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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Identification of cathepsin B as a novel target of hypoxia-inducible factor-1-alpha in HepG2 cells

Highlights: • Cathepsin B (CTSB) is a novel target gene of hypoxia-inducible factor-1-alpha (HIF-1α). • CTSB mRNA and protein levels can be up-regulated in a HIF-1α-dependent manner. • CTSB promoter activity can be elevated by the HIF-1α protein. • HIF-1α protein binds the CTSB promoter directly. Hypoxia-inducible factor-1-alpha (HIF-1α) activates the transcription of many genes that code for proteins involved in angiogenesis, glucose metabolism, cell proliferation/survival, and invasion/metastasis. However, the mechanisms between HIF-1 and its downstream target genes are still poorly understood. Our experimental results had shown that nuclear HIF-1α proteins were significantly induced after HepG2 cells treatment with 1% O{sub 2} for 6 h and reached the peak expression level in 24 h. Meanwhile, the results of RT-qPCR and Western-blotting showed that HIF-1α and cathepsin B (CTSB) expressions increased with a similar pattern in response to hypoxia in the HepG2 cells. Additionally, based on bioinformatics analysis, we identified a hypoxia response element in the CTSB promoter, indicating a possible association between HIF-1α and CTSB. Moreover, luciferase assay was performed to reflect the transcriptional activity mediated through the HIF-1α binding HRE within the CTSB promoter. Furthermore, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) revealed a specific HIF-1α binding activity to the CTSB gene promoter. For the first time, we demonstrated that CTSB is a new HIF-1α-target gene. We believe these findings will contribute to the research and development of neoplasm-targeted therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A negative feedback loop between nuclear factor 90 (NF90) and an anti-oncogenic microRNA, miR-7

Highlights: • miR-7, an anti-oncogenic miRNA, represses NF90 at the mRNA level. • The coding region of the NF90 mRNA is directly targeted by miR-7. • A rise in NF90 is attributed to negative feedback between NF90 and miR-7 in tumors. Alterations in microRNAs (miRNAs) levels deeply correlate with tumorigenesis. However, the molecular mechanism for the regulation of the miRNA production in tumors is not fully understood. We previously reported that downregulation of miR-7, which is an anti-oncogenic miRNA, was caused by overexpression of the nuclear factor 90 (NF90)-nuclear factor 45 (NF45) complex through the binding of double-stranded (ds) RNA-binding proteins to primary miR-7, resulting in promotion of tumorigenesis (Higuchi et al 2016). During this study, we found that the level of NF90 protein was dramatically decreased by overexpression of miR-7. Interestingly, the miR-7-mediated reduction in NF90 family proteins was only observed in NF90 protein, but not in NF110 protein, which is a longer form of the NF90 gene. Luciferase reporter analysis indicated that the overexpression of miR-7 significantly repressed the luciferase activity in the coding region of NF90 mRNA harboring a predicted target sequence of miR-7. The luciferase activity of the reporter vector, which has a mutated miR-7 target site in the coding region, was the same in the control and miR-7 overexpressed cells. Furthermore, the translation of TARGET-tagged NF90 mRNA without the 3′UTR of the NF90 mRNA was inhibited by the overexpression of miR-7. These results imply that miR-7 suppresses NF90 at the protein level through the binding of miR-7 to the complementary site of the seed sequence in the coding region of the NF90 mRNA. We further confirmed increased endogenous NF90 protein levels in SK-N-SH cells transfected with antisense oligonucleotides targeting miR-7, indicating that miR-7-mediated translational repression of NF90 is a physiological event. Taken together with our previous findings (Higuchi et al 2016), it suggests that the level of NF90 is increased by a negative feedback loop between NF90 and miR-7 in tumor tissues under physiological conditions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Effect of growth differentiation factor-15 secreted by human umbilical cord blood-derived mesenchymal stem cells on amyloid beta levels in in vitro and in vivo models of Alzheimer's disease

