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At least 55 records · Page 3

Human Adaptation Genetic Response Suites: Toward New Interventions and Countermeasures for Spaceflight

Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in lg and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

Sundaresan, A.↗

A digital audio/video interleaving system

A method of interleaving an audio signal with its associated video signal for simultaneous transmission or recording, and the subsequent separation of the two signals, is described. Comparisons are made between the new audio signal interleaving system and the Skylab Pam audio/video interleaving system, pointing out improvements gained by using the digital audio/video interleaving system. It was found that the digital technique is the simplest, most effective and most reliable method for interleaving audio and/or other types of data into the video signal for the Shuttle Orbiter application. Details of the design of a multiplexer capable of accommodating two basic data channels, each consisting of a single 31.5-kb/s digital bit stream are given. An adaptive slope delta modulation system is introduced to digitize audio signals, producing a high immunity of work intelligibility to channel errors, primarily due to the robust nature of the delta-modulation algorithm.

Richards, R. W.↗

Intelligent Control Approaches for UAVs

This talk will present overviews of various intelligent control technologies currently being developed and studied at the NASA Ames Research Center as applicable to Unmanned Aerial Vehicles (UAVs), Mars flyers, and to the next generation of flight controllers for manned aircraft. The approaches being examined include: (a) direct adaptive dynamic inverse controller, (b) adaptive critic-based optimal trajectory generator; (c) optimal allocation technique based on linear programming; (4) immunized maneuvering using autopilot building blocks. These approaches can utilize, but do not require, fault detection and isolation information. Piloted and unmanned simulation studies are performed to examine if the intelligent flight control techniques adequately: 1) match flying qualities of modem fly-by-wire flight controllers under nominal conditions; 2) improve performance under failure conditions when sufficient control authority is available; and 3) achieve intelligent maneuvering capabilities for unmanned vehicles. Results obtained so far will be presented and discussed.

KrisnaKumar, Kalmanje↗

Synthetic Biology and Human Health: Potential Applications for Spaceflight

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

Karouia, Fathi↗

Optical Monitoring of Weld Penetration

Robotic welding controlled by reliable, relatively-noise-free optoelectronic unit. Bounding off meniscus of pool of molten metal, laser beam impinges on position-sensitive photodetector. Beam diameter adjusted for width of weld. Optical filters screen out light from arc. Made from small, low-cost components and utilizing optical fibers to conduct signals, system immune to electromagnetic interference common in industrial environments. Aimed for automatic welders, robot welders in particular and also adaptable to other types of welding, including tungsten/inert-gas, laser, and electron-beam techniques.

Maram, J.↗

Risk of Crew Adverse Health Event Due to Altered Immune Response

Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture. Ground analog testing of humans and animals, as well as microgravity-analog cell culture, has demonstrated utility. However, in all cases, it is not known with certainty if these data would reflect similar testing during space travel. Given their ready availability, ground analogs may be extremely useful for assay development and the evaluation of potential countermeasures. In general, the evidence base suffers from widely disparate studies on small numbers of subjects that do not directly correlate well with each other or spaceflight itself. Also lacking are investigations of the effect of gender on adaption to spaceflight. This results in significant knowledge 'gaps' that must be filled by future studies to completely determine any clinical risk related to immunity for human exploration-class space missions. These gaps include a significant lack of in-flight data, particularly during long-duration space missions. The International Space Station represents an excellent science platform with which to address this knowledge gap. Other knowledge gaps include lack of a single validated ground analog for the phenomenon and a lack of flight-compatible laboratory equipment capable of monitoring astronauts (for either clinical or research purposes). However, enough significant data exist, as described in this manuscript, to warrant addressing this phenomenon during the utilization phase of the ISS. A recent Space Shuttle investigation has confirmed the 31 in-flight nature of immune dysregulation, demonstrating that it is not merely a post-flight phenomenon. Several current studies are ongoing onboard the ISS that should thoroughly characterize the phenomenon. NASA recognizes that if spaceflight-associated immune dysregulation persists during exploration flights in conjunction with other dangers, such as high-energy radiation, the result may be a significant clinical risk. This emphasizes the need for a continued integrated comprehensive approach to determining the effect of prolonged spaceflight, separated from transient launch and landing stresses, on human immunity. After such studies, the phenomenon will be understood, and, hopefully, a monitoring strategy will have been developed that could be used to monitor the effectiveness of countermeasure

