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NASA NTRS1998

A Search for Giant Convection Cells on the Sun

Giant convection cells (slow, long-lived cellular flows in the Sun's convection zone with typical diameters greater than about 100,000 km) have been the subject of many searches over the last 30 years. If such flows exist, they should play a key role in structuring the Sun's large scale magnetic field and in driving the large scale axisymmetric flows: the differential rotation and meridional circulation. Detailed observations of the flows in these cells may also allow us to better predict future magnetic field configurations and the solar activity associated with them. Line-of-sight velocity data from the Michelson Doppler Interferometer on the ESA/NASA Solar and Heliospheric Observatory provides us with new opportunities to search for giant cells. This data is free of any atmospheric distortion and has been obtained continuously without any day/night gaps for more than two months at a time. These two-month datasets are important because giant cells are expected to have lifetimes somewhat longer that the Sun's 27 day rotation period. Any reappearance of a flow pattern after 27 days would be an important confirmation of the existence of these cells. The approach taken in this search is to separate the giant cell velocity signal from the other, stronger velocity signals by using a spherical harmonic representation of the spatial structures and a fourier decomposition of the temporal behavior. Any giant cell signal should be characterized by low spatial wavenumbers with temporal frequencies appropriate to the solar rotation of these patterns.

Hathaway, David H.↗

NASA NTRS2017

Candidate Nutritional Countermeasure to Mitigate Adverse Effects of Spaceflight

Problem statement: During spaceflight, astronauts are subjected to microgravity as well as radiation, both of which have adverse effects on bones, soft tissues and organs, possibly by shared mechanisms. For this reason there is a need to identify broad-spectrum countermeasures to protect multiple tissues from both insults.6.The spaceflight environment poses multiple challenges to homeostasis, including microgravity and ionizing radiation. Together, these factors contribute to cellular stress, and effects include increased generation of reactive oxygen species (ROS), oxidative and DNA damage, cell cycle arrest and cell senescence. We have shown that a purified diet supplemented with dried plum (DP, 25) conferred full protection of cancellous structure from the rapid bone loss caused by exposure to ionizing radiation (Schreurs et al. 2016). Based on these promising results for a new countermeasure to prevent space radiation induced-tissue damage, we will conduct additional studies to advance the potential countermeasure to a higher CRL level. We will test the DP diet for its ability to prevent bone loss caused by simulated microgravity as well as exposure to radiation. This will be achieved by exposing mice to each factor (simulated microgravity and radiation) alone and in combination. We hypothesize that spaceflight conditions lead to oxidative damage and bone loss, and that DP, a dietary additive rich in antioxidant and polyphenolic compounds, is an effective countermeasure for multiple tissues, including bone. To test this hypothesis we will accomplish the following aims: Aim 1 Determine if the antioxidant rich diet DP prevents simulated microgravity-induced bone loss. Aim 2 Determine if DP prevents simulated spaceflight-induced bone loss (microgravity and radiation combined). Aim 3 Determine if DP is effective as a countermeasure for adverse effects of simulated microgravity and radiation on non-skeletal tissues (brain, eye).

Schreurs, Ann-Sofie↗

NASA NTRS1996

Cellular Basis of Mechanotransduction

Physical forces, such as those due to gravity are fundamental regulators of tissue development. To influence morphogenesis, mechanical forces must alter growth and function. Yet little is known about how cells convert mechanical signals into a chemical response. This presentation attempts to place the potential molecular mediators of mechanotransduction within the context of the structural complexity of living cells.

