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NASA NTRS2008

The GEOS Chemistry Climate Model: Comparisons to Satellite Data

The Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) has been developed by combining the atmospheric chemistry and transport modules developed over the years at Goddard and the GEOS general circulation model, also developed at Goddard. We will compare model simulations of ozone, and the minor constituents that affect ozone, for the period around 1980 with newly released revised data from the Limb Infrared Monitor of the Stratosphere (LIMS) instrument on Nimbus 4. We will also compare model simulations for the period of the early 2000s with the data from the Microwave Limb Sounder (MLS) and the High Resolution Dynamic Limb Sounder (HRDLS) on the Aura satellite. We will use these comparisons to examine the performance of the model for the present atmosphere and for the change that has occurred during the last 2 decades of ozone loss due to chlorine and bromine compounds released from chlorofluorocarbons and halons.

Stolarski, Richard S.↗
NASA NTRS2014

Magnetic Field Amplification in the Thin X-Ray Rims of SN 1006

Several young supernova remnants, including SN 1006, emit synchrotron X-rays in narrow filaments, hereafter thin rims, along their periphery. The widths of these rims imply 50–100 μG fields in the region immediately behind the shock, far larger than expected for the interstellar medium compressed by unmodified shocks, assuming electron radiative losses limit rim widths. However, magnetic field damping could also produce thin rims. Here we review the literature on rim width calculations, summarizing the case for magnetic field amplification. We extend these calculations to include an arbitrary power-law dependence of the diffusion coefficient on energy, D ∝ Eμ. Loss-limited rim widths should shrink with increasing photon energy, while magnetic-damping models predict widths almost independent of photon energy. We use these results to analyze Chandra observations of SN 1006, in particular the southwest limb. We parameterize the FWHM in terms of energy as FWHM ∝ EmE γ. Filament widths in SN 1006 decrease with energy; mE ∼ −0.3 to −0.8, implying magnetic field amplification by factors of 10–50, above the factor of four expected in strong unmodified shocks. For SN 1006, the rapid shrinkage rules out magnetic damping models. It also favors short mean free paths (small diffusion coefficients) and strong dependence of D on energy (μ ≥ 1).

MAGNETIC FIELD AMPLIFICATION IN THE THIN X-RAY RIM↗
NASA NTRS1993

The Guitar nebula - A bow shock from a slow-spin, high-velocity neutron star

The discovery is reported of a prominent nebula produced by the motion of a high-velocity pulsar, PSR 2224 + 65, through partially neutral gas. The pulsar's transverse speed of over about 800 km/s makes it arguably the fastest known star in the Galaxy and guarantees that it will ultimately escape the Galactic potential well. A deep H-alpha image reveals a bright head and a giant limb-brightened 'body' whose variable width suggests that the ambient interstellar gas has density variations on length scales less than 0.1 pc. Thermalization of shock energy occurs at a rate of about 0.01 times the pulsar's spindown loss rate. These observations provide some insights into the likelihood of finding shocks around other pulsars and the use of nebulae to find high-velocity neutron stars either not acting as pulsars or with their radiation beamed away from the earth.

Cordes, James M.↗
NASA NTRS2004

Measured and modeled HOCl profiles in the mid-latitude stratosphere : implication for ozone loss

The HOCl catalytic cycle is an efficient ozone loss mechanism in the lower mid-latitude stratosphere. We use a diurnal steady-state photochemical model to calculate profiles of HOCl for conditions encountered by a number of high-altitude balloon flights. To assess how well this model represents ozone loss by the HOCl cycle, we compare our calculations of HOCl and its precursors Cl0 and HO2 with measurements obtained by an FTIR solar absorption spectrometer (MkIV), a far-infrared emission spectrometer (FIRS-2), and a submillimetenvave limb sounder (SLS). We then evaluate these comparisons in light of a number of recent laboratory studies of the main formation mechanism of HOCl, the reaction of Cl0 + HO2. Those studies measured both the reaction rate constant and the quantum yield for a second product pathway, formation of HCl.

