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NASA NTRSDate not supplied

Developing High-Throughput Organ-on-a-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to the galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neuronal damage and neuroinflammation associated with cognitive and behavioral dysfunction. In general, the extent of CNS damage is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we established a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments in response to ionizing radiation, based on commercially available OrganoPlates (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells. We investigated both immediate and delayed CNS responses to major GCR components: 0.15-0.5 Gy 250MeV/n 4-He, and 0.3-0.8 Gy 600 MeV/n 56-Fe; as well as to 0.5-1 Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by morphological changes in endothelial cells and tight junctions, altered cytokine profile including TNFa upregulation, and increased oxidative stress. We also quantified irradiation-mediated changes in astrocyte activation and neuronal functions, revealing major astrocyte damage mediated by 600MeV/n 56-Fe particles. Thus, we demonstrate that deep space radiation may contribute to CNS damage by disrupting both astrocyte and endothelial cell components of the blood-brain barrier. Our next steps include mapping and validating the transcriptomic changes induced by simulated GCRs and their components in human CNS models. Ultimately, we aim to uncover potential novel targets for countermeasure developments to mitigate CNS damage in long duration spaceflight.

Radiation↗

NASA NTRS1972

The velocity fields in active regions.

Investigation of the nature of the apparent downward flow of matter over plages indicated by Doppler shifts observed in photospheric spectral lines. From further line-shift observations in two spectral lines, it is determined that the downward motions observed over plages may represent a real downward transport of material, and not a merely apparent downward flow due to brightness or ionization differences in a multistream velocity model.

Howard, R.↗

NASA NTRS1972

Long duration solar active regions

Nimbus 3 and 4 observations of ultraviolet active regions of the sun have been investigated. It is not clear what is producing these UV-active regions, however, it could be changes in the overall intensity of the solar continuum near the region of the temperature minimum, or the solar flux variations that have been seen could be due to a continuous type of absorption like that associated with the ionization limits of elements such as aluminum, silicon, or magnesium.

Heath, D.↗

NASA NTRS1982

Goddard X-ray astronomy contributions to the IAU/COSPAR (1982)

The relation of X-ray flux to both the continuum flux in the optical and radio bands, and to the line emission properties of these objects were studied. The Einstein Observatory, because of increased sensitivity and improved angular resolution, increased substantially the number of known X-ray emitting active galactic nuclei. The Einstein imaging instruments detected morphology in AGN X-ray emission, in particular from jetlike structures in Cen-A, M87, and 3C273. The improved energy resolution and sensitivity of the spectrometers onboard the Observatory provide information on the geometry and ionization structure of the region responsible for the broad optical emission lines in a few AGN's. This information, combined with theoretical modeling and IUE and optical observations, allows the construction of a moderately detailed picture of the broad line region in these objects.

Holt, S. S.↗

NASA NTRS1991

Impact and collisional processes in the solar system

As impact cratered terrains have been successively recognized on certain planets and planetary satellites, it has become clear that impact processes are important to the understanding of the accretion and evolution of all solid planets. The noble gases in the normalized atmospheric inventories of the planets and the normalized gas content of meteorites are grossly similar, but demonstrate differences from each other which are not understood. In order to study shock devolatilization of the candidate carrier phases which are principally thought to be carbonaceous or hydrocarbons in planetesimals, experiments were conducted on noble gase implantation in various carbons: carbon black, activated charcoal, graphite, and carbon glass. These were candidate starting materials for impact devolatilization experiments. Initial experiments were conducted on vitreous amorphous carbon samples which were synthesized under vapor saturated conditions using argon as the pressurizing medium. An amino acid and surface analysis by laser ionization analyses were performed on three samples of shocked Murchison meteorite. A first study was completed in which a series of shock loading experiments on a porous limestone and on a non-porous gabbro in one and three dimensions were performed. Also a series of recovery experiments were conducted in which shocked molten basalt a 1700 C is encapsulated in molybdenum containers and shock recovered from up to 6 GPa pressures.

