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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.↗

DOE OSTI2024

Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction

Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes. This causes enhanced osteoblast proliferation, followed by disruption in lacunar-canalicular connectivity and massive osteocyte death by 10 wk of age. We hypothesized that reduced viable osteocyte density would decrease the magnitude of systemic bone loss after femur fracture, reduce perilacunar remodeling, and alter callus formation. Bone remodeling was assessed using serum biomarkers of bone formation and resorption at 5 d post-fracture. We used micro-computed tomography, high resolution x-ray microscopy, mechanical testing, and Raman spectroscopy to quantify the magnitude of systemic bone loss, as well as changes in osteocyte lacunar volume, bone strength, and bone composition 2 wk post-fracture. Fracture was associated with a reduction in circulating markers of bone resorption in non-transgenic (TG-) animals. TG+ mice exhibited high bone mass in the limbs, greater cortical elastic modulus and reduced post-yield displacement. After fracture, TG+ mice lost less trabecular bone than TG- mice, but conversely TG+ mice exhibited trends toward a lower yield point and reduced femoral cortical thickness after fracture, though these were not statistically significant. Lacunar density was greater in TG+ mice, but fracture did not alter lacunar volume in TG+ or TG- mice. These findings suggest that osteocytes potentially play a significant role in the post-traumatic systemic response to fracture, though the effects differ between trabecular and cortical bone.

60 APPLIED LIFE SCIENCES↗

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.↗

NASA NTRS2003

Development of a Vibration Based Countermeasure to Inhibit the Bone Erosion and Muscle Deterioration That Parallels Spaceflight

The extent of bone and muscle loss in astronauts on missions longer than 30 days poses significant acute and chronic health risks. Recent work in a variety of species has revealed that low magnitude, high frequency (25-90 Hz) mechanical stimulation is anabolic and may inhibit hypothesis that short-term, low-intensi(y mechanical in the lower limb that parallels extended exposure to microgravity. If this experiment is selected for flight, 12 right leg serves as a contralateral control. Each astronaut will undergo treatment for 10 minutes per day, five days Pre- and post-flight bone and muscle testing will be used to assess efficacy as well as intra-subject comparison of the experimental leg to the control leg.

Kaplan, Tamara↗

NASA NTRS1987

A radiative bow shock wave (?) driven by nuclear ejecta in a Seyfert galaxy

New VLA maps at 2 cm of the 13-arcsec-scale linear radio source in the center of NGC 1068 are described. The northeast lobe shows a limb-brightened conical morphology, very sharp 'leading' edges, and a magnetic field running parallel to these edges. The spectral index between 2 and 6 cm in these line-brightened regions is near 1.0. The northeast subpeak has a very steep radio spectrum between 18 and 2 cm which is attributed to inverse Compton losses of the relativistic electrons on the infrared photons. The spectral indices in the southwest lobe lie in the range 0.9-1.5 except in its northern parts, where a much larger index is found. The northeast lobe radio emission could arise in either the cocoon of old jet material which has passed through the internal shock in the ejecta and blown out to either side, or in interstellar material compressed by a bow shock wave driven into the galactic ISM.

Wilson, Andrew S.↗

DOE OSTI2025

In vivo mapping of mutagenesis sensitivity of human enhancers

Distant-acting enhancers are central to human development1. However, our limited understanding of their functional sequence features prevents the interpretation of enhancer mutations in disease2. Here we determined the functional sensitivity to mutagenesis of human developmental enhancers in vivo. Focusing on seven enhancers that are active in the developing brain, heart, limb and face, we created over 1,700 transgenic mice for over 260 mutagenized enhancer alleles. Systematic mutation of 12-base-pair blocks collectively altered each sequence feature in each enhancer at least once. We show that 69% of all blocks are required for normal in vivo activity, with mutations more commonly resulting in loss (60%) than in gain (9%) of function. Using predictive modelling, we annotated critical nucleotides at the base-pair resolution. The vast majority of motifs predicted by these machine learning models (88%) coincided with changes in in vivo function, and the models showed considerable sensitivity, identifying 59% of all functional blocks. Taken together, our results reveal that human enhancers contain a high density of sequence features that are required for their normal in vivo function and provide a rich resource for further exploration of human enhancer logic.

