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At least 73 records · Page 4

Rapid susceptibility testing of mycobacterium avium complex and mycobacterium tuberculosis isolated from AIDS patients

In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of the Human Immunodeficiency Virus (HIV) infection will continue to rise more rapidly worldwide than predicted earlier. The Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to diseases called opportunistic infections of which tuberculosis and M. avium Complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, Maryland, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. Therefore, we proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis. The work was initiated in June 1992. In the last report, we described our efforts in developing ATP assay method using MAC. Studies were continued further, and during the period of this report, we established the relationship between colony forming units and ATP levels of these organisms during the growth cycle. Also, we evaluated the effects of standard antimycobacterial drugs using ATP assay technique and compared the results with those obtained with conventional tube dilution proportional method.

Dhople, Arvind M.↗

Cytokines and immune surveillance in humans

Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to further explore the effects of space flight on cytokines and cytokine-directed immunological function.

Sonnenfeld, Gerald↗

Altered immunological response in mice subjected to stress and exposed to fungal spores

Space flight and related factors such as stress appear to have an adverse effect on astronauts' immune systems. The presence of potentially pathogenic microbes including several genera of fungi reported from spacecraft environment may be a cause of concern in such situations. In order to study the role of such organisms in causing opportunistic or allergic diseases in crewmembers, we have tried to develop an animal model. BALB/c mice were suspended upside down for varying periods of time to induce stress, and their lymphocyte functions were evaluated. These studies indicate that the stress resulted in lowered mitogen induced lymphocyte stimulation as represented by 3H-thymidine uptake. We have also studied the ability of these animals to respond to Aspergillus fumigatus spores. The results of the study clearly demonstrate a definite down-regulation in T-cell proliferation and a higher incidence of infection with A. fumigatus.

Kurup, Viswanath P.↗

Cytokines and immune surveillance in humans

Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

Sonnenfeld, Gerald↗

Automated analysis of complex data

We have examined some of the issues involved in automating exploratory data analysis, in particular the tradeoff between control and opportunism. We have proposed an opportunistic planning solution for this tradeoff, and we have implemented a prototype, Igor, to test the approach. Our experience in developing Igor was surprisingly smooth. In contrast to earlier versions that relied on rule representation, it was straightforward to increment Igor's knowledge base without causing the search space to explode. The planning representation appears to be both general and powerful, with high level strategic knowledge provided by goals and plans, and the hooks for domain-specific knowledge are provided by monitors and focusing heuristics.

Saintamant, Robert↗

Rapid susceptibility testing of Mycobacterium avium complex and Mycobacterium tuberculosis isolated from AIDS patients

In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of HIV infection will continue to rise more rapidly worldwide than predicted earlier. The AIDS patients are susceptible to diseases called opportunistic infections of which tuberculosis and Mycobacterium avium complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, MD, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. We proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis.

Dhople, Arvind M.↗

High performance techniques for space mission scheduling

In this paper, we summarize current research at Carnegie Mellon University aimed at development of high performance techniques and tools for space mission scheduling. Similar to prior research in opportunistic scheduling, our approach assumes the use of dynamic analysis of problem constraints as a basis for heuristic focusing of problem solving search. This methodology, however, is grounded in representational assumptions more akin to those adopted in recent temporal planning research, and in a problem solving framework which similarly emphasizes constraint posting in an explicitly maintained solution constraint network. These more general representational assumptions are necessitated by the predominance of state-dependent constraints in space mission planning domains, and the consequent need to integrate resource allocation and plan synthesis processes. First, we review the space mission problems we have considered to date and indicate the results obtained in these application domains. Next, we summarize recent work in constraint posting scheduling procedures, which offer the promise of better future solutions to this class of problems.

Smith, Stephen F.↗

The Challenges of Field Testing the Traffic Management Advisor (TMA) in an Operational Air Traffic Control Facility

The Traffic Management Advisor (TMA), the sequence and schedule tool of the Center/TRACON Automation System (CTAS), was evaluated at the Fort Worth Center (ZFW) in the summer of 1996. This paper describes the challenges encountered during the various phases of the TMA field evaluation, which included system (hardware and software) installation, personnel training, and data collection. Operational procedures were developed and applied to the evaluation process that would ensure air safety. The five weeks of field evaluation imposed minimal impact on the hosting facility and provided valuable engineering and human factors data. The collection of data was very much an opportunistic affair, due to dynamic traffic conditions. One measure of the success of the TMA evaluation is that, rather than remove TMA after the evaluation until it could be fully implemented, the prototype TMA is in continual use at ZFW as the fully operational version is readied for implementation.

