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NASA NTRS1995

Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Center JSC↗

DOE OSTI2025

HBET V3.0 Installation Manual

The Hydropower Biological Evaluation Toolset (HBET) V3.0 now requires Python v3.11.0 to be installed, following the addition of the absolute fish injury rate prediction feature. This version introduces two new strike metrics—based on velocity and pressure—to provide a more precise understanding of the biological effects of fish collisions with rigid structures within the fish passage system. Additionally, SQL Server 2019 is the supported database for this release. This installation guide will walk users through the process of installing HBET V3.0 along with all necessary dependencies.

13 HYDRO ENERGY↗

DOE OSTI2022

A small molecule inhibitor prevents gut bacterial genotoxin production

Abstract The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.

Biochemistry & Molecular Biology↗

NASA NTRS2017

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

The high relative biological effectiveness (RBE) of high charged and energy (HZE) particles for cell death, DNA mutations and cancer remain based on experimental data. In this work, we propose that the existence of DNA repair domains is sufficient to predict both cell death and mutation frequencies for any LET by only taking into account experimental data from low-LET, offering one mechanism for RBE across LET. We hypothesize that whenever multiple DNA double-strand breaks (DSBs) are generated within the same DNA repair domain, DSBs are actively regrouped for more efficient repair [1]. This hypothesis has been supported by the low-LET sublinear dose response observed at doses greater than ~1Gy for 53BP1 radiation-induced foci (RIF) reflecting increasing DSB/RIF with dose [2]. Previously, we modeled radiation-induced cell death of human breast cells by first inferring the size of these domains from the dose dependence of low-LET RIF, and by associating a lethality factor to the number of pairs of DSBs in each RIF [1]. In this work, we first integrate the new NASA computer models RITCARD (Relativistic Ion Tracks, Chromosome Aberrations, Repair, and Damage) [3] and BDSTracks (Biological Damage by Stochastic Tracks) for a more accurate microdosimetry and a better model of the nuclear organization to predict the location of DSBs. A large array of particles and energy are simulated, covering more than three orders of magnitude for LET (~1-1000 keV/Âµm). Next, we extend our previous model to predict mutation frequencies by assuming that clustered DSBs increase mutation probability, which is formalized by the mutation frequency being linearly dependent on both the number of DSBs and the number of pairs of DSBs inside individual RIF. Linear coefficients are estimated so that simulations predict accurately mutation frequencies observed in Chinese hamster cells exposed to low-LET. Keeping these coefficients unchanged, we then predict mutation frequencies induced by HZE by simulating DSBs and obtain RBEs for mutations and cell death following the expected experimental bell shape for LET dependence. We also observe an orientation effect that needs to be confirmed, showing different RBE depending on the angle of the HZE beam hitting the main axis of the cell.

Plante, Ianik↗

NASA NTRSDate not supplied

BioSentinel: NASA’s First Deep Space Biological Mission

Since Apollo 17 in 1972, NASA has sent no humans or other biological organisms outside of Earth’s protective magnetosphere. NASA’s current Artemis program plans to put astronauts back on the Moon and eventually land human missions on Mars. One of the major challenges to long-duration crewed travel and habitation in deep space is an in-depth understanding of the biological effects of space radiation, often convoluted by the impact of reduced gravity. Such missions will require significant countermeasures, likely both technological and biomedical, to protect organisms from chronic radiation exposure. Small satellite missions like CubeSats can inform these countermeasures by investigating model organisms in relevant space environments. The BioSentinel mission is comprised of four segments developed at NASA Ames Research Center: a 6U CubeSat (1U = 10-cm cube), an ISS payload launched in December 2021 and two ground units, one for the mission’s CubeSat and one for the ISS payload. The last three segments have been operational since January 2022 and serve as experimental controls. BioSentinel’s 6U CubeSat is planned to launch as a secondary payload on the Artemis-1 rocket. It will be deployed on a lunar fly-by trajectory and into a heliocentric orbit. BioSentinel will be the first interplanetary satellite to study the biological response to space radiation outside Low Earth Orbit (LEO) in almost 50 years. BioSentinel is a complete, autonomous spacecraft capable of conducting experiments in deep space. Its 4U BioSensor payload is a fully automated and adaptable platform that can perform biological measurements with a range of microorganisms in multiple space environments, including the ISS, free flyers, and other platforms like the Lunar Gateway and lander vehicles. Once it reaches its orbit, BioSentinel’s CubeSat will measure the DNA damage response to ambient radiation in a model organism, the budding yeast Saccharomyces cerevisiae, which will be compared to information provided by an onboard radiation sensor and to data obtained in LEO (on ISS) and on Earth. Once in interplanetary space, fluidic cards containing desiccated yeast will be activated by growth medium addition at different time points throughout the mission. Growth and metabolic activity will be tracked continuously via optical measurements. This paper describes BioSentinel’s objectives, science, data management, and preliminary results from the ISS and ISS ground control segments.

