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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 307 records · Page 17

Titanospirillum velox: a huge, speedy, sulfur-storing spirillum from Ebro Delta microbial mats

A long (20-30 micrometer), wide (3-5 micrometer) microbial-mat bacterium from the Ebro Delta (Tarragona, Spain) was grown in mixed culture and videographed live. Intracellular elemental sulfur globules and unique cell termini were observed in scanning-electron-microprobe and transmission-electron micrographs. A polar organelle underlies bundles of greater than 60 flagella at each indented terminus. These Gram-negative bacteria bend, flex, and swim in a spiral fashion; they translate at speeds greater than 10 body lengths per second. The large size of the spirillum permits direct observation of cell motility in single individual bacteria. After desiccation (i.e., absence of standing water for at least 24 h), large populations developed in mat samples remoistened with sea water. Ultrastructural observations reveal abundant large sulfur globules irregularly distributed in the cytoplasm. A multilayered cell wall, pliable and elastic yet rigid, distends around the sulfur globules. Details of the wall, multiflagellated termini, and large cytoplasmic sulfur globules indicate that these fast-moving spirilla are distinctive enough to warrant a genus and species designation: Titanospirillum velox genus nov., sp. nov. The same collection techniques at a similar habitat in the United States (Plum Island, northeast Essex County, Massachusetts) also yielded large populations of the bacterium among purple phototrophic and other inhabitants of sulfurous microbial-mat muds. The months-long survival of T. velox from Spain and from the United States in closed jars filled with mud taken from both localities leads us to infer that this large spirillum has a cosmopolitan distribution.

Non-NASA Center↗

Experimental measurement of the orbital paths of particles sedimenting within a rotating viscous fluid as influenced by gravity

Measurements were taken of the path of a simulated typical tissue segment or 'particle' within a rotating fluid as a function of gravitational strength, fluid rotation rate, particle sedimentation rate, and particle initial position. Parameters were examined within the useful range for tissue culture in the NASA rotating wall culture vessels. The particle moves along a nearly circular path through the fluid (as observed from the rotating reference frame of the fluid) at the same speed as its linear terminal sedimentation speed for the external gravitational field. This gravitationally induced motion causes an increasing deviation of the particle from its original position within the fluid for a decreased rotational rate, for a more rapidly sedimenting particle, and for an increased gravitational strength. Under low gravity conditions (less than 0.1 G), the particle's motion through the fluid and its deviation from its original position become negligible. Under unit gravity conditions, large distortions (greater than 0.25 inch) occur even for particles of slow sedimentation rate (less than 1.0 cm/sec). The particle's motion is nearly independent of the particle's initial position. Comparison with mathematically predicted particle paths show that a significant error in the mathematically predicted path occurs for large particle deviations. This results from a geometric approximation and numerically accumulating error in the mathematical technique.

Wolf, David A.↗

Elucidating Microbial Adaptation Dynamics via Autonomous Exposure and Sampling

The adaptation of micro-organisms to their environments is a complex process of interaction between the pressures of the environment and of competition. Reducing this multifactorial process to environmental exposure in the laboratory is a common tool for elucidating individual mechanisms of evolution, such as mutation rates. Although such studies inform fundamental questions about the way adaptation and even speciation occur, they are often limited by labor-intensive manual techniques. Current methods for controlled study of microbial adaptation limit the length of time, the depth of collected data, and the breadth of applied environmental conditions. Small idiosyncrasies in manual techniques can have large effects on outcomes; for example, there are significant variations in induced radiation resistances following similar repeated exposure protocols. We describe here a project under development to allow rapid cycling of multiple types of microbial environmental exposure. The system allows continuous autonomous monitoring and data collection of both single species and sampled communities, independently and concurrently providing multiple types of controlled environmental pressure (temperature, radiation, chemical presence or absence, and so on) to a microbial community in dynamic response to the ecosystem's current status. When combined with DNA sequencing and extraction, such a controlled environment can cast light on microbial functional development, population dynamics, inter- and intra-species competition, and microbe-environment interaction. The project's goal is to allow rapid, repeatable iteration of studies of both natural and artificial microbial adaptation. As an example, the same system can be used both to increase the pH of a wet soil aliquot over time while periodically sampling it for genetic activity analysis, or to repeatedly expose a culture of bacteria to the presence of a toxic metal, automatically adjusting the level of toxicity based on the number or growth rate of surviving cells. We are on our second prototype iteration, with demonstrated functions of microbial growth monitoring and dynamic exposure to UV-C radiation and temperature. We plan to add functionality for general chemical presence or absence by Nov. 2013. By making the project low-cost and open-source, we hope to encourage others to use it as a basis for future development of a common microbial environmental adaptation testbed.

