The Health Risks of Extraterrestrial Environments
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Welcome to The Health Risks of Extraterrestrial Environments (THREE), an encyclopedic site whose goal is to present a discussion of the space radiation environment and its health risks to humans. The intent is to make this a good starting point for researchers new to either space, radiation, or both; a source of useful information for established investigators; and a teaching tool for students.

There are links across the top of the website to five distinct pages including the Home page you are reading.

The Encyclopedia link leads to a set of articles covering all aspects of space radiation concern, as well as an introduction to each topic. Early articles contain, in Flash format, slides that were presented to students of the NASA Space Radiation Summer School. Later articles have been written by investigators active in the relevant research area and have been peer reviewed under supervision of an associate editor. These articles may be viewed in PDF format. Click on Recent Articles below for a list of the most recent postings.

Citations to reports and to articles published in the scientific literature, that the associate editors consider to be of interest to the space radiation community, are listed monthly; in most cases, together with a brief description by one of the article authors. The current month's listing may be accessed by clicking on the Current Research Citations link below. These citations are collected and archived on the Bibliography page, sorted by Encyclopedia topics, as a living bibliographic complement to the encyclopedia articles.

Reviews of recently published books on topics related to space radiation may be found under the Book Reviews link below. General news items of interest to the THREE community are listed under the In the News link below.

The Archive is a repository of material kept for reference; the site contains records documenting the history of the NASA Space Radiation Summer School, as well as information from prior Space Radiation Investigators’ Workshops and a history of Featured Articles previously featured under the Featured Article link below. A few important topics are accessible from the Multimedia link; future material will be added as appropriate.

Finally, a glossary of terms related to space radiation research is available on the similarly named page.

The THREE Editorial Board is responsible for oversight of the content and policies for this site. It is hosted by the NASA Johnson Space Center. For further information, including the latest Annual Report, please refer to the links on the left-hand side.

Contributions to any part of THREE, especially submissions for articles, are welcome. Please send your comments and contributions along with your contact information to the THREE Page Editor.

Walter Schimmerling
THREE Chief Editor

  • PolyFit: A C++ code for polynomial curve fit with calculation of error bars (Article) Ianik Plante

    Posted May 28, 2021

  • Microglia Cells, The Brain Innate Immune System: Friend or Foe? (Article) Maria Serena Paladini, Xi Feng, Karen Krukowski and Susanna Rosi

    Posted February 24, 2021

  • The Galactic Cosmic Ray Simulator at the NASA Space Radiation Research Laboratory (Article) Lisa C. Simonsen, Tony C. Slaba, Peter Guida, and Adam Rusek

    Posted December 16, 2020

  • Current Active Detectors for Dosimetry and Spectrometry on the International Space Station (Article) Cary Zeitlin, Larry Pinsky

    Posted May 5, 2020

  • MicroRNAs (miRNAs), the Final Frontier: The Hidden Master Regulators Impacting Biological Response in All Organisms Due to Spaceflight (Article) Charles Vanderburg, Afshin Beheshti

    Posted March 9, 2020

  • TOPAS-nBio: A Monte Carlo simulation toolkit for cell-scale radiation effects (Article) J. Schuemann, A. McNamara, J. Ramos, J. Perl, K. Held, H. Zhu, S. Incerti, H. Paganetti, B. Faddegon

    Posted December 6, 2019

  • Space Radiation-Induced Cognitive Deficits Following Head-Only, Whole Body, or Body-Only Exposures (Article) Catherine M. Davis and Bernard M. Rabin

    Posted September 11, 2019

  • Track structure and the quality factor for space radiation cancer risk (PDF) Dudley T. Goodhead

    Correction Posted September 28, 2018

  • Abortive apoptosis and its profound effects on radiation‐, chemical‐, and oncogene induced carcinogenesis (PDF) Xinjian Liu, Ian Cartwright, Fang Li, and Chuan-Yuan Li

    Posted June 21, 2018

  • Using Proteomics Approaches to Assess Mechanisms Underlying Low Linear Energy Transfer or Galactic Cosmic Radiation-Induced Cardiovascular Disease (PDF) Zachary D. Brown, Muath Bishawi, and Dawn E. Bowles

    Posted May 21, 2018

  • The Emerging Role of Exosomes in the Biological Processes Initiated by Ionizing Radiation (PDF) Munira A Kadhim, Scott J Bright, Ammar H J Al-Mayah, and Edwin Goodwin

    Posted April 11, 2018

  • Solar Particle Events and Radiation Exposure in Space (PDF) Shaowen Hu

    Posted March 31, 2017

  • An introduction to space radiation and its effects on the cardiovascular system (PDF) Marjan Boerma

    Posted October 13, 2016

  • Precise Genome Engineering and the CRISPR Revolution (Boldly Going Where No Technology Has Gone Before.) (PDF) Eric A. Hendrickson

    Posted April 6, 2016

Microglia Cells, The Brain Innate Immune System: Friend or Foe? (PDF)

Paladini Maria Serena,a,b Feng Xi,a,b Krukowski Karen,a,b and Rosi Susannaa,b,c,d,e
a Department of Physical Therapy and Rehabilitation Science, University of California at San Francisco, San Francisco, CA, USA.
b Brain and Spinal Injury Center, University of California at San Francisco, San Francisco, CA, USA.
c Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA, USA.
d Weill Institute for Neuroscience, University of California at San Francisco, San Francisco, CA, USA.
e Kavli Institute of Fundamental Neuroscience, University of California at San Francisco, San Francisco, CA, USA.

Microglial cells are the resident immune cells of the Central Nervous System (CNS). Under physiological conditions, microglia constantly surveil their surrounding parenchyma and act as scavenger cells to maintain a healthy environment within the CNS. Following different insults to the CNS, microglia turn into a "reactive" state characterized by the production of inflammatory mediators that promote tissue repair to restore homeostasis. If inflammation is not in check, chronic microglia activation results in damage to the brain and leads to persistent cognitive impairments. Microglia display sex-specific features in adult mice; specifically, microglia from female mice have been found to be less reactive. Exposure to space radiation results in chronic activation of microglia in male but not in female mice. Interestingly, manipulating microglia after exposure to space radiation can prevent the development of cognitive deficits in adult male mice. These discoveries may provide clues in how to protect astronauts' cognitive functions both during the missions and after return.

Space radiation exposure triggers chronic microglia activation and subsequent memory impairments. Microglia depletion and complete repopulation prevent memory deficits after space radiation.

Donald V. Reames: “Solar Energetic Particles: A Modern Primer on Understanding Sources, Acceleration, and Propagation” (Springer, 2017). (PDF); reviewed by Stephen Kahler.

Laurence R. Young, ScD 1936-2021

It is with great sadness that we learned about the death of Laurence (Larry) R. Young, Apollo program professor emeritus of astronautics from the Massachusetts Institute of Technology. As the linked obituary notes, Dr. Young was influential in many aspects of space research. Most recently, Dr. Young was the Director of The Academy of Bioastronautics arm of The Translational Research Institute for Space Health (TRISH), which emerged from a cooperative agreement between NASA and a consortium led by Baylor College of Medicine. Despite his exceptional career achievements, Dr. Young was an extremely approachable leader of the Academy, frequently offering kind, inspirational, yet practical advice to these rising stars in space research. Dr. Young will be greatly missed.
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2022 Investigators' Workshop

Due to the uncertainties surrounding COVID-19 and the Human Research Program (HRP) emphasis on the health and safety of our investigator community, HRP has decided to conduct the 2022 Investigators' Workshop (IWS) as a virtual meeting. The Workshop will be held online February 7-10, 2022.
Abstract submission will be open through October 18, 2021.

To submit your abstract, please click on this link abstract submittal.
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Radiation Research Society 67th Annual International Meeting

As you are all aware the Delta variant of COVID-19 has drastically changed the pandemic landscape, and resulted in a new surge of infections in the US and worldwide. This has resulted in the implementation of new; and/or the extension, of travel restrictions and mandates. Recently, the governor of Puerto Rico has implemented a very strict vaccine and mask mandate with stiff financial and legal penalties for non-compliance. With these new restrictions in mind, the RRS Governing Council has made the important decision to transition the live meeting in San Juan to an immersive virtual meeting that will occur over the same dates, October 3rd - 6th, 2021. This decision was based on our overwhelming concern for the safety and well-being of our members, invited speakers, exhibitors, staff, local island community and the families of all involved.
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WRMISS 2021 postponement

It is still too early to run our face-to-face meeting in this year. Target is a meeting in the last week of March or the first week in April. We need to settle this and let you know in a couple of weeks. Return to top

Information on NASA Portal for Grantee Accepted Manuscripts

The NASA Scientific and Technical Information (STI) Program is developing an external submission portal for NASA-funded investigators to submit Accepted Manuscripts and other STI products. The portal is expected to be available later this summer.

The external portal will be used in place of the National Institutes of Health Manuscripts System (NIHMS), for grant and cooperative agreement recipients. The external portal will provide a more direct and streamlined Accepted Manuscript submission process for recipients. The STI Program will send communications prior to the start date with instructions and reminders.

As part of this transition, an information page about the new portal is available on the STI Program website which will be updated throughout the process:

The STI Program invites comments and questions about this new external manuscript submission portal via the Research Access Help Desk at
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NASA's STAR Program

