Heavy Ion Exposure Research Articles

Toxic heavy metal ions contamination in water and their sustainable reduction by eco-friendly methods: isotherms, thermodynamics and kinetics study

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

β-D-Glucan promotes NF-κB activation and ameliorates high-LET carbon-ion irradiation-induced human umbilical vein endothelial cell injury.

Heavy-ion irradiation seriously perturbs cellular homeostasis and thus damages cells. Vascular endothelial cells (ECs) play an important role in the pathological process of radiation damage. Protecting ECs from heavy-ion radiation is of great significance in the radioprotection of normal tissues. In this study, the radioprotective effect of β-D-glucan (BG) derived from Saccharomyces cerevisiae on human umbilical vein endothelial cell (EA.hy926) cytotoxicity produced by carbon-ion irradiation was examined and the probable mechanism was established. EA.hy926 cells were divided into seven groups: a control group; 1, 2, or 4 Gy radiation; and 10 μg/mL BG pretreatment for 24 h before 1, 2, or 4 Gy irradiation. Cell survival was assessed by colony formation assay. Cell cycles, apoptosis, DNA damage, and reactive oxygen species (ROS) levels were measured through flow cytometry. The level of malondialdehyde and antioxidant enzyme activities were analyzed using assay kits. The activation of NF-κB was analyzed using western blotting and a transcription factor assay kit. The expression of downstream target genes was detected by western blotting. BG pretreatment significantly increased the survival of irradiated cells, improved cell cycle progression, and decreased DNA damage and apoptosis. The levels of ROS and malondialdehyde were also decreased by BG. Further study indicated that BG increased the antioxidant enzyme activities, activated Src, and promoted NF-κB activation, especially for the p65, p50, and RelB subunits. The activated NF-κB upregulated the expression of antioxidant protein MnSOD, DNA damage-response and repair-related proteins BRCA2 and Hsp90α, and antiapoptotic protein Bcl-2. Our results demonstrated that BG protects EA.hy926 cells from high linear-energy-transfer carbon-ion irradiation damage through the upregulation of prosurvival signaling triggered by the interaction of BG with its receptor. This confirms that BG is a promising radioprotective agent for heavy-ion exposure.

Response of ZrC to swift heavy ion irradiation

Zirconium carbide (ZrC) is commonly used for energy sector research, as well as a surrogate for the proposed advanced nuclear fuel candidate uranium carbide. This study investigates structural modifications to nanocrystalline and microcrystalline ZrC resulting from dense electronic excitations induced by swift heavy ion exposure. Samples were irradiated with 946 MeV Au ions to various fluences up to 6 × 1013 ions cm−2 and characterized using synchrotron-based x-ray diffraction. The evolution of the unit-cell parameter and heterogeneous microstrain were evaluated as a function of fluence and compared with those of nanocrystalline and microcrystalline CeO2 (a surrogate for UO2 fuel) irradiated under identical conditions. Distinct differences were observed in the radiation responses of the carbide and oxide across both grain sizes. Most notably, microcrystalline ZrC exhibits swelling characterized by two distinct regimes, which does not result in saturation at the ion fluences achieved. This contrasts with CeO2, which exhibits the well-documented direct-impact defect accumulation mechanism, reaching a steady-state saturation of swelling at higher fluences. Nanocrystalline CeO2 undergoes more pronounced swelling compared with microcrystalline CeO2, in contrast to nanocrystalline ZrC, which exhibits only minimal unit-cell changes. These results demonstrate that swift heavy ion-induced structural changes can be quite different in carbides and oxides, which must be considered when extrapolating fission-fragment type damage in current fuels to advanced fuels.