Crucian, Brian↗

Microgravity and Cellular Consequences in Lymphocyte Function

Mammalian cells adapt to the environment of low gravity and express a series of responses, some possibly from direct effects on cells and others based on environmental conditions created by microgravity. Human lymphocytes in microgravity culture are functionally diminished in activation and locomotion. Both processes are integral to optimal immune response to fight pathogens. The NASA Rotating-wall vessel (RWV) is a well-accepted analog for microgravity culture on the ground. Gene array experiments and immunoblotting identified upstream events in human lymphocytes adapting to microgravity analog culture. Microgravity induces selective changes, many of which are cell membrane related. Results showed that upstream of PKC in the T cell activation cascade, PLC-gamma and LAT are significantly diminished. ZAP 70 which controls LAT activation is also down regulated in modeled microgravity. Thus events governing cell shape might warrant attention in microgravity conditions. The goal of this study is to delineate response suites that are consequential, direct or indirect effects of the microgravity environment and which of these are essential to lymphocytes

Pellis, Neal R.↗

Fuel Manifold Resists Embrittlement by Hydrogen

Completely-cast hydrogen-compatible alloy preferable to protective plating. Complexity of plating, welding, and brazing unnecessary if hydrogen-compatible alloy used for entire casting instead of protective overlay. Parts exposed to high-pressure hydrogen made immune to hydrogen embrittlement if fabricated from new alloy, Incoly 903 (or equivalent). Material strong and compatible with hydrogen at all temperatures and adapted for outlet manifold of Space Shuttle main combustion chamber.

Adams, T.↗

Physics, chemistry and pulmonary sequelae of thermodegradation events in long-mission space flight

An event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom is considered experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity enviroment impacts various stages of event simulation. Vapor-phase and particulate thermodegradation products were considered as potential spacecraft contaminants. A potential pathway for the production of ultrafine particles was identified. Different approaches to the simulation and prediction of contaminant transport were studied and used to predict the distribution of generic vapor-phase products in a Space Station model. A lung transport model was used to assess the pulmonary distribution of inhaled particles, and, finally, the impact of adaptation to low gravity on the human response to this inhalation risk was explored on the basis of known physiological modifications of the immune, endocrine, musculoskeletal and pulmonary systems that accompany space flight.

Todd, Paul↗

Maintaining the Body's Immune System: Incidence of Latent Virus Shedding During Space Flight

Your body protects you from illness with its own security system - the immune system. This system keeps illness at bay not only by mounting a defense against foreign organisms, but also by controlling the population of bacteria and viruses that normally live in your body. But there's no need to panic: certain microbes can actually exist in your body without causing illness. Some bacteria are even beneficial - like the E. coli in the large intestine that are an important source of vitamin K. While viruses are not exactly considered beneficial, they can also inhabit the human body without causing immediate harm or infection. A good example is the herpes simplex virus type 1 (HSV1), more commonly known as cold sores or fever blisters. This virus infects 70 to 80 percent of all adults but remains latent much of the time. While latent, the virus within cells remains dormant. Activation of the dormant virus causes it to make copies of itself (known as replication) constantly detectable in body fluids such as urine or saliva in a process called shedding. When a person becomes sick or stressed, however, this weakened condition allows the virus to reactivate and multiply. These elevated levels may be enough to produce symptoms, but shedding can also occur without symptoms. This ability to shed without showing signs of infection, or asymptomatic shedding, is of great interest, as it increases the chances of infecting others. The stresses associated with space flight - adapting to microgravity, isolation from family and friends, living and working in a confined space, sleep deprivation, and busy schedules, to name but a few - may weaken astronauts' immune systems, leaving them at greater risk of viral reactivation. Members of the STS-107 crew will participate in this experiment, Incidence of Latent Viral Shedding in Space Flight, to help scientists understand how reactivation works in space, and at what level replication reaches before symptoms begin to show. This study also promises more insight into the behavior of the larger virus family, herpesvirus, which will help us understand how to prevent infection in populations on Earth and reactivation in those already infected.

Pierson, Duane↗

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗

Immunity-Based Aircraft Fault Detection System

In the study reported in this paper, we have developed and applied an Artificial Immune System (AIS) algorithm for aircraft fault detection, as an extension to a previous work on intelligent flight control (IFC). Though the prior studies had established the benefits of IFC, one area of weakness that needed to be strengthened was the control dead band induced by commanding a failed surface. Since the IFC approach uses fault accommodation with no detection, the dead band, although it reduces over time due to learning, is present and causes degradation in handling qualities. If the failure can be identified, this dead band can be further A ed to ensure rapid fault accommodation and better handling qualities. The paper describes the application of an immunity-based approach that can detect a broad spectrum of known and unforeseen failures. The approach incorporates the knowledge of the normal operational behavior of the aircraft from sensory data, and probabilistically generates a set of pattern detectors that can detect any abnormalities (including faults) in the behavior pattern indicating unsafe in-flight operation. We developed a tool called MILD (Multi-level Immune Learning Detection) based on a real-valued negative selection algorithm that can generate a small number of specialized detectors (as signatures of known failure conditions) and a larger set of generalized detectors for unknown (or possible) fault conditions. Once the fault is detected and identified, an adaptive control system would use this detection information to stabilize the aircraft by utilizing available resources (control surfaces). We experimented with data sets collected under normal and various simulated failure conditions using a piloted motion-base simulation facility. The reported results are from a collection of test cases that reflect the performance of the proposed immunity-based fault detection algorithm.

