Galactic cosmic ray environment predictions for the NASA BioSentinel mission.

BioSentinel is a nanosatellite deployed from Artemis-I designed to conduct in-situ biological measurements on yeast cells in the deep space radiation environment. Along with the primary goal of measuring damage and response in cells exposed during spaceflight, on-board active dosimetry will provide measurements of the radiation field encountered behind moderate shielding provided by the BioSentinel housing and internal components. The measurements are particularly important to enable interpretation of biological observations but also provide an opportunity to validate integrated computational models used to calculate radiation environments. In this work, models are used to predict the galactic cosmic ray exposure anticipated for the BioSentinel payload and on-board dosimeter. The model calculations presented herein were completed prior to the Artemis-I launch on November 16, 2022, and therefore represent actual predictions (i.e., unbiased by a priori knowledge of on-board measurements). Such time-forward predictions are rarely performed for space radiation applications due to limitations of environmental models, but truly independent model validation will be possible in the future when on-board measurements become available. The method used to facilitate future projections within an existing GCR (galactic cosmic ray) environmental model is described, and projection uncertainties are quantified and contextualized.

Application of fluorescent nuclear track detectors for cellular dosimetry.

Ion beams radiotherapy with charged particles show greater relative biological effectiveness (RBE) compared to conventional photon therapy. This enhanced RBE is due to a localized energy deposition pattern, which is subject to large fluctuations on cellular scales. Fluorescent nuclear track detectors (FNTDs) based on Al2O3:C,Mg crystals coated with cells (Cell-Fit-HD) can provide information on individual cellular energy deposition. In this study we provide a theoretical framework to obtain the distribution of microscopic energy deposition and ionization density in cells exposed to ion beams and identifies contributions of five different sources of variations to the overall energy fluctuation at different depths of a biologically optimized spread-out Bragg peak. We show that fluctuation in the individual energy loss of the particles is the major source of variability while the fluctuation in particle hits plays a minor role. With the Cell-Fit-HD system the uncertainty arising from four of these sources, namely the nucleus area, the number of nuclear hits, the particle linear energy transfer and the chord length can be reduced and only energy loss straggling remains fundamentally unknown. The ability to quantify these factors results in a reduction of the uncertainty in cellular energy deposition from 24-55% down to only 7-12%. We have also shown current experimental results with FNTDs which show promising results, but need further improvements to reach the ideals predicted in this study.

Involvement of interleukin 2 receptors in conceptus-derived suppression of T and B cell proliferation in horses.

The mechanism by which a horse conceptus-derived immunosuppressive factor (HCS) of M(r) > 100,000 inhibits lymphocyte proliferation was investigated. The factor was obtained from the culture supernatants of 20-day-old horse conceptuses; activity, identified by reduced uptake of [3H]thymidine by mitogen-stimulated lymphocytes, was greatest (P < 0.01) in cultures stimulated by mitogen from pokeweed. HCS also suppressed cell proliferation stimulated by phytohaemagglutinin (P < 0.01), but had no effect on lipopolysaccharide-stimulated cells (P > 0.05). Data from a fluorescence-activated cell sorter indicated that supplementation with HCS reduced the number of T cells in phytohaemagglutinin-stimulated cultures and suppressed proliferation of T and B cells in pokeweed-mitogen-stimulated cultures compared with controls. Cell proliferation was greater (P < 0.01) in cultures supplemented with HCS 24 h after stimulation than in those treated at the start of stimulation, and was even greater (P < 0.01) when cells were treated 48 h after stimulation. The removal of HCS from treated lymphocyte cultures resulted in complete recovery of cell responsiveness, and stimulated proliferation of treated cells did not differ (P > 0.05) from that of control cells. The addition of stimulated equine lymphocyte supernatant to cultures supplemented with HCS did not significantly increase (P > 0.05) cell proliferation in response to pokeweed mitogen. Addition of recombinant human interleukin 2 (rIL-2) to HCS-treated cultures did not alter the suppressive activity of HCS, although cell proliferation was greater in cultures supplemented with rIL-2 than in controls (P < 0.01). HCS inhibition of IL-2 receptor (IL-2R) function was investigated using an IL-2-dependent murine cytolytic T lymphocyte cell line; the fraction of HCS of M(r) > 100,000 had no effect (P > 0.05) on proliferation of IL-2-dependent murine cytolytic T lymphocyte cells induced by rIL-2. Together, these data suggest that HCS suppresses proliferation of T lymphocytes during the early stages of cell activation by inhibiting IL-2R interaction and that this suppression interferes with interactions between T cells and B cells, thereby also indirectly inhibiting proliferation of B cells. The potent immunosuppressive capacity of HCS may be one factor responsible for inhibiting cell-mediated fetal allograft rejection during pregnancy.