Identification of the Kupffer cell-derived circulating IGFBP-3 as a universal radiation biomarker for heavy ion, proton, and X-ray exposure

The minimally invasive biomarkers that can facilitate a rapid dose assessment are valuable for the early medical treatment when accidental or occupational radiation exposure happens. Our previous proteomic research identified one kind of circulating protein, Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), which showed a significant increase after total body exposure of mice to carbon ions and X-rays. However, several critical issues such as the responses to diverse radiation, the origin and underlying mechanism in radiation response obstruct the utilization of circulating IGFBP-3 as a reliable radiation biomarker. In this study, mice were subjected to total or partial body irradiation with carbon ions, protons or X-rays, or treated with chloroform as a comparison. The level of IGFBP-3 in serum and different organs were measured via Enzyme Linked Immunosorbent Assay (ELISA), Western blot (WB) and Immunohistochemistry (IHC). A significant increase of IGFBP-3 was discovered in serum and liver tissue post-irradiation with three kinds of radiation, but absent when challenged with chloroform. Likewise, a similar response was also observed in blood samples from patients receiving radiotherapy. Moreover, the effect of radiation on three main hepatic cells was investigated, the findings indicated that IGFBP-3 could be detected in the culture medium of Kupffer cells (MKC) alone and was elevated in cells and cultured medium of MKC post-irradiation. Additionally, we observed a co-expression effect between P53 and IGFBP-3 in liver tissues and MKC post-irradiation. Along with down-regulation of Trp53 by siRNA, the response of IGFBP-3 to radiation was attenuated. The present study demonstrated that circulating IGFBP-3 could be a promising universal biomarker for complex environmental radiation exposure, and the upregulation of IGFBP-3 is attributed to the MKC in a P53-dependent manner. Circulating IGFBP-3 assays would offer rapid, convenient and effective dose and toxicity assessment methods in occupational exposure or radiation disaster management.

Simulation study of single-event burnout in hardened GaN MISFET

This paper presents simulation results of a single event burnout (SEB), for a hardened GaN metal-insulator-semiconductor field-effect transistor (MISFET), employing a dual channel p-type buried layer structure (DCP-MISFET). After irradiance with a heavy ion beam, the peak electric field around the gate channel was observed to move towards the drain channel. In addition, the electrons released by the bombardment of heavy ions were also seen to move towards the drain channel, resulting in strong impact ionization at the drain terminal. Compared to the conventional MISFET with field plates (FPC-MISFET), the distribution of electric field and the impact ionization, after heavy ion's exposure around the drain channel are improved in the GaN DCP-MISFET. Because of the second channel, the electrons induced by the heavy ion beam, change their direction. The proposed DCP-MISFET can achieve a better SEB performance than FPC-MISFET. with a heavy ion beam having the linear energy transfer (LET) value of 0.6 pC/μm at x = 7.5 μm striking vertically, the SEB threshold voltages that were obtained in FPC-MISFET and DCP-MISFET were 520 and 920 V, respectively.

Analysis of Single Event Transients in Arbitrary Waveforms Using Statistical Window Analysis

Window or taper functions are commonly used in data processing to detect transient events or for time-averaging of frequency spectra. A generalized window function is demonstrated using the Ionizing Radiation Effects Spectroscopy (IRES) technique to enhance the measurement of transient anomalies within arbitrary waveforms. The IRES filter is used to convolve time data with a sliding window consisting of a moment-generating function. The resulting time-dependent statistical moments can be used to eliminate any steady-state signatures, including noise, and extract transient behaviors. The IRES filter is used to analyze data from heavy-ion exposures of commercial off-the-shelf (COTS) operational amplifiers, laser-induced transients in CMOS phase-locked loops, and simulated transients in digital and analog circuits. The performance of the IRES filter in noisy environments shows that transients can be measured with higher fidelity than standard amplitude thresholding. This statistical window analysis technique may remove the need for complex triggering mechanisms on instrumentation and does not require <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">a-priori</i> knowledge of transient characteristics. Potential applications of IRES include real-time measurement, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in-situ</i> data analysis, and machine learning.