Microbiology↗

Lipid biomarkers for bacterial ecosystems: studies of cultured organisms, hydrothermal environments and ancient sediments

This paper forms part of our long-term goal of using molecular structure and carbon isotopic signals preserved as hydrocarbons in ancient sediments to improve understanding of the early evolution of Earth's surface environment. We are particularly concerned with biomarkers which are informative about aerobiosis. Here, we combine bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems to construct models for the nature, behaviour and preservation potential of primitive microbial communities. We use a combined molecular and isotopic approach to characterize lipids produced by cultured bacteria and test a variety of culture conditions which affect their biosynthesis. This information is then compared with lipid mixtures isolated from contemporary hot springs and evaluated for the kinds of chemical change that would accompany burial and incorporation into the sedimentary record. In this study we have shown that growth temperature does not appear to alter isotopic fractionation within the lipid classes produced by a methanotropic bacterium. We also found that cultured cyanobacteria biosynthesize diagnostic methylalkanes and dimethylalkanes with the latter only made when growing under low pCO2. In an examination of a microbial mat sample from Octopus Spring, Yellowstone National Park (USA), we could readily identify chemical structures with 13C contents which were diagnostic for the phototrophic organisms such as cyanobacteria and Chloroflexus. We could not, however, find molecular evidence for operation of a methane cycle in the particular mat samples we studied.

NASA Discipline Exobiology↗

Safety Expertise and the Perils of Novelty

Emerging aviation markets such as urban air mobility are giving rise to new technologies and means of operation. However, novelty may hide ‘unknown unknowns,’ raising new hazards. This paper examines how expertise and safety techniques enable transformative technologies such as reduced crew operations, hybrid wing-borne and rotor-born flight, federated air traffic services, and urban operations. We explore how analysts use expertise to address common-cause failures, collect and interpret safety data, and perform exacting tradeoffs between dissimilarity, redundancy, independence, and diversity (human, process lifecycle, or otherwise) to ensure safety. When novelty is present, analysts might not possess the expertise needed to fully understand the implications of design decisions and tradeoffs being made, especially in early lifecycle phases, on emergent properties such as safety. Safety expertise must be carefully cultivated. The conflicting views of safety experts must be unpacked to identify the divergence in fundamental assumptions, models, means, and methods that may be causing them. Once systems venture beyond the basis of what safety expertise can reliably guarantee, projects take on risk that must be managed. The paper contains key takeaways and actionable recommendations for novel OEMs and regulators touching on topics such as robust monitoring; clear and transparent reporting; incremental approaches to fielding novel systems in hazard-rich, risk-tolerant environments; the cultivation of safety culture and expertise in an organization; and the use of scientific study to reduce epistemic uncertainty in novel operations with new technologies. Since excessive novelty in aviation can undermine the current foundation of safety, humility and incrementalism are necessary to enable emerging aviation markets safely.

