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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 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Effects of biometrics, location and persistent organic pollutants on blood clinical-chemical parameters in polar bears (Ursus maritimus) from Svalbard, Norway

Highlights: • BCCPs in polar bears may be affected by sex, age, biometrics, lipids and location. • POPs were correlated with HCT and HDL in females, and HCT, GGT, ASAT and CHOL in males. • POPs related biological effects on liver and kidney BCCP values were suggested. • HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. • POPs effects on HDL and CHOL may indicate increased risk of cardiovascular disease in polar bears. In the present study, blood clinical-chemical parameters (BCCPs) were analysed in 20 female and 18 male Svalbard polar bears (Ursus maritimus) captured in spring 2007. The aim was to study how age, body condition (BC), biometrics, plasma lipid content and geographical location may confound the relationship between persistent organic pollutants (POPs) including PCBs, HCB, chlordanes, DDTs, HCHs, mirex and OH-PCBs and the concentrations of 12 specific BCCPs (hematocrit [HCT], hemoglobin [HB], aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], γ-glutamyltransferase [GGT], creatine kinase [CK], triglycerides [TG], cholesterol [CHOL], high-density lipoprotein [HDL], creatinine (CREA], urea, potassium (K]), and to investigate if any of these BCCPs may be applied as potential biomarkers for POP exposure in polar bears. Initial PCA and O-PLS modelling showed that age, lipids, BC and geographical location (longitude and latitude) were important parameters explaining BCCPs in females. Following subsequent partial correlation analyses correcting for age and lipids, multiple POPs in females were still significantly correlated with HCT and HDL (all p < 0.05). In males, age, BM, BC and longitude were important parameters explaining BCCPs. Following partial correlation analyses correcting for age, biometrics, lipids and longitude in males, multiple POPs were significantly correlated with HCT, ASAT, GGT and CHOL (all p < 0.05). In conclusion, several confounding parameters has to be taken into account when studying the relations between BCCPs and POPs in polar bears. When correcting for these, in particular HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. Furthermore, decreasing HDL concentrations and increasing CHOL concentration with increasing POP concentrations may indicate responses related to increased risk of cardiovascular disease. We therefore suggest to further study POP exposure and lipidome response to increase knowledge of the risk of cardiometabolic syndrome in polar bears.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Persistent organic pollutants in fish from Charleston Harbor and tributaries, South Carolina, United States: A risk assessment

Highlights: • Higher contaminant levels in fish from Cooper/Ashley Rivers than Charleston Harbor. • Mullet and spot were significantly higher in PCBs and pesticides than red drum. • PCBs were the predominant contaminant in whole fish and fillets from Charleston SC. • PCBs in all fillets exceed EPA human health values, consumption advisories warranted. • Whole fish PCBs, PBDEs exceed wildlife screening values, a concern for local dolphins. Fish consumption is an important route of exposure to persistent organic pollutants (POPs) in dolphins as well as humans. In order to assess the potential risks associated with these contaminants, 39 whole fish and 37 fillets from fish representing species consumed by dolphins and humans captured from Charleston Harbor and tributaries, South Carolina, USA, were measured for a suite of POPs. Polychlorinated biphenyls (PCBs) were the predominant contaminant with concentrations ranging from 5.02 to 232.20 ng/g in whole fish and 5.42–131.95 ng/g in fillets (weight weight ww) followed by total organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). Total POPs levels varied by location and species with general trends indicating significantly higher levels in fish from the Cooper (93.4 ng/g ww) and Ashley Rivers (56.2 ng/g ww) compared to Charleston Harbor (31.6 ng/g ww). Mullet and spot were found to have significantly higher PCBs, OCPs and total POPs, 2–3 times higher than red drum; mullet were also significantly higher in OCPs compared to seatrout. PCB concentrations in whole fish and fillets exceeded EPA human screening values for cancer risk in all fish sampled. For PCBs in fillets, all samples had values of maximum allowable meals per month that were less than the EPA, FDA guidelines for recommended fish meals per month, suggesting lower (more stringent) allowable fish meals per month. All fish exceeded PBDE wildlife values and all fish except two exceeded the level where 95% of the dolphin population would have tissue levels below the health effect threshold. Considering that POP concentrations in fish potentially consumed by humans exceed human health effect thresholds levels, consumption advisories should be considered as a prudent public health measure.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Subclinical Cardiac Dysfunction Detected by Strain Imaging During Breast Irradiation With Persistent Changes 6 Weeks After Treatment