Combined effects of heavy ion exposure and simulated Lunar gravity on skeletal muscle

BackgroundThe limitations to prolonged spaceflight include unloading-induced atrophy of the musculoskeletal system which may be enhanced by exposure to the space radiation environment. Previous results have concluded that partial gravity, comparable to the Lunar surface, may have detrimental effects on skeletal muscle. However, little is known if these outcomes are exacerbated by exposure to low-dose rate, high-energy radiation common to the space environment. Therefore, the present study sought to determine the impact of highly charge, high-energy (HZE) radiation on skeletal muscle when combined with partial weightbearing to simulate Lunar gravity. We hypothesized that partial unloading would compromise skeletal muscle and these effects would be exacerbated by radiation exposure. MethodsFor month old female BALB/cByJ mice were -assigned to one of 2 groups; either full weight bearing (Cage Controls, CC) or partial weight bearing equal to 1/6th bodyweight (G/6). Both groups were then divided to receive either a single whole body absorbed dose of 0.5 Gy of 300 MeV 28Si ions (RAD) or a sham treatment (SHAM). Radiation exposure experiments were performed at the NASA Space Radiation Laboratory (NSRL) located at Brookhaven National Laboratory on Day 0, followed by 21 d of CC or G/6 loading. Muscles of the hind limb were used to measure protein synthesis and other histological measures. ResultsTwenty-one days of Lunar gravity (G/6) resulted in lower soleus, plantaris, and gastrocnemius muscle mass. Radiation exposure did not further impact muscle mass. 28Si exposure in normal ambulatory animals (RAD+CC) did not impact gastrocnemius muscle mass when compared to SHAM+CC (p>0.05), but did affect the soleus, where mass was higher following radiation compared to SHAM (p<0.05). Mixed gastrocnemius muscle protein synthesis was lower in both unloading groups. Fiber type composition transitioned towards a faster isoform with partial unloading and was not further impacted by radiation. The combined effects of partial loading and radiation partially mitigated fiber cross-sectional area when compared to partial loading alone. Radiation and G/6 reduced the total number of myonuclei per fiber while leading to elevated BrdU content of skeletal muscle. Similarly, unloading and radiation resulted in higher collagen content of muscle when compared to controls, but the effects of combined exposure were not additive. ConclusionsThe results of this study confirm that partial weightbearing causes muscle atrophy, in part due to reductions of muscle protein synthesis in the soleus and gastrocnemius as well as reduced peripheral nuclei per fiber. Additionally, we present novel data illustrating 28Si exposure reduced nuclei in muscle fibers despite higher satellite cell fusion, but did not exacerbate muscle atrophy, CSA changes, or collagen content. In conclusion, both partial loading and HZE radiation can negatively impact muscle morphology.

Heavy-ion radiation-induced colitis and colorectal carcinogenesis in Il10-/- mice display co-activation of β-catenin and NF-κB signaling.

Space radiation-induced gastrointestinal (GI) cancer risk models for future interplanetary astronauts are being developed that primarily rely on quantitative animal model studies to assess radiation-quality effects of heavy-ion space radiation exposure in relation to γ-rays. While current GI-cancer risk estimation efforts are focused on sporadic GI-cancer mouse models, emerging in-vivo data on heavy-ion radiation-induced long-term GI-inflammation are indicative of a higher but undetermined risk of GI-inflammation associated cancers, such as colitis-associated cancer (CAC). Therefore, we aimed to assess radiation quality effects on colonic inflammation, colon cancer incidence, and associated signaling events using an in-vivo CAC model i.e., Il10-/- mice. Male Il10-/- mice (8-10 weeks, n = 12/group) were irradiated with either sham, γ-rays or heavy-ions (28Si or 56Fe), and histopathological assessments for colitis and CAC were conducted at 2.5 months post-exposure. qPCR analysis for inflammation associated gene transcripts (Ptges and Tgfb1), and in-situ staining for markers of cell-proliferation (phospho-histone H3), oncogenesis (active-β-catenin, and cyclin D1), and inflammation (phospho-p65NF-κB, iNOS, and COX2) were performed. Significantly higher colitis and CAC frequency were noted after heavy-ion exposure, relative to γ and control mice. Higher CAC incidence after heavy-ion exposure was associated with greater activation of β-catenin and NF-κB signaling marked by induced expression of common downstream inflammatory (iNOS and COX2) and pro-proliferative (Cyclin D1) targets. In summary, IR-induced colitis and CAC incidence in Il10-/- mice depends on radiation quality and display co-activation of β-catenin and NF-κB signaling.

Uncovering the morphological effects of high-energy Ga+ focused ion beam milling on hBN single-photon emitter fabrication.

