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

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At least 541 records · Page 30

Combining genome-wide association studies and expression quantitative trait nucleotide mapping with molecular and genetic validations to identify transcriptional networks regulating drought tolerance in Populus

Objectives: (i). To deploy a large-scale experimental drought trial for up to 1000 unique genotypes of Populus equipping the sites with controlled irrigation and drought treatments that are fully automated and monitored. FULLY COMPLETED (ii) To test the hypothesis that a suite of traits identified for drought tolerance in P. nigra can be measured in drought and control treatments in the wide germplasm collection of P. trichocarpa. FULLY COMPLETED (iii) To use established and novel GWAS model approaches to identify gene loci linked to drought tolerance traits on interest in P. trichocarpa. FULLY COMPLETED (iv) To undertake comparative analysis of GWAS results for drought tolerance traits in P. nigra and P. trichocarpa. PARTIALLY COMPLETED – remains active (v) Using RNAseq in P. trichocarpa, in droughted and control treatments to identify cis- and trans-regulated eQTN. FULLY COMPLETED (vi) Validate up to 50 cis-QTNs, from network hubs using transient protoplast assays. FULLY COMPLETED (vii) To establish Agrobacterium-based gene editing protocols in Populus. FULLY COMPLETED (viii) To utilize early leads from previous research to investigate at least 6 candidate genes for drought tolerance in Populus. FULLY COMPLETED (ix) To validate up to 20 candidate genes for drought tolerance in P. trichocarpa refined from the long-list tested in the transient assays for cis-acting hub gene targets. PARTIALLY COMPLETED- remains active.

60 APPLIED LIFE SCIENCES↗

Mechanisms for ribotoxin-induced ribosomal RNA cleavage

The Type B trichothecene deoxynivalenol (DON), a ribotoxic mycotoxin known to contaminate cereal-based foods, induces ribosomal RNA (rRNA) cleavage in the macrophage via p38-directed activation of caspases. Here we employed the RAW 264.7 murine macrophage model to test the hypothesis that this rRNA cleavage pathway is similarly induced by other ribotoxins. Capillary electrophoresis confirmed that the antibiotic anisomycin (≥ 25 ng/ml), the macrocylic trichothecene satratoxin G (SG) (≥ 10 ng/ml) and ribosome-inactivating protein ricin (≥ 300 ng/ml) induced 18s and 28s rRNA fragmentation patterns identical to that observed for DON. Also, as found for DON, inhibition of p38, double-stranded RNA-activated kinase (PKR) and hematopoietic cell kinase (Hck) suppressed MAPK anisomycin-induced rRNA cleavage, while, in contrast, their inhibition did not affect SG- and ricin-induced rRNA fragmentation. The p53 inhibitor pifithrin-μ and pan caspase inhibitor Z-VAD-FMK suppressed rRNA cleavage induced by anisomycin, SG and ricin, indicating that these ribotoxins shared with DON a conserved downstream pathway. Activation of caspases 8, 9 and 3 concurrently with apoptosis further suggested that rRNA cleavage occurred in parallel with both extrinsic and intrinsic pathways of programmed cell death. When specific inhibitors of cathepsins L and B (lysosomal cysteine cathepsins active at cytosolic neutral pH) were tested, only the former impaired anisomycin-, SG-, ricin- and DON-induced rRNA cleavage. Taken together, the data suggest that (1) all four ribotoxins induced p53-dependent rRNA cleavage via activation of cathepsin L and caspase 3, and (2) activation of p53 by DON and anisomycin involved p38 whereas SG and ricin activated p53 by an alternative mechanism. Highlights: ► Deoxynivalenol (DON) anisomycin, satratoxin G (SG) and ricin are ribotoxins. ► Ribotoxins induce 18s and 28s rRNA cleavage in the RAW 264.7 macrophage model. ► Ribotoxins induce rRNA cleavage via activation of p53, caspases and cathepsins. ► DON- and anisomycin-triggered rRNA cleavage is p38-dependent. ► SG- and ricin-induced rRNA cleavage is p38-independent.