Purpose: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). Methods and Materials: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. Results: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) −20.44 ± 2.66 baseline vs −18.60 ± 2.70* during RT vs −18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s{sup −1}) −1.19 ± 0.21 vs −1.06 ± 0.18* vs −1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s{sup −1}) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s{sup −1}) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). Conclusions: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Persistence of Late Substantial Patient-Reported Symptoms (LAPERS) After Radiochemotherapy Including Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: A Report From the EMBRACE Study

This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Persistent compositions of non-stoichiometric compounds with low bulk diffusivity: A theory and application to Nb3Sn superconductors

Non-stoichiometric compounds may develop a composition gradient when they are formed by reactive diffusional processes. This paper reports an interesting phenomenon that in compounds with low bulk diffusivities, which rely mainly on grain boundary diffusion for their growth, the final bulk compositions may be far from equilibrium, with a very low bulk diffusivity leading to fixed (persistent) compositions – one such example is Nb 3 Sn, a superconductor. We investigated the microchemistry at the reactive interface using atom probe tomography to clarify the diffusion reaction mechanism for this low-bulk-diffusivity case and thus propose a theory for what determines the compound composition, using Nb 3 Sn as an example for concreteness. Using certain approximations, we derive an explicit analytical equation that illustrates what factors determine its composition profile. We compare our model with the known facts of Nb 3 Sn and see good agreement. In particular, this model predicts that internal oxidation may lead to higher Sn contents than conventional, non-oxidized Nb 3 Sn. Our measurements show that this is indeed true, and that the internally-oxidized Nb 3 Sn also has higher upper critical fields, achieving up to 28.2 T at 4.2 K. We discuss the general applicability of this model to non-stoichiometric compounds with low bulk diffusivity, and propose it as a tool to help in the design and processing of such materials for compositional control.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Long persistent and optically stimulated luminescence behaviors of calcium aluminates with different trap filling processes

Properties of long persistent luminescence (LPL) and optically stimulated luminescence (OSL) of CaAl{sub 2}O{sub 4}:Eu{sup 2+}, R{sup 3+} (R=Nd, Dy, Tm) materials were investigated. The observed phenomenon indicates that R{sup 3+} ions (R=Nd, Dy, Tm) have different effects on trap properties of CaAl{sub 2}O{sub 4}:Eu{sup 2+}. The greatly improved LPL performance was observed in Nd{sup 3+} co-doped samples, which indicates that the incorporation of Nd{sup 3+} creates suitable traps for LPL. While co-doping Tm{sup 3+} ions, the intensity of high temperature of thermoluminescence band in CaAl{sub 2}O{sub 4}:Eu{sup 2+} phosphors is enhanced for the formation of the most suitable traps which benefits the intense and stable OSL. These results suggest that the effective traps contributed to the LPL/OSL are complex, of which could be an aggregation formation with shallow and deep traps other than simple traps from co-doped R{sup 3+} ions. The mechanism presented in the end potentially provides explanations of why the OSL of CaAl{sub 2}O{sub 4}:Eu{sup 2+}, R{sup 3+} exhibits different read-in/read-out performance as well. - Graphical abstract: OSL emission spectra of Ca{sub 0.995}Al{sub 2}O{sub 4}:0.0025Eu{sup 2+}, 0.0025R{sup 3+} (R=Nd, Dy, Tm) taken under varying stimulation time (0, 25, 50, 75, 100 s). Inset: Blue emission pictures under varying stimulation time. - Highlights: • The LPL and OSL properties of CaAl{sub 2}O{sub 4}:Eu{sup 2+}, R{sup 3+} were investigated. • An alternative approach to control the trap depth of CaAl{sub 2}O{sub 4}:Eu{sup 2+} phosphor was proposed. • A new oxide ETM phosphor exhibiting intense and stable OSL was explored.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Optical property investigations of polystyrene capped Ca{sub 2}P{sub 2}O{sub 7}:Dy{sup 3+} persistent phosphor

