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At least 73 records · Page 4

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↗

Experimental Studies of the Formation/Deposition of Sodium Sulfate in/from Combustion Gases

Processes related to the hot corrosion of gas turbine components were examined in two separate investigations. Monochromatic laser light was used to probe condensation onset and condensate film growth (via interference of reflected light) on electrically heated ribbons immersed in seeded, flat flame combustion product gases. Boron trichloride is used as the seed gas in these preliminary experiments conducted to obtain precise measurements of the dew point/deposition rates. Because of the importance of gaseous Na(g) as a precursor to NaSO4 formation, the kinetics and mechanisms of the heterogeneous reaction H(g) + NaCl(s) yields Na(g) + HCl(g) was studied using atomic absorption spectroscopy combined with microwave discharge-vacuum flow reactor techniques at moderate temperatures. Preliminary results indicate the H-atom attack of solid NaCl vaporization is negligible; hence the corresponding gas phase (homogeneous) reaction no role in the observed Na(g) production.

Rosner, D. E.↗

Technical and economic aspects of hydrogen storage in metal hydrides

The recovery of hydrogen from such metal hydrides as LiH, MgH2, TiH2, CaH2 and FeTiH compounds is studied, with the aim of evaluating the viability of the technique for the storage of hydrogen fuel. The pressure-temperature dependence of the reactions, enthalpies of formation, the kinetics of the hydrogen absorption and desorption, and the mechanical and chemical stability of the metal hydrides are taken into account in the evaluation. Economic aspects are considered. Development of portable metal hydride hydrogen storage reservoirs is also mentioned.

Schmitt, R.↗

Shock tube study of the fuel structure effects on the chemical kinetic mechanisms responsible for soot formation

Soot formation in toluene-, benzene-, and acetylene-oxygen-argon mixtures was investigated to study soot formation in a combustion environment. High concentrations of oxygen completely suppress soot formation. The addition of oxygen at relatively low concentrations uniformly suppresses soot formation at high pressures, while at relatively lower pressures it suppresses soot formation at higher temperatures while promoting soot production at lower temperatures. The observed behavior indicates that oxidation reactions compete with ring fragmentation. The main conclusion to be drawn from the results is that the soot formation mechanism is probably the same for the pyrolysis and oxidation of hydrocarbons. That is, the addition of oxygen does not alter the soot route but rather promotes or inhibits this route by means of competitive reactions. An approach to empirical modeling of soot formation during pyrolysis of aromatic hydrocarbons is also presented.

Frenklach, M.↗

Recovery of precious metals from space

The overall objective is to develop efficient and economical separation and recovery methods for the platinum group and other precious metals. The separation of Pd(II) from Pt(II), Ir(III), and Rh(III) with trioctylphosphine oxide (TOPO) in heptane using centrifugal partition chromatography (CPC) was investigated. Activities to achieve this objective focussed on selection and evaluation of extraction systems for the PGM and modification of selected systems for multistage operation with a view to scaling up to desired macro levels. On the basis of preliminary evaluation of a series of simple metal complexing agents and chelating agents, the TOPO in heptane was selected as a likely system for isolating of Pd(II) and Pt(II) from the other PGM. A multistage apparatus capable of configuration as a simple rugged device, a centrifugal partition chromatograph (CPC), was shown to be effective. The extraction of Pd(II) was studied by CPC and batch solvent extraction. The distribution ratios for Pd(II) determined by both methods agree well. In low HCl concentrations (less than 0.1 M), the extracted species was PdCl2.(TOPO)2, irrespective of the chloride concentration, while at acid concentrations above 0.1 M, the Pd was extracted as the ion pair, 2(TOPO.H+).(PdCl4)2-. Base line separation of Pd(II) and Pt(II) in CPC was obtained under a variety of chloride and HCl concentration. It was demonstrated that the efficiency of CPC for metal separation was limited by chemical kinetic factors rather than instrumental factors, strongly suggesting that dramatic improvements can be achieved by studying reaction kinetics of formation and dissociation of the extractable metal complex.

Freiser, Henry↗

Real-Time X-Ray Transmission Microscopy for Fundamental Studies Solidification

High resolution real-time X-ray Transmission Microscopy, XTM, has been applied to obtain information fundamental to solidification of optically opaque metallic systems. We have previously reported the measurement of solute profile in the liquid, phase growth, and detailed solid-liquid interfacial morphology of aluminum based alloys with exposure times less than 2 seconds. Recent advances in XTM furnace design have provided an increase in real-time magnification (during solidification) for the XTM from 4OX to 16OX. The increased magnification has enabled for the first time the XTM imaging of real-time growth of fibers and particles with diameters of 5 micrometers. We have applied this system to study of the kinetics of formation and morphological evolution of secondary fibers and particles in Al-Bi monotectic alloys to observe a previously unreported velocity dependent thermo-capillary depletion mechanism for Bi rich liquid which can penetrate many fiber diameters into the solid-liquid interface. In this talk we will discuss application of the XTM to the study the fundamentals of monotectic and eutectic solidification, the enhancement of XTM data with precise solid liquid interfacial temperature and thermal gradient measurement techniques, and the application of this technology to the study of the fundamentals of solidification in microgravity,