Ingber, Donald E.↗

NASA NTRS2001

Hypergravity Loading the Cultured Osteoblasts: Modeling and Experimental Analysis of Cellular Morphology and the Cytoskeleton

Bone forming cells, osteoblasts, respond to various mechanical forces, including mechanical strain and fluid-induced shear stress. This study examined whether osteoblasts detect changes in gravity as a mechanical force, as assessed by cellular morphology and dimensions of the cytoskeletal network. We used modeling to evaluate how gravity influences cell morphology given theoretical differences in densities between the surrounding medium, cytoplasm, and nucleus. A mechanical model was built based on analysis of axisymmetric shell structures (Fast4 software) to study the effects of 10 times gravity (10G) on cell height. The model indicated 0.02% decrease in overall cell height when the medium was 10% denser than the nucleus or cytoplasm, 5.9 x 10(exp-5)% decrease when the nucleus was 10% denser than the cytoplasm or medium, and 1.3 x 10(exp-5)% decrease when the cell cytoplasm was 10% denser than the nucleus or medium. To experimentally evaluate the influence of gravity, cultured primary fetal rat osteoblasts were grown to near confluence and centrifuged at 10G for 3 hours. Actin, microtubules, and nuclei were fluorescently labeled and analyzed by confocal microscopy to determine overall microtubule and actin network height. Centrifugation led to an apparent reduction in height of both the microtubule (-16%) and the actin (-20%) networks relative to stationary controls. Thus, both modeling and experiments indicate that hypergravity reduces the height of the osteoblast cell layer and their microtubule and actin networks. This combination of modeling and experimental analyses will help us to better understand the mechanical loading of osteoblasts.

Searby, N. D.↗

NASA NTRS2014

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

Preliminary data from a prior tissue‐sharing experiment has suggested that early growth response protein‐1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia‐ or inflammation‐driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated‐weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS‐induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell‐specific isolectin binding, coupled to Alexa‐488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z‐axis. This new confocal microscope has the added capability of dye separation using the Linear Unmixing method and allows us to remove the autofluorescence originating from the photoreceptor layer. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recentlyinitiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Theriot, Corey A.↗

NASA NTRS2007

NanoSIMS opens a New Window for Deciphering Organic Matter in Terrestrial and Extraterrestrial Samples

Recognition of the earliest morphological or chemical evidence of terrestrial life has proved to be challenging, as organic matter in ancient rocks is commonly fragmentary and difficult to distinguish from abiotically-produced materials (Schopf, 1993; Van Zuilen et al., 2002; Altermann & Kazmierczak, 2003; Cady et al., 2003; Brasier et al., 2002, 2004, 2005; Hofmann, 2004; Skrzypczak et al., 2004, 2005). Yet, the ability to identify remnants of earliest life is critical to our understanding of the timing of life's origin on earth, the nature of earliest terrestrial life, and recognition of potential remnants of microbial life that might occur in extraterrestrial materials. The search for earliest life on Earth now extends to early Archean organic remains; these tend to be very poorly preserved and considerably more difficult to interpret than the delicately permineralized microfossils known from many Proterozoic deposits. Thus, recent efforts have been directed toward finding biosignatures that can help distinguish fragmentary remnants of ancient microbes from either pseudofossils or abiotic organic materials that may have formed hydrothermally or in extraterrestrial processes (House et al., 2000; Boyce et al., 2001; Kudryavtsev et al., 2001; Schopf, 2002; Schopf et al., 2002, 2005a,b; Cady et al., 2003; Garc a-Ruiz et al., 2003; Hofmann, 2004; Brasier et al., 2005; Rushdi and Simoneit, 2005; Skrzypczak et al., 2005). An exciting area of biosignature research involves the developing technology of NanoSIMS. NanoSIMS is secondary ion mass spectrometry (SIMS) for ultrafine feature, elemental and isotopic analysis. Its resolution approaches 0.05 micrometers for element mapping, which is 10-50 times finer than that attainable with conventional SIMS or electron microprobes. Consequently, NanoSIMS has the potential to reveal previously unknown, chemical and structural characteristics of organic matter preserved in geologic materials. Robert et al. (2005) were the first to combine NanoSIMS element maps with optical microscopic imagery in an effort to develop a new method for assessing biogenicity. They showed that the ability to simultaneously map the distribution of organic elements [such as carbon (C), nitrogen (N), and sulfur (S)] and compare those element distributions with optically recognizable, cellularly preserved fossils could provide significant new insights into the origin of organic materials in ancient sediments. This chapter details a recent NanoSIMS study which was designed to acquire new data relevant to establishing critical biosignatures (Oehler et al., 2006a-c). In this study, NanoSIMS was used to characterize element distributions of spheroidal and filamentous microfossils and associated organic laminae in chert from the approx. 0.85 billion year old (Ga) Bitter Springs Formation of Australia. Previous work established preservation of a diverse microbiota in the Bitter Springs Formation (Schopf, 1968; Schopf and Blacic, 1971), and there is no dispute within the scientific community regarding the biogenicity of any of the Bitter Springs structures evaluated in this new study. Thus, the NanoSIMS results described below provide new insight into - and can be used as a guide for assessing - the origin of less well understood organic materials that may occur in early Archean samples and in meteorites or other extraterrestrial samples.

