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Deletion of Cdkn1a in Mice Rescues Reduced Osteogenesis in Microgravity and Increases Coupled Osteoclastic Bone Degenerative Activity and Bone Loss

Elevated Cdkn1a/p21 levels in mouse bone during spaceflight have led us to hypothesize that this cell cycle inhibitor could regulate osteogenesis in response to mechanical unloading in microgravity. Cdkn1a interacts with cyclins CDK1/2/4,6 during G1 and S phases, and suppression of its expression by mechanical stretch enhances proliferation and mineralization in osteoblastic cell cultures. To test this hypothesis in a whole-organism model, we used C57BL/J6 WT/Cdkn1a-null mice in the NASA RR-10, 30-day ISS microgravity experiment. To quantify active mineralization in microgravity mice were injected with Calcein seven and two days before euthanasia on-orbit, followed by high-resolution confocal imaging of optically cleared femoral endosteal surfaces. To quantify cortical and cancellous bone parameters we conducted microCT analyses of the femur and tibia. Confocal imaging revealed a population of mineralizing calcein-positive single osteoblasts, and multicellular surfaces of mineralization by osteocytes in lacunae. The Cdkn1a-null genotype shows a greater ratio of early-osteoblasts to late-osteocytes and reduced mineralization versus WT. Additionally, in microgravity WT bones have a large (80%) decrease in active mineralization, but remarkably Cdkn1a deletion fully rescued mineralized surface loss. MicroCT shows trends for moderate spaceflight bone loss in WT femurs, and significant losses in the tibia, while Cdkn1a-null femurs showed much larger significant tissue losses, including 25% thinner trabeculae (p < 0.01),40% thinner cortical bone (p < 0.005), and 10% lower percent cortical bone area (p < 0.05). These results indicate that endogenous bone Cdkn1a plays a key role in mechanosensitive downregulation of osteoprecursor proliferation and promotes osteocytic differentiation. In microgravity however, while Cdkn1a deletion rescues mineralization, bone loss quantified by microCT is greatly increased, likely due to the molecular coupling of osteogenesis and osteoclastogenesis. This molecular mechanism opens the possibility for potential pharmacological approaches to mitigate bone loss in space simultaneously targeting Cdkn1a and osteoclast inhibition.

Eduardo A.C. Almeida↗

NASA NTRS2003

New Technologies Being Developed for the Thermophoretic Sampling of Smoke Particulates in Microgravity

The Characterization of Smoke Particulate for Spacecraft Fire Detection, or Smoke, microgravity experiment is planned to be performed in the Microgravity Science Glovebox Facility on the International Space Station (ISS). This investigation, which is being developed by the NASA Glenn Research Center, ZIN Technologies, and the National Institute of Standards and Technologies (NIST), is based on the results and experience gained from the successful Comparative Soot Diagnostics experiment, which was flown as part of the USMP-3 (United States Microgravity Payload 3) mission on space shuttle flight STS-75. The Smoke experiment is designed to determine the particle size distributions of the smokes generated from a variety of overheated spacecraft materials and from microgravity fires. The objective is to provide the data that spacecraft designers need to properly design and implement fire detection in spacecraft. This investigation will also evaluate the performance of the smoke detectors currently in use aboard the space shuttle and ISS for the test materials in a microgravity environment.

Sheredy, William A.↗

NASA NTRS2001

Equiaxed Dendritic Solidification Experiment (EDSE)

The objective of the research is to quantitatively determine and understand the fundamental mechanisms that control the microstructural evolution during equiaxed dendritic solidification. A microgravity experiment will be conducted to obtain benchmark data on the transient growth and interaction of up to four equiaxed crystals of a pure and transparent metal analog (succinonitrile, SCN) under strictly diffusion-dominated conditions. Of interest in the experiment are the transient evolution of the primary and secondary dendrite tip speeds, the dendrite morphology and solid fraction, the tip selection criterion, and the temperature field in the melt for a range of interaction "strengths" between the crystals. The experiment extends the microgravity measurements of Glicksman and co-workers isothermal dendritic growth experiment (IDGE) for steady growth of a single dendrite to a case where growth transients are introduced due to thermal interactions between neighboring dendrites - a situation closer to actual casting conditions. Corresponding Earth-based experiments will be conducted to ascertain the influence of melt convection. The experiments are supported by a variety of analytical models and numerical simulations. The data will be used to develop and test theories of transient dendritic growth and the solidification of multiple interacting equiaxed crystals in a supercooled melt.