safety expertise↗

Safety Expertise and the Perils of Novelty

Emerging aviation markets such as urban air mobility are giving rise to new technologies and means of operation. However, novelty may hide ‘unknown unknowns,’ raising new hazards. This paper examines how expertise and safety techniques enable transformative technologies such as reduced crew operations, hybrid wing-borne and rotor-born flight, federated air traffic services, and urban operations. We explore how analysts use expertise to address common-cause failures, collect and interpret safety data, and perform exacting tradeoffs between dissimilarity, redundancy, independence, and diversity (human, process lifecycle, or otherwise) to ensure safety. When novelty is present, analysts might not possess the expertise needed to fully understand the implications of design decisions and tradeoffs being made, especially in early lifecycle phases, on emergent properties such as safety. Safety expertise must be carefully cultivated. The conflicting views of safety experts must be unpacked to identify the divergence in fundamental assumptions, models, means, and methods that may be causing them. Once systems venture beyond the basis of what safety expertise can reliably guarantee, projects take on risk that must be managed. The paper contains key takeaways and actionable recommendations for novel OEMs and regulators touching on topics such as robust monitoring; clear and transparent reporting; incremental approaches to fielding novel systems in hazard-rich, risk-tolerant environments; the cultivation of safety culture and expertise in an organization; and the use of scientific study to reduce epistemic uncertainty in novel operations with new technologies. Since excessive novelty in aviation can undermine the current foundation of safety, humility and incrementalism are necessary to enable emerging aviation markets safely.

safety expertise↗

Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer

A magnetic tweezer was constructed to apply controlled tensional forces (10 pN to greater than 1 nN) to transmembrane receptors via bound ligand-coated microbeadswhile optically measuring lateral bead displacements within individual cells. Use of this system with wild-type F9 embryonic carcinoma cells and cells from a vinculin knockout mouse F9 Vin (-/-) revealed much larger differences in the stiffness of the transmembrane integrin linkages to the cytoskeleton than previously reported using related techniques that measured average mechanical properties of large cell populations. The mechanical properties measured varied widely among cells, exhibiting an approximately log-normal distribution. The median lateral bead displacement was 2-fold larger in F9 Vin (-/-) cells compared to wild-type cells whereas the arithmetic mean displacement only increased by 37%. We conclude that vinculin serves a greater mechanical role in cells than previously reported and that this magnetic tweezer device may be useful for probing the molecular basis of cell mechanics within single cells. Copyright 2000 Academic Press.

Non-NASA Center↗

Modeling transport kinetics in clinoptilolite-phosphate rock systems

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

NASA Center JSC↗

Planetary Protection, Parts, and Perception: The Ranger Missions as the Origin Story of the Myth of Planetary Protection-Related Mission Failures

There has been a long-standing perspective in the planetary engineering community that the use of planetary protection sterilization techniques such as dry heat microbial reduction (DHMR) have led to significant mission failures in the past. This perception has led to a hesitation to craft mission designs that incorporate sterilization beyond the component-level. Via interviews with long-standing members of the planetary engineering community across the Agency, we have identified the root historical missions that have driven this perspective. The source, or Origin Story, which has been passed down to subsequent generations of engineers, is the failures tied to the early series of the Ranger missions. In this presentation, we examine the details behind the Ranger failures, the majority of which are non-planetary protection sterilization-related, and bring to light the myth of this perception.