Ahrens, Thomas J.↗

NASA NTRSDate not supplied

Application of EUV and SXR Spectra from the EUNIS Sounding Rocket to Solar Coronal Heating

The nanoflare model is among the most actively investigated approaches to the longstanding problem of solar coronal heating. According to this model, the ~2 MK corona is heated by numerous tiny impulsive heating events, each of which is too small to be detected individually. Evidence for nanoflares is faint emission from small amounts of plasma at flare-like temperatures (4-10 MK) in non-flaring regions. The Extreme Ultraviolet Normal Incidence Spectrograph (EUNIS) sounding rocket instrument was designed to investigate coronal heating by observing emission lines of Fe XVIII, whose maximum ionization fraction occurs at temperatures around 7.1 MK, and Fe XIX (8.9 MK). Although expected to be faint, emission from hot plasma to which these lines are sensitive provides compelling evidence for the nanoflare model. EUNIS observes spectral line emission at 92-115 A in 3rd order, 277-344 A in 1st order, and 530-640 A in 1st order. These wavebands include lines from Fe XVIII and Fe XIX, as well as lines from ions formed over a wide range of lower temperatures (0.1-3.5 MK). We present preliminary results for a quiescent solar active region observed during the flight of 2021 May 18.

ultraviolet radiation↗

NASA NTRS1983

A comparison of wind observations of the upper thermosphere from the Dynamics Explorer satellite with the predictions of a global time-dependent model

Experimental and theoretical investigations of high-latitude circulation in the upper thermosphere are reported. Vector-wind plots constructed by combining remotely sensed meridional-wind and in situ zonal-wind data obtained during four south-polar and three north-polar passes of the NASA Dynamics Explorer satellite in October and December, 1981, are presented and analyzed, taking the geomagnetic activity level and local solar time into account. The results are then compared with the predictions of 3D time-dependent global models of thermospheric neutral winds (Fuller-Rowell and Rees, 1980, 1981, 1983) adjusted to account for both solar-UV/EUV heating and ionization effects and quiet (Kp from 1 to 2) or moderately disturbed (Kp from 3 to 4) geomagnetic conditions (models Q and MD). An MD model incorporating a self-consistent description of the high-latitude ionosphere and a Q model excluding high-latitude effects are found to give the most accurate predictions for the respective geomagnetic conditions.

Rees, D.↗

NASA NTRS1993

Implications of Lyman-alpha equivalent widths in active galactic nuclei

Results of photoionization calculations that examine the sensitivity of Ly-alpha emission to parameters describing the broadline clouds and incident radiation field are reported. The case of the Seyfert I galaxy NGC 5548 is considered, and good consistency is found with observed properties of the Ly-alpha zone for a cloud density of about 10 exp 11/cu cm and ratio of ionizing photon to hydrogen density near 0.2. Estimation of the cloud covering factor depends on the extrapolation of the EUV continuum. EUV cutoffs at 20 and 60 eV correspond to a range of covering factors between 0.8 and 0.5, which is larger than typically assumed in the past for luminous Seyferts. Equivalent width observations of Fairall 9 show that its continuum cannot be as soft as suggested by previous line ratio analyses and imply that its EUV continuum persists to 20 eV or more before cutting off. A method by which variability measurements can be combined with the present calculations to measure the distances to AGN, and hence the Hubble constant, is outlined.