Beckermann, C.↗

NASA NTRS1993

Vibration isolation technology: An executive summary of systems development and demonstration

A program was organized to develop the enabling technologies needed for the use of Space Station Freedom as a viable microgravity experimental platform. One of these development programs was the Vibration Isolation Technology (VIT). This technology development program grew because of increased awareness that the acceleration disturbances present on the Space Transportation System (STS) orbiter can and are detrimental to many microgravity experiments proposed for STS, and in the future, Space Station Freedom (SSF). Overall technological organization are covered of the VIT program. Emphasis is given to the results from development and demonstration of enabling technologies to achieve the acceleration requirements perceived as those most likely needed for a variety of microgravity science experiments. In so doing, a brief summary of general theoretical approaches to controlling the acceleration environment of an isolated space based payload and the design and/or performance of two prototype six degree of freedom active magnetic isolation systems is presented.

Grodsinsky, Carlos M.↗

NASA NTRS1993

Vibration isolation technology - An executive summary of systems development and demonstration

Grodsinsky, C. M.↗

NASA NTRS1992

Effects of refrigerating preinoculated Vitek cards on microbial physiology and antibiotic susceptibility

Reference cultures of 16 microorganisms obtained from the American Type Culture Collection and four clinical isolates were used in standardized solutions to inoculate 60 cards for each test strain. A set of three ID and three susceptibility cards was processed in the Vitek AutoMicrobic System (AMS) immediately after inoculation. The remaining cards were refrigerated at 4 C, and sets of six cards were removed and processed periodically for up to 17 days. The preinoculated AMS cards were evaluated for microorganism identification, percent probability of correct identification, length of time required for final result, individual substrate reactions, and antibiotic minimal inhibitory/concentration (MIC) values. Results indicate that 11 of the 20 microbes tested withstood refrigerated storage up to 17 days without detectable changes in delineating characteristics. MIC results appear variable, but certain antibiotics proved to be more stable than others. The results of these exploratory studies will be used to plan a microgravity experiment designed to study the effect of microgravity on microbial physiology and antibiotic sensitivity.

Skweres, Joyce A.↗

NASA NTRS1994

Fluids flight hardware

The following are discussed in this viewgraph presentation: Glovebox-2 investigations, study of oscillatory thermocapillary flows and validate physical models on the second U.S. Microgravity Laboratory Mission (USML-2), pool boiling experiment, critical fluid viscosity measurement experiment, Hitchhiker-G typical structural configuration, ZENO-critical fluid light scattering experiment, isothermal dendritic growth experiment, microgravity acceleration environment support, and the space acceleration measurement system (SAMS).

Shaw, Nancy↗

NASA NTRS1999

Solidification of II-VI Compounds in a Rotating Magnetic Field

This project is aimed at using a rotating magnetic field (RMF) to control fluid flow and transport during directional solidification of elemental and compound melts. Microgravity experiments have demonstrated that small amounts of residual acceleration of less than a micro-g can initiate and prolong fluid flow, particularly when there is a static component of the field perpendicular to the liquid solid interface. Thus a true diffusion boundary layer is not formed, and it becomes difficult to verify theories of solidification or to achieve diffusion controlled solidification. The RMF superimposes a stirring effect on an electrically conducting liquid, and with appropriate field strengths and frequencies, controlled transport of material through a liquid column can be obtained. As diffusion conditions are precluded and complete mixing conditions prevail, the technique is appropriate for traveling solvent zone or float zone growth methods in which the overall composition of the liquid can be maintained throughout the growth experiment. Crystals grown by RMF techniques in microgravity in previous, unrelated missions have shown exceptional properties. The objective of the project is two-fold, namely (1) using numerical modeling to simulate the behavior of a solvent zone with applied thermal boundary conditions and demonstrate the effects of decreasing gravity levels, or an increasing applied RMF, or both, and (2) to grow elements and II-VI compounds from traveling solvent zones both with and without applied RMFs, and to determine objectively how well the modeling predicts solidification parameters. Numerical modeling has demonstrated that, in the growth of CdTe from a tellurium solution, a rotating magnetic field can advantageously modify the shape of the liquid solid interface such that the interface is convex as seen from the liquid. Under such circumstances, the defect structure is reduced as any defects which are formed tend to grow out and not propagate. The flow of liquid, however, is complex due to the competing flow induced by the rotating magnetic field and the buoyancy driven convection. When the acceleration forces are reduced to one thousandth of gravity, the flow pattern is much simplified and well controlled material transport through the solvent zone can be readily achieved. Triple axis diffractometry and x-ray synchrotron topography have demonstrated that there is no significant improvement in crystal quality for HgCdTe grown on earth from a tellurium solution when a rotating magnetic field is applied. However, modeling shows that the flow in microgravity with a rotating magnetic field would produce a superior product.