planetary protection↗

Experiences with Testing the Largest Ground System NASA Has Ever Built

In the 1980s, the National Aeronautics and Space Administration (NASA) embarked upon a major Earth-focused program called Mission to Planet Earth. The Goddard Space Flight Center (GSFC) was selected to manage and develop a key component - the Earth Observing System (EOS). The EOS consisted of four major missions designed to monitor the Earth. The missions included 4 spacecraft. Terra (launched December 1999), Aqua (launched May 2002), ICESat (Ice, Cloud, and Land Elevation Satellite, launched January 2003), and Aura (scheduled for launch January 2004). The purpose of these missions was to provide support for NASA s long-term research effort for determining how human-induced and natural changes affect our global environment. The EOS Data and Information System (EOSDIS), a globally distributed, large-scale scientific system, was built to support EOS. Its primary function is to capture, collect, process, and distribute the most voluminous set of remotely sensed scientific data to date estimated to be 350 Gbytes per day. The EOSDIS is composed of a diverse set of elements with functional capabilities that require the implementation of a complex set of computers, high-speed networks, mission-unique equipment, and associated Information Technology (IT) software along with mission-specific software. All missions are constrained by schedule, budget, and staffing resources, and rigorous testing has been shown to be critical to the success of each mission. This paper addresses the challenges associated with the planning, test definition. resource scheduling, execution, and discrepancy reporting involved in the mission readiness testing of a ground system on the scale of EOSDIS. The size and complexity of the mission systems supporting the Aqua flight operations, for example, combined with the limited resources available, prompted the project to challenge the prevailing testing culture. The resulting success of the Aqua Mission Readiness Testing (MRT) program was due in no small measure to re-structuring the traditional programmatic and technical approach to a more efficient and robust program. Programmatically, it meant gaining the endorsement, commitment, and cooperation of the numerous subsystem element managers and other stakeholder organizations. Technically, it required an MRT program that was agile, could rapidly adapt to requirements changes, and was flexible in its overall approach. Furthermore, this paper addresses the following questions: 1. What are the key ingredients (e.g., test tools, organization) needed to conduct a successful MRT program? 2. What distinguishes EOS MRT from the traditional system testing approach? 3. Where should the focus of testing be since it is infeasible to test every element or subsystem? 4. How can MRT be applied effectively to other systems or missions? To provide answers to these questions, this paper relies heavily on real-life, hands-on experiences ("lessons learned") gained during mission readiness testing of the Terra ground system and, most recently, the Aqua and ICESat missions. Moreover, this paper explores how lessons learned were turned into lessons applied for the upcoming Aura mission. Although derived from the EOS missions, MRT techniques and strategies can be applied to enhance the testing of other missions.

Lehtonen, Ken↗

Induction of chromosome aberrations in human cells by charged particles

Chromosome aberrations induced by high-energy charged particles in normal human lymphocytes and human fibroblasts have been investigated. The charged particles included 250 MeV/nucleon protons, 290 MeV/nucleon carbon ions and 1 GeV/nucleon iron ions. The energies of the charged particles were higher than in most of the studies reported in the literature. Lymphocytes were stimulated to grow immediately after irradiation, while fibroblasts were incubated at 37 degrees C for 24 h for repair. Chromosomes were collected at the first mitosis after irradiation and chromosome aberrations were scored using the fluorescence in situ hybridization (FISH) technique with a whole-chromosome 4 probe. Chromosome aberrations were classified as reciprocal exchanges, incomplete exchanges, deletions and complex exchanges. The relative biological effectiveness (RBE) for each type of aberration was calculated by dividing a dose of 4 Gy by the dose of the charged particles producing the same effect as 4 Gy of gamma rays. Results of this study showed that complex aberrations have the highest RBE for radiation of high linear energy transfer (LET) for human lymphocytes, but for fibroblasts, the greatest effect was for incomplete exchanges. For both lymphocytes and fibroblasts, iron ions induced a similar fraction of aberrant cells.

NASA Center JSC↗

Three-dimensional tissue assemblies: novel models for the study of Salmonella enterica serovar Typhimurium pathogenesis

The lack of readily available experimental systems has limited knowledge pertaining to the development of Salmonella-induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at the National Aeronautics and Space Administration in conjunction with cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to study the infectivity of Salmonella enterica serovar Typhimurium for human intestinal epithelium. Immunohistochemical characterization and microscopic analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407 revealed that the 3-D cells more accurately modeled human in vivo differentiated tissues than did conventional monolayer cultures of the same cells. Results from infectivity studies showed that Salmonella established infection of the 3-D cells in a much different manner than that observed for monolayers. Following the same time course of infection with Salmonella, 3-D Int-407 cells displayed minimal loss of structural integrity compared to that of Int-407 monolayers. Furthermore, Salmonella exhibited significantly lower abilities to adhere to, invade, and induce apoptosis of 3-D Int-407 cells than it did for infected Int-407 monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and monolayers following infection with Salmonella revealed significant differences in expression of interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-1Ra, and tumor necrosis factor alpha mRNAs between the two cultures. In addition, uninfected 3-D Int-407 cells constitutively expressed higher levels of transforming growth factor beta1 mRNA and prostaglandin E2 than did uninfected Int-407 monolayers. By more accurately modeling many aspects of human in vivo tissues, the 3-D intestinal cell model generated in this study offers a novel approach for studying microbial infectivity from the perspective of the host-pathogen interaction.

