Low Linear Energy Transfer Research Articles

Evaluation of Soft-Error Tolerance by Neutrons and Heavy Ions on Flip Flops With Guard Gates in a 65-nm Thin BOX FDSOI Process

We evaluated soft-error tolerance by neutrons and heavy ions on four types of flip flops (FFs) called D-type flip flop (DFF), guard-gate FF (GGFF), feedback recovery FF (FRFF), and dual FRFF (DFRFF) in a 65-nm thin buried oxide (BOX) fully depleted silicon on insulator (FDSOI). FRFF has a guard-gate structure only in the master latch. GGFF and DFRFF have the guard-gate structure in both master and slave latches. The guard-gate structure resolves a single-event transient (SET) pulse by delaying it through the guard gate. FRFF and DFRFF have smaller area and shorter delay overheads than GGFF. We revealed that the guard-gate structure has high soft-error tolerance by low-linear energy transfer (LET) heavy ions, but the larger-LET ions over 40 MeV-cm2/mg cause upset even in the guard-gate structures. We revealed that longer delay in the guard-gate can resolve these issues by circuit simulations.

Targeted Alpha Therapy: Current Clinical Applications.

α-Emitting radionuclides have been approved for cancer treatment since 2013, with increasing degrees of success. Despite this clinical utility, little is known regarding the mechanisms of action of α particles in this setting, and accurate assessments of the dosimetry underpinning their effectiveness are lacking. However, targeted alpha therapy (TAT) is gaining more attention as new targets, synthetic chemistry approaches, and α particle emitters are identified, constructed, developed, and realized. From a radiobiological perspective, α particles are more effective at killing cells compared to low linear energy transfer radiation. Also, from these direct effects, it is now evident from preclinical and clinical data that α emitters are capable of both producing effects in nonirradiated bystander cells and stimulating the immune system, extending the biological effects of TAT beyond the range of α particles. The short range of α particles makes them a potent tool to irradiate single-cell lesions or treat solid tumors by minimizing unwanted irradiation of normal tissue surrounding the cancer cells, assuming a high specificity of the radiopharmaceutical and good stability of its chemical bonds. Clinical approval of 223RaCl2 in 2013 was a major milestone in the widespread application of TAT as a safe and effective strategy for cancer treatment. In addition, 225Ac-prostate specific membrane antigen treatment benefit in metastatic castrate-resistant prostate cancer patients, refractory to standard therapies, is another game-changing piece in the short history of TAT clinical application. Clinical applications of TAT are growing with different radionuclides and combination therapies, and in different clinical settings. Despite the remarkable advances in TAT dosimetry and imaging, it has not yet been used to its full potential. Labeled 227Th and 225Ac appear to be promising candidates and could represent the next generation of agents able to extend patient survival in several clinical scenarios.

Mutual interference induced by single event effects in CMOS circuits

Single event effect (SEE) induced mutual interference in CMOS circuits, including single event (SE) induced coupling effects (crosstalk) and modulation in local supply voltage on power-supply rails, was studied based on the increase in metal interconnect density. The dependence of SE vulnerability on metal interconnects was experimentally investigated using heavy ions and pulsed laser. Numerical simulation was performed to evaluate the modulation in local supply voltage induced by SEEs. Two groups of test structures with various metal interconnects between well contacts and the first metal layer were designed and fabricated. All other parts, including well contacts in the active regions, are of the same structures. Experimental results show that the upset cross section decreases with an increase in metal interconnect contact (CT) density between the active region and the first metal layer, suggesting a dominant contribution of rail voltage drop induced by charge sharing rather than SE-induced crosstalk. The differences in upset cross sections with cells of different CT hole densities appear the most evident ones under low frequency and high linear energy transfer value conditions. When transient-induced upsets play a more important role, the differences get weakened due to masking effects.

The Unfolded Protein Response: Neutron-Induced Therapy Autophagy as a Promising Treatment Option for Osteosarcoma.