Many techniques to fabricate complex nanostructures and quantum emitting defects in low dimensional materials for quantum information technologies rely on the patterning capabilities of focused ion beam (FIB) systems. In particular, the ability to pattern arrays of bright and stable room temperature single-photon emitters (SPEs) in 2D wide-bandgap insulator hexagonal boron nitride (hBN) via high-energy heavy-ion FIB allows for direct placement of SPEs without structured substrates or polymer-reliant lithography steps. However, the process parameters needed to create hBN SPEs with this technique are dependent on the growth method of the material chosen. Moreover, morphological damage induced by high-energy heavy-ion exposure may further influence the successful creation of SPEs. In this work, we perform atomic force microscopy to characterize the surface morphology of hBN regions patterned by Ga+ FIB to create SPEs at a range of ion doses and find that material swelling, and not milling as expected, is most strongly and positively correlated with the onset of non-zero SPE yields. Furthermore, we simulate vacancy concentration profiles at each of the tested doses and propose a qualitative model to elucidate how Ga+ FIB patterning creates isolated SPEs that is consistent with observed optical and morphological characteristics and is dependent on the consideration of void nucleation and growth from vacancy clusters. Our results provide novel insight into the formation of hBN SPEs created by high-energy heavy-ion milling that can be leveraged for monolithic hBN photonic devices and could be applied to a wide range of low-dimensional solid-state SPE hosts.

Schottky Barrier Characteristic Analysis on 4H-SiC Schottky Barrier Diodes With Heavy Ion-Induced Degradation

Leakage current of 1200-V 4H-SiC Schottky barrier diodes (SBDs) with different structures increased by various degrees after heavy-ion exposure. By taking <inline-formula> <tex-math notation="LaTeX">${I}$ </tex-math></inline-formula>&#x2013;<inline-formula> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> measurements in a range of 298 to 448 K, the voltage dependence of saturation current (<inline-formula> <tex-math notation="LaTeX">$I_{0}$ </tex-math></inline-formula>), barrier height (<inline-formula> <tex-math notation="LaTeX">$\phi _{B0}$ </tex-math></inline-formula>), and ideality factor (<inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>) were obtained. The dependence of these parameters with temperature illustrates the Gaussian distribution of barrier height. The inhomogeneity of the Schottky barrier height (SBH) distribution was successfully described using a modified thermionic emission (TE) model with Gaussian distribution, and the average barrier height (<inline-formula> <tex-math notation="LaTeX">$\bar {\phi }_{B0}$ </tex-math></inline-formula>) was gained. The results show that the barrier height distribution of all SBDs remain unchanged after the irradiation which means heavy-ion exposure did not affect the Schottky barrier.

A practical approach for continuous in situ characterization of radiation quality factors in space

The space radiation environment is qualitatively different from Earth, and its radiation hazard is generally quantified relative to photons using quality factors that allow assessment of biologically-effective dose. Two approaches exist for estimating radiation quality factors in complex low/intermediate-dose radiation environments: one is a fluence-based risk cross-section approach, which requires very detailed in silico characterization of the radiation field and biological cross sections, and thus cannot realistically be used for in situ monitoring. By contrast, the microdosimetric approach, using measured (or calculated) distributions of microdosimetric energy deposition together with empirical biological weighting functions, is conceptually and practically simpler. To demonstrate feasibility of the microdosimetric approach, we estimated a biological weighting function for one specific endpoint, heavy-ion-induced tumorigenesis in APC1638N/+ mice, which was unfolded from experimental results after a variety of heavy ion exposures together with corresponding calculated heavy ion microdosimetric energy deposition spectra. Separate biological weighting functions were unfolded for targeted and non-targeted effects, and these differed substantially. We folded these biological weighting functions with microdosimetric energy deposition spectra for different space radiation environments, and conclude that the microdosimetric approach is indeed practical and, in conjunction with in-situ measurements of microdosimetric spectra, can allow continuous readout of biologically-effective dose during space flight.

Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters

The human body is constantly exposed to ionizing radiation of different qualities. Especially the exposure to high-LET (linear energy transfer) particles increases due to new tumor therapy methods using e.g. carbon ions. Furthermore, upon radiation accidents, a mixture of radiation of different quality is adding up to human radiation exposure. Finally, long-term space missions such as the mission to mars pose great challenges to the dose assessment an astronaut was exposed to. Currently, DSB counting using γH2AX foci is used as an exact dosimetric measure for individuals. Due to the size of the γH2AX IRIF of ~ 0.6 µm, it is only possible to count DSB when they are separated by this distance. For high-LET particle exposure, the distance of the DSB is too small to be separated and the dose will be underestimated. In this study, we developed a method where it is possible to count DSB which are separated by a distance of ~ 140 nm. We counted the number of ionizing radiation-induced pDNA-PKcs (DNA-PKcs phosphorylated at T2609) foci (size = 140 nm ± 20 nm) in human HeLa cells using STED super-resolution microscopy that has an intrinsic resolution of 100 nm. Irradiation was performed at the ion microprobe SNAKE using high-LET 20 MeV lithium (LET = 116 keV/µm) and 27 MeV carbon ions (LET = 500 keV/µm). pDNA-PKcs foci label all DSB as proven by counterstaining with 53BP1 after low-LET γ-irradiation where separation of individual DSB is in most cases larger than the 53BP1 gross size of about 0.6 µm. Lithium ions produce (1.5 ± 0.1) IRIF/µm track length, for carbon ions (2.2 ± 0.2) IRIF/µm are counted. These values are enhanced by a factor of 2–3 compared to conventional foci counting of high-LET tracks. Comparison of the measurements to PARTRAC simulation data proof the consistency of results. We used these data to develop a measure for dosimetry of high-LET or mixed particle radiation exposure directly in the biological sample. We show that proper dosimetry for radiation up to a LET of 240 keV/µm is possible.

Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure.

The effective and minimally invasive radiation biomarkers are valuable for exposure scenarios in nuclear accidents or space missions. Recent studies have opened the new sight of circulating small non-coding RNA (sncRNA) as radiation biomarkers. The tRNA-derived small RNA (tsRNA) is a new class of sncRNA. It is more abundant than other kinds of sncRNAs in extracellular vesicles or blood, presenting great potential as promising biomarkers. However, the circulating tsRNAs in response to ionizing radiation have not been reported. In this research, Kunming mice were total-body exposed to 0.05–2 Gy of carbon ions, protons, or X-rays, and the RNA sequencing was performed to profile the expression of sncRNAs in serum. After conditional screening and validation, we firstly identified 5 tsRNAs including 4 tRNA-related fragments (tRFs) and 1 tRNA half (tiRNA) which showed a significant level decrease after exposure to three kinds of radiations. Moreover, the radiation responses of these 5 serum tsRNAs were reproduced in other mouse strains, and the sequences of them could be detected in serum of humans. Furthermore, we developed multi-factor models based on tsRNA biomarkers to indicate the degree of radiation exposure with high sensitivity and specificity. These findings suggest that the circulating tsRNAs can serve as new minimally invasive biomarkers and can make a triage or dose assessment from blood sample collection within 4 h in exposure scenarios.

Impact of heavy-ion irradiation on gate oxide reliability of silicon carbide power MOSFET

SiC power MOSFETs were exposed to 79Br, 64Cu, and 47Ti ions with different biases. After irradiation, the static parameters of the device did not change significantly. The oxide reliability is also not affected after ON-state irradiation. However, noticeable degradation of gate oxide reliability has been found after heavy-ion exposure with extremely low drain bias(50 V). The degradation is attributed to defects in the gate oxide. According to the analysis of the experimental results, the defects are caused by the high electric field induced by the partial SEGR effect during heavy-ion irradiation.

