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NASA NTRS2011

Space Weathering Impact on Solar System Surfaces and Planetary Mission Science

We often look "through a glass, darkly" at solar system bodies with tenuous atmospheres and direct surface exposure to the local space environment. Space weathering exposure acts via universal space-surface interaction processes to produce a thin patina of outer material covering, potentially obscuring endogenic surface materials of greatest interest for understanding origins and interior evolution. Examples of obscuring exogenic layers are radiation crusts on cometary nuclei and iogenic components of sulfate hydrate deposits on the trailing hemisphere of Europa. Weathering processes include plasma ion implantation into surfaces, sputtering by charged particles and solar ultraviolet photons, photolytic chemistry driven by UV irradiation, and radiolytic chemistry evolving from products of charged particle irradiation. Regolith structure from impacts, and underlying deeper structures from internal evolution, affects efficacy of certain surface interactions, e.g. sputtering as affected by porosity and surface irradiation dosage as partly attenuated by local topographic shielding. These processes should be regarded for mission science planning as potentially enabling, e.g. since direct surface sputtering, and resultant surface-bound exospheres, can provide in-situ samples of surface composition to ion and neutral mass spectrometers on orbital spacecraft. Sample return for highest sensitivity compOSitional and structural analyses at Earth will usually be precluded by limited range of surface sampling, long times for return, and high cost. Targeted advancements in instrument technology would be more cost efficient for local remote and in-situ sample analysis. More realistic laboratory simulations, e.g. for bulk samples, are needed to interpret mission science observations of weathered surfaces. Space environment effects on mission spacecraft and science operations must also be specified and mitigated from the hourly to monthly changes in space weather and from longer term (e.g., solar cycle) evolution of space climate. Capable instrumentation on planetary missions can and should be planned to contribute to knowledge of interplanetary space environments. Evolving data system technologies such as virtual observatories should be explored for more interdisciplinary application to the science of planetary surface, atmospheric, magnetospheric, and interplanetary interactions.

Cooper, John F.↗
NASA NTRS2011

Summer Research Paper

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Patel, Zarana↗
NASA NTRS2011

Space Motion Sickness - Analysis of Medical Debriefs Data for Incidence and Treatment

Astronauts use medications for the treatment of a variety of illnesses during space travel. Data mining efforts to assess minor clinical conditions occurring during Shuttle flights STS-1 through STS-94 revealed that space motion sickness (SMS) was the most common ailment during early flight days, occurring in approx.40% of crewmembers, followed by digestive system disturbances (9%) and infectious diseases, which most commonly involved the respiratory or urinary tracts. A more recent analysis of postflight medical debriefs data to examine trends with respect to medication use by astronauts during spaceflights indicated that ~37% of all prescriptions recorded was for pain followed by sleep (22%), SMS (18%), decongestion (14%), and all others (14%). Further analysis revealed that about 150 of 317 crewmembers experienced symptoms of SMS. Nearly all (132 of 150) crewmembers took medication for the treatment of symptoms with a total of 387 doses. Promethazine was taken most often (201 doses); in most cases this resulted in alleviation of symptoms with 130 crewmembers (65%) reporting feeling much or somewhat better. Although fewer total doses of the combination of promethazine and dextroamphetamine (Phen/Dex) were taken (45 doses), slightly more than half of these doses resulted in improvement. The combination of scopolamine and dextroamphetamine (Scop/Dex) was reported to be effective in only 37% of cases, with 36 of 97 total doses resulting in improvement. A higher percentage (24%) of Scop/Dex doses was reported to be ineffective compared with promethazine alone or as Phen/Dex (10% and 7%, respectively). Comparisons of the effectiveness of the different dosage forms of promethazine revealed that intramuscular injection was most effective in alleviating symptoms with 55% feeling much better, 16% feeling somewhat better, and only 7% feeling no effect or worse. Overall, it appears that promethazine alone was used more frequently during flight and was reported effective for the treatment of SMS.

