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Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

NASA Discipline Radiation Health↗

Modular, Reconfigurable, High-Energy Technology Development

The Modular, Reconfigurable High-Energy (MRHE) Technology Demonstrator project was to have been a series of ground-based demonstrations to mature critical technologies needed for in-space assembly of a highpower high-voltage modular spacecraft in low Earth orbit, enabling the development of future modular solar-powered exploration cargo-transport vehicles and infrastructure. MRHE was a project in the High Energy Space Systems (HESS) Program, within NASA's Exploration Systems Research and Technology (ESR&T) Program. NASA participants included Marshall Space Flight Center (MSFC), the Jet Propulsion Laboratory (JPL), and Glenn Research Center (GRC). Contractor participants were the Boeing Phantom Works in Huntsville, AL, Lockheed Martin Advanced Technology Center in Palo Alto, CA, ENTECH, Inc. in Keller, TX, and the University of AL Huntsville (UAH). MRHE's technical objectives were to mature: (a) lightweight, efficient, high-voltage, radiation-resistant solar power generation (SPG) technologies; (b) innovative, lightweight, efficient thermal management systems; (c) efficient, 100kW-class, high-voltage power delivery systems from an SPG to an electric thruster system; (d) autonomous rendezvous and docking technology for in-space assembly of modular, reconfigurable spacecraft; (e) robotic assembly of modular space systems; and (f) modular, reconfigurable distributed avionics technologies. Maturation of these technologies was to be implemented through a series of increasingly-inclusive laboratory demonstrations that would have integrated and demonstrated two systems-of-systems: (a) the autonomous rendezvous and docking of modular spacecraft with deployable structures, robotic assembly, reconfiguration both during assembly and (b) the development and integration of an advanced thermal heat pipe and a high-voltage power delivery system with a representative lightweight high-voltage SPG array. In addition, an integrated simulation testbed would have been developed containing software models representing the technologies being matured in the laboratory demos. The testbed would have also included models for non-MRHE developed subsystems such as electric propulsion, so that end-to-end performance could have been assessed. This paper presents an overview of the MRHE Phase I activities at MSFC and its contractor partners. One of the major Phase I accomplishments is the assembly demonstration in the Lockheed Martin Advanced Technology Center (LMATC) Robot-Satellite facility, in which three robot-satellites successfully demonstrated rendezvous & docking, self-assembly, reconfiguration, adaptable GN&C, deployment, and interfaces between modules. Phase I technology maturation results from ENTECH include material recommendations for radiation hardened Stretched Lens Array (SLA) concentrator lenses, and a design concept and test results for a hi-voltage PV receiver. UAH's accomplishments include Supertube heatpipe test results, which support estimates of thermal conductivities at 30,000 times that of an equivalent silver rod. MSFC performed systems trades and developed a preliminary concept design for a 100kW-class modular reconfigurable solar electric propulsion transport vehicle, and Boeing Phantom Works in Huntsville performed assembly and rendezvous and docking trades. A concept animation video was produced by SAIC, wllich showed rendezvous and docking and SLA-square-rigger deployment in LEO.

Carrington, Connie↗

A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice receiving only 2 Gy of protons. Tissue of the gastrointestinal tract was also homogenized and RNA was isolated for cDNA synthesis and real-time PCR analysis. Inspecting apoptotic lesions of the duodenum of the small intestine as an endpoint of damage did not reveal a radio-adaptive response in C57BL/6 mice at the four hour time point. Results of gene expression changes showed consistent up or down regulation of a number of genes for all of the exposure doses that may play a role in proton-induced apoptosis. Preliminary results of gene expression alterations as a result of gamma-irradiation revealed a wealth of genes involved in oxidative stress and antioxidant defense processes being up- or down-regulated only at the highest exposure dose of 6 Gy and the combined dose of 5 cGy with 6 Gy. Those animals undergoing only 5 cGy of gamma-irradiation showed very little modification of gene expression. Taken together these results lead us to conclude that protons cause more severe morphologic damage to the duodenum of the small intestine at a dose of 2 Gy than a higher dose of 6 Gy of gamma rays to the same organ. Both protons and gamma rays lead to significant variation in gene expression at high doses in the small intestine and these changes may provide insight into the mechanism of injury seen in the gastrointestinal tract following radiation exposure. Astronauts experiencing prolonged exposure to protons in the low Earth orbit and in deep space, and experiencing acute exposure to protons from solar particle events, may face biological consequences that will impact a mission s success. We will continue this work by studying, quantifying, and comparing damage due to protons and gamma rays in the small intestine as well as other organs in a time-dependent manner.