stratosphere↗
NASA NTRS2016

Acute Effects of Simulated Space Radiation and Micro-Gravity on Cancellous Bone Loss in Mice Tibiae

Space radiation and micro-gravity are the two major obstacles impeding human exploration of Mars and beyond. Long-duration space flights expose astronauts to high doses of high linear energy transfer (LET) radiation as well as prolonged periods of skeletal disuse due to weightlessness. One important consequence of both radiation exposure and micro-gravity is acute bone loss. However, biological responses to different radiation types and combined radiation and micro-gravity environments remain unknown. Thus, the purpose of this study is to compare the acute effects of different radiation species and simulated weightlessness on bone degeneration for the purpose of developing accurate risk assessments of prolonged space flight. Mouse models were used to simulate space flight-relevant doses of different radiation types as well as weightlessness via hind-limb unloading. Three groups of mice (n 9) were irradiated with 1 Gy (Gray) H+, 1 Gy 56Fe, and 1 Gy combined H+ and 56Fe (dual ion) respectively and compared to sham irradiated (n 9) and 2 Gy 56Fe irradiated positive controls (n 6). Two groups of mice (n 9) were hind-limb unloaded for three days and then either sham irradiated or dual ion irradiated respectively, followed by subsequent hind-limb unloading for 11 days. Cancellous tissue from tibiae metaphyses were harvested 11 days post-irradiation for ex vivo micro-computed tomography analysis. Microarchitecture parameters including bone volume to total volume ratio (BVTV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.S), and connectivity density (Conn.D) will be quantified using a novel automated segmentation procedure developed in our lab. The anticipated results will be instrumental in developing counter-measures against micro-gravity and radiation-induced bone loss. Moreover, possible synergistic effects may provide insight into underlying mechanisms mediating biological response.

Micro-Gravity↗
NASA NTRS1999

Skeletal Structural Consequences of Reduced Gravity Environments

The overall goal of this project is to provide structurally meaningful data on bone loss after exposure to reduced gravity environments so that more precise estimates of fracture risk and the effectiveness of countermeasures in reducing fracture risk can be developed. The project has three major components: (1) measure structural changes in the limb bones of rats subjected to complete and partial nonweightbearing, with and without treatment with ibandronate and periodic full weightbearing; (2) measure structural changes in the limb bones of human bedrest subjects, with and without treatment with alendronate and resistive exercise, and Russian cosmonauts flying on the Mir Space Station; and (3) validate and extend the 2-dimensional structural analyses currently possible in the second project component (bedrest and Mir subjects) using 3-dimensional finite element modeling techniques, and determine actual fracture-producing loads on earth and in space.

Ruff, Christropher B.↗
NASA NTRS2014

Oxidative Stress Responses to Simulated Spaceflight in Mineralized and Marrow Compartments of Bone and Associated Vasculature