Gillies, D. C.↗

NASA NTRS1999

Third and Final Shuttle Mission of the Isothermal Dendritic Growth Experiment Conducted: Highest Supercooling Ever Recorded Achieved

Dendrites describe the treelike crystal morphology commonly assumed in metals and alloys that freeze from supercooled or supersaturated melts. There remains a high level of engineering interest in dendritic solidification because the size, shape, and orientation of the dendrites determine the final microstructure of a material. It is the microstructure that then determines the physical properties of cast or welded products. Although it is well known that dendritic growth is controlled by the transport of latent heat from the moving solid-liquid interface, an accurate and predictive model has not yet been developed. The effects of gravity-induced convection on the transfer of heat from the interface have prevented adequate testing, under terrestrial conditions, of solidification models. The Isothermal Dendritic Growth Experiment (IDGE) constituted a series of three microgravity experiments flown aboard the Space Shuttle Columbia. The apparatus was used to grow and record dendrite solidification in the absence of gravity-induced convective heat transfer, thereby producing a wealth of benchmark-quality data for testing solidification models and theories.

Glicksman, Martin E.↗

NASA NTRS1998

Characterization of Metalorganic Chemical Vapor Deposition

A series of experimental and numerical investigations to develop a more complete understanding of the reactive fluid dynamics of chemical vapor deposition were conducted. In the experimental phases of the effort, a horizontal CVD reactor configuration was used for the growth of InP at UVA and for laser velocimetry measurements of the flow fields in the reactor at LaRC. This horizontal reactor configuration was developed for the growth of III-V semiconductors and has been used by our research group in the past to study the deposition of both GaAs and InP. While the ultimate resolution of many of the heat and mass transport issues will require access to a reduced-gravity environment, the series of groundbased research makes direct contributions to this area while attempting to answer the design questions for future experiments of how low must gravity be reduced and for how long must this gravity level be maintained to make the necessary measurements. It is hoped that the terrestrial experiments will be useful for the design of future microgravity experiments which likely will be designed to employ a core set of measurements for applications in the microgravity environment such as HOLOC, the Fluid Physics/Dynamics Facility, or the Schlieren photography, the Laser Imaging Velocimetry and the Laser Doppler Velocimetry instruments under development for the Advanced Fluids Experiment Module.

Jesser, W. A.↗

NASA NTRS1999

SAMS Acceleration Measurements on Mir from May 1997 to June 1998 (NASA Increments 5, 6, and 7)

During NASA Increments 5, 6, and 7 (May 1997 to June 1998), about eight gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station Mir. The data were recorded on twenty-seven optical disks which were returned to Earth on Orbiter missions STS-86, STS-89, and STS-91. During these increments, SAMS data were collected in the Priroda module to support various microgravity experiments. This report points out some of the salient features of the microgravity acceleration environment to which the experiments were exposed. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous Mir increment summary reports prepared by the Principal Investigator Microgravity Services project.

DeLombard, Richard↗

NASA NTRS1999

SAMS Acceleration Measurements on Mir from May 1997 to June 1998 (NASA Increments 5, 6, and 7)

DeLombard, Richard↗

NASA NTRS1994

Preliminary flight results from the second U.S. Microgravity Payload (USMP-2)

The second U.S. Microgravity Payload (USMP-2) was flown on the Space Shuttle in March 1994. It carried four major microgravity experiments plus a sophisticated accelerometer system to record the microgravity environment during USMP-2 operations. The USMP program is designed to accommodate experiments requiring extensive resources short of a full Spacelab mission, and the experiments are remotely operated and monitored. Results are reviewed from the four experiments: the Advanced Automated Directional Solidification Facility (AADSF), the Isothermal Dendrite Growth Experiment (IDGE), the Materiel por Etude des Phenomenes Interessant la Soldification sur Terre et en Orbite (MEPHISTO), and the Critical Fluid Light Scattering Experiment (Zeno). AASDF grew what is expected to be the largest steady-state sample ever of HgCdTe during 240 hours of operation. IDGE provided 60 growth cycles over a wide range of supercooling conditions studying the dendritic solidification of succinonitrile. MEPHISTO achieved 55 melt-solidify cycles and grew over 1 m of Bi/Sn alloy. Zeno located the critical point temperature for liquid Xe to 0.00001 K. IDGE and Zeno also provided the most extensive demonstrations to date of telescience.