Shields, Joseph C.↗

NASA NTRS1994

The Fraternal Twins of Quartet O4(+)

Eleven stationary geometries of quartet O4(+) have been studied by ab initio methods. The geometries were optimized at the Complete Active Space Self-Consistent Field (CASSCF) level of theory and the energies were calculated by the multiconfigurational second order pertubation method (CASPT2), using Double-Zeta Plus polarization (DZP), Triple-Zeta Plus Double Polarization (TZ2P), average Atomic Natural Orbital (ANO) (5s4p2d) and average ANO (6s5p3d2f) basis sets. The rectangular and trans-planar structures are found to be the most stable, with an energy barrier to conversion between the two at the threshold of dissociation. Both have a delocalized hole and are stable relative to separated 02 and 02(+)by 11.0 and 11.5 kcal/mol for the rectangular and the 2 trans-planar structure, respectively, compared with the experimentally deduced energy in the range of 9.2 to 10.8 kcal/mol. The adiabatic ionization potentials of 04 and 02 are computed to be 11.67 and 12.21 eV, while experimental values are 11.66 and 12.07 eV, respectively. The vibrational frequencies have been computed for all degrees of freedom at the CASSCF level of theory. Symmetry breaking is found to be a particular problem in the computation of the antisymmetric stretch frequency for the delocalized structures at the CASSCF level of theory. Attempts to rectify these problems using the restricted active space self-consistent field (RASSCF) method leads to additional difficulties, but further analysis yields insight into the symmetry breaking and problems with earlier calculations. Finally, a nonorthogonal configuration interaction (CI) calculation based on the interaction of localized CASSCF wave functions using the Complete Active Space State Interation (CASSI) method leads to a balanced treatment of the antisymmetric stretch which is free from symmetry breaking. The study explains the four most prominent absorption frequencies observed in the partially unassigned IR spectrum of O4(+) isolated in solid neon as the antisymmetric OO stretch, and the combination band of the symmetric and antisymmetric 00 stretch of both the rectangular and trans-planar structures.

Lindh, Roland↗

NASA NTRS1972

Radiative transfer effects behind reflected shock waves

Theoretical studies are reported which were largely centered on the nonequilibrium coupling of collisional, ionization, and radiative transfer processes behind reflected shock waves in nitrogen. Experimental studies included broad-band photomultiplier radiative intensity measurements, luminosity photographs of the reflected shock wave front, end-wall heat transfer measurements, and reflected shock velocity time-history measurements. The results of these activities are summarized, and comparisons between the theoretical and experimental results are discussed.

Nerem, R. M.↗

NASA NTRS1975

A search for chemical laser action in low pressure metal vapor flames

Optical emissions were studied from low pressure (approximately 1 torr) dilute diffusion flames of Ca and Mg vapor with O2, N2O and mixtures of CCl4 and O2. The Ca flames with O2 and N2O revealed high vibrational excitation of the product CaO molecule (up to v=30). The flames with CCl4 revealed extreme nonequilibrium metal atom electronic excitation, up to the metal atom ionization limit (6.1 eV for Ca, 7.6 eV for Mg). The metal atom excited electronic state populations did not follow a Boltzmann distribution, but the excitation rates ('pumping rate') were found to obey an Arrhenius-type expression, with the electronic excitation energy playing the role of activation energy and a temperature of about 5000 K for triplet excited states and 2500 K for singlets (vs. approximately 500 K translational temperature).

Zwillenberg, M. L.↗

NASA NTRS1990

The interstellar halo of spiral galaxies: NGC 891

Researchers have detected the Warm Ionized Medium (WIM) phase in the galaxy NGC 891. They found that the radial distribution of the WIM follows the molecular or young star distribution - an expected dependence. The amount of the WIM in this galaxy exceeds that in our Galaxy. The major surprize is the large thickness of the WIM phase - about 9 kpc instead 3 kpc as in our Galaxy. Clearly, this is the most significant result of the observations. The presence of low ionization gas at high z as well as at large galactocentric radii (where young stars are rare) is an important clue to the origin of the halo and observations such as the one reported here provide important data on this crucial question. In particular, the ionization of gas at high absolute z implies that either the UV photons manage to escape from the disk of the galaxy or that the extragalactic UV background plays an important role. The bulk of the WIM in spiral galaxies is a result of star-formation activity and thus these results can be understood by invoking a high star formation rate in NGC 891. Only the concerted action of supernovae can get the gas to the large z-heights as is observed in this galaxy. Support for this view comes from our detection of many worms i.e., bits and pieces of supershells in the form of kilo-parsec long vertical filaments. Researchers also saw a 600-pc size supershell located nearly one kpc above the plane of the galaxy.

