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At least 1,009 records · Page 56

Terrestrial Microgravity Model and Threshold Gravity Simulation sing Magnetic Levitation

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successiblly simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Ramachandran, N.↗

Terrestrial Microgravity Model and Threshold Gravity Simulation using Magnetic Levitation

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars. The paper will discuss experiments md modeling work to date in support of this project.

Ramachandran, N.↗

Threshold Gravity Determination and Artificial Gravity Studies Using Magnetic Levitation

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required (magnitude and duration)? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for a variable gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Ramachandran, N.↗

Onboard Radar Processor Development for Disaster Response

Natural hazards often result in significant loss of human lives, economic assets and productivity as well as significant damage to the ecosystem. Scientists have reported more frequent and intense natural disasters in recent years, which may well be attributed to climate change. Many of the disaster response efforts were hampered by lack of up-to-date knowledge of the state of the affected areas because damaged infrastructure rendered the areas inaccessible. Radar remote sensing is playing an increasingly critical role in providing timely information to disaster response agencies due to the increasing fidelity and availability of geospatial information products.

VV (vertical transmit and vertical receive)↗

NASA seat experiment and occupant responses

Results of the crash test of a remotely piloted transport aircraft instrumented to measure a NASA energy-absorbing transport seat are given. Human tolerance limits to acceleration and a dynamic response index model are discussed. It was found that the acceleration levels at the rear of the airplane were quite low and were below the stroking threshold of the NASA EA-seat. Therefore, dummies in the standard and EA-seat responded approximately the same. All longitudinal accelerations were quite low for the primary impact with very low forces measured in the lap belts. The vertical (spineward) acceleration levels measured in the dummies were also relatively low and very survivable from an impact tolerance standpoint. The pilot with an 18 G peak acceleration received by far the highest vertical acceleration and could have possibly received slight spinal injury.

Fasanella, E. L.↗

Duration versus response to space-flight exposure

The duration of human expeditions into space has been as short as a few hours and as long as a year, and although we still need much more information, we can identify some trends indicating effects of flight duration on the physiologic response to space flight. Evidence suggests that after a period of dynamic change that varies for each physiologic system, some physiologic variable stabilize at levels that may differ from those at 1 G. Other variables appear to undergo change from time to time even after months in space, and others have not been observed to reach a plateau. Effects on the neurovestibular system begin very early and certain ones diminish rapidly. Effects of weightlessness on fluid and electrolyte physiology appear to reach a peak after that of neurophysiologic effects. It is possible that the initial responses of these two systems follow a more similar time course than is now apparent. Responses of the cardiovascular system reach a peak that approaches clinical significance after about 3 weeks. The mass of red blood cells is maximally altered after about a month. Bone mineral and lean body mass are lost gradually for at least 6 months, perhaps longer.

Leach, Carolyn S.↗

Pros and Cons of Using Water Immersion to Simulate Physiological Responses to Microgravity

Head-out water immersion (HOI) has been employed as a remedial treatment for various ills and ailments for many millennia, and total body immersion even longer as protective encapsulation for the mammalian fetus. Two discrete differences between stimuli induced by true microgravity (10(exp -4) g) and HOI are readily apparent. External water pressure on the skin and accompanying negative pressure breathing cause blood to shift headward. Secondly, the gravitational force is ever present during immersion and microgravity, but its effect is essentially neutralized during Earth orbital flight. Thus, the physiological responses to immersion should not be expected to match those during microgravity. Immersion has been used mainly to study and understand kidney function and associated cardiovascular responses for control of body fluid volume and osmotic content, with some application to and simulation of microgravity responses. There is a plethora of data from human HOI studies, but relatively few controlled data from microgravity studies. In general, it appears that physiological responses occur more quickly with water immersion than in microgravity, but this may be due to less rigorous control (voluntary and involuntary) of the preflight state of crew members. The central venous pressure-vasopressin (Gauer-Henry) reflex control for fluid balance may not be of prime importance in microgravity. Gross functions such as reduced body weight and water, level of hypovolemia, decreased isokinetic strength, and lower nitrogen balance found during immersion are qualitatively similar in microgravity, but the mechanisms controlling these and other functions are, for the most part, unclear. Only acquisition of data from well-controlled microgravity experiments will resolve this discrepancy.