Highlights: • Synthesis of polymer capped pyrophosphate phosphors by citrate gel method. • Radiative lifetime is calculated from parameters of Judd-Ofelt theory and ICP-AES. • Reaction mechanism is discussed leading to high photoluminescence efficiency. • PL emission spectrum reveals broad band emission suitable for solid state lighting. - Abstract: By virtue of enhanced photosensivity, good optical response and better thermal stability, organic–inorganic hybrid materials are contemplated as one of the alternatives for designing advanced optoelectronic devices and innovative photonic applications. A novel inorganic organic hybrid Ca{sub 2}P{sub 2}O{sub 7}:Dy{sup 3+} phosphor has been fabricated by Pechini method. The optical property of synthesized phosphor is successfully altered by the in corporation of polystyrene sulfonic acid as capping agent in the colloidal solution. The phase purity and the average particle size of the prepared phosphor were calculated from X-ray diffraction (XRD) employing Debye Scherrer method. The morphological and chemical investigations were carried out through scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analysis. The radiative transitions are explained on the basis of Judd-Ofelt theory and on the basis of derived parameters, the radiative lifetime of persistent hybrid Ca{sub 2}P{sub 2}O{sub 7}:Dy{sup 3+} phosphor is calculated as 5.33 ms. This paper explores the mechanism leading to high photoluminescence efficiency using organic capping additives. The photoluminescence (PL) graphs reveal broad band emission at 482 nm (blue) and 573 nm (yellow) corresponding to {sup 4}F{sub 9/2}-{sup 6}H{sub 15/2} and {sup 4}F{sub 9/2}-{sup 6}H{sub 13/2} transitions of Dy{sup 3+}, respectively. The Commission International De I-Eclairage (CIE) chromaticity co-ordinates were calculated from emission spectra and the values (x, y) were approaching to standard value of white emission. The synthesized pyrophosphate phosphors can thereby account in multiple potential applications including white light emitting diodes.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2022

Persistent hot carrier diffusion in boron arsenide single crystals imaged by ultrafast electron microscopy

Cubic boron arsenide (BAs) is promising for microelectronics thermal management because of its high thermal conductivity. Recently, its potential as an optoelectronic material is also being explored. However, it remains challenging to measure its photocarrier transport properties because of small sizes of available high-quality crystals. Here, we use scanning ultrafast electron microscopy (SUEM) to directly visualize the diffusion of photocarriers in BAs single crystals. Surprisingly, we observed ambipolar diffusion at low optical fluence with persistent hot carrier dynamics for above 200 ps, which can likely be attributed to the large frequency gap between acoustic and optical phonons, the same feature that is responsible for the high thermal conductivity. At higher optical fluence, we observed spontaneous electron-hole separation. Our results show BAs is an attractive optoelectronic material combining high thermal conductivity and excellent photocarrier transport properties. Finally, our study also demonstrates the capability of SUEM to probe photocarrier transport in emerging materials.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Persistent mysteries of jet engines, formation, propagation, and particle acceleration: Have they been addressed experimentally?

Here, the physics of astrophysical jets can be divided into three regimes: (i) engine and launch (ii) propagation and collimation, (iii) dissipation and particle acceleration. Since astrophysical jets comprise a huge range of scales and phenomena, practicality dictates that most studies of jets intentionally or inadvertently focus on one of these regimes, and even therein, one body of work may be simply boundary condition for another. We first discuss long standing persistent mysteries that pertain the physics of each of these regimes, independent of the method used to study them. This discussion makes contact with frontiers of plasma astrophysics more generally. While observations theory, and simulations, and have long been the main tools of the trade, what about laboratory experiments? Jet related experiments have offered controlled studies of specific principles, physical processes, and benchmarks for numerical and theoretical calculations. We discuss what has been accomplished on these fronts. Although experiments have indeed helped us to understand certain processes, proof of principle concepts, and benchmarked codes, they have yet to solved an astrophysical jet mystery on their own. A challenge is that experimental tools used for jet-related experiments so far, are typically not machines originally designed for that purpose, or designed with specific astrophysical mysteries in mind. This presents an opportunity for a different way of thinking about the development of future platforms: start with the astrophysical mystery and build an experiment to address it.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

Persistent global greening over the last four decades using novel long-term vegetation index data with enhanced temporal consistency

