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NASA NTRS2009

The Elephant in the Room: Biomedical Challenges for Long Duration Lunar Habitation

This slide presentation reviews 4 biomedical challenges that are involved in long duration lunar habitation: dust, radiation, hypogravity and synergistic effects. The first two of these challenges are reviewed with more in-depth information. The dangers of dust relate to the particle deposition in the lungs. The dangers of radiation are related to the permissible exposure limit (PEL) and the Risk of Exposure Induced Death (REID), a statistical approach pegged to a single radiation effect: Death from cancer directly attributable to the exposure. There has been a realization that radiation is more harmful than predicted. This is demonstrated by showing the change in the recommended career dose limits, have changed between 1989 and 2000.

Logan, James S.↗

NASA NTRS2009

NASA Benefits Earth

This slide presentation reviews several ways in which NASA research has benefited Earth and made life on Earth better. These innovations include: solar panels, recycled pavement, thermometer pill, invisible braces for straightening teeth, LASIK, aerodynamic helmets and tires for bicycles, cataract detection, technology that was used to remove Anthrax spores from mail handling facilities, study of atomic oxygen erosion of materials has informed the restoration of artwork, macroencapsulation (a potential mechanism to deliver anti cancer drugs to specific sites), and research on a salmonella vaccine. With research on the International Space Station just beginning, there will be opportunities for entrepreneurs and other government agencies to access space for their research and development. As well as NASA continuing its own research on human health and technology development.

Robinson, Julie A.↗

NASA NTRS2009

Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome condensation (PCC) technique at the first mitosis post-irradiation. Chromosomes were analyzed using a multicolor fluorescence in-situ hybridization (mFISH) chromosome painting method. Preliminary analysis showed that chromosomal exchanges were increased in the cells treated with the specific ATM inhibitor. Possible cytogenetic signatures of acute and low dose-rate gamma irradiation in ATM or Nibrin deficient and suppressed cells will be discussed.

Hada, M.↗

NASA NTRS2008

Molecules for Fluorescence Detection of Specific Chemicals

A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at wavelengths of about 600 nm.

Fedor, Steve↗

NASA NTRS2009

The Use of Pro/Engineer CAD Software and Fishbowl Tool Kit in Ray-tracing Analysis

This document is designed as a manual for a user who wants to operate the Pro/ENGINEER (ProE) Wildfire 3.0 with the NASA Space Radiation Program's (SRP) custom-designed Toolkit, called 'Fishbowl', for the ray tracing of complex spacecraft geometries given by a ProE CAD model. The analysis of spacecraft geometry through ray tracing is a vital part in the calculation of health risks from space radiation. Space radiation poses severe risks of cancer, degenerative diseases and acute radiation sickness during long-term exploration missions, and shielding optimization is an important component in the application of radiation risk models. Ray tracing is a technique in which 3-dimensional (3D) vehicle geometry can be represented as the input for the space radiation transport code and subsequent risk calculations. In ray tracing a certain number of rays (on the order of 1000) are used to calculate the equivalent thickness, say of aluminum, of the spacecraft geometry seen at a point of interest called the dose point. The rays originate at the dose point and terminate at a homogenously distributed set of points lying on a sphere that circumscribes the spacecraft and that has its center at the dose point. The distance a ray traverses in each material is converted to aluminum or other user-selected equivalent thickness. Then all equivalent thicknesses are summed up for each ray. Since each ray points to a direction, the aluminum equivalent of each ray represents the shielding that the geometry provides to the dose point from that particular direction. This manual will first list for the user the contact information for help in installing ProE and Fishbowl in addition to notes on the platform support and system requirements information. Second, the document will show the user how to use the software to ray trace a Pro/E-designed 3-D assembly and will serve later as a reference for troubleshooting. The user is assumed to have previous knowledge of ProE and CAD modeling.