Radiotherapy using high linear energy transfer (LET) radiation results in effectively killing tumor cells while minimizing dose (biological effective) to normal tissues to block toxicity. It is well known that high LET radiation leads to lower cell survival per absorbed dose than low LET radiation. High-linear energy transfer (LET) neutron treatment induces autophagy in tumor cells, but its precise mechanisms in osteosarcoma are unknown. Here, we investigated this mechanism and the underlying signaling pathways. Autophagy induction was examined in gamma-ray-treated KHOS/NP and MG63 osteosarcoma cells along with exposure to high-LET neutrons. The relationship between radiosensitivity and autophagy was assessed by plotting the cell surviving fractions against autophagy levels. Neutron treatment increased autophagy rates in irradiated KHOS/NP and MG63 cells; neutrons with high-LETs showed more effective inhibition than those with lower LET gamma-rays. To determine whether the unfolded protein response and Akt-mTOR pathways triggered autophagy, phosphorylated eIF2α and JNK levels, and phospho-Akt, phosphor-mTOR, and phospho-p70S6 levels were, respectively, investigated. High-LET neutron exposure inhibited Akt phosphorylation and increased Beclin 1 expression during the unfolded protein response, thereby enhancing autophagy. The therapeutic efficacy of high-LET neutron radiation was also assessed in vivo using an orthotopic mouse model. Neutron-irradiated mice showed reduced tumor growth without toxicity relative to gamma-ray-treated mice. The effect of high-LET neutron exposure on the expression of signaling proteins LC3, p-elF2a, and p-JNK was investigated by immunohistochemistry. Tumors in high-LET-neutron radiation-treated mice showed higher apoptosis rates, and neutron exposure significantly elevated LC3 expression, and increased p-elF2a and p-JNK expression levels. Overall, these results demonstrate that autophagy is important in radiosensitivity, cell survival, and cellular resistance against high-LET neutron radiation. This correlation between cellular radiosensitivity and autophagy may be used to predict radiosensitivity in osteosarcoma.

Clinical implications of variable relative biological effectiveness in proton therapy for prostate cancer

Purpose To study the potential consequences of differences in the evaluation of variable versus uniform relative biological effectiveness calculations in proton radiotherapy for prostate cancer. Methods and material Experimental data with proton beams suggest that relative biological effectiveness increases with linear energy transfer. This relation also depends on the ratio, characteristic of a tissue and a considered endpoint. Three phenomenological models (Carabe et al., Wedenberg et al. and McNamara et al.) are compared to a mechanistic model based on microdosimetry (microdosimetric kinetic model) and to the current assumption of uniform relative biological effectiveness equal to 1.1 in a prostate case. Results and conclusions Phenomenological models clearly predict higher relative biological effectiveness values compared to microdosimetric kinetic model, that seems to approach to the constant value of 1.1 adopted in the clinics, at least for low linear energy transfer values achieved in typical prostate proton plans. All models predict a higher increase of the relative biological effectiveness-weighted dose for the prostate tumor than for the rest of structures involved due to its lower ratio, even when linear energy transfer is, in general, lower in the tumor than on the surroundings tissues. Prostate cancer is, therefore, a good candidate to take advantage of variable relative biological effectiveness, especially if linear energy transfer is enhanced within the tumor. However, the discrepancies among models hinder the clinical implementation of variable relative biological effectiveness.

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio.

The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle. The misrepair of DNA damage results in genomic rearrangement and causes mutations and chromosome aberrations, which are drivers of cell death. This work presents an integrated study of simulating cell response after proton irradiation with energies of 0.5-500 MeV (LET of 60-0.2 keV/µm). A model of a whole nucleus with fractal DNA geometry was implemented in TOPAS-nBio for initial DNA damage simulations. The default physics and chemistry models in TOPAS-nBio were used to describe interactions of primary particles, secondary particles, and radiolysis products within the nucleus. The initial DNA double-strand break (DSB) yield was found to increase from 6.5 DSB/Gy/Gbp at low-linear energy transfer (LET) of 0.2 keV/µm to 21.2 DSB/Gy/Gbp at high LET of 60 keV/µm. A mechanistic repair model was applied to predict the characteristics of DNA damage repair and dose response of chromosome aberrations. It was found that more than 95% of the DSBs are repaired within the first 24 h and the misrepaired DSB fraction increases rapidly with LET and reaches 15.8% at 60 keV/µm with an estimated chromosome aberration detection threshold of 3 Mbp. The dicentric and acentric fragment yields and the dose response of micronuclei formation after proton irradiation were calculated and compared with experimental results.

