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Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Cellular immunity, which is decreased during and after space flight, is responsible for controlling EBV replication in vivo. In this study, we investigated the effects of short-term space flight on latent EBV reactivation.
Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. We hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B-lymphocytes. If increased virus production and clonal expansion of infected B-lymphocytes are detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease. More importantly, we will begin to understand the basic mechanisms involved in stress-induced reactivation of EBV in circulating B-lymphocytes.
Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth's magnetosphere is particularly worrisome because it includes ionizing radiation from cosmic galactic radiation. Increased stress levels appear even before flight, presumably from the rigors of preflight training and the anticipation of the mission (12, 32, 38, 39). Space flight causes significant changes in human immune function (32), but the means by which these changes come about have been difficult to discern. Consistent indicators of stress associated with space flight include increased production of stress hormones, and changes in cells of the immune system. These changes include elevated white blood cell (WBC) and neutrophil counts at landing (15, 16, 35, 37). Activation of generalized stress responses before, during, and after space flight probably affects the function of the immune system. Space flight has been shown to decrease many aspects of immune function, including natural killer (NK) cell activity, interferon production, the blastogenic response of leukocytes to mitogens, cell-mediated immunity, neutrophil function and monocyte function (5, 16, 18, 21, 35-37).
This slide presentation opens with views of the shuttle in various stages of preparation for launch, a few moments after launch prior to external fuel tank separation, a few pictures of the earth,and several pictures of astronomical interest. The presentation reviews the factors effecting the risks of infectious disease during space flight, such as the crew, water, food, air, surfaces and payloads and the factors that increase disease risk, the factors affecting the risk of infectious disease during spaceflight, and the environmental factors affecting immunity, such as stress. One factor in space infectious disease is latent viral reactivation, such as herpes. There are comparisons of the incidence of viral reactivation in space, and in other analogous situations (such as bed rest, or isolation). There is discussion of shingles, and the pain and results of treatment. There is a further discussion of the changes in microbial pathogen characteristics, using salmonella as an example of the increased virulence of microbes during spaceflight. A factor involved in the risk of infectious disease is stress.
Over the past decade the concept of space weather has been introduced and matured in both the scientific community and popular press. Likewise the concept of space climatology recently also is being advanced. Closely linked to these concepts are their impacts on ground- and space-based technological systems; one such system commonly mentioned is manned space flight exemplified by the Space Shuttle and International Space Station (ISS). From a manned space flight perspective, space weather and space climatology have significant effects on the amount of radiation exposure received by humans in space from the ambient high-energy charged particles present in interplanetary space and trapped in the geomagnetosphere. Whereas the impact of space weather for most technological systems is usually discrete and well correlated in time, the principle impact of space weather and space climatology is to increase the probability of latent cancer formation in thetraveler cohort. In this regard, while space weather may be the dominating factor for a given mission, over the life of a long-term program such as the Space Shuttle or ISS space climatology is the controlling factor of latent cancer risk. Human radiation exposure enhancements associated with space weather disturbances has been a concern among scientist and mission controllers since the inception of manned spaceflight nearly forty years ago. This led NASA to develop, in conjunction with the Environmental Science Services Administration s Space Disturbance Forecast Center and the USAF/AWS, the Solar Particle Alert Network (SPAN)-the foundation of an initial U.S. space weather monitoring and forecasting service. Since Apollo, routine space flight operations have evolved to include the use of space weather and climatology data provided through a world-wide network of operational space weather data services to predict and recommend actions to minimize astronaut radiation exposures. NASA Space Radiation Analysis Group (SRAG) flight controllers use real-time space weather data to detect and assess the impact of solar particle events, outer electron belt enhancements, the formation of pseudo-stable additional trapped radiation belts, and the solar cycle modulation of trapped radiation belts and galactic cosmic rays. Energetic particle data from GOES spacecraft are automatically ingested from NOAA Space Environment Center data servers and used to drive a model for the estimating the exposure to astronauts from solar particle events. While adequate for current manned space flight support, the existing operational space weather support system requires improvements to address the anticipated evolution in both the character of manned missions as well as space flight operations management. Necessary space weather data improvements include: reliably available (near) real-time space weather data on a fixed schedule via redundant access methods that support autonomous data acquisition by computer systems behind enterprise firewalls; and rapid transition of promising research sensors into operational systems.