Oehler, Dorothy ZS.↗

NASA NTRS1995

Differential localization of cytoplasmic myosin II isoforms A and B in avian interphase and dividing embryonic and immortalized cardiomyocytes and other cell types in vitro

Two principal isoforms of cytoplasmic myosin II, A and B (CMIIA and CMIIB), are present in different proportions in different tissues. Isoform-specific monoclonal and polyclonal antibodies to avian CMIIA and CMIIB reveal the cellular distributions of these isoforms in interphase and dividing embryonic avian cardiac, intestinal epithelial, spleen, and dorsal root ganglia cells in primary cell culture. Embryonic cardiomyocytes react with antibodies to CMIIB but not to CMIIA, localize CMIIB in stress-fiber-like-structures during interphase, and markedly concentrate CMIIB in networks in the cleavage furrow during cytokinesis. In contrast, cardiac fibroblasts localize both CMIIA and CMIIB in stress fibers and networks during interphase, and demonstrate slight and independently regulated concentration of CMIIA and CMIIB in networks in their cleavage furrows. V-myc-immortalized cardiomyocytes, an established cell line, have regained the ability to express CMIIA, as well as CMIIB, and localize both CMIIA and CMIIB in stress fibers and networks in interphase cells and in cleavage furrows in dividing cells. Conversely, some intestinal epithelial, spleen, and dorsal root ganglia interphase cells express only CMIIA, organized primarily in networks. Of these, intestinal epithelial cells express both CMIIA and CMIIB when they divide, whereas some dividing cells from both spleen and dorsal root ganglia express only CMIIA and concentrate it in their cleavage furrows. These results suggest that within a given tissue, different cell types express different isoforms of CMII, and that cells expressing either CMIIA or CMIIB alone, or simultaneously, can form a cleavage furrow and divide.

NASA Discipline Developmental Biology↗

NASA NTRS2003

Motor System Development Depends on Experience: A Microgravity Study of Rats

Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation to the rearing environment. These observations provide support for the idea that an animal's motor system adapts for optimal function within the environment experienced during a critical period in early postnatal life.

Walton, Kerry D.↗

NASA NTRS2021

A Mathematical Analysis of an Example Delay Tolerant Network using the Theory of Sheaves