Highlights: • Paracrine action of hUCB-MSCs enhances Aβ clearance through microglial modulation. • GDF-15 secreted from hUCB-MSCs promotes the decrease of Aβ levels via enhancing IDE expression in microglia. • TGFβRII is involved in GDF-15-enhanced IDE expression in microglia. Alzheimer's disease (AD), which is the most common progressive neurodegenerative disease, causes learning and memory impairment. The pathological progress of AD can derive from imbalanced homeostasis of amyloid beta (Aβ) in the brain. In such cases, microglia play important roles in regulating the brain Aβ levels. In the present study, we found that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) can increase, through paracrine action, the ability of microglial cells to clear Aβ. In order to identify the associated paracrine factors, a secretome of hUCB-MSCs co-cultured with Aβ-treated BV2 microglial cells was analyzed using a human cytokine protein array. As a result, growth differentiation factor-15 (GDF-15) was identified as a predominant candidate, and its association with Aβ clearance by microglial cells was investigated in vitro and in a 5XFAD mouse model. When Aβ-treated BV2 cells were treated with exogenous recombinant GDF-15, the Aβ levels in the culture medium decreased. Moreover, GDF-15 injection in the brain parenchyma of 5XFAD mice also led to decrease in Aβ plaques. In contrast, co-culture of BV2 cells and hUCB-MSCs treated with GDF-15-specific siRNA did not influence the Aβ levels in the culture medium. To elucidate how these phenomena are related, we confirmed that GDF-15 specifically increases insulin-degrading enzyme (IDE) expression in microglial cells through TGFβ receptor type II (TGFβRII), both in vitro and in vivo. These findings suggest that hUCB-MSCs promote the Aβ clearance ability of microglial cells through regulation of GDF-15 secretion, thus elucidating a therapeutic mechanism for AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium. The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via mtCOJO, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Understanding of the factors slowing down metakaolin reaction in limestone calcined clay cement (LC3) at late ages

Factors which could explain the slowing down of the metakaolin reaction in LC{sup 3} blends are investigated. Portlandite availability and the presence of aluminium ions in the pore solution are shown not to be limiting factors. Hydrates can only precipitate in solution filled pores. Internal relative humidity measurements indicate that at 28 days solution is present only in pores with radii below 13 nm. An enhancement of metakaolin reaction was obtained at late ages when the larger capillaries are filled with solution. The lower limit of the water filled pores was more difficult to analyse since there is a lack of precision in determining interfacial energies of hydrates and pore solution of the system. However, this study gives an indication of order of magnitude where the growth of hydrates could be slowed down.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Lessons from the Crystal Structure of the S. aureus>/em> Surface Protein Clumping Factor A in Complex With Tefibazumab, an Inhibiting Monoclonal Antibody

The Staphylococcus aureus fibrinogen binding MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules), ClfA (clumping factor A) is an important virulence factor in staphylococcal infections and a component of several vaccines currently under clinical evaluation. The mouse monoclonal antibody aurexis (also called 12-9), and the humanized version tefibazumab are therapeutic monoclonal antibodies targeting ClfA that in combination with conventional antibiotics were effective in animal models but showed less impressive efficacy in a limited Phase II clinical trial. We here report the crystal structure and a biochemical characterization of the ClfA/tefibazumab (Fab) complex. The epitope for tefibazumab is located to the “top” of the N3 subdomain of ClfA and partially overlaps with a previously unidentified second binding site for fibrinogen. A high-affinity binding of ClfA to fibrinogen involves both an interaction at the N3 site and the previously identified docking of the C-terminal segment of the fibrinogen γ-chain in the N2N3 trench. Although tefibazumab binds ClfA with high affinity we observe a modest IC50 value for the inhibition of fibrinogen binding to the MSCRAMM. This observation, paired with a common natural occurring variant of ClfA that is not effectively recognized by the mAb, may partly explain the modest effect tefibazumab showed in the initial clinic trail. This information will provide guidance for the design of the next generation of therapeutic anti-staphylococcal mAbs targeting ClfA.

General & Internal Medicine↗
DOE OSTI2017

Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to iodine-131 from the accident at the Chernobyl Nuclear Plant

Background: Serum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency. Methods: We screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality. Results: Mean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values<0.001), and Tg increased with increasing thyroid volume, and serum thyrotropin (p-values for trend<0.001). We found no evidence of significant associations between iodine-131 thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt intake (PC=−7.90, 95% confidence interval: −12.08, −3.52), and over the range of urinary iodine concentration, the odds of having elevated serum Tg showed a U-shaped curve with elevated Tg at low and high urinary iodine concentrations. Conclusion: Serum Tg may be a useful indicator of population iodine status and a non-specific biomarker of structural and functional thyroid abnormalities in epidemiological studies. - Highlights: • We evaluated serum thyroglobulin (Tg) in 10,430 irradiated, mostly iodine deficient Ukrainians. • Tg levels were higher among subjects with abnormal thyroid structure/function. • Increased Tg was associated with increasing age, thyroid volume and thyrotropin levels. • The odds of elevated Tg showed a U-shaped curve over categories of dietary iodine status. • Serum Tg is a useful indicator of population iodine status and thyroid abnormalities.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Contribution of diet and other factors to the observed levels of selected perfluoroalkyl acids in serum among US children aged 3-11 years