NASA Discipline Environmental Health↗

NASA Risk Management Handbook: Version 2.0, Part 1

The purpose of this handbook is to provide an in-depth reference for the practice of risk management in NASA, updating the guidance offered in its original version, NASA/SP-2011-3422 (November 2011), and closely aligning the updated guidance with the current NASA Procedural Requirements for Agency Risk Management, NPR 8000.4, and the parent NASA Policy Directive for NASA Governance and Strategic Management, NPD 1000.0. NPD 1000.0 introduces with emphasis the concept of “Risk Leadership,” making it a fundamental tenet and pillar of the risk management culture that it advocates for the Agency. NPR 8000.4 applies this concept and establishes Risk Management (RM) requirements for the Agency as an integrated enterprise, as well as the RM requirements for portfolio elements within the enterprise. Such elements include the various programs and projects that contribute to the Agency’s objectives and the various institutional activities carried out by entities that contribute to mission support. The present version of the handbook also emphasizes the integration of risk management processes across activity and project life cycles and their coordination and interaction with day-to-day programmatic and organizational functions. Areas of application of risk assessment and management that were not covered with specific guidance in the preceding version are addressed in this version with in-depth examples. The handbook is structured into two parts, whose chapters are in turn organized in a sequential order intended to facilitate a gradual and progressive introduction of the reader to risk management principles and practices. Part 1 of the handbook is dedicated to the introduction of the basic foundations of the NASA integrated risk management framework, the related fundamental risk concepts, the description of the risk management and decision processes that are to be implemented within the framework, the discussion of the risk assessment techniques that should be utilized in support of such processes, and the management and organizational interactions and interfaces that should be enabled to implement an effective integration of risk management activities within the Agency. Part 2 provides self-contained, end-to-end examples of application of the processes and techniques introduced in Part 1, in the context of both programmatic (i.e., project and/or mission related) and institutional activities.

Uncertainty↗

NASA Risk Management Handbook: Version 2.0, Part 2

The purpose of this handbook is to provide an in-depth reference for the practice of risk management in NASA, updating the guidance offered in its original version, NASA/SP-2011-3422 (November 2011), and closely aligning the updated guidance with the current NASA Procedural Requirements for Agency Risk Management, NPR 8000.4, and the parent NASA Policy Directive for NASA Governance and Strategic Management, NPD 1000.0 (January 2020). NPD 1000.0 introduces with emphasis the concept of “Risk Leadership,” making it a fundamental tenet and pillar of the risk management culture that it advocates for the Agency. NPR 8000.4 applies this concept and establishes Risk Management (RM) requirements for the Agency as an integrated enterprise, as well as the RM requirements for portfolio elements within the enterprise. Such elements include the various programs and projects that contribute to the Agency’s objectives and the various institutional activities carried out by entities that contribute to mission support. The present version of the handbook also emphasizes the integration of risk management processes across activity and project life cycles and their coordination and interaction with day-to-day programmatic and organizational functions. Areas of application of risk assessment and management that were not covered with specific guidance in the preceding version are addressed in this version with in-depth examples. The handbook is structured into two parts, whose chapters are in turn organized in a sequential order intended to facilitate a gradual and progressive introduction of the reader to risk management principles and practices. Part 1 of the handbook is dedicated to the introduction of the basic foundations of the NASA integrated risk management framework, the related fundamental risk concepts, the description of the risk management and decision processes that are to be implemented within the framework, the discussion of the risk assessment techniques that should be utilized in support of such processes, and the management and organizational interactions and interfaces that should be enabled to implement an effective integration of risk management activities within the Agency. Part 2 provides self-contained, end-to-end examples of application of the processes and techniques introduced in Part 1, in the context of both programmatic (i.e., project and/or mission related) and institutional activities.