60 APPLIED LIFE SCIENCES↗

DIFFERENTIAL CANID PREDATION OF TRANSLOCATED JUVENILE DESERT TORTOISES AND CHEMICAL SIGNATURE DIFFERENCES BETWEEN FEMALE AND MALE ADULT AND JUVENILE DESERT TORTOISES

Differential predation was observed in a population of 59 translocated juvenile Desert Tortoises (Gopherus agassizii) of known sex during a juvenile translocation survival study between September 2012 and November 2017. The main source of mortality (77%; 24 of 31 deaths) was attributed to Coyote (Canis latrans) and Kit Fox (Vulpes macrotis) predation. Predation was skewed with 71% (n = 17) female mortality versus 29% (n = 7) male mortality. We tested the hypothesis that juvenile females smell different than males which leads to increased canid predation. We also explored differences in chemical signatures of resident adult female and male Desert Tortoises. We collected oral, cloacal and chin/forelimb swabs from translocated juvenile and resident adult female and male tortoises during fall 2015 and fall 2017 and analyzed them using headspace gas chromatography/mass spectrometry to determine potential differences in the chemical signatures among the four groups. Standardized chromatographic peak responses were subjected to repeated analyses of variance (ANOVA). For development of artificial scents, mean responses were calculated for each juvenile tortoise from standardized responses representing all collections (i.e., oral, cloacal, and chin/forelimb swabs) and grand means were determined for males and females. Repeated measures ANOVAs clearly demonstrated that the collections of volatiles differed according to age and/or sex depending on the body location of collection. Among the plausibly endogenous volatiles that differed by age, many of them are alcohols. Two field trials using captive Coyotes and one field trial partially within the translocation area were conducted to test if Coyotes showed a preference for female or bias against male synthesized scent. No consistent preference or bias was shown, suggesting that no innate preference for female odor was evident.

60 APPLIED LIFE SCIENCES↗

Is Terzan 5 the remnant of a building block of the Galactic bulge? Evidence from APOGEE

ABSTRACT It has been proposed that the globular cluster-like system Terzan 5 is the surviving remnant of a primordial building block of the Milky Way bulge, mainly due to the age/metallicity spread and the distribution of its stars in the α–Fe plane. We employ Sloan Digital Sky Survey data from the Apache Point Observatory Galactic Evolution Experiment to test this hypothesis. Adopting a random sampling technique, we contrast the abundances of 10 elements in Terzan 5 stars with those of their bulge field counterparts with comparable atmospheric parameters, finding that they differ at statistically significant levels. Abundances between the two groups differ by more than 1σ in Ca, Mn, C, O, and Al, and more than 2σ in Si and Mg. Terzan 5 stars have lower [α/Fe] and higher [Mn/Fe] than their bulge counterparts. Given those differences, we conclude that Terzan 5 is not the remnant of a major building block of the bulge. We also estimate the stellar mass of the Terzan 5 progenitor based on predictions by the Evolution and Assembly of GaLaxies and their Environments suite of cosmological numerical simulations, concluding that it may have been as low as ∼3 × 108 M⊙ so that it was likely unable to significantly influence the mean chemistry of the bulge/inner disc, which is significantly more massive (∼1010 M⊙). We briefly discuss existing scenarios for the nature of Terzan 5 and propose an observational test that may help elucidate its origin.

79 ASTRONOMY AND ASTROPHYSICS↗

Acetaminophen-induced acute liver injury in HCV transgenic mice

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

60 APPLIED LIFE SCIENCES↗

Effects of Ringed Structures and Dust Size Growth on Millimeter Observations of Protoplanetary Disks