Putcha, Lakshmi↗
NASA NTRS2004

Photodiode-Based, Passive Ultraviolet Dosimeters

Simple, passive instruments have been developed for measuring the exposure of material specimens to vacuum ultraviolet (VUV) radiation from the Sun. Each instrument contains a silicon photodiode and a coulometer. The photocharge generated in the photodiode is stored in the coulometer. The accumulated electric charge measured by use of the coulometer is assumed to be proportional to the cumulative dose of VUV radiation expressed in such convenient units as equivalent Sun hours (ESH) [defined as the number of hours of exposure to sunlight at normal incidence]. Intended originally for use aboard spacecraft, these instruments could also be adapted to such terrestrial uses as monitoring the curing of ultraviolet-curable epoxies. Each instrument includes a photodiode and a coulometer assembly mounted on an interface plate (see figure). The photodiode assembly includes an aluminum housing that holds the photodiode, a poly(tetrafluoroehylene) cosine receptor, and a narrow-band optical filter. The cosine receptor ensures that the angular response of the instrument approximates the ideal angular response (proportional to the cosine of the angle of incidence). The filter is chosen to pass the ultraviolet wavelength of interest in a specific experiment. The photodiode is electrically connected to the coulometer. The factor of proportionality between the charge stored in the coulometer and ultraviolet dosage (in units of ESH) is established, prior to use, in calibration experiments that involve the use of lamps and current sources traceable to the National Institute of Standards and Technology.

Vaughn, Jason A.↗
NASA NTRS2012

Protein Innovations Advance Drug Treatments, Skin Care

Dan Carter carefully layered the sheets of tracing paper on the light box. On each sheet were renderings of the atomic components of an essential human protein, one whose structure had long been a mystery. With each layer Carter laid down, a never-before-seen image became clearer. Carter joined NASA s Marshall Space Flight Center in 1985 and began exploring processes of protein crystal growth in space. By bouncing intense X-rays off the crystals, researchers can determine the electron densities around the thousands of atoms forming the protein molecules, unveiling their atomic structures. Cultivating crystals of sufficient quality on Earth was problematic; the microgravity conditions of space were far more accommodating. At the time, only a few hundred protein structures had been mapped, and the methods were time consuming and tedious. Carter hoped his work would help reveal the structure of human serum albumin, a major protein in the human circulatory system responsible for ferrying numerous small molecules in the blood. More was at stake than scientific curiosity. Albumin has a high affinity for most of the world s pharmaceuticals, Carter explains, and its interaction with drugs can change their safety and efficacy. When a medication enters the bloodstream a cancer chemotherapy drug, for example a majority of it can bind with albumin, leaving only a small percentage active for treatment. How a drug interacts with albumin can influence considerations like the necessary effective dosage, playing a significant role in the design and application of therapeutic measures. In spite of numerous difficulties, including having no access to microgravity following the 1986 Space Shuttle Challenger disaster, the image Carter had hoped to see was finally clarifying. In 1988, his lab had acquired specialized X-ray and detection equipment a tipping point. Carter and his colleagues began to piece together albumin s portrait, the formation of its electron densities coalescing on the sheets of tracing paper he arranged on the light box. While space-grown crystals were ultimately not involved in the achievement, a year later, Carter says, we were on the cover of Science magazine, having determined the atomic structure of albumin.

