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NASA NTRSDate not supplied

Impacts of Non-Simultaneous Global Photospheric Magnetic Measurements on Coronal and Solar Wind Modeling

The intensity and arrival time of coronal mass ejections (CMEs) can be significantly influenced by the background solar wind encountered as they propagate outward from the Sun into the interplanetary medium. In addition, solar energetic particles (SEPs) race ahead of CME shock fronts and flare regions along magnetic field lines largely determined by the background solar wind. Predicting the solar wind accurately is therefore critical for improving forecasts of CMEs, SEPs, and high-speed streams. Modeling of the corona and solar wind is challenging in general, as it is highly dependent on global photospheric magnetic field maps, which serve as the boundary conditions to all coronal models that drive solar wind models. Unfortunately, less than half of the Sun’s photospheric magnetic field is reliably measured from any given vantage point and thus it is common for the maps to have highly dated and unreliable measurements in them. While Solar Obiter (SolO) now provides for the first time the opportunity to have simultaneous measurements of nearly the entire surface magnetic field of Sun (e.g., when SolO/PHI measurements are combined with those from SDO/HMI), the required alignment to accomplish this occurs only occasionally. Further, coronal models are extremely sensitive to the strengths of the polar magnetic fields of the Sun, which remain poorly observed. Recently, efforts to mitigate this problem include using flux transport models such as the Air Force Data Assimilative Photospheric Flux Transport (ADAPT) model, which evolves the field forward in time using well known transport processes occurring on the Sun. However, it cannot account for the emergence of new magnetic flux without direct observations. The ESA VIGIL mission will eventually provide continuous observations from the L5, and the proposed SunCHASER mission will likewise do this at the L4 vantage point should it be funded. Ultimately, what is needed is a constellation of spacecraft distributed around the Sun with magnetographs that continuously measure the global surface magnetic field. In this talk, we discuss how the lack of simultaneous global measurements of the photospheric magnetic field adversely impacts the predictive performance of coronal and solar wind models.

C. Nick Arge↗

DOE OSTI2021

19-LW-045 Full Length Final Report. Molecular Mechanisms of Bacterial Pathogenesis: Waging the Arms Race with Superbugs

As the current global pandemic makes abundantly clear, we need a better understanding of infectious disease to safeguard human health, the economy and global security. Modern omics techniques hold the promise of providing a comprehensive understanding of the molecular mechanisms of life, including causes of pathogenesis from infectious disease at the molecular level, but we there is a serious gap in annotation of gene function. For as much as half of the genes and gene products encoded in genomes the molecular and/or cellular function is unknown or only partially understood. Recent innovations in fluorescence microscopy for live cell imaging and genetic engineering make it possible to determine the temporal correlation between molecular events, such as a gene being expressed due to host-pathogen interaction, and cellular events, such as bacterial invasion of immune cells. This is turn allows us to gain new insight as to the molecular and cellular role of individual genes and will enable the discovery and validation of new molecular mechanisms essential for infectious disease. Knowing the molecular mechanisms of disease processes will provide new therapeutic targets or novel countermeasure strategies. We aimed to develop a lattice light sheet fluorescence microscope as a unique resource at LLNL for long time course live cell imaging experiments; to develop the reagents and cell lines needed to monitor molecular events during the course pathogenic bacteria infecting mammalian immune cells; and to demonstrate that we could capture molecular events during an infection. We fully commissioned the LLNL lattice light sheet microscope and conducted initial proof of principle imaging experiments on mammalian immune cells and pathogenic bacteria. It is clear from the experience gained that long time course live cell imaging has tremendous potential to help elucidate molecular mechanisms of host-pathogen interactions and to help annotate gene function, which would establish a basis for new countermeasures. It is also clear that if live cell imaging is to realize its full potential new data processing and analysis tools will need to be developed to facilitate analysis of molecular events within cells; new sample chambers and stages could facilitate studies with a wider range of cell and tissue types; and alternative molecular tagging methods need to be explored to enable more facile engineering of cells labeled with molecular specificity.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Comparison of Mammographic Changes Across Three Different Fractionation Schedules for Early-Stage Breast Cancer

