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NASA NTRS2010

Resilience of Alaska's Boreal Forest to Climatic Change

This paper assesses the resilience of Alaska s boreal forest system to rapid climatic change. Recent warming is associated with reduced growth of dominant tree species, plant disease and insect outbreaks, warming and thawing of permafrost, drying of lakes, increased wildfire extent, increased postfire recruitment of deciduous trees, and reduced safety of hunters traveling on river ice. These changes have modified key structural features, feedbacks, and interactions in the boreal forest, including reduced effects of upland permafrost on regional hydrology, expansion of boreal forest into tundra, and amplification of climate warming because of reduced albedo (shorter winter season) and carbon release from wildfires. Other temperature-sensitive processes for which no trends have been detected include composition of plant and microbial communities, long-term landscape-scale change in carbon stocks, stream discharge, mammalian population dynamics, and river access and subsistence opportunities for rural indigenous communities. Projections of continued warming suggest that Alaska s boreal forest will undergo significant functional and structural changes within the next few decades that are unprecedented in the last 6000 years. The impact of these social ecological changes will depend in part on the extent of landscape reorganization between uplands and lowlands and on policies regulating subsistence opportunities for rural communities.

Chapin, F. S., III↗
NASA NTRS2011

Crowdsourcing for Challenging Technical Problems - It Works!

The NASA Johnson Space Center Space Life Sciences Directorate (SLSD) and Wyle Integrated Science and Engineering (Wyle) will conduct a one-day business cluster at the 62nd IAC so that IAC attendees will understand the benefits of open innovation (crowdsourcing), review successful results of conducting technical challenges in various open innovation projects, and learn how an organization can effectively deploy these new problem solving tools to innovate more efficiently and effectively. Results from both the SLSD open innovation pilot program and the open innovation workshop conducted by the NASA Human Health and Performance Center will be discussed. NHHPC members will be recruited to participate in the business cluster (see membership http://nhhpc.nasa.gov) and as IAF members. Crowdsourcing may be defined as the act of outsourcing tasks that are traditionally performed by an employee or contractor to an undefined, generally large group of people or community (a crowd) in the form of an open call. The open call may be issued by the organization wishing to find a solution to a particular problem or complete a task, or by an open innovation service provider on behalf of that organization. In 2008, the SLSD, with the support of Wyle, established and implemented pilot projects in open innovation (crowdsourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical challenges. These unsolved technical problems were converted to problem statements, called Challenges by some open innovation service providers, and were then posted externally to seek solutions to these problems. In addition, an open call was issued internally to NASA employees Agency wide (11 Field Centers and NASA HQ) using an open innovation service provider crowdsourcing platform to post NASA challenges from each Center for the others to propose solutions). From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external problems or challenges were posted through three different vendors: InnoCentive, yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive crowdsourcing platform designed for use internal to an organization and customized for NASA use, and promoted as NASA@Work. The results were significant. Of the seven InnoCentive external challenges, two full and five partial awards were made in complex technical areas such as predicting solar flares and long-duration food packaging.

Davis, Jeffrey R.↗
NASA NTRS2011

Extreme Tele-Echocardiography: Methodology for Remote Guidance of In-flight Echocardiography Aboard the International Space Station

Echocardiography is ideally suited for cardiovascular imaging in remote environments, but the expertise to perform it is often lacking. In 2001, an ATL HDI5000 was delivered to the International Space Station (ISS). The instrument is currently being used in a study to investigate the impact of long-term microgravity on cardiovascular function. The purpose of this report is to describe the methodology for remote guidance of echocardiography in space. Methods: In the year before launch of an ISS mission, potential astronaut echocardiographic operators participate in 5 sessions to train for echo acquisitions that occur roughly monthly during the mission, including one exercise echocardiogram. The focus of training is familiarity with the study protocol and remote guidance procedures. On-orbit, real-time guidance of in-flight acquisitions is provided by a sonographer in the Telescience Center of Mission Control. Physician investigators with remote access are able to relay comments on image optimization to the sonographer. Live video feed is relayed from the ISS to the ground via the Tracking and Data Relay Satellite System with a 2 second transmission delay. The expert sonographer uses these images along with two-way audio to provide instructions and feedback. Images are stored in non-compressed DICOM format for asynchronous relay to the ground for subsequent off-line analysis. Results: Since June, 2009, a total of 19 resting echocardiograms and 4 exercise studies have been performed in-flight. Average acquisition time has been 45 minutes, reflecting 26,000 km of ISS travel per study. Image quality has been adequate in all studies, but remote guidance has proven imperative for fine-tuning imaging and prioritizing views when communication outages limit the study duration. Typical resting studies have included 12 video loops and 21 still-frame images requiring 750 MB of storage. Conclusions: Despite limited crew training, remote guidance allows research-quality echocardiography to be performed by non-experts aboard the ISS. Analysis is underway and additional subjects are being recruited to define the impact of microgravity on cardiac structure and systolic and diastolic function.