Purgason, Ashley↗

Advances in Rodent Research Missions on the International Space Station

A research platform for rodent experiment on the ISS is a valuable tool for advancing biomedical research in space. Capabilities offered by the Rodent Research project developed at NASA Ames Research Center can support experiments of much longer duration on the ISS than previous experiments performed on the Space Shuttle. NASAs Rodent Research (RR)-1 mission was completed successfully and achieved a number of objectives, including validation of flight hardware, on-orbit operations, and science capabilities as well as support of a CASIS-sponsored experiment (Novartis) on muscle atrophy. Twenty C57BL6J adult female mice were launched on the Space-X (SpX) 4 Dragon vehicle, and thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all flight animals were healthy and displayed normal behavior, and higher levels of physical activity compared to ground controls. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized on-orbit and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. In general, the data obtained from the flight mice were comparable to those from the three groups of control mice (baseline, vivarium and ground controls, which were housed in flight hardware), showing that the ISS has adequate capability to support long-duration rodent experiments. The team recovered 35 tissues from 40 RR-1 frozen carcasses, yielding 3300 aliquots of tissues to distribute to the scientific community in the U.S., including NASAs GeneLab project and scientists via Space Biology's Biospecimen Sharing Program Ames Life Science Data Archive. Tissues also were distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were analyzed for transcriptomic, epigenomic and proteomic profiles; some of the data sets are now available to the scientific community through GeneLabs open science data website. A second long duration mission, Rodent Research-2 (RR-2) was completed on the ISS in 2015; 20 female C57BL6J mice were successfully maintained on the ISS for various durations, with the last group of 5 animals living on-orbit for 54 days. Furthermore, we continue to expand the ISSs capabilities by introducing new on-orbit technologies including blood collection and separation, bone densitometry scanning, muscle grip strength and anesthesia with recovery. In addition, series of ground-based verification testing to fly male mice and increase the total number of mice on-orbit from 20 to 40. Subsequent missions will provide the capability to return live mice from the ISS animals to evaluate recovery on Earth, further expanding operational and science capabilities of the RR project on the ISS.

Choi, S. Y.↗

A Novel Shape Parameterization Approach

This paper presents a novel parameterization approach for complex shapes suitable for a multidisciplinary design optimization application. The approach consists of two basic concepts: (1) parameterizing the shape perturbations rather than the geometry itself and (2) performing the shape deformation by means of the soft objects animation algorithms used in computer graphics. Because the formulation presented in this paper is independent of grid topology, we can treat computational fluid dynamics and finite element grids in a similar manner. The proposed approach is simple, compact, and efficient. Also, the analytical sensitivity derivatives are easily computed for use in a gradient-based optimization. This algorithm is suitable for low-fidelity (e.g., linear aerodynamics and equivalent laminated plate structures) and high-fidelity analysis tools (e.g., nonlinear computational fluid dynamics and detailed finite element modeling). This paper contains the implementation details of parameterizing for planform, twist, dihedral, thickness, and camber. The results are presented for a multidisciplinary design optimization application consisting of nonlinear computational fluid dynamics, detailed computational structural mechanics, performance, and a simple propulsion module.

Samareh, Jamshid A.↗

Multidisciplinary Aerodynamic-Structural Shape Optimization Using Deformation (MASSOUD)

This paper presents a multidisciplinary shape parameterization approach. The approach consists of two basic concepts: (1) parameterizing the shape perturbations rather than the geometry itself and (2) performing the shape deformation by means of the soft object animation algorithms used in computer graphics. Because the formulation presented in this paper is independent of grid topology, we can treat computational fluid dynamics and finite element grids in the same manner. The proposed approach is simple, compact, and efficient. Also, the analytical sensitivity derivatives are easily computed for use in a gradient-based optimization. This algorithm is suitable for low-fidelity (e.g., linear aerodynamics and equivalent laminate plate structures) and high-fidelity (e.g., nonlinear computational fluid dynamics and detailed finite element modeling) analysis tools. This paper contains the implementation details of parameterizing for planform, twist, dihedral, thickness, camber, and free-form surface. Results are presented for a multidisciplinary application consisting of nonlinear computational fluid dynamics, detailed computational structural mechanics, and a simple performance module.

