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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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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Two genes with similarity to bacterial response regulators are rapidly and specifically induced by cytokinin in Arabidopsis

Cytokinins are central regulators of plant growth and development, but little is known about their mode of action. By using differential display, we identified a gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated within 10 min by the exogenous application of cytokinin, and this induction did not require de novo protein synthesis. IBC6 was not induced by other plant hormones or by light. A second Arabidopsis gene with a sequence highly similar to IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with somewhat slower kinetics and to a lesser extent. The pattern of expression of the two genes was similar, with higher expression in leaves, rachises, and flowers and lower transcript levels in roots and siliques. Sequence analysis revealed that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component response regulators. This homology, coupled with previously published work on the CKI1 histidine kinase homolog, suggests that these proteins may play a role in early cytokinin signaling.

Non-NASA Center↗
NASA NTRS1996

Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer

Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

NASA Discipline Radiation Health↗
NASA NTRS1994

Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress

Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS2005

The effect of purified compared with nonpurified diet on bone changes induced by hindlimb suspension of female rats

The purpose of this study was to compare the bone changes induced by unloading in rats fed different diets, because space flight studies use a semipurified diet, whereas space flight simulation studies typically use nonpurified diets. Female Sprague-Dawley rats were fed a purified American Institute of Nutrition (AIN) 93G diet or a standard nonpurified diet and kept ambulatory or subjected to unloading by hindlimb suspension (HLS) for 38 days. Bone mineral content (BMC), mechanical strength, and factors related to the diet that affect bone (i.e., urinary calcium excretion, estradiol, and corticosterone) were measured. Average food intakes (grams per day) differed for diets, but caloric intake (kilocalories per day) and the final body masses of treatment groups were similar. The HLS-induced decrease in femoral BMC was not statistically different for rats fed a nonpurified diet (-8.6%) compared with a purified AIN-93G diet (-11.4%). The HLS-induced decrease in femoral mechanical strength was not statistically different for rats fed a nonpurified diet (-24%) compared with a purified AIN-93G diet (-31%). However, bone lengths were decreased (P < 0.05) in rats fed a nonpurified diet compared with a purified diet. Plasma estradiol levels were lower (P < 0.05) in the HLS/AIN-93G group but similar in the HLS and ambulatory rats fed a nonpurified diet. Plasma estradiol was related to femoral BMC (r = 0.85, P < 0.01). Urinary calcium excretion was higher (P < 0.05) in rats fed a nonpurified diet than those fed a purified AIN-93G diet, which is consistent with the higher level of calcium in the nonpurified diet. Urinary corticosterone levels were higher (P < 0.05) in rats fed a nonpurified diet than rats fed the AIN-93G diet. Although the osteopenia induced by unloading was similar in both diet groups, there were differences in longitudinal bone growth, calcium excretion, plasma estradiol levels, and urinary corticosterone levels. Results indicate that the type of standard diet used is an important factor to consider when measuring bone end points.

Bone and Bones/pathology↗
NASA NTRS2005

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Non-NASA Center↗
NASA NTRS2007

Self-consistent Model of Magnetospheric Ring Current and Propagating Electromagnetic Ion Cyclotron Waves. 2. Wave Induced Ring Current Precipitation and Thermal Electron Heating