Rainfall production is the fundamental variable within the Earth's hydrological cycle because it is both the principal forcing term in surface water budgets and its energetics corollary, latent heating, is the principal source of atmospheric diabatic heating. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water. The properties of the vertical distribution of latent heat release modulate large-scale meridional and zonal circulations within the tropics - as well as modifying the energetic efficiencies of midlatitude weather systems. This paper focuses on the retrieval of latent heat release from satellite measurements generated by the Tropical Rainfall Measuring Mission (TRMM) satellite observatory, which was launched in November 1997 as a joint American-Japanese space endeavor. Since then, TRMM measurements have been providing an accurate four-dimensional account of rainfall over the global tropics and sub-tropics, information which can be used to estimate the space-time structure of latent heating across the Earth's low latitudes. The paper examines how the observed TRMM distribution of rainfall has advanced an understanding of the global water and energy cycle and its consequent relationship to the atmospheric general circulation and climate via latent heat release. A set of algorithm methodologies that are being used to estimate latent heating based on rain rate retrievals from the TRMM observations are described. The characteristics of these algorithms and the latent heating products that can be generated from them are also described, along with validation analyses of the heating products themselves. Finally, the investigation provides an overview of how TRMM-derived latent heating information is currently being used in conjunction with global weather and climate models, concluding with remarks intended to stimulate further research on latent heating retrieval from satellites.
Tropical Rain Measuring Mission (TRMM) is an experiment in measuring rainfall and the associated latent heat release from space. A primary goal is to help in initializing the large-scale weather and climate models for crucial improvement in location and profile of atmospheric heat release. For this, precipitation and latent heating profiles are needed. This goal requires cloud-resolving models. The basic approach was to use passive microwave and rain radar in combination to issue a limited number of products, improving the retrieval algorithms by testing during flight, so the products are updated annually. Despite a tight budget, the TRMM observatory and data system worked excellently from launch for the past three years. A basic philosophy has been to do physical validation as much as possible, in preference to empirical adjustments for algorithm improvement. Additional information is contained in the original extended abstract.
Rainfall production is a fundamental process within the Earth's hydrological cycle because it represents both a principal forcing term in surface water budgets, and its energetics corollary, latent heating, is the principal source of atmospheric diabatic heating. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water. The properties of the vertical distribution of latent heat release modulate large-scale meridional and zonal circulations within the Tropics - as well as modify the energetic efficiencies of mid-latitude weather systems. This paper highlights the retrieval of latent heat release from satellite measurements generated by the Tropical Rainfall Measuring Mission (TRMM) and Global Precipitation Mission (GPM) satellite observatory, which were launched in November 1997 and February 2014, respectively. Both TRMM and GPM measurements have been providing an accurate four-dimensional account of rainfall over the global Tropics and mid-latitudes: information that can be used to estimate the space-time structure of latent heating. Two sets of latent heating retrieval algorithm methodologies (Goddard Convective-Stratiform or CSH, and Japan Spectral Latent Heating or SLH) have been developed to estimate latent heating based on rain rate profile retrievals obtained from TRMM and GPM measurements. The CSH algorithm will be described followed by a discussion its improvements and performance against the combined derived surface ran rates. We will also present the CSH retrieved LH for TRMM and GPM.
Rainfall production is a fundamental process within the Earth's hydrological cycle because it represents both a principal forcing term in surface water budgets, and its energetics corollary, latent heating, is the principal source of atmospheric diabatic heating. Latent heat release itself is a consequence of phase changes between the vapor, liquid, and frozen states of water. The properties of the vertical distribution of latent heat release modulate large-scale meridional and zonal circulations within the Tropics - as well as modify the energetic efficiencies of mid-latitude weather systems. This paper highlights the retrieval of latent heat release from satellite measurements generated by the Tropical Rainfall Measuring Mission (TRMM) and Global Precipitation Measurement (GPM) Mission satellite observatory, which were launched in November 1997 and February 2014, respectively. Both TRMM and GPM measurements have been providing an accurate four-dimensional account of rainfall over the global Tropics and mid-latitudes: information that can be used to estimate the space-time structure of latent heating.Two sets of latent heating (LH) retrieval algorithm methodologies (Goddard Convective-Stratiform Heating or CSH, and Japan's Spectral Latent Heating or SLH) have been developed to estimate latent heating based on rain rate profile retrievals obtained from TRMM and GPM measurements. The differences and similarities between the CSH and SLH algorithm designs will be presented. The presentation then will provide the results of LH structures derived from the TRMM and GPM. At the end of presentation, the further research on latent heating retrieval from satellites will be discussed.