Samareh, Jamshid A.↗

Multidisciplinary Aerodynamic-Structural Shape Optimization Using Deformation (MASSOUD)

This paper presents a multidisciplinary shape parameterization approach. The approach consists of two basic concepts: (1) parameterizing the shape perturbations rather than the geometry itself and (2) performing the shape deformation by means of the soft object animation algorithms used in computer graphics. Because the formulation presented in this paper is independent of grid topology, we can treat computational fluid dynamics and finite element grids in a similar manner. The proposed approach is simple, compact, and efficient. Also, the analytical sensitivity derivatives are easily computed for use in a gradient-based optimization. This algorithm is suitable for low-fidelity (e.g., linear aerodynamics and equivalent laminated plate structures) and high-fidelity (e.g., nonlinear computational fluid dynamics and detailed finite element modeling analysis tools. This paper contains the implementation details of parameterizing for planform, twist, dihedral, thickness, camber, and free-form surface. Results are presented for a multidisciplinary design optimization application consisting of nonlinear computational fluid dynamics, detailed computational structural mechanics, and a simple performance module.

Samareh, Jamshid A.↗

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. These decrements were less pronounced in the female Atg12 iKOs. Cancellous bone structure was not significantly different between iKOs and controls in both genders. Histological analysis also revealed that compared to male controls, male iKOs showed a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of proosteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

autophagy↗

New Development in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research program at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. Throughout phases of these missions, our practices, hardware and operations have evolved from tested to developed standards, and we are able to modify and customize our procedure and operations for mission specific requirements. The Rodent Research Habitat is capable of providing a living environment for animals on ISS according to standard animal welfare requirements. Using the cameras in the Habitat, the Rodent Research team has the ability to perform daily health checks on animals, and further analyze the collected videos for behavioral studies. A recent development of the Rodent Research hardware is inclusion of enrichment, to provide the animals the ability to rest and huddle. The Enrichment Hut is designed carefully for adult mice (up to 35 week old) within animal welfare, engineering, and operations constraints. The Hut is made out of the same stainless steel mesh as the cage interior, it has an ingress and an egress to allow animals move freely, and a hinge door to allow crewmembers remove the animals easily. The Rodent Research team has also developed Live Animal Return (LAR) capability, which will be implemented during Rodent Research-5 mission for the first time. The animals will be transported from the Habitat to a Transporter, which will return on the Dragon capsule and splashes down in the Pacific Ocean. Once SpaceX retrieves the Dragon, all powered payloads will be transferred to a SeaVan and transferred to the Long Beach pier. The NASA team then receives the transporter and delivers to a PI-designated laboratory within 120 mile radius of Long Beach. This is a significant improvement allowing researchers to examine animals within 72 hrs. of reentry or to conduct recovery experiments. Together, the hardware improvements and experience that the Rodent Research team has gained working with principal investigators and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical objectives.

ISS↗

Image processing methods in two and three dimensions used to animate remotely sensed data

Image processing methods and software used to animate nonimaging remotely sensed data on cloud cover are described. Three FORTRAN programs were written in the VICAR2/TAE image processing domain to perform 3D perspective rendering, to interactively select parameters controlling the projection, and to interpolate parameter sets for animation images between key frames. Operation of the 3D programs and transferring the images to film is automated using executive control language and custom hardware to link the computer and camera.

Hussey, K. J.↗

Maiden Voyage of the Rodent Habitat on ISS: Opportunities for Investigating Molecular Mechanisms and Biomedical Consequences of Long Duration Spaceflight

