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NASA NTRS1998

Current concepts in the pathophysiology, evaluation, and diagnosis of compartment syndrome

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

NASA Discipline Cardiopulmonary↗

NASA NTRS1997

Further Developments of BEM for Micro and Macromechanical Analyses of Composites: Boundary Element Software Technology-Composite User's Manual

BEST-CMS (Boundary Element Solution Technology - Composite Modeling System) is an advanced engineering system for the micro-analysis of fiber composite structures. BEST-CMS is based upon the boundary element program BEST3D which was developed for NASA by Pratt and Whitney Aircraft and the State University of New York at Buffalo under contract NAS3-23697. BEST-CMS presently has the capabilities for elastostatic analysis, steady-state and transient heat transfer analysis, steady-state and transient concurrent thermoelastic analysis and elastoplastic and creep analysis. The fibers are assumed to be perfectly bonded to the composite matrix, or in the case of static or steady-state analysis, the fibers may be assumed to have spring connections, thermal resistance, and/or frictional sliding between the fibers and the composite matrix. The primary objective of this User's Manual is to provide an overview of all BEST-CMS capabilities, along with detailed descriptions of the input data requirements. A brief review of the theoretical background is presented for each analysis category. Then, Chapter 3 discusses the key aspects of the numerical implementation, while Chapter 4 provides a tutorial for the beginning BEST-CMS user. The heart of the manual, however, is in Chapter 5, where a complete description of all data input items is provided. Within this chapter, the individual entries are grouped on a functional basis for a more coherent presentation. Chapter 6 includes sample problems and should be of considerable assistance to the novice. Chapter 7 includes capsules of a number of fiber-composite analysis problems that have been solved using BEST-CMS. This chapter is primarily descriptive in nature and is intended merely to illustrate the level of analysis that is possible within the present BEST-CMS system. Chapter 8 contains a detailed description of the BEST-CMS Neutral File which is helpful in writing an interface between BEST- CMS and any graphic post-processor program. Finally, all pertinent references are listed in Chapter 9.

Banerjee, P. K.↗

NASA NTRS1993

Development of BEM for ceramic composites

BEST-CMS (boundary element solution technology - composite modeling system) is an advanced engineering system for the micro-analysis of fiber composite structures. BEST-CMS is based upon the boundary element program BEST3D which was developed for NASA by Pratt and Whitney Aircraft and the State University of New York at Buffalo under contract NAS3-23697. BEST-CMS presently has the capabilities for elastostatic analysis, steady-state and transient heat transfer analysis, steady-state and transient concurrent thermoelastic analysis, and elastoplastic and creep analysis. The fibers are assumed to be perfectly bonded to the composite matrix, or in the case of static or steady-state analysis, the fibers may be assumed to have spring connections, thermal resistance, and/or frictional sliding between the fibers and the composite matrix. The primary objective of this user's manual is to provide an overview of all BEST-CMS capabilities, along with detailed descriptions of the input data requirements. In the next chapter, a brief review of the theoretical background is presented for each analysis category. Then, chapter three discusses the key aspects of the numerical implementation, while chapter four provides a tutorial for the beginning BEST-CMS user. The heart of the manual, however, is in chapter five, where a complete description of all data input items is provided. Within this chapter, the individual entries are grouped on a functional basis for a more coherent presentation. Chapter six includes sample problems and should be of considerable assistance to the novice. Chapter seven includes capsules of a number of fiber-composite analysis problems that have been solved using BEST-CMS. This chapter is primarily descriptive in nature and is intended merely to illustrate the level of analysis that is possible within the present BEST-CMS system. Chapter eight contains a detail description of the BEST-CMS Neutral File which is helpful in writing an interface between BEST-CMS and any graphic post-processor program. Finally, all pertinent references are listed in chapter nine.

Henry, D. P.↗

NASA NTRS2002

The immune system in space and microgravity

Space flight and models that created conditions similar to those that occur during space flight have been shown to affect a variety of immunological responses. These have primarily been cell-mediated immune responses including leukocyte proliferation, cytokine production, and leukocyte subset distribution. The mechanisms and biomedical consequences of these changes remain to be established. Among the possible causes of space flight-induced alterations in immune responses are exposure to microgravity, exposure to stress, exposure to radiation, and many more as yet undetermined causes. This review chronicles the known effects of space flight on the immune system and explores the possible role of stress in contributing to these changes.