Long-term spaceflight causes profound changes to the musculoskeletal system attributable to unloading and fluid shifts in microgravity. Future space explorations beyond the earth’s magnetosphere will expose astronauts to space radiation, which may cause additional skeletal deficits that are not yet fully understood. Our long-term goals are twofold: to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures if necessary. Our central hypothesis is that oxidative stress plays a key role in progressive bone loss and vascular dysfunction caused by spaceflight. In animal’s models, overproduction of free radicals is associated with increased bone resorption, lower bone formation, and decrements in bone mineral density and structure which can ultimately lead to skeletal fragility. Evidence in support of a possible causative role for oxidative stress in spaceflight-induced bone loss derive from knockout and transgenic mouse studies and the use of pharmacological interventions with known anti-oxidant properties. In our studies to simulate spaceflight, 16-wk old, male C56Bl/6J mice were assigned to one of four groups: hind limb unloading to simulate weightlessness (HU), normally loaded Controls (‘NL’) (sham irradiated, no hind limb unloading), irradiated at NASA Space Radiation Laboratory ‘IR’ with 1-2Gy of (600MeV/n) alone, or in combination with protons (0.5Gy Protons/0.5Gy 56Fe), (IR) or both hind limb unloaded and irradiated, ‘HU+IR’. Mice were exposed to radiation 3 days after initiating HU and tissues harvested were 1-14 days after initiating treatments for analyses. Results from our laboratories, which employ various biochemical, gene expression, functional, and transgenic animal model methods, implicate dynamic regulation of redox-related pathways by spaceflight-related environmental factors. As one example, we found that combined HU and radiation exposure caused oxidative damage in skeletal tissues (lipid peroxidation) of wildtype mice, whereas bone from transgenic mice that overexpress human catalase in mitochondria were protected. Interestingly, marrow cells grown under culture conditions that select for endothelial progenitor cells (EPC), showed that HU but not IR reduced EPC cell migration; in contrast HU and IR each inhibited growth of marrow-derived osteoblast progenitors. Taken together, these results indicate that unloading and ionizing elicit distinct effects on progenitor and mature cells of vascular and skeletal tissue, and that oxidative damage may contribute to skeletal and vascular deficits that may emerge during extended space travel.

Globus, R. K.↗
NASA NTRSDate not supplied

TPSAS-NF1676L-29062-DND

After more than three decades of research, the role of polar stratospheric clouds (PSCs) in stratospheric ozone depletion is well established. However, important questions remain unanswered that have limited our understanding of PSC processes and how to accurately represent them in global models, calling into question our prognostic capabilities for future ozone loss in a changing climate. A more complete picture of PSC processes on vortex-wide scales is emerging from a suite of contemporary satellite missions: the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on Envisat (2002-2012), the Microwave Limb Sounder (MLS) on Aura (2004-present), and the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) on CALIPSO (2006-present). These datasets have motivated numerous research activities that both extend and challenge our present knowledge of PSC processes and modeling capabilities. The SPARC PSC initiative was organized in January 2015 to address key questions related to PSCs and their representation in global models with the following main objectives: identify key PSC parameters required by global models; identify strengths and limitations of the PSC datasets; define a methodology to obtain the key PSC properties required by models from the observational datasets; develop a state of the art PSC climatology; and identify remaining open science questions. In this presentation, we describe the PSCi activity, key findings, and remaining open questions.

Michael C Pitts↗
NASA NTRS2012

International Space Station as Analog of Interplanetary Transit Vehicle For Biomedical Research

Astronaut missions lasting up to six months aboard the International Space Station (ISS) have much in common with interplanetary flights, especially the outbound, Earth-to-Mars transit portion of a Mars mission. Utilization of ISS and other appropriate platforms to prepare for crewed expeditions to planetary destinations including Mars has been the work of NASA's Human Research Program (HRP) since 2005. HRP is charged specifically to understand and reduced the risks to astronaut health and performance in space exploration missions: everything HRP does and has done is directly related to that responsibility. Two major categories of human research have capitalized on ISS capabilities. The first category centers on the biomedical aspects of long-duration exposure to spaceflight factors, including prolonged weightlessness, radiation exposure, isolation and confinement, and actual risk to life and limb. These studies contribute to astronaut safety, health and efficiency on any long-duration missions, whether in low Earth orbit (LEO) or beyond. Qualitatively, weightlessness is weightlessness, whether in LEO or en route to Mars. The HRP sponsors investigations into losses in muscle and bone integrity, cardiovascular function, sensory-motor capability, immune capacity and psychosocial health, and development and demonstration of appropriate treatments and preventative measures. The second category includes studies that are focused on planetary expeditions beyond LEO. For these, ISS offers a high fidelity analog to investigate the combined effects of spaceflight factors (described above) plus the isolation and autonomy associated with simulated increasing distance from Earth. Investigations address crew cohesion, performance and workload, and mission control performance. The behavioral health and performance and space human factors aspects of planetary missions dominate this category. Work has already begun on a new investigation in this category which will examine the effects of a simulated lag in communications (mimicking that expected in transit to Mars) on astronaut performance aboard ISS. Extension of the current ISS increment duration from six months to nine or even twelve months would provide opportunities for expanded research relevant to long duration missions, albeit at the cost of fewer astronauts as subjects for those investigations. Given the possible limited access to ISS after 2020, if ISS is intended to facilitate future exploration missions, then the in-flight human investigations should focus on those that clearly enable future exploration missions.