Curreri, Peter↗

NASA NTRS1992

Cells In Space

Report of "Cells in Space - II" conference held from 31 October through 4 November 1988 in San Juan Bautista, CA, contains abstracts of 32 oral presentations discussing 3 aspects of cell research in space: suitability of cell as subject in microgravity experiments; requirements of generic flight equipment to support microgravity cell research; and potential for collaboration between academia, industry, and government to develop these studies in space.

Callahan, P. X.↗

NASA NTRS1996

Space Station Biological Research Project: Reference Experiment Book

The Space Station Biological Research Project (SSBRP), which is the combined efforts of the Centrifuge Facility (CF) and the Gravitational Biology Facility (GBF), is responsible for the development of life sciences hardware to be used on the International Space Station to support cell, developmental, and plant biology research. The SSBRP Reference Experiment Book was developed to use as a tool for guiding this development effort. The reference experiments characterize the research interests of the international scientific community and serve to identify the hardware capabilities and support equipment needed to support such research. The reference experiments also serve as a tool for understanding the operational aspects of conducting research on board the Space Station. This material was generated by the science community by way of their responses to reference experiment solicitation packages sent to them by SSBRP scientists. The solicitation process was executed in two phases. The first phase was completed in February of 1992 and the second phase completed in November of 1995. Representing these phases, the document is subdivided into a Section 1 and a Section 2. The reference experiments contained in this document are only representative microgravity experiments. They are not intended to define actual flight experiments. Ground and flight experiments will be selected through the formal NASA Research Announcement (NRA) and Announcement of Opportunity (AO) experiment solicitation, review, and selection process.

Johnson, Catherine↗

NASA NTRS1999

Equiaxed Dendritic Solidification Experiment (EDSE)

The objective of the research is to quantitatively determine and understand the fundamental mechanisms that control the microstructural evolution during solidification of an assemblage of equiaxed dendritic crystals. A microgravity experiment will be conducted to obtain benchmark data on the transient growth and interaction of up to four equiaxed crystals of a pure and transparent metal analog (succinonitrile, SCN) under strictly diffusion dominated conditions. Of interest in the experiment are the transient evolution of the primary and secondary dendrite tip speeds, the dendrite morphology (i.e., tip radii, branch spacings, etc.) and solid fraction, the tip selection criterion, and the temperature field in the melt for a range of initial supercoolings and, thus, interaction "strengths" between the crystals. The experiment thus extends the microgravity measurements of Glicksman and coworkers for steady growth of a single dendrite [Isothermal Dendritic Growth Experiment (IDGE), first flown on USMP-2] to a case where growth transients are introduced due to thermal interactions between neighboring dendrites - a situation more close to actual casting conditions. Corresponding earth-based experiments will be conducted to ascertain the influence of melt convection. The experiments are supported by a variety of analytical models and numerical simulations. The data will primarily be used to develop and test theories of transient dendritic growth and the solidification of multiple interacting equiaxed crystals in a supercooled melt.

Beckermann, C.↗

NASA NTRS1995

Effect of CF3H and CF3Br on laminar diffusion flames in normal and microgravity

Chemical inhibition of diffusion flames through addition of halogenated inhibitors is a problem of significant practical and scientific interest. Extensive studies on diffusion flames in microgravity have shown that these flames have significantly different characteristics than those under normal gravity. However, the mechanisms through which inhibitors reach the reaction zone to suppress combustion in diffusion flames and the effectiveness of these compounds under reduced gravity have yet to be investigated. This study reports preliminary results of investigations on the behavior of laminar jet diffusion flames upon the addition of bromotrifluoromethane (CF3Br) and trifluoromethane (CF3H) to the surroundings under normal and microgravity conditions. The results show that the flame structure in microgravity is significantly different from that under normal gravity conditions, and more importantly, that conditions for flame stability are less stringent under microgravity. Experiments show that flames that cannot be stabilized under normal gravity are quite stable under microgravity conditions. In addition, normal gravity experiments at reduced pressure (low buoyancy) did not reproduce the structure or stability limits of inhibited flames in microgravity.

Vanderwege, B. A.↗

NASA NTRS1994

Clover development during spaceflight: A model system

The development of legume root nodules was studied as a model system for the examination of gravitational effects on plant root development. In order to examine whether rhizobial association with clover roots can be achieved in microgravity, experiments were performed aboard the KC-135 parabolic aircraft and aboard the sounding rocket mission Consort 3. Binding of rhizobia to roots and the initial stages of root nodule development successfully occurred in microgravity. Seedling germination experiments were performed in the sliding block device, the Materials Dispersion Apparatus, aboard STS-37. When significant hydration of the seeds was achieved, normal rates of germination and seedling development were observed.

Guikema, James A.↗