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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 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Gain and offset calibration reduces variation in exposure-dependent SNR among systems with identical digital flat-panel detectors

Purpose: The conditions under which vendor performance criteria for digital radiography systems are obtained do not adequately simulate the conditions of actual clinical imaging with respect to radiographic technique factors, scatter production, and scatter control. Therefore, the relationship between performance under ideal conditions and performance in clinical practice remains unclear. Using data from a large complement of systems in clinical use, the authors sought to develop a method to establish expected performance criteria for digital flat-panel radiography systems with respect to signal-to-noise ratio (SNR) versus detector exposure under clinical conditions for thoracic imaging. Methods: The authors made radiographic exposures of a patient-equivalent chest phantom at 125 kVp and 180 cm source-to-image distance. The mAs value was modified to produce exposures above and below the mAs delivered by automatic exposure control. Exposures measured free-in-air were corrected to the imaging plane by the inverse square law, by the attenuation factor of the phantom, and by the Bucky factor of the grid for the phantom, geometry, and kilovolt peak. SNR was evaluated as the ratio of the mean to the standard deviation (SD) of a region of interest automatically selected in the center of each unprocessed image. Data were acquired from 18 systems, 14 of which were tested both before and after gain and offset calibration. SNR as a function of detector exposure was interpolated using a double logarithmic function to stratify the data into groups of 0.2, 0.5, 1.0, 2.0, and 5.0 mR exposure (1.8, 4.5, 9.0, 18, and 45 {mu}Gy air KERMA) to the detector. Results: The mean SNR at each exposure interval after calibration exhibited linear dependence on the mean SNR before calibration (r{sup 2} = 0.9999). The dependence was greater than unity (m = 1.101 {+-} 0.006), and the difference from unity was statistically significant (p < 0.005). The SD of mean SNR after calibration also exhibited linear dependence on the SD of the mean SNR before calibration (r{sup 2} = 0.9997). This dependence was less than unity (m = 0.822 {+-} 0.008), and the difference from unity was also statistically significant (p < 0.005). Systems were separated into two groups: systems with a precalibration SNR higher than the median SNR (N = 7), and those with a precalibration SNR lower than the median SNR (N = 7). Posthoc analysis was performed to correct for expanded false positive results. After calibration, the authors noted differences in mean SNR within both high and low groups, but these differences were not statistically significant at the 0.05 level. SNR data from four additional systems and one system from those previously tested after replacement of its detector were compared to the 95% confidence intervals (CI) calculated from the postcalibration SNR data. The comparison indicated that four of these five systems were consistent with the CI derived from the previously tested 14 systems after calibration. Two systems from the paired group that remained outside the CI were studied further. One system was remedied with a grid replacement. The nonconformant behavior of the other system was corrected by replacing the image receptor. Conclusions: Exposure-dependent SNR measurements under conditions simulating thoracic imaging allowed us to develop criteria for digital flat-panel imaging systems from a single manufacturer. These measurements were useful in identifying systems with discrepant performance, including one with a defective grid, one with a defective detector, and one that had not been calibrated for gain and offset. The authors also found that the gain and offset calibration reduces variation in exposure-dependent SNR performance among the systems.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

Human behavior determinants of exposure to Anopheles vectors of malaria in Sumba, Indonesia

