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NASA NTRS2011

New Modeling Approaches to Investigate Cell Signaling in Radiation Response

Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine and paracrine cell communication and signal transduction.

Plante, Ianik↗

NASA NTRS2016

In-Flight Personalized Medication Management

Current medication selection for treatment of astronauts during spaceflight missions is primarily dictated by the task of efficiently treating the widest possible range of physiological conditions and illnesses with a limited set of medications. Dosage and recommendations on the combination of drugs are based on the assumption of genetically equal drug sensitivity and unchanged metabolism. To our knowledge, there was no pre-flight drug sensitivity testing on a genetic level for any of the previous manned NASA space missions. Although many of the common, binary drug-drug interactions are, most likely, already considered in the ISS Medical kit composition, multi-drug and multi-drug-gene factors are not incorporated in the medication selection or prescription. Furthermore, due to the physiological changes occurring in microgravity environments, astronauts might be susceptible to potential increased drug toxicity as a result of decreased clearance of numerous drugs. In particular, perturbation of CYP450 enzymes which contribute to the hepatic metabolism of the majority of drugs may have significant effects on therapeutic efficacy and increase treatment-related toxicity5. The genes encoding the CYP450 enzymes are highly variable in humans. Inheritable variations of CYP450 hepatic metabolizer enzymes and transport proteins play a crucial role in the inter-individual variability of drug efficiency and risks of adverse drug reactions5. Additionally, there are some reports that document changes in the levels of production of drug-metabolizing enzymes in microgravity. These data can be extrapolated to provide reasonable assumptions of decreased levels of expression for most CYP450 enzymes in human body during prolonged space travel. If the prescribed medication regiment is not fully effective or causes undesirable side effects, the ability of the astronauts to function and maintain peak performance levels during space flight could be seriously compromised. Therefore, technologies capable of predicting and managing medication side effects, interactions, and toxicity of drugs during spaceflight are needed. We propose to develop and customize for NASAs applications available on the market Personalized Prescribing System (PPS) that would provide a comprehensive, non-invasive solution for safer, targeted medication management for every crew member resulting in safer and more effective treatment and, consequently, better performance. PPS will function as both decision support and record-keeping tool for flight surgeons and astronauts in applying the recommended medications for situations arising in flight. The information on individual drug sensitivity will translate into personalized risk assessment for adverse drug reactions and treatment failures for each drug from the medication kit as well as predefined outcome of any combination of them. Dosage recommendations will also be made individually. The mobile app will facilitate ease of use by crew and medical professionals during training and flight missions.

Personalized Medication↗

NASA NTRS2005

Interaction Challenges in Human-Robot Space Exploration

In January 2004, NASA established a new, long-term exploration program to fulfill the President's Vision for U.S. Space Exploration. The primary goal of this program is to establish a sustained human presence in space, beginning with robotic missions to the Moon in 2008, followed by extended human expeditions to the Moon as early as 2015. In addition, the program places significant emphasis on the development of joint human-robot systems. A key difference from previous exploration efforts is that future space exploration activities must be sustainable over the long-term. Experience with the space station has shown that cost pressures will keep astronaut teams small. Consequently, care must be taken to extend the effectiveness of these astronauts well beyond their individual human capacity. Thus, in order to reduce human workload, costs, and fatigue-driven error and risk, intelligent robots will have to be an integral part of mission design.

Fong, Terrence↗

NASA NTRS2021

Space Biology Beyond LEO Instrumentation & Science Series - Science Working Group 2021 Annual Report

Human space exploration was never intended to stop within low Earth orbit (LEO). Although nearly all of biological research in space has taken place in LEO, on the Space Shuttle, International Space Station (ISS), and free-flyer CubeSat missions, NASA's recent shift in emphasis toward human exploration of the Moon and ultimately Mars necessitates a shift in the focus of its research in the biological sciences [1]. Specifically, in 2022 and beyond, the Division of Biological and Physical Sciences seeks to pivot toward a focus on Thriving In DEep Space (TIDES), furthering the fundamental research necessary for understanding risks and mitigation strategies for deep-space stressors on human crew, plants, and their microbiomes. This effort entails both research on model organisms to elucidate the molecular processes underlying the biological consequences of deep-space exposure, and research on the organisms that will be necessary companions to sustain life and facilitate resource utilization in long-duration missions.