NASA’s High-Data Rate Architecture (HiDRA) project is working towards a general yet practical toolkit and knowledge base to help usher in the era of new technologies for space systems communications, such as optical links. The High-Rate Delay Tolerant Networking (HDTN) implementation falls under the umbrellas of both the toolkit and the knowledge base, as its advancements illuminate more general areas of Delay Tolerant Networking (DTN) that need growth. The goal of this paper is to explore the usage of particular mathematical machineries, namely temporal flow networks and sheaves, to identify fundamental, underlying structures in DTN for space systems. Satellites, space assets, ground stations, etc. give rise to a disconnected network, and it is the goal of DTN to glue disparate links together into a cohesive system, that is, a network. Depending on a given link, the latencies might be beyond that which the Transmission Control Protocol (TCP) can handle, and contact times might have one-way light times in excess of minute (sometimes significantly longer). Some links might be periodic (say, due to orbital mechanics) or they might not be. This diversity has made it difficult to probe the underlying structure. An immediate consequence is that DTNs in practice today are controlled by globally distributed contact plans (schedules), which are the input to the contact graph routing (CGR) algorithm. While this is effective for smaller networks, it will be very difficult to scale for future networks. Deeper and more rigorous theory is needed to bring DTN to the next evolutionary step. To this end, this paper introduces and suggests a mathematical framework for DTN, and applies it to a space network that is simulated using an orbital analysis toolkit. The tag-line for the structure known as sheaves is that they are the mathematically precise way of gluing local data together into unique, global data. If we consider routing, we see that networking is a “sheafy” science. We then discuss a simplified sheaf model, known as the cellular sheaf. The sheaf-theoretic analysis is presented and discussed, as it is hoped that this and related papers will help form the primordial ooze of DTN theory. Finally there is a section of future work suggesting follow-on research.

Delay Tolerant Networking↗

NASA NTRS1985

Calcium movement, graviresponsiveness and the structure of columella cells and columella tissues in roots of Allium cepa L

Roots of Allium cepa L. cv. Yellow are differentially responsive to gravity. Long (e.g. 40 mm) roots are strongly graviresponsive, while short (c.g. 4 mm) roots are minimally responsive to gravity. Although columella cells of graviresponsive roots are larger than those of nongraviresponsive roots, they partition their volumes to cellular organelles similarly. The movement of amyloplasts and nuclei in columella cells of horizontally-oriented roots correlates positively with the onset of gravicurvature. Furthermore, there is no significant difference in the rates of organellar redistribution when graviresponsive and nongraviresponsive roots are oriented horizontally. The more pronounced graviresponsiveness of longer roots correlates positively with (1) their caps being 9-6 times more voluminous, (2) their columella tissues being 42 times more voluminous, (3) their caps having 15 times more columella cells, and (4) their columella tissues having relative volumes 4.4 times larger than those of shorter, nongraviresponsive roots. Graviresponsive roots that are oriented horizontally are characterized by a strongly polar movement of 45Ca2+ across the root tip from the upper to the lower side, while similarly oriented nongraviresponsive roots exhibit only a minimal polar transport of 45Ca2+. These results indicate that the differential graviresponsiveness of roots of A. cepa is probably not due to either (1) ultrastructural differences in their columella cells, (2) differences in the rates of organellar redistribution when roots are oriented horizontally. Rather, these results indicate the graviresponsiveness may require an extensive columella tissue, which, in turn, may be necessary for polar movement of 45Ca2+ across the root tip.