(Invited) Total Dose Effects and Single Event Upsets During Radiation Damage of GaN and SiC

In critical defense applications and autonomous vehicles, there is an increasing transition from high-voltage Si power devices, which are limited in current ratings and power efficiency, to commercial wide bandgap (WBG) power devices. SiC and GaN power devices are now used in the automotive, wireless, and industrial power markets, but their adoption into space and avionic applications is hindered by their susceptibility to permanent degradation and catastrophic failure from heavy-ion exposure. Efforts to space qualify WBG power devices have revealed they are susceptible to damage from the high-energy, heavy-ion space radiation environment (galactic cosmic rays) that cannot be shielded. Higher voltage devices are more susceptible to these effects; as a result, to date, there are space-qualified GaN transistors now available, but limited to 300 V. Recent radiation testing of 600-V and higher GaN transistors has shown failure susceptibility at about 50% of the rated voltage, or less. Similarly, SiC power devices have undergone several generations of advances commercially, improving their overall reliability, but catastrophically fail at less than 50% of their rated voltage. SiC components have demonstrated susceptibility to radiation damage under heavy-ion single-event effects testing, reducing their utility in the space galactic cosmic ray (GCR) environment. In SiC-based Schottky diodes, catastrophic single-event burnout (SEB) and other single-event effects (SEE) have been observed at ~40% of the rated operating voltage, as well as an unacceptable degradation in leakage current at ~20% of the rated operating voltage. SEE caused by terrestrial cosmic radiation (neutrons) have also been identified by industry as a limiting factor for the use of SiC-based electronics in aircraft. Currently, small satellite applications require a Total Ionizing Dose (TID) resilience of 30 krad (Si) and Single Event Latch-up (SEL) hardened up to 80 MeV-cm2/mg linear energy transfer. Radiation hardening comes with a cost. As with Si power MOSFETs, electrical performance will suffer from hardening techniques. The two primary failure radiation damage concerns in current generations of electronics for space applications are (i) Single event upset, in which incident ionizing radiation results in the flipping of a bit from 0 to 1 or vice versa. While this may be a problem for data loss or operation, it does not lead to permanent damage of the device and (ii) Total dose failure, in which irradiation leads to the creation of a sufficient density of defects. These then lead to degradation of the electrical properties to the point of permanent failure. In this talk we will review radiation damage results for GaN and SiC and compare these to initial data for Ga2O3.Work performed as part of Interaction of Ionizing Radiation with Matter University Research Alliance (IIRM-URA ) , sponsored by the Department of the Defense, Defense Threat Reduction Agency under award HDTRA1-20-2-0002. The content of the information does not necessarily reflect the position or the policy of the federal government, and no official endorsement should be inferred. *Current address: Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53706

(Invited) Total Dose Effects and Single Event Upsets During Radiation Damage of GaN and SiC

SiC and GaN power devices are used in the automotive, wireless, and industrial power markets, but their adoption into space and avionic applications is hindered by their susceptibility to permanent degradation and catastrophic failure from heavy-ion exposure. Efforts to space-qualify wide bandgap power devices have revealed that they are susceptible to damage from the high-energy, heavy-ion space radiation environment (galactic cosmic rays) that cannot be shielded. GaN and SiC transistors have shown failure susceptibility at about 50% of the rated voltage. SiC components have demonstrated susceptibility to radiation damage under heavy-ion single-event effects testing, reducing their utility in the space galactic cosmic ray (GCR) environment. In SiC-based Schottky diodes, catastrophic single-event burnout (SEB) and other single-event effects (SEE) have been observed at ~40% of the rated operating voltage, as well as an unacceptable degradation in leakage current at ~20% of the rated operating voltage.

Abstract 3059: Heavy ion radiation exposure perturbs intestinal stem cell homeostasis and induces accelerated tumorigenesis in apc mutant mouse intestine