R Craig Everroad↗

NASA NTRS2012

Using the Design for Demise Philosophy to Reduce Casualty Risk Due to Reentering Spacecraft

Recently the reentry of a number of vehicles has garnered public attention due to their risk of human casualty due to fragments surviving reentry. In order to minimize this risk for their vehicles, a number of NASA programs have actively sought to minimize the number of components likely to survive reentry at the end of their spacecraft's life in order to meet and/or exceed NASA safety standards for controlled and uncontrolled reentering vehicles. This philosophy, referred to as "Design for Demise" or D4D, has steadily been adopted, to at least some degree, by numerous programs. The result is that many programs are requesting evaluations of components at the early stages of vehicle design, as they strive to find ways to reduce the number surviving components while ensuring that the components meet the performance requirements of their mission. This paper will discuss some of the methods that have been employed to ensure that the consequences of the vehicle s end-of-life are considered at the beginning of the design process. In addition this paper will discuss the technical challenges overcome, as well as some of the more creative solutions which have been utilized to reduce casualty risk.

Kelley, R. L.↗

NASA NTRS2010

Molecular and Histopathological Changes in Mouse Intestinal Tissue After Proton Exposure

Radiation in space, including types from solar particle events (SPE's), poses serious health risks to astronauts and is especially dangerous for long duration missions. Protons are the most abundant particles in deep space and to date there is little known about the details of the negative consequences crew members will face upon exposure to them. This ongoing project involves a mouse model subjected to several minutes of proton radiation at an energy of 250 MeV and doses of 0 Gy, 0.1 Gy, 1 Gy, and 2 Gy. The gastrointestinal tract of each animal was dissected four hours post-irradiation and the small intestine was isolated and flash-frozen. Three specimens per dose were studied. Tissue was homogenized and RNA was isolated in order for cDNA synthesis and real-time PCR to be performed. Gene expression changes are currently being analyzed specific to mouse apoptosis. Immunohistochemistry will be used to confirm any significant changes found in the analyses. Immunohistochemistry is also being used to observe gamma H2AX staining to learn of any DNA damage that occurred as a result of proton exposure. We expect to see increased DNA damage due to proton exposure. Finally, histopathologic observation of the tissue will be completed using standard H&E staining methods to screen for morphologic changes. Increased apoptosis is expected to be seen in the tissues which is typical of radiation damage. Observations will be confirmed by a pathologist.

Purgason, A.↗

NASA NTRS2010

Shuttle Environmental Assurance: Brominated Flame Retardants - Concerns, Drivers, Potential Impacts and Mitigation Strategies

Brominated Flame Retardants (BFRs) are widely used in the manufacture of electrical and electronic components and as additives in formulations for foams, plastics and rubbers. The United States (US) and the European Union (EU)have increased regulation and monitoring of of targeted BFRs, such as Polybrominated Diphenyl Ethers (PBDEs) due to the bioaccumulative effects in humans and animals. In response, manufacturers and vendors of BFR-containing materials are changing flame-retardant additives, sometimes without notifying BFR users. In some instances, Deca-bromodiphenylether (Deca-BDE) and other families of flame retardants are being used as replacement flame retardants for penta-BDE and octa-BDE. The reformulation of the BFR-containing material typically results in the removal of the targeted PBDE and replacement with a non-PBDE chemical or non-targeted PBDE. Many users of PBDE -based materials are concerned that vendors will perform reformulation and not inform the end user. Materials performance such as flammability, adhesion , and tensile strength may be altered due to reformulation. The requalification of newly formulated materials may be required, or replacement materials may have to be identified and qualified. The Shuttle Enviornmental Assurance (SEA) team indentified a risk to the Space Shuttle Program associated with the possibility that targeted PBDEs may be replaced without notification. Resultant decreases in flame retardancy, Liquid Oxygen (LOX) compatibility, or material performance could have serious consequences.

Clark-Ingram, Marceia↗

NASA NTRS1973

Meeting the challenge of advanced helicopters.

Wind tunnel tests that are conducted during the course of a typical aircraft development program are considered. The objectives of a test program are to reduce technical and financial risk and to improve product performance. Typical fixed-wing and rotary-wing aircraft development programs are compared. It is concluded that existing wind tunnel practice is not adequate in relation to the consequences from serious problems remaining undetected until flight test. In fact, the ultimate goal of the wind tunnel test program should leave nothing for the flight test program but the demonstration of the final product.-