Purpose: As the use of hypofractionated breast radiation therapy (RT) increases, so will the need for long-term data on post-RT mammographic changes. The purpose of the present study was to longitudinally compare the incidence of common mammographic sequelae seen after breast conserving surgery and RT in patients treated with accelerated partial breast irradiation (APBI), hypofractionated whole breast irradiation (HWBI), and conventionally fractionated whole breast irradiation (WBI). Methods and Materials: Patients treated with either APBI or HWBI after breast conserving therapy and with ≥3 mammograms of the treated breast were identified. They were matched 1:1 by age ±5 years to patients treated with WBI. The mammograms were evaluated for common post-RT breast findings by a mammographer who was unaware of the treatment. The outcomes were analyzed using a cumulative logistic regression model; P<.05 indicated statistically significance. Results: Of 89 patients treated with RT from 2006 to 2011, 29 had received APBI, 30 had received HWBI, and 30 had received WBI. Their median age was 60 years (range 33-83). A total of 605 mammograms were evaluated, with a median follow-up of 48 months. The treatment technique did not affect the severity of architectural distortion when the groups were evaluated longitudinally. The likelihood of finding skin thickening decreased with increasing follow-up duration (odds ratio 0.6; P<.001) adjusted for fractionation schemes. No differences were seen with respect to changes in skin thickening, fluid collections, or calcifications among the treatment groups, after adjustment for the follow-up time. The clinical characteristics, including age, race, T stage, and chemotherapy use, were not linked to the likelihood of finding several mammographic phenomena over time. Conclusions: Although specific post-treatment imaging findings evolved over time, RT fractionation did not alter the relative incidence or severity of architectural distortion, skin thickening, fluid collections, or calcifications. These findings will be useful to both radiologists and radiation oncologists when counseling patients regarding follow-up studies after RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2005

Materials Control for Aerospace Applications

The distant future of mankind and the ultimate survivability of the human race, as it is known today, will depend on mans' ability to break earthly bonds and establish new territorial positions throughout the universe. Man must therefore be positioned to not only travel to, but also, to readily adapt to numerous and varying environments. For this mass migration across the galaxies nothing is as import to the human race as is NASA's future missions into Low Earth Orbit (LEO), to the moon, and/or Mars. These missions will form the building blocks to eternity for mankind. From these missions, NASA will develop the foundations for these building blocks based on sound engineering and scientific principles, both known and yet to be discovered. The integrity of the program will lead to development, tracking and control of the most basic elements of hardware production: That being development and control of applications of space flight materials. Choosing the right material for design purposes involves many considerations, such as governmental regulations associated with manufacturing operations, both safety of usage and of manufacturing, general material usage requirements, material longevity and performance requirements, material interfacing compatibility and material usage environments. Material performance is subject to environmental considerations in as much as a given material may perform exceptionally well at standard temperatures and pressures while performing poorly under non-standard conditions. These concerns may be found true for materials relative to the extreme temperatures and vacuum gradients of high altitude usage. The only way to assure that flight worthy materials are used in design is through testing. However, as with all testing, it requires both time on schedule and cost to the operation. One alternative to this high cost testing approach is to rely on a materials control system established by NASA. The NASA community relies on the MAPTIS materials control system founded at MSFC and supported by the other NASA Centers. This system is a data bank of all materials used in space flight operations. These materials are rated for several characteristics that are common concerns in high altitude or deep space usage: Odor, off gassing, material fluid compatibility, toxicity, corrosion susceptibility, stress corrosion susceptibility, etc.