Source record↗
NASA NTRS2011

Method for Impeding Degradation of Porous Silicon Structures

This invention relates to surface modification of porosified silicon (pSi) structures with poly(alkylene) glycols for the purpose of controlled degradation of the silicon matrix and tailored release of encapsulated substances for biomedical applications. The pSi structures are currently used in diverse biomedical applications including bio-molecular screening, optical bio-sensoring, and drug delivery by means of injectable/orally administered carriers and implantable devices. The size of the pores and the surface chemistry of the pSi structure can be controlled during the microfabrication process and thereafter. A fine regulation of the degradation kinetics of mesoporous silicon structures is of fundamental importance. Polyethylene glycols (PEGs) represent the major category of surface modifying agents used in classical drug delivery systems and in pharmaceutical dosage forms. PEGylation enables avoidance of RES uptake, thus prolonging circulation time of intravenously injectable nanovectors. PEG molecules demonstrate little toxicity and immunogenicity, and are cleared from the body through the urine (molecular weight, MW less than 30 kDa) or in the feces (MW greater than 30kDa). The invention focuses on the possibility of finely tuning the degradation kinetics of the pSi nanovectors and other structures through surface conjugation of PEGs with various backbone lengths/MWs. To prove the concept, pSi nanovectors were covalently conjugated to seven PEGs with MW from 245 to 5,000 Da and their degradation kinetics in physiologically relevant media (phosphate buffer saline, PBS pH7.4, and fetal bovine serum) was assessed by the elemental analysis of the Si using inductive coupled plasma atomic emission spectroscopy (ICP-AES). The conjugation of the PEG with lowest MW to the nanovectors surface did not induce any change in the degradation kinetics in serum, but inhibited degradation and consequently the release of orthosilicic acid into buffer. When PEGs with the longer chains were evaluated, Si mass loss from the nanovectors was slowed down, and the PEGylated structures were almost fully degraded within 18 24 hours in serum and within 48 hours in PBS. The most dramatic effect was observed for high MW PEGs 3,400 and 5,000 Da, which prominently inhibited the degradation of the systems, with complete degradation achieved only after four days. For these PEGs, during the early stages of the degradation, there was a lag period of little or no Si mass loss from the nanovector. The obtained profiles were in agreement with the erosion of the nanovector surface as observed by scanning electron microscopy.

Vilentchouk, Biana Godin↗
NASA NTRS2012

Advances in Nanotechnology for Efficacious and Stable Formulation Development

Current operational medical kits aboard the International Space Station (ISS) include an array of medications intended for the treatment of minor ambulatory care symptoms, first aid, and basic life support. All medications contained in the flight kits are commercially available off-the-shelf formulations used for treatment of illnesses on Earth. However, transport and stowage of supplies including medications for space missions are exposed to adverse environmental conditions and extended shelf-life demands. Proposed missions to Mars and near-Earth objects such as asteroid 1999 AO10 will present crew health risk that is different both quantitatively and qualitatively from those encountered on ISS missions. Few drug options are available at the present time for mitigation of crew health risk of planned space exploration missions. Alternatives to standard oral formulations that include sustained and targeted delivery technologies for preventive healthcare in space will be a welcome addition to the space formulary and may include controlled release topical, sub-cutaneous, intranasal and inhalation dosage forms. An example of such a technology development endeavor can be nanotechnology-based multi-stage drug cocktail and vaccine delivery systems. Nanostructures also have the ability to protect drugs encapsulated within them from physiologic degradation, target their delivery with sustained release and are suitable for per oral routes of administration. The use of nanostructures such as polymeric nanoparticles offers a non-invasive approach for penetrating the blood brain barrier. Finally, nanotechnology offers great potential for the development of safe and efficacious drug delivery systems for preventive health care in space and on Earth.

Putcha, Lakshimi↗
NASA NTRS2012

Visible Light Responsive Catalysts Using Quantum Dot-Modified Ti02 for Air and Water Purification

The method of photocatalysis utilizing titanium dioxide, TiO2, as the catalyst has been widely studied for trace contaminant control for both air and water applications because of its low energy consumption and use of a regenerable catalyst. Titanium dioxide requires ultraviolet light for activation due to its band gap energy of 3.2 eV. Traditionally, Hg-vapor fluorescent light sources are used in PCO reactors and are a setback for the technology for space application due to the possibility of Hg contamination. The development of a visible light responsive (VLR) TiO2-based catalyst could lead to the use of solar energy in the visible region (approx.45% of the solar spectrum lies in the visible region; > 400 nm) or highly efficient LEDs (with wavelengths > 400 nm) to make PCO approaches more efficient, economical, and safe. Though VLR catalyst development has been an active area of research for the past two decades, there are few commercially available VLR catalysts; those that are available still have poor activity in the visible region compared to that in the UV region. Thus, this study was aimed at the further development of VLR catalysts by a new method - coupling of quantum dots (QD) of a narrow band gap semiconductor (e.g., CdS, CdSe, PbS, ZnSe, etc.) to the TiO2 by two preparation methods: 1) photodeposition and 2) mechanical alloying using a high-speed ball mill. A library of catalysts was developed and screened for gas and aqueous phase applications, using ethanol and 4-chlorophenol as the target contaminants, respectively. Both target compounds are well studied in photocatalytic systems serve as model contaminants for this research. Synthesized catalysts were compared in terms of preparation method, type of quantum dots, and dosage of quantum dots.