Spaceflight Technologies, Application, and Research (STAR) is a virtual NASA program for space biosciences training. The annual course targets principal investigators (PIs), senior research scientists, and postdoctoral scholars and aims to facilitate their entry to space biology and preparation for conducting spaceflight experiments using NASA and commercial platforms. A call for the second cohort of participants is due to be released. The 2021 STAR Course will take place virtually between September 2021 – February 2022. and will consist of 2 seminars per month, 2 hours long each, on weekday afternoons EST. STAR 2021 Solicitation will be open on NSPIRES in March 2021, with the deadline at the end of May 2021. Selections and announcements will be made in July 2021.
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Radiation countermeasures for hematopoietic acute radiation syndrome: Growth factors, cytokines and beyond
Singh VK, Seed TM. in Int J Radiat Biol. 2021 Aug 17;1-67. Review. [8/30/2021]
This article reports the status of pharmaceuticals currently being developed for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. A limited number of medicinals (namely filigrastim, pegfiligrastim, sargramostim and romiplostim) have been deemed sufficiently safe and effective by the US FDA for use in treating the ‘hematopoietic acute radiation syndrome. All of these agents are recombinant growth factors that target and stimulate progenitors within bone marrow, thus serving to foster hematopoietic recovery following acute irradiation. Comparable medicinals for the other major sub-syndromes of ARS are currently lacking, but much needed. The research and development of such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.
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Protective Effects of Amino Acids on Plasmid DNA Damage Induced by Therapeutic Carbon Ions
Katsunori Yogo, Chieko Murayama, Ryoichi Hirayama, Ken-ichiro Matsumoto, Ikuo Nakanishi, Hiromichi Ishiyama, Hiroshi Yasuda Radiation Research, 196(2), 197-203, (27 May 2021) [8/25/2021]
With the aim of finding the most effective radioprotector against heavy ions, we investigated systematically the radioprotective effects of five amino acids: tryptophan (Trp), cysteine (Cys), methionine (Met), valine (Val) and alanine (Ala) on the damage yields of plasmid DNA. The samples were irradiated with 290 MeV/u carbon-ion beams on spread-out Bragg peak at HIMAC, Japan. As results, some amino acids such as Trp, Cys and Met showed good radioprotective effects in regard to the double strand breaks of plasmid DNA. It was indicated that the radioprotective effects against carbon ions could be explained primarily based on the scavenging capacity of radiation-induced radicals.
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A proposed change to astronaut exposures limits is a giant leap backwards for radiation protection
Francis A. Cucinotta, Walter Schimmerling, Eleanor A. Blakely, Tom K. Hei, Life Sciences in Space Research, 31, 2021, 59-70,ISSN 2214-5524 [8/16/2021]
A recent NAS report, in an effort to minimize differences in age and sex on flight opportunities, suggests a 600 mSv career effective dose limit based on a median estimate to reach 3% cancer fatality for 35-year old females. The NAS report does not call out examples where females would be excluded from space missions planned in the current decade using the current radiation limits at NASA. In addition, there are minimal considerations of the level of risk to be encountered at this exposure level with respect to the uncertainties of heavy ion radiobiology, and risks of cancer, as well as cognitive detriments and circulatory diseases. Furthermore, their recommendation to limit Sieverts and not risk in conjunction with a waiver process is essentially a recommendation to remove radiation limits for astronauts. We discuss issues with several of the NAS recommendations with the conclusion that the recommendations could have negative impacts on crew health and safety, and violate the three principles of radiation protection (to prevent clinically significant deterministic effects, limit stochastic effects, and practice ALARA), which would be a giant leap backwards for radiation protection.
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Space Radiation Dosimetry at the Exposure Facility of the International Space Station for the Tanpopo Mission
Kodaira S, Naito M, Uchihori Y, Hashimoto H, Yano H, Yamagishi A. Astrobiology. 2021 Aug 4.. doi: 10.1089/ast.2020.2427. Epub ahead of print. PMID: 34348047. [8/14/2021]
Radiation dosimetry was carried out at the exposure facility (EF) and the pressurized module (PM) of the Japanese Kibo module installed in the International Space Station as one study on environmental monitoring for the Tanpopo mission. Three exposure panels and three references including biological and organic samples and luminescence dosimeters were launched to obtain data for different exposure durations during 3 years from May 2015 to July 2018. The dosimeters were equipped with additional shielding materials (0.55, 2.95, and 6.23 g/cm2 mass thickness). The relative dose variation, as a function of shielding mass thickness, was observed and compared with Monte Carlo simulations with respect to galactic cosmic rays (GCRs) and typical solar energetic particles (SEPs). The mean annual dose rates were DEF = 231 ± 5 mGy/year at the EF and DPM = 82 ± 1 mGy/year at the PM during the 3 years. The PM is well shielded, and the GCR simulation indicated that the measured mean dose reduction ratio inside the module (DPM/DEF = 0.35) required ∼26 g/cm2 additional shielding mass thickness. Observed points of the dose reduction tendency could be explained by the energy ranges of protons (10-100 MeV), where the protons passed through, or were absorbed in, the shielding materials of different mass thickness that surrounded dosimeters.
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Space radiation-induced alterations in the hippocampal ubiquitin-proteome system
Tidmore A, Dutta SM, Fesshaye AS, Russell WK, Duncan VD, Britten RA. Int J Mol Sci. 2021 Jul 19;22(14):7713. [8/9/2021]
Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.
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Associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation
Minnier J, Emmett MR, Perez R, Ding LH, Barnette BL, Larios RE, Hong C, Hwang TH, Yu Y, Fallgren CM, Story MD, Weil MM, Raber J. Sci Rep. 2021 Jul 21;11(1):14899. [7/31/2021]
To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.
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Transcriptomic analysis links hepatocellular carcinoma (HCC) in HZE ion irradiated mice to a human HCC subtype with favorable outcomes
Ding LH, Yu Y, Edmondson EF, Weil MM, Pop LM, McCarthy M, Ullrich RL, Story MD. Sci Rep. 2021 Jul 7; 11(1): 14052 [7/20/2021]
High-charge, high-energy ion particle (HZE) radiations are extraterrestrial in origin and characterized by high linear energy transfer (high-LET), which causes more severe cell damage than low-LET radiations like γ-rays or photons. High-LET radiation poses potential cancer risks for astronauts on deep space missions, but the studies of its carcinogenic effects have relied heavily on animal models. It remains uncertain whether such data are applicable to human disease. Here, we used genomics approaches to directly compare high-LET radiation-induced, low-LET radiation-induced and spontaneous hepatocellular carcinoma (HCC) in mice with a human HCC cohort from The Cancer Genome Atlas (TCGA). We identified common molecular pathways between mouse and human HCC and discovered a subset of orthologous genes (mR-HCC) that associated high-LET radiation-induced mouse HCC with a subgroup (mrHCC2) of the TCGA cohort. The mrHCC2 TCGA cohort was more enriched with tumor-suppressing immune cells and showed a better prognostic outcome than other patient subgroups.
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What can space radiation protection learn from radiation oncology?
Tinganelli W, Luoni F, Durante M.Life Sci Space Res. 2021 Aug;30:82-95. [7/16/2021]
Protection from cosmic radiation of crews of long-term space missions is now becoming an urgent requirement to allow a safe colonization of the moon and Mars. Epidemiology provides little help to quantify the risk, because the astronaut group is small and as yet mostly involved in low-Earth orbit mission, whilst the usual cohorts used for radiation protection on Earth (e.g. atomic bomb survivors) were exposed to a radiation quality substantially different from the energetic charged particle field found in space. However, there are over 260,000 patients treated with accelerated protons or heavier ions for different types of cancer, and this cohort may be useful for quantifying the effects of space-like radiation in humans. Space radiation protection and particle therapy research also share the same tools and devices, such as accelerators and detectors, as well as several research topics, from nuclear fragmentation cross sections to the radiobiology of densely ionizing radiation. The transfer of the information from the cancer radiotherapy field to space is manifestly complicated, yet the two field should strengthen their relationship and exchange methods and data.
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Cancer incidence and mortality in the USA Astronaut Corps, 1959-2017
Reynolds R, Little MP, Day S, Charvat J, Blattnig S, Huff J, Patel ZS. Occup Environ Med. 2021 May 26. Online ahead of print. [6/29/2021]
Cancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. In this work, we compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with those in the US general population. Overall cancer incidence and mortality were slightly lower than expected from national rates with SIR = 82 (95% CI=63–104) and SMR 72 (95% CI 44–111) with a modest 14% reduction in case-fatality ratio. We note a significant increase in incidence of melanoma that is consistent with that observed in aircraft pilots, suggesting this may be associated with ultraviolet radiation or lifestyle factors rather than any astronaut-specific exposure. Reductions in lung cancer incidence and mortality, and trends toward such reductions in colon cancer, may be explained in part by healthy lifestyle, as well as differential screening among astronauts.
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Evaluating the long-term effect of space radiation on the reproductive normality of mammalian sperm preserved on the International Space Station
Wakayama S, Ito D, Kamada Y, Shimazu T, Suzuki T, Nagamatsu A, Araki R, Ishikawa T, Kamimura S, Hirose N, Kazama K, Yang L, Inoue R, Kikuchi Y, Hayashi E, Emura R, Watanabe R, Nagatomo H, Suzuki H, Yamamori T, Tada MN, Osada I, Umehara M, Sano H, Kasahara H, Higashibata A, Yano S, Abe M, Kishigami S, Kohda T, Ooga M, Wakayama T. Sci Adv. 2021 Jun 11;7(24):eabg5554. [6/28/2021]
Space radiation may cause DNA damage to cells and concern for the inheritance of mutations in offspring after deep space exploration. However, there is no way to study the long-term effects of space radiation using biological materials. Here, we developed a method to evaluate the biological effect of space radiation and examined the reproductive potential of mouse freeze-dried spermatozoa stored on the International Space Station (ISS) for the longest period in biological research. The space radiation did not affect sperm DNA or fertility after preservation on ISS, and many genetically normal offspring were obtained without reducing the success rate compared to the ground-preserved control. The results of ground x-ray experiments showed that sperm can be stored for more than 200 years in space. These results suggest that the effect of deep space radiation on mammalian reproduction can be evaluated using spermatozoa, even without being monitored by astronauts in Gateway.
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An easy-to-use function to assess deep space radiation in human brains
Khaksarighiri S, Guo J, Wimmer-Schweingruber R, Narici L. Sci Rep. 2021 Jun 3;11(1):11687. [6/14/2021]
Health risks from radiation exposure in space are an important factor for astronauts' safety as they venture on long-duration missions to the Moon or Mars. It is important to assess the radiation level inside the human brain to evaluate the possible hazardous effects on the central nervous system especially during solar energetic particle (SEP) events. We use a realistic model of the head/brain structure and calculate the radiation deposit therein by realistic SEP events, also under various shielding scenarios. We then determine the relation between the radiation dose deposited in different parts of the brain and the properties of the SEP events and obtain some simple and ready-to-use functions which can be used to quickly and reliably forecast the event dose in the brain. Such a novel tool can be used from fast nowcasting of the consequences of SEP events to optimization of shielding systems and other mitigation strategies of astronauts in space.
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Radiation Risks in a Mission to Mars for a SolarParticle Event Similar to the AD993/4 Event
Zaman, F.A.; Townsend,L.W.; Burahmah, N.T. Aerospace2021,8, 143 [5/3/2021]
Recent studies of excess atmospheric 14C production in tree rings and in annually resolved measurements of 10Be in Arctic and Antarctic ice cores, indicate that an extremely large solar particle event (SPE) occurred in AD 993/4. The production of cosmogenic nuclei (e.g., 36Cl) indicate that the event possessed a very energetic "hard" particle spectrum, comparable to the February 1956 SPE. Estimates of the potential radiation risk to male and female crew members on a mission to Mars, from an event comparable to the AD 993/4 one, are reported in this paper. These estimates suggest that severe consequences to a crew in transit to Mars are possible. However, on the Martian surface, the additional protection afforded by the Mars atmosphere reduces but does not eliminate the risk from such an event.
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Rad-Bio-App: A discovery environment for biologists to explore spaceflight-related radiation exposures
Barker R, Costes SV, Miller J, Gebre SG, Lombardino J, Gilroy S. npj Microgravity. 2021 May 11;7(1):15. [5/23/2021]
Data on how organisms respond to radiation exposure during space missions is often complex to access and to understand. The Rad-Bio-App is a web-accessible database that addresses this challenge by allowing the user to explore the space biology experiments deposited in NASA’s GeneLab data repository in the context of their radiation exposure. The graphical user interface allows rapid searching and cross-referencing of results using a wide array of features related to each experiment, such as flight hardware or tissues sampled. Interactive filtering then helps the researcher focus on both unique and common aspects of experimental designs and associated data on radiation exposures providing target datasets for further analysis.
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The individual and combined effects of spaceflight radiation and microgravity on biologic systems and functional outcomes
Willey JS, Britten RA, Blaber E, Tahimic CGT, Chancellor J, Mortreux M, Sanford LD, Kubik AJ, Delp MD, Mao XW.and published in J Environ Sci Health C Toxicol Carcinog. 2021;39(2):129-179. [5/18/2021]
Microgravity and radiation present outside of low earth orbit represent risks to astronaut health and performance during and/or after planned long-duration missions. Most ground-based analogues (e.g., mouse or rat studies) that investigate these risks focus on each individual hazard in isolation. However, astronauts will face these (and other) hazards simultaneously during future missions, and thus understanding the biologic and functional responses of combined hazards are necessary for developing appropriate countermeasures. This review describes the biologic and functional outcomes observed in the skeletal, ocular, cardiovascular, and central nervous systems, and also stem cell responses, after exposure to ground-based microgravity (e.g., tail suspension to impart hind limb unloading and partial weight bearing models) and radiation simulations. In vitro studies and spaceflight data are discussed as appropriate.
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The role of nutrition in space exploration: Implications for sensorimotor, cognition, behavior and the cerebral changes due to the exposure to radiation, altered gravity, and isolation/confinement hazards of spaceflight
Zwart SR, Mulavara AP, Williams TJ, George K, Smith SM. Neurosci Biobehav Rev. 2021 Apr 26;S0149-7634(21)00185-8. Review. [5/12/2021]
Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut’s brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions.
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Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
Shuryak I, Brenner DJ, Blattnig SR, Shukitt-Hale B, Rabin BM. Sci Rep. 2021 Apr 23;11(1):8845 [4/30/2021]
Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal of cells by ionizing tracks, and non-targeted effects (NTE), caused by responses of other cells to signals released by traversed cells. The results of modeling analysis based on these mechanisms suggest that NTE-based radiation effects on brain function are potentially important for astronaut health and for space mission risk assessments.
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Observations of neutron radiation environment during Odyssey cruise to Mars
M.L. Litvak, I.G. Mitrofanov, A.B. Sanin, B. Bakhtin, D.V. Golovin, C. Zeitlin, Life Sciences in Space Research, 2021, Volume 29, May 2021, Pages 53-62 [4/23/2021]
In April 2001, Mars Odyssey spacecraft with the High Energy Neutron Detector (HEND) onboard was launched to Mars. HEND/Odyssey was switched on measurement mode for most of transit to Mars to monitor variations of spacecraft background and solar activity. Although HEND/Odyssey was originally designed to measure Martian neutron albedo and to search for Martian subsurface water/water ice, its measurements during cruise phase to Mars are applicable to evaluate spacecraft ambient radiation background. We have modeled the spacecraft neutron spectral density and compared it with HEND measurements to estimate neutron dose equivalent rates during Odyssey cruise phase, which occurred during the maximum period of solar cycle 23. We find that the Odyssey ambient neutron environment during May – September 2001 yields 10.6 ± 2.0 μSv per day in the energy range from 0 to 15 MeV, and about 29 μSv per day when extrapolated to the 0–1000 MeV energy range during solar quiet time (intervals without Solar Particle Events, SPEs). We have also extrapolated HEND/Odyssey measurements to different periods of solar cycle and find that during solar minimum (maximum of GCR flux), the neutron dose equivalent rate during cruise to Mars could be as high as 52 μSv per day with the same shielding. These values are in good agreement with results reported for a similar measurement made with an instrument aboard the Mars Science Laboratory during its cruise to Mars in 2011–2012.
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Effects of low dose space radiation exposures on the splenic metabolome
Laiakis EC, Shuryak I, Deziel A, Wang YW, Barnette BL, Yu Y, Ullrich RL, Fornace AJ Jr, Emmett MR., Int J Mol Sci. 2021 Mar 17;22(6):3070. [4/20/2021]
In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
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Dose fractionation during puberty is more detrimental to mammary gland development than an equivalent acute dose of radiation exposure
Wiedmeyer B, To J, Sridharan DM, Chien LC, Snijders AM, Mori H, Pluth JM. Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1521-32. [4/11/2021]
In this work we have investigated using a mouse model system how two types of radiation dose regimens may differentially impact mammary organ formation during an especially sensitive window in development, puberty. Our data revealed that fractionated radiation exposures produced greater immune and mammary defects as compared to controls and that these effects were more pronounced in the more radiation sensitive, BALB/c mice. Together, these findings suggest that fractionated low dose exposures are potentially more damaging to organ development as compared to an equivalent single acute exposure and that genetic background is an important parameter that can modify the severity of these effects.
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Tumor aggressiveness is independent of radiation quality in murine hepatocellular carcinoma and mammary tumor models
Udho EB, Huebner SM, Albrecht DM, Matkowskyj KA, Clipson L, Hedican CA, Koth R, Snow SM, Eberhardt EL, Miller D, Van Doorn R, Gjyzeli G, Spengler EK, Storts DR, Thamm DH, Edmondson EF, Weil MM, Halberg RB, Bacher JW. in Int J Radiat Biol. 2021 Mar 15;1-35. Online ahead of print. [4/2/2021]
The goal of this research is to test whether high-LET HZE radiation induced tumors are more aggressive. Murine models of mammary and liver cancer were used to compare the impact of exposure to 0.2Gy of 300MeV/n silicon ions, 3 Gy of γ-rays or no radiation. For the mammary cancer models, there was no significant change in the tumor latency or metastasis in silicon-irradiated mice compared to controls. For the liver cancer models, we observed an increase in tumor incidence but not tumor aggressiveness in irradiated mice. Thus, enhanced aggressiveness does notappear to be a uniform characteristic of all tumors in HZE-irradiated animals.
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Comparison between PHITS and GEANT4 Simulations of the Heavy Ion Beams at the BEVALAC at LBNL and the Booster Accelerator at BNL
Sungmin Pak, Francis A. Cucinotta, Life Sciences in Space Research, 29,2021,Pages 38-45, [3/24/2021]
Heavy charged particles have been discussed for clinical use due to their superior dose-depth distribution compared to conventional radiation such as X-rays. In addition, high-charge and energy (HZE) ions in galactic cosmic rays (GCR) present important health risks for crewed space missions to the Earth's moon or Mars. Experiments at heavy ion accelerators are used in radiobiology studies; however, numerical simulations of track segment or Bragg peak irradiations are complicated by the details of the beam-line and dosimetry systems. The goal of the present work is in support of biophysics modeling of historical radiobiology data at Lawrence Berkeley National Laboratory (LBNL) and more recent results from the Brookhaven National Lab (BNL) facility (NASA Space Radiation Lab (NSRL)). In this work, the Spread-Out Bragg Peak (SOBP) of 4He, 12C, and 20Ne particles, and a Bragg curve of 56Fe ion have been simulated numerically in the geometries of LBNL and BNL using the Monte-Carlo based PHITS and GEANT4 simulation toolkits. The dose contributions of primary particles and secondary particles, including neutrons and photons, in the target material are computed and discussed as well. Comparisons suggest more contributions of secondaries in GEANT4 simulations compared to PHITS simulations, and less statistical fluctuation and better prediction of neutrons in PHITS simulations. Neutrons and gamma-rays are estimated to make minor contributions to absorbed doses for these beams.
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Double-Differential FRaGmentation (DDFRG) models for proton and light ion production in high energy nuclear collisions
J. Norbury. Nuclear Instruments and Methods in Physics Research A, vol. 986, p. 164681, 2021. [3/23/2021]
A new set of Double-Differential FRaGmentation (DDFRG) models for proton and light ion production from high energy nucleus–nucleus collisions, relevant to space radiation, is introduced. The proton model employs thermal production from the projectile, central fireball and target sources, as well as quasi-elastic direct knockout production. The light ion model uses a hybrid coalescence model. The data show a prominent quasi-elastic peak at small angles which becomes highly suppressed at large angles. The models are able to describe this wide range of experimental data with only a limited set of model parameters. Closed form analytic formulas for double-differential energy and angle cross-sections as well as single-differential spectral cross-sections are developed. These analytic formulas enable highly efficient computation for radiation transport codes.
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Are Further Cross Section Measurements Necessary for Space Radiation Protection or Ion Therapy Applications? Helium Projectiles
J. Norbury, G. Battistoni, J. Besuglow, L. Bocchini, D. Boscolo, A. Botvina, M. Clowdsley, W. de Wet, M. Durante, M. Giraudo, T. Haberer, L. Heilbronn, F. Horst, M. Krämer, C. La Tessa, F. Luoni, A. Mairani, S. Muraro, R. Norman, V. Patera, G. Santin, C. Schuy, L. Sihver, T. Slaba, N. Sobolevsky, A. Topi, U. Weber, C. Werneth, C. Zeitlin Frontiers in Physics, vol. 8, pp. 1-30, 2020. [3/23/2021]
This work reviews the importance of 4He projectiles to space radiation and ion therapy, and outline the present status of neutron and light ion production cross section measurements and modeling, with recommendations for future needs.
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Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars
Z. Patel, T. Brunstetter, W. Tarver, A. Whitmire, S. Zwart, S. Smith, J. Huff. Nature Partner Journals Microgravity , vol. 6, article 33, 2020 [3/23/2021]
NASA’s plans for space exploration include a return to the Moon to stay on the lunar surface with an orbital outpost. This station will be a launch point for voyages to destinations further away in our solar system, including journeys to the red planet Mars. To ensure success of these missions, health and performance risks associated with the unique hazards of spaceflight must be adequately controlled. These hazards are linked with over 30 human health risks as documented by NASA’s Human Research Program. The risks ranked as “red” have the highest priority based on both the likelihood of occurrence and the severity of their impact on human health, performance in mission, and long-term quality of life. These include: (1) space radiation health effects of cancer, cardiovascular disease, and cognitive decrements (2) Spaceflight-Associated Neuro-ocular Syndrome (3) behavioral health and performance decrements, and (4) inadequate food and nutrition. In this review, we provide a primer on these “red” risks for the research community. The aim is to inform the development of studies and projects with high potential for generating both new knowledge and technologies to assist with mitigating multisystem risks to crew health during exploratory missions.
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Long-term effects of very low dose particle radiation on gene expression in the heart: Degenerative disease risks
Garikipati VNS, Arakelyan A, Blakely EA, Chang PY, Truongcao MM, Cimini M, Malaredy V, Bajpai A, Addya S, Bisserier M, Brojakowska A, Eskandari A, Khlgatian MK, Hadri L, Fish KM, Kishore R, Goukassian DA Cells. 2021 Feb 13;10(2):387 [3/16/2021]
In this study, we provide the transcriptome analysis of mouse hearts exposed to low and very low doses of gamma-IR 137Cs (40-160 cGy), 14Si-IR (4-32 cGy, 260 MeV/n) or 22Ti-IR (3-26 cGy, 1 GeV/n) ion irradiation. Our results show that 16 months after a single low- or very low doses of IR exposure, the gene expression in the heart tissue is significantly differentially regulated compared to the sham-treated, non-irradiated controls, suggesting there are long-term effects on dysregulation of different molecular pathways that are associated with various disease and biological processes. Additionally, our bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common differentially expressed genes across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs.
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Life-long brain compensatory responses to galactic cosmic radiation exposure
Miry O, Zhang XL, Vose LR, Gopaul KR, Subah G, Moncaster JA, Wojnarowicz MW, Fisher AM, Tagge CA, Goldstein LE, Stanton PK. Sci Rep. 2021 Feb 22;11(1):4292.).
To our knowledge, this study is the first to uncover lifespan-long effects of high-energy heavy particle radiation mimicking exposure to galactic cosmic radiation (GCR), on neurogenesis, synaptic plasticity, and learning and memory in mice. Changes observed 2 months after a single GCR exposure were characterized by reductions in hippocampal neurogenesis, smaller activity-dependent long-term potentiation of synaptic strength (LTP), and impaired spatial, hippocampus-dependent, learning acquisition. Six months after GCR exposure, impairments in learning disappeared, and LTP was actually enhanced. 12-20 months post-GCR exposure, we observed dramatic rebound increases in neurogenesis of newborn neurons in the dentate gyrus, larger LTP, and more rapid learning acquisition in a spatial learning task.
The GCR exposure studied was designed to mimic cumulative exposure levels expected on long-term manned missions to Mars. This lifespan study shows that such exposure can produce complex effects on the brain that are lifelong. The neurophysiological, cognitive and behavioral results of such long-term effects on astronauts is likely to be a complex combination of deficits and compensatory recovery mechanisms with their own unpredictable consequences. These consequences have the potential to affect the success of deep space manned missions, and the intrepid explorers throughout their lives. Deeper studies of the consequences of these long-lasting effects, and a search for ways to ameliorate them, will be a key goal in maximizing mission performance and success.
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Quantitative modeling of multigenerational effects of chronic ionizing radiation using targeted and nontargeted effects
Shuryak I, Brenner DJ. Sci Rep. 2021 Feb 26;11(1):4776.[3/8/2021]
Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation (e.g. energy depositions and ionizations in the nucleus) and undamaged "bystander" cells, sometimes over long distances. Their consequences, called non-targeted effects (NTE), can substantially contribute to radiation-induced damage (e.g. cell death, genomic instability, carcinogenesis), particularly at low doses/dose rates (e.g. space exploration, some occupational and accidental exposures). In addition to controlled laboratory experiments, analysis of observational data on wild animal and plant populations from areas contaminated by radionuclides can enhance our understanding of radiation responses because such data span wide ranges of dose rates applied over many generations. Here we used a mechanistically-motivated mathematical model of TE and NTE to analyze published embryonic mortality data for plants (Arabidopsis thaliana) and rodents (Clethrionomys glareolus) from the Chernobyl nuclear power plant accident region. Although these species differed strongly in intrinsic radiosensitivities and post-accident radiation exposure magnitudes, model-based analysis suggested that NTE rather than TE dominated the responses of both organisms to protracted low-dose-rate irradiation. TE were predicted to become dominant only above the highest dose rates in the data. These results support the concept of NTE involvement in radiation-induced health risks from chronic radiation exposures.
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On the radiation environment during consecutive balloon flights over New Mexico and Antarctica
Berger Thomas, Matthiä Daniel, Marsalek Karel, Przybyla Bartos, Aeckerlein Joachim, Rohde Markus. Wirtz Michael, Moeller Ralf, James Leandro M. and Lane Michael. Earth and Space Science Open Archive}, 2021 (in review) [3/7/2021]
The maximum measured daily dose values over Antarctica reached 202 μGy/day (at RC =0 GV), a level of particular significance for the space exploration community, considering we have observed similar dose values (212 μGy/day) on the surface of Mars across equivalent time periods, as measured by the Curiosity rover (Berger et al., 2020). Short of sending experiments or instruments to the Red Planet, or as a progressive stepping stone for eventually journeying into deep space, our results support the idea that long duration Antarctic balloon missions can be used for accurately introducing experiments or instruments to sustained Mars-like radiation conditions.
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The effect of helium ion radiation on the material properties of bone
Thomas PK, Sullivan LK, Dickinson GH, Davis CM, Lau AG. Calcif Tissue Int. 2021 Jan 30. Online ahead of print.[2/24]
Ionizing radiation is known to affect bone health. This study investigated the effects of helium ion radiation exposure on the material properties of bone. Rats were exposed to 0, 5, or 25 cGy doses of helium-4 radiation and evaluated at 7, 30, 90, and 180 day time points after radiation exposure. The shear modulus of the femur cortical bone was investigated using spherical micro-indentation.
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Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation
Oizumi T, Ohno R, Yamabe S, Funayama T, Nakamura AJ. Life (Basel). 2020 Dec 10;10(12):341. doi: 10.3390/life10120341. PMID: 33321941; PMCID: PMC7763067 [1/31/2021]
In this study, normal human fibroblasts were irradiated with proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.
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Impact of galactic cosmic ray simulation on nutritional content of foods
Douglas GL, Cooper MR, Wu H, Gaza R, Guida P, Young M. Life Sci Space Res. 2021 Feb;28:22-5 .[1/31/2021]
Foods packaged for future deep-space exploration missions may be prepositioned ahead of astronaut arrival and will be exposed to galactic cosmic rays (GCRs) and solar radiation in deep space at higher levels and different spectrums than those found in low-Earth orbit (LEO). In this study, we have evaluated the impact of a GCR simulation (approximately 0.5 and 5 Gy doses) at the NASA Space Radiation Laboratory (NSRL) on two retort thermostabilized food products that are good sources of radiation labile nutrients (thiamin, vitamin E, or unsaturated fats). No trends or nutritional differences were found between the radiation-treated samples and the control immediately after treatment or one-year after treatment. Small changes in a few nutrients were measured following one-year of storage. Further studies may be needed to confirm these results, as the foods in this study were heterogeneous, and this may have masked meaningful changes due to pouch-to-pouch variations.