The growth of solids from sub-micron to millimeter and centimeter sizes is the early step toward the formation of planets inside protoplanetary disks (PPDs). However, such processes and their potential impact on the later stages of solid growth are still poorly understood. In this work, we test the hypothesis that most disks contain at least one ringed structure with a relative small radius. We have carried out a large family of 1D two-fluid (gas+dust) hydrodynamical simulations by evolving the gas and dust motion self-consistently while allowing dust size to evolve via coagulation and fragmentation. We investigate the joint effects of ringed structures and dust size growth on the overall sub-millimeter and millimeter (mm) flux and spectral index of PPDs. Ringed structures slow down the dust radial drift and speed up the dust growth. In particular, we find that those unresolved disks with a high fragmentation velocity (~10 m s -1 ) and a high dust surface density (~10 g cm -2 in the ring) can have mm spectral indices as low as ~2.0, consistent with mm observations of faint disks in nearby star forming regions. Furthermore, disks with more than one ringed structure can potentially reproduce brighter disks with spectral indices lower than ~2.5. Future multi-wavelength high-resolution observations of these low spectral index sources can be used to test the existence of the ringed structures in the unresolved disks and differentiate the effects of dust size growth from optical depth.

79 ASTRONOMY AND ASTROPHYSICS↗

Influence of Heat Flow from the Planetary Interior on Surface Habitability

an primordial and/or radiogenic heat flow from a rocky planet’s interior help maintain a surface environment amenable to life?On rocky Earth-like planets with shallow oceans (≤5 km depth) that are on the outer edge of the habitable zone, the additional energy provided might make the difference between a world supporting regional habitat space and a world uninhabitable by any known life-form. To test this hypothesis, we introduce heat flux from the planetary interior as a forcing to the NASA/GISSROCKE-3D exoplanet GCM, and explore whether it can enhance the habitability of marginal terrestrial rocky planets (e.g.,paleo Earth in a “snowball” climate state).GCM simulations of modern Earth have not included geothermal heat flux as a climate forcing, as it is more than an order of magnitude less than the 2.9 W/m heating caused by anthropogenic greenhouse gases [Flanner, GRL 2009]. Modern Earth measurements in the oceans [Downes et al., GRL 2019] and results from ocean GCMs [Barnes et al., Ocean Model. 2017]suggest that localized higher heat flux can have measurable thermodynamic and dynamic impacts, such as weakening deep ocean stratification and increased poleward ocean heat transports. A similar result with ROCKE-3D would be important, since our snowball Earth simulations without heat flux produce features like ocean stratification that should have hampered the survival of life. We have created a set of spatially variable geothermal heat fluxes at varying horizontal resolutions based on modern Earth heat flow patterns [Davies, Geochem. Geophys. Geosys. 2013] to test the sensitivity of the ROCKE-3D GCM initially in a modern Earth context. Preliminary results show that even modest heat fluxes have a measurable impact on deep ocean temperatures (upto +0.9°C locally) and that this heat can be transported at depth along ocean circulation paths. Estimates of heat flux impacts on vertical ocean mixing and surface ocean conditions require long simulations at the higher spatial resolutions needed to express heat flow at the scale of most ocean ridges. Ongoing simulations are focused on testing the impacts of horizontal resolution and flux scaling on surface environments, especially for “snowball” climate scenarios.

Heat flow↗

Cardiovascular function following reduced aerobic activity

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance, despite the accentuated aortic and cardiopulmonary baroreflex function following deconditioning.

Non-NASA Center↗

A Chlorine Isotope Transect Across the Sudbury Impact Deposits Reveals Enigmatic Isotopic Fractionation

Volatile elements play an important role in a variety of cosmochemical and geochemical processes. As such, there has been significant interest in their abundance and isotopic composition. Chlorine is an important element for tracing these processes because it is incompatible in nearly all minerals, extremely volatile, and strongly hydrophilic [1]. The Cl isotope composition ( 37 Cl/ 35 Cl) of meteoritic components, therefore, can provide useful information regarding the isotopic reservoirs that were present in the early Solar System and any secondary processes that may have occurred on different parent bodies (e.g., [2-4]). There is a relatively narrow range in the Cl isotope compositions of terrestrial, Martian, and chondritic meteorites (δ 37 Cl ~ −6 to +4‰) (e.g., [2,3,5,6]), with exceptions to this being the Moon and Vesta (up to ~ +81‰ and ~ +40‰, respectively) [4, 5, 7-10]. One hypothesis for the extreme Cl isotope fractionation observed on the Moon is degassing following large-scale (possibly even crust-breaching) impact events [7-9]. The role of hypervelocity impacts and impact-generated magmatism in the isotopic evolution of planetary materials, however, has been until recently an area of limited published research with the majority of works focusing on the effects of impact shock (e.g., [10-13]). The ~ 1.85 Ga Sudbury impact crater [14] located in Ontario, Canada, is one of the three largest impact craters on Earth with good exposures of its impact melt sheet and overlying breccias [15,16]. The impact melt sheet, called the Sudbury Igneous Complex (SIC), is up to 5 km thick [17], with an estimated original volume of >10 4 km 3 [18], and differentiated. Recent work demonstrated evaporative loss and isotope fractionation of the moderately volatile element zinc and suggest melt sheets produced by impacts could have a significant effect on the Earth’s volatile inventory [19]. In this study we investigate the abundance and isotopic composition of Cl as well the water abundance of apatite from the SIC and the overlying crater-fill to test the hypothesis that large-scale impacts may have generated the extensive Cl isotopic fractionation observed on the Moon.