Greenleaf, J. E.↗

Age-related changes in human vestibulo-ocular and optokinetic reflexes: Pseudorandom rotation tests

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR and OKR reflex dynamics, and to identify the distributions of parameters which describe VOR and OKR responses to pseudorandom stimuli in a putatively normal population. In general, VOR and OKR response parameters changed in a manner consistent with declining function with increasing age. For the VOR this was reflected in declining response amplitudes, although the magnitude of the decline was small relative to the variability of the data. For the OKR the lag time of the response, probably associated with the time required for visual information processing, increased linearly with age at a rate of about 1 ms per year.

Peterka, R. J.↗

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Chappelli, Lori J.↗

Quantifying Pilot Contribution to Flight Safety During an In-Flight Airspeed Failure

Accident statistics cite the flight crew as a causal factor in over 60% of large transport fatal accidents. Yet a well-trained and well-qualified crew is acknowledged as the critical center point of aircraft systems safety and an integral component of the entire commercial aviation system. A human-in-the-loop test was conducted using a Level D certified Boeing 737-800 simulator to evaluate the pilot's contribution to safety-of-flight during routine air carrier flight operations and in response to system failures. To quantify the human's contribution, crew complement was used as an independent variable in a between-subjects design. This paper details the crew's actions and responses while dealing with an in-flight airspeed failure. Accident statistics often cite flight crew error (Baker, 2001) as the primary contributor in accidents and incidents in transport category aircraft. However, the Air Line Pilots Association (2011) suggests "a well-trained and well-qualified pilot is acknowledged as the critical center point of the aircraft systems safety and an integral safety component of the entire commercial aviation system." This is generally acknowledged but cannot be verified because little or no quantitative data exists on how or how many accidents/incidents are averted by crew actions. Anecdotal evidence suggest crews handle failures on a daily basis and Aviation Safety Action Program data generally supports this assertion, even if the data is not released to the public. However without hard evidence, the contribution and means by which pilots achieve safety of flight is difficult to define. Thus, ways to improve the human ability to contribute or overcome deficiencies are ill-defined.

Etherington, Timothy J.↗

The Near Earth Asteroid Medical Conditions List

Purpose: The Exploration Medical Capability (ExMC) element is one of six elements within NASA s Human Research Program (HRP) and is responsible for addressing the risk of "the inability to adequately recognize or treat an ill or injured crewmember" for exploration-class missions. The Near Earth Asteroid (NEA) Medical Conditions List, constructed by ExMC, is the first step in addressing the above-mentioned risk for the 13-month long NEA mission. The NEA mission is being designed by NASA's Human Space Flight Architecture Team (HAT). The purpose of the conditions list is to serve as an evidence-based foundation for determining which medical conditions could affect a crewmember during the NEA mission, which of those conditions would be of concern and require treatment, and for which conditions a gap in knowledge or technology development exists. This information is used to focus research efforts and technology development to ensure that the appropriate medical capabilities are available for exploration-class missions. Scope and Approach: The NEA Medical Conditions List is part of a broader Space Medicine Exploration Medical Conditions List (SMEMCL), which incorporates various exploration-class design reference missions (DRMs). The conditions list contains 85 medical conditions which could occur during space flight and which are derived from several sources: Long-Term Surveillance of Astronaut Health (LSAH) in-flight occurrence data, The Space Shuttle (STS) Medical Checklist, The International Space Station (ISS) Medical Checklist, and subject matter expert opinion. Each medical condition listed has been assigned a clinical priority and a clinical priority rationale based on incidence, consequence, and mitigation capability. Implementation: The conditions list is a "living document" and as such, new conditions can be added to the list, and the priority of conditions on the list can be adjusted as the DRM changes, and as screening, diagnosis, or treatment capabilities change. The NEA medical conditions list was used recently as the basis for identifying gaps in in-flight medical evaluation (screening) capabilities. Learning Objectives: The audience will become familiar with the approach taken by NASA's Exploration Medical Capability element in addressing the risk of inability to recognize and treat medical conditions in the setting of a Near Earth Asteroid mission. Which one of the following statements is incorrect? a) The Near Earth Asteroid (NEA) medical conditions list includes 85 medical conditions which could occur during space flight. b) Each condition on the NEA medical conditions list has been assigned a clinical priority and a clinical priority rationale. c) The NEA medical conditions list targets a mission to Mars. d) The NEA medical conditions list should be viewed as a "living document" where new conditions can be added and clinical priorities adjusted to address changes in the design reference mission or medical capabilities. The incorrect answer is c). The NEA medical conditions list targets a mission to a Near Earth Asteroid.