Martin, David↗
NASA NTRS2011

Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there is still high variability in individual response. Three additional crewmembers have been recruited to participate in this experiment, with expected completion in late 2011.

LeBlanc, Adrian↗
NASA NTRS2011

Teaching the Next Generation of Scientists and Engineers the NASA Design Process

The Integrated Product Team (IPT) program, led by The University of Alabama in Huntsville (UAH), is a multidisciplinary, multi-university, multi-level program whose goal is to provide opportunities for high school and undergraduate scientists and engineers to translate stakeholder needs and requirements into viable engineering design solutions via a distributed multidisciplinary team environment. The current program supports three projects. The core of the program is the two-semester senior design experience where science, engineering, and liberal arts undergraduate students from UAH, the College of Charleston, Southern University at Baton Rouge, and Ecole Suprieure des Techniques Aronautiques et de Construction Automobile (ESTACA) in Paris, France form multidisciplinary competitive teams to develop system concepts of interest to the local aerospace community. External review boards form to provide guidance and feedback throughout the semester and to ultimately choose a winner from the competing teams. The other two projects, the Innovative Student Project for the Increased Recruitment of Engineering and Science Students (InSPIRESS) Level I and Level II focus exclusively on high school students. InSPIRESS Level I allows high schools to develop a payload to be accommodated on the system being developed by senior design experience teams. InSPIRESS Level II provides local high school students first-hand experience in the senior design experience by allowing them to develop a subsystem or component of the UAH-led system over the two semesters. This program provides a model for NASA centers to engage the local community to become more involved in design projects.

Caruso, Pamela W.↗
NASA NTRS2011

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the majority of RPA-coated ssDNA is generally present only during DNA replication, ATR activation in G1 and G2-phase might still require formation of RPA-coated ssDNA, probably initiated by the MRN-CtIP complex and then extended by the Exo1- or BLM-dependent mechanisms at the sites of DSBs. Evidence accumulates that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated at the break sites by processes mentioned above and these stretches of single stranded overhangs hold the clue for ATM to ATR switch at broken DNA ends. We irradiated 82-6hTERT human fibroblast cells with low LET gamma-rays and high LET Fe and Si particles. Preliminary results with cells exposed to 1Gy gamma-rays show that the kinetics of pChk2-pT68 foci formation is comparable to that of gamma-H2AX although they appear to recede quicker. The number and intensity of observed foci reaches a maximum at 30 min and 60 min post IR for Chk2-pT68 and gamma-H2AX foci respectively and all Chk2-pT68 foci colocalize with gamma-H2AX foci. The kinetics of Chk1-pS345 and ATRIP are being determined. Results of Chk2-pT68 foci kinetics was also corroborated by western blot experiments, although phosphorylation was detected as early as 10 min and started receding 30 min post IR with 2Gy of gamma-rays. On the other hand, level of ATR-pS428 reached its maximum between 60 and 120 min and was maintained until the last measured time point of 4 hours post IR as determined by western blotting. Experiments performed with high LET Fe and Si particles will be reported.

Saha, Janapriya↗
NASA NTRS2011

Deployment of an Advanced Electrocardiographic Analysis (A-ECG) to Detect Cardiovascular Risk in Career Firefighters