Hoang, Ty↗

Study Design to Test the Hypothesis That Long-Term Space Travel Harms the Human and Animal Immune Systems

The potential threat of immunosuppression and abnormal inflammatory responses in long-term space travel, leading to unusual predilection for opportunistic infections, malignancy, and death, is of ma or concern to the National Aeronautics and Space Administration (NASA) Program. This application has been devised to seek answers to questions of altered immunity in space travel raised by previous investigations spanning 30-plus years. We propose to do this with the help of knowledge gained by the discovery of the molecular basis of many primary and secondary immunodeficiency diseases and by application of molecular and genetic technology not previously available. Two areas of immunity that previously received little attention in space travel research will be emphasized: specific antibody responses and non-specific inflammation and adhesion. Both of these areas of research will not only add to the growing body of information on the potential effects of space travel on the immune system, but be able to delineate any functional alterations in systems important for antigen presentation, specific immune memory, and cell:cell and cell:endothelium interactions. By more precisely defining molecular dysfunction of components of the immune system, it is hoped that targeted methods of prevention of immune damage in space could be devised.

Shearer, William T.↗

Impact Crises, Mass Extinctions, and Galactic Dynamics: A Unified Theory

A general hypothesis linking mass extinctions of life with impacts of large asteroids and comets is based on astronomical data, impact dynamics, and geological information. The waiting times of large-body impacts on the Earth, derived from the flux of Earth-crossing asteroids and comets, and the estimated size of impacts capable of causing large-scale environmental disasters predict that impacts of objects (sup 3)5 km in diameter ((sup 3)10(exp 7) Mt TNT equivalent) could be sufficient to explain the record of about 25 extinction pulses in the last 540 m.y., with the five recorded major mass extinctions related to the impacts of the largest objects of (sup 3)10 km in diameter ( (sup 3)10(exp 8) Mt events). Smaller impacts (about 10(exp 6)-10(exp 7) Mt), with significant regional and even global environmental effects, could be responsible for the lesser boundaries in the geologic record. Tests of the "kill curve" relationship for impact-induced extinctions based on new data on extinction intensities and several well-dated large impact craters suggest that major mass extinctions require large impacts, and that a step in the kill curve may exist at impacts that produce craters of -100 km diameter, with smaller impacts capable of only relatively weak extinction pulses. Single impact craters < about 60 km in diameter should not be associated with global extinction pulses detectable in the Sepkoski database (although they may explain stage and zone boundaries marked by lesser faunal turnover), but multiple impacts in that size range may produce significant stepped extinction pulses. Statistical tests of the last occurrences of species at mass-extinction boundaries are generally consistent with predictions for abrupt or stepped extinctions, and several boundaries are known to show "catastrophic" signatures of environmental disasters and biomass crash, impoverished postextinction fauna and flora dominated by stress-tolerant and opportunistic species, and gradual ecological recovery and radiation of new taxa. Isotopic and other geochemical signatures are also generally consistent with the expected after-effects of catastrophic impacts. Seven of the recognized extinction pulses are associated with concurrent (in some cases multiple) stratigraphic impact markers (e.g., layers with high Ir, shocked minerals, microtektites), and/or large, dated impact craters. Other less-well-studied crisis intervals show elevated Ir, still well below that of the K/T spike, which might be explained by low-Ir impactors, ejecta blowoff, or the sedimentary reworking and dilution of impact signatures. The best explanation for a possible periodic component of about 30 m.y. in mass extinctions and clusters of impacts is the modulation of the comet flux associated with the solar system's periodic passage through the plane of the Milky Way Galaxy. The quantitative agreement among paleontological, geological, and astronomical data suggests an important underlying unification of the processes involved.

Rampino, M.R.↗

Findings from the X-33 Hydrogen Tank Failure Investigation

The X-33 Hydrogen tank failed during test in November of 1999 at MSFC. The tank completed the structural loading phase of the test successfully and was drained of hydrogen prior to the failure. The failure initiated in the acreage of Lobe 1 and was instantaneous, peeling the outer skin and core away from the inner skin. It was determined there were several factors that provided the opportunity for the tank to fail in this way. The factor giving life to these opportunistic circumstances was hydrogen infiltration into the core of the tank. The mechanism for this phenomenon will be discussed in this presentation.