Kelly, M. W.↗

NASA NTRS2001

Remote Sensing, GIS, and Vector-Borne Disease

The concept of global climate change encompasses more than merely an alteration in temperature; it also includes spatial and temporal covariations in precipitation and humidity, and more frequent occurrence of extreme weather events. The impact of these variations, which can occur at a variety of temporal and spatial scales, could have a direct impact on disease transmission through their environmental consequences for pathogen, vector, and host survival, as well as indirectly through human demographic and behavioral responses. New and future sensor systems will allow scientists to investigate the relationships between climate change and environmental risk factors at multiple spatial, temporal and spectral scales. Higher spatial resolution will provide better opportunities for mapping urban features previously only possible with high resolution aerial photography. These opportunities include housing quality (e.g., Chagas'disease, leishmaniasis) and urban mosquito habitats (e.g., dengue fever, filariasis, LaCrosse encephalitis). There are or will be many new sensors that have higher spectral resolution, enabling scientists to acquire more information about parameters such as soil moisture, soil type, better vegetation discrimination, and ocean color, to name a few. Although soil moisture content is now detectable using Landsat, the new thermal, shortwave infrared, and radar sensors will be able to provide this information at a variety of scales not achievable using Landsat. Soil moisture could become a key component in transmission risk models for Lyme disease (tick survival), helminthiases (worm habitat), malaria (vector-breeding habitat), and schistosomiasis (snail habitat).

Beck, Louisa R.↗

NASA NTRS2012

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

Westby, Christian M.↗

NASA NTRS2017

Young People's Burden: Requirement of Negative CO2 Emissions

Global temperature is a fundamental climate metric highly correlated with sea level, which implies that keeping shorelines near their present location requires keeping global temperature within or close to its preindustrial Holocene range. However, global temperature excluding short-term variability now exceeds +1 C relative to the 1880 - 1920 mean and annual 2016 global temperature was almost +1.3 C. We show that global temperature has risen well out of the Holocene range and Earth is now as warm as it was during the prior (Eemian) interglacial period, when sea level reached 6 - 9 m higher than today. Further, Earth is out of energy balance with present atmospheric composition, implying that more warming is in the pipeline, and we show that the growth rate of greenhouse gas climate forcing has accelerated markedly in the past decade. The rapidity of ice sheet and sea level response to global temperature is difficult to predict, but is dependent on the magnitude of warming. Targets for limiting global warming thus, at minimum, should aim to avoid leaving global temperature at Eemian or higher levels for centuries. Such targets now require "negative emissions", i.e., extraction of CO2 from the air. If phasedown of fossil fuel emissions begins soon, improved agricultural and forestry practices, including reforestation and steps to improve soil fertility and increase its carbon content, may provide much of the necessary CO2 extraction. In that case, the magnitude and duration of global temperature excursion above the natural range of the current interglacial (Holocene) could be limited and irreversible climate impacts could be minimized. In contrast, continued high fossil fuel emissions today place a burden on young people to undertake massive technological CO2 extraction if they are to limit climate change and its consequences. Proposed methods of extraction such as bioenergy with carbon capture and storage (BECCS) or air capture of CO2 have minimal estimated costs of USD 89 - 535 trillion this century and also have large risks and uncertain feasibility. Continued high fossil fuel emissions unarguably sentences young people to either a massive, implausible cleanup or growing deleterious climate impacts or both.

Hansen, James↗

NASA NTRS1975

Contamination, misuse and abuse of the global oceans leading to ecosystem damage and destruction, health consequences and international conflict

Unregulated uses of the oceans may threaten the global ecological balance, alter plant and animal life and significantly impact the global climatic systems. Recent plans to locate large scale structures on the oceans and to exploit the mineral riches of the seas pose even greater risk to the ecological system. Finally, increasing use of the oceans for large scale transport greatly enhances the probability of collision, polluting spills and international conflict.

Source record↗

NASA NTRS1972

Manned space flight nuclear system safety. Volume 3: Reactor system preliminary nuclear safety analysis. Part 3: Nuclear Safety Analysis Document (NSAD)

Nuclear safety analysis as applied to a space base mission is presented. The nuclear safety analysis document summarizes the mission and the credible accidents/events which may lead to nuclear hazards to the general public. The radiological effects and associated consequences of the hazards are discussed in detail. The probability of occurrence is combined with the potential number of individuals exposed to or above guideline values to provide a measure of accident and total mission risk. The overall mission risk has been determined to be low with the potential exposure to or above 25 rem limited to less than 4 individuals per every 1000 missions performed. No radiological risk to the general public occurs during the prelaunch phase at KSC. The most significant risks occur from prolonged exposure to reactor debris following land impact generally associated with the disposal phase of the mission where fission product inventories can be high.

Source record↗

NASA NTRSDate not supplied

Track Structure Components: Characterizing Energy Deposition from Direct and Peripheral Hits in Spherical Cells

Energy deposition by ionizing radiation in micrometric targets (microdosimetry), representative of cells, is very important to understand the effect of radiation and the cellular and biological response. Microdosimetry is used to estimate quality factors for risk assessment in radiation protection and quantify Relative Biological Effectiveness (RBE) for treatment planning of hadron radiation therapy. Radiation physics has shown that ionizing radiation deposit their energy in a complex manner, the track structure. Consequently, energy deposited in a target is a function of factors like the ion type, its energy and the irradiated volume.