BioSentinel↗

NASA NTRSDate not supplied

BioSentinel: NASA’s First Deep Space Biological Mission

BioSentinel↗

NASA NTRS2024

Enhancing the Payload Development Process for Lunar Gateway and Lunar Surface Science & Exploration: Space Biology Beyond Low-Earth-Orbit Instrumentation and Science Series (BLISS) Science Working Group 2023-2024 Annual Report

Space biology BLEO research is inherently driven by the differences between the LEO and BLEO environments, which can be broadly characterized by the five-hazard “RIDGE” paradigm (Radiation, Isolation, Distance, Gravity, Environment, e.g., similar to Figure 2 in (1)). Thus, the envisioned goals over the next decade will include using the cislunar and lunar surface environments to (A) characterize deep-space environments including biological effects of radiation and other stressors, (B) gain experience from isolation of very small groups in very small enclosures, (C) learn to compensate for distance from Earth via in situ resource utilization (ISRU) and bioregenerative life support, (D) gain assurance that all aspects of deep-space exploration can proceed in altered or artificial gravity environments, (E) develop essential adaptation scenarios for the built (e.g., low pressure) and external (e.g., temperature extremes, dust) environments.

Biology↗

DOE OSTI2025

Rhamnogalacturonan I is a recalcitrant pectin domain during Clostridium thermocellum -mediated deconstruction of switchgrass biomass

Background Liquid fuels from lignocellulosic feedstocks are required for transition to a sustainable bioeconomy. However, the recalcitrance of carbon-containing feedstock cell walls to deconstruction poses a barrier to cost effective biological conversion of plant biomass to biofuels. One-step consolidated bioprocessing (CBP) in which anaerobic thermophilic bacteria convert lignocellulosic biomass into liquid fuels is a platform for overcoming the recalcitrance of plant biomass. Results The amounts of hemicellulosic and pectic polysaccharides, two complex cell wall glycans that contribute to plant biomass recalcitrance and that are partially solubilized during CBP of switchgrass aerial biomass by Clostridium thermocellum were evaluated in the liquor, solid residues and residue washate recovered during a 120-h CBP process. After 120 h, 24% of milled switchgrass was solubilized in the C. thermocellum CBP platform. Higher concentrations of arabinose, xylose, galactose, and glucose accumulated in the CBP-fermentation liquor and washate compared to fermentation controls without C. thermocellum, indicating that C. thermocellum solubilized hemicelluloses, but did not fully metabolize them. After five days of fermentation, the relative amount of rhamnose in the solid residues increased by 16% compared to controls, and CBP solid residues had more than 23% increased reactivity against RG-I reactive monoclonal antibodies, indicating that the pectic polymer rhamnogalacturonan I (RG-I) was not effectively solubilized from switchgrass biomass by C. thermocellum CBP. Similarly, the amount of mannose (Man) in the CBP solid residues increased by 7% and reactivity against galactomannan reactive antibodies increased by greater than 14%, indicating that the hemicellulosic polymer galactomannan was also resistant to degradation by C. thermocellum during CBP fermentation. Conclusions These findings show that C. thermocellum is unable to effectively degrade RG-I pectic and galactomannan hemicellulosic components in switchgrass biomass. Targeting these polymers for improved solubilization could enhance the efficiency of conversion of grass biomass to biofuels.

09 BIOMASS FUELS↗

NASA NTRS2010

Human Research Program Space Radiation Standing Review Panel (SRP)

The Space Radiation Standing Review Panel (SRP) met at the NASA Johnson Space Center (JSC) on December 9-11, 2009 to discuss the areas of current and future research targeted by the Space Radiation Program Element (SRPE) of the Human Research Program (HRP). Using evidence-based knowledge as a background for identified risks to astronaut health and performance, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Space Radiation SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the SRP's review. The SRP was requested to evaluate the practicality of the proposed efforts in light of the demands placed on the HRP. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the SRP charge. The SRP made a final debriefing to the HRP Program Scientist, Dr. John B. Charles, on December 11, 2009. The SRP noted that current SRPE strategy is properly science-based and views this as the best assurance of the likelihood that answers to the questions posed as gaps in knowledge can be found, that the uncertainty in risk estimates can be reduced, and that a solid, cost-effective approach to risk reduction solutions is being developed. The current approach of the SRPE, based on the use of carefully focused research solicitations, requiring thorough peer-review and approaches demonstrated to be on the path to answering the NASA strategic questions, addressed to a broad extramural community of qualified scientists, optimally positioned to take advantage of serendipitous discoveries and to leverage scientific advances made elsewhere, is sound and appropriate. The SRP viewed with concern statements by HRP implying that the only science legitimately deserving support should be "applied" or, in some instances that the very term "research" might be frowned upon. We understand the desire of management to ensure that research stay focused on mission objectives, but the terms used are code words fraught with different meaning for scientists. Such expressions, taken at face value, convey a profoundly flawed view of science, can easily lead down counterproductive paths, and have the potential to irretrievably corrupt NASA requirements. The SRP understands and endorses the mandate to keep research efforts focused on the mission needs. However, thoughtful application of knowledge gained by understanding the mechanisms and pathways of biological effects cannot be replaced.