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Systemic HDAC3 inhibition ameliorates impairments in synaptic plasticity caused by simulated galactic cosmic radiation exposure in male mice
Keiser AA, Kramár EA, Dong T, Shanur S, Pirodan M, Ru N, Acharya MM, Baulch JE, Limoli CL, Wood MA., Neurobiol Learn Mem. 2020 Dec 23. Online ahead of print.[1/29/2021]
Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.
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Predicting the Radiation Sensitivity of Male and Female Rhesus Macaques Using Gene Expression
P. Ostheim, M. Majewski, Z. Gluzman-Poltorak, V. Vainstein, L. A. Basile, A. Lamkowski, S. Schüle, H. L. Kaatsch, M. Haimerl, C. Stroszczynski, M. Port, and M. Abend Radiation Research 195(1), 25-37, (12 November 2020) [1/18/2021]
Radiosensitivity differs in humans and likely among closely-related primates. Reasons for variation in radiosensitivity are not well known. We examined preirradiation gene expression in peripheral blood among male and female rhesus macaques (n=142) which did or did not survive (up to 60 days) after whole-body irradiation with 700 cGy (LD66/60). We evaluated gene expression in a two-phase study design where phase I was a whole genome screen [next generation sequencing (NGS)] for mRNAs (RNA-seq). Differential gene expression (DGE) was defined as a statistically significant and 2-fold up- or downregulation of mRNA species and was calculated between groups of survivors and non-survivors (reference) and by gender. Altogether 659 genes were identified, but the overlapping number of differentially expressed genes (DGE) observed in both genders was small (n = 36). Fifty-eight candidate mRNAs were chosen for independent validation in phase II using qRT-PCR. Among the 58 candidates, 16 were of significance or borderline significance (t test) by DGE. Univariate and multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis further refined and identified the most outstanding validated genes and gene combinations. The combination of EPX with SLC22A4 (P = 0.03, ROC=0.85) appeared most predictive for the clinical outcome of male macaque groups and MBOAT4 (P = 0.0004, ROC = 0.81) was most predictive for females.
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Inflammation mediates the development of aggressive breast cancer following radiotherapy
Ma L, Gonzalez-Junca A, Zheng Y, Ouyang H, Illa-Bochaca I, Horst KC, Krings G, Wang Y, Fernandez-Garcia I, Chou W, Barcellos-Hoff MH. in Clin Cancer Res. 2021 Jan 5. Online ahead of print. [1/15/2021]
The mechanisms by which radiation increases cancer risk include targeted effects in the irradiated cell, like mutation, and non-targeted effects that signal among cells in response to damage. The research reported by Ma et al. evaluates the contribution of targeted versus non-targeted radiation effects to the development of breast cancer. In women treated with radiation for early cancer, breast cancer risk is significantly elevated, but more importantly, radiation-preceded breast cancer is a more aggressive disease. Ma et al. analyzed the composition of breast cancers arising in women who treated for Hodgkin's lymphoma and used a series of genetic-chimera mouse experiments to examine how a single, low dose radiation exposure altered mammary carcinogenesis. They show that the tumor microenvironment of radiation-preceded breast cancer was markedly immunosuppressive compared to that of age-matched sporadic breast cancer as evidenced by high levels of cyclooxygenase-2 and transforming growth factor-beta and low lymphocytic infiltrate. Mouse tumors arising after irradiation were also characterized by an immunosuppressive microenvironment. A series of experiments showed that this feature of radiation-preceded breast cancers occurred even when the epithelium was not irradiated and in the absence of adaptive immunity. However, the immunosuppressive features were eliminated by administration of a short course of aspirin after irradiation to reduce low-level inflammation. These studies support anti-inflammatory treatments as a means to reduce aggressive cancers that occur after radiation exposure.
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Microglia depletion and cognitive functions after brain injury: From trauma to galactic cosmic ray
Paladini MS, Feng X, Krukowski K, Rosi S. Neurosci Lett. 2020 Nov 28. [Epub ahead of print] Review. [12/31]
Microglia are the resident immune cells of the central nervous system. Insults such as traumatic brain injury, therapeutic brain irradiation and galactic cosmic ray exposure are associated with maladaptive chronic microglia activation. Chronic microglia activation contributes to injury-related impairments in cognitive functions. Microglia depletion represents a useful tool for more extensive investigations of microglia roles, but also a potential therapeutic approach to ameliorate or prevent cognitive dysfunctions following brain injury.
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Multiple sensory illusions are evoked during the course of proton therapy
Narici L, Titova E, Obenaus A, Wroe A, Loredo L, Schulte R, Slater JD, Nelson GA. Life Sci Space Res. 2020 Aug;26:140-8. [12/21/20]
The effects of radiation on sensory physiological responses have been reported in astronauts and in patients undergoing radiotherapy. A retrospective study in a cohort of proton radiotherapy patients found conscious reporting of sensory illusions in visual, olfactory auditory and gustatory senses. Further, brain regions receiving the highest proton doses corresponded to the sensory anatomical structures. This study suggests that prospective studies interrogating illusions from all sensory modalities are warranted and could contribute to radiation risk assessments for space exploration and for radiotherapy patients.
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Can a comparison of clinical and deep space irradiation scenarios shed light on the radiation response of the brain?
C. Limoli, Br J Radiol. 2020 Nov 1;93(1115):20200245. [12/20/20]
The purpose of this article was to draw comparisons between two very different and distinct radiation exposure scenarios, and to discern whether any similarities between clinical brain tumor treatments and space radiation exposure could help in the assessment of clinical outcomes and/or risk mitigation following deep space travel.
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DNA damage baseline predicts resilience to space radiation and radiotherapy
Pariset E, Bertucci A, Petay M, Malkani S, Lopez Macha A, Paulino Lima IG, Gomez Gonzalez V, Tin AS, Tang J, Plante I, Cekanaviciute E, Vazquez M, Costes SV. Cell Rep. 2020 Nov 21:108434. [Epub ahead of print] [12/15]
In this work we measure genotoxic stress in humans by quantifying the amount of DNA double-strand breaks (DSBs) in immune cells in vivofrom a simple finger prick and ex-vivo using a blood draw. We first showed in 674 healthy donors that the endogenous level of DSBs increases with age and with latent cytomegalovirus infection. Two smaller cohorts were analyzed for DSB induction and repair by exposing lymphocytes ex-vivo to either galactic cosmic ray components or protons/gamma rays under a radiotherapy protocol. Our work suggests low baseline DSB is a potential biomarker for health resilience in space as indicated by fewer clinical complications for radiotherapy patients, and enhanced DNA damage repair and cytokine responses for healthy donors.
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Sex-specific cognitive deficits following space radiation exposure
Parihar VK, Angulo MC, Allen BD, Syage A, Usmani MT, Passerat de la Chapelle E, Amin AN, Flores L, Lin X, Giedzinski E, Limoli CL Front Behav Neurosci. 2020 Sep 16;14:535885 [12/2/20]
Data included in this manuscript indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.
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53P1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains
Eloise Pariset, Sébastien Penninckx, Charlotte Degorre Kerbaul, Elodie Guiet, Alejandra Lopez Macha, Egle Cekanaviciute, Antoine M. Snijders, Jian-Hua Mao, François Paris, Sylvain V. Costes Radiation Research, 194(5), 485-499, (29 September 2020) [12/1/20]
This report introduces a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to X-rays and space radiation components, with potential applications in radiotherapy and human space exploration. Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 different mice strains. We show that genetics is a key factor in individual speed and the efficiency of DNA damage repair. We further link kinetics metrics to in vivo phenotypes in these strains, illustrating such metrics as potential surrogate biomarkers for in vivo radiation toxicity, specifically survival levels of immune cells in irradiated mice and spontaneous cancer incidence. This study is part of a series of manuscripts published in Radiation Research that reports clustering of nearby DSB into single repair units in the same mouse fibroblasts [] and optimizes 53BP1 foci detection based on cell proliferation levels []. In addition, our group showed that monitoring 53BP1 foci levels can be used to predict radiation sensitivity, not only in mouse fibroblasts but also in human immune cells [], with correlations between the level of spontaneous foci and secondary effects to radiotherapy in 30 prostate cancer patients, as well as ex vivo responses to space radiation components in 300+ healthy donors. Genetic Wide Association studies in both these 15 strains of mice and our cohort of 800+ patients is ongoing in the Radiation Biophysics Laboratory at NASA Ames Research Center.
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Updated deterministic radiation transport for future deep space missions
Slaba TC, Wilson JW, Werneth CM, Whitman K. Life Sci Space Res. 2020 Nov;27:6-18. [11/30/20]
NASA's deterministic transport code HZETRN, and its three-dimensional (3D) counterpart, 3DHZETRN, are being used to characterize the space radiation environment over a wide range of scenarios, including future planned missions to the moon or Mars. Combined with available spaceflight measurements, these tools provide the fundamental input for biological risk projection models used to verify astronaut safety and satisfy agency limits in support of exploration initiatives. In this work, significant updates to the deterministic radiation transport models are presented. Charged muons and pions are fully coupled to neutron and light ion (Z < 2) transport solutions in 1D and 3D. A direct comparison of deterministic and Monte Carlo transport methodologies using the same nuclear interaction databases is also provided. It is shown that Geant4 and 3DHZETRN are in excellent agreement when the same cross sections are used. The deterministic codes are also compared to ISS data, and it is found that the updated 3D procedures are within measurement uncertainty (+5%) at cutoff rigidities below 1 GV, which approaches free space conditions.
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Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions
Li Z, Jella KK, Jaafar L, Moreno CS, Dynan WS. Life Sci Space Res. 2020 Nov 5. [Article in Press] [11/15/20]
Exposure of human bronchial epithelial cells to energetic heavy ions, representative of species found in galactic cosmic rays, stimulates exosome release. Preparations enriched for these nanometer-scale extracellular vesicles contain pro-inflammatory damage-associated molecular patterns, together with a variety of microRNAs (miRNAs). The miRNA profile is skewed toward a small number of species involved in cancer initiation and progression, consistent with a role in mediating non-targeted radiation effects.
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Heavy ion space radiation triggers ongoing DNA base damage by downregulating DNA repair pathway
Suman S, Jaruga P, Dizdaroglu M, Fornace AJ Jr, Datta K. Life Sci Space Res. 2020 Nov 27:27-32. [10/28/2020]
Persistent sub-lethal oxidative stress and ongoing DNA damage have been attributed to the enhanced risk of gastrointestinal (GI) carcinogenesis after ionizing radiation (IR) exposure. IR-induced oxidative stress is known to cause a myriad of oxidative DNA damages to DNA bases and the sugar moiety, while base excision repair (BER) and nucleotide excision repair (NER) mechanisms are predominantly involved in removing these oxidative DNA lesions. In our earlier studies, we demonstrated that exposure to 56Fe-ion caused persistent oxidative stress in intestinal epithelial cells (IECs), so the purpose of the recent study was to detect and quantify oxidative DNA-lesions and respective repair pathways in the mouse intestine. Gas chromatography/tandem mass spectrometry (GC-MS/MS) was used to detect and quantify oxidative DNA damage, while qPCR and western-blot analysis was done to assess alterations in BER and NER pathways in γ and 56Fe-exposed mouse intestine. Exposure to 56Fe-ion resulted in significantly higher levels of oxidative DNA base lesions relative to control and γ exposed animals. Assessment of BER and NER also showed greater downregulation of pathway factors at both mRNA and protein levels after 56Fe-ion exposure. These results clearly indicate that downregulation of the BER and NER pathways can contribute to ongoing DNA base damages a long time after radiation exposure and has implications for GI-carcinogenesis after energetic heavy ion (HZE) exposure during space travel.
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Spaceflight medical countermeasures: A strategic approach for mitigating effects from solar particle events
Cantrell, Int J Radiat Biol. 2020 Sep 18. [10/18/20]
NASA was recently charged with returning humans to the lunar surface within the next five years. This will require preparation for spaceflight missions of longer distance and duration than ever performed in the past. Protecting the crew and mission from the hazards associated with spaceflight will be a priority, particularly space radiation. Physical shielding, space weather monitoring, and more recently storm shelters are all possible means of protecting crew during a SPE. This paper discusses the mitigation strategies in the event of a SPE that can be implemented for Artemis missions and identifies numerous areas of research for future improvements.
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Radiation dose and its protection in the moon from galactic cosmic rays and solar energetic particles: At the lunar surface and in a lava tube
Naito M, Hasebe N, Shikishima M, Amano, Y, Haruyama J, Matias-Lopes JA, Kim KJ, Kodaira S. J Radiol Prot. 2020 Sep 23;40(4):947-61. [10/11/2020]
Radiation environment at the lunar surface and in a lunar vertical hole with a horizontal lava tube was estimated. The effective dose equivalent due to galactic cosmic ray (GCR) particles at the lunar surface reached 416 mSv/year at most, and that due to solar energetic particles reached 2190 mSv. On the other hand, the vertical hole of the lava tube provides significant radiation protection. The exposure by GCR particles at the bottom of the vertical hole was found to be below 30 mSv/year while inside the horizontal lava tube, the value was less than 1 mSv/year, which corresponds to the reference values for human exposure on the Earth. We expect that the lunar holes will be useful components in the practical design of a lunar base to reduce radiation risk and to expand mission terms.
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Response to comments by Bevelacqua and Mortazavi
Rabin BM, Cahoon DS, Shukitt-Hale B.Sci Space Res. 2020 Nov;27:111-2. Epub 2020 Sep 23 [10/11/20]
The main thrust of the comments by Bevelacqua and Mortazavi (2020) about the paper by Cahoon et al. (2020) is that we ignored the potential adaptive responses resulting from low level exposure to radiation, a phenomenon known as “radiation hormesis”. The adaptive response produced by preexposure to a low dose of radiation is considered a non-targeted effect of ionizing radiation. While we did show a non-targeted effect on brain function following exposure of the body only, we did not raise the issue of an adaptive response to radiation in our paper because our experimental design, using only a single exposure, did not allow an evaluation of the possible effects of preexposure on the production of neurochemical changes in the brain and the concomitant disruption of cognitive performance. Because the experiment was not designed to evaluate possible adaptive effects of preexposure to a low dose of radiation, we do not think that their comments are relevant.
Bevelacqua, J.J., Mortazavi, S.M.J., 2020. Comments on "Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats". Life Sci. Space Res.
Cahoon, D.S., Shukitt-Hale, B., Bielinski, D.F., Hawkins, E.M., Cacioppo, A.M., Rabin, B.M., 2020. Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats. Life Sci. Space Res. 27, 56–63.
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Practicalities of dose management for Japanese astronauts staying at the International Space Station