Barr, Yael R.↗

Inactivation of Human Coronavirus by FATHHOME’s Dry Sanitizer Device: Rapid and Eco-Friendly Ozone-Based Disinfection of SARS-CoV-2

The pandemic of SARS-CoV-2/COVID-19 was reported in December 2019 in Wuhan, China. Pertaining to its high transmissibility and wide host adaptability, this unique human coronavirus spread across the planet inflicting 115 million people and causing 2.5 million deaths (as of March 3rd, 2021). Limited or negligible pre-existing immunity to multiple SARS-CoV-2 variants has resulted in severe morbidity and mortality worldwide, as well as a record-breaking surge in the use of medical-surgical supplies and personal protective equipment. In response to the global need for effective sterilization techniques, this study evaluated the virucidal efficacy of FATHHOME’s self-contained, ozone-based dry-sanitizing device, by dose and time response assessment. We tested inactivation of human coronavirus, HCoV-OC43, a close genetic model of SARS-CoV-2, on porous (N95 filtering facepiece respirator/FFR) and nonporous (glass) surfaces. We started our assays with 20 ppm-10 min ozone exposure, and effectively reduced 99.8% and 99.9% of virus from glass and N95 FFR surfaces, respectively. Importantly, the virus was completely inactivated, below the detection limit (over 6-log10 reduction) with 25 ppm-15 min ozone exposure on both tested surfaces. As expected, a higher ozone exposure (50 ppm-10 min) resulted in faster inactivation of HCoV-OC43 with 100% inactivation from both the surfaces, with no residual ozone present after completion of the 5-min post exposure recapture cycle and no measurable increase in ambient ozone levels. These results confirmed that FATHHOME’s device is suitable for rapid decontamination of SARS-CoV-2- from worn items, frequently touched items, and PPE including N95 FFRs, face shields, and other personal items. View Full-Text

59 BASIC BIOLOGICAL SCIENCES↗

Virtual agents in a simulated virtual training environment

A drawback to live-action training simulations is the need to gather a large group of participants in order to train a few individuals. One solution to this difficulty is the use of computer-controlled agents in a virtual training environment. This allows a human participant to be replaced by a virtual, or simulated, agent when only limited responses are needed. Each agent possesses a specified set of behaviors and is capable of limited autonomous action in response to its environment or the direction of a human trainee. The paper describes these agents in the context of a simulated hostage rescue training session, involving two human rescuers assisted by three virtual (computer-controlled) agents and opposed by three other virtual agents.

Achorn, Brett↗

A framework to implement human reliability analysis during early design stages of advanced reactors

Nuclear power plants require human actions throughout their lifecycle from design, construction, operation, and decommissioning. However, for advanced reactors (e.g., Generation IV), the reliance on human intervention in safety-related actions is expected to be reduced or completely replaced by automated actions. The Probabilistic Risk Assessment (PRA) Standard for Advanced Non-LWR Nuclear Power Plants requires that the impacts of all operator actions are captured and incorporated in the risk of the modeled plant. Moreover, the Modernization of Technical Requirements for Licensing Advanced Reactors requires human reliability analysis (HRA) to be included throughout all design and PRA development stages. However, due to the lack of details during the early design stages, HRA is often postponed until the design is mature enough. Conducting HRA in later design stages, though it may be adequate in capturing pre-, at-, and post-initiators comes short of informing the design itself in the iterative design lifecycle. Hence, this paper presents a framework to include HRA during the design's early stages, pre-conceptual or conceptual. The proposed framework provides a process for the removal of operator actions that do not contribute to the risk and the identification of all key operator actions that are critical to the safety of the design. The results of this framework are then used to inform the design of those safety-related operator actions to update the design further. Then, using information from the updated design, this framework can be reapplied to investigate the impact of the design update on human reliability. The PRA model of the X-energy's pre-conceptual Xe-100 high-temperature gas-cooled pebble-bed reactor (HTGR-PB) design is used to demonstrate the approach. In the pre-conceptual Xe-100 PRA model, also called Phase 0 PRA model, human actions were considered an integral part of analyzing the plant response to different initiating events. Hence, in this paper, all possible human actions in the Xe-100 PRA model are identified, analyzed, and removed to emulate a design relying only on the available automated control systems. The preliminary results of this assessment show how safe the Xe-100 design is even without crediting any human actions. The results also list necessary sequences in which operator actions are critical to the risk profile of the design.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Glucose-dependent insulinotropic peptide stimulates thymidine incorporation in endothelial cells: role of endothelin-1