Coutts, Janelle L.↗
NASA NTRS2013

Population Pharmacokinetics of Intranasal Scopolamine

Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

Wu, L.↗
NASA NTRS2013

Thick Galactic Cosmic Radiation Shielding Using Atmospheric Data

NASA is concerned with protecting astronauts from the effects of galactic cosmic radiation and has expended substantial effort in the development of computer models to predict the shielding obtained from various materials. However, these models were only developed for shields up to about 120 g!cm2 in thickness and have predicted that shields of this thickness are insufficient to provide adequate protection for extended deep space flights. Consequently, effort is underway to extend the range of these models to thicker shields and experimental data is required to help confirm the resulting code. In this paper empirically obtained effective dose measurements from aircraft flights in the atmosphere are used to obtain the radiation shielding function of the earth's atmosphere, a very thick shield. Obtaining this result required solving an inverse problem and the method for solving it is presented. The results are shown to be in agreement with current code in the ranges where they overlap. These results are then checked and used to predict the radiation dosage under thick shields such as planetary regolith and the atmosphere of Venus.

Youngquist, Robert C.↗
NASA NTRS2013

Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at P<0.05(ΔOFV=3.84). Results: No significant difference in PK parameters between male and female subjects was observed with 0.1 and 0.2 mg doses. However, CL and Vd were significantly different between male and female subjects at the 0.4 mg dose. Results from population covariate modeling analysis indicate that a onecompartment PK model with first-order elimination rate offers best fit for describing INSCOP concentration-time profiles. The inclusion of sex as a covariate enhanced the model fitting (ΔOFV=-4.1) owing to the genderdependent CL and Vd differences after the 0.4 mg dose. Conclusion: Statistical modeling of scopolamine concentration-time data suggests gender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

Putcha, L.↗
NASA NTRS2014

Visible-Light-Responsive Catalysts Using Quantum Dot-Modified TiO2 for Air and Water Purification

Photocatalysis, the oxidation or reduction of contaminants by light-activated catalysts, utilizing titanium dioxide (TiO2) as the catalytic substrate has been widely studied for trace contaminant control in both air and water applications. The interest in this process is due primarily to its low energy consumption and capacity for catalyst regeneration. Titanium dioxide requires ultraviolet light for activation due to its relatively large band gap energy of 3.2 eV. Traditionally, Hg-vapor fluorescent light sources are used in PCO reactors; however, the use of mercury precludes the use of this PCO technology in a spaceflight environment due to concerns over crew Hg exposure. The development of a visible-light responsive (VLR) TiO2-based catalyst would eliminate the concerns over mercury contamination. Further, VLR development would allow for the use of ambient visible solar radiation or highly efficient LEDs, both of which would make PCO approaches more efficient, flexible, economical, and safe. Though VLR catalyst development has been an active area of research for the past two decades, there are few commercially available VLR catalysts. Those VLR catalysts that are commercially available do not have adequate catalytic activity, in the visible region, to make them competitive with those operating under UV irradiation. This study was initiated to develop more effective VLR catalysts through a novel method in which quantum dots (QD) consisting of narrow band gap semiconductors (e.g., CdS, CdSe, PbS, ZnSe, etc.) are coupled to TiO2 via two preparation methods: 1) photodeposition and 2) mechanical alloying using a high-speed ball mill. A library of catalysts was developed and screened for gas and aqueous phase applications using ethanol and 4-chlorophenol as the target contaminants, respectively. Both target compounds are well studied in photocatalytic systems and served as model contaminants for this research. Synthesized catalysts were compared in terms of preparation method, nature of the quantum dots, and dosage of quantum dots.