A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric–kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.

Cytogenetically-based biodosimetry after high doses of radiation.

Dosimetry is an important tool for triage and treatment planning following any radiation exposure accident, and biological dosimetry, which estimates exposure dose using a biological parameter, is a practical means of determining the specific dose an individual receives. The cytokinesis-blocked micronucleus assay (CBMN) is an established biodosimetric tool to measure chromosomal damage in mitogen-stimulated human lymphocytes. The CBMN method is especially valuable for biodosimetry in triage situations thanks to simplicity in scoring and adaptability to high-throughput automated sample processing systems. While this technique produces dose-response data which fit very well to a linear-quadratic model for exposures to low linear energy transfer (LET) radiation and for doses up for 5 Gy, limitations to the accuracy of this method arise at larger doses. Accuracy at higher doses is limited by the number of cells reaching mitosis. Whereas it would be expected that the yield of micronuclei increases with the dose, in many experiments it has been shown to actually decrease when normalized over the total number of cells. This variation from a monotonically increasing dose response poses a limitation for retrospective dose reconstruction. In this study we modified the standard CBMN assay to increase its accuracy following exposures to higher doses of photons or a mixed neutron–photon beam. The assay is modified either through inhibitions of the G2/M and spindle checkpoints with the addition of caffeine and/or ZM447439 (an Aurora kinase inhibitor), respectively to the blood cultures at select times during the assay. Our results showed that caffeine addition improved assay performance for photon up to 10 Gy. This was achieved by extending the assay time from the typical 70 h to just 74 h. Compared to micronuclei yields without inhibitors, addition of caffeine and ZM447439 resulted in improved accuracy in the detection of micronuclei yields up to 10 Gy from photons and 4 Gy of mixed neutrons-photons. When the dose-effect curves were fitted to take into account the turnover phenomenon observed at higher doses, best fitting was achieved when the combination of both inhibitors was used. These techniques permit reliable dose reconstruction after high doses of radiation with a method that can be adapted to high-throughput automated sample processing systems.

Preliminary study on radiosensitivity to carbon ions in human breast cancer.

The aim of the study was to investigate the various effects of high linear energy transfer (LET) carbon ion (12C6+) and low LET X-ray radiation on MDA-MB-231 and MCF-7 human breast cancer cells and to explore the underlying mechanisms of radiation sensitivity. Cell proliferation, cell colony formation, cell cycle distribution, cell apoptosis and protein expression levels [double-strand break marker γ-H2AX, cell cycle-related protein cyclin B1, apoptosis-related proteins Bax and Bcl-2, and the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase B1 (p70S6K) pathway] were detected after irradiation with carbon ions or X-rays at doses of 0, 2, 4 and 8 Gy. Our results showed that the inhibition of cell proliferation and cell colony formation and the induction of G2/M phase arrest, DNA lesions and cell apoptosis/necrosis elicited by carbon ion irradiation were more potent than the effects elicited by X-ray radiation at the same dose. Simultaneously, compared with X-ray radiation, carbon ion radiation induced a marked increase in Bax and prominent decreases in cyclin B1 and Bcl-2 in a dose-dependent manner. Furthermore, the Akt/mTOR/p70S6K pathway was significantly inhibited by carbon ion radiation in both breast cancer cell lines. These results indicate that carbon ion radiation kills MDA-MB-231 and MCF-7 breast cancer cells more effectively than X-ray radiation, which might result from the inhibition of the Akt/mTOR/p70S6K pathway.