Sudbury↗

Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca{sup 2+} flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation of cardiotoxicity is possible in a high-throughput format. • The assay shows benefits of automated data integration across multiple parameters. • Quantitative assessment of concentration–response is possible using iPSCs. • Multi-parametric screening allows for cardiotoxicity risk assessment.

60 APPLIED LIFE SCIENCES↗

Renal and Cardio-Endocrine Responses in Humans to Simulated Microgravity

The volume regulating systems are integrated to produce an appropriate response to both acute and chronic volume changes. Their responses include changing the levels of the hormones and neural inputs of the involved systems and/or changing the responsiveness of their target tissues. Weightlessness during space travel produces a volume challenge that is unfamiliar to the organism. Thus, it is likely that these volume regulatory mechanisms may respond inappropriately, e.g., a decrease in total body volume in space and abnormal responses to upright posture and stress on return to Earth. A similar "inappropriateness" also can occur in disease states, e.g., congestive heart failure. While it is clear that weightlessness produces profound changes in sodium and volume homeostasis, the mechanisms responsible for these changes are incompletely understood. Confounding this analysis is sleep deprivation, common in space travel, which can also modify volume homeostatic mechanisms. The purpose of this project is to provide the required understanding and then to design appropriate countermeasures to reduce or eliminate the adverse effects of microgravity. To accomplish this we are addressing five Specific Aims: (1) To test the hypothesis that microgravity modifies the acute responsiveness of the renin-angiotensin-aldosterone system (RAAS) and renal blood flow; (2) Does simulated microgravity change the circadian rhythm of the volume- regulating hormones?; (3) Does simulated microgravity change the target tissue responsiveness to angiotensin 11 (AngII)?; (4) Does chronic sleep deprivation modify the circadian rhythm of the RAAS and change the acute responsiveness of this system to posture beyond what a microgravity environment alone does? and (5) What effect does salt restriction have on the volume homeostatic and neurohumoral responses to a microgravity environment? Because the RAAS plays a pivotal role in blood pressure control and volume homeostasis, it likely is a major mediator of the adaptive cardio-renal responses observed during space missions and is a special focus of this project. Thus, the overall goal of this project is to assess the impact of microgravity and sleep deprivation in humans on volume-regulating systems. To achieve this overall objective, we are evaluating renal blood flow and the status and responsiveness of the volume- regulating systems (RAAS, atrial natriuretic peptide and vasopressin), and the adrenergic system (plasma and urine catecholamines) in both simulated microgravity and normal gravity with and -Without sleep deprivation. Furthermore, the responses of the volume homeostatic mechanisms to acute stimulation by upright tilt testing, standing and exercise are being evaluated before and after achieving equilibrium with these interventions.