Highlights: • Diet was the predominant factor in explaining variability associated with PFAAs. • Boys had higher adjusted geometric mean than girls for MPAH and NPFOS. • Exposure to ETS was associated with 12.6% increase in the levels of NPFOA. Data from National Health and Nutrition Examination Survey for 2013–2014 for children aged 3–11 years (N = 639) were analyzed to evaluate the contribution of diet and other factors in variability associated with the observed levels of seven perfluoroalkyl acids in serum, namely, 2(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), perfluorodecanoic acid (PFDE), perfluorononanoic acid (PFNA), perflurorohexane sulfonic acid (PFHxS), linear isomer of PFOA (NPFOA), linear isomer of PFOS (NPFOS), and monomethyl isomer of PFOS (MPFOS). Diet accounted for a low of 18.6% of the total explained variance in the adjusted levels of NPFOA and a high of 72.3% for PFNA. Consumption of meat other than fish and poultry was associated with increased levels of NPFOS (β = 0.00035, p < 0.01) and MPFOS (β = 0.00027, p=0.02). However, consumption of fish was associated with decreased levels of PFDE (β = − 0.00058, p=0.01). Consumption of eggs was associated with higher levels of PFDE (β = 0.00105, p=0.04). Higher levels of PFHxS were associated with consumption of fruits and juices (β = 0.00019, p = 0.03). Exposure to environmental tobacco smoke in indoor environments other than home was associated with 12.6% increase in the levels of NPFOA. Boys had higher adjusted geometric mean (AGM) than girls for MPAH (0.88 vs. 0.70 ng/mL, p = 0.04) and NPFOS (2.73 vs. 2.27 ng/mL, p = 0.04). Non-Hispanic white had higher AGMs than Hispanics for MPAH (0.15 vs. 0.07, p < 0.01), for NPFOA (1.98 vs. 1.64 ng/mL, p < 0.01), and MPFOS (1.39 vs. 1.18 ng/mL, p = 0.03). Non-Hispanic white also had higher AGM than non-Hispanic Asians and others for PFHxS (0.99 vs. 0.63 ng/mL, p < 0.01) and NPFOA (1.98 vs. 1.53 ng/mL, p < 0.01).

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Relationships between physical–geographical factors and soil degradation on agricultural land

Highlights: • Connection of soil degradation to seven physical-geographical variables was revealed. • New method of threshold data analysis was proposed. • Precise treshold values where soil degradation starts and ends were revealed. • Study area covered the entire area of Czech agricultural land – 13027 cadastres (78,866 km{sup 2}). It is a well-known fact that soil degradation is dramatically increasing and currently threatens agricultural soils all around the world. The objective of this study was to reveal the possible connection between soil degradation and seven physical-geographical factors - slope steepness, altitude, elevation differences, rainfall, temperature, soil texture and solar radiation – in the form of threshold values (if these exist), where soil degradation begins and ends. The analysis involved the whole area of the Czech Republic which consists of 13,027 cadasters (78,866 km{sup 2}). The greatest total degradation threat occurs in areas with slope steepness >7 degrees, average annual temperature 10.54, altitude >766 m a.s.l. Similarly, the results for water erosion, wind erosion, soil compaction, loss of organic matter, acidification and heavy metal contamination were processed. The results enable us to identify the relationships of different levels of threats which could consequently be used in various ways – for classification of threatened areas, for more effective implementation of anti-degradation measures, or purely for a better understanding of the role of physical geographical factors in soil degradation in the Czech Republic, and thus could increase the chances of reducing vulnerability to land degradation not only in the Czech Republic.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

National and subnational mortality and disability-adjusted life years (DALYs) attributable to 17 occupational risk factors in Iran, 1990–2015

