-FY16-10512) aimed to develop CYCAMORE demand-driven deployment capabilities and thereby automate transition scenario definition. The developed software package, d3ploy, in the form of a CYCLUS Institution agent, deploys Facilities to meet the front-end and back-end demands of the fuel cycle. The University of South Carolina and the University of Illinois applied multiple algorithmic approaches to this challenge. This project developed an in situ demand-driven development schedule calculation through non-optimizing, deterministic-optimizing, and stochastic-optimizing algorithms as CYCLUS archetypes and demonstrated these new archetypes in program-supporting fuel cycle transition scenarios. Both objectives were achieved. This report documents the results and deliverables obtained toward these achievements in detail.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

NASA NTRSDate not supplied

Deep Space navigation for the BioSentinel spacecraft science orbit

BioSentinel is an astrobiology small spacecraft mission. The payload consists of two parts, the first has optical and microfluidics sensors, and the second is a Linear Energy Transfer spectrometer that has the objective to measure deep space radiation from events such as coronal mass ejections. The goal of the mission is to observe potential DNA damage due to the radiation in heliocentric space on the living organism Saccharomyces cerevisiae, which is a budding yeast. Two types of this living organism are included in the payload. The first is a natural type that is more radiation tolerant, while the second is a mutant strain that has a deficiency in a gene that allows DNA repair once damage occurs. The impact caused by the radiation on the DNA is compared to an identical sample aboard the International Space Station, as well as another identical sample at a laboratory on the ground. The BioSentinel mission consists of a 6U CubeSat currently ,as of January 2024, active in heliocentric orbit. The spacecraft was launched aboard the first SLS flight as part of the Artemis-I campaign in November 2022. After successful deployment from the launch vehicle, it performed a lunar flyby with an altitude of 406 km. The delta-V imparted by the flyby provided the necessary energy to achieve a heliocentric orbit, in an Earth-trailing pattern. The navigation analysis consisted of a Kalman-filter that utilized data from the Deep Space Network and the ESA Estrack network. All those antennas were needed since the Artemis-1 campaign included the deployment of several other cubesats, therefore the scheduling process required more antenna assets than usual due to simultaneous demands from various missions. The processed tracking data was later also refined with a smoother in order to obtain a more accurate solution. The type of tracking data included TCP, Sequential Range, Doppler and Range formats. The solar radiation pressure coefficient, as well as the delta-V from the deployment and the flyby were modeled to obtain suitable solutions that could decrease the position and velocity uncertainties at several steps along the mission concept of operations. The final product each time resulted in updated ephemeris files that were used by the mission and the antenna networks as the mission progressed. Once in the final science orbit, the utilized antennas are only from the DSN network and the data format is bounded to just TCP. Regular orbit determination is performed, every two weeks. The spacecraft is in a nominal well-known orbit, performing regular operations. This paper includes an analysis of the final science orbit, the techniques and procedures utilized to perform orbit determination and a description of the overall navigation campaign produced during the mission and, more specifically, during the final science operations in Deep Space.

BioSentinel↗

DOE OSTI2025

Dynamic Charging Rendezvous and Motion Planning for a Multi-AGV Team Including a Mobile Charging Host

Teams of automated battery-powered electric vehicles have the potential to execute complex mission tasks in off-road environments for agriculture, military, and other applications. Limited onboard energy reserves hinder their adoption in large-scale resource-constrained environments, where recharging is a necessity. It may be infeasible to install a network of static charging stations in off-road environments. For this reason, dedicated mobile host vehicles with charging capabilities are proposed as a means to increase range and capabilities of the multivehicle team. Here, in this study, we consider an ad hoc planning framework, where results from a high-confidence trajectory planner are leveraged to plan charging rendezvous between a host and other worker vehicles in a receding horizon fashion to provide high confidence that energy reserves will not be prematurely exhausted. The core problem is posed so as to minimize the impact of recharging on the mission in terms of task delays, overall energy utilization, and costs of fast charging. Through extensive Monte Carlo simulations of an off-road mission, we show a decrease in task delays without substantial increases in energy needs by updating the charging rendezvous plan during the mission. However, if updates are made too often, model mismatch may cause unnecessary cycling and mission failure.