This paper continues presentation and discussion of the results from our new global self-consistent theoretical model of interacting ring current ions and propagating electromagnetic ion cyclotron waves [Khazanov et al., 2006]. To study the effects of electromagnetic ion cyclotron wave propagation and refraction on the wave induced ring current precipitation and heating of the thermal plasmaspheric electrons, we simulate the May 1998 storm. The main findings after a simulation can be summarized as follows. Firstly, the wave induced ring current precipitation exhibits quite a lot of fine structure, and is highly organized by location of the plasmapause gradient. The strongest fluxes of about 4 x 10(exp 6) (cm(raised dot) s(raised dot) sr(raised dot) (sup -1)) are observed during the maill and early recovery phases of the storm. The very interesting and probably more important finding is that in a number of cases the most intense precipitating fluxes are not connected to the most intense waves in simple manner. The characteristics of the wave power spectral density distribution over the wave normal angle are extremely crucial for the effectiveness of the ring current ion scattering. Secondly, comparison of the global proton precipitating patterns with the results from RAM [Kozyra et al., 1997a] reveals that although we observe a qualitative agreement between the localizations of the wave induced precipitations in the models, there is no quantitative agreement between the magnitudes of the fluxes. The quantitative differences are mainly due to a qualitative difference between the characteristics of the wave power spectral density distributions over the wave normal angle in RAM and in our model. Thirdly, the heat fluxes to plasmaspheric electrons caused by Landau resonate energy absorption from electromagnetic ion cyclotron waves are observed in the postnoon-premidnight MLT sector, and can reach the magnitude of 10(exp 11) eV/(cm(sup 2)(raised dot)s). The Coulomb energy degradation of the RC H(+) and O(+) ions maximizes at about 10(exp 11) (eV/(cm(sup 2) (raised dot) s), and typically leads to electron energy deposition rates of about 2(raised dot) 10(exp 10) (eV/(cm(sup 2)(raised dot)s) which are observed during two periods; 32-48 hours, and 76-86 hours after 1 May, 0000 UT. The theoretically derived spatial structure of the thermal electron heating caused by interaction of the ring current with the plasmasphere is strongly supported by concurrent and conjugate plasma measurements from the plasmasphere, ring current, and topside ionosphere [Gurgiolo et al., 2005]. Finally, the wave induced intense electron heating has a structure of the spot-like patches along the most enhanced density gradients in the plasmasphere boundary layer and can be a possible driver to the observed but still not explained small-scale structures of enhanced emissions in the stable auroral red arcs.

Khazanov, G. V.↗
NASA NTRS2006

Atmospheric Teleconnection over Eurasia Induced by Aerosol Radiative Forcing during Boreal Spring

The direct effects of aerosols on global and regional climate during boreal spring are investigated based on numerical simulations with the NASA Global Modeling and Assimilation Office finite-volume general circulation model (fvGCM) with Microphyics of Clouds with the Relaxed Arakawa Schubert Scheme (McRAS), using aerosol forcing functions derived from the Goddard Ozone Chemistry Aerosol Radiation and Transport model (GOCART). The authors find that anomalous atmospheric heat sources induced by absorbing aerosols (dust and black carbon) excite a planetary-scale teleconnection pattern in sea level pressure, temperature, and geopotential height spanning North Africa through Eurasia to the North Pacific. Surface cooling due to direct effects of aerosols is found in the vicinity and downstream of the aerosol source regions, that is, South Asia, East Asia, and northern and western Africa. Significant atmospheric heating is found in regions with large loading of dust (over northern Africa and the Middle East) and black carbon (over Southeast Asia). Paradoxically, the most pronounced feature in aerosol-induced surface temperature is an east west dipole anomaly with strong cooling over the Caspian Sea and warming over central and northeastern Asia, where aerosol concentrations are low. Analyses of circulation anomalies show that the dipole anomaly is a part of an atmospheric teleconnection pattern driven by atmospheric heating anomalies induced by absorbing aerosols in the source regions, but the influence was conveyed globally through barotropic energy dispersion and sustained by feedback processes associated with the regional circulations. The surface temperature signature associated with the aerosol-induced teleconnection bears striking resemblance to the spatial pattern of observed long-term trend in surface temperature over Eurasia. Additionally, the boreal spring wave train pattern is similar to that reported by Fukutomi et al. associated with the boreal summer precipitation seesaw between eastern and western Siberia. The results of this study raise the possibility that global aerosol forcing during boreal spring may play an important role in spawning atmospheric teleconnections that affect regional and global climates.