Ferguson, Michael↗

NASA NTRS2011

Ground Processing Affordability for Space Vehicles

Launch vehicles and most of their payloads spend the majority of their time on the ground. The cost of ground operations is very high. So, why so often is so little attention given to ground processing during development? The current global space industry and economic environment are driving more need for efficiencies to save time and money. Affordability and sustainability are more important now than ever. We can not continue to treat space vehicles as mere science projects. More RLV's (Reusable Launch Vehicles) are being developed for the gains of reusability which are not available for ELV's (Expendable Launch Vehicles). More human-rated vehicles are being developed, with the retirement of the Space Shuttles, and for a new global space race, yet these cost more than the many unmanned vehicles of today. We can learn many lessons on affordability from RLV's. DFO (Design for Operations) considers ground operations during design, development, and manufacturing-before the first flight. This is often minimized for space vehicles, but is very important. Vehicles are designed for launch and mission operations. You will not be able to do it again if it is too slow or costly to get there. Many times, technology changes faster than space products such that what is launched includes outdated features, thus reducing competitiveness. Ground operations must be considered for the full product Lifecycle, from concept to retirement. Once manufactured, launch vehicles along with their payloads and launch systems require a long path of processing before launch. Initial assembly and testing always discover problems to address. A solid integration program is essential to minimize these impacts, as was seen in the Constellation Ares I-X test rocket. For RLV's, landing/recovery and post-flight turnaround activities are performed. Multi-use vehicles require reconfiguration. MRO (Maintenance, Repair, and Overhaul) must be well-planned--- even for the unplanned problems. Defect limits and standard repairs need to be in-place as well as easily added. Many routine inspections and maintenance can be like an aircraft overhaul. Modifications and technology upgrades should be expected. Another factor affecting ground operations efficiency is trending. It is essential for RLV's, and also useful for ELV's which fly the same or similar models again. Good data analysis of technical and processing performance will determine fixes and improvements needed for safety, design, and future processing. Collecting such data on new or low-frequency vehicles is a challenge. Lessons can be learned from the Space Shuttle, or even the Concorde aircraft. For all of the above topics, efficient business systems must be established for comprehensive program management and good throughput. Drawings, specifications, and manuals for an entire launch vehicle are often in different formats from multiple vendors, plus they have proprietary constraints. Nonetheless, the integration team must ensure that all data needed is compatible and visible to each appropriate team member. Ground processing systems for scheduling, tracking, problem resolution, etc. must be well laid-out. The balance between COTS (commercial off the shelf) and custom software is difficult. Multiple customers, vendors, launch sites, and landing sites add to the complexity of efficient IT (Information Technology) tools.

Ingalls, John↗

DOE OSTI2013

Is Ki-67 Expression Prognostic for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast Conservation Therapy (BCT)?

Purpose: Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breast cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists. Methods and Materials: Ki-67 staining was conducted on a tissue microarray of 438 patients previously treated with BCT, and expression was analyzed with clinicopathologic features and outcomes from our database. Results: Ki-67 expression was more prevalent in black patients (37% of black patients vs 17% of white patients, P<.01), younger patients (27% of patients aged ≤50 years vs 15% of patients aged >50 years, P<.01), estrogen receptor (ER)–negative tumors (25% of ER-negative tumors vs 17% of ER-positive tumors, P=.04), human epidermal growth factor receptor 2 (HER2)/neu–positive tumors (35% of HER2-positive tumors vs 18% of HER2-negative tumors, P=.01), and larger tumors (26% of T2 tumors vs 16% of T1 tumors, P=.03). On univariate/multivariate analysis, Ki-67 did not predict for overall survival (74.4% vs 72.6%), cause-specific survival (82.9% vs 82.1%), local relapse-free survival (83.6% vs 88.5%), distant metastasis-free survival (76.1% vs 81.4%), recurrence-free survival (65.5% vs 74.6%), and locoregional recurrence-free survival (81.6% vs 84.7%): P>.05 for all. Conclusions: Ki-67 appears to be a surrogate marker for aggressive disease and significantly correlates with known prognostic features such as age, race, hormone receptor status, and HER2 status but independently does not predict for locoregional outcomes after BCT when these other prognostic clinicopathologic features are taken into consideration. The independent associations of Ki-67 with race and age appear to be novel to our study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2013