The changes in immune function which occur during space flight potentially expose the crews to an increased risk for development of illness. Decreased cellular immune function has been repeatedly documented after space flight and confirmed during flight by in vivo delayed-type hypersensitivity testing. However, correlation of immune changes with a clinically significant risk factor has not yet been performed. Our hypothesis is that space flight induces a decrease in cell-mediated immune function accompanied by a shift from a type 1 cytokine pattern (favoring cell-mediated immunity) to a type 2 cytokine pattern (favoring humoral immunity). We further hypothesize that reactivation of latent viruses will occur during space flight in association with the decreased cellular immunity. To test these hypotheses, we will determine the effects of space flight on cell-mediated immunity and viral reactivation. We will utilize delayed-type hypersensitivity testing as an in vivo measure of integrated cell-mediated immune function. The production of cytokines and immunoregulatory factors by lymphocytes and monocytes will be measured to determine whether changes in cytokine patterns are associated with the space flight-induced immune dysregulation. Correlation of antigen-specific immune changes with reactivation of latent herpes viruses will be determined by measuring peripheral levels of viral (CMV, VZV, EBV) antigen-specific T cells and comparing to the levels of EBV-infected B-cells by fluorescence in situ hybridization and flow cytometry. A comparison of cell-mediated immune function, cytokine regulation and viral reactivation will provide new insights into crew member health risks during flight.
A major concern associated with long-duration space flight is the possibility of infectious diseases posing an unacceptable medical risk to crew members. One major hypothesis addressed in this project is that space flight will cause alterations in the immune system that will allow latent viruses that are endogenous in the human population to reactivate and shed to higher levels than normal, which may affect the health of crew members. The second major hypothesis being examined is that the effects of space flight will alter the mucosal immune system, the first line of defense against many microbial infections, including herpesviruses, polyomaviruses, and gastroenteritis viruses, rendering crew members more susceptible to virus infections across the mucosa. We are focusing the virus studies on the human herpesviruses and polyomaviruses, important pathogens known to establish latent infections in most of the human population. Both primary infection and reactivation from latent infection with these groups of viruses (especially certain herpesviruses) can cause a variety of illnesses that result in morbidity and, occasionally, mortality. Both herpesviruses and polyomaviruses have been associated with human cancer, as well. Effective vaccines exist for only one of the eight known human herpesviruses and available antivirals are of limited use. Whereas normal individuals display minimal consequences from latent viral infections, events which alter immune function (such as immunosuppressive therapy following solid organ transplantation) are known to increase the risk of complications as a result of viral reactivations.
It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.
This application proposes a continuation of our current effort, which has provided the first demonstration of viral reactivation during space flight. We have used the herpesvirus EBV as a model for latent viral reactivation and have shown that increased amounts of EBV DNA were shed by astronauts during space flight. Analysis of the Antarctic space flight analog indicated that the frequency of viral shedding may also increase (along with the increased numbers of virus) during long periods of isolation. However, a number of critical questions remain before the findings may be considered a significant health risk during extended space flight. These include: Are other latent viruses (e.g., other herpesviruses and polyornaviruses) in addition to EBV also reactivated and shed more frequently and/or in higher numbers during space flight? Is the viral reactivation observed in space flight and ground-based analogs mediated through the hypothalamus-pituitary-adrenal (HPA) axis resulting in a decreased cell-mediated immune response? How does detection of viral DNA by PCR analysis correlate with infectious virus? How does the amount of virus found during flight compare with viral levels observed in acute/chronic viral illnesses and in control individuals? This expanded study will examine the phenomenon of viral reactivation from the initiating stress through the HPA axis with the accompanying suppression of the immune system resulting in viral reactivation. This information is essential to determine if latent viral reactivation among crewmembers represents a sufficient medical risk to space travel to require the development of suitable countermeasures.