Onions/cytology/growth & development/metabolism/ul↗

NASA NTRS2004

The Direct Digital Modulation of Traveling Wave Tubes

Traveling wave tube (TWT) technology, first described by Rudolf Kompfner in the early 1940s, has been a key component of space missions from the earliest communication satellites in the 1960s to the Cassini probe today. TWTs are essentially signal amplifiers that have the special capability of operating at microwave frequencies. The microwave frequency range, which spans from approximately 500 MHz to 300 GHz, is shared by many technologies including cellular phones, satellite television, space communication, and radar. TWT devices are superior in reliability, weight, and efficiency to solid-state amplifiers at the high power and frequency levels required for most space missions. TWTs have three main components -an electron gun, slow wave structure, and collector. The electron gun generates an electron beam that moves along the length of the tube axis, inside of the slow wave circuit. At the same time, the inputted signal is slowed by its travel through the coils of the helical slow wave circuit. The interaction of the electron beam and this slowed signal produces a transfer of kinetic energy to the signal, and in turn, amplification. At the end of its travel, the spent electron beam moves into the collector where its remaining energy is dissipated as heat or harnessed for reuse. TWTs can easily produce gains in the tens of decibels, numbers that are suitable for space missions. To date, however, TWTs have typically operated at fixed levels of gain. This gain is determined by various, unchanging, physical factors of the tube. Traditionally, to achieve varying gain, an input signal s amplitude has had to first be modulated by a separate device before being fed into the TWT. This is not always desirable, as significant distortion can occur in certain situations. My mentor, Mr. Dale Force, has proposed an innovative solution to this problem called direct digital modulation . The testing and implementation of this solution is the focus of my summer internship. The direct digital modulation of a TWT removes the need for a separate amplitude modulation device. Instead, different levels of gain are achieved by varying the electron beam current. The lower the current, the less kinetic energy is available to be transferred to the signal. To vary the current, a grid is placed in-between the electron gun and the slow wave circuit. By changing the voltage across the grid, the electron beam current can be controlled. Grid technology has mostly been used in pulse applications such as radar, where only two voltage states are necessary. For direct digital modulation, however, a continuous range of voltages is required.

Radhamohan, Ranjan S.↗

NASA NTRS2000

Monitoring Astronaut Health at the Nanoscale Cellular Level Through the Eye

A user friendly goggles-like head-mounted device equipped with a suite of instruments for several non-invasive and quantitative medical evaluation of the eye, skin, and brain is desired for monitoring the health of astronauts during space travel and exploration of neighboring and distant planets. Real-time non-invasive evaluation of the different structures within the above organs can provide indices of the health of not just these organs, but the entire body. The techniques such as dynamic light scattering (for the early detection of uveitis, cholesterol levels, cataract, changes in the vitreous and possibly Alzheimer's disease), corneal autofluorescence (to assess extracellular matrix biology e.g., in diabetes), optical activity measurements (of anterior ocular fluid to evaluate blood-glucose levels), laser Doppler velocimetry (to assess retinal, optic nerve, and choroidal blood flow), reflectometry/oximetry (for assessing ocular and central nervous system oxygen metabolism), optical coherence tomography (to determine retinal tissue microstructure) and possibly scanning laser technology (for intraocular tissue imaging and scanning) will he integrated into this compact device. Skin sensors will also be mounted on the portion of the device in contact with the periocular region. This will enable monitoring of body temperature, EEG, and electrolyte status. This device will monitor astronaut health during long-duration space travel by detecting aberrations from pre-established "nonns", enabling prompt diagnosis and possibly the initiation of early preventative/curative therapy. The non-invasive nature of the device technologies permits frequent repetition of tests, enabling real-time complete crew health monitoring. This device may ultimately be useful in tele-medicine to bring modern healthcare to under-served areas on Earth as well as in so-called "advanced" care settings (e.g. diabetes in the USA).

Ansari, Rafat R.↗

NASA NTRS2010

Monte-Carlo Simulation of Radiation Track Structure and Calculation of Dose Deposition in Nanovolumes