Mars Sample Return Using Commercial Capabilities: Mission Architecture Overview

Mars Sample Return (MSR) is the highest priority science mission for the next decade as recommended by the recent Decadal Survey of Planetary Science. This paper presents an overview of a feasibility study for a MSR mission. The objective of the study was to determine whether emerging commercial capabilities can be used to reduce the number of mission systems and launches required to return the samples, with the goal of reducing mission cost. The major element required for the MSR mission are described and include an integration of the emerging commercial capabilities with small spacecraft design techniques; new utilizations of traditional aerospace technologies; and recent technological developments. We report the feasibility of a complete and closed MSR mission design using the following scenario that covers three synodic launch opportunities, beginning with the 2022 opportunity: A Falcon Heavy injects a SpaceX Red Dragon capsule and trunk onto a Trans Mars Injection (TMI) trajectory. The capsule is modified to carry all the hardware needed to return samples collected on Mars including a Mars Ascent Vehicle (MAV); an Earth Return Vehicle (ERV); and hardware to transfer a sample collected in a previously landed rover mission to the ERV. The Red Dragon descends to land on the surface of Mars using Supersonic Retro Propulsion (SRP). After previously collected samples are transferred to the ERV, the single-stage MAV launches the ERV from the surface of Mars to a Mars phasing orbit. The MAV uses a storable liquid, pump fed bi-propellant propulsion system. After a brief phasing period, the ERV, which also uses a storable bi-propellant system, performs a Trans Earth Injection (TEI) burn. Once near Earth the ERV performs Earth and lunar swing-bys and is placed into a Lunar Trailing Orbit (LTO0 - an Earth orbit, at lunar distance. A later mission, using a Dragon and launched by a Falcon Heavy, performs a rendezvous with the ERV in the lunar trailing orbit, retrieves the sample container and breaks the chain of contact with Mars by transferring the sample into a sterile and secure container. With the sample contained, the retrieving spacecraft, makes a controlled Earth re-entry preventing any unintended release of pristine Martian materials into the Earth's biosphere. Other capsule type vehicles and associated launchers may be applicable. The analysis methods employed standard and specialized aerospace engineering tools. Mission system elements were analyzed with either direct techniques or by using parametric mass estimating relationships (MERs). The architecture was iterated until overall mission convergence was achieved on at least one path. Subsystems analyzed in this study include support structures, power system, nose fairing, thermal insulation, actuation devices, MAV exhaust venting, and GN&C. Best practice application of loads, mass growth contingencies, and resource margins were used. For Falcon Heavy capabilities and Dragon subsystems we utilized publically available data from SpaceX; published analyses from other sources; as well as our own engineering and aerodynamic estimates. Earth Launch mass is under 11 mt, which is within the estimated capability of a Falcon Heavy, with margin. Total entry masses between 7 and 10 mt were considered with closure occurring between 9 and 10 mt. Propellant mass fractions for each major phase of the EDL - Entry, Terminal Descent, and Hazard Avoidance - have been derived. An assessment of the entry conditions on the thermal protection system (TPS), currently in use for Dragon missions, has been made. And shows no significant stressors. A useful mass of 2.0 mt is provided and includes mass growth allowances for the MAV, the ERV, and mission unique equipment. We also report on alternate propellant options for the MAV and options for the ERV, including propulsion systems; crewed versus robotic retrieval mission; as well as direct Earth entry. International Planetary Protection Policies as well as verifiable means of compliance will have a large impact on any MSR mission design. We identify areas within our architecture where such impacts occur. This work shows that emerging commercial capabilities can be used to effectively integrated into a mission to achieve an important planetary science objective.