T Komiyama, Ann ICRP. 2020 Sep 24. [10/11/20]
Japanese astronauts started staying at the International Space Station (ISS) in 2009, with each stay lasting for approximately 6 months. In total, seven Japanese astronauts have stayed at the ISS eight times. As there is no law for protection against space radiation exposure of astronauts in Japan, the Japan Aerospace Exploration Agency (JAXA) created its own rules and has applied them successfully to radiation exposure management for Japanese ISS astronauts, collaborating with ISS international partners. Regarding dose management, JAXA has implemented several dose limits to protect against both the stochastic effects of radiation and dose-dependent tissue reactions. The scope of the rules includes limiting exposure during spaceflight, exposure during several types of training, and exposure from astronaut-specific medical examinations. We, therefore, are tasked with calculating the dose from all exposure types applied to the dose limits annually for each astronaut. Whenever a Japanese astronaut is at the ISS, we monitor readings of an instrument in real-time to confirm that the exposed dose is below the set limits, as the space radiation environment can fluctuate in relation to solar activity.
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Benchmarking risk predictions and uncertainties in the NSCR model of GCR cancer risks with revised low LET risk coefficients
Cucinotta FA, Cacao E, Kim M-HY, Saganti PB. Life Sci Space Res. 2020 Jul 26. [9/29/20]
We report on the contributions of model factors that appear in projection models to the overall uncertainty in cancer risks predictions for exposures to galactic cosmic ray (GCR) in deep space, including comparisons with revised low LET risks coefficients. Annual GCR exposures to astronauts at solar minimum are considered. Uncertainties in low LET risk coefficients, dose and dose-rate modifiers, quality factors (QFs), space radiation organ doses, non-targeted effects (NTE) and increased tumor lethality at high LET compared to low LET radiation are considered. For the low LET reference radiation parameters we use a revised assessment of excess relative risk (ERR) and excess additive risk (EAR) for radiation induced cancers in the Life-Span Study (LSS) of the Atomic bomb survivors that was recently reported, and also consider ERR estimates for males from the International Study of Nuclear Workers (INWORKS). For 45-y old females at mission age the risk of exposure induced death (REID) per year and 95% confidence intervals is predicted as 1.6% [0.71, 1.63] without QF uncertainties and 1.64% [0.69, 4.06] with QF uncertainties. However, fatal risk predictions increase to 5.83% [2.56, 9.7] based on a sensitivity study of the inclusion of non-targeted effects on risk predictions. For males a comparison using LSS or INWORKS lead to predictions of 1.24% [0.58, 3.14] and 2.45% [1.23, 5.9], respectively without NTEs. The major conclusion of our report is that high LET risk prediction uncertainties due to QFs parameters, NTEs, and possible increase lethality at high LET are dominant contributions to GCR uncertainties and should be the focus of space radiation research.
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Lack of supporting data make the risks of a clinical trial of radiation therapy as a treatment for COVID-19 pneumonia unacceptable
David G. Kirsch, Maximilian Diehn, Francis A. Cucinotta, Ralph Weichselbaum. Radiotherapy and Oncology 147 (2020) 217–220 [9/29/20]
With large numbers of patients dying from COVID-19 and because there are no approved treatments, some investigators have proposed testing low dose (≤1 Gy) radiotherapy to the thorax for COVID-19 pneumonia. However, based on (a) the limited anecdotal data of radiotherapy to treat human viral pneumonia, (b) preclinical models reporting minimal to no efficacy of radiotherapy for viral pneumonia, and (c) the real risks of whole thorax radiotherapy for study subjects, there are currently inadequate data to justify the risks of a clinical trial of radiotherapy for COVID-19. In addition, a clinical trial of COVID-19 would present a risk of infecting medical staff with SARS-CoV-2. Therefore, clinical trials of radiotherapy for COVID-19 should only be started after robust results in preclinical models demonstrate efficacy. In this scenario, informed consent must include providing subjects with transparent risks of long-term side effects of radiation exposure.
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First measurements of the radiation dose on the lunar surface
Shenyi Zhang, Robert f. Wimmer-Schweingruber, Jia Yu, Chi Wang, Qiang Fu, Yongliao Zou, Yueqiang Sun, Chunqin Wang, Donghui Hou, Stephan i. Böttcher, Sönke Burmeister, Lars Seimetz, Björn Schuster, Violetta Knierim, Guohong Shen, Bin Yuan, Henning Lohf, Jingnan Guo, Zigong Xu, Johan l. Freiherr von Forstner, Shrinivasrao r. Kulkarni, Haitao Xu, Changbin Xue, Jun Li, Zhe Zhang, He Zhang, Thomas Berger, Daniel Matthiä, Christine e. Hellweg, Xufeng Hou, Jinbin Cao, Zhen Chang, Binquan Zhang, Yuesong Chen, Hao Geng, Zida Quan. Science Advances 25 Sep 2020:Vol. 6, no. 39, eaaz1334 [9/26/2020]
The Lunar Lander Neutrons and Dosimetry experiment aboard China’s Chang’E 4 lander has made measurements of the radiation exposure to both charged and neutral particles on the lunar surface. We measured an average total absorbed dose rate in silicon of 13.2 ± 1 micro-Gy/hour and a neutral particle dose rate of 3.1 ± 0.5 micro-Gy/hour. The instrumentation is described in:
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Determination of Chromosome Aberrations in Human Fibroblasts Irradiated by Mixed Fields Generated with Shielding
Tony C. Slaba, Ianik Plante, Artem Ponomarev, Zarana S. Patel, Megumi Hada. Radiat Res 1 September 2020; 194 (3): 246–258. [9/26/2020]
To better study biological effects of space radiation using ground-based facilities, the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory has been upgraded to rapidly switch ions and energies. This has allowed investigators to design irradiation protocols comprising a mixture of ions and energies more indicative of the galactic cosmic ray (GCR) environment. In this work, human fibroblasts were placed behind 20 g/cm2 aluminum and 10.345 g/cm2 polyethylene and irradiated separately by 344 MeV hydrogen, 344 MeV/n helium, 450 MeV/n oxygen, and 950 MeV/n iron ions at various doses. A multi-scale modeling approach utilizing Geant4, RITRACKS, and RITCARD was developed to predict the formation of chromosome aberrations in these experiments. The multi-scale model described herein is a significant advancement for the computational tools used to predict biological outcomes in cells exposed to highly complex, mixed ion fields related to the GCR environment. Results show that the simulation and experimental data are in good agreement for the complex radiation fields generated by all ions incident on shielding for most data points. Although improvements are needed, the model extends current capabilities for evaluating beam selection and delivery schemes at the NSRL ground-based GCR simulator and for informing NASA risk projection models in the future.
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Cancer incidence risks above and below 1 Gy for radiation protection in space
Hafner L, Walsh L, Schneider U. Life Sci Space Res. 2020 Sep 14. [9/22/2020]
The risk assessment quantities called lifetime attributable risk (LAR) and risk of exposure-induced cancer (REIC) are used to calculate the cumulative cancer incidence risks for astronauts, attributable to radiation exposure accumulated during long term lunar and Mars missions. In order to analyse the impact of a different neutron RBE on the risk quantities, a model for the neutron relative biological effectiveness (RBE) relative to gammas in the Life Span Study (LSS) is developed. The suitability of these risk assessment measures for the use of cancer risk calculation for astronauts as well as the impact of including an excess absolute risk (EAR) baseline scaling and different weightings of the excess risk models is discussed.
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The effect of low temperatures on environmental radiation damage in living systems: Does hypothermia show promise for space travel?
Fukunaga H. Int J Mol Sci. 2020 Sep 1;21(17):E6349. Review.
This literature review provides an overview of the progress to date in the interdisciplinary research field of radiation biology and hypothermia and addresses possible issues related to hypothermic treatments as countermeasures against GCR.
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Suppression of innate immune signaling molecule, MAVS, reduces radiation-induced bystander effect
Rong Jia, Yaxiong Chen, Cong Jia, Burong Hu & Yarong Du (2020) International Journal of Radiation Biology, DOI: 10.1080/09553002.2020.1807642 [8/31/20]
Mitochondrial antiviral signaling (MAVS) protein, located in the mitochondrial out-membrane, is necessary for IFN-beta induction and IFN-stimulated gene expression in response to external stress such as viral invasion and ionizing radiation (IR). Although the involvement of radiation induced bystander effect (RIBE) has been investigated for decades for secondary cancer risk related to radiotherapy, the underlying regulatory mechanisms remain largely unclear, especially the roles played by the immune factors such as MAVS. Our results indicated that the innate immune signaling molecule MAVS in recipient cells participate in RIBE. ROS is an important factor in RIBE via MAVS pathway and MAVS may be a potential target for the precise radiotherapy and radioprotection.
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Mitigation of helium irradiation-induced brain injury by microglia depletion
Allen BD, Syage AR, Maroso M, Baddour AAD, Luong V, Minasyan H, Giedzinski E, West BL, Soltesz I, Limoli CL, Baulch JE, Acharya MM.and published in J Neuroinflammation. 2020 May 19;17(1):159. [8/29/20]
The efficacy of microglial depletion in restoring the cognitive health of mice exposed to cosmic radiation was demonstrated. Specifically, long term feeding of mice with the CSF1R inhibitor to deplete microglia after a single exposure with 30 Gy of (4)HE attenuated the alterations in a battery of neurological, and learning and memory tests in mice when compared to cohorts not given the inhibitor. Collectively data suggest that microglia play a critical role in cosmic radiation-induced cognitive deficits in mice and, that approaches targeting microglial function are poised to provide considerable benefit to the charged-particle exposed brain.
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Do we really need the "detriment" for radiation protection?
Breckow, J. Radiat Environ Biophys 59, 343–348 (2020). [8/29/20]
The purpose of the ICRP detriment concept is to enable a quantitative comparison of stochastic radiation damage for the various organs. For this purpose, the organ-specific nominal risk coefficients are weighted with a function that is intended to express the amount of damage or, respectively, the severity of a disease. This function incorporates a variety of variables that do not depend on radiation parameters, but on characteristics of the disease itself. The question is raised as to whether the rather subtle way of defining the amount of damage is necessary for radiation protection purposes and whether a much simpler relationship can serve for this purpose as well or even better.
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Late effects of 1H + 16O on short-term and object memory, hippocampal dendritic morphology and mutagenesis
Kiffer F, Alexander T, Anderson J, Groves T, McElroy T, Wang J, Sridharan V, Bauer M, Boerma M, Allen A. and published in Front Behav Neurosci. 2020 Jun 26;14:96. [8/28/20]
We exposed 6-month-old male mice to whole-body 1H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to 16O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). We detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci.
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CRaTER observations and permissible mission duration for human operations in deep space
de Wet WC, Slaba TC, Rahmanifard F, Wilson JK, Jordan AP, Townsend LW, Schwadron NA, Spence HE. Life Sci Space Res. 2020 Aug;26:149-62 [8/28/20]
Dose rates observed by the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument were used to obtain the local GCR intensity and composition as a function of time. A response function is constructed that relates observed dose rates to solar modulation potential using a series of Monte Carlo radiation transport calculations. The record of observed solar modulation potential vs. time is then used to calculate a recent historical record of permissible mission duration (PMD) according to NASA's permissible exposure limits (PEL). Tables are provided for extreme values of PMD.
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Sleep Fragmentation Exacerbates Executive Function Impairments Induced by Low Doses of Si Ions
Richard A. Britten, Arriyam S. Fesshaye, Vania D. Duncan, Laurie L. Wellman, and Larry D. Sanford Radiation Research 194(2), 116-123, (30 June 2020). [8/25/20]
Astronauts on deep space missions will be required to work autonomously and thus their ability to perform executive functions could be critical to mission success. In addition to the health risks associated with SR exposure, astronauts have to contend with other stressors, of which inadequate sleep quantity and quality are considered to be major concerns. We have previously shown that a single session of fragmented sleep uncovered latent attentional set shifting (ATSET) performance deficits in rats exposed to protracted neutron irradiation that had no obvious defects in performance under rested wakefulness conditions. It was unclear if the exacerbating impact of sleep fragmentation (SF) only occurs in rats exposed to protracted low dose rate neutron exposures. In this study, we assessed whether SF also unmasks latent ATSET deficits in rats exposed to 5 cGy 600 MeV/n 28Si ions.
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The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation
Nipa H. Patel, Sahib S. Sohal, Masoud H Manjili, J. Chuck Harrell, David A. Gewirtz. Radiation Research 194(2), 103-115, (30 June 2020). [8/24/20]
Although the scientific literature generally focuses on cell death induced by exposure to ionizing radiation, in fact, the more likely outcomes are responses to evade cell death, such as autophagy and/or senescence. This article explores the roles/involvement of autophagy (cellular self-digestion) and senescence ( a prolonged and durable form of growth arrest) in tumor cells exposed to radiation as a therapeutic modality.
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Space radiation does not alter amyloid or tau pathology in the 3xTg mouse model of Alzheimer's
Owlett L, Belcher EK, Dionisio-Santos DA, Williams JP, Olschowka JA, O'Banion MK Life Sci Space Res. 2020 Nov;27:89-98. Epub2020 Aug 3. [8/9/2020]
Space radiation can cause neuronal damage and degeneration, glial activation, and oxidative stress in the brain. Previous work demonstrated a worsening of Alzheimer’s disease-associated amyloid pathology in male APP/PS1 transgenic mice after HZE exposure. To determine whether tau pathology is altered by HZE particle or proton irradiation, we exposed 3xTg mice, which acquire both amyloid plaque and tau pathology with age, to iron, silicon, or solar particle event (SPE) irradiation at 9 months of age and evaluated behavior and brain pathology at 16 months of age. We found no differences in performance in fear conditioning and novel object recognition tasks between groups of mice exposed to sham, iron (10 and 100 cGy), silicon (10 and 100 cGy), or solar particle event radiation (200 cGy). 200 cGy SPE irradiated female mice had fewer plaques than sham-irradiated females but had no differences in tau pathology. Overall, females had worse amyloid and tau pathology at 16 months of age and demonstrated a reduced neuroinflammatory gene response to radiation. These findings uncover differences between mouse models following radiation injury and corroborate prior reports of sex differences within the 3xTg mouse model.
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Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats
Cahoon DS, Shukitt-Hale B, Bielinski DF, Hawkins EM, Cacioppo AM, Rabin BM. , Life Sci Space Res. 2020 Nov;27:56-63. Epub 2020 Jul 24. [8/4/2020]
To determine the possible effects that irradiation of the body might have on neuronal function and cognitive performance, rats were given head-only, body-only or whole-body exposures to 56Fe particles. Cognitive performance (novel object recognition, operant responding) was tested in one set of animals; changes in neuronal function (oxidative stress, neuroinflammation) was tested in a second set of rats. The results indicated that there were no consistent differences in either behavioral or neurochemical endpoints as a function of the location of the irradiation.
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Older Research Citations may be found in the Bibliography.