INTRODUCTION: The radiation track structure is of crucial importance to understand radiation damage to molecules and subsequent biological effects. Of a particular importance in radiobiology is the induction of double-strand breaks (DSBs) by ionizing radiation, which are caused by clusters of lesions in DNA, and oxidative damage to cellular constituents leading to aberrant signaling cascades. DSB can be visualized within cell nuclei with gamma-H2AX experiments. MATERIAL AND METHODS: In DSB induction models, the DSB probability is usually calculated by the local dose obtained from a radial dose profile of HZE tracks. In this work, the local dose imparted by HZE ions is calculated directly from the 3D Monte-Carlo simulation code RITRACKS. A cubic volume of 5 micron edge (Figure 1) is irradiated by a (Fe26+)-56 ion of 1 GeV/amu (LET approx.150 keV/micron) and by a fluence of 450 H+ ions, 300 MeV/amu (LET approx. 0.3 keV/micron). In both cases, the dose deposited in the volume is approx.1 Gy. The dose is then calculated into each 3D pixels (voxels) of 20 nm edge and visualized in 3D. RESULTS AND DISCUSSION: The dose is deposited uniformly in the volume by the H+ ions. The voxels which receive a high dose (orange) corresponds to electron track ends. The dose is deposited differently by the 56Fe26+ ion. Very high dose (red) is deposited in voxels with direct ion traversal. Voxels with electron track ends (orange) are also found distributed around the path of the track. In both cases, the appearance of the dose distribution looks very similar to DSBs seen in gammaH2AX experiments, particularly when the visualization threshold is applied. CONCLUSION: The refinement of the dose calculation to the nanometer scale has revealed important differences in the energy deposition between high- and low-LET ions. Voxels of very high dose are only found in the path of high-LET ions. Interestingly, experiments have shown that DSB induced by high-LET radiation are more difficult to repair. Therefore, this new approach may be useful to understand the nature of DSB and oxidative damage induced by ionizing radiation.

Plante, I.↗

NASA NTRS1998

The universal ancestor

A genetic annealing model for the universal ancestor of all extant life is presented; the name of the model derives from its resemblance to physical annealing. The scenario pictured starts when "genetic temperatures" were very high, cellular entities (progenotes) were very simple, and information processing systems were inaccurate. Initially, both mutation rate and lateral gene transfer levels were elevated. The latter was pandemic and pervasive to the extent that it, not vertical inheritance, defined the evolutionary dynamic. As increasingly complex and precise biological structures and processes evolved, both the mutation rate and the scope and level of lateral gene transfer, i.e., evolutionary temperature, dropped, and the evolutionary dynamic gradually became that characteristic of modern cells. The various subsystems of the cell "crystallized," i.e., became refractory to lateral gene transfer, at different stages of "cooling," with the translation apparatus probably crystallizing first. Organismal lineages, and so organisms as we know them, did not exist at these early stages. The universal phylogenetic tree, therefore, is not an organismal tree at its base but gradually becomes one as its peripheral branchings emerge. The universal ancestor is not a discrete entity. It is, rather, a diverse community of cells that survives and evolves as a biological unit. This communal ancestor has a physical history but not a genealogical one. Over time, this ancestor refined into a smaller number of increasingly complex cell types with the ancestors of the three primary groupings of organisms arising as a result.

NASA Discipline Exobiology↗

NASA NTRS1990

Radiation biology of HZE particles

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

Nelson, Gregory A.↗

NASA NTRS2008

High- and low-LET Radiation-induced Chromosome Aberrations in Human Epithelial Cells Cultured in 3-dimensional Matrices

Energetic heavy ions pose a great health risk to astronauts who participate in extended ISS missions and will be an even greater concern for future manned lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D in vitro cellular environment can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelial cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultured at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected in the first cell cycle after irradiation using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference in the chromosome aberration yield between 2D and 3D cell cultures after gamma exposures, but not after Fe ion exposures. Therefore, the Relative Biological Effect (RBE) for induction of chromosome aberrations obtained in a 2D model may not accurately represent RBE values obtained for tissue exposure.

Hada, M.↗

NASA NTRS1999

Novel Approaches to Cellular Transplantation from the US Space Program

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

Pellis, Neal R.↗

NASA NTRS2008

M-BAND Analysis of Chromosome Aberration Induced by Fe-Ions in Human Epithelial Cells Cultured in 3-Dimensional Matrices

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D cellular environment in vitro can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelia cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultued at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference of the chromosome aberration yield between 2D and 3D cell cultures for gamma exposures, but not for Fe ion exposures. Therefore, the RBE for chromosome aberrations obtained in a 2D model may not represent accurately the RBE for tissues.

Hada, M.↗