Mars Sample Return↗

DOE OSTI2021

Deep Sequencing of MHC-Adapted Viral Lines Reveals Complex Recombinational Exchanges With Endogenous Retroviruses Leading to High-Frequency Variants

Experimental evolution (serial passage) of Friend virus complex (FVC) in mice demonstrates phenotypic adaptation to specific host major histocompatibility complex (MHC) genotypes. These evolved viral lines show increased fitness and virulence in their host-genotype-of-passage, but display fitness and virulence tradeoffs when infecting unfamiliar host MHC genotypes. Here, we deep sequence these viral lines in an attempt to discover the genetic basis of FVC adaptation. The principal prediction for genotype-specific adaptation is that unique mutations would rise to high frequency in viral lines adapted to each host MHC genotype. This prediction was not supported by our sequencing data as most observed high-frequency variants were present in each of our independently evolved viral lines. However, using a multi-variate approach to measure divergence between viral populations, we show that populations of replicate evolved viral lines from the same MHC congenic mouse strain were more similar to one another than to lines derived from different MHC congenic mouse strains, suggesting that MHC genotype does predictably act on viral evolution in our model. Sequence analysis also revealed rampant recombination with endogenous murine leukemia virus sequences (EnMuLVs) that are encoded within the BALB/c mouse genome. The highest frequency variants in all six lines contained a 12 bp insertion from a recombinant EnMuLV source, suggesting such recombinants were either being favored by selection or were contained in a recombinational hotspot. Interestingly, they did not reach fixation, as if they are low fitness. The amount of background mutations linked to FVC/EnMuLV variable sites indicated that FVC/EnMuLV recombinants had not reached mutation selection equilibrium and thus, that EnMuLV sequences are likely continuously introgressing into the replicating viral population. These discoveries raise the question: is the expression of EnMuLV sequences in mouse splenocytes that permit recombination with exogenous FVC a pathogen or host adaptation?

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2014

Mars Sample Return Using Commercial Capabilities: Mission Architecture Overview

Mars Sample Return (MSR) is the highest priority science mission for the next decade as recommended by the recent Decadal Survey of Planetary Science. This paper presents an overview of a feasibility study for an MSR mission. The objective of the study was to determine whether emerging commercial capabilities can be used to reduce the number of mission systems and launches required to return the samples, with the goal of reducing mission cost. We report the feasibility of a complete and closed MSR mission design using the following scenario that covers three synodic launch opportunities, beginning with the 2022 opportunity: A Falcon Heavy injects a SpaceX Red Dragon capsule and trunk onto a Trans Mars Injection (TMI) trajectory. The capsule is modified to carry all the hardware needed to return samples collected on Mars including a Mars Ascent Vehicle (MAV), an Earth Return Vehicle (ERV), and hardware to transfer a sample collected in a previously landed rover mission to the ERV. The Red Dragon descends to land on the surface of Mars using Super Sonic Retro Propulsion (SSRP). After previously collected samples are transferred to the ERV, the single-stage MAV launches the ERV from the surface of Mars. The MAV uses a storable liquid bi-propellant propulsion system to deliver the ERV to a Mars phasing orbit. After a brief phasing period, the ERV, which also uses a storable bi-propellant system, performs a Trans Earth Injection (TEI) burn. Upon arrival at Earth, the ERV performs Earth and lunar swing-bys and is placed into a lunar trailing circular orbit - an Earth orbit, at lunar distance. A later mission, using Dragon and launched by a Falcon Heavy, performs a rendezvous with the ERV in the lunar trailing orbit, retrieves the sample container and breaks the chain of contact with Mars by transferring the sample into a sterile and secure container. With the sample contained, the retrieving spacecraft makes a controlled Earth re-entry preventing any unintended release of pristine martian materials into the Earth's biosphere. The analysis methods employed standard and specialized aerospace engineering tools. Mission system elements were analyzed with either direct techniques or by using parametric mass estimating relationships (MERs). The architecture was iterated until overall mission convergence was achieved on at least one path. Subsystems analyzed in this study include support structures, power system, nose fairing, thermal insulation, actuation devices, MAV exhaust venting, and GN&C. Best practice application of loads, mass growth contingencies, and resource margins were used. For Falcon Heavy capabilities and Dragon subsystems we utilized publically available data from SpaceX, published analyses from other sources, as well as our own engineering and aerodynamic estimates. Earth Launch mass is under 11 mt, which is within the estimated capability of a Falcon Heavy, with margin. Total entry masses between 7 and 10 mt were considered with closure occurring between 9 and 10 mt. Propellant mass fractions for each major phase of the EDL - Entry, Terminal Descent, and Hazard Avoidance - have been derived. An assessment of the effect of the entry conditions on the thermal protection system (TPS), currently in use for Dragon missions, shows no significant stressors. A useful payload mass of 2.0 mt is provided and includes mass growth allowances for the MAV, the ERV, and mission unique equipment. We also report options for the MAV and ERV, including propulsion systems, crewed versus robotic retrieval mission, as well as direct Earth entry. International planetary protection policies as well as verifiable means of compliance will have a large impact on any MSR mission design. We identify areas within our architecture where such impacts occur. We also describe preliminary compliance measures that will be the subject of future work. This work shows that emerging commercial capabilities as well as new methodologies can be used to efficiently support an important planetary science objective. The work also has applications for human exploration missions that use propulsive EDL techniques