SE Response of Guard-Gate FF in 16- and 7-nm Bulk FinFET Technologies

Single-event (SE) performance of the guard-gate flip-flop (GG-FF) and conventional D-FF designs is evaluated at the 16- and 7-nm FinFET technology nodes. The heavy-ion test results show that at the 16-nm node, the GG-FF shows better SE performance for low-linear energy transfer (LET) particles and similar performance for high-LET particles compared with D-FF design. However, at the 7-nm node, the GG-FF shows better SE performance than the D-FF across a wide range of particle LET values. This behavior is due to the higher number of short SE transient (SET) pulses for high-LET particles at the 7-nm node. The heavy-ion test results are used to estimate the number of short SET pulses as a function of particle LET values.

Dose- rather than fluence-averaged LET should be used as a single-parameter descriptor of proton beam quality for radiochromic film dosimetry.

PurposeThe dose response of Gafchromic EBT3 films exposed to proton beams depends on the dose, and additionally on the beam quality, which is often quantified with the linear energy transfer (LET) and, hence, also referred to as LET quenching. Fundamentally different methods to determine correction factors for this LET quenching effect have been reported in literature and a new method using the local proton fluence distribution differential in LET is presented. This method was exploited to investigate whether a more practical correction based on the dose‐ or fluence‐averaged LET is feasible in a variety of clinically possible beam arrangements.MethodsThe relative effectiveness (RE) was characterized within a high LET spread‐out Bragg peak (SOBP) in water made up by the six lowest available energies (62.4–67.5 MeV, configuration “b1”) resulting in one of the highest clinically feasible dose‐averaged LET distributions. Additionally, two beams were measured where a low LET proton beam (252.7 MeV) was superimposed on “b1”, which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration “b2” and “b3,” respectively. The proton LET spectrum was simulated with GATE/Geant4 at all measurement positions. The net optical density change differential in LET was integrated over the local proton spectrum to calculate the net optical density and therefrom the beam quality correction factor. The LET dependence of the film response was accounted for by an LET dependence of one of the three parameters in the calibration function and was determined from inverse optimization using measurement “b1.” This method was then validated on the measurements of “b2” and “b3” and subsequently used to calculate the RE at 900 positions in nine clinically relevant beams. The extrapolated RE set was used to derive a simple linear correction function based on dose‐averaged LET (Ld) and verify the validity in all points of the comprehensive RE set.ResultsThe uncorrected film dose deviated up to 26% from the reference dose, whereas the corrected film dose agreed within 3% in all three beams in water (“b1”, “b2” and “b3”). The LET dependence of the calibration function started to strongly increase around 5 keV/μm and flatten out around 30 keV/μm. All REs calculated from the proton fluence in the nine simulated beams could be approximated with a linear function of dose‐averaged LET (RE = 1.0258−0.0211 μm/keV Ld). However, no functional relationship of RE‐ and fluence‐averaged LET could be found encompassing all beam energies and modulations.ConclusionsThe film quenching was found to be nonlinear as a function of proton LET as well as of the dose‐averaged LET. However, the linear relation of RE on dose‐averaged LET was a good approximation in all cases. In contrast to dose‐averaged LET, fluence‐averaged LET could not describe the RE when multiple beams were applied.

Scintillator screen for measuring low-dose halo in scanning carbon-ion therapy

To ensure safe administration and quality assurance (QA) of scanning carbon-ion therapy doses, an efficient and reliable method to measure the lateral dose profile of a carbon-ion pencil beam, including the low-dose halo, is required. We developed a simple, expeditious dose measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator, which shows a low linear energy transfer (LET) dependency, to measure the low-dose halo of a carbon-ion pencil beam with high spatial resolution.

