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Non-DNA radiosensitive targets that initiate persistent behavioral deficits in rats exposed to space radiation

Predicting future CNS risks for astronauts during deep-space missions will rely substantially on ground-based rodent data with space-relevant ions and behaviors. For rats, the accumulated evidence indicates that less densely ionizing radiation, such as 4 He and 12 C ions, induce behavior deficits at lower doses than densely ionizing ions, such as 48 Ti and 56 Fe. However, this observation conflicts with standard somatic radiobiology, in which densely ionizing ions are generally more effective than less densely ionizing ions, and where the DNA/nucleus is the accepted target for radiation-induced tumorigenesis, cytogenetic aberrations, genetic mutations, and reproductive cell death. To gain deeper insight into the subcellular nature of the radiation targets for behavior risks, we compared the effects of dose, fluence, and linear energy transfer (LET) of 4 He and 56 Fe particles using existing datasets for four distinct behavioral outcomes in rats: elevated plus maze (EPM-anxiety), novel object recognition (NOR-memory), operant responding (OR-response to environmental stimuli), and attentional set-shifting (ATSET-cognitive flexibility). We confirmed that less densely ionizing particles (except protons) showed ~100-fold lower threshold doses than densely ionizing particles for behavioral deficits (0.1–1 cGy for 4 He vs. 15–100 cGy for 56 Fe). However, when analyzed by fluence the behavioral responses converged, indicating that 4 He and 56 Fe were equally effective on a per-track basis. When analyzed by LET, there were ~100-fold differences in the LET for maximum effectiveness for behavioral deficits and DNA endpoints (~1 vs ~100 keV/μm, respectively). These unique features of radiation-induced behavioral deficits (high sensitivity to particles in the 1-keV/μm range, insensitivity to protons in the 0.2 keV/μm range, and isofluence dependence for particles with LET>1 keV/μm) provide evidence in support of a new hypothesis of sub-micron sized radiosensitive targets for behavioral effects consistent with the thickness of plasma membranes and/or small subcellular structures, smaller than a whole synapse. Like our behavior findings, mouse immature oocyte killing which is known to have a plasma membrane target was also better explained by fluence, rather than dose. In contrast, fluence analyses for DNA/nuclear endpoints in somatic cells (e.g., tumor induction, chromosome aberrations) showed opposite results, suggesting that behavior targets are not DNA. Our findings raise questions regarding the identity of subcellular targets and the multi-cellular functional unit for behavior risks, low-dose susceptibility, and generalizability from rat to other species and astronauts.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN

In situ cryogenic characterization of proton damage in thick p-channel skipper CCDs

Skipper charge-coupled devices (CCDs) are an offshoot of standard silicon pixel detectors and are capable of performing repeated non-destructive charge measurements, enabling deeply sub-electron readout noise. This capability has opened the door to single-photon counting from the near-infrared ($\sim$1.1 $μ$m) to the soft X-ray (several keV), making these devices strong candidates for future astronomical instruments operating in the photon-starved limit. Furthermore, the p-channel architecture used to fabricate Skipper CCDs on n-type silicon has been demonstrated to have an increased hardness to the intense radiation environment of space. Building upon previous irradiation campaigns on room-temperature sensors, here we describe the first radiation-hardness tests of p-channel skipper CCDs at their cryogenic operating temperatures. We assess the performance of the floating-gate output stage and global CCD parameters (charge transfer inefficiency, dark current, hot pixels, and charge traps). We find that these devices maintain excellent performance after displacement damage doses equivalent to ${\sim}$10 years at the Earth/Sun L2 Lagrange point, demonstrating for the first time that these sensors remain radiation-hard in realistic deep-space thermal and radiation environments.

Roach, Brandon M. [Chicago U., KICP] (ORCID:000000