Kulkarni, Shrinivas R.↗

NASA NTRS1992

Summary of ionizing radiation analysis on the Long Duration Exposure Facility

The ionizing radiation measurements flown on the Long Duration Exposure Facility (LDEF) were contained in 15 experiments which utilized passive detectors to pursue objectives in astrophysics and to measure the radiation environment and dosimetric quantities. The spacecraft structure became sufficiently radioactive to permit additional important studies. The induced activity allows extensive radiation mapping in the structure, and independent comparison with experiment dosimetric techniques, and significant studies of secondary effects. The long exposure time, attitude stability, and number and types of measurements produced a unique and critical set of data for low Earth orbit that will not be duplicated for more than a decade. The data allow an unprecedented test, and improvement if required, of models of the radiation environment and the radiation transport methods that are used to calculate the internal radiation and its effects in spacecraft. Results of measurements in the experiments, as well as from radioactivity in the structure, have clearly shown effects from the directional properties of the radiation environment, and progress was made in the dosimetric mapping of LDEF. These measurements have already influenced some Space Station Freedom design requirements. Preliminary results from experiments, reported at this symposium and in earlier papers, show that the 5.8 years exposure considerably enhanced the scientific return of the radiation measurements. The early results give confidence that the experiments will make significant advances in the knowledge of ultra heavy cosmic rays, anomalous cosmic rays, and heavy ions trapped in the radiation belts. Unexpected phenomena were observed, which require explanation. These include stopping iron group ions between the energy ranges anticipated for anomalous and galactic cosmic rays in the LDEF orbit. A surprising concentration of the Be-7 nuclide was discovered on the 'front' surface of LDEF, apparently transported up from the stratosphere with exceptional efficiency.

Parnell, T. A.↗

NASA NTRS2001

An Imaging Calorimeter for Access-Concept Study

A mission concept study to define the "Advanced Cosmic-ray Composition Experiment for Space Station (ACCESS)" was sponsored by the National Aeronautics and Space Administration (NASA). The ACCESS instrument complement contains a transition radiation detector and an ionization calorimeter to measure tile spectrum of protons, helium, and heavier nuclei up to approximately 10(exp 15) eV to search for the limit of S/N shock wave acceleration, or evidence for other explanations of the spectra. Several calorimeter configurations have been studied, including the "baseline" totally active bismuth germanate instrument and sampling calorimeters utilizing various detectors. The Imaging Calorimeter for ACCESS (ICA) concept comprises a carbon target and a calorimeter using a high atomic number absorber sampled approximately each radiation length (rl) by thin scintillating fiber (SCIFI) detectors. The main features and options of the ICA instrument configuration are described in this paper. Since direct calibration is not possible over most of the energy range, the best approach must be decided from simulations of calorimeter performance extrapolated from CERN calibrations at 0.375 TeV. This paper presents results from the ICA simulations study.

Parnell, T. A.↗

NASA NTRS2002

Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Compounds and their Ions: Polycyclic Aromatic Nitrogen Heterocycles - 6

The matrix-isolation technique has been employed to measure the mid-infrared spectra of several polycyclic aromatic nitrogen heterocycles in both neutral and cationic forms. The species studied include: 7,8 benzoquinoline (C13H9N); 2-azapyrene (C15H9N); 1- and 2-azabenz(a)anthracene (C17H11N); and 1-, 2-, and 4-azachrysene (also C17H11N). The experimentally measured band frequencies and intensities for each molecule are tabulated and compared with their theoretically calculated values computed using density functional theory at the B3LYP/4-31G level. The overall agreement between experiment and theory is quite good, in keeping with previous investigations involving the parent aromatic hydrocarbons. Several interesting spectroscopic trends are found to accompany nitrogen substitution into the aromatic framework of these compounds. First, for the neutral species, the nitrogen atom produces a significant increase in the total integrated infrared intensity across the 1600 - 1100/cm region and plays an essential role in the molecular vibration that underlies an uncharacteristically intense, discrete feature that is observed near 1400/cm in the spectra of 7,8 benzoquinoline, 1-azabenz(a)anthracene, and 4-azachrysene. The origin of this enhanced infrared activity and the nature of the new 1400/cm vibrational mode are explored. Finally, in contrast to the parent hydrocarbon species, these aromatic nitrogen heterocycles possess a significant permanent dipole moment. Consequently, these dipole moments and the rotational constants are reported for these species in their neutral and ionized forms.