Nounu, Hatem N.↗

NASA NTRS2008

Using Light to Treat Mucositis and Help Wounds Heal

A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

Ignatius, Robert W.↗

NASA NTRS2008

Countermeasure for Radiation Protection and Repair

Exposure to ionizing radiation during long-duration space missions is expected to cause short-term illness and increase long-term risk of cancer for astronauts. Radiation-induced free radicals overload the antioxidant defense mechanisms and lead to cellular damage at the membrane, enzyme, and chromosome levels. A large number of radioprotective agents were screened, but most had significant side effects. But there is increasing evidence that significant radioprotective benefit is achieved by increasing the dietary intake of foods with high antioxidant potential. Early plant-growing systems for space missions will be limited in both size and volume to minimize power and mass requirements. These systems will be well suited to producing plants containing high concentrations of bioprotective antioxidants. This project explored whether the production of bioprotective compounds could be increased by altering the lighting system, without increasing the space or power requirements for production, and evaluated the effects of environmental conditions (light quantity, light quality, and carbon dioxide [CO2] concentration) on the production of bioprotective compounds in lettuce, which provide a biological countermeasure for radiation exposure. The specific deliverables were to develop a database of bioprotectant compounds in plants that are suitable for use on longduration space missions, develop protocols for maintaining and increasing bioprotectant production under light emitting diodes (LEDs), recommend lighting requirements to produce dietary countermeasures of radiation, and publish results in the Journal of the American Society for Horticultural Science.

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NASA NTRS2009

An Update on Mortality in the U.S. Astronaut Corps: 1959-2009

Although it has now been over 50 years since mankind first ventured into space, the long-term health impacts of human space flight remain largely unknown. Identifying factors that affect survival and prognosis among those who participate in space flight is vitally important, as the era of commercial space flight approaches and NASA prepares for missions to Mars. The Longitudinal Study of Astronaut Health is a prospective study designed to examine trends in astronaut morbidity and mortality. The purpose of this analysis was to describe and explore predictors of overall and cause-specific mortality among individuals selected for the U.S. astronaut corps. All U.S. astronauts (n=321), regardless of flight status, were included in this analysis. Death certificate searches were conducted to ascertain vital status and cause of death through April 2009. Data were collected from medical records and lifestyle questionnaires. Multivariable Cox regression modeling was used to calculate the mortality hazard associated with embarking on space flight, adjusted for sex, race, and age at selection. Between 1959 and 2009, there were 39 (12.1%) deaths. Of these deaths, 18 (42.2%) were due to occupational accidents; 7 (17.9%) were due to other accidents; 6 (15.4%) were attributable to cancer; 6 (15.4%) resulted from cardiovascular/circulatory diseases; and 2 (5.1%) were from other causes. Participation in space flight did not significantly increase mortality hazard over time (adjusted hazard ratio=0.57; 95% confidence interval=0.26-1.26. Because our results are based on a small sample size, future research that includes payload specialists, other space flight participants, and international crew members is warranted to maximize statistical power.

Amirian, E.↗

NASA NTRS2009

Identification of Trends into Dose Calculations for Astronauts through Performing Sensitivity Analysis on Calculational Models Used by the Radiation Health Office

The Radiation Health Office (RHO) determines each astronaut s cancer risk by using models to associate the amount of radiation dose that astronauts receive from spaceflight missions. The baryon transport codes (BRYNTRN), high charge (Z) and energy transport codes (HZETRN), and computer risk models are used to determine the effective dose received by astronauts in Low Earth orbit (LEO). This code uses an approximation of the Boltzman transport formula. The purpose of the project is to run this code for various International Space Station (ISS) flight parameters in order to gain a better understanding of how this code responds to different scenarios. The project will determine how variations in one set of parameters such as, the point of the solar cycle and altitude can affect the radiation exposure of astronauts during ISS missions. This project will benefit NASA by improving mission dosimetry.

Adams, Thomas↗

NASA NTRS2009

Distribution of Chromosome Breakpoints in Human Epithelial Cells Exposed to Low- and High-LET Radiations

The advantage of the multicolor banding in situ hybridization (mBAND) technique is not only its ability to identify simultaneously both inter- and intrachromosome exchanges, but also the ability to measure the breakpoint location along the length of the chromosome in a precision that is unmatched with other traditional banding techniques. Breakpoints on specific regions of a chromosome have been known to associate with specific cancers. The breakpoint distribution in cells after low- and high-LET radiation exposures will also provide the data for biophysical modeling of the chromatin structure, as well as the data for the modeling the formation of radiation-induced chromosome aberrations. In a series of experiments, we studied low- and high-LET radiation-induced chromosome aberrations using the mBAND technique with chromosome 3 painted in 23 different colored bands. Human epithelial cells (CH1 84B5F5/M10) were exposed in vitro to Cs- 137 rays at both low and high dose rates, secondary neutrons with a broad energy spectrum at a low dose rate and 600 MeV/u Fe ions at a high dose rate. The data of both inter- and intrachromosome aberrations involving the painted chromosome have been reported previously. Here we present data of the location of the chromosome breaks along the length of chromosome 3 in the cells after exposures to each of the four radiation scenarios. In comparison to the expected breakpoint distribution based on the length of the bands, the observed distribution appeared to be non-random for both the low- and high-LET radiations. In particular, hot spots towards both ends of the chromosome were found after low-LET irradiations of either low or high dose rates. For both high-LET radiation types (Fe ions and neutrons), the breakpoint distributions were similar, and were much smoother than that for low-LET radiation. The dependence of the breakpoint distribution on the radiation quality requires further investigations.