Woloschak, Gayle↗

NASA NTRSDate not supplied

RadLab: Graphical and Programming Interfaces for Interrogation of Space Telemetry Data

Sensors on multiple spacecraft in and beyond low Earth orbit continuously monitor and collect space radiation data and transmit it back to Earth. These data are of vast importance to space biology research, as ionizing radiation affects living organisms—astronauts and non-human experiment subjects alike—placing them at higher risk of carcinogenesis, degenerative diseases, and radiation sickness. Therefore, knowledge of the biological effects of space radiation is essential for planning future crewed missions beyond low Earth orbit. The RadLab project, initiated by GeneLab and ALSDA (the Open Science Data Repository; OSDR) and sponsored by the NASA Human Research Program, is a new effort aimed at connecting dosimetry data from radiation detectors located on the International Space Station (ISS), as well as other spacecraft. To date, access to these data has been fragmented across space agencies and databases; to address this issue, we have developed an application programming interface (API) and an associated graphical user interface (GUI) designed to provide a single point of access to the data. As of now, OSDR has focused on the detectors located on the ISS, with the long-term goal to establish a self-sustained portal receiving continuous updates through APIs connecting to multiple radiation databases of varying scope, as well as individual investigator contributions. The RadLab API implements a request syntax enabling users to query data by craft, sensor type, timespan, etc, allowing for arbitrary combinations of original source data, thus providing programmatic access for use in computational pipelines, while the GUI facilitates data visualization and exploration, making these data FAIR (Findable, Accessible, Interoperable, and Reusable), complementing the biological data contained in OSDR, and providing the space science community with a valuable resource for scientific analyses.

radiation↗

NASA NTRS2015

Spaceflight Causes Increased Virulence of Serratia Marcescens on a Drosophila Melanogaster Host

Drosophila melanogaster, or the fruit fly, has long been an important organism for Earth-based research, and is now increasingly utilized as a model system to understand the biological effects of spaceflight. Studies in Drosophila melanogaster have shown altered immune responses in 3rd instar larvae and adult males following spaceflight, changes similar to those observed in astronauts. In addition, spaceflight has also been shown to affect bacterial physiology, as evidenced by studies describing altered virulence of Salmonella typhimurium following spaceflight and variation in biofilm growth patterns for the opportunistic pathogen Pseudomonas aeruginosa during flight. We recently sent Serratia marcescens Db11, a Drosophila pathogen and an opportunistic human pathogen, to the ISS on SpaceX-5 (Fruit Fly Lab-01). S. marcescens samples were stored at 4degC for 24 days on-orbit and then allowed to grow for 120 hours at ambient station temperature before being returned to Earth. Upon return, bacteria were isolated and preserved in 50% glycerol or RNAlater. Storage, growth, and isolation for ground control samples were performed using the same procedures. Spaceflight and ground samples stored in 50% glycerol were diluted and injected into 5-7-day-old ground-born adult D. melanogaster. Lethality was significantly greater in flies injected with the spaceflight samples compared to those injected with ground bacterial samples. These results indicate a shift in the virulence profile of the spaceflight S. marcescens Db11 and will be further assessed with molecular biological analyses. Our findings strengthen the conclusion that spaceflight impacts the virulence of bacterial pathogens on model host organisms such as the fruit fly. This research was supported by NASA's ISS Program Office (ISSPO) and Space Life and Physical Sciences Research and Applications (SLPSRA).

Serratia marcescens↗

DOE OSTI2021

A High Separation Factor for 165Er from Ho for Targeted Radionuclide Therapy

Background: Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide 177Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce 165Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho(m) targets to produce 165Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified 165Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [165Er]PSMA-617. Results: Irradiation of 80–180 mg natHo targets with 40 µA of 11–12.5 MeV protons produced 165Er at 20–30 MBq·µA−1·h−1. The 4.9 ± 0.7 h radiochemical isolation yielded 165Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/165Er separation factor of (2.8 ± 1.1) · 105. Radiolabeling experiments synthesized [165Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol−1. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [165Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.