Highlights: • Mortality and morbidity from 17 occupational risks in Iran, 1990–2015 were estimated. • During 1990–2015, national DALYs from occupational risks increased by 65%. • During 1990–2015, the share of women in the attributable DALYs rose from 13% to 20%. • Proportion of YLLs in national DALYs due to occupational risks in 2015 was 23%. • Spatial inequality in the attributable DALY rate decreased from 1990 to 2015. We estimated age-sex specific and cause-specific mortality, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) attributable to 17 individual occupational risks in Iran at the national and subnational levels in 1990–2015 based on the Global Burden of Disease Study 2015 (GBD 2015). The burden of disease attributable to occupational risk factors was calculated using the comparative risk assessment methodology based on 10 outcomes and 21 risk-outcome pairs. The temporal changes in the attributable burden of disease were decomposed into the contribution of population growth, population ageing, risk-deleted DALY rate, and risk exposure. National DALYs attributable to occupational risks at the national level in 1990, 2005, and 2015 were 138,210 (95% uncertainty interval 64,429–223,028), 193,243 (91,645–310,281), and 228,310 (106,782–371,709), respectively indicating a total increase of 65% (65–67) during the study period. Between 1990 and 2015, the share of the attributable DALYs for women rose by 55% (51–58) from 13% (12–14) to 20% (19–21). The proportion of YLLs in national DALYs attributable to occupational risks during the study period slightly decreased from 24% in 1990 to 23% in 2015. The five occupational risks with the highest contributions in the national attributable DALYs in 2015 were ergonomic factors (107,490), noise (52,122), exposure to particulate matter, gases, and fumes (26,847), asthmagens (19,347), and exposure to asbestos (7842). From 1990 to 2015, the increase in total DALYs attributable to occupational carcinogens (112%) was higher than that for other occupational risks. During the study period, changes in risk deleted DALY rate and risk exposure led to decreases in total DALYs attributable to occupational risks by 14% and 30%, respectively. Based on the Gini coefficient, spatial inequality in DALY rate attributable to occupational risks at the provincial level decreased during 1990–2015. A comprehensive plan for management of exposure to occupational risks, especially occupational carcinogens can cause an important effect for control of the increasing trend of occupational health losses.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Impact of meteorological factors on mumps and potential effect modifiers: An analysis of 10 cities in Guangxi, Southern China

Highlights: • A total of 183,341 cases from 10 cities, daily weather data and 10 socioeconomic factors were included in the analysis. • Mean temperature and wind velocity are associated with the elevated risks of mumps incidence. • Male and adolescent aged 5–14 y are the most sensitive population to extreme weather conditions. • Several socioeconomic indicators may have a certain degree of modification on the climate-related incidence of mumps. In the current context of global climate change, understanding the impact of climate on respiratory infectious diseases such as mumps and the potential modified factors is crucial, especially in developing countries. However, research on the climate-related incidence of mumps is rare, inconsistent and mainly limited to a single city or region.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Climatic factors and long-term trends of influenza-like illness rates in The Netherlands, 1970–2016

Highlights: • We studied the link between climatic factors and influenza-like illness (ILI) rate. • In the Netherlands, ILI rates dropped during 1970–2003, then started to rise again. • Weekly ILI count was inversely associated with humidity and temperature. • The early 2000s were a trend-reversal point for the climatic time series as well. • Seasonal average ILI rates and humidity (or temperature) were inversely correlated. Climatic factors affect the survival and transmissibility of respiratory viruses causing influenza-like illness (ILI), and we hypothesized that changes in absolute humidity and temperature may affect long-term trends of ILI incidence rate in temperate countries. We tested this hypothesis using ILI and meteorological time series in the Netherlands for the period 1970–2016.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Oil/water/rock wettability: Influencing factors and implications for low salinity water flooding in carbonate reservoirs

Wettability of the oil/brine/rock system is an essential petro-physical parameter which governs subsurface multiphase flow behaviour and the distribution of fluids, thus directly affecting oil recovery. Recent studies [1–3] show that manipulation of injected brine composition can enhance oil recovery by shifting wettability from oil-wet to water-wet. However, what factor(s) control system wettability has not been completely elucidated due to incomplete understanding of the geochemical system. To isolate and identify the key factors at play we used in this paper SO 4 2 —free solutions to examine the effect of salinity (formation brine/FB, 10 times diluted formation brine/10 dFB, and 100 times diluted formation brine/100 dFB) on the contact angle of oil droplets at the surface of calcite. We then compared contact angle results with predictions of surface complexation by low salinity water using PHREEQC software. We demonstrate that the conventional dilution approach likely triggers an oil-wet system at low pH, which may explain why the low salinity water EOR-effect is not always observed by injecting low salinity water in carbonated reservoirs. pH plays a fundamental role in the surface chemistry of oil/brine interfaces, and wettability. Our contact angle results show that formation brine triggered a strong water-wet system (35°) at pH 2.55, yet 100 times diluted formation brine led to a strongly oil-wet system (contact angle = 175°) at pH 5.68. Surface complexation modelling correctly predicted the wettability trend with salinity; the bond product sum ([>CaOH 2 + ][–COO - ] + [>CO 3 - ][–NH + ] + [>CO 3 - ][–COOCa + ]) increased with decreasing salinity. Finally, at pH < 6 dilution likely makes the calcite surface oil-wet, particularly for crude oils with high base number. Yet, dilution probably causes water wetness at pH > 7 for crude oils with high acid number.