Charles, John B.↗
NASA NTRS2011

Determination of Non-Thermal Velocity Distributions from SERTS Linewidth Observations

Non-thermal velocities obtained from the measurement of coronal Extreme Ultraviolet (EUV) linewidths have been consistently observed in solar EUV spectral observations and have been theorized to result fro m many plausible scenarios including wave motions, turbulence, or magnetic reconnection. Constraining these velocities can provide a physical limit for the available energy resulting from unresolved motions in the corona. We statistically determine a series of non-thermal velocity distributions from linewidth measurements of 390 emission lines from a wide array of elements and ionization states observed during the Solar Extreme Ultraviolet Research Telescope and Spectrograph 1991-1997 flights covering the spectral range 174-418 A and a temperature range from 80,000 K to 12.6 MK. This sample includes 248 lines from active regions, 101 lines from quiet-Sun regions, and 41 lines were observed from plasma off the solar limb. We find a strongly peaked distribution corresponding to a non-thermal velocity of 19-22 km/s in all three of the quiet-Sun, active region, and off-limb distributions. For the possibility of Alfven wave resonance heating, we find thai velocities in the core of these distributions do not provide sufficient energy, given typical densities and magnetic field strengths for the coronal plasma, to overcome the estimated coronal energy losses required to maintain the corona at the typical temperatures working as the sole mechanism. We find that at perfect efficiency 50%-60% of the needed energy flux can be produced from the non-thermal velocities measured.

Coyner, Aaron J.↗
NASA NTRS1993

Prostaglandin E2 Restores Cancellous Bone to Immobilized Limb and Adds Bone to Overloaded Limb in Right Hindlimb Immobilization Rats

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127 to +188 percent) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels. Our findings indicate that daily 3 or 6 mg PGE2/kg/d treatment restores and maintains PTM cancellous bone mass in continuously immobilized (right) tibiae, and adds and maintains extra bone to slightly overloaded PTM cancellous bone in female rats.

Li, M.↗
NASA NTRS2000

An Investigation of Polar Ozone Recovery in the 1997 Southern Hemisphere Spring

A chemical transport model is used to investigate the processes that control the depth and duration of the ozone 'hole' in the lower stratosphere through comparisons of model output with measurements from the Total Ozone Mapping Spectrometer (TOMS) and from the Microwave Limb Sounder (MLS) and Halogen Occultation Experiment (HALOE), both on the Upper Atmosphere Research Satellite (UARS). This study extends previous model comparisons with observations into October and November and examine levels in (greater than 31 hPa) and above (less than 31 hPa) the chemical loss region. Averages of column ozone in the model decrease through mid-October below 31 hPa but begin to increase in mid-September above 31 hPa. An investigation of model-tracer data comparisons and other meteorological parameters indicate that the model presents a consistent picture of top-down recovery and tracer transport. An O03budget study at 500 K (below 31 hPa) and 840 K (above 31 hPa) is carried out to investigate the processes that control the timing of the transition of ozone from a chemical to dynamically driven regime. The model ozone decrease at 500 K is due to chemical loss in August and September but is due to upward motion in October. The ozone increase at 840 K is primarily due to photochemical production, with a smaller contribution from transport. These results show that chemistry and dynamics can play different roles in polar vortex ozone recovery at different levels.