Hada, Megumi↗

NASA NTRS2009

Cell separation using electric fields

The present invention involves methods and devices which enable discrete objects having a conducting inner core, surrounded by a dielectric membrane to be selectively inactivated by electric fields via irreversible breakdown of their dielectric membrane. One important application of the invention is in the selection, purification, and/or purging of desired or undesired biological cells from cell suspensions. According to the invention, electric fields can be utilized to selectively inactivate and render non-viable particular subpopulations of cells in a suspension, while not adversely affecting other desired subpopulations. According to the inventive methods, the cells can be selected on the basis of intrinsic or induced differences in a characteristic electroporation threshold, which can depend, for example, on a difference in cell size and/or critical dielectric membrane breakdown voltage. The invention enables effective cell separation without the need to employ undesirable exogenous agents, such as toxins or antibodies. The inventive method also enables relatively rapid cell separation involving a relatively low degree of trauma or modification to the selected, desired cells. The inventive method has a variety of potential applications in clinical medicine, research, etc., with two of the more important foreseeable applications being stem cell enrichment/isolation, and cancer cell purging.

Mangano, Joseph↗

NASA NTRS2010

Polarization Imaging Apparatus

A polarization imaging apparatus has shown promise as a prototype of instruments for medical imaging with contrast greater than that achievable by use of non-polarized light. The underlying principles of design and operation are derived from observations that light interacts with tissue ultrastructures that affect reflectance, scattering, absorption, and polarization of light. The apparatus utilizes high-speed electro-optical components for generating light properties and acquiring polarization images through aligned polarizers. These components include phase retarders made of OptoCeramic (registered TradeMark) material - a ceramic that has a high electro-optical coefficient. The apparatus includes a computer running a program that implements a novel algorithm for controlling the phase retarders, capturing image data, and computing the Stokes polarization images. Potential applications include imaging of superficial cancers and other skin lesions, early detection of diseased cells, and microscopic analysis of tissues. The high imaging speed of this apparatus could be beneficial for observing live cells or tissues, and could enable rapid identification of moving targets in astronomy and national defense. The apparatus could also be used as an analysis tool in material research and industrial processing.

Zou, Yingyin K.↗

NASA NTRS2010

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

Chappell, Lori J.↗

NASA NTRS2010

Overview of the Graphical User Interface for the GERMcode (GCR Event-Based Risk Model)

The descriptions of biophysical events from heavy ions are of interest in radiobiology, cancer therapy, and space exploration. The biophysical description of the passage of heavy ions in tissue and shielding materials is best described by a stochastic approach that includes both ion track structure and nuclear interactions. A new computer model called the GCR Event-based Risk Model (GERM) code was developed for the description of biophysical events from heavy ion beams at the NASA Space Radiation Laboratory (NSRL). The GERMcode calculates basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at NSRL for the purpose of simulating space radiobiological effects. For mono-energetic beams, the code evaluates the linear-energy transfer (LET), range (R), and absorption in tissue equivalent material for a given Charge (Z), Mass Number (A) and kinetic energy (E) of an ion. In addition, a set of biophysical properties are evaluated such as the Poisson distribution of ion or delta-ray hits for a specified cellular area, cell survival curves, and mutation and tumor probabilities. The GERMcode also calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle. The contributions from primary ion and nuclear secondaries are evaluated. The GERMcode accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections, and has been used by the GERMcode for application to thick target experiments. The GERMcode provides scientists participating in NSRL experiments with the data needed for the interpretation of their experiments, including the ability to model the beam line, the shielding of samples and sample holders, and the estimates of basic physical and biological outputs of the designed experiments. We present an overview of the GERMcode GUI, as well as providing training applications.