unmanned↗

NASA NTRS2003

Role of genetic background in induced instability

Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

NASA Discipline Radiation Health↗

NASA NTRS1992

Reaction cycle and thermodynamics in bacteriorhodopsin

Light causes the all-trans to 13-cis isomerization of the retinal in bacteriorhodopsin; the thermal relaxation leading back to the initial state drives proton transport first via proton transfer between the retinal Schiff base and D85 and then between the Schiff base and D96. The reaction sequence and thermodynamics of this photocycle are described by measuring time-resolved absorption changes with a gated multichannel analyzer between 100 ns and 100 ms, at six temperatures between 5 degrees C and 30 degrees C. Analysis of the energetics of the chromophore reaction sequence is on the basis of a recently proposed model (Varo & Lanyi, Biochemistry 30, 5016-5022, 1991) which consists of a single cycle and many reversible reactions: BR -hv-->K<==>L<==>M1-->M2<==>N<==>O-->BR. The existence of the M1-->M2 reaction, which functions as the switch in the proton transfer, is confirmed by spectroscopic evidence. The calculated thermodynamic parameters indicate that the exchange of free energy between the protein and the protons is at the switch step. Further, a large entropy decrease at this reaction suggests a protein conformation change which will conserve delta G for driving the completion of the reaction cycle. The results provide insights to mechanism and energy coupling in this system, with possible relevance to the general question of how ion pumps function.

Review↗

NASA NTRS1999

Statistical Perspectives on Stratospheric Transport

Long-lived tropospheric source gases, such as nitrous oxide, enter the stratosphere through the tropical tropopause, are transported throughout the stratosphere by the Brewer-Dobson circulation, and are photochemically destroyed in the upper stratosphere. These chemical constituents, or "tracers" can be used to track mixing and transport by the stratospheric winds. Much of our understanding about the stratospheric circulation is based on large scale gradients and other spatial features in tracer fields constructed from satellite measurements. The point of view presented in this paper is different, but complementary, in that transport is described in terms of tracer probability distribution functions (PDFs). The PDF is computed from the measurements, and is proportional to the area occupied by tracer values in a given range. The flavor of this paper is tutorial, and the ideas are illustrated with several examples of transport-related phenomena, annotated with remarks that summarize the main point or suggest new directions. One example shows how the multimodal shape of the PDF gives information about the different branches of the circulation. Another example shows how the statistics of fluctuations from the most probable tracer value give insight into mixing between different regions of the atmosphere. Also included is an analysis of the time-dependence of the PDF during the onset and decline of the winter circulation, and a study of how "bursts" in the circulation are reflected in transient periods of rapid evolution of the PDF. The dependence of the statistics on location and time are also shown to be important for practical problems related to statistical robustness and satellite sampling. The examples illustrate how physically-based statistical analysis can shed some light on aspects of stratospheric transport that may not be obvious or quantifiable with other types of analyses. An important motivation for the work presented here is the need for synthesis of the large and growing database of observations of the atmosphere and the vast quantities of output generated by atmospheric models.

Sparling, L. C.↗

NASA NTRS2002

Plant adaptation to low atmospheric pressures: potential molecular responses

There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

NASA Discipline Plant Biology↗

NASA NTRS2000

Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

Review, Tutorial↗

NASA NTRS1993

Nutrition and human physiological adaptations to space flight

Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

Review↗

NASA NTRS2001

Plants, plant pathogens, and microgravity--a deadly trio

Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.

NASA Discipline Plant Biology↗

NASA NTRS1997

Signal transduction in T lymphocytes in microgravity

More than 120 experiments conducted in space in the last 15 years have shown that dramatic changes are occurring in several types of single cells during their exposure to microgravity. One focus of today's research on cells in space is on signal transduction, especially those steps involving the cytoskeleton and cell-cell interactions. Signal transduction is often altered in microgravity as well as in hypergravity. This leads to changes in cell proliferation, genetic expression and differentiation. Interesting examples are leukocytes, HeLa cells, epidermoid cells and osteoblastic cells. Signalling pathways were studied in T lymphocytes in microgravity by several investigators after the discovery that mitogenic activation in vitro is virtually nil at 0g. T cells are a good model to study signal transduction because three extracellular signals (mitogen, IL-1 and IL-2) are required for full activation, and two classical pathways (via proteins G and PKC) are activated within the cell. In addition, low molecular weight GTP-binding proteins (Ras and Rap) are interacting with the cytoskeleton. The data at 0g support the notion that the expression of IL-2 receptor is inhibited at 0g, while mitogen binding and the transmission of IL-1 by accessory cells occur normally. In addition, alterations of the cytoskeleton suggest that the interaction with Rap proteins is disturbed. Data obtained with phorbol esters indicate that the function of PKC is changed in microgravity. Similar conclusions are drawn from the results with epidermoid cells A431.