Kosicki, Michael↗

NASA NTRS1974

Spectral irradiance curve calculations for any type of solar eclipse

A simple procedure is described for calculating the eclipse function (EF), alpha, and hence the spectral irradiance curve (SIC), (1-alpha), for any type of solar eclipse: namely, the occultation (partial/total) eclipse and the transit (partial/annular) eclipse. The SIC (or the EF) gives the variation of the amount (or the loss) of solar radiation of a given wavelength reaching a distant observer for various positions of the moon across the sun. The scheme is based on the theory of light curves of eclipsing binaries, the results of which are tabulated in Merrill's Tables, and is valid for all wavelengths for which the solar limb-darkening obeys the cosine law: J = sub c (1 - X + X cost gamma). As an example of computing the SIC for an occultation eclipse which may be total, the calculations for the March 7, 1970, eclipse are described in detail.

Deepak, A.↗

NASA NTRS1993

Skeletal muscle metabolism in hypokinetic rats

This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

Tischler, Marc E.↗

NASA NTRS1995

Mineral distribution in rat skeletons after exposure to a microgravity model

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days shown non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These finds are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.

Arnaud, Sara B.↗

NASA NTRS1993

Stratospheric ClO and ozone from the Microwave Limb Sounder on the Upper Atmosphere Research Satellite

Concentrations of atmospheric ozone and of ClO (the predominant form of reactive chlorine responsible for stratospheric ozone depletion) are reported for both the Arctic and Antarctic winters of the past 18 months. Chlorine in the lower stratosphere was almost completely converted to chemically reactive forms in both the northern and southern polar winter vortices. This occurred in the south long before the development of the Antarctic ozone hole, suggesting that ozone loss can be masked by influx of ozone-rich air.

Waters, J. W.↗

NASA NTRS1998

A Spaceflight Magnetic Bearing Equipped Optical Chopper with Six-Axis Active Control

This paper describes the development of an ETU (Engineering Test Unit) rotary optical chopper with magnetic bearings. An ETU is required to be both flight-like, nearly identical to a flight unit without the need for material certifications, and demonstrate structural and performance integrity. A prototype breadboard design previously demonstrated the feasibility of meeting flight performance requirements using magnetic bearings. The chopper mechanism is a critical component of the High Resolution Dynamics Limb Sounder (HIRDLS) which will be flown on EOS-CHEM (Earth Observing System-Chemistry). Particularly noteworthy are the science requirements which demand high precision positioning and minimal power consumption along with full redundancy of coils and sensors in a miniature, lightweight package. The magnetic bearings are unique in their pole design to minimize parasitic losses and utilize collocated optical sensing. The motor is of an unusual disk-type ironless stator design. The ETU design has evolved from the breadboard design. A number of improvements have been incorporated into the ETU design. Active thrust control has been added along with changes to improve sensor stability, motor efficiency, and touchdown and launch survivability. It was necessary to do all this while simultaneously reducing the mechanism volume. Flight-like electronics utilize a DSP (Digital Signal Processor) and contain all sensor electronics and drivers on a single five inch by nine inch circuit board. Performance test results are reported including magnetic bearing and motor rotational losses.

Blumenstock, Kenneth A.↗

NASA NTRS1998

A Spaceflight Magnetic Bearing Equipped Optical Chopper with Six-Axis Active Control

Blumenstock, K. A.↗

NASA NTRS1998

A Spaceflight Magnetic Bearing Equipped Optical Chopper with Six-Axis Active Control

Blumenstock, Kenneth A.↗