02 PETROLEUM↗
DOE OSTI2023

Walking on the dark side: Anthropogenic factors limit suitable habitat for gray wolf ( Canis lupus ) in a large natural area covering Belarus and Ukraine

Due to successful conservation initiatives and legislations, the grey wolf (Canis lupus) is recolonising its historic range in Europe. However, wolves have never been extirpated across large areas in Eastern Europe but are often constrained to remote and inaccessible places due to centuries of persecution. This study aimed to identify the potentially suitable wolf habitats in Polesia, a massive cross-border lowland region extending over southern Belarus and northern Ukraine, which are often neglected in large carnivore studies at the continental scale. We hypothesized that anthropogenic rather than environmental factors govern wolf habitat suitability. We used a dataset of 4191 GPS locations obtained from radio-collared wolves (n = 26) and confirmed observations (n = 231) during 2014–2021 and applied maximum entropy method to estimate relative habitat suitability for wolves in Polesia. Artificial light at night (ALAN), proportion of cropland and tree cover were the most important factors affecting wolf habitat suitability. Road densities contributed poorly to predicting habitat suitability for wolves. Our models predicted a quarter of Polesia as suitable habitat and revealed priority areas connecting the important source populations in the Chornobyl Exclusion Zone in the east and the Bialowieza Forest in the west and thus essential for long-term wolf conservation. Our results provide the bases for effective, long-term wolf monitoring and management programs in both Belarus and Ukraine. However, national and transboundary wolf management in Polesia has been extremely challenging since 2022 due to the ongoing war and subsequent habitat degradation in this part of Europe.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Modeling and mitigating airborne pathogen risk factors in school buses

Computational fluid dynamics (CFD) models were developed to simulate the impact of different ventilation scenarios on airborne exposure risks in a 72-passenger school bus. Here, scenarios and factors that were investigated included a moving vs. stationary bus, impacts of a heating unit within the bus, and impacts of alternative ventilation scenarios with different combinations of openings (e.g., windows, door, emergency hatch). Results of the simulations showed that when the bus was stationary, use of the heater increased receptor concentrations unless there was another opening. When the bus was moving, simulations with at least two sets of openings separated from each other in the forward and aft directions produced a through-flow condition that reduced concentrations via dilution from outside air by a factor of ten or more. A single opening in a moving bus generally increased concentrations throughout the cabin due to increased mixing with minimal ventilation. The cumulative exposure risk (time-averaged concentrations) was found to be inversely correlated to the air exchange rate. Stationary and moving-bus scenarios that yielded above ~20 air changes per hour resulted in the lowest cumulative exposures. Recommendations from this study were implemented in new safety and operating procedures by the Albuquerque Public Schools Transportation Center.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Skin factor and potential formation damage from chemical and mechanical processes in a naturally fractured carbonate aquifer with implications to CO 2 sequestration

Here, in this study, we investigate formation damage due to acidization and water injection tests into the naturally fractured carbonate Middle Duperow Formation at Kevin Dome, Montana, potentially diminishing the chance of a future successful Geological Carbon Sequestration (GCS) project. Multiple well-test analytical models, correlated with core description and lithology data, are used to determine flow behavior and communication between the water injection interval and surrounding formations. An improved three-dimensional (3D) geologic model with dual-continuum matrix and fracture properties is constructed based on most recent seismic, core, and water sample measurements. Brine injection is simulated to verify the interpretation from the analytical models, followed by CO 2 injection simulation. Geochemical calculations are performed to understand the in-situ processes that led to formation damage. Our findings suggest: (1) there are two possible scenarios that could lead to a positive total effective skin factor and permeability decline: partial penetration and formation damage; (2) analytical models indicate a positive total skin factor, contradicting results of a previous study suggesting that the well was mildly stimulated; (3) numerical simulation supports the formation damage hypothesis by matching the pressure buildup observed during the latter two brine injection tests; (4) several mechanical and chemical processes may have occurred during injection to clog the matrix/fracture system: anhydrite fines migration and/or calcite precipitation. We then make preventative suggestions for future GCS projects into carbonate reservoirs and remediation recommendations for GCS operation at the Kevin Dome.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact with mediastinal structures, although adhesion to parietal pleura did not necessarily reduce tumor motion amplitudes. The most variable lung tumors were metastatic lesions in women.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