Basic Concepts of Space Radiation

In order to understand the space radiation risks faced by human explorers, it is necessary to have a clear idea of what it is, where it is, and what happens when space radiation interacts with matter. The articles in this section describe the space radiation environment, the nuclear and atomic interactions with the constituent atoms of materials – especially living materials – in space, and the ways in which energy is deposited in biologically significant molecules.

Some of the articles are taken from the Appendices of a 1998 Strategic Plan I authored during my tenure at NASA and others are presentations given by NASA Summer School faculty. There is a fair amount of overlap, both within this section and between this section and other sections, where the subjects are discussed in greater detail. This is welcome, reflecting as it does, different – and broadening – perspectives on the topics covered.

Walter Schimmerling
THREE Chief Editor

  • The Space Radiation Environment
    • The Natural space Ionizing Radiation Environment* – Patrick O’Neill (Article)
    • Fluence Rates, Delta Rays and Cell Nucleus Hit Rates from Galactic Cosmic Rays – Stanley B Curtis (PDF)
    • Solar Particle Events and Radiation Exposure in Space* – Shaowen Hu (PDF)
  • Interactions of Radiation with Matter
    • Interactions of Radiation with Matter – Walter Schimmerling (Article)
    • Particle Interactions Overview – Lawrence Heilbronn (html)
    • Physics Summary – Lawrence Heilbronn (html)
    • Neutron Properties and Definitions – Lawrence Heilbronn (html)
    • Neutron Lectures Supplement – Lawrence Heilbronn (PDF)
  • Dose and Dose Rate Effectiveness Factors – Walter Schimmerling  (Article)
    • Low LET Physics Topics – Gregory Nelson (html)  Introduction (PDF)
    • A Note On The Dose-Rate-Effectiveness Factor and its Progeny 
      DDREF -  R.J.M. Fry (PDF)
  • Track Structure
    • Introduction to Track Structure and z*22 - Stanley B. Curtis (PDF)
    • Radiation Quality and Space Radiation Risks – Francis Cucinotta (html)
    • Development of Monte Carlo Track Structure Codes – Larry Toburen (PDF)
    • Microdosimetry and Detector Responses – Leslie A. Braby (PDF)
    • Interpreting Microdosimetric Spectra – J. F. Dicello and F. A Cucinotta (PDF)
    • Monte Carlo Track Simulations – Michael Dingfelder (PDF)
    • Radiation Track Structure – Dudley T. Goodhead (html) Abstract (PDF)
  • Elementary Concepts of Shielding – Walter Schimmerling  (PDF)
    • Heavy Ions and Shielding Physics – Lawrence Heilbronn (html)


Introduction to THREE
Walter Schimmerling

Video presentation of
Research Solutions to Space Radiation Impacts on Human Exploration
Slides in PDF format
Francis A. Cucinotta, Ph.D.
Chief Scientist, Space Radiation Program
NASA Johnson Space Center
Houston, Texas
Aerospace Medicine Grand Rounds
March 23, 2010

Radiation and Human Space Exploration Video
NASA Human Research Program

Radiation tracks and radiation track simulation video
Ianik Plante, Ph.D.
Universities Space Research Association
Division of Space Life Sciences
NASA Johnson Space Center
Houston, Texas

Radiation tracks and radiation track simulation video is excerpted from the article:
Radiation chemistry and oxidative stress (PDF)
Ianik Plante, Ph.D.

Video Presentation of
Space Radiation and Cataracts
Eleanor Blakely
Life Sciences, Lawrence Berkeley National Laboratory
Berkeley, California
July 16, 2003


Glossary derived from:
Human Research Program Integrated Research Plan, Revision A, (January 2009). National Aeronautics and Space Administration, Johnson Space Center, Houston, Texas 77058, pages 232-280.

Exploration Systems Radiation Monitoring Requirements (Sept 2012). Page ii. Ronald Turner.

Report No. 153: Information Needed to Make Radiation Protection Recommendations for Space Missions Beyond Low-Earth Orbit (2006). National Council on Radiation Protection and Measurements, pages 309-318.  Reprinted with permission of the National Council on Radiation Protection and Measurements.

Managing Space Radiation Risk in the New Era of Space Exploration (2008). Committee on the Evaluation of Radiation Shielding for Space Exploration, National Research Council. National Academies Press, pages 111-118.

Contents: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

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AAPM: American Association of Physicists in Medicine.

absolute risk: Expression of excess risk due to exposure as the arithmetic difference between the risk among those exposed and that obtaining in the absence of exposure.

absorbed dose (D): Average amount of energy imparted by ionizing particles to a unit mass of irradiated material in a volume sufficiently small to disregard variations in the radiation field but sufficiently large to average over statistical fluctuations in energy deposition, and where energy imparted is the difference between energy entering the volume and energy leaving the volume. The same dose has different consequences depending on the type of radiation delivered. Unit: gray (Gy), equivalent to 1 J/kg.

ACE: Advanced Composition Explorer Mission, launched in 1997 and orbiting the L1 libration point to sample energetic particles arriving from the Sun and interstellar and galactic sources.  It also provides continuous coverage of solar wind parameters and solar energetic particle intensities (space weather).  When reporting space weather, it can provide an advance warning (about one hour) of geomagnetic storms that can overload power grids, disrupt communications on Earth, and present a hazard to astronauts.

acute effects: short-term biological effects of exposure to radiation, including headaches, dizziness, nausea, and illness that can range from mild to fatal.

acute exposure: Radiation exposure of short duration.

AGS: Alternating Gradient Synchrotron (at Brookhaven National Laboratory).

ALARA (As Low As Reasonably Achievable):  An essential operational safety requirement, as well as a regulatory requirement, that em­phasizes keeping exposure to radiation as low as possible using reasonable methods, and not treating dose limits as “tolerance values”; defined at NASA as limiting radiation exposure to a level that will result in an estimated risk below the limit of the 95 percent confidence level.

albedo: secondary radiation produced by interactions of galactic cosmic rays and high-energy solar protons with matter in the atmosphere or on the surface.

ALL: acute lymphocytic leukemia.

alpha particle: An energetic charged nucleus consisting of two protons and two neutrons. This particle is identical to the 4He nucleus.

ALTEA: Anomalous Long-Term Effects in Astronauts study .

AM: amplitude modulation.

AMA: American Medical Association.

AMAC: American Medical Advisory Committee.

AML: acute myelogenous leukemia.

Amu: atomic mass unit (ALSO: u).

ANLL: acute nonlymphocytic leukemia.

annual risk: The risk in a given year from an earlier exposure. The annual risk (average) from an exposure is the lifetime risk divided by the number of years of expression.

ANP: atrial natriuretic peptide.

ANS: American Nuclear Society.

ANSI: American National Standards Institute.

AU: Astronomical Unit (distance from the Earth to the Sun)

Apoe4: Apoliprotein E isoform 4. Modification of Apo4 is major risk factor in Alzheimer's disease.

apoptosis: A specific mode of cell death (also known as programmed cell death) that can be triggered by exposure to radiation, especially in cells of lymphoid/myeloid or epithelial lineage. Extensive apoptosis contributes to the hematopoietic and gastrointestinal symptoms seen in acute radiation syndrome.

ARC: NASA Ames Research Center.

Ares V/Heavy Lift Launch Vehicle: a NASA vehicle intended to deliver cargo from Earth to low Earth orbit.

ARM: Atmospheric Radiation Measurements.

ascent stage: The pressurized upper stage of the Lunar Lander in which the crew pilots the lander from lunar orbit to the lunar surface and return. The ascent stage takes off from the descent stage, leaving the latter behind on the surface.

AT: ataxia telangiectasia.

ATM: ataxia telangiectasia mutated.

AU: Astronomical Unit (Approx. distance from the Earth to the Sun)

AX-2: NASA Ames Research Center Experimental Suit 2, designed during the Apollo program as a lunar surface hard suit to bend at the waist and rotate in the torso so that the crew member can reach down to the ground with one hand. Fabricated from fiberglass.

AX-5: NASA Ames Research Center Experimental Suit 5, designed during the Space Station Advanced Development program to provide a durable hard suit for extended operations in zero gravity. Fabricated from numerically milled aluminum forgings.

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background radiation: The amount of radiation to which a member of the population is exposed from natural sources, such as terrestrial radiation from naturally-occurring radionuclides in the soil, cosmic radiation originating in outer space, and naturally-occurring radionuclides deposited in the human body. The natural background radiation received by an individual depends on geographic location and living habits. In the United States, the background radiation is on the order of 1 mSv y–1, excluding indoor radon which amounts to ~2 mSv/year on average.

BAF: Booster Applications Facility (the name used to designate the NSRL during planning and construction phases).

BaRyoN: Quark bound state with zero strangeness.

BCC: basal cell carcinoma.

BCD: budget change directive.

BEIR: Biological Effects of Ionizing Radiation. One of a series of reports on the health risks from exposure to low levels of ionizing radiation issued by the Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, Board on Radiation Effects, Research Division on Earth and Life Studies, National Research Council of the National Academies of Science of the United States, referred to by a Roman number denoting its position in the sequence of reports. At the time of this writing, the latest report is BEIR VII.

BEVALAC: An accelerator system at Lawrence Berkeley National Laboratory consisting of the Bevatron (an early, high-energy synchrotron accelerator constructed in the 1950s and used to discover the antiproton), accelerating particles delivered by the SuperHILAC (first built as the HILAC - Heavy Ion Linear Accelerator - in 1957; along with a similar one at Yale University, the first machine in the US built specifically to accelerate heavy ions, completely rebuilt into the SuperHILAC in 1971). Closed in 1993.

biological end point: effect or response being assessed, e.g., cancer, cataracts.

bipolar device: a type of semiconductor whose operation is based on both majority and minority carriers.

BNL: Brookhaven National Laboratory in Upton (Long Island), New York.

BRCA1: breast cancer 1 tumor suppressor gene.

BRCA2: breast cancer 2 tumor suppressor gene.

BrdU: bromodeoxyuridine.

BRYNTRN: BaRYoN TRaNsport code, a computer code for simulating baryon transport.

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CAD: computer aided design.

CaLV: Cargo Launch Vehicle.

CAM : computerized anatomical man model.

carbon composite: a composite incorporating carbon and other materials for use in lightweight structures, strong enough to substitute for aluminum and other metals in the construction of many parts of a spacecraft, notably the pressure vessel shell. It may incorporate boron, epoxy, polyethylene, hydrogen, or other materials that enhance radiation shielding properties.

CARD: Constellation Architecture Requirements Document; CxP 7000

cargo habitat: a crew habitat that the Lunar Lander carries for delivery to the Lunar Outpost as a key part of the “Outpost-first” strategy considered by NASA as part of the Space Exploration Initiative program.

CB: Control Board.

CDC: Center for Disease Control and Prevention.

CEDE: committed effective dose equivalent.

CENELEC: European Committee for Electrotechnical Standardization.

CEQATR: Constellation Program Environmental Qualification and Acceptance Testing Requirements; CxP 70036

CERN: European Organization for Nuclear Research.

CEV: Crew Exploration Vehicle.

CFR: Code of Federal Regulations.

CHMO: Chief Health And Medical Officer (NASA).

chronic effects: long-lasting effects of exposure to radiation; includes cancer, cataracts, and nervous system damage.

chronic exposure: Radiation exposure over long times (continuous or fractionated).

CI: confidence interval.

CL: confidence level.

CLV: Crew Launch Vehicle.

CME: coronal mass ejection, an explosion of plasma released from the atmosphere (or corona) of the Sun.

CML: chronic myelogenous leukemia.

CNP: cyclic nucleotide phosphatase.

CNS: central nervous system.

Composites: materials made from two or more constituent materials with significantly different physical or chemical properties which remain separate and distinct at the macroscopic or microscopic scale within the finished structure.

computerized anatomical male/female: a model of human geometry used to evaluate radiation doses at various points inside the body.

Constellation system: the complete ensemble of launch vehicles, flight vehicles, ground support, support services, and lunar and planetary surface systems associated with the Vision for Space Exploration initiated during the Bush administration.

coronal mass ejection (CME): A transient outflow of plasma from or through the solar corona which may be associated with the generation of solar-particle events.

cosmic-ray modulation: The variation of the observed cosmic-ray intensity as a function of the solar cycle. The cosmic-ray intensity within the solar system is observed to vary approximately inversely with the solar activity cycle that controls the interplanetary magnetic field.

COTS: commercial, off-the-shelf.

CPD: crew passive dosimeter.

CPU: central processor unit.

CRaTER: Cosmic Ray Telescope for the Effects of Radiation.

CRCPD: Conference of Radiation Control Program Directors.

CREME96: Cosmic Ray Effects on Micro-Electronics (1996 revision), a computer code.

cross section (σ): probability per unit particle fluence of a given end point. Unit: cm2.

CT: computed tomography.

CTA: conditioned taste aversion.

CVD: cardiovascular disease.

CW: continuous wave.

CxP: Constellation Program.

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Dr: dose-rate (Gy/hr).

DAAC: Distributed Active Archive Center.

DDREF: dose and dose-rate effectiveness factor (the degree to which both dose and dose rate may influence the biological effects of exposure to a given dose of radiation).

delta rays: Electrons directly ejected from atoms in matter by radiation.

descent stage: The lower stage of the Lunar Lander that includes the descent and landing engines and propellant tanks to serve them. The crew ascending back to lunar orbit in the ascent stage leaves the descent stage behind on the lunar surface.

descent stage habitat: in the descent stage, a pressurized crew habitat in which the crew would live during sortie missions.

deterministic process: process whereby a given event will occur whenever its dose threshold is exceeded.

deterministic effects: early radiation effects usually related to a significant fraction of cell loss, exceeding the threshold for impairment of function in a tissue; so called because the statistical fluctuations in the number of affected cells are very small compared to the number of cells required to reach the threshold (ICRP 1991), above which the severity varies with dose.

detriment: Health detriment is the sum of the probabilities of all the components of health effects. These include in addition to fatal cancer the probability of heritable effects and the probability of morbidity from nonfatal cancer.

DHS: Department of Homeland Security.

DNA: deoxyribonucleic acid.

DOD: Department of Defense.

DOE: Department of Energy.

dose: A general term used when the context is not specific to a particular dose quantity. When the context is specific, the name or symbol for the quantity is used [i.e., absorbed dose (D), mean absorbed dose (DT), dose equivalent (H), effective dose (E), equivalent dose (HT), or organ dose equivalent].

dose equivalent ( H ): Estimate of radiation risk that accounts for differences in the biological effectiveness of different types of charged particles that produce the absorbed dose. H=Q × D, where Q is a quality factor based on the type of radiation (Q = 1 for x-rays). NASA uses Q as specified in ICRP Publication 60 (ICRP, 1991). Unit: sievert (Sv), equivalent to 1 J/kg.

dose limit: A limit on radiation dose that is applied by restricting exposure to individuals or groups of individuals in order to prevent the occurrence of radiation-induced deterministic effects or to limit the probability of radiation related stochastic effects to an acceptable level. For astronauts working in low-Earth orbit, unique dose limits for deterministic and stochastic effects have been recommended by NCRP.

dose rate: Dose delivered per unit time. Can refer to any dose quantity (e.g., absorbed dose, dose equivalent).

dose-response model: A mathematical formulation of the way in which the effect, or response, depends on dose.

dosimeter: A radiation detection device worn or carried by an individual to monitor the individual's radiation exposure. For space activities, a device worn or carried by an astronaut in-flight.