Williams, Gordon H.↗

Ion Acceleration by Laser Plasma Interaction from Cryogenic Microjets

Processes that occur in extreme conditions, such as in the center of stars and large planets, can be simulated in the laboratory using facilities such as SLAC National Accelerator Laboratory and the Jupiter Laser Facility (JLF) at Lawrence Livermore National Laboratory (LLNL). These facilities allow scientists to investigate the properties of matter by observing their interactions with high-power lasers. Ion acceleration from laser plasma interaction is gaining greater attention today due to its widespread potential applications, including proton beam cancer therapy and fast ignition for energy production. Typically, ion acceleration is achieved by focusing a high power laser on thin foil targets through a mechanism called Target Normal Sheath Acceleration. However, this mechanism is not ideal for creating the high-energy proton beams needed for future applications. Based on research and recent experiments, we hypothesized that a pure liquid cryogenic jet would be an ideal target for exploring new regimes of ion acceleration. Furthermore, it would provide a continuous, pure target, unlike metal foils which are consumed in the interaction and easily contaminated. In an effort to test this hypothesis, we used the 527 nm split beam, frequency-doubled TITAN laser at JLF. Data from the cryogenic jets was limited due to the flow of current up the jet into the nozzle during the interaction, heating the jet and damaging the orifice. However, we achieved a pure proton beam with evidence of a monoenergetic feature. Furthermore, data from gold and carbon wires showed surprising and interesting results. Preliminary analysis of data from two ion emission diagnostics, Thomson parabola spectrometers (TPs) and radio chromic films (RCFs), suggests that shockwave acceleration occurred rather than target normal sheath acceleration, the standard mechanism of ion acceleration. Upon completion of the experiment at TITAN, I researched the possibility of transforming our liquid cryogenic jets into droplet streams. This type of target should solve our problems with the jet as it will prevent the flow of exocurrent into the nozzle. It is also highly effective as it is even more mass-limited than standard cryogenic jets. Furthermore, jets break up spontaneously anyway. If we can control the breakup, we can synchronize the droplet emission with the laser pulses. In order to assist the team prepare for an experiment later this year, I familiarized myself with the physics and theory of droplet formation, calculated values for the required parameters, and ordered the required materials for modification of the jet. Future experiments will test these droplet streams and continue towards the goal of ion acceleration using cryogenic targets.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Ion acceleration by laser plasma interaction from liquid cryogenic microjets [Abstract]

Processes that occur in extreme conditions, such as in the center of stars and large planets, can be simulated in the laboratory using facilities such as SLAC National Accelerator Laboratory and the Jupiter Laser Facility (JLF) at Lawrence Livermore National Laboratory (LLNL). These facilities allow scientists to investigate the properties of matter by observing their interactions with high power lasers. Ion acceleration from laser plasma interaction is gaining greater attention today due to its widespread potential applications, including proton beam cancer therapy and fast ignition for energy production. Typically, ion acceleration is achieved by focusing a high power laser on thin foil targets through a mechanism called Target Normal Sheath Acceleration. Based on research and recent experiments, we hypothesized that a pure liquid cryogenic jet would be an ideal target for this type of interaction, capable of producing the highest proton energies possible with todays laser technologies. Furthermore, it would provide a continuous, pure target, unlike metal foils which are consumed in the interaction and easily contaminated. In an effort to test this hypothesis and investigate new, potentially more efficient mechanisms of ion acceleration, we used the 527 nm split beam, frequency-doubled TITAN laser at JLF. Data from the cryogenic jets was limited due to the flow of current up the jet into the nozzle during the interaction, heating the jet and damaging the orifice. However, we acheived a pure proton beam with an indiciation of a monoenergetic feature. Furthermore, data from gold and carbon wires showed surprising and interesting results. Preliminary analysis of data from two ion emission diagnostics, Thomson parabola spectrometers (TPs) and radio chromic films (RCFs), suggests that shockwave acceleration occurred rather than target normal sheath acceleration, the standard mechanism of ion acceleration. Upon completion of the experiment at TITAN, I researched the possibility of transforming our liquid cryogenic jets into droplet streams. This type of target should solve our problems with the jet as it will prevent the flow of exocurrent into the nozzle. It is also highly effective as it is even more mass-limited than standard cryogenic jets. Furthermore, jets break up spontaneously anyway. If we can control the breakup, we can synchronize the droplet emission with the laser pulses. In order to assist the team prepare for an experiment later this year, I familiarized myself with the physics and theory of droplet formation, calculated values for the required parameters, and ordered the required materials for modification of the jet. Future experiments will test these droplet streams and continue towards the goal of ion acceleration using cryogenic targets.