Red Dragon↗

NASA NTRS2004

A Survey of Formal Methods for Intelligent Swarms

Swarms of intelligent autonomous spacecraft, involving complex behaviors and interactions, are being proposed for future space exploration missions. Such missions provide greater flexibility and offer the possibility of gathering more science data than traditional single spacecraft missions. The emergent properties of swarms make these missions powerful, but simultaneously far more difficult to design, and to assure that the proper behaviors will emerge. These missions are also considerably more complex than previous types of missions, and NASA, like other organizations, has little experience in developing or in verifying and validating these types of missions. A significant challenge when verifying and validating swarms of intelligent interacting agents is how to determine that the possible exponential interactions and emergent behaviors are producing the desired results. Assuring correct behavior and interactions of swarms will be critical to mission success. The Autonomous Nano Technology Swarm (ANTS) mission is an example of one of the swarm types of missions NASA is considering. The ANTS mission will use a swarm of picospacecraft that will fly from Earth orbit to the Asteroid Belt. Using an insect colony analogy, ANTS will be composed of specialized workers for asteroid exploration. Exploration would consist of cataloguing the mass, density, morphology, and chemical composition of the asteroids, including any anomalous concentrations of specific minerals. To perform this task, ANTS would carry miniaturized instruments, such as imagers, spectrometers, and detectors. Since ANTS and other similar missions are going to consist of autonomous spacecraft that may be out of contact with the earth for extended periods of time, and have low bandwidths due to weight constraints, it will be difficult to observe improper behavior and to correct any errors after launch. Providing V&V (verification and validation) for this type of mission is new to NASA, and represents the cutting edge in system correctness, and requires higher levels of assurance than other (traditional) missions that use a single or small number of spacecraft that are deterministic in nature and have near continuous communication access. One of the highest possible levels of assurance comes from the application of formal methods. Formal methods are mathematics-based tools and techniques for specifying and verifying (software and hardware) systems. They are particularly useful for specifying complex parallel systems, such as exemplified by the ANTS mission, where the entire system is difficult for a single person to fully understand, a problem that is multiplied with multiple developers. Once written, a formal specification can be used to prove properties of a system (e.g., the underlying system will go from one state to another or not into a specific state) and check for particular types of errors (e.g., race or livelock conditions). A formal specification can also be used as input to a model checker for further validation. This report gives the results of a survey of formal methods techniques for verification and validation of space missions that use swarm technology. Multiple formal methods were evaluated to determine their effectiveness in modeling and assuring the behavior of swarms of spacecraft using the ANTS mission as an example system. This report is the first result of the project to determine formal approaches that are promising for formally specifying swarm-based systems. From this survey, the most promising approaches were selected and are discussed relative to their possible application to the ANTS mission. Future work will include the application of an integrated approach, based on the selected approaches identified in this report, to the formal specification of the ANTS mission.

Truszkowski, Walt↗