Energy constraints↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

DOE OSTI2021

Coupled Microbial-Conversion and Computational-Fluid-Dynamics (CFD) Models for Butanediol Production in Micro-Aerated Reactors

Microbial conversion of substrates to macromolecules has been widely used in the synthesis of value-added products in pharmaceutical and biotechnology industries. These bioreactions are also being investigated in the production of low-value commodities such as biofuels [1]. Gas-liquid mass-transfer and transport-reaction coupling are important challenges when designing and scaling up these reactor systems. Experiments in wellmixed small-scale reactors have enabled characterization of microbial reactivity, while their coupling with macroscale transport remains relatively unexplored. In this work, we use a coupled metabolic-CFD model to study the action of a genetically engineered microbe Zymomonas mobilis [2] on sugars to produce 2,3-Butanediol (BDO). BDO is an important hydrocarbon intermediate that can be catalytically upgraded to several fuels and chemicals [3]. An important aspect to this particular microbial conversion is the need for micro-aerated environments as opposed to traditional aerobic fermentation. Slight variations in oxygen concentration can result in competing reaction pathways that disable BDO production. Hence, gas-liquid mass transfer and transport need to be optimized in large-scale reactors to maximize BDO production, for which CFD is a valuable tool. The aerobic-fermentation CFD model previously developed by the authors [5] for simulating bubble-column and airlift reactors at scale was used in this study. The Reynolds-averaged mass, momentum and energy transport equations for interpenetrating gas and liquid phase are solved in this model along with the transport and interphase mass transfer of oxygen. Our previous work used a phenomenological model for microbial oxygen uptake that neglected microbial growth and other reaction pathways. In this work, a detailed metabolic model enabled prediction of product formation and inhibition pathways. In order to manage computational cost, we used a subcycling technique [6] that takes advantage of the clear separation in transport (~ 200 sec) and reaction (~ 2-3 hours) timescales. The CFD model is first solved to steady state, after which the metabolic model is advanced at every cell in the computational domain using the local oxygen concentration. The CFD model is then run to achieve a new steady state that provides a new oxygen distribution for the metabolic model. This process, where reaction and fluid updates are interleaved together, is iterated until reactants are completely exhausted. This work will examine the performance of different reactor designs such as bubble column and airlift reactors at scale (250-500 m3). Oxygen mass-transfer coefficient and distribution are critically analyzed among reactors, and optimization studies pertaining to aeration is presented. Furthermore, it has been observed in experiments that high BDO production may be achieved by manipulating the aerobic environment over the course of reaction, such that oxygen concentration is high during the growth phase, and very low as sugar is depleted. This characteristic will be addressed by our simulations for which a timedependent scheduling strategy for aeration is presented that maximizes BDO production. [1] Humbird, D., Davis, R., and McMillan, J., Aeration costs in stirred-tank and bubble column bioreactors, Biochemical Engineering Journal, 127, 161—166, 2017 [2] Yang, S., Mohagheghi, A., Franden, M. A., Chou, Y.-C., Chen, X., Dowe, N., Himmel, M. E., and Zhang, M., Metabolic engineering of zymomonas mobilis for 2, 3-butanediol production from lignocellulosic biomass sugars. Biotechnology for biofuels, 9(1):189, 2016 [3] Kim, S. J., Sim, H. J., Kim, J. W., Lee, Y. G., Park, Y. C., and Seo, J. H., Enhanced production of 2,3-butanediol from xylose by combinatorial engineering of xylose metabolic pathway and cofactor regeneration in pyruvate decarboxylase-deficient Saccharomyces cerevisiae. Bioresource Technology, 245:1551–1557, 2017 [4] Weller, H., Tabor, G., Jasak, H. and Fureby, C., A tensorial approach to computational continuum mechanics using object-oriented techniques, Computers in physics, 12, 6, 620--631, 1998

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

NASA NTRS2014

Scientific Impact of MODIS C5 Calibration Degradation and C6+ Improvements

The Collection 6 (C6) MODIS (Moderate Resolution Imaging Spectroradiometer) land and atmosphere data sets are scheduled for release in 2014. C6 contains significant revisions of the calibration approach to account for sensor aging. This analysis documents the presence of systematic temporal trends in the visible and near-infrared (500 m) bands of the Collection 5 (C5) MODIS Terra and, to lesser extent, in MODIS Aqua geophysical data sets. Sensor degradation is largest in the blue band (B3) of the MODIS sensor on Terra and decreases with wavelength. Calibration degradation causes negative global trends in multiple MODIS C5 products including the dark target algorithm's aerosol optical depth over land and Ångstrom exponent over the ocean, global liquid water and ice cloud optical thickness, as well as surface reflectance and vegetation indices, including the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). As the C5 production will be maintained for another year in parallel with C6, one objective of this paper is to raise awareness of the calibration-related trends for the broad MODIS user community. The new C6 calibration approach removes major calibrations trends in the Level 1B (L1B) data. This paper also introduces an enhanced C6C calibration of the MODIS data set which includes an additional polarization correction (PC) to compensate for the increased polarization sensitivity of MODIS Terra since about 2007, as well as detrending and Terra- Aqua cross-calibration over quasi-stable desert calibration sites. The PC algorithm, developed by the MODIS ocean biology processing group (OBPG), removes residual scan angle, mirror side and seasonal biases from aerosol and surface reflectance (SR) records along with spectral distortions of SR. Using the multiangle implementation of atmospheric correction (MAIAC) algorithm over deserts, we have also developed a detrending and cross-calibration method which removes residual decadal trends on the order of several tenths of 1% of the top-of-atmosphere (TOA) reflectance in the visible and near-infrared MODIS bands B1-B4, and provides a good consistency between the two MODIS sensors. MAIAC analysis over the southern USA shows that the C6C approach removed an additional negative decadal trend of Terra (Delta)NDVI approx.0.01 as compared to Aqua data. This change is particularly important for analysis of vegetation dynamics and trends in the tropics, e.g., Amazon rainforest, where the morning orbit of Terra provides considerably more cloud-free observations compared to the afternoon Aqua measurements.