The present investigation is concerned with the evolution of a space station in terms of the progression of autonomy, as systems perspectives and architectural concepts permit. The distinction between automation and autonomy is considered along with the evolution of autonomy, and the evolution of automation in station operations. Attention is given to the startup of a complex technological system, aspects of station control, questions of crew operational support, factors regarding the habitability of a space station, system design philosophy for autonomy, evolvability, latent capability, stage commonality, and multiple modularity. It is concluded that an evolutionary space station operating over a period of 10-20 years with a great increase in capability over that time will require a design philosophy which is more flexible and open-ended than for previous space systems.
The mechano-caloric effect is potentially useful in the He II temperature range. Aside from demonstration work, little quantification effort appears to have been known since other refrigeration possibilities have been available for some time. Successful He II use-related system examples are as follows: in space, the utilization of the latent heat of vaporization has been quite successful in vapor-liquid phase separation (VLPS) in conjunction with thermomechanical force application in plugs. In magnet cooling systems, the possibility of using the mechano-caloric cooling effect in conjunction with thermo-mechanical circulation pump schemes, has been assessed (but not quantified yet to the extent desirable). A third example is quoted in conjunction with superfluid wind tunnel studies and liquid helium tow tank for surface vessels respectively. In all of these (partially future) R and D areas, the question of refrigerator effectiveness using the mechano-caloric effect appears to be relevant, possibly in conjunction with questions of reliability and simplicity. The present work is concerned with quantification of phenomena including simplified thermodynamic cycle calculations.
Problem reports at NASA are similar to bug reports: they capture defects found during test, post-launch operational anomalies, and document the investigation and corrective action of the issue. These artifacts are a rich source of lessons learned for NASA, but are expensive to analyze since problem reports are comprised primarily of natural language text. We apply topic modeling to a corpus of NASA problem reports to extract trends in testing and operational failures. We collected 16,669 problem reports from six NASA space flight missions and applied Latent Dirichlet Allocation topic modeling to the document corpus. We analyze the most popular topics within and across missions, and how popular topics changed over the lifetime of a mission. We find that hardware material and flight software issues are common during the integration and testing phase, while ground station software and equipment issues are more common during the operations phase. We identify a number of challenges in topic modeling for trend analysis: 1) that the process of selecting the topic modeling parameters lacks definitive guidance, 2) defining semantically-meaningful topic labels requires nontrivial effort and domain expertise, 3) topic models derived from the combined corpus of the six missions were biased toward the larger missions, and 4) topics must be semantically distinct as well as cohesive to be useful. Nonetheless,topic modeling can identify problem themes within missions and across mission lifetimes, providing useful feedback to engineers and project managers.
Clinical-microbiological investigations are an important aspect of the crew health stabilization program. To ensure that space crews have neither active nor latent infections, clinical specimens, including throat and nasal swabs and urine samples, are collected at 10 days (L-10) and 2days (L-2) before launch, and immediately after landing (L+0). All samples are examined for the presence of bacteria and fungi. In addition, fecal samples are collected at L-10 and examined for bacteria, fungi and parasites. This paper describes clinical-microbiological findings from 144 astronauts participating in 25 Space Shuttle missions spanning Space Transportation System (STS)-26 to STS-50. The spectrum of microbiological findings from the specimens included 25 bacterial and 11 fungal species. Among the bacteria isolated most frequently were Staphylococcus aureus, Enterobacter aerogenes, Enterococcus faecalis, Escherichia coli, Proteus mirabilis and Streptococcus agalactiae. Candida albicans was the most frequently isolated fungal pathogen.
Two phase thermal management systems that capitalize on both latent and sensible heats of the working fluid can yield orders of magnitude enhancements in flow boiling and condensation heat transfer coefficients and reduce size and weight of future space systems. Because the understanding of microgravity influences on two-phase flow and heat transfer is quite limited, there is presently an urgent need for a new experimental microgravity facility to enable investigators to perform long-duration flow boiling and condensation experiments in pursuit of reliable databases. This presentation will discuss evolution of the Flow Boiling and Condensation Experiment (FBCE), a collaborative effort between Purdue University and NASA Glenn Research Center, from initial concept with clearly defined objectives to full implementation on the International Space Station (ISS). It will be shown how this facility will serve as a primary platform for obtaining two-phase flow and heat transfer data in microgravity. By comparing the microgravity data against those obtained in Earth gravity, it will be possible to ascertain the influence of body force on two-phase transport phenomena in pursuit of mechanistic models as well as correlations, and to help determine the minimum flow criteria to ensure gravity independent flow boiling and condensation.