Alkaline hydrolysis of radio-oxidized aliphatic polymers

Organic molecules are part of the Long-Lived Intermediate-Level Waste (LL-ILW) packages. These packages are planned to be delivered at the French deep geological repository, consequently their degradation has to be thoroughly understood in order to support the safety studies. In a first period, these organic molecules, which include polymers, are radio-oxidized because of their close proximity with radionuclides. In a second period, water will diffuse inside the site up to the packages, leading to the alkaline hydrolysis of the radio-oxidized polymers. The objective of this study is to evaluate the parameters having a major influence on these radio-oxidized polyolefins hydrolysis at high pH. Aliphatic polymers are chosen because of their relative importance, in quantity, in the French LL-ILW packages.In this work, we have first radio-oxidized aliphatic polymers in conditions that are representative of their ageing in the first period of the LL-ILW packages: we have employed different doses up to 10 MGy, different emitters - or their equivalent -, i.e. γ-rays and swift heavy ions (SHI) irradiation to model α-rays. To model the second period of ageing of these LL-ILW packages, we have hydrolyzed under alkaline conditions and under inert atmosphere these radio-oxidized polymers.We have evaluated the influence of the materials’ composition (the resin chemical structure, presence of charges and fillers) and of the irradiation conditions (irradiation type, linear energy transfer (LET) and dose). We observed that hydrolysis is influenced not only by the molecular structure of the polymer, but also by the presence of inorganic fillers and organic additives. The hydrolysis increases with increasing dose and increasing LET for SHI. The most penalizing conditions were encountered under low LET ionizing rays. This is related to the higher oxidation level induced under γ-rays: the higher the oxidation rate, the higher the polyolefins sensitivity to alkaline hydrolysis.

Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy.

Cells manage to survive, thrive, and divide with high accuracy despite the constant threat of DNA damage. Cells have evolved with several systems that efficiently repair spontaneous, isolated DNA lesions with a high degree of accuracy. Ionizing radiation and a few radiomimetic chemicals can produce clustered DNA damage comprising complex arrangements of single-strand damage and DNA double-strand breaks (DSBs). There is substantial evidence that clustered DNA damage is more mutagenic and cytotoxic than isolated damage. Radiation-induced clustered DNA damage has proven difficult to study because the spectrum of induced lesions is very complex, and lesions are randomly distributed throughout the genome. Nonetheless, it is fairly well-established that radiation-induced clustered DNA damage, including non-DSB and DSB clustered lesions, are poorly repaired or fail to repair, accounting for the greater mutagenic and cytotoxic effects of clustered lesions compared to isolated lesions. High linear energy transfer (LET) charged particle radiation is more cytotoxic per unit dose than low LET radiation because high LET radiation produces more clustered DNA damage. Studies with I-SceI nuclease demonstrate that nuclease-induced DSB clusters are also cytotoxic, indicating that this cytotoxicity is independent of radiogenic lesions, including single-strand lesions and chemically “dirty” DSB ends. The poor repair of clustered DSBs at least in part reflects inhibition of canonical NHEJ by short DNA fragments. This shifts repair toward HR and perhaps alternative NHEJ, and can result in chromothripsis-mediated genome instability or cell death. These principals are important for cancer treatment by low and high LET radiation.

Impact of Target Oxygenation on the Chemical Track Evolution of Ion and Electron Radiation.

The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( and ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the and production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of and in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( and ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the and production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of and in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

The Potential Effects of Radiation on the Gut-Brain Axis.

Over the course of a lifetime, humans may be exposed to different types of radiation, typically in the form of low-linear energy transfer (LET) radiation, which is used, for example, in cancer treatment. In addition, astronauts may be exposed to high-LET radiation in outer space. Here, we propose that alterations to the gastrointestinal (GI) microbiota may occur when exposure to either low- or high-LET radiation, and that these alterations may perturb important relationships that exist between the GI microbiota and human health. For example, the GI microbiota can communicate with the brain via various pathways and molecules, such as the enteric nervous system, the vagus nerve, microbial metabolites and the immune system. This relationship has been termed the "gut-brain axis". Alterations to the composition of the GI microbiome can lead to alterations in its functional metabolic output and means of communication, therefore potentially causing downstream cognitive effects. Consequently, studying how radiation can affect this important network of communication could lead to new and critical interventions, as well as prevention strategies. Herein, we review the evidence supporting a relationship between radiation exposure and disruption of the gut-brain axis as well as summarize strategies that may be used to counter the effects of radiation exposure on the GI microbiome.