Mattioda, A. L.↗

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 NTRS2024

Comparison of Geant4-DNA and RITRACKS/RITCARD: Microdosimetry, Nanodosimetry and DNA Damage Predictions for Low to High LET Ions

Low linear energy transfer (LET) ionizing radiations induce homogeneously distributed DNA damage at the cellular scale, while high LET ionizing radiations are well known to create complex biological damage including clustered double strand breaks (DSB). Clustered DSB are critical events that are difficult to repair, leading to increased biological outcomes compared to low LET radiation exposure. Recent studies have shown that DNA compaction, which can be actively modified by the cell to allow DNA repair, influences the yield of DSB [1]. The goal of this work is to determine the impact of DNA compaction on chromosome aberration formation, a biomarker of radiation-induced cancer risk. The RITRACKS track structure code [2], together with the RITCARD code [3], allow one to simulate the transport of high LET ions, calculate DNA damage and repair, and chromosome aberration formation, but does not include detailed geometrical models of DNA. The Geant4-DNA toolkit provides such detailed models with different levels of DNA compaction [1,4], but does not model chromosome aberration formation. In this work, these highly detailed DNA geometries are used to compute DNA breaks with Geant4-DNA and combine the results with the RITCARD tool to compute chromosome aberrations. As a first step, we compared the transport models used in RITRACKS and Geant4-DNA and newly released heavy ion model transport (G4DNARuddIonisationExtendedModel Geant4 v11.2) to ensure consistency between the physical stage of the two radiation transport codes. We compared energy deposition at the micrometric and nanometric scales for different ions (H 250 MeV, H 150 Me, He 250 MeV/n, C 290 MeV/n, O 350 MeV/n, O 55 MeV/n, Si 170MeV/n, Ti 300 MeV/n, Ti 300 MeV/n, Fe 600 MeV/n, Fe 450 MeV/n and Fe 300 MeV/n) with LET ranging from ~0.4 keV/μm up to 235 keV/μm. Excellent agreement is found for both microdosimetric and nanodosimetric spectra for all ion types and energies. The calculation of DNA breaks and their complexity with the Geant4-DNA is an ongoing work, and comparison with RITCARD will be presented based on result availability at the time of the conference. [1] Tang et al. (2019). Med. Phys., 46(3), 1501-1511. [2] Plante et al. (2008). NJP, 10(12), 125020. [3] Plante et al. (2019). Rad. Res., 192(3), 282-298. [4] Incerti et al. (2018). Med. Phys., 45(8), e722-e739.

Floriane Poignant↗

NASA NTRS1976

H2O(+) ions in comets: Comet Kohoutek (1973f) and comet Bradfield (1974b)

The image tube Cassegrain slit spectra of comet Kohoutek and Bradfield calibrated and reduced to relative intensities are discussed. Monochromatic changes in the surface brightness for various neutral and ionized molecules are determined. The intensities of C2 and CN decreased approximately four times faster than the intensity change for the H2O(+) features. It is shown that the excitation mechanism for the observed H2O(+) bands is by fluorescent scattering of the incident solar radiation. The effects of solar activity on the photoionization rate of H2O in a comet are discussed. Observations of another bright comet at the time of maximum solar activity are needed to determine changes in band intensities of comet tail ions due to solar activity.

Wehinger, P.↗