short duration↗

NASA NTRS2001

Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

NASA Discipline Musculoskeletal↗

NASA NTRS1996

Hydrothermal systems on Mars: an assessment of present evidence

Hydrothermal processes have been suggested to explain a number of observations for Mars, including D/H ratios of water extracted from Martian meteorites, as a means for removing CO2 from the Martian atmosphere and sequestering it in the crust as carbonates, and as a possible origin for iron oxide-rich spectral units on the floors of some rifted basins (chasmata). There are numerous examples of Martian channels formed by discharges of subsurface water near potential magmatic heat sources, and hydrothermal processes have also been proposed as a mechanism for aquifer recharge needed to sustain long term erosion of sapping channels. The following geological settings have been identified as targets for ancient hydrothermal systems on Mars: channels located along the margins of impact crater melt sheets and on the slopes of ancient volcanoes; chaotic and fretted terranes where shallow subsurface heat sources are thought to have interacted with ground ice; and the floors of calderas and rifted basins (e.g. chasmata). On Earth, such geological environments are often a locus for hydrothermal mineralization. But we presently lack the mineralogical information needed for a definitive evaluation of hypotheses. A preferred tool for identifying minerals by remote sensing methods on Earth is high spatial resolution, hyperspectral, near-infrared spectroscopy, a technique that has been extensively developed by mineral explorationists. Future efforts to explore Mars for ancient hydrothermal systems would benefit from the application of methods developed by the mining industry to look for similar deposits on Earth. But Earth-based exploration models must be adapted to account for the large differences in the climatic and geological history of Mars. For example, it is likely that the early surface environment of Mars was cool, perhaps consistently below freezing, with the shallow portions of hydrothermal systems being dominated by magma-cryosphere interactions. Given the smaller gravitational field, declining atmospheric pressure, and widespread, permeable megaregolith on Mars, volatile outgassing and magmatic cooling would have been more effective than on Earth. Thus, hydrothermal systems are likely to have had much lower average surface temperatures than comparable geological settings on Earth. The likely predominance of basaltic crust on Mars suggests that hydrothermal fluids and associated deposits should be enriched in Fe, Mg, Si and Ca, with surficial deposits being dominated by lower temperature, mixed iron oxide and carbonate mineralogies.

Review↗

NASA NTRS1996

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

NASA Discipline Musculoskeletal↗

NASA NTRS2003

Exploration of Advanced Probabilistic and Stochastic Design Methods

The primary objective of the three year research effort was to explore advanced, non-deterministic aerospace system design methods that may have relevance to designers and analysts. The research pursued emerging areas in design methodology and leverage current fundamental research in the area of design decision-making, probabilistic modeling, and optimization. The specific focus of the three year investigation was oriented toward methods to identify and analyze emerging aircraft technologies in a consistent and complete manner, and to explore means to make optimal decisions based on this knowledge in a probabilistic environment. The research efforts were classified into two main areas. First, Task A of the grant has had the objective of conducting research into the relative merits of possible approaches that account for both multiple criteria and uncertainty in design decision-making. In particular, in the final year of research, the focus was on the comparison and contrasting between three methods researched. Specifically, these three are the Joint Probabilistic Decision-Making (JPDM) technique, Physical Programming, and Dempster-Shafer (D-S) theory. The next element of the research, as contained in Task B, was focused upon exploration of the Technology Identification, Evaluation, and Selection (TIES) methodology developed at ASDL, especially with regards to identification of research needs in the baseline method through implementation exercises. The end result of Task B was the documentation of the evolution of the method with time and a technology transfer to the sponsor regarding the method, such that an initial capability for execution could be obtained by the sponsor. Specifically, the results of year 3 efforts were the creation of a detailed tutorial for implementing the TIES method. Within the tutorial package, templates and detailed examples were created for learning and understanding the details of each step. For both research tasks, sample files and tutorials are attached in electronic form with the enclosed CD.

Marvis, Dimitri N.↗

NASA NTRS2003

Exploration of Advanced Probabilistic and Stochastic Design Methods

Mavris, Dimitri N.↗

NASA NTRS2003

Fundamental space radiobiology

The unique feature of the space radiation environment is the dominance of high-energy charged particles (HZE or high LET radiation) emitted by the Sun and galactic sources, or trapped in the Van Allen radiation belts. These charged particles present a significant hazard to space flight crews, and accelerator-based experiments are underway to quantify the health risks due to unavoidable radiation exposure. There are three principal properties of charged particles that distinguish them from conventional radiation, i.e. gamma rays and x-rays. First, they have a defined range in matter rather than an exponential absorption profile. Second, they undergo nuclear reactions to produce secondary particles. Third, and most important, they deposit their energy along well-defined linear paths or tracks rather than diffuse fields. The structured energy deposition pattern interacts on multiple scales with the biological structures of DNA, cells and tissues to produce correlated patterns of damage that evade repair systems. Traditional concepts of dose and its associated normalization parameter, RBE (relative biological effectiveness), break down under experimental scrutiny, and probabilistic models of risk based on the number of particle traversals per cell may be more appropriate. Unique patterns of DNA damage, gene expression, mobilization of repair proteins, activation of cytokines and remodeling of cellular microenvironment are observed following exposure to high LET radiation. At low levels of exposure the communication of bioactive substances from irradiated to unirradiated "bystander" cells can amplify the damage and cause a significant deviation from linearity in dose vs. response relations. Under some circumstances, there is even a multigenerational delay in the expression of radiation-induced genetic damage (genomic instability) which is not strictly dose dependent. These issues and the experimental evidence derived from ground based experiments at particle accelerators are presented along with speculation about how modified inertial conditions might perturb homeostatic responses to radiation to further complicate risk assessment for space flight.

NASA Discipline Radiation Health↗