DREF: dose rate effectiveness factor (the degree to which dose rate may influence the biological effects of exposure to a given dose of radiation).

DRM: Design Reference Mission.

DSB: double strand break.

DSNE: Constellation Program Design Specification for Natural Environments; CxP 70023

DTRA: Defense Threat Reduction Agency.

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E: effective dose/ energy.

EAR:excess additive risk (cf. absolute risk).

ED50: dose to cause 50 % of the population to have the effect (e.g., nausea).

EDS: Earth departure stage.

EEG: electroencephalogram.

effective dose ( E ): The sum over specified tissues of the products of the equivalent dose in a tissue (HT) and the tissue weighting factor for that tissue or organ (wT) (i.e., E = wTHT). Effective dose (E) applies only to stochastic effects. Unit: sievert (Sv), equivalent to 1 J/kg.

electron volt (eV): a unit of energy equivalent to 1.602 × 10–19 joules.

ELF: extremely low frequency.

ELR: excess lifetime risk.

EMF: electromagnetic field.

EML: Environmental Measurements Laboratory, New York, NY.

EMS: emergency medical services.

EMU: Extravehicular mobility unit, the space suit developed for space shuttle crews that also serves on the ISS.  The EMU features a hard upper torso and soft lower torso, arms, and legs over the pressure bladder. The entire EMU except the helmets and boots is covered by the thermal micrometeoroid garment.

electron volt (eV): A unit of energy = 1.6 x 10–12 ergs = 1.6 x 10–19 J; 1 eV is equivalent to the energy gained by an electron in passing through a potential difference of 1 V; 1 keV = 1,000 eV; 1 MeV = 1,000,000 eV.

EOS: Earth Observing System.

EPA: Environmental Protection Agency.

equivalent dose ( HT): The product of the mean absorbed dose in an organ or tissue and the radiation weighting factor (wR) of the radiation type of interest. For external exposure wR applies to the radiation type incident on the body.

ERR:excess relative risk.

erythema: A redness of the skin.

ESA: European Space Agency.

ESMD: Exploration Systems Mission Directorate (NASA).

ESP: energetic storm particle.

ESTEC: European Space Research and Technology Centre.

EVCPDS: Extra Vehicle Charged Particle Directional Spectrometer

excess relative risk (ERR): The ratio between the total risk, including the increase due to radiation exposure, and the baseline risk in the absence of radiation exposure; if the excess equals the baseline the relative risk is two.

exposure (technical use): A measure of the ionization produced in air by x or gamma radiation. Exposure is the sum of electric charges on all ions of one sign produced in air when all electrons liberated by photons in a volume of air are completely stopped, divided by the mass of the air in the volume. The unit of exposure in air is the roentgen (R) or in SI units it is expressed in coulombs (C), 1 R = 2.58 x 10–4 C/kg.

exposure (non-technical use): the presentation of an individual or material to radiation likely to deliver a significant dose over a period of time.

EVA: extravehicular activity.

excess risk: the increase in the probability of a certain effect on an individual who has been exposed to a given dose of radiation over the probability of that effect in the absence of radiation exposure.

extravehicular activity: Any activity undertaken by the crew outside a space vehicle or habitat.

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favorable propagation path: A concept suggesting that the Archimedean spiral path from the earth to the sun would connect to a specific solar longitude. It is based on the concept that charged particles travel along the interplanetary magnetic field which is transported out from the sun. For an idealized constant speed solar wind flow, if the interplanetary magnetic field is frozen in the plasma, then the result would form an Archimedean spiral.

FEMA: Federal Emergency Management Agency.

FIRE: First ISCCP Regional Experiment.

first ionization potential: The energy required to remove the least bound electron from an electrically neutral atom. (The ionization potential is usually given in electron volts.)

FISH: fluorescence in situ hybridization.

fluence: (1) ICRU definition : The quotient of dN by da, where dN is the number of particles incident on a sphere of cross-sectional area da (i.e., Φ = dN/da). The unit for fluence is 1/m2, but cm–2 is frequently used; (fluence may be a function of one or more other variables [e.g., Φ (L,t), the distribution of fluence as a function of linear energy transfer (L) and time (t)]. (2) planar fluence (F): The net number of charged particles traversing a given area. Unit: particles/cm2.

fluence rate (dF/dt): Change in fluence over a given small time interval, or the time derivative of the fluence. Unit: 1/m2s.

FLUKA: a general purpose Monte-Carlo computer code for calculations of particle transport and interactions with matter

flux ): Term used historically by the nuclear community for fluence rate and also used for particle flux density, but deprecated by the ICRU convention to eliminate confusion between the terms “particle flux density” and “radiant flux.” See fluence rate.

FM: frequency modulation.

FR: fixed-ratio.

fractionation: The delivery of a given total dose of radiation as several smaller doses, separated by intervals of time.

FSP: fission surface power.

FY: Fiscal Year.

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galactic cosmic rays: the components of galactic cosmic radiation.

galactic cosmic radiation (GCR): The charged-particle radiation outside the Earth magnetosphere comprised of 2 % electrons and positrons, and 98 % nuclei, the latter component consisting (by fluence) of 87 % protons, 12 % helium ions, and 1 % high atomic number, high-energy (HZE) particles.

gamma rays: Short-wavelength electromagnetic radiation of nuclear origin (approximate range of energy: 10 keV to 9 MeV).

GCR: galactic cosmic radiation/ galactic cosmic rays.

GCR: galactic cosmic radiation.

GEANT: A computer application for the simulation of the passage of particles through matter including detector description and simulation.

GEO: Geostationary or Geosynchronous Earth Orbit.

Geostationary Operational Environmental Satellite ( GOES): A satellite in geosynchronous orbit used for monitoring protons. The satellite travel at the same angular speed above the equator as Earth’s rotation and therefore appears stationary when observed from Earth’s surface.

GGTP: gamma-glutamyl transpeptidase.

GI: gastrointestinal.

GLE: ground level event.

GM: geometric mean.

GPM: Global Precipitation Measurement.

gray (Gy): The International System (SI) unit of absorbed dose of radiation, 1 Gy = 1 J kg–1.

gray equivalent (GT or Gy-Eq): The product of DT and Ri, where DT is the mean absorbed dose in an organ or tissue and Ri is a recommended value for relative biological effectiveness for deterministic effects for a given particle type i incident on the body ( GT = Ri × DT). The SI unit is J/kg (NCRP, 2000).

GSD: geometric standard deviation (the standard deviation of the logarithms of a set of random variables, for which the geometric mean is the square root of their product.

GSI(Gesellschaft für Schwerionenforschung): Helmholtz Centre for Heavy Ion Research in Darmstadt, Germany.

GSM: global system for mobile communications.

GT: gray equivalent.

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HACD: Human Adaptation and Countermeasures Division.

HDPE: high-density polyethylene, defined as having a density greater than 0.94 g/cm3.

heavy charged particles: Atomic and subatomic charged particles with masses substantially heavier than that of an electron.

heavy ions: Nuclei of elements heavier than helium such as nitrogen, carbon, boron, neon, argon or iron which are positively charged due to some or all of the atomic electrons having been stripped from them.

HEDS: Human Exploration and Development of Space.

HEFD: Habitability and Environmental Factors Division.

heliocentric: A measurement system with its origin at the center of the sun.

heliolongitude: Imaginary lines of longitude on the sun measured east (left) or west (right) of the central meridian (imaginary north-south line through the middle of the visible solar disk) as viewed from Earth. The left edge of the solar disk is 90°E and the right edge is 90°W.

heliosphere: The magnetic bubble containing the solar system, solar wind, and entire solar magnetic field. It extends beyond the orbit of Pluto.

HEPAD: High Energy Proton and Alpha Detector.

HIDH: Human Integration Design Handbook; NASA/SP-2010-3407

high atomic number, high-energy ( HZE) particles: Heavy ions having an atomic number greater than that of helium (such as nitrogen, carbon, boron, neon, argon or iron ions that are positively charged) and having high kinetic energy.

high-LET: Radiation having a high-linear energy transfer; for example, protons, alpha particles, heavy ions, and interaction products of fast neutrons.

HIMAC: Heavy Ion Medical Accelerator, Chiba Japan.

HMF: heliospheric magnetic field.

HPC: Hydrological Process and Climate.

HPRT: hypoxanthine-guanine phosphoribosyl transferase.

HQ: Headquarters.

HRP: Human Research Program.

HRP CB: Human Research Program Control Board.

HSIR: Constellation Program Human Systems Integration Requirements; CxP 70024

H T : equivalent dose.

HZE: high atomic number and energy.

HZETRN: a transport code developed specifically for high-charge, high-energy particles that is widely used for space radiation shielding and design calculations.

HZE: high atomic number, high energy/ highly energetic, heavy, charged particles.

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IACUC: Institutional Animal Care and Use Committee.

IAEA: International Atomic Energy Agency.

ICNIRP: International Commission on Non-Ionizing Radiation Protection.

ICRP: International Commission on Radiation Protection.

ICRU: International Commission on Radiation Units and Measurements.

IDIQ: Indefinite delivery/indefinite quantity.

IEEE: Institute of Electrical and Electronics engineers.

IL-2: interleukin-2.

IL-6: interleukin-6.

incidence: The rate of occurrence of a disease, usually expressed in number of cases per million .

IND: improvised (or otherwise acquired) nuclear device.

interplanetary magnetic field: The magnetic field in interplanetary space. The interplanetary magnetic field is transported out from the sun via the solar wind.

interplanetary shocks: An abrupt change in the velocity or density of charged particles moving faster than the wave propagation speed in interplanetary space, so that higher velocity components bunch into lower velocity components before these can get out of the way.

ionizing radiation: Any electromagnetic or particulate radiation capable of producing ions, directly or indirectly, in its passage through matter.

ionization: The process by which a neutral atom or molecule acquires a positive or negative charge through the loss or gain of one or more orbital electrons.

IPT: Integrated Product Team.

IRMA: Integrated Risk Management Application.

ISCCP: International Satellite Cloud Climatology Project.

ISS: International Space Station.

ISSMP: ISS Medical Project.

ITA: Internal Task Agreement.

IVCPDS: Intra Vehicle Charged Particle Directional Spectrometer

IV & V: Independent Validation & Verification.

IWG: Investigator Working Group.

IWS: Investigator Workshop.

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JSC: NASA Johnson Space Center.

JWST: James Webb Space Telescope.

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kerma: (an acronym for “Kinetic energy released in materials;” the sum of the initial kinetic energies for all charged particles released by uncharged ionizing radiation in a small sample of material divided by the mass of the sample. Kerma is the same as dose when charged particle equilibrium exists (i.e., when, on the average, the number of charged particles leaving the sample is compensated by an equal number of charged particles entering the sample).

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LAP: latency associated peptide.

LAR: lifetime attributable risk.

LaRC: NASA Langley Research Center.

LAT: Lunar Architecture Team.

latchup: an anomalous state in a semiconductor in which the device no longer responds to input signals.

latent period: Period or state of seeming inactivity between time of exposure of tissue to an injurious agent and an observed response (also time to response or induction period).

LBNL: Lawrence Berkeley National Laboratory.

LCD: liquid crystal display.

LCVG: liquid cooling and ventilation garment.

LDEF: Long Duration Exposure Facility.

LDL: low-density lipoproteins.

LEND: Low Energy Neutron Detector.

LEO (low Earth orbit): the environment in which most recent space missions have been concentrated, where the magnetic field of Earth provides protection against much of the radiation that would be encountered on more distant exploration missions, approximately 300 to 600 mile orbit radius.

LET (linear energy transfer): Measure of the average local energy deposition per unit length of distance traveled by a charged particle in a material. Unit: keV/μm.

lifetime risk: The lifetime probability of suffering from the consequences of a specific health effect. The total risk in a lifetime resulting from an exposure(s) is equal to the average annual risk times the period of expression.

light ions: Nuclei of hydrogen and helium which are positively charged due to some or all of the planetary electrons having been stripped from them.

lineal energy ( y ): The quotient of ε by , where ε is the energy imparted to the matter in a given volume by a single (energy deposition) event and is the mean chord length of that volume ( i.e., y = ε/ l ). The unit for lineal energy is J /m, but keV/ μm is often used in practice (1 keV/µm ~ 1.6x10-10 J/m).

linear energy transfer ( LET): Average amount of energy lost per unit of particle track length as an ionizing particle travels through material, related to the microscopic density distribution of energy deposited in the material and, therefore, a major characteristic of radiation leading to different effects for the same dose of ionizing radiation of different LET on biological specimens or electronic devices.

linear-quadratic model (also linear-quadratic dose-response relationship): expresses the incidence of (e.g., mutation or cancer) as partly directly proportional to the dose (linear term) and partly proportional to the square of the dose (quadratic term).

LIS: local interstellar energy spectrum.

LIS: local interstellar GCR spectrum.

LIS: Local interplanetary Spectra.

LLD: lower limit of detection.

LLU: Loma Linda University.

LLO: low lunar orbit.

lognormal: If the logarithms of a set of values are distributed according to a normal distribution the values are said to have a lognormal distribution, or be distributed log normally.

low-LET: Radiation having a low-linear energy transfer; for example, electrons, x rays, and gamma rays.

LRV: Lunar Roving Vehicle.

LSAC: Life Sciences Applications Advisory Committee.

LSS: Life Span Study.

LSS: Life-Span Study of the Japanese atomic-bomb survivors.

Lunar Lander: the Constellation system vehicle that will travel between the Orion and the surface of the Moon.

LWS: Living With a Star (a NASA program).

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MARIE: Mars Radiation Environment Experiment.

mass stopping power: (see stopping power ).

MAT: Mars Architecture Team.

MCNPX: Monte Carlo N-Particle eXtended.

MDO: Multi-disciplinary Optimization.

mean absorbed (tissue) dose ( DT): The mean absorbed dose in an organ or tissue, obtained by integrating or averaging absorbed doses at points in the organ or tissue.

mean-free path: The average distance between particle collisions with nuclei, atoms or molecules in a material. Also, the average distance between scattering events in interplanetary particle propagation.