INTRODUCTION Sudden cardiac death is the leading cause of line of duty death among firefighters, accounting for approximately 45% of fatalities annually. Firefighters perform strenuous muscular work while wearing heavy, encapsulating personal protective equipment in high ambient temperatures, under chaotic and emotionally stressful conditions. These factors can precipitate sudden cardiac events like myocardial infarction, serious dysrhythmias, or cerebrovascular accidents in firefighters with underlying cardiovascular disease. Screening for cardiovascular risk factors is recommended but not always followed in this population. PHASER is a project charged with identifying and prioritizing risk factors in emergency responders. We have deployed an advanced ECG (A-ECG) system developed at NASA for improved sensitivity and specificity in the detection of cardiac risk. METHODS Forty-four professional firefighters were recruited to perform comprehensive baseline assessments including tests of aerobic performance and laboratory tests for fasting lipid profiles and glucose. Heart rate and conventional 12-lead ECG were obtained at rest and during incremental treadmill exercise testing (XT). In addition, a 5-min resting 12-lead A-ECG was obtained in a subset of firefighters (n=18) and transmitted over a secure networked system to a physician collaborator at NASA for advanced-ECG analysis. This A-ECG system has been proven, using myocardial perfusion and other imaging, to accurately identify a number of cardiac pathologies including coronary artery disease (CAD), left ventricular hypertrophy, hypertrophic cardiomyopathy, non-ischemic cardiomyopathy, and ischemic cardiomyopathy. RESULTS Subjects mean (SD) age was 43 (8) years, weight 91 (13) kg, and BMI of 28 (3) kg/square meter. Maximum oxygen uptake (VO2max) was 39 (9) ml/kg/min. This compares with the 45th %ile in healthy reference values and a recommended standard of 42 ml/kg/min for firefighters. The metabolic threshold (VO2Theta) above which lactate accumulates was 23 (8) ml/kg/min. The chronotropic index, a measure of cardiovascular strain during XT was 35 (8) /L compared with reference values for men of 40 /L. Total cholesterol, LDL-C and HDL-C were 202 (34),126 (29), and 55 (15) mg/dl, respectively. Fifty-one percent of subjects had .3 cardiovascular risk factors, 2 subjects had resting hypertension (BP.140/90), and 23 had pre-hypertension (.120/80 but <140/90). Seven had exaggerated exercise induced hypertension but only one had ST depression on XT ECG, at least one positive A-ECG score for CAD, and documented CAD based on cardiology referral. While all other subjects, including those with fewer risk factors, higher aerobic fitness, and normal exercise ECGs, were classified as healthy by A-ECG, there was no trend for association between risk factors and any of 20 A-ECG parameters in the grouped data. CONCLUSIONS A-ECG screening correctly identified the individual with CAD although there was no trend for A-ECG parameters to distinguish those with elevated BP or multiple risk factors but normal XT ECG. We have demonstrated that a new technology, advanced-ECG, can be introduced for remote firefighter risk assessment. This simple, time and cost-effective approach to risk identification that can be acquired remotely and transmitted securely can detect individuals potentially at risk for line-of-duty death. Additional research is needed to further document its value.

Dolezal, B. A.↗
NASA NTRS2011

Deployment of an Advanced Electrocardiographic Analysis (A-ECG) to Detect Cardiovascular Risk in Career Firefighters

INTRODUCTION: Sudden cardiac death is the leading cause of line of duty death among firefighters, accounting for approximately 45% of fatalities annually. Firefighters perform strenuous muscular work while wearing heavy, encapsulating personal protective equipment in high ambient temperatures, under chaotic and emotionally stressful conditions. These factors can precipitate sudden cardiac events like myocardial infarction, serious dysrhythmias, or cerebrovascular accidents in firefighters with underlying cardiovascular disease. PURPOSE: The purpose of this study was to deploy and then evaluate the contribution of resting advanced ECG (A-ECG) in addition to other screening tools (family history, lipid profiles, and cardiopulmonary exercise tests, XT) in assessment of an individual fs cardiac risk profile. METHODS: Forty-four career firefighters were recruited to perform comprehensive baseline assessments including tests of aerobic performance, fasting lipids and glucose. Five-min resting 12-lead A-ECGs were obtained in a subset of firefighters (n=21) and transmitted over a secure networked system to a NASA physician collaborator. Using myocardial perfusion and other imaging as the gold standard, A-ECG scoring has been proven useful in accurately identifying a number of cardiac pathologies including coronary artery disease (CAD), left ventricular hypertrophy, hypertrophic cardiomyopathy, and non-ischemic and ischemic cardiomyopathy. RESULTS: Subjects f mean (SD) age was 43 (8) years, weight 91 (13) kg, and BMI 28 (3) kg/m2. Fifty-one percent of subjects had .3 cardiovascular risk factors. One subject had ST depression on XT ECG, at least one positive A-ECG score for CAD, and documented CAD based on cardiology referral. While all other subjects, including those with fewer risk factors, higher aerobic fitness, and normal exercise ECGs, were classified as healthy by A-ECG, there was no trend for association between risk factors and any of 20 A-ECG parameters in the grouped data.