Pierson, J. M.↗
NASA NTRS2006

Tropospheric and stratospheric ozone from assimilation of Aura data

Ozone is an atmospheric trace gas with multiple impacts on the environment. Global ozone fields are needed for air quality predictions, estimation of the ultraviolet radiation reaching the surface, climate-radiation studies, and may also have an impact on longer-term weather predictions. We estimate global ozone fields in the stratosphere and troposphere by combining the data from EOS Aura satellite with an ozone model using data assimilation. Ozone exhibits a large temporal variability in the lower stratosphere. Our previous work showed that assimilation of satellite data from limb-sounding geometry helps constrain ozone profiles in that region. We assimilated ozone data from the Aura Microwave Limb Sounder (MLS) and the Ozone Monitoring Instrument (OMI) into the ozone system at NASA's Global Modeling and Assimilation Office (GMAO). Ozone is transported within a general circulation model (GCM) which includes parameterizations for stratospheric photochemistry, tropospheric chemistry, and a simple scheme for heterogeneous ozone loss. The focus of this study is on the representation of ozone in the lower stratosphere and tropospheric ozone columns. We plan to extend studies of tropospheric ozone distribution through assimilation of ozone data from the Tropospheric Emission Spectrometer (TES). Comparisons with ozone sondes and occultation data show that assimilation of Aura data reproduces ozone gradients and variability in the lower stratosphere well. We proceed by separating the contributions to temporal changes in the ozone field into those that are due to the model and those that are due to the assimilation of Aura data. The impacts of Aura data are illustrated and their role in the representation of ozone variability in the lower stratosphere and troposphere is shown.

Stajner, I.↗
NASA NTRS1999

The Biomechanics of Exercise Countermeasures

The Penn State Zero-gravity Simulator (PSZS) is a device developed by the Center for Locomotion Studies (CELOS) to enable ground studies of exercise countermeasures for the bone loss that has been shown to occur during long-term exposure to zero gravity (0G). The PSZS simulates 0G exercise by providing a suspension system that holds an individual in a horizontal (supine) position above the floor in order to enable exercise on a wall-mounted treadmill. Due to this orientation, exercise performed in the PSZS is free of the force of -ravity in the direction that would normally contribute to ground reaction forces. In order for movements to be more similar to those in 0G, a constant force suspension of each segment (equal to the segment weight) is provided regardless of limb position. During the preliminary development of the PSZS, CELOS researchers also designed an optional gravity-replacement simulation feature for the PSZS. This feature was a prototype tethering system that consisted of a spring tension system to pull an exercising individual toward the treadmill. The immediate application of the tethering system was to be the provision of gravity-replacement loading so that exercise in 0G- and 1G-loading conditions could be compared, and the PSZS could then be used to evaluate exercise countermeasures for bone loss during space flight. This tethering system would also be a model for the further refinement of gravity-replacement systems provided for astronaut usage while performing prescribed exercise countermeasures for bone loss during long-term space flights.

Cavanagh, Peter R.↗
NASA NTRS1992

Cryogenic limb array etalon spectrometer (CLAES) - Experiment description and initial results

The primary objective of the CLAES experiment is to measure the altitude profiles of temperature and of a series of minor and trace species important to stratospheric ozone layer photochemistry and radiative structure. Ways in which the species to be measured by CLAES are distributed among the broad categories of source, radical, and reservoir species involved in ozone production and loss are illustrated. CLAES requires high spectral resolution and high radiometric sensitivity to isolate and accurately measure weak emissions from trace species such as HCl and NO against intense backgrounds from abundant emitters such as CO2, H2O, and O3. Spectroscopy is performed by tilt scanning one of the four solid etalons between 0 and 23 deg in conjunction with one or more of the nine selectable discrete interference filters.