MEEP: Mir Environment Effects Payload.

MEO: Medium Earth Orbit.

MeV: Mega-electron Volts: 106 electron volts

mFISH: Multiplex Fluorescence In Situ Hybridization.

Mir: The Russian (previously Soviet) orbital space station.

MISSE: Materials on International Space Station Experiment.

MML: mouse myelogenous leukemia.

MMOP: Multilateral Medical Operations Panel.

MOA: Memorandum of Agreement.

MODIS: Moderate Resolution Imaging Spectrometer.

MORD: Medical Operations Requirements Documents.

MOU: Memorandum of Understanding.

Mrem: millirem.

MRI: magnetic resonance imaging.

MS: Mission Systems

mSv: millisievert.

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N: nucleon.

NAR: Non-Advocate Review.

NAS: National Academy of Sciences.

NASA: National Aeronautics and Space Administration.

NCI: National Cancer Institute.

NCRP: National Council on Radiation Protection and Measurements.

NEDD: Constellation Program Natural Environment Definition for Design; CxP 70044

neutrons: Particles with a mass similar to that of a proton, but with no electrical charge. Because they are electrically neutral, they cannot be accelerated in an electrical field.

NIEL: Non-ionizing energy loss, also called displacement kerma. The total kerma can be divided into an ionizing component and a displacement, or NIEL, component.

NIH: National Institutes of Health.

NM: neutron monitor.

NOAA: National Oceanic and Atmospheric Administration.

noncancer: Health effects other than cancer (e.g., cataracts, cardiovascular disease) that occur in the exposed individual.

Nowcasting: prediction of total doses and the future temporal evolution of the dose once a solar particle event has begun.

NOVICE: Radiation Transport/Shielding Code.

NPR: NASA Procedural Requirements.

NRA: NASA Research Announcement.

NRC: National Research Council.

NRC: Nuclear Regulatory Commission (US).

NSBRI: National Space Biomedical Research Institute.

NSCOR: NASA Specialized Center of Research.

NSF: National Science Foundation.

NSRL: NASA Space Radiation Laboratory (at BNL).

NTE: Non-Targeted Effects.

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OBPR: Office of Biological and Physical Research.

OCHMO: Office of Chief Health and Medical Officer.

organ dose equivalent ( DET): The mean dose equivalent for an organ or tissue, obtained by integrating or averaging dose equivalents at points in the organ or tissue. It is the practice in the space radiation protection community to obtain point values of absorbed dose (D) and dose equivalent (H) using the accepted quality factor-LET relationship [Q(L)], and then to average the point quantities over the organ or tissue of interest by means of computational models to obtain the organ dose equivalent (DET ). For space radiations, NCRP adopted the organ dose equivalent as an acceptable approximation for equivalent dose (HT) for stochastic effects.

Orion Crew Exploration Vehicle: The Constellation system vehicle that will carry passengers in low Earth orbit, or from low Earth orbit to the Moon or Mars, and then back to Earth. Often referred to as CEV; in this report referred to as the Orion crew module.

OSHA: Occupational Safety and Health Administration.

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PC: Probability of Causation.

PCC: premature chromosome condensation.

PCS: personal communication system.

PDF: probability density function.

PDF: probability distribution function.

PE: Project Executive.

PEL (permissible exposure limit): Maximum amount of radiation to which an astronaut may be exposed. For terrestrial workers, PELs are legal limits, defined by OSHA. NASA PELs are set by the chief health and medical officer.

PET: positron emission tomography.

photosphere: The portion of the sun visible in white light. Also the limit of seeing down through the solar atmosphere in white light.

PI: Principal Investigator.

PLR: pressurized lunar rover.

PLSS: personal life support system.

PM: Project Manager.

PP: Project Plan.

PPBE: Planning, Programming, Budgeting and Execution.

PPS: proton prediction system/ pulses per second.

PRD: Passive Radiation Detector; Program Requirements Document.

prevalence: The number of cases of a disease in existence at a given time per unit of population, usually per 100,000 persons.

protons: The nucleus of the hydrogen atom. Protons are positively charged.

protraction: Extending the length of exposure, for example, the continuous delivery of a radiation dose over a longer period of time.

PS: Project Scientist.

PSD: Position-Sensitive Detector; also, Pulse Shape Discrimination.

PVAMU: Prairie View A&M University.

PW: pulsed wave.

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Q: quality factor.

Q(L): quality factor as a function of linear energy transfer.

Qleukemia: quality factor for estimating leukemia risks.

Qsolid: quality factor for estimating solid cancer risks.

QMSFRG: quantum multiple scattering fragmentation model.

quality factor ( Q ): The factor by which absorbed dose (D) at a point is modified to obtain the dose equivalent (H) at the point (i.e., H = Q D), in order to express the effectiveness of an absorbed dose (in inducing stochastic effects) on a common scale of risk for all types of ionizing radiation. There is a specified dependence [Q(L)] of the quality factor (Q) as a function of the unrestricted linear energy transfer (L) in water at the point of interest.

quasithreshold dose: The dose at which the extrapolated straight portion of the dose-response curve intercepts the dose axis at unity survival fraction.

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RAD: Radiation Assessment Detector.

RAM: Radiation Area Monitor.

radiation: 1. The emission and propagation of energy through space or through matter in the form of waves, such as electromagnetic, sound, or elastic waves; 2. The energy propagated through space or through matter as waves; radiation or radiant energy, when unqualified, usually refers to electromagnetic radiation; commonly classified by frequency— Hertzian, infrared, visible, ultraviolet, x and gamma rays; 3. Corpuscular emission, such as alpha and beta particles, or rays of mixed or unknown type, such as cosmic radiation.

radiation quality: A general term referring to the microscopic distribution of of the energy absorbed to yield a given total dose. For example, at resolutions of a few micrometers ionizing events will be more uniformly dispersed for gamma-ray radiation than for the neutron radiation, producing quantitatively different biological effects (see relative biological effectiveness ).

radiation weighting factor ( wR): A factor related to the relative biological effectiveness of different radiations in the calculation of equivalent dose (HT) (see equivalent dose ), independently of the tissue or organ irradiated.

RBE (relative biological effectiveness): Measure of the effectiveness of a specific type of radiation for producing a specific biological outcome, relative to a reference radiation (generally, 250 kVp x-rays). For a defined endpoint, RBE = Dref/Dnew. For HZE particles, RBE generally is greater than 1, meaning that a lower dose of more effective HZE particles will have the same effect as a given dose of the reference radiation.

RCT: Radiation Coordination Team.

RDD: radiological dispersal device.

RDWG: Radiation Discipline Working Group.

regolith: A layer of loose, heterogeneous material covering solid rock on the surface of a moon or planet (including Earth).

REIC: risk of exposure-induced cancer incidence.

REID (risk of exposure induced death): Measure of risk used by NASA as a standard for radiation protection; reflects a calculation of the probability of death due to exposure to radiation in space.

relative biological effectiveness (cf. RBE)

relative risk (cf. excess relative risk)

REM: rapid eye movement.

RF: radiofrequency.

RFI: request for information.

RHIC: Relativistic Heavy Ion Collider (at BNL).

RHO: Radiation Health Officer.

rigidity: The momentum of a charged particle per unit charge. Determines the curvature of the particle’s trajectory in a magnetic field. Two particles with different charge but the same rigidity will travel along a path having the same curvature in a given magnetic field.

risk: The probability of a specified effect or response occurring.

risk coefficient: The increase in the annual incidence or mortality rate per unit dose: (1) absolute risk coefficient is the observed minus the expected number of cases per person year at risk for a unit dose; (2) the relative risk coefficient is the fractional increase in the baseline incidence or mortality rate for a unit dose.

risk cross section: The probability of a particular excess cancer mortality per particle fluence (excluding delta rays).

risk estimate: The number of cases (or deaths) that are projected to occur in a specified exposed population per unit dose for a defined exposure regime and expression period; number of cases per person-gray or, for radon, the number of cases per person cumulative working level month.

roentgen: A unit of radiation exposure. Exposure in SI units is expressed in C kg–1 of air.

ROS: reactive oxygen species.

RRS: radiation Research Society.

RSNA: Radiological Society of North America.

R&T: Research and Technology.

RTG: radioisotope thermoelectric generator.

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SAA: South Atlantic Anomaly.

SACR: Science Advisory Committee on Radiobiology.

SAMPEX: Solar Anomalous and Magnetospheric Particle Explorer.

SAR: specific absorption rate.

SBIR: Small Business Innovation Research.

SCAR: Smoke/Sulfate Clouds and Radiation Experiment.

SCC: squamous cell carcinoma/ small cell cancer.

SCE: sister chromatid exchange.

SCLS: small cell lung carcinoma.

SD: single dose.

SD: standard deviation.

SDO: Solar Dynamic Observatory.

SEC: Space Environment Center. (NOAA).

secondary radiation: radiation that has been generated by the interaction of radiation with the atoms or nuclei of a traversed material.

SEE (single-event effect): a class of effects in which damage results from a single ionizing particle traversing a microelectronic device, rather than the accumulated impact of a large number of particles.

SEE: single event effect/ Space Environment and Effects Program.

SEER: surveillance, epidemiology, and end results.

SET: Space Environment Testbeds.

SEU (single event upset): a change of state caused by ions or electro-magnetic radiation striking a sensitive node in a micro-electronic device.

SFHSS: Space Flight Human Systems Standard; NASA-STD-3001

SGZ: subgranular zone.

SI: International System of Units.

sievert ( Sv): The special name for the SI unit of effective dose (E), equivalent dose (HT), dose equivalent (H), and organ dose equivalent (DT ), 1 Sv = 1 J /kg.

SLSD: Space Life Sciences Directorate (NASA).

S&MA: Safety and Mission Assurance (NASA).

SMD: Science Mission Directorate (NASA).

SMO: Science Management Office (NASA).

SOHO: Solar and Heliospheric Observatory.

Solar cycle: The periodic variation in the intensity of solar activity, as measured, for example, by the numbers of sunspots, flares, CMEs, and SPEs. The average length of solar cycles since 1900 is 11.4 y.

solar flare: The name given to the sudden release of energy (often >1032 ergs) in a relatively small volume of the solar atmosphere. Historically, an optical brightening in the chromosphere, now expanded to cover almost all impulsive radiation from the sun.

solar-particle event (SPE): An eruption at the sun that releases a large number of energetic particles (primarily protons) over the course of hours or days. Signatures of solar energetic-particle events may include significant increases in types of electro­magnetic radiation such as radio waves, x-rays, and gamma rays.

solar wind: The plasma flowing into space from the solar corona. The ionized gas carrying magnetic fields can alter the intensity of the interplanetary radiation.

SOMD: Space Operations Mission Directorate (NASA).

spallation: A high-energy nuclear reaction in which a high-atomic-number target nucleus is struck by a high-energy, light particle (typically a proton); this causes the target nucleus to break up into many components, releasing many neutrons, protons, and higher Z particles.

SPE (cf. solar particle event).

Space Radiation Analysis Group (SRAG): the radiation protection group at NASA’s Johnson Space Center, responsible for radiation monitoring, projecting exposures, and ensuring adherence to principles of ALARA for crews on spaceflight missions.

SPENVIS (SPace ENVironment Information System) : a series of computer programs developed by the European Space Agency for the simulation of radiation effects in flight.

SRA: Society for Risk Analysis.

SRAG: Space Radiation Analysis Group

sRBC: Serum deprivation response factor-related gene product that binds to C-kinase.

SRPE: Space Radiation Program Element (NASA).

SSA: Social Security Administration.

STEREO: Solar-Terrestrial Relations Observatory (NASA mission).

stochastic effects: radiation effects attributed to the consequences of changes caused by radiation in one or a few cells; so called because the statistical fluctuations in the number of initial cells are large compared to the number of cells observed when radiation effects, such as cancer, become manifest (ICRP 1991). The probability of occurrence, rather than the severity, is a function of radiation dose.

stochastic process: process whereby the likelihood of the occurrence of a given event can be described by a probability distribution.

stopping power (lineal stopping power): The quotient of the energy lost (dE) by a charged particle in traversing a distance (dx) in a material. Can also be expressed as mass stopping power by dividing the lineal stopping power by the density (ρ) of the material.

STS: Space Transportation System.

STTR: Small Business Technical Transfer Research.

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TEDE: total effective dose equivalent.

TEPC: tissue equivalent proportional counter.

TGF: transforming growth factor.

TIGER: Grid Generation Code.

tissue weighting factor ( wT): A factor representing the ratio of risk of stochastic effects attributable to irradiation of a given organ or tissue to the total risk when the whole body is irradiated uniformly. The factor is independent of the type of radiation or energy of the radiation.

TLD: thermoluminescent dosimeter.

TMG: thermal micrometeoroid garment.

TMI: Three Mile Island.

TOGA/COARE: Tropical Ocean Global Atmosphere/Coupled Ocean-Atmosphere Experiment.  transport (of radiation): the sequence of interactions between radiation traversing one or more materials and their atoms and nuclei; calculations of the relevant characteristics; transport code: computer program to calculate radiation transport.

trapped radiation: Ionized particles held in place by Earth’s magnetic fields. Also known as the Van Allen belt.

TRL: Technology Readiness Level.

TRMM: Tropical Rainfall Measuring Mission.

TVD: tenth-value distance.

TVL: tenth-value layer.

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UNSCEAR: United Nations Scientific Committee on the Effects Of Atomic Radiation.

US: United States.

USAF: United States Air Force.

US NRC: United States Nuclear Regulatory Commission.

USRA: Universities Space Research Association.

UV: ultraviolet.

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vitreous: The semifluid, transparent substance which lies between the retina and the lens of the eye.

VSE: Vision for Space Exploration.

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WBS: Work Breakdown Structure.

WHO: World Health Organization.

Wind: a NASA spacecraft that observes the Sun and solar wind.

WL: working level.

WLM: working level month (170 h).

w R: radiation weighting factor.

w T: tissue weighting factor.

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Z: atomic number, the number of protons in the nucleus of an atom.

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