43 PARTICLE ACCELERATORS↗

Ion Acceleration by Laser Plasma Interaction from Cryogenic Micro Jets - Oral Presentation [Slides]

Processes that occur in extreme conditions, such as in the center of stars and large planets, can be simulated in the laboratory using facilities such as SLAC National Accelerator Laboratory and the Jupiter Laser Facility (JLF) at Lawrence Livermore National Laboratory (LLNL). These facilities allow scientists to investigate the properties of matter by observing their interactions with high power lasers. Ion acceleration from laser plasma interaction is gaining greater attention today due to its widespread potential applications, including proton beam cancer therapy and fast ignition for energy production. Typically, ion acceleration is achieved by focusing a high power laser on thin foil targets through a mechanism called Target Normal Sheath Acceleration. Based on research and recent experiments, we hypothesized that a pure liquid cryogenic jet would be an ideal target for this type of interaction, capable of producing the highest proton energies possible with today’s laser technologies. Furthermore, it would provide a continuous, pure target, unlike metal foils which are consumed in the interaction and easily contaminated. In an effort to test this hypothesis and investigate new, potentially more efficient mechanisms of ion acceleration, we used the 527 nm split beam, frequency-doubled TITAN laser at JLF. Data from the cryogenic jets was limited due to the flow of current up the jet into the nozzle during the interaction, heating the jet and damaging the orifice. However, we achieved a pure proton beam with an indication of a monoenergetic feature. Furthermore, data from gold and carbon wires showed surprising and interesting results. Preliminary analysis of data from two ion emission diagnostics, Thomson parabola spectrometers (TPs) and radio chromic films (RCFs), suggests that shockwave acceleration occurred rather than target normal sheath acceleration, the standard mechanism of ion acceleration. Upon completion of the experiment at TITAN, I researched the possibility of transforming our liquid cryogenic jets into droplet streams. This type of target should solve our problems with the jet as it will prevent the flow of exocurrent into the nozzle. It is also highly effective as it is even more mass-limited than standard cryogenic jets. Furthermore, jets break up spontaneously anyway. If we can control the breakup, we can synchronize the droplet emission with the laser pulses. In order to assist the team prepare for an experiment later this year, I familiarized myself with the physics and theory of droplet formation, calculated values for the required parameters, and ordered the required materials for modification of the jet. Future experiments will test these droplet streams and continue towards the goal of ion acceleration using cryogenic targets.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

FEEDBACK FROM MASSIVE STARS AND GAS EXPULSION FROM PROTO-GLOBULAR CLUSTERS

Globular clusters (GCs) are considerably more complex structures than previously thought, harboring at least two stellar generations that present clearly distinct chemical abundances. Scenarios explaining the abundance patterns in GCs mostly assume that originally the clusters had to be much more massive than today, and that the second generation of stars originates from the gas shed by stars of the first generation (FG). The lack of metallicity spread in most GCs further requires that the supernova-enriched gas ejected by the FG is completely lost within ∼30 Myr, a hypothesis never tested by means of three-dimensional hydrodynamic simulations. In this paper, we use 3D hydrodynamic simulations including stellar feedback from winds and supernovae, radiative cooling and self-gravity to study whether a realistic distribution of OB associations in a massive proto-GC of initial mass M{sub tot} ∼ 10{sup 7} M{sub ⊙} is sufficient to expel its entire gas content. Our numerical experiment shows that the coherence of different associations plays a fundamental role: as the bubbles interact, distort, and merge, they carve narrow tunnels that reach deeper and deeper toward the innermost cluster regions, and through which the gas is able to escape. Our results indicate that after 3 Myr, the feedback from stellar winds is responsible for the removal of ∼40% of the pristine gas, and that after 14 Myr, 99% of the initial gas mass has been removed.