Advanced Very High-Resolution Radiometer (AVHRR) satellite observations have provided the longest global daily records from 1980s, but the remaining temporal inconsistency in vegetation index datasets has hindered reliable assessment of vegetation greenness trends. To tackle this, we generated novel global long-term Normalized Difference Vegetation Index (NDVI) and Near-Infrared Reflectance of vegetation (NIRv) datasets derived from AVHRR and Moderate Resolution Imaging Spectroradiometer (MODIS). We addressed residual temporal inconsistency through three-step post processing including cross-sensor calibration among AVHRR sensors, orbital drifting correction for AVHRR sensors, and machine learning-based harmonization between AVHRR and MODIS. After applying each processing step, we confirmed the enhanced temporal consistency in terms of detrended anomaly, trend and interannual variability of NDVI and NIRv at calibration sites. Our refined NDVI and NIRv datasets showed a persistent global greening trend over the last four decades (NDVI: 0.0008 yr -1 ; NIRv: 0.0003 yr -1 ), contrasting with those without the three processing steps that showed rapid greening trends before 2000 (NDVI: 0.0017 yr -1 ; NIRv: 0.0008 yr -1 ) and weakened greening trends after 2000 (NDVI: 0.0004 yr -1 ; NIRv: 0.0001 yr -1 ). These findings highlight the importance of minimizing temporal inconsistency in long-term vegetation index datasets, which can support more reliable trend analysis in global vegetation response to climate changes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

While legume-based rotation influences the chemical composition of mineral-associated organic matter, tillage has little effect on its persistence

Legume-based rotations are key to enhancing soil carbon (C) storage in stable forms such as mineral-associated organic matter (MAOM), improving soil health, and helping maintain long-term C stock. This study investigates how plant inputs and tillage practices influence the distribution, composition, and persistence of MAOM in wheat cropping systems when legumes are incorporated into the rotation. Soil samples were collected from Walla Walla silty loam of northeast Oregon, including conventional tillage (CT) and no-till (NT) treatments in a long-term dryland winter wheat (Triticum aestivum L.) and spring pea (Pisum sativum L.) rotation experiment, with an adjacent grass pasture (GP) plot serving as the baseline. Bulk soil, particulate organic matter (POM), and MAOM fractions were scanned using mid-infrared (Mid-IR) spectroscopy and analyzed for total C and nitrogen (N) as well as radiocarbon age, aggregate stability, and mineralizable C. In WP systems, NT promoted greater C accumulation and stabilization in MAOM than CT, reaching levels similar to those under native GP conditions. Furthermore, our findings indicate that decades of continuous legume-based rotation were insufficient to restore total bulk C content to levels observed in the undisturbed reference site (GP) in the 0–30 cm layer, with increases limited to the surface layer. The Mid-IR data provided insights into how cultivation may alter the chemical composition of MAOM. An increase in amide bands was observed in GP, while legume-based rotation systems favored an abundance of aliphatic (C-H) components in the MAOM fraction. In cultivated soils, C in MAOM exhibited longer residence times under arable conditions than in grassland, while POM remained an actively cycled pool across all treatments. Despite variations in the chemical composition of MAOM across treatments, mineralizable C emissions from MAOM fractions remained statistically unchanged during the 96-hour incubation period. Our findings suggest that soil physical protection, enhanced by reduced tillage, is the primary factor influencing MAOM cycling.

Carbon stabilization↗
DOE OSTI2013

Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a CSAA diet. ► Fibrosis is sustained, possibly due to continuing hypoxia and oxidative stress.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Environmentally persistent free radicals inhibit cytochrome P450 activity in rat liver microsomes

Combustion processes generate particulate matter that affects human health. When incineration fuels include components that are highly enriched in aromatic hydrocarbons (especially halogenated varieties) and redox-active metals, ultrafine particulate matter containing air-stable, environmentally persistent free radicals (EPFRs) is generated. The exposure to fine EPFRs (less than 2.5 μm in diameter) has been shown to negatively influence pulmonary and cardiovascular functions in living organisms. The goal of this study was to determine if these EPFRs have a direct effect on cytochrome P450 function. This was accomplished by direct addition of the EPFRs to rat liver microsomal preparations and measurement of several P450 activities using form-selective substrates. The EPFRs used in this study were formed by heating vapors from an organic compound (either monochlorophenol (MCP230) or 1,2-dichlorobenzene (DCB230)) and 5% copper oxide supported on silica (approximately 0.2 μm in diameter) to 230 °C under vacuum. Both types of EPFRs (but not silica, physisorbed silica, or silica impregnated with copper oxide) dramatically inhibited the activities of CYP1A, CYP2B, CYP2E1, CYP2D2 and CYP3A when incubated at concentrations less than 0.1 mg/ml with microsomes and NADPH. Interestingly, at the same concentrations, the EPFRs did not inhibit HO-1 activity or the reduction of cytochrome c by NADPH-cytochrome P450 reductase. CYP2D2-selective metabolism by rat liver microsomes was examined in more detail. The inhibition of CYP2D2-selective metabolism by both DCB230- and MCP230-EPFRs appeared to be largely noncompetitive and was attenuated in the presence of catalase suggesting that reactive oxygen species may be involved in the mechanism of inhibition. - Highlights: • Combustion of organic pollutants generates long-lived particulate radicals (EPFRs). • EPFRs inhibit metabolism by all cytochromes P450 tested in rat liver microsomes. • EPFR-mediated inhibition is related to spin content and is sensitive to catalase. • EPFR inhibition of CYP2D2 is noncompetitive with respect to substrate. • Exposure to EPFRs may impair the ability to eliminate xenobiotics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Environmentally persistent free radical-containing particulate matter competitively inhibits metabolism by cytochrome P450 1A2