Dasgupta, D.↗

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Goodwin, T. J.↗

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Goodwin, Thomas J.↗

An object-oriented, technology-adaptive information model

The primary objective was to develop a computer information system for effectively presenting NASA's technologies to American industries, for appropriate commercialization. To this end a comprehensive information management model, applicable to a wide variety of situations, and immune to computer software/hardware technological gyrations, was developed. The model consists of four main elements: a DATA_STORE, a data PRODUCER/UPDATER_CLIENT and a data PRESENTATION_CLIENT, anchored to a central object-oriented SERVER engine. This server engine facilitates exchanges among the other model elements and safeguards the integrity of the DATA_STORE element. It is designed to support new technologies, as they become available, such as Object Linking and Embedding (OLE), on-demand audio-video data streaming with compression (such as is required for video conferencing), Worldwide Web (WWW) and other information services and browsing, fax-back data requests, presentation of information on CD-ROM, and regular in-house database management, regardless of the data model in place. The four components of this information model interact through a system of intelligent message agents which are customized to specific information exchange needs. This model is at the leading edge of modern information management models. It is independent of technological changes and can be implemented in a variety of ways to meet the specific needs of any communications situation. This summer a partial implementation of the model has been achieved. The structure of the DATA_STORE has been fully specified and successfully tested using Microsoft's FoxPro 2.6 database management system. Data PRODUCER/UPDATER and PRESENTATION architectures have been developed and also successfully implemented in FoxPro; and work has started on a full implementation of the SERVER engine. The model has also been successfully applied to a CD-ROM presentation of NASA's technologies in support of Langley Research Center's TAG efforts.

Anyiwo, Joshua C.↗

Space analogue studies in Antarctica

Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

NASA Center HQS↗

Materials dispersion and biodynamics project research

The Materials Dispersion and Biodynamics Project (MDBP) focuses on dispersion and mixing of various biological materials and the dynamics of cell-to-cell communication and intracellular molecular trafficking in microgravity. Research activities encompass biomedical applications, basic cell biology, biotechnology (products from cells), protein crystal development, ecological life support systems (involving algae and bacteria), drug delivery (microencapsulation), biofilm deposition by living organisms, and hardware development to support living cells on Space Station Freedom (SSF). Project goals are to expand the existing microgravity science database through experiments on sounding rockets, the Shuttle, and COMET program orbiters and to evolve,through current database acquisition and feasibility testing, to more mature and larger-scale commercial operations on SSF. Maximized utilization of SSF for these science applications will mean that service companies will have a role in providing equipment for use by a number of different customers. An example of a potential forerunner of such a service for SSF is the Materials Dispersion Apparatus (MDA) 'mini lab' of Instrumentation Technology Associates, Inc. (ITA) in use on the Shuttle for the Commercial MDAITA Experiments (CMIX) Project. The MDA wells provide the capability for a number of investigators to perform mixing and bioprocessing experiments in space. In the area of human adaptation to microgravity, a significant database has been obtained over the past three decades. Some low-g effects are similar to Earth-based disorders (anemia, osteoporosis, neuromuscular diseases, and immune system disorders). As new information targets potential profit-making processes, services and products from microgravity, commercial space ventures are expected to expand accordingly. Cooperative CCDS research in the above mentioned areas is essential for maturing SSF biotechnology and to ensure U.S. leadership in space technology. Currently, the MDBP conducts collaborative research with investigators at the Rockefeller University, National Cancer Institute, and the Universities of California, Arizona, and Alabama in Birmingham. The growing database from these collaborations provides fundamental information applicable to development of cell products, manipulation of immune cell response, bone cell growth and mineralization, and other processes altered by low-gravity. Contacts with biotechnology and biopharmaceutical companies are being increased to reach uninformed potential SSF users, provide access through the CMDS to interested users for feasibility studies, and to continue active involvement of current participants. We encourage and actively seek participation of private sector companies, and university and government researchers interested in biopharmaceuticals, hardware development and fundamental research in microgravity.

Lewis, Marian L.↗

The effect of interference on delta modulation encoded video signals

An adaptive delta modulator which encodes composite color video signals was shown to provide a good response when operating at 16 Mb/s and near-commercial quality at 23Mb/s. The ADM was relatively immune to channel errors. The system design is discussed and circuit diagrams are included.

Schilling, D. L.↗