Dolezal, B. A.↗
NASA NTRS2011

Optimizing Muscle Parameters in Musculoskeletal Modeling Using Monte Carlo Simulations

Astronauts assigned to long-duration missions experience bone and muscle atrophy in the lower limbs. The use of musculoskeletal simulation software has become a useful tool for modeling joint and muscle forces during human activity in reduced gravity as access to direct experimentation is limited. Knowledge of muscle and joint loads can better inform the design of exercise protocols and exercise countermeasure equipment. In this study, the LifeModeler(TM) (San Clemente, CA) biomechanics simulation software was used to model a squat exercise. The initial model using default parameters yielded physiologically reasonable hip-joint forces. However, no activation was predicted in some large muscles such as rectus femoris, which have been shown to be active in 1-g performance of the activity. Parametric testing was conducted using Monte Carlo methods and combinatorial reduction to find a muscle parameter set that more closely matched physiologically observed activation patterns during the squat exercise. Peak hip joint force using the default parameters was 2.96 times body weight (BW) and increased to 3.21 BW in an optimized, feature-selected test case. The rectus femoris was predicted to peak at 60.1% activation following muscle recruitment optimization, compared to 19.2% activation with default parameters. These results indicate the critical role that muscle parameters play in joint force estimation and the need for exploration of the solution space to achieve physiologically realistic muscle activation.

Hanson, Andrea↗
NASA NTRS2011

NASA, Building Tomorrow's Future

We, as NASA, continue to Dare Mighty Things. Here we are in October. In my country, the United States of America, we celebrate the anniversary of Christopher Columbus's arrival in the Americas, which occurred on October 12, 1492. His story, although happening over 500 years ago, is still very valid today. It is a part of the American spirit; part of the international human spirit. Columbus is famous for discovering the new world we now call America, but he probably never envisioned what great discoveries would be revealed many generations later. But in order for Columbus to begin his great adventure, he needed a business plan. Ho~ would he go about obtaining the funds and support necessary to build, supply, and man the ships required for his travels? He had a lot of obstacles and distractions. He needed a strong, internal drive to achieve his plans and recruit a willing crew of explorers also ready to risk their all for the unknown journey ahead. As Columbus set sail, he said "By prevailing over all obstacles and distractions, one may unfailingly arrive at his chosen goal or destination." Columbus may not have known he was on a journey for all human exploration. Recently, Charlie Bolden, the NASA Administrator, said, "Human exploration is and has always been about making life better for humans on Earth." Today, NASA and the U.S. human spaceflight program hold many of the same attributes as did Columbus and his contemporaries - a willing, can-do spirit. We are on the threshold of exciting new times in space exploration. Like Columbus, we need a business plan to take us into the future. We need to design the best ships and utilize the best designers, with their past knowledge and experience, to build those ships. We need funding and support from governments to achieve these goals of space exploration into the unknown. NASA does have that business plan, and it is an ambitious plan for human spaceflight and exploration. Today, we have a magnificent spaceflight laboratory, built over many years by the United States and other nations. Last month, the last man to step off the moon, Gene Cernan, told the U.S. Congress, "Today the International Space Station, the assembly of which may well go down in history as man's greatest engineering accomplishment of all time, circles the globe sixteen times every day - all in keeping with JFK's challenge to do the other things." The International Space Station (ISS) is a ship which provides an outstanding platform 'for performing spaceborne scientific, engineering, and Earth studies. Numerous nations utilize this unique cooperative partnership by sending scientists, engineers, astronauts, and cosmonauts to the ISS to spend time aboard the station in order to further scientific research, truly an asset for the entire planet.

Mango, Edward↗
NASA NTRS2005

The Influence of Ecological Isolation on the Structural and Functional Stability of Complex Microbial Communities

To help understand how the behavior of microorganisms and microbial communities in insular space habitats may differ from the behavior of these groups on Earth, long-term incubations (100+ days) were conducting using wastewater bioreactors (batch fed) designed to mimic "closed" and "open" ecological systems. The issue of immigration was considered, and the goal of the research was to determine whether the stability of microbial communities in space is reduced due to their prolonged isolation. Bioreactors were established by inoculating flasks of sterile synthetic wastewater with the microbial community obtained from a local treatment facility; each day, one-third of the medium in the flask was replaced with an equal volume of sterile artificial wastewater. Flasks were divided into two treatments: "closed" and "open" to recruitment of additional microorganisms. "Closed" flasks were maintained as described above, while the medium used to feed the "open" flasks was supplemented daily with a small amount of raw sewage (which provided a continuous source of new potential community members). Significant differences in microbial community structure and function developed in the two sets of communities, and the results suggest that the open community was more stable and better able to adjust to changing environmental conditions. Each community's resistance to environmental (temperature fluctuations) and biological stresses (starvation and invasion by an opportunistic pathogen Pseudomonas aeruginosa) was monitored. Experiments were also conducted to determine whether the effect of isolation changes depending on the microbial communities' initial diversity or composition; communities with a low(er) initial diversity were less stable. Overall, the results indicate that isolation will be an important factor influencing the activity of microbial communities on board spacecraft. A possible way of mitigating these effects would be to include communities with high initial diversity or to periodically re-inoculate the systems using diverse inocula transported from Earth.