Ianik Plante↗

NASA NTRSDate not supplied

Developing Standards for AI/ML Systems in Civil Aviation: Challenges and Barriers

The inability to establish appropriate assurance methods for AI/ML components in safety critical systems leaves us unable to effectively manage the risks and benefits of such systems. It drives cost of development for systems with AI/ML components uneconomically high, it delays the adoption of systems with AI/ML components at scale, and it can result in catastrophic consequences in terms of the safety of systems with AI/ML components. In this presentation we will explore what constitutes sufficient scientific-based evidence to substantiate a safety claim related to an AI/ML component performing a safety-critical function.

AI/ML Standards↗

NASA NTRSDate not supplied

Validation of A Simulation Environment for Future Space Traffic Management

This study presents initial results of a newly developed simulation environment intendedto explore and assess future Space Traffic Management (STM) scenarios. The number ofnew Resident Space Objects (RSOs) in near-Earth orbit is expected to increase significantlywith the expected future deployment of a number of large constellations. These futurescenarios involve the addition of many tens of thousands of new RSOs, making the analysisinto their impact on collision risk extend beyond what traditional data-mining of present-dayconjunction data can reliably predict. To address this, a robust simulation environment wasdeveloped that implements a full force-model for orbit propagation, and computes continuousall-on-all conjunction statistics for arbitrarily large catalog sizes and simulation timeframes.Collision avoidance and station-keeping maneuvers can be optionally implemented based onconfigurable user inputs including physical characteristics and spacecraft meta-data (e.g.,commercial/government, owner country, etc.). Constellation build-out and de-orbit scenarioswere also implemented and modeled based on real-data analysis. Validation of the simulationresults was a critical component of the simulation development, and was done using the currentcatalog with comparisons against both public and internal NASA data-sets. The comparisonsdemonstrate that, with the appropriate settings, representative levels of conjunction ratesand probabilities can be obtained, providing confidence that the simulation tool can generatemeaningful outcomes for test scenarios. As an initial demonstration of the tool’s capabilities,year-long simulations with station-keeping were conducted to examine conjunction historiesusing both the current object catalog (5800 active satellites) and a hypothetical 60,000 objectscenario involving five potential large constellations. Output metrics include the number ofconjunction events, estimates of collision consequence (fragmentation), delta-V maneuver costs,and the probability of at least one collision occurring. The results highlight the potential thatthe simulation tool has for incorporating and running performance comparisons between, e.g.,various sets of maneuver guidelines, industry norms, and definitions of risk, with the overallobjective of providing actionable data to STM policy makers. The presentation will providean overview of the simulation development and validation efforts, as well as a discussion ofobservations gathered from the initial simulations performed.

conjunction assessment↗

NASA NTRS2010

Risk Control Through the Use of Procedures - A Method for Evaluating the Change in Risk

Organizations use procedures to influence or control the behavior of their workers, but often have no basis for determining whether an additional rule, or procedural control will be beneficial. This paper outlines a proposed method for determining if the addition or removal of procedural controls will impact the occurrences of critical consequences. The proposed method focuses on two aspects: how valuable the procedural control is, based on the inevitability of the consequence and the opportunity to intervene; and how likely the control is to fail, based on five procedural design elements that address how well the rule or control has been Defined, Assigned, Trained, Organized and Monitored-referred to as the DATOM elements

Praino, Gregory↗

NASA NTRS2017

Cross-Disciplinarity in the Advance of Antarctic Ecosystem Research

The biodiversity, ecosystem services and climate variability of the Antarctic continent, and the Southern Ocean are major components of the whole Earth system. Antarctic ecosystems are driven more strongly by the physical environment than many other marine and terrestrial ecosystems. As a consequence, to understand ecological functioning, cross-disciplinary studies are especially important in Antarctic research. The conceptual study presented here is based on a workshop initiated by the Research Programme Antarctic Thresholds - Ecosystem Resilience and Adaption of the Scientific Committee on Antarctic Research, which focused on challenges in identifying and applying cross-disciplinary approaches in the Antarctic. Novel ideas, and first steps in their implementation, were clustered into eight themes, ranging from scale problems, risk maps, organism and ecosystem responses to multiple environmental changes, to evolutionary processes. Scaling models and data across different spatial and temporal scales were identified as an overarching challenge. Approaches to bridge gaps in the research programmes included multi-disciplinary monitoring, linking biomolecular findings and simulated physical environments, as well as integrative ecological modelling. New strategies in academic education are proposed. The results of advanced cross-disciplinary approaches can contribute significantly to our knowledge of ecosystem functioning, the consequences of climate change, and to global assessments that ultimately benefit humankind.

Scaling↗