Abstract In a previous study, we demonstrated long-term decreased intestinal epithelial cell migration after low-dose heavy ion iron radiation, and this was associated with increased senescence-associated secretory phenotype (SASP) signaling. However, we know very little about the long-term effects of low dose space radiation on intestinal stem cell (ISC) senescence and SASP that have implications for intestinal homeostasis. Male Lgr5+ (Lgr5-EGFP-IRES-creERT) mice or Lgr5+/APC1638N/+ were exposed to 0.5 Gy of sham, γ-rays, or 28Si (69 keV/μm) radiation and were euthanized 60 or 150 days after irradiation. ISCs were FACS sorted for oxidative stress analysis and assessed for senescence and SASP signaling in tissue sections by immunostaining. Greater cellROX or mitoSOX staining was observed after 28Si indicating higher oxidative stress compared to γ-rays or control Lgr5 positive cells. β-gal co-staining with Lgr5, lysozyme, IL1R, or ILβ showed highest staining in 28Si irradiated compared to controls ISCs samples. γ-H2AX staining showed greater foci numbers in 28Si relative to γ-rays or control group. Higher expression of secretory cytokines IL8 and IL15 was observed in 28Si irradiated ISCs relative to γ-rays or control group at both time points. Elevated expression of DKK2 and activation of NF-κB and p38 MAPK were observed in senescent stem cells of 28Si irradiated relative to γ-rays or control group at these time points. A higher GI tumor count was observed in 28Si compared to γ-irradiated or control Lgr5+/APC1638N/+ mice. In summary, our results demonstrate low dose heavy ion exposure induces ongoing DNA damage, persistent oxidative stress, senescence and acquisition of the SASP in ISCs. Higher levels of oxidative stress, senescence and SASP were observed at 150 compared to the 60-day timepoint. Overall, space radiation-induced oxidative stress, senescence, SASP, and activated p38MAPK/NF-κB pathway may very well have implications in GI carcinogenesis, accelerated aging, and pathological conditions, such as intestinal dysfunction, in astronauts during deep space flights. Since similar effects have been seen in our studies with other particle beams including carbon ions, this has potential relevance to particle radiotherapy as well. This work was supported by NASA NNX15AI21G Citation Format: Santosh Kumar, Shubhankar Suman, Kamal Datta, Albert J. Fornace. Heavy ion radiation exposure perturbs intestinal stem cell homeostasis and induces accelerated tumorigenesis in apc mutant mouse intestine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3059.

Identification of novel biomarkers of heavy ion exposure: Proteins, miRNAs and tRNA-derived fragments in serum

Space radiation is a major concern for human spaceflight. Especially, the heavy ions in cosmic rays can result in more serious DNA damage and uncertain consequences in carcinogenesis comparing with conventional radiation such as X- or γ-rays. Minimally invasive biomarkers that can be easily and quickly detected at an early stage are valuable for risk assessment of astronauts' space radiation exposure. Serum molecules originating from tissues and blood cells have been emerging as ideal biomarkers. However, the molecules that respond to low dose of heavy ion radiation have not been reported. Here, mice were total-body exposed to different doses of carbon ions with linear energy transfer (LET) of 30 keV/μm. Mouse Antibody Array and RNA sequencing were performed to detect expression profiles of serum proteins and small non-coding RNAs (sncRNAs) at 24 h post-irradiation. After conditional screening and further validation, the expression of 2 proteins, 3 miRNAs and 2 tRNA-derived fragments showed obvious increase or decrease with increasing dose, even in the mice that received as low as 0.1 Gy or 0.5 Gy of carbon ion radiation. In this study, we identified some new proteins, miRNAs and tRNA-derived fragments in serum showing great potential as early biomarkers of exposure to energetic heavy ions. These results might be useful to dose reconstruction and risk assessment of heavy ion exposure in deep space exploration.

Research of single-event burnout and hardened GaN MISFET with embedded PN junction

This paper describes a single-event burnout (SEB) simulation for a conventional GaN MISFET field plate (FPC-MISFET) and a MISFET with an embedded pn junction (EJ-MISFET). The SEB triggering mechanism is affected by impact ionization. The electrons, which are induced by heavy ion exposure, can rapidly move to the drain, which leads to strong impact ionization around the drain. Compared to the FPC-MISFET, both the peak electric field and the impact ionization around the drain are reduced in the GaN MISFET with the embedded pn junction. The proposed EJ-MISFET also shows improved SEB performance. For a heavy ion, with a linear energy transfer (LET) of 0.6 pC/μm (hitting the devices) vertically, the SEB threshold voltages for the FPC-MISFET and EJ-MISFET are 520 and 760 V, respectively.

NASA's first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research.

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the “GCR Simulator” to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%–75%) and helium ions (approximately 10%–20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.