Malaria vector control interventions in Sumba, Indonesia, have not been able to eliminate malaria. Human drivers of exposure to Anopheles bites were investigated as part of a larger clinical trial evaluating the impact of a spatial repellent product on malaria incidence. Human behavioral observations (HBOs) evaluating temporal and spatial presence, sleeping behaviors, and insecticide treated net (ITN) use, were collected parallel to entomological collections—indoor and outdoor human landing catches (HLCs), and house hold surveys. Data demonstrates that mosquito access to humans, enabled by structurally open houses, is evident by the similar entomological landing rates both inside and outside households. The presence of animals inside houses was associated with increased mosquito entry–however, the number of humans present inside houses was not related to increased mosquito landing. Analyzing mosquito landing rates with human behavior data enables the spatial and temporal estimation of exposure to Anopheles bites, accounting for intervention (ITN) presence and usage. Human behavior adjusted exposure to Anopheles bites was found to be highest in the early in the evening, but continued at lower levels throughout the night. Over the night, most exposure (53%) occurred when people were indoors and not under the protection of nets (asleep or awake) followed by exposure outside (44%). Characterized gaps in protection are outdoor exposure as well as exposure indoors–when awake, and when asleep and not using ITNs. Interestingly, in the primary trial, even though there was not a significant impact of the spatial repellent on vector biting rates by themselves (16%), when factoring in human behavior, there was approximately 28% less exposure in the intervention arm than in the placebo arm. The treated arm had less human behavior adjusted bites in all spaces evaluated though there was proportionally higher exposure indoors. This analysis points to the importance of using HBOs both towards understanding gaps in protection as well as how interventions are evaluated. To mitigate ongoing transmission, understanding context specific spatial and temporal exposure based on the interactions of vectors, humans and interventions would be vital for a directed evidence-based control or elimination strategy.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2002

Effects of Thermal Exposure on Properties of Al-Li Alloys

Aluminum-Lithium (Al-Li) alloys offer significant performance benefits for aerospace structural applications due to their higher specific properties compared with conventional Al alloys. For example, the application of Al-Li alloy 2195 to the space shuffle external cryogenic fuel tank resulted in weight savings of over 7,000 lb, enabling successful deployment of International Space Station components. The composition and heat treatment of 2195 were optimized specifically for strength-toughness considerations for an expendable cryogenic tank. Time-dependent properties related to reliability, such as thermal stability, fatigue, and corrosion, will be of significant interest when materials are evaluated for a reusable cryotank structure. Literature surveys have indicated that there is limited thermal exposure data on Al-Li alloys. The effort reported here was designed to establish the effects of thermal exposure on the mechanical properties and microstructure of Al-Li alloys C458, L277, and 2195 in plate gages. Tensile, fracture toughness, and corrosion resistance were evaluated for both parent metal and friction stir welds (FSW) after exposure to temperatures as high as 300 F for up to 1000 hrs. Microstructural changes were evaluated with thermal exposure in order to correlate with the observed data trends. The ambient temperature parent metal data showed an increase in strength and reduction in elongation after exposure at lower temperatures. Strength reached a peak with intermediate temperature exposure followed by a decrease at highest exposure temperature. Friction stir welds of all alloys showed a drop in elongation with increased length of exposure. Understanding the effect of thermal exposure on the properties and microstructure of Al-Li alloys must be considered in defining service limiting temperatures and exposure times for a reusable cryotank structure.

Shah, Sandeep↗
DOE OSTI2011

Association between environmental exposure to pesticides and neurodegenerative diseases

Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black-Right-Pointing-Pointer Males from areas with high pesticide exposure had a higher risk of polyneuropathy. Black-Right-Pointing-Pointer Males from high exposure areas had a higher risk of affective psychosis and suicide. Black-Right-Pointing-Pointer Nerve tissue degeneration due to oxidative damage may underlie the pathomechanism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Personal PM2.5 exposure among wildland firefighters working at prescribed forest burns in southeastern United States.