Combustion processes generate different types of particulate matter (PM) that can have deleterious effects on the pulmonary and cardiovascular systems. Environmentally persistent free radicals (EPFRs) represent a type of particulate matter that is generated after combustion of environmental wastes in the presence of redox-active metals and aromatic hydrocarbons. Cytochromes P450 (P450/CYP) are membrane-bound enzymes that are essential for the phase I metabolism of most lipophilic xenobiotics. The EPFR formed by chemisorption of 2-monochlorophenol to silica containing 5% copper oxide (MCP230) has been shown to generally inhibit the activities of different forms of P450s without affecting those of cytochrome P450 reductase and heme oxygenase-1. The mechanism of inhibition of rat liver microsomal CYP2D2 and purified rabbit CYP2B4 by MCP230 has been shown previously to be noncompetitive with respect to substrate. In this study, MCP230 was shown to competitively inhibit metabolism of 7-benzyl-4-trifluoromethylcoumarin and 7-ethoxyresorufin by the purified, reconstituted rabbit CYP1A2. MCP230 is at least 5- and 50-fold more potent as an inhibitor of CYP1A2 than silica containing 5% copper oxide and silica, respectively. Thus, even though PM generally inhibit multiple forms of P450, PM interacts differently with the forms of P450 resulting in different mechanisms of inhibition. P450s function as oligomeric complexes within the membrane. We also determined the mechanism by which PM inhibited metabolism by the mixed CYP1A2–CYP2B4 complex and found that the mechanism was purely competitive suggesting that the CYP2B4 is dramatically inhibited when bound to CYP1A2. - Highlights: • Combustion of organic pollutants generates long-lived particulate radicals (EPFRs). • Particulate matter (PM) competitively inhibited CYP1A2 activity. • EPFRs were much more potent CYP1A2 inhibitors than other types of PM. • PM interacts differently with different forms of P450. • PM competitively inhibited metabolism by the mixed CYP1A2–CYP2B4 complex.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Persistent dopants and phase segregation in organolead mixed-halide perovskites

Organolead mixed-halide perovskites such as CH 3 NH 3 PbX 3–a X' a (X, X' = I, Br, Cl) are interesting semiconductors because of their low cost, high photovoltaic power conversion efficiencies, enhanced moisture stability, and band gap tunability. Using a combination of optical absorption spectroscopy, powder X-ray diffraction (XRD), and, for the first time, 207 Pb solid state nuclear magnetic resonance (ssNMR), we probe the extent of alloying and phase segregation in these materials. Because 207 Pb ssNMR chemical shifts are highly sensitive to local coordination and electronic structure, and vary linearly with halogen electronegativity and band gap, this technique can provide the true chemical speciation and composition of organolead mixed-halide perovskites. We specifically investigate samples made by three different preparative methods: solution phase synthesis, thermal annealing, and solid phase synthesis. 207 Pb ssNMR reveals that nonstoichiometric dopants and semicrystalline phases are prevalent in samples made by solution phase synthesis. We show that these nanodomains are persistent after thermal annealing up to 200 °C. Further, a novel solid phase synthesis that starts from the parent, single-halide perovskites can suppress phase segregation but not the formation of dopants. Our observations are consistent with the presence of miscibility gaps and spontaneous spinodal decomposition of the mixed-halide perovskites at room temperature. This underscores how strongly different synthetic procedures impact the nanostructuring and composition of organolead halide perovskites. In conclusion, better optoelectronic properties and improved device stability and performance may be achieved through careful manipulation of the different phases and nanodomains present in these materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