visible light↗
NASA NTRS2014

Innovative Technologies for Efficient Pharmacotherapeutic Management in Space

Current and future Space exploration missions and extended human presence in space aboard the ISS will expose crew to risks that differ both quantitatively and qualitatively from those encountered before by space travelers and will impose an unknown risk of safety and crew health. The technology development challenges for optimizing therapeutics in space must include the development of pharmaceuticals with extended stability, optimal efficacy and bioavailability with minimal toxicity and side effects. Innovative technology development goals may include sustained/chronic delivery preventive health care products and vaccines, low-cost high‐efficiency noninvasive, non‐oral dosage forms with radio‐protective formulation matrices and dispensing technologies coupled with self‐reliant tracking technologies for quality assurance and quality control assessment. These revolutionary advances in pharmaceutical technology will assure human presence in space and healthy living on Earth. Additionally, the Joint Commission on Accreditation of Healthcare Organizations advocates the use of health information technologies to effectively execute all aspects of medication management (prescribing, dispensing, and administration). The advent of personalized medicine and highly streamlined treatment regimens stimulated interest in new technologies for medication management. Intelligent monitoring devices enhance medication accountability compliance, enable effective drug use, and offer appropriate storage and security conditions for dangerous drug and controlled substance medications in remote sites where traditional pharmacies are unavailable. These features are ideal for Exploration Medical Capabilities. This presentation will highlight current novel commercial off‐the‐shelf (COTS) intelligent medication management devices for the unique dispensing, therapeutic drug monitoring, medication tracking, and drug delivery demands of exploration space medical operations.

Putcha, Lakshmi↗
NASA NTRS2015

Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC‐MS‐MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (‐2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non‐invasive sampling of saliva and/or urine.

Wu, L.↗
NASA NTRS2015

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

Patel, Zarana↗
NASA NTRS2015

Determination of Roles of Microgravity and Ionizing Radiation on the Reactivation of Epstein-Barr Virus In Vitro

Astronauts experience symptomatic and asymptomatic herpes virus reactivation during spaceflight. We have shown increases in reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella zoster virus (VZV) and shedding in body fluids (saliva and urine) in astronauts during space travel. Alterations in immunity, increased stress hormone levels, microgravity, increased radiation, and other conditions unique to spaceflight may promote reactivation of latent herpes viruses. Unique mechanico-physico forces associated with spaceflight can have profound effects on cellular function, especially immune cells. In space flight analog studies such as Antarctica, bed rest studies, and NASA's undersea habitat (Aquarius), reactivation of these viruses occurred, but to a lesser extent than spaceflight. Spaceflight analogs model some spaceflight factors, but none of the analogs recreates all factors experienced in space. Most notably, microgravity and radiation are not included in many analogs. Stress, processed through the HPA axis and SAM systems, induces viral reactivation. However, the respective roles of microgravity and increased space radiation levels or if any synergy exists are not known. Therefore, we studied the effect of modeled space radiation and/or microgravity, independent of the immune system on the changes in cellular gene expression that results in viral (EBV) reactivation. The effects of modeled microgravity and low shear on EBV replication and cellular and EBV gene expression were studied in human B-lymphocyte cell cultures. Latently infected B-lymphocytes were propagated in the rotating wall bioreactor and irradiated with the various dosages of gamma irradiation. At specific time intervals following exposure to modeled microgravity, the cells and supernatant were harvested and reactivation of EBV were assessed by measuring EBV and gene expression, DNA methylation, and infectious virus production.