Franklin, R. B.↗
NASA NTRS2012

Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.

Deatly, Anne M.↗
NASA NTRS2012

System Engineering Paper

The Iowa State University team, Team LunaCY, is composed of the following sub-teams: the main student organization, the Lunabotics Club; a senior mechanical engineering design course, ME 415; a senior multidisciplinary design course, ENGR 466; and a senior design course from Wartburg College in Waverly, Iowa. Team LunaCY designed and fabricated ART-E III, Astra Robotic Tractor- Excavator the Third, for the team's third appearance in the NASA Lunabotic Mining competition. While designing ART-E III, the team had four main goals for this year's competition:to reduce the total weight of the robot, to increase the amount of regolith simulant mined, to reduce dust, and to make ART-E III autonomous. After many designs and research, a final robot design was chosen that obtained all four goals of Team LunaCY. A few changes Team LunaCY made this year was to go to the electrical, computer, and software engineering club fest at Iowa State University to recruit engineering students to accomplish the task of making ART-E III autonomous. Team LunaCY chose to use LabView to program the robot and various sensors were installed to measure the distance between the robot and the surroundings to allow ART-E III to maneuver autonomously. Team LunaCY also built a testing arena to test prototypes and ART-E III in. To best replicate the competition arena at the Kennedy Space Center, a regolith simulant was made from sand, QuickCrete, and fly ash to cover the floor of the arena. Team LunaCY also installed fans to allow ventilation in the arena and used proper safety attire when working in the arena . With the additional practice in the testing arena and innovative robot design, Team LunaCY expects to make a strong appearance at the 2012 NASA Lunabotic Mining Competition. .

Heise, James↗
NASA NTRS2012

Extreme Tele-Echocardiography: Methodology for Remote Guidance of In-Flight Echocardiography Aboard the International Space Station

Methods: In the year before launch of an ISS mission, potential astronaut echocardiographic operators participate in 5 sessions to train for echo acquisitions that occur roughly monthly during the mission, including one exercise echocardiogram. The focus of training is familiarity with the study protocol and remote guidance procedures. On-orbit, real-time guidance of in-flight acquisitions is provided by a sonographer in the Telescience Center of Mission Control. Physician investigators with remote access are able to relay comments on image quality to the sonographer. Live video feed is relayed from the ISS to the ground via the Tracking and Data Relay Satellite System with a 2- second transmission delay. The expert sonographer uses these images, along with twoway audio, to provide instructions and feedback. Images are stored in non-compressed DICOM format for asynchronous relay to the ground for subsequent off-line analysis. Results: Since June, 2009, a total of 27 resting echocardiograms and 5 exercise studies have been performed during flight. Average acquisition time has been 45 minutes, reflecting 26,000 km of ISS travel per study. Image quality has been adequate in all studies, and remote guidance has proven imperative for fine-tuning imaging and prioritizing views when communication outages limit the study duration. Typical resting studies have included 27 video loops and 30 still-frame images requiring 750 MB of storage. Conclusions: Despite limited crew training, remote guidance allows research-quality echocardiography to be performed by non-experts aboard the ISS. Analysis is underway and additional subjects are being recruited to define the impact of microgravity on cardiac structure and systolic and diastolic function.