Curreri, Peter A.↗

Model of statoconia accumulation in gravireceptors of mollusks

The kinetics of formation and accumulation of statoconia are different for Aplysia californica and Biomphalaria glabrata. In Aplysia californica, the fast growth of statoconia number occurs after the critical size (approximately 45 micrometers) of statocyst is reached; then the increase of statoconia number is proceeding with the nonmonotonic rate during the life of an animal. In Biomphalaria the growth of statoconia number occurs only in the initial phase. Then long-term evolution of statoconia in the absence of their generation is the result of their growth in the cyst lumen. In the case of Aplysia californica it is not clear whether a temporal change of the statoconia size distribution (SSD) is caused by statoconia growth in the cyst lumen similar to that in Biomphalaria (Model 1) or statoconia growth takes place in supporting cells until their release into the cyst lumen occurs. (Model 2). This problem is of practical importance because the majority of experiments related to the development of molluscan gravireceptors in altered gravity dealt with an initial phase of statoconia evolution in Aplysia californica and Biomphalaria glabrata. The purpose of the present work is the application of mathematical modeling to the analysis of mechanisms of statoconia formation by supporting cells.

Non-NASA Center↗

Glycolonitrile oligomerization: structure of isolated oxazolines, potential heterocycles on the early earth

A study of glycolonitrile polymerization has led to the isolation and characterization of two 2,5-dihydro-4-aminooxazoles, 4 and 5. Previous reports have misassigned these structures as s-triazines or pyrimidines. X-ray diffraction analysis of crystals of 4 and an acetylated oxazole derivative of 5 (6) confirm the proposed structures. Ab initio computations are used to assess the relative thermodynamic stability of three trimer isomers (an s-triazine, an aminohydroxypyrimidine, and an aminooxazoline), and the results indicate that 4 is a novel kinetic product. Mechanistic considerations rationalize kinetic oxazole formation over the more customary triazine or pyrimidine trimers.

Non-NASA Center↗

Gas-Phase Formation Rates of Nitric Acid and Its Isomers Under Urban Conditions

Ozone formation in urban smog is controlled by a complex set of reactions which includes radical production from photochemical processes, catalytic cycles which convert NO to NO2, and termination steps that tie up reactive intermediates in long-lived reservoirs. The reaction OH + NO2 + M -4 HONO2 + M (la) is a key termination step because it transforms two short-lived reactive intermediates, OH and NO2, into relatively long-lived nitric acid. Under certain conditions (low VOC/NOx), ozone production in polluted urban airsheds can be highly sensitive to this reaction, but the rate parameters are not well constrained. This report summarizes the results of new laboratory studies of the OH + NO2 + M reaction including direct determination of the overall rate constant and branching ratio for the two reaction channels under atmospherically relevant conditions.

Air pollution↗

A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron).

Huff, Janice L.↗

Chemical interactions in the aluminum-carbon and aluminum-silicon carbide systems

XPS was used to investigate the influence of O2 and H2O on the formation of aluminum carbide at Al-C and Al-SiC interfaces. It was determined that dosing the interfaces with H2O catalyzed the formation of aluminum carbide in both systems. This result is consistent with the oxidation model of carbide formation (developed to understand the kinetics of aluminum carbide formation at graphite-aluminum interfaces). These results imply that the formation of aluminum carbide in graphite- and SiC-reinforced metal-matrix composites, which severely degrades the composite mechanical properties by degrading the fiber and interface strength is catalyzed.

Maruyama, Benji↗

Experimental and theoretical studies of NO/x/ formation in a jet-stirred combustor.

As an approach to testing kinetic models which couple NO formation to combustion reactions, a jet-stirred combustor was used to study NO(x) formation under kinetically controlled combustion conditions. The experimental data were compared with kinetic calculations for a well-stirred reactor. The agreement between theory and experiment was quite good for the combustion of hydrogen/air and carbon monoxide/air, for which detailed mechanisms were used. A quasi-global mechanism for the combustion of propane/air resulted in substantial underprediction of NO(x) formation.

Engleman, V. S.↗

Storing hydrogen in the form of light alloy hydrides

Different hydrides are investigated to find a system with a sufficiently high storage density (at least 3%). The formation of hydrides with light alloys is examined. Reaction kinetics for hydride formation were defined and applied to the systems Mg-Al-H, Mg-Al-Cu-H, Ti-Al-H, Ti-Al-Cu-H, and Ti-Al-Ni-H. Results indicate that the addition of Al destabilizes MgH2 and TiH2 hydrides while having only a limited effect on the storage density.

Freund, E.↗

Condensation in CO2 free jet expansions. I - Dimer formation.

A theoretical and experimental investigation of the kinetics of CO2 dimer formation in the adiabatically expanding core of a free jet expansion has been carried out. The theoretical analysis is based on dimer formation by an efficient termolecular process and dimer destruction by bimolecular collisions. Account is taken of the expected variation of the specific heat ratio during the expansion and of the effective increase in the termolecular collision rate at low temperatures due to the presence of loosely bound orbiting pairs. Experimental dimer concentrations were measured mass spectrometrically by forming a molecular beam from the expanded gas mixture after the onset of molecular flow. Observed dimer concentrations, for a range of pre-expansion conditions of 400 to 900 torr pressure and room temperature, are in good agreement with the theoretical analysis, provided that account is taken of the effect of loosely bound orbiting pairs at low temperatures.

Dorfeld, W. G.↗

Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model

A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.

NASA Center JSC↗