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. The National Research Counsel’s Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored research. In preparation for the maiden voyage of the Rodent Habitat hardware and operations system (Rodent Research-1), and in close consultation with a Science Working Group comprised of veterinarians and experienced spaceflight investigators, we modified existing Animal Enclosure Module hardware, developed new hardware, operations, and science activities, and performed a series of ground-based verification tests. Preflight, ground based hardware tests included a simulation of SpaceX Dragon launch conditions (vibration and hypergravity) using the Transporter, and also two long-term biocompatibility tests (32 and 92 days) using the Habitat developed for long term housing on the ISS. The launch simulation test showed that adult mice housed in Transporter hardware adapted well, even if launch simulation was followed by a period of simulated weightlessness (via hind limb unloading). The biocompatibility tests demonstrated that the Habitat successfully supported animal health and also provided a useful video imaging system that enables frequent monitoring of animal health and behavior by veterinary and scientific experts on the ground, independent of ISS crew intervention. At the conclusion of all tests, mice were deemed healthy and suitable for conducting biological research. Additional preflight analyses of tissues preserved by freezing or fixation for gene expression analyses revealed that spleen and liver tissues recovered under conditions that simulated on-orbit activities yielded high quality RNA (RIN values 8-10) and liver enzyme activities and protein content (e.g. catalase). In addition, new methods were developed to optimize future science return by dissecting tissues post-euthanasia and storage. Various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for ~2-6 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and skeletal muscle) were of high RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrated the protocols developed for future flight experiments supported science return despite delayed preservation post-euthanasia or prolonged storage, and furthermore, that high-quality RNA samples from many different tissues can be recovered by dissection following prolonged storage of the tissue in situ at -80˚C. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 is dedicated to achieving both NASA validation and CASIS science objectives. Ground based control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis. The 10 mice for validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully on Oct 12 and 13, 2014, and the validation mice will reside on ISS for up to 30 days. In conclusion, new capability for long duration rodent research is under development, including in-flight sample collection (which avoids the complication of reentry); results obtained to date will be described. This new Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.

maiden voyage↗

Cosmos 1887 - Science overview

Twenty two groups of U.S. investigators participated in joint studies of ten male rats flown on the Cosmos 1887 biosatellite. A summary of these studies embracing skeletal muscle, bone, endocrine, neural, intestinal, metabolic, immunology, cardiac, and gonadal investigations is presented. Three general objectives of the rat experiments are outlined - verification of previous observations of the biological responses to microgravity; clarification of the effects of microgravity on both the tissues investigated and the measurements performed; and relation of biological responses to flight duration. It is concluded that the first objective is met fully and the second with a varying degree of success. The confounding effects of overshooting the designated landing site and delayed recovery of the animals largely precluded meeting the last objective. It is also noted that investigations were performed for the first time on brain and spinal cord enzymes, a neurotransmitter, transmitter receptors, hypothalamic regulatory factors, pineal metabolites, atrial granules, liver histology, and jejunal mitotic rate in spaceflight animals.

Grindeland, R. E.↗

Centrifuge Facility for the International Space Station Alpha

The Centrifuge Facility planned for the International Space Station Alpha has under-one considerable redesign over the past year, primarily because the Station is now viewed as a 10 year mission rather than a 30 year mission and because of the need to simply the design to meet budget constraints and a 2000 launch date. The basic elements of the Centrifuge Facility remain the same, i.e., a 2.5 m diameter centrifuge, a micro-g holding unit, plant and animal habitats, a glovebox and a service unit. The centrifuge will still provide the full range of artificial gravity from 0.01 a to 2 - as originally planned; however, the extractor to permit withdrawal of habitats from the centrifuge without stopping the centrifuge has been eliminated. The specimen habitats have also been simplified and are derived from other NASA programs. The Plant Research Unit being developed by the Gravitational Biology Facility will be used to house plants in the Centrifuge Facility. Although not as ambitious as the Centrifuge Facility plant habitat, it will provide much better environmental control and lighting than the current Shuttle based Plant Growth Facility. Similarly, rodents will be housed in the Advanced Animal Habitat being developed for the Shuttle program. The Centrifuge Facility and ISSA will provide the opportunity to perform repeatable, high quality science. The long duration increments available on the Station will permit multigeneration studies on both plants and animals which have not previously been possible. The Centrifuge Facility will accommodate sufficient number of specimens to permit statistically significant sampling of specimens to investigate the time course of adaptation to altered gravity environments. The centrifuge will for the first time permit investigators to use gravity itself as a tool to investigate fundamental processes, to investigate the intensity and duration of gravity to maintain normal structure and function, to separate the effects of micro-g from other 0 environmental factors and to examine artificial gravity as a potential countermeasure for the physical deconditioning observed during spaceflight.

Johnson, Catherine C.↗

Bone Loss During Spaceflight: Available Models and Counter-Measures

There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground analogs to experiments on the ISS. With regards to testing, further evaluation to determine the association between non-invasive tests and fracture during and after spaceflight needs to be performed.