We have previously characterized the receptor for glucose-dependent insulinotropic polypeptide (GIPR) in vascular endothelial cells (EC). Different EC types were found to contain distinct GIPR splice variants. To determine whether activation of the GIPR splice variants resulted in different cellular responses, we examined GIP effects on human umbilical vein endothelial cells (HUVEC), which contain two GIPR splice variants, and compared them with a spontaneously transformed human umbilical vein EC line, ECV 304, which contains four GIPR splice variants. GIP dose-dependently stimulated HUVEC and ECV 304 proliferation as measured by [3H]thymidine incorporation. GIP increased endothelin-1 (ET-1) secretion from HUVEC but not from ECV 304. Use of the endothelin B receptor blocker BQ-788 resulted in an inhibition of [3H]thymidine incorporation in HUVEC but not in ECV 304. These findings suggest that, although GIP increases [3H]thymidine incorporation in both HUVEC and ECV 304, this proliferative response is mediated by ET-1 only in HUVEC. These differences in cellular response to GIP may be related to differences in activation of GIPR splice variants.

NASA Discipline Clinical Medicine↗

Zika virus dynamics: Effects of inoculum dose, the innate immune response and viral interference

Experimental Zika virus infection in non-human primates results in acute viral load dynamics that can be well-described by mathematical models. The inoculum dose that would be received in a natural infection setting is likely lower than the experimental infections and how this difference affects the viral dynamics and immune response is unclear. Here we study a dataset of experimental infection of non-human primates with a range of doses of Zika virus. We develop new models of infection incorporating both an innate immune response and viral interference with that response. We find that such a model explains the data better than models with no interaction between virus and the immune response. We also find that larger inoculum doses lead to faster dynamics of infection, but approximately the same total amount of viral production.

59 BASIC BIOLOGICAL SCIENCES↗

Biological dosimetry by interphase chromosome painting

Both fluorescence in situ hybridization of metaphase spreads with whole-chromosome probes and premature chromosome condensation in interphase nuclei have been used in the past to estimate the radiation dose to lymphocytes. We combined these techniques to evaluate the feasibility of using painted interphase chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma rays and fused to mitotic Chinese hamster cells either immediately after irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase human chromosomes were hybridized with a composite probe specific for human chromosomes 3 and 4. The dose-response curve for fragment induction immediately after irradiation was linear; these results reflected breakage frequency in the total genome in terms of DNA content per chromosome. At 8 h after irradiation, the dose-response curve for chromosome interchanges, the prevalent aberration in interphase chromosomes, was linear-quadratic and similar to that observed for metaphase chromosomes. These results suggest that painting prematurely condensed chromosomes can be useful for biological dosimetry when blood samples are available shortly after the exposure, or when interphase cells are to be scored instead of mitotic cells.

NASA Discipline Radiation Health↗

Comparative assessment of psychomotor performance - Target prediction by humans and macaques (Macaca mulatta)

Although nonhuman primates such as rhesus monkeys (Macaca mulatta) have been useful models of many aspects of cognition and performance, it has been argued that, unlike humans, they may lack the capacity to respond as predictor-operators. Data from the present series of experiments undermine this claim, suggesting instead a continuity of predictive competency between humans and nonhuman primates. A prediction coefficient was devised to examine the degree to which each subject's response path approximated the optimal predictive strategy. Whereas human subjects (N= 30) generally predicted more accurately, rhesus monkeys (N= 10) also significantly anticipated the movements of the target in all conditions. It appears that humans and rhesus monkeys both exhibit the capacity to respond to where a stimulus is going.

Washburn, David A.↗