Kim, Maeng-Ki↗
NASA NTRS2009

Effect of Pharmacologically-Induced Hypovolemia on Aerobic Capacity

Decreased peak oxygen consumption (VO2pk) and an elevated exercise heart rate (HR) response are associated with a reduction in plasma volume (PV) after space flight and bed rest, a space flight analog. Reduced VO2pk and submaximal exercise tolerance would negatively impact an astronaut s ability to perform near maximal work that would be required in the event of an emergency. We previously have administered IV furosemide followed by a low salt diet to model PV loss and orthostatic intolerance observed after spaceflight. Purpose: To determine whether a pharmacologically-induced reduction in PV results in decreased VO2pk and elevated exercise HR response. Methods: Six subjects (5M, 1F) performed two graded peak cycle tests (work rate increased by 35 or 50 W every 3 min), once while normovolemic and once while hypovolemic. HR and expired respiratory gases were continuously measured. To induce hypovolemia, subjects were administered a single dose of IV furosemide (0.5 mg.kg-1) 30 hr before exercise testing and then consumed a low-salt diet (10 mEq.d(sup -1)). PV was measured using carbon monoxide rebreathing. Exercise HR and VO2 responses were quantified as the area under the curve (AUC) calculated over each quartile of the peak test, based on test time in the hypovolemia condition. Paired t-tests were used to test for differences in PV, VO2pk, and peak HR between conditions. Repeated-measures ANOVAs were used to test for differences in AUC between conditions. Results: PV (3.32+/-0.12 vs. 2.77+/-0.16 L, p<0.05) and VO2pk (3.30+/-0.67 vs. 2.90+/-0.57 L.min(sup -1), p<0.05) were lower during hypovolemia than during normovolemia, but peak HR was not different (187+/-5 vs. 187+/-5 bpm). The AUC for VO2 and HR was different (p<0.05) between conditions only in the highest quartile: HR was 4% higher and VO2 was 5% lower during the hypovolemia condition. Conclusion: The mean difference in VO2pk (-12%) between normovolemia and hypovolemia was similar to the mean difference in PV (-17%). Similar decreases in PV and VO2pk have been observed following short duration space flight, suggesting that pharmacologically-induced PV loss can be used to model microgravity-induced reductions in VO2pk.

Everett, Meghan E.↗
NASA NTRS2006

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

Shuryak, Igor↗
NASA NTRS2011

Study of Unsteady, Sphere-Driven, Shock-Induced Combustion for Application to Hypervelocity Airbreathing Propulsion

A premixed, shock-induced combustion engine has been proposed in the past as a viable option for operating in the Mach 10 to 15 range in a single stage to orbit vehicle. In this approach, a shock is used to initiate combustion in a premixed fuel/air mixture. Apparent advantages over a conventional scramjet engine include a shorter combustor that, in turn, results in reduced weight and heating loads. There are a number of technical challenges that must be understood and resolved for a practical system: premixing of fuel and air upstream of the combustor without premature combustion, understanding and control of instabilities of the shock-induced combustion front, ability to produce sufficient thrust, and the ability to operate over a range of Mach numbers. This study evaluated the stability of the shock-induced combustion front in a model problem of a sphere traveling in a fuel/air mixture at high Mach numbers. A new, rapid analysis method was developed and applied to study such flows. In this method the axisymmetric, body-centric Navier-Stokes equations were expanded about the stagnation streamline of a sphere using the local similarity hypothesis in order to reduce the axisymmetric equations to a quasi-1D set of equations. These reduced sets of equations were solved in the stagnation region for a number of flow conditions in a premixed, hydrogen/air mixture. Predictions from the quasi-1D analysis showed very similar stable or unstable behavior of the shock-induced combustion front as compared to experimental studies and higher-fidelity computational results. This rapid analysis tool could be used in parametric studies to investigate effects of fuel rich/lean mixtures, non-uniformity in mixing, contaminants in the mixture, and different chemistry models.