79 ASTRONOMY AND ASTROPHYSICS↗

Naphthalene DNA adduct formation and tolerance in the lung

Naphthalene (NA) is a respiratory toxicant and possible human carcinogen. NA is a ubiquitous combustion product and significant component of jet fuel. The National Toxicology Program found that NA forms tumors in two species, in rats (nose) and mice (lung). However, it has been argued that NA does not pose a cancer risk to humans because NA is bioactivated by cytochrome P450 monooxygenase enzymes that have very high efficiency in the lung tissue of rodents but low efficiency in the lung tissue of humans. It is thought that NA carcinogenesis in rodents is related to repeated cycles of lung epithelial injury and repair, an indirect mechanism. Repeated in vivo exposure to NA leads to development of tolerance, with the emergence of cells more resistant to NA insult. We tested the hypothesis that tolerance involves reduced susceptibility to the formation of NA-DNA adducts. NA-DNA adduct formation in tolerant mice was examined in individual, metabolically-active mouse airways exposed ex vivo to 250 μM 14 C-NA. Ex vivo dosing was used since it had been done previously and the act of creating a radioactive aerosol of a potential carcinogen posed too many safety and regulatory obstacles. Following extensive rinsing to remove unbound 14 C-NA, DNA was extracted and 14 C-NA-DNA adducts were quantified by accelerator mass spectrometry (AMS). The tolerant mice appeared to have slightly lower NA-DNA adduct levels than non-tolerant controls, but intra-group variations were large and the difference was statistically insignificant. It appears the tolerance may be more related to other mechanisms, such as NA-protein interactions in the airway, than DNA-adduct formation.

59 BASIC BIOLOGICAL SCIENCES↗

Feasibility study of a dual detector configuration concept for simultaneous megavoltage imaging and dose verification in radiotherapy

Purpose: To test the feasibility of a dual detector concept for comprehensive verification of external beam radiotherapy. Specifically, the authors test the hypothesis that a portal imaging device coupled to a 2D dosimeter provides a system capable of simultaneous imaging and dose verification, and that the presence of each device does not significantly detract from the performance of the other. Methods: The dual detector configuration comprised of a standard radiotherapy electronic portal imaging device (EPID) positioned directly on top of an ionization-chamber array (ICA) with 2 cm solid water buildup material (between EPID and ICA) and 5 cm solid backscatter material. The dose response characteristics of the ICA and the imaging performance of the EPID in the dual detector configuration were compared to the performance in their respective reference clinical configurations. The reference clinical configurations were 6 cm solid water buildup material, an ICA, and 5 cm solid water backscatter material as the reference dosimetry configuration, and an EPID with no additional buildup or solid backscatter material as the reference imaging configuration. The dose response of the ICA was evaluated by measuring the detector’s response with respect to off-axis position, field size, and transit object thickness. Clinical dosimetry performance was evaluated by measuring a range of clinical intensity-modulated radiation therapy (IMRT) beams in transit and nontransit geometries. The imaging performance of the EPID was evaluated quantitatively by measuring the contrast-to-noise ratio (CNR) and spatial resolution. Images of an anthropomorphic phantom were also used for qualitative assessment. Results: The measured off-axis and field size response with the ICA in both transit and nontransit geometries for both dual detector configuration and reference dosimetry configuration agreed to within 1%. Transit dose response as a function of object thickness agreed to within 0.5%. All IMRT test patterns and clinical IMRT beams had gamma pass rates of ≥98% at 2%/2 mm criteria. In terms of imaging performance, the measured CNR and spatial resolution (f{sub 50}) were 263.23 ± 24.85 and 0.4025 ± 1.25 × 10{sup −3} for dual detector configuration and 324 ± 26.65 and 0.4141 ± 1.14 × 10{sup −3} for reference imaging configuration, respectively. The CNR and spatial resolution were quantitatively worse in the dual detector configuration due to the additional backscatter. The difference in imaging performance was not visible in qualitative assessment of phantom images. Conclusions: Combining a commercially available ICA dosimetry device with a conventional EPID did not significantly detract from the performance of either device. Further improvements in imaging performance may be achieved with an optimized design. This study demonstrates the feasibility of a dual detector concept for simultaneous imaging and dosimetry in radiation therapy.

60 APPLIED LIFE SCIENCES↗

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