LET Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of Mi RNAs that Drive Inhibition

Space Radiation inhibits angiogenesis by two mechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of the early motile stage of angiogenesis was determined to occur after exposure to low LET ions ( 8 KeV/AMU). Strikingly, the combined effect is synergistic, detectible as low as 0.6 cGy making mixed ion Space Radiation more potent. Candidates for bystander transmission are microRNAs (miRNAs) and analysis on miRNA-seq data from irradiated mice shows that angiogenesis would in theory, be downregulated. Further analysis of three previously identified miRNAs showed downregulation of their targets associated with angiogenesis and confirmed their involvement in angiogenesis pathways and increased health risks associated with cardiovascular disease. Finally, synthetic molecules (Antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis.

Low-dose radiobiology: Opportunities for new research and technology for anticancer and anti-COVID-19 strategies

Biological responses to low-dose and high-dose radiations are markedly different; the former produce beneficial effects and the latter at acute doses cause detrimental health effects such as cancer induction. High-dose radiations (>2 Gy) of low linear energy transfer are widely used in the treatment of cancer, but limitations are imposed due to normal tissue adverse reactions. Low-dose radiations (LDRs), such as X-rays (a few mGy), have been widely used in diagnosis of many diseases without any known adverse health effects. LDR preexposures have been known to suppress cancer induction by acute doses of radiation. This article briefly reviews the possible applications of LDR in cancer therapy and delineates the underlying radiobiological mechanisms in suppressing high-dose-induced cancer. It is further argued to develop LDR technology in preventing and for palliative outcomes in fighting COVID-19 pandemic infection among the populations. Furthermore, it is suggested to examine the average number of people living in high background radiation areas for susceptibility to COVID-19 infection and compare with the average infection rate in the general public for gaining new knowledge on the response of LDR-exposed population.

Yields of primary species in the low-linear energy transfer radiolysis of water in the temperature range of 25-700 °C.

Monte Carlo track chemistry simulations were used to calculate the time-dependent yields (G values) for the radical (eaq-, H˙, ˙OH) and molecular (H2, H2O2) "primary species" formed in the low-linear energy transfer (LET) radiolysis of deaerated, pure water (H2O) in the range of ∼1 ps to 1 ms between 25 and 700 °C, at 25 MPa pressure. Beyond the critical point, we used in the calculations the new supercritical water (SCW) radiolysis database of Liu et al., in particular their reported reaction rate constants. A striking conclusion of these simulations is the sharp increase in G(˙OH) and G(H2), and the corresponding decrease in G(H˙), which are observed above 200 °C, due to the oxidation of water by the H˙ atom (H˙ + H2O → ˙OH + H2) in the homogeneous chemical stage of radiolysis. These results may have important implications for proposed Generation-IV SCW-cooled reactors for the control and management of water chemistry and for the maintenance of the structural integrity of materials.

Response to the Commentary from Bevelacqua et al.

This response clarifies certain misconceptions published in the commentary by Bevelacqua et al. (2019). We are pleased that our article entitled “New concerns for neurocognitive function during deep space exposures to chronic, low dose rate, neutron radiation” (Acharya et al., 2019) has stimulated interesting discussions and different perspectives on what may or may not be relevant to estimating the risks of CNS dysfunction following exposure to the space radiation environment. Here we provide our response to the commentary from Bevelacqua et al. (2019). Bevelacqua et al. (2019) stated that there were a few major shortcomings with our approach, and we would like to clarify our stance regarding those statements. The first and perhaps most disconcerting statement was their assertion that we have ignored “…that in a realistic space environment, cells will be exposed to multiple low LET (linear energy transfer) protons before being traversed by intermediate and high-LET HZE (high charge and energy) particles.” The authors of Acharya et al. (2019) have conducted research at heavy ion particle accelerators around the world for more than a decade, and the implication that we might be unaware of the complexities of the radiation fields in space is misguided (Parihar et al., 2015, 2016, 2018; Lee et al., 2017). During long-term missions into deep space, astronauts will be exposed to a complex radiation field that includes high LET components from high energy, heavy ions (HZE particles) at low dose rates of ∼0.5 mGy/d for long durations. About 20% of the dose is delivered with LET >10 keV/μm. Particle accelerators are capable of simulating components of the galactic cosmic radiation (GCR) spectrum. The main impediment to performing accelerator-based experiments, which are designed to simulate exposures to …