Axdahl, Erik↗
NASA NTRS2011

CFD Study of the J2-X LOX Two-Bladed Inducer in the Presence of a Circumferential Groove

Results are presented of a computational fluid dynamics (CFD) study done in support of water flow experiments of the J-2X Oxidizer Turbopump (OTP) 2-bladed inducer with a circumferential groove that were conducted at Marshall Space Flight Center (MSFC). Sub-scale water flow testing results indicate that the circumferential groove greatly reduces synchronous cavitation and subsequent bearing loads at a minimal performance cost, but the energy reappears as high order cavitation (HOC) that spans a relatively large frequency range. Thus, HOC may have implications for the full-scale OTP inducer in terms of reduced structural margin at higher mode frequencies. Simulations using the LOCI-Stream CFD program were conducted in order to explore the root physical cause of the HOC. It was found that the axial recirculation pattern in the circumferential groove causes high-swirl fluid to interact with the nearly-axial incoming fluid just above the inducer blades. The high-shear interface between the fluids is Kelvin-Helmholtz unstable, resulting in trains of low pressure regions or 'pearls' forming near the upstream edge of the groove. When the pressure in these regions becomes low enough and they get cut by the blade leading edge, HOC is thought to occur. Although further work is required, the numerical models indicate that the root cause of HOC is hydrodynamic. That is, the pearls are always present, even when cavitation is not. Comparisons to ongoing water flow experiments will be discussed, as well as predictions for the full-scale OTP inducer.

Coker, Robert↗
NASA NTRS2013

Chromatin Folding, Fragile Sites, and Chromosome Aberrations Induced by Low- and High- LET Radiation

We previously demonstrated non-random distributions of breaks involved in chromosome aberrations induced by low- and high-LET radiation. To investigate the factors contributing to the break point distribution in radiation-induced chromosome aberrations, human epithelial cells were fixed in G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome in separate colors. After the images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multimega base pair scale. Specific locations of the chromosome, in interphase, were also analyzed with bacterial artificial chromosome (BAC) probes. Both mBAND and BAC studies revealed non-random folding of chromatin in interphase, and suggested association of interphase chromatin folding to the radiation-induced chromosome aberration hotspots. We further investigated the distribution of genes, as well as the distribution of breaks found in tumor cells. Comparisons of these distributions to the radiation hotspots showed that some of the radiation hotspots coincide with the frequent breaks found in solid tumors and with the fragile sites for other environmental toxins. Our results suggest that multiple factors, including the chromatin structure and the gene distribution, can contribute to radiation-induced chromosome aberrations.

Zhang, Ye↗
NASA NTRS2015

Impact-Induced Clay Mineral Formation and Distribution on Mars

Clay minerals have been identified in the central peaks and ejecta blankets of impact craters on Mars. Several studies have suggested these clay minerals formed as a result of impact induced hydrothermalism either during Mars' Noachian era or more recently by the melting of subsurface ice. Examples of post-impact clay formation is found in several locations on Earth such as the Mjolnir and Woodleigh Impact Structures. Additionally, a recent study has suggested the clay minerals observed on Ceres are the result of impact-induced hydrothermal processes. Such processes may have occurred on Mars, possibly during the Noachian. Distinguishing between clay minerals formed preor post-impact can be accomplished by studying their IR spectra. In fact, showed that the IR spectra of clay minerals is greatly affected at longer wavelengths (i.e. mid-IR, 5-25 micron) by impact-induced shock deformation while the near-IR spectra (1.0-2.5 micron) remains relatively unchanged. This explains the discrepancy between NIR and MIR observations of clay minerals in martian impact craters noted. Thus, it allows us to determine whether a clay mineral formed from impact-induced hydrothermalism or were pre-existing and were altered by the impact. Here we study the role of impacts on the formation and distribution of clay minerals on Mars via a fully 3-D Monte Carlo cratering model, including impact- melt production using results from modern hydrocode simulations. We identify regions that are conducive to clay formation and the location of clay minerals post-bombardment.