Morris, Jonathan↗

The Biological Flight Research Facility

NASA Ames Research Center (ARC) is building a research facility, the Biological Flight Research Facility (BFRF), to meet the needs of life scientists to study the long-term effects of variable gravity on living systems. The facility will be housed on Space Station Freedom and is anticipated to operate for the lifetime of the station, approximately thirty years. It will allow plant and animal biologists to study the role of gravity, or its absence, at varying gravity intensities for varying periods of time and with various organisms. The principal difference between current Spacelab missions and those on Space Station Freedom, other than length of mission, will be the capability to perform on-orbit science procedures and the capability to simulate earth gravity. Initially the facility will house plants and rodents in habitats which can be maintained at microgravity or can be placed on a 2.5 meter diameter centrifuge. However, the facility is also being designed to accommodate future habitats for small primates, avian, and aquatic specimens. The centrifuge will provide 1 g for controls and will also be able to provide gravity from 0.01 to 2.0 g for threshold gravity studies as well as hypergravity studies. Included in the facility are a service unit for providing clean chambers for the specimens and a glovebox for manipulating the plant and animal specimens and for performing experimental protocols. The BFRF will provide the means to conduct basic experiments to gain an understanding of the effects of microgravity on the structure and function of plants and animals, as well as investigate the role of gravity as a potential countermeasure for the physiological changes observed in microgravity.

Johnson, Catherine C.↗

The Impact of Pictorial Display on Operator Learning and Performance

The effects of pictorially displayed information on human learning and performance of a simple control task were investigated. The controlled system was a harmonic oscillator and the system response was displayed to subjects as either an animated pendulum or a horizontally moving dot. Results indicated that the pendulum display did not effect performance scores but did significantly effect the learning processes of individual operators. The subjects with the pendulum display demonstrated more vertical internal models early in the experiment and the manner in which their internal models were tuned with practice showed increased variability between subjects.

Miller, R. A.↗

Spacelab Life Sciences 1 results

Results are presented from the experiments conducted by the first Shuttle/Spacelab mission dedicated entirely to the life sciences, the Spacelab Life Sciences 1, launched on June 5, 1991. The experiments carried out during the 9-day flight included investigations of changes in the human cardiovascular, pulmonary, renal/endocrine, blood, and vestibular systems that were brought about by microgravity. Results were also obtained from the preflight and postflight complementary experiments performed on rats, which assessed the suitability of rodents as animal models for humans. Most results verified, or expanded on, the accepted theories of adaptation to zero gravity.

Seddon, Rhea↗

Environmental Variation and Cohort Effects in an Antarctic Predator

Understanding the potential influence of environmental variation experienced by animals during early stages of development on their subsequent demographic performance can contribute to our understanding of population processes and aid in predicting impacts of global climate change on ecosystem functioning. Using data from 4,178 tagged female Weddell seal pups born into 20 different cohorts, and 30 years of observations of the tagged seals, we evaluated the hypothesis that environmental conditions experienced by young seals, either indirectly through maternal effects and/or directly during the initial period of juvenile nutritional independence, have long-term effects on individual demographic performance. We documented an approximately 3-fold difference in the proportion of each cohort that returned to the pupping colonies and produced a pup within the first 10 years after birth. We found only weak evidence for a correlation between annual environmental conditions during the juvenile-independence period and cohort recruitment probability. Instead, the data strongly supported an association between cohort recruitment probability and the regional extent of sea ice experienced by the mother during the winter the pup was in utero. We suggest that inter-annual variation in winter sea-ice extent influences the foraging success of pregnant seals by moderating the regional abundance of competing predators that cannot occupy areas of consolidated sea ice, and by directly influencing the abundance of mid-trophic prey species that are sea-ice obligates. We hypothesize that this environmentally-induced variation in maternal nutrition dictates the extent of maternal energetic investment in offspring, resulting in cohort variation in mean size of pups at weaning which, in turn, contributes to an individual?s phenotype and its ultimate fitness. These linkages between sea ice and trophic dynamics, combined with demonstrated and predicted changes in the duration and extent of sea ice associated with climate change, suggest significant alterations in Antarctic marine ecosystems in the future.

Garrott, Robert A.↗