Kim, Myung-Hee Y.↗

NASA NTRS2010

NASA Self-Assessment of Space Radiation Research

Space exploration involves unavoidable exposures to high-energy galactic cosmic rays whose penetration power and associated secondary radiation makes radiation shielding ineffective and cost prohibitive. NASA recognizing the possible health dangers from cosmic rays notified the U.S. Congress as early as 1959 of the need for a dedicated heavy ion accelerator to study the largely unknown biological effects of galactic cosmic rays on astronauts. Information and scientific tools to study radiation health effects expanded over the new decades as NASA exploration programs to the moon and preparations for Mars exploration were carried out. In the 1970 s through the early 1990 s a more than 3-fold increase over earlier estimates of fatal cancer risks from gamma-rays, and new knowledge of the biological dangers of high LET radiation were obtained. Other research has increased concern for degenerative risks to the central nervous system and other tissues at lower doses compared to earlier estimates. In 1996 a review by the National Academy of Sciences Space Science Board re-iterated the need for a dedicated ground-based accelerator facility capable of providing up to 2000 research hours per year to reduce uncertainties in risks projections and develop effective mitigation measures. In 1998 NASA appropriated funds for construction of a dedicated research facility and the NASA Space Radiation Laboratory (NSRL) opened for research in October of 2003. This year marks the 8th year of NSRL research were about 1000 research hours per year have been utilized. In anticipation of the approaching ten year milestone, funded investigators and selected others are invited to participate in a critical self-assessment of NSRL research progress towards NASA s goals in space radiation research. A Blue and Red Team Assessment format has been integrated into meeting posters and special plenary sessions to allow for a critical debate on the progress of the research and major gaps areas. Blue teams will highlight progress and important new knowledge gained. Red teams will challenge the Blue teams on proposed highlights and point to Gaps not considered. We will review the current space radiation Risks and Gaps under investigation at NASA, critical data sets and research highlights anticipated, and possible goals for future research at NSRL.

Cucinotta, Francis A.↗

NASA NTRS2010

Photoreceptor System for Melatonin Regulation and Phototherapy

The present invention involves a light system for stimulating or regulating neuroendocrine, circadian, and photoneural systems in mammals based upon the discovery of peak sensitivity ranging from 425-505 nm; a light meter system for quantifying light which stimulates or regulates mammalian circadian, photoneural, and neuroendocrine systems. The present invention also relates to translucent and transparent materials, and lamps or other light sources with or without filters capable of stimulating or regulating neuroendocrine, circadian, and photoneural systems in mammals. Additionally, the present invention involves treatment of mammals with a wide variety of disorders or deficits, including light responsive disorders, eating disorders, menstrual cycle disorders, non-specific alerting and performance deficits, hormone-sensitive cancers, and cardiovascular disorders.

Brainard, George↗

NASA NTRS2010

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Chappelli, Lori J.↗

NASA NTRS2010

Overview of the Graphical User Interface for the GERM Code (GCR Event-Based Risk Model

The descriptions of biophysical events from heavy ions are of interest in radiobiology, cancer therapy, and space exploration. The biophysical description of the passage of heavy ions in tissue and shielding materials is best described by a stochastic approach that includes both ion track structure and nuclear interactions. A new computer model called the GCR Event-based Risk Model (GERM) code was developed for the description of biophysical events from heavy ion beams at the NASA Space Radiation Laboratory (NSRL). The GERM code calculates basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at NSRL for the purpose of simulating space radiobiological effects. For mono-energetic beams, the code evaluates the linear-energy transfer (LET), range (R), and absorption in tissue equivalent material for a given Charge (Z), Mass Number (A) and kinetic energy (E) of an ion. In addition, a set of biophysical properties are evaluated such as the Poisson distribution of ion or delta-ray hits for a specified cellular area, cell survival curves, and mutation and tumor probabilities. The GERM code also calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle. The contributions from primary ion and nuclear secondaries are evaluated. The GERM code accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections, and has been used by the GERM code for application to thick target experiments. The GERM code provides scientists participating in NSRL experiments with the data needed for the interpretation of their experiments, including the ability to model the beam line, the shielding of samples and sample holders, and the estimates of basic physical and biological outputs of the designed experiments. We present an overview of the GERM code GUI, as well as providing training applications.

Kim, Myung-Hee↗