165Er↗

DOE OSTI2021

Dual arginine recognition of LRRK2 phosphorylated Rab GTPases

Parkinson’s-disease-associated LRRK2 is a multidomain Ser/Thr kinase that phosphorylates a subset of Rab GTPases to control their effector functions. Rab GTPases are the prime regulators of membrane trafficking in eukaryotic cells. Rabs exert their biological effects by recruitment of effector proteins to subcellular compartments via their Rab-binding domain (RBD). Effectors are modular and typically contain additional domains that regulate various aspects of vesicle formation, trafficking, fusion, and organelle dynamics. The RBD of effectors is typically an α-helical coiled coil that recognizes the GTP conformation of the switch 1 and switch 2 motifs of Rabs. LRRK2 phosphorylates Rab8a at T72 (pT72) of its switch 2 α-helix. This post-translational modification enables recruitment of RILPL2, an effector that regulates ciliogenesis in model cell lines. A newly identified RBD motif of RILPL2, termed the X-cap, has been shown to recognize the phosphate via direct interactions between an arginine residue (R132) and pT72 of Rab8a. Here, we show that a second distal arginine (R130) is also essential for phospho-Rab binding by RILPL2. Through structural, biophysical, and cellular studies, we find that R130 stabilizes the primary R132:pT72 salt bridge through favorable enthalpic contributions to the binding affinity. These findings may have implications for the mechanism by which LRRK2 activation leads to assembly of phospho-Rab complexes and subsequent control of their membrane trafficking functions in cells.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2002

Retinoid quantification by HPLC/MS(n)

Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

NASA Discipline Developmental Biology↗

DOE OSTI2021

Stereotactic Body Radiation Therapy With a High Maximum Dose Improves Local Control, Cancer-Specific Death, and Overall Survival in Peripheral Early-Stage Non-Small Cell Lung Cancer

We investigated whether delivery of a high biologically effective dose (BED) to primary tumors affects systemic outcomes of cancer-specific death (CSD) and overall survival (OS) rates after stereotactic body radiation therapy (SBRT) in patients with early-stage non-small cell lung cancer (ES-NSCLC).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2021

Regulatory T Cells Shape the Differential Impact of Radiation Dose-Fractionation Schedules on Host Innate and Adaptive Antitumor Immune Defenses

We examined how radiation dose per fraction (DPF) and total dose, as represented by biological effective dose (BED), can independently and differentially affect the immunomodulatory capacity of radiation therapy (RT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2022

Arctic Ocean annual high in ${{\boldsymbol{p}}}_{{{\bf{CO}}}_{{\bf{2}}}}$ could shift from winter to summer

Long-term stress on marine organisms from ocean acidification will differ between seasons. As atmospheric carbon dioxide (CO 2 ) increases, so do seasonal variations of ocean CO 2 partial pressure (p co 2 ), causing summer and winter long-term trends to diverge. Trends may be further influenced by an unexplored factor—changes in the seasonal timing of p co 2 . In Arctic Ocean surface waters, the observed timing is typified by a winter high and summer low because biological effects dominate thermal effects. Here we show that 27 Earth system models simulate similar timing under historical forcing but generally project that the summer low, relative to the annual mean, eventually becomes a high across much of the Arctic Ocean under mid-to-high-level CO 2 emissions scenarios. Often the greater increase in summer p co 2 , although gradual, abruptly inverses the chronological order of the annual high and low, a phenomenon not previously seen in climate-related variables. The main cause is the large summer sea surface warming from earlier retreat of seasonal sea ice. Warming and changes in other drivers enhance this century’s increase in extreme summer p co 2 by 29 ± 9 per cent compared with no change in driver seasonalities. Thus the timing change worsens summer ocean acidification, which in turn may lower the tolerance of endemic marine organisms to increasing summer temperatures.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2020

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Rationale and Framework for the Monograph and Overview of Eligible Studies

Abstract Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings. We conducted a systematic review of epidemiological studies with mean doses less than 100 mGy published 2006–2017. We required individualized doses and dose-response estimates with confidence intervals. We identified 26 eligible studies (eight environmental, four medical, and 14 occupational), including 91 000 solid cancers and 13 000 leukemias. Mean doses ranged from 0.1 to 82 mGy. The excess relative risk at 100 mGy was positive for 16 of 22 solid cancer studies and 17 of 20 leukemia studies. The aim of this monograph was to systematically review the potential biases in these studies (including dose uncertainty, confounding, and outcome misclassification) and to assess whether the subset of minimally biased studies provides evidence for cancer risks from low-dose radiation. Here, we describe the framework for the systematic bias review and provide an overview of the eligible studies.

Berrington de Gonzalez, Amy↗