Niedermeyer, Melinda↗

Autonomous Rovers for Mars Exploration

Rovers will play a critical role in the exploration of Mars. Near-term mission plans call for long traverses over unknown terrain, robust navigation and instrument placement, and reliable operations for extended periods of time. Longer-term missions may visit multiple science sites in a single day and perform opportunistic science data collection, as well as complex scouting, construction, and maintenance tasks in preparation for an eventual human presence. The Pathfinder mission demonstrated the potential for robotic Mars exploration but at the same time indicated the need for more rover autonomy. The highly ground-intensive control with infrequent communication and high latency limited the effectiveness of the Sojourner rover. When failures occurred, Sojourner often sat idle for extended periods of time, awaiting further commands from earth. In future missions, the tasks will be more complex and extended; hence there will be even more situations where things do not go exactly as planned. Significant advances in rover autonomy are needed to cope with increasing task complexity and greater execution uncertainty. Towards this end, we have designed an on-board executive architecture that incorporates robust operation, resource utilization, and failure recovery. In addition, we have designed ground tools to produce and refine contingent schedules that take advantage of the on-board architecture's flexible execution characteristics. Together, the on-board executive and the ground tools constitute an integrated rover autonomy architecture. This work draws from our experience with the Deep Space One autonomy experiment, with enhancements to ensure robust operation in the face of the unpredictable, complex environment that the rover will encounter on Mars. The rover autonomy architecture is currently being developed and deployed on the Marsokhod rover platform at NASA Ames Research Center. The capabilities of the rover autonomy architecture to support autonomous operations will be demonstrated concretely in upcoming field tests.

Anderson, Corin↗

Science Goal Driven Automation for NASA Missions: The Science Goal Monitor

Infusion of automation technologies into NASA s future missions will be essential not only to achieve substantial reduction in mission operations staff and costs, but also in order to both effectively handle an exponentially increasing volume of scientific data and to successfully meet dynamic, opportunistic scientific goals and objectives. Current spacecraft operations cannot respond to science driven events, such as intrinsically variable or short-lived phenomena in a timely manner. For such investigations, we must teach our platforms to dynamically understand, recognize, and react to the scientists goals. While much effort has gone into automating routine spacecraft operations to reduce human workload and hence costs, applying intelligent automation to the science side, i.e., science data acquisition, data analysis and reactions to that data analysis in a timely and still scientifically valid manner, has been relatively under-emphasized.

Korathkar, Anuradha↗

Toll-like receptor 4-positive macrophages protect mice from Pasteurella pneumotropica-induced pneumonia

This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4(Lps-del) mouse strains C57BL10/ScN (B10) and STOCK Abb(tm1) TLR4(Lps-del) Slc11a1(s)(B10 x C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4(Lps-del) genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 x C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 x C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 x C2D mice, and there was earlier transcription of KC and MIP-1alpha in B10 x C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 x C2D mice, which lack CD4(+) T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.

Non-NASA Center↗

Classification of ion mobility spectra by functional groups using neural networks

Neural networks were trained using whole ion mobility spectra from a standardized database of 3137 spectra for 204 chemicals at various concentrations. Performance of the network was measured by the success of classification into ten chemical classes. Eleven stages for evaluation of spectra and of spectral pre-processing were employed and minimums established for response thresholds and spectral purity. After optimization of the database, network, and pre-processing routines, the fraction of successful classifications by functional group was 0.91 throughout a range of concentrations. Network classification relied on a combination of features, including drift times, number of peaks, relative intensities, and other factors apparently including peak shape. The network was opportunistic, exploiting different features within different chemical classes. Application of neural networks in a two-tier design where chemicals were first identified by class and then individually eliminated all but one false positive out of 161 test spectra. These findings establish that ion mobility spectra, even with low resolution instrumentation, contain sufficient detail to permit the development of automated identification systems.