Terra and Aqua↗

NASA NTRSDate not supplied

Manual Crew Override of Vehicle Landings Following G-Transitions

BACKGROUND Manual control during exploration spaceflight consists of both planned automated supervisory control and unplanned crew override. This crew override capability is critical to enable overall mission success during landing contingencies. However, the introduction of manual override capabilities must be implemented to enable crews to mitigate risks introduced by human error. Adaptive changes in the sensorimotor system can manifest during g-transitions as spatial disorientation. While training and landing aids enable successful landing through disorientation, these adaptive changes may increase cognitive demand that needs to be accounted for in the manual control strategy. It is important to characterize these effects as soon as possible following the G-transition to develop appropriate countermeasures. METHODS The following study seeks to inform the risk associated with altered sensorimotor and vestibular function impacting critical mission tasks. We aim to characterize the effects of short and long-duration weightlessness on manual control following G-transitions using simulated lunar landing on a six-degree-of-freedom (6DOF) motion base, a fixed base simulation, and a supervisory control tablet task. The primary goal is to understand the impact of spaceflight on crew ability to perform manual crew override and supervisory control. This aim will be assessed by comparing pre- versus postflight simulation performance in crewmembers assigned to either short duration (< 30 day) or long duration (~6- month) missions to the International Space Station (ISS). We hypothesize there will be postflight increases in the percent time that pilots are outside of the acceptable range for recommended vehicle state parameters and the reaction time for secondary cognitive tasks. Ground-based control subjects, who are demographically matched to the crew considering age (± 5 years) and gender, will undergo the same testing schedule as the crew to examine the effects of flight phase independent of microgravity exposure. The second aim is to examine how adaptive changes in vestibular and cognitive function relate to changes in manual crew override proficiency. Crew performance for a sensorimotor perceptual test battery will evaluate motion perception tracking, roll nulling, and/or vection sensitivity using the 6DOF motion base. We hypothesize that a higher severity of vestibular alterations will be associated with increased percent time outside of guidance limits. Motion sickness severity and sleepiness will also be evaluated. To determine the impact of “just-in-time” training, the third aim seeks to compare performance during on-board lunar landing tasks conducted late in-flight to early postflight. We hypothesize that proficiency on the “just-in-time” laptop trainer late in mission will be positively correlated with early postflight proficiency on the same task. The final aim will establish assessments of performance, training protocols, and the learning progression in a ground-control cohort of first-time users. RESULTS The assessment of the learning progression associated with the piloting task on the motion base system with thirty ground subjects will be reported. Learning curves will be established across four distinct sessions and within session considering trial difficulty. The difficulty of the landing task can be modulated with the landing divert distance and cross or downrange difficulty. Results may include changes in performance across multiple trials of a multi-attribute lunar tablet supervisory control task. Preliminary investigations of eighteen subjects who completed vestibular threshold and motion perception tasks offer expected performance ranges for upcoming preflight crew evaluations. The results yielded an average roll threshold of 0.46 ± 0.30 deg/s and an average roll nulling root mean square error performance of 2.52 ± 0.52 deg/s. RELEVANCE This project will deliver an operational demonstration of crew monitoring capability following spaceflight and identify potential deficits that may require remediation. Comparison of individual vestibular and cognitive changes with crew performance will help better characterize the manual control risks associated with sensorimotor alterations. Ground testing will evaluate learning progression, refine training protocols, and serve as a control cohort for comparisons to crew performance. ACKNOWLEDGEMENTS: The authors acknowledge contributions from Draper, the Dynamic Skills Trainer (DST) Lab, and the Software, Robotics, and Simulation Division toward the development of the lunar landing simulation platforms. This project is funded by the Human Health Countermeasures Element.

Hannah M. Weiss↗