Martin, David S.↗
NASA NTRS2012

Virtual Guidance Ultrasound: A Tool to Obtain Diagnostic Ultrasound for Remote Environments

Astronauts currently acquire ultrasound images on the International Space Station with the assistance of real-time remote guidance from an ultrasound expert in Mission Control. Remote guidance will not be feasible when significant communication delays exist during exploration missions beyond low-Earth orbit. For example, there may be as much as a 20- minute delay in communications between the Earth and Mars. Virtual-guidance, a pre-recorded audio-visual tutorial viewed in real-time, is a viable modality for minimally trained scanners to obtain diagnostically-adequate images of clinically relevant anatomical structures in an autonomous manner. METHODS: Inexperienced ultrasound operators were recruited to perform carotid artery (n = 10) and ophthalmic (n = 9) ultrasound examinations using virtual guidance as their only instructional tool. In the carotid group, each each untrained operator acquired two-dimensional, pulsed, and color Doppler of the carotid artery. In the ophthalmic group, operators acquired representative images of the anterior chamber of the eye, retina, optic nerve, and nerve sheath. Ultrasound image quality was evaluated by independent imaging experts. RESULTS: Eight of the 10 carotid studies were judged to be diagnostically adequate. With one exception the quality of all the ophthalmic images were adequate to excellent. CONCLUSION: Diagnostically-adequate carotid and ophthalmic ultrasound examinations can be obtained by untrained operators with instruction only from an audio/video tutorial viewed in real time while scanning. This form of quick-response-guidance, can be developed for other ultrasound examinations, represents an opportunity to acquire important medical and scientific information for NASA flight surgeons and researchers when trained medical personnel are not present. Further, virtual guidance will allow untrained personnel to autonomously obtain important medical information in remote locations on Earth where communication is difficult or absent.

Caine,Timothy L.↗
NASA NTRS2012

Pulmonary Toxicity Studies of Lunar Dust in Rodents

NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological changes, a similar study was conducted to microscopically examine rat lung tissue and the associated lymph nodes for lesions, including fibrosis, 1 or 3 months after the instillation. The results from this ITI study led us to select two concentrations (20 and 60 mg/cu m) for an inhalation study, in which rats were exposed to lunar dust 6 h daily for 4 weeks (5d/wk). Similar biochemical and histopathological assessments were carried out in these rats 1 day or 1, 4, or 13 weeks after the dust exposure. Rats exposed to lunar dust by ITI or inhalation showed effects indicating that the dust is moderately toxic. The data will be useful to establish safe exposure limits for astronauts working in a lunar habitat and also help engineers designing dust mitigation systems for lunar vehicles and habitats.

Lam, Chiu-Wing↗
NASA NTRS2012

Varying Levels of Automation on UAS Operator Responses to Traffic Resolution Advisories in Civil Airspace

Continuing demand for the use of Unmanned Aircraft Systems (UAS) has put increasing pressure on operations in civil airspace. The need to fly UAS in the National Airspace System (NAS) in order to perform missions vital to national security and defense, emergency management, and science is increasing at a rapid pace. In order to ensure safe operations in the NAS, operators of unmanned aircraft, like those of manned aircraft, may be required to maintain separation assurance and avoid loss of separation with other aircraft while performing their mission tasks. This experiment investigated the effects of varying levels of automation on UAS operator performance and workload while responding to conflict resolution instructions provided by the Tactical Collision Avoidance System II (TCAS II) during a UAS mission in high-density airspace. The purpose of this study was not to investigate the safety of using TCAS II on UAS, but rather to examine the effect of automation on the ability of operators to respond to traffic collision alerts. Six licensed pilots were recruited to act as UAS operators for this study. Operators were instructed to follow a specified mission flight path, while maintaining radio contact with Air Traffic Control and responding to TCAS II resolution advisories. Operators flew four, 45 minute, experimental missions with four different levels of automation: Manual, Knobs, Management by Exception, and Fully Automated. All missions included TCAS II Resolution Advisories (RAs) that required operator attention and rerouting. Operator compliance and reaction time to RAs was measured, and post-run NASA-TLX ratings were collected to measure workload. Results showed significantly higher compliance rates, faster responses to TCAS II alerts, as well as less preemptive operator actions when higher levels of automation are implemented. Physical and Temporal ratings of workload were significantly higher in the Manual condition than in the Management by Exception and Fully Automated conditions.

Kenny, Caitlin↗
NASA NTRS2013

Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

Background: Aspects of immune system dysregulation associated with long‐duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long‐duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3‐5 times during flight (depending on mission duration), at landing and 30 days post‐landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (<10 pg/ml) were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines, however IL‐1ra and several chemokines were constitutively present. An increase in the plasma concentration IL‐8, IL‐1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM‐CSF and VEGF was observed associated with spaceflight. Significant post‐flight increases were observed for IL‐6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T‐regulatory cytokines (IL‐2, IFN(gamma), IL‐17, IL4, IL‐5, IL‐10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

Crician, Brian E.↗