Non-NASA Center↗

Science Goal Monitor: Science Goal Driven Automation for NASA Missions

Infusion of automation technologies into NASA s future missions will be essential because of the need to: (1) effectively handle an exponentially increasing volume of scientific data, (2) successfully meet dynamic, opportunistic scientific goals and objectives, and (3) substantially reduce mission operations staff and costs. While much effort has gone into automating routine spacecraft operations to reduce human workload and hence costs, applying intelligent automation to the science side, i.e., science data acquisition, data analysis and reactions to that data analysis in a timely and still scientifically valid manner, has been relatively under-emphasized. In order to introduce science driven automation in missions, we must be able to: capture and interpret the science goals of observing programs, represent those goals in machine interpretable language; and allow spacecrafts onboard systems to autonomously react to the scientist's goals. In short, we must teach our platforms to dynamically understand, recognize, and react to the scientists goals. The Science Goal Monitor (SGM) project at NASA Goddard Space Flight Center is a prototype software tool being developed to determine the best strategies for implementing science goal driven automation in missions. The tools being developed in SGM improve the ability to monitor and react to the changing status of scientific events. The SGM system enables scientists to specify what to look for and how to react in descriptive rather than technical terms. The system monitors streams of science data to identify occurrences of key events previously specified by the scientist. When an event occurs, the system autonomously coordinates the execution of the scientist s desired reactions. Through SGM, we will improve om understanding about the capabilities needed onboard for success, develop metrics to understand the potential increase in science returns, and develop an operational prototype so that the perceived risks associated with increased use of automation can be reduced.

Koratkar, Anuradha↗

Enhanced Characterization of Microorganisms in the Spacecraft Environment

Spacecraft such as the International Space Station (ISS) and the space shuttles are enclosed environments where crewmembers may spend long periods of time. Currently, crewmembers spend approximately a period of 6 months in the ISS. It is known that these prolonged stays in space may result in weakening of the immune system. Therefore, exposure to opportunistic pathogens or high concentrations of environmental microorganisms may compromise the health of the crew. The detection of biocontaminants in spacecraft environments utilizes culture-based methodology, omitting greater than 90% of all microorganisms including pathogens such as Legionella and Cryptosporidium. Culturable bacteria and fungi have been the only allergens studied; the more potent allergens, such as those from dust mites, have never been tested for in spacecraft environments. In addition, no attempts have been made to monitor microbial toxins in spacecrafts. The present study utilized quantitative polymerase chain reaction (QPCR) as a novel approach for monitoring microorganisms in the spacecraft environment. QPCR is a molecular biology technique that does not rely on the physiological state of the organisms for identification, thereby enabling detection of both culturable and non-culturable organisms. In this project, specific molecular primers and probes were utilized for the detection and quantitation of two fungi of concern in indoor environments, Aspergillus fumigatus and Stachybotrys chartarum. These organisms were selected because of the availability of PCR primers and probes, and to establish the sample processing and analysis methodology that may be employed with additional organisms. Purification methods and QPCR assays were optimized for the detection of these organisms in air, surface, and water; and sample processing and analysis protocols were developed. Preliminary validation of these protocols was conducted in the laboratory with air, surface, and water samples seeded with known concentrations of the target organisms. Additional studies were conducted with bulk materials (HEPA filter pleats and particulate found on the filter screen) obtained from the ISS.

Cruz, Patricia↗

Microbial monitoring of spacecraft and associated environments

Rapid microbial monitoring technologies are invaluable in assessing contamination of spacecraft and associated environments. Universal and widespread elements of microbial structure and chemistry are logical targets for assessing microbial burden. Several biomarkers such as ATP, LPS, and DNA (ribosomal or spore-specific), were targeted to quantify either total bioburden or specific types of microbial contamination. The findings of these assays were compared with conventional, culture-dependent methods. This review evaluates the applicability and efficacy of some of these methods in monitoring the microbial burden of spacecraft and associated environments. Samples were collected from the surfaces of spacecraft, from surfaces of assembly facilities, and from drinking water reservoirs aboard the International Space Station (ISS). Culture-dependent techniques found species of Bacillus to be dominant on these surfaces. In contrast, rapid, culture-independent techniques revealed the presence of many Gram-positive and Gram-negative microorganisms, as well as actinomycetes and fungi. These included both cultivable and noncultivable microbes, findings further confirmed by DNA-based microbial detection techniques. Although the ISS drinking water was devoid of cultivable microbes, molecular-based techniques retrieved DNA sequences of numerous opportunistic pathogens. Each of the methods tested in this study has its advantages, and by coupling two or more of these techniques even more reliable information as to microbial burden is rapidly obtained. Copyright 2004 Springer-Verlag.

Environmental Monitoring/methods↗