Rivera-Valentin, E. G.↗
NASA NTRS2015

Reducing the Effect of Transducer Mount Induced Noise on Aeroacoustic Wind Tunnel Testing Data with a New Transducer Mount Design

Flight vehicle aeroacoustic environments induced during transonic and supersonic flight are usually predicted by subscale wind tunnel testing utilizing high frequency miniature pressure transducers. In order to minimize noise induced by the measurement itself, transducer flush mounting with the model surface is very important. The National Aeronautics and Space Administration (NASA) has accomplished flushness in recent testing campaigns via use of a transducer holder that can be machined and sanded. A single hole in the holder allows the flow medium to interact with the transducer diaphragm. Noise is induced by the resulting cavity however, and is a challenge to remove in post-processing. A new holder design has been developed that minimizes the effects of this transducer mount induced noise (XMIN) by reducing the resonance amplitude or increasing its resonance frequency beyond the range of interest. This paper describes a test conducted at the NASA/George C. Marshall Space Flight Center Trisonic Wind Tunnel intended to verify the effectiveness of this design. The results from this test show that this new transducer holder design does significantly reduce the influence of XMIN on measured fluctuating pressure levels without degrading a transducer's ability to accurately measure the noise external to the model.

Herron, Andrew J.↗
NASA NTRS2015

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Oxidative Stress↗
NASA NTRS2018

Stress-Induced Heat Shock Protein 40 and Immune Function in Altered Gravity

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role of HSP40 during stress-induced altered gravity conditions, wild-type and Hsp40 mutant Drosophila melanogaster were exposed to ground-based chronic hypergravity conditions, followed by quantitative PCR (qPCR) analysis of immune gene expression. In addition, larval hemocytes were collected to determine the functional output in response to E. coli bioparticle phagocytosis. Preliminary data indicates a required role for Hsp40 in strengthening immune function during stress-induced spaceflight in flies. In short, a critical need to evaluate the relationship between HSPs and immune suppression during space flight is necessary. Since space travel may become available to the general public in the not too distant future, and for the possibility of long-term space missions, a more comprehensive evaluation of the molecules responsible for immune dysfunction observed during space flight is required.

hypergravity↗
NASA NTRS2017

Zoledronate Prevents Simulated Weightlessness-Induced Bone Loss in the Cancellous Compartment While Blunting the Efficacy of a Mechanical Loading Countermeasure

Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45μg/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200μstrain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo μCT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P < 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective.

bone↗
NASA NTRS2020

A Deformed Geometry Synthesis Technique for Determining Stacking and Cryogenically Induced Preloads for the Space Launch System

The Space Launch System (SLS) stacking and Core Stage (CS) fueling induce significant preloads that contribute to the liftoff pad separation “twang”. To accurately capture this, an approach is required that can replicate the physics of all SLS physical stacking steps, CS cryogenic shrinkage, associated geometric nonlinearities, and the transient behavior and decay of the preloads with changing boundary conditions as the vehicle separates from the pad. The Deformed Geometry Synthesis (DGS) approach presented here satisfies the above requirements. DGS determines induced preloads by modeling components in their deformed geometry states and then enforcing compatibility by closing the resulting “deadbands”. DGS seamlessly integrates into the multibody modal synthesis framework and does not require the use of artificial external loads to enforce preloads or post-processing steps to remove their influence. Since DGS iterates to solve for the deformed state inclusive of geometric nonlinearities, running linearized parametrics to exercise different potential orientations of ball jointed struts that connect the CS to Boosters for cryo-shrinkage analyses is entirely avoided. Relative to the transient behavior and decay of stacking and cryo-induced preloads with SLS liftoff pad separation, this is an area of considerable interest to the SLS program. To capture this in the most accurate way possible, DGS algorithms are designed to work with Henkel-Mar nonlinear pad separation algorithms which operate on the separating longitudinal and lateral degrees of freedom (DoFs) between the vehicle and the pad. As the separating DoFs release, in whatever manner as dictated by the interface geometries, interface loads and interface flexibilities as well as the external loading on the vehicle, the subject preloads generate a complex twang/decay time-trace as dictated by the physics of the problem. This paper presents DGS numerical verification against the closed-form solution for Timoshenko’s 3 ball-jointed strut preload problem. This problem is then extended by the authors to the geometric nonlinear case where DGS is compared to the Newton-Raphson solution of the nonlinear equations. Next, DGS is utilized to solve the SLS stacking and cryogenic shrinkage coupled loads analyses. Finally, Henkel-Mar pad separation simulations are executed that isolate the impact of the induced preloads’ twang and decay characteristics.

Space Launch System↗