Risk Leadership↗

Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension

We have investigated how extracellular matrix (ECM) alters the mechanical properties of the cytoskeleton (CSK). Mechanical stresses were applied to integrin receptors on the apical surfaces of adherent endothelial cells using RGD-coated ferromagnetic microbeads (5.5-microns diameter) in conjunction with a magnetic twisting device. Increasing the number of basal cell-ECM contacts by raising the fibronectin (FN) coating density from 10 to 500 ng/cm2 promoted cell spreading by fivefold and increased CSK stiffness, apparent viscosity, and permanent deformation all by more than twofold, as measured in response to maximal stress (40 dyne/cm2). When the applied stress was increased from 7 to 40 dyne/cm2, the stiffness and apparent viscosity of the CSK increased in parallel, although cell shape, ECM contacts, nor permanent deformation was altered. Application of the same stresses over a lower number ECM contacts using smaller beads (1.4-microns diameter) resulted in decreased CSK stiffness and apparent viscosity, confirming that this technique probes into the depth of the CSK and not just the cortical membrane. When magnetic measurements were carried out using cells whose membranes were disrupted and ATP stores depleted using saponin, CSK stiffness and apparent viscosity were found to rise by approximately 20%, whereas permanent deformation decreased by more than half. Addition of ATP (250 microM) under conditions that promote CSK tension generation in membrane-permeabilized cells resulted in decreases in CSK stiffness and apparent viscosity that could be detected within 2 min after ATP addition, before any measurable change in cell size.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗

Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts

DNA double-strand breaks (DSBs) were measured within a 3.2-Mbp NotI fragment on chromosome 21 of cells of a normal human fibroblast cell line. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rejoining as measured by a conventional pulsed-field gel electrophoresis technique (FAR assay). After 80 Gy of particle irradiations with LETs in the range of 7-150 keV/microm, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compared to X irradiation and that a larger proportion of the breaks remained unrepaired after 24 h. On the other hand, the misrejoining frequency as measured by the difference between correct and total rejoining after 24 h did not change with LET, but was approximately the same for all radiations at this dose, equal to 25-30% of the initial breaks. This result is discussed in relation to formation of chromosomal aberrations, deletion mutations and other biological end points.

NASA Discipline Radiation Health↗

Ionizing radiation induces heritable disruption of epithelial cell interactions

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

Non-NASA Center↗

A Biodosimeter for Multiparametric Determination of Radiation Dose, Radiation Quality, and Radiation Risk

Predicting risk of human cancer following exposure of an individual or a population to ionizing radiation is challenging. To an approximation, this is because uncertainties of uniform absorption of dose and the uniform processing of dose-related damage at the cellular level within a complex set of biological variables degrade the confidence of predicting the delayed expression of cancer as a relatively rare event. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the risk of developing cancer by the cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported. This is the demonstration of a dose responsive field effect of enhanced expression of keratin 18 (K18) in cultures of human mammary epithelial cells irradiated with cesium-1 37 gamma-rays. Dose response of enhanced K18 expression was experimentally extended over a range of 30 to 90 cGy for cells evaluated at mid-log phase. K18 has been reported to be a marker for tumor staging and for apoptosis, and thereby serves as an example of a potential marker for cancer risk, where the reality of such predictive value would require additional experimental development. Since observed radiogenic increase in expression of K18 is a field effect, ie., chronically present in all cells of the irradiated population, it may be hypothesized that K18 expression in specific cells absorbing particulate irradiation, such as the high-LET-producing atomic nuclei of space radiation, will report on both the single-cell distributions of those particles amongst cells within the exposed population, and that the relatively high dose per cell delivered by densely ionizing tracks of those intersecting particles will lead to cell-specific high-expression levels of K18, thereby providing analytical end points that may be used to resolve both the quantity and the quality of the radiation dose absorbed by individual cells. The principal value of this reported potential multiparametric cellular biodosimeter is suggested to be that it justifies a search for similar but more robust radiogenic assays. That is, K18 is only one radiation dose-sensitive expressed protein, whereas analytical techniques of genomics and proteomics can be used to simultaneously analyze multiple gene and protein expressions resulting from radiation-dose absorption. The potential usefulness of multiparametric cellular biodosimeters will be best realized from quantitatively profiling these multiple markers using these modern techniques.

Richmond, Robert↗