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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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41 records · Page 3

Effects of Low Dose Space Radiation Exposures on the Splenic Metabolome

Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Benchmarking of massively parallel phase-field codes for directional solidification

We present a detailed benchmark comparing two state-of-the-art phase-field implementations for simulating alloy solidification under experimentally relevant conditions. The study investigates the directional solidification of Al-3wt%Cu under high-velocity solidification conditions and SCN-0.46wt% camphor under microgravity conditions from National Aeronautics and Space Administration (NASA) DECLIC-DSI-R experiments. Both codes, one employing finite-difference discretization with uniform mesh and GPU-acceleration (GPU-PF) and the other one employing finite-element discretization with adaptive-mesh and CPU-parallelization (PRISMS-PF), solve the same quantitative phase-field formulation that incorporates an anti-trapping current for the solidification of dilute alloys. We evaluate the predictions of each code for dendritic morphology, primary spacing, and tip dynamics in both 2D and 3D, as well as their numerical convergence and computational performance. While existing benchmark problems have primarily focused on simplified or small-scale simulations, they do not reflect the computational and modeling challenges posed by employing experimentally relevant time and length scales. Our results provide a practical framework for assessing phase-field code performance as well as validating and facilitating their application in integrated computational materials engineering (ICME) workflows that require integration with realistic experimental data.

36 MATERIALS SCIENCE↗

Vaccination efficacy with marrow mesenchymal stem cell against cancer was enhanced under simulated microgravity

Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG). In this study, BALB/c mice were vaccinated with MSCs or MSC/SMG, compared with mice vaccinated with phosphate buffered saline (PBS) as negative controls. We then subcutaneously implanted the A549 human lung cancer cell line into vaccinated mice and monitored tumor growth potential in vivo. The smaller tumor size and less tumor weight were observed in mice vaccinated with MSCs or MSC/SMG, compared with that of the Control group. Particularly, it was much more significant in the group of MSC/SMG than that group of the MSCs. Vaccination with SMG treated MSCs inhibited proliferation and promoted apoptosis of tumor tissue. SMG/MSC vaccination induced bothTh1-mediated cytokine response; CD8-dependent cytotoxic response which reduced the proportion of Treg cells. Furthermore, SMG/MSC vaccination significantly increased MHC1 and HSPs proteins expression. In conclusion, we demonstrated the SMG could improve tumor-suppressive activity of MSC. The enhanced anti-tumor immune response of MSCs/SMG was strongly associated with the higher expression of MHC class I molecule on DCs, and the abundance of HSPs in the SMG treated MSCs may make antigens in the MSC more cross-presentable to the host DCs for generating protective antitumor activity. This study gains an insight into the mechanism of MSCs anti-tumor efficacy and gives a new strategy for cancer therapies in the future. - Highlights: • Vaccination with SMG treated MSCs inhibited tumor growth. • SMG/MSC vaccination induced Th1-mediated cytokine response, elicited CD8-dependent cytotoxic response and reduced the proportion of Treg cells. • SMG/MSC vaccination increased MHC1 and HSPs proteins expression.

60 APPLIED LIFE SCIENCES↗

Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats

The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures. These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.

59 BASIC BIOLOGICAL SCIENCES↗

Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. - Highlights: • We here characterized the first cell line derived from an estrogen reporter mouse. • In the RCCS cells express an immortalized behavior but not a transformed phenotype. • The RCCS provides a system for maintaining cells in more physiological conditions. • RCCS-cultured fibroblasts showed higher hormonal sensitivity to estradiol. • This bioreactor is a novel 3D model to be applied to pharmacotoxicological studies.

60 APPLIED LIFE SCIENCES↗