Roche, Aidan E.↗
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 NTRS1999

Pharmacological Inhibitors of the Proteosome in Atrophying Muscles

It is now clear that the marked loss of muscle mass that occurs with disuse, denervation or in many systemic diseases (cancer cachexia, sepsis, acidosis, various endocrine disorders) is due primarily to accelerated degradation of muscle proteins, especially myofibrillar components. Recent work primarily in Dr. Goldberg's laboratory had suggested that in these diverse conditions, the enhancement of muscle proteolysis results mainly from activation of the Ub-proteasome degradative pathway. In various experimental models of atrophy, rat muscles show a common series of changes indicative of activation of this pathway, including increases in MRNA for Ub and proteasome subunits, content of ubiquitinated proteins, and sensitivity to inhibitors of the proteasome. In order to understand the muscle atrophy seen in weightlessness, Dr. Goldberg's laboratory is collaborating with Dr. Baldwin in studies to define the changes in these parameters upon hind-limb suspension. Related experiments will explore the effects on this degradative system of exercise regimens and also of glucocorticoids, which are known to rise in space personnel and to promote muscle, especially in inactive muscles. The main goals will be: (A) to define the enzymatic changes leading to enhanced activity of the Ub-proteasome pathway in inactive muscles upon hind-limb suspension, and the effects on this system of exposure to glucocorticoids or exercise; and (B) to learn whether inhibitors of the Ub-proteasome pathway may be useful in retarding the excessive proteolysis in atrophying muscles. Using muscle extracts, Dr. Goldberg's group hopes to define the rate-limiting, enzymatic changes that lead to the accelerated Ub-conjugation and protein degradation. They have recently developed cell-free preparations from atrophying rat muscles, in which Ub-conjugation to muscle proteins is increased above control levels. Because these new preparations seem to reproduce the changes occurring in vivo, they will analyze in depth extracts from normal and atrophying muscles to compare the activities of the Ub-activating enzyme (El), the various LTh-carrier proteins (E2s), and Ub-protein ligases (E3s). Recent studies of other types of muscle wasting -suggest a very important role in muscle proteolysis of certain ubiquitination enzymes, E214k and E3-alpha(i.e. components of the "N-end pathway"). Future studies will focus in understanding their role and test whether they are in fact critical for muscle atrophy in vivo. Since weightlessness leads to a specific loss of contractile proteins and to a switching of myosin isotypes, Dr. Goldberg's group will attempt to identify the ubiquitination enzymes specifically involved in myosin degradation both in normal muscle and after hind-limb suspension.

Goldberg, Alfred↗
NASA NTRS1996

Ground Reaction Forces During Locomotion in Simulated Microgravity

Significant losses in bone density and mineral, primarily in the lower extremities have been reported following exposure to weightlessness. Recent investigations suggest that mechanical influences such as bone deformation and strain rate may be critically important in stimulating new bone formation. It was hypothesized that velocity, cadence and harness design would significantly affect lower limb impact forces during treadmill exercise in simulated zero gravity (0G). A ground-based hypogravity simulator was used to investigate which factors affect limb loading during tethered treadmill exercise. A fractional factorial design was used and 12 subjects were studied. The results showed that running on active and passive treadmills in the simulator with a tethering force close to the maximum comfortable level produced similar magnitudes for the peak ground reaction force. It was also found that these maximum forces were significantly lower than those obtained during overground trials, even when the speeds of locomotion in the simulator were 66 % greater than those in 1 G. Cadence had no effect on any of the response variables. The maximum rate of force application (DFDT-Max) was similar for overground running and exercise in simulated 0G, provided that the "weightless subjects ran on a motorized treadmill. These findings have implications for the use of treadmill exercise as a countermeasure for hypokinetic osteoporosis. As the relationship between mechanical factors and osteogenesis becomes better understood, results from human experiments in 0G simulators will help to design in-flight exercise programs that are more closely targeted to generate appropriate mechanical stimuli.

Davis, B. L.↗