Mehta, Satish K↗
NASA NTRS2016

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment /Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure. The ITD works by providing up to 7 cm H2O (approximately 5 mmHg) resistance to inspiratory air flow, effectively turning the thorax into a vacuum pump upon each inhalation which lowers the intrathoracic pressure (ITP) and facilitates venous return to the heart. The ITD is FDA-approved and was developed to augment venous return to the central circulation and increase cardiac output during cardiopulmonary resuscitation (CPR) and in patients with hypotension. While the effect of ITD on CPR survival outcomes is controversial, the ITD's ability to lower ITP with a concomitant decrease in intracranial pressure (ICP) is well documented. A similar concept that creates negative ITP during exhalation (intrathoracic pressure regulator; ITPR) decreased ICP in 16 of 20 patients with elevated ICP in a hospital pilot study. ITP and central venous pressure (CVP) have been shown to decrease in microgravity however ITP drops more than CVP, indicating an increased transmural CVP. This could explain the paradoxical distention of jugular veins (JV) in microgravity despite lower absolute CVP and also suggests that JV transmural pressure is not dramatically elevated. Use of an ITD may lower JV pressure enough to remove or relieve cephalic venous congestion. During spaceflight experiments with Braslet thigh cuffs and modified (open-glottis) Mueller maneuvers, Braslets alone reduced cardiac preload but only reduced the internal JV (IJV) cross sectional area by 23%. The addition of Mueller maneuvers resulted in an IJV area reduction of 48%. This project will test if ITD essentially applies a Mueller maneuver with added negative ITP in every respiratory cycle, acting to: 1) reduce venous congestion in the neck and 2) potentially lower ICP. The expected mechanism of action is that in microgravity (or an analog) blood is relocated toward the heart from vasculature in the head and neck. Once validated, the ITD would be an exceptionally easy countermeasure to deploy and test on the ISS. Dosage could be altered though 1) duration of application and 2) inspiratory resistance set point. Effects could be additionally enhanced through co-application with other countermeasures such as thigh cuffs or LBNP.

Ebert, D.↗
NASA NTRS2014

The Affect of the Space Environment on the Survival of Halorubrum Chaoviator and Synechococcus (Nageli): Data from the Space Experiment OSMO on EXPOSE-R

We have shown using ESA's Biopan facility flown in Earth orbit that when exposed to the space environment for 2 weeks the survival rate of Synechococcus (Nageli), a halophilic cyanobacterium isolated from the evaporitic gypsum-halite crusts that form along the marine intertidal, and Halorubrum chaoviator a member of the Halobacteriaceae isolated from an evaporitic NaCl crystal obtained from a salt evaporation pond, were higher than all other test organisms except Bacillus spores. These results led to the EXPOSE-R mission to extend and refine these experiments as part of the experimental package for the external platform space exposure facility on the ISS. The experiment was flown in February 2009 and the organisms were exposed to low-Earth orbit for nearly 2 years. Samples were either exposed to solar ultraviolet (UV)-radiation (lambda is greater than 110 nm or lambda is greater than 200 nm, cosmic radiation (dosage range 225-320 mGy), or kept in darkness shielded from solar UV-radiation. Half of each of the UV-radiation exposed samples and dark samples were exposed to space vacuum and half kept at 105 pascals in argon. Duplicate samples were kept in the laboratory to serve as unexposed controls. Ground simulation control experiments were also performed. After retrieval, organism viability was tested using Molecular Probes Live-Dead Bac-Lite stain and by their reproduction capability. Samples kept in the dark, but exposed to space vacuum had a 90 +/- 5% survival rate compared to the ground controls. Samples exposed to full UV-radiation for over a year were bleached and although results from Molecular Probes Live-Dead stain suggested approximately 10% survival, the data indicate that no survival was detected using cell growth and division using the most probable number method. Those samples exposed to attenuated UV-radiation exhibited limited survival. Results from of this study are relevant to understanding adaptation and evolution of life, the future of life beyond earth, the potential for interplanetary transfer of viable microbes via meteorites and dust particles as well as spacecraft, and the physiology of halophiles.

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