This study investigated occupational exposure to wood and vegetative smoke in a group of 28 forest firefighters at prescribed forest burns in a southeastern U.S. forest during the winters of 2003-2005. During burn activities, 203 individual person-day PM{sub 2.5} and 149 individual person-day CO samples were collected; during non-burn activities, 37 person-day PM{sub 2.5} samples were collected as controls. Time-activity diaries and post-work shift questionnaires were administered to identify factors influencing smoke exposure and to determine how accurately the firefighters qualitative assessment estimated their personal level of smoke exposure with discrete responses: 'none' or 'very little,' 'low,' 'moderate,' 'high,' and 'very high.' An average of 6.7 firefighters were monitored per burn, with samples collected on 30 burn days and 7 non-burn days. Size of burn plots ranged from 1-2745 acres (avg = 687.8). Duration of work shift ranged from 6.8-19.4 hr (avg = 10.3 hr) on burn days. Concentration of PM{sub 2.5} ranged from 5.9-2673 {mu}g/m{sup 3} on burn days. Geometric mean PM{sub 2.5} exposure was 280 {mu}g/m{sup 3} (95% CL = 140, 557 {mu}g/m{sup 3}, n = 177) for burn day samples, and 16 {mu}g/m{sup 3} (95% CL = 10, 26 {mu}g/m{sup 3}, n = 35) on non-burn days. Average measured PM{sub 2.5} differed across levels of the firefighters categorical self-assessments of exposure (p < 0.0001): none to very little = 120 {mu}g/m{sup 3} (95% CL = 71, 203 {mu}g/m{sup 3}) and high to very high = 664 {mu}g/m{sup 3} (95% CL = 373, 1185 {mu}g/m{sup 3}); p < 0.0001 on burn days. Time-weighted average PM{sub 2.5} and personal CO averaged over the run times of PM{sub 2.5} pumps were correlated (correlation coefficient estimate, r = 0.79; CLs: 0.72, 0.85). Overall occupational exposures to particulate matter were low, but results indicate that exposure could exceed the ACGIH{reg_sign}-recommended threshold limit value of 3 mg/m{sup 3} for respirable particulate matter in a few extreme situations. Self-assessed exposure levels agreed with measured concentrations of PM{sub 2.5}. Correlation analysis shows that either PM{sub 2.5} or CO could be used as a surrogate measure of exposure to woodsmoke at prescribed burns.

09 BIOMASS FUELS↗
DOE OSTI2014

Prenatal exposure to environmental contaminants and body composition at age 7–9 years

The study aim was to investigate the association between prenatal exposure to endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old Flemish children. The subjects were 114 Flemish children (50% boys) that took part in the first Flemish Environment and Health Study (2002–2006). Cadmium, PCBs, dioxins, p,p′-DDE and HCB were analysed in cord blood/plasma. When the child reached 7–9 years, height, weight, waist circumference and skinfolds were measured. Significant associations between prenatal exposure to EDCs and indicators of body composition were only found in girls. After adjustment for confounders and covariates, a significant negative association was found in girls between prenatal cadmium exposure and weight, BMI and waist circumference (indicator of abdominal fat) and the sum of four skinfolds (indicator of subcutaneous fat). In contrast, a significant positive association (after adjustment for confounders/covariates) was found between prenatal p,p′-DDE exposure and waist circumference as well as waist/height ratio in girls (indicators of abdominal fat). No significant associations were found for prenatal PCBs, dioxins and HCB exposure after adjustment for confounders/covariates. This study suggests a positive association between prenatal p,p′-DDE exposure and indicators of abdominal fat and a negative association between prenatal cadmium exposure and indicators of both abdominal as well as subcutaneous fat in girls between 7 and 9 years old. - Highlights: • Associations between prenatal contaminant exposure and anthropometrics in children. • Significant association only found in girls. • No significant associations found for prenatal PCBs, dioxins and HCB exposure. • Girls: negative association between cadmium and abdominal and subcutaneous fat. • Girls: positive association between p,p′-DDE and indicators of abdominal fat.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Environmental exposures and pediatric kidney function and disease: A systematic review

Background: Environmental chemical exposures have been implicated in pediatric kidney disease. No appraisal of the available evidence has been conducted on this topic. Methods: We performed a systematic review of the epidemiologic studies that assessed association of environmental exposures with measures of kidney function and disease in pediatric populations. The search period went through July 2016. Results: We found 50 studies that met the search criteria and were included in this systematic review. Environmental exposures reviewed herein included lead, cadmium, mercury, arsenic, fluoride, aflatoxin, melamine, environmental tobacco, bisphenol A, dental procedures, phthalates, ferfluorooctanoic acid, triclosan, and thallium/uranium. Most studies assessed environmental chemical exposure via biomarkers but four studies assessed exposure via proximity to emission source. There was mixed evidence of association between metal exposures, and other non-metal environmental exposures and pediatric kidney disease and other kidney disease biomarkers. The evaluation of causality is hampered by the small numbers of studies for each type of environmental exposure, as well as lack of study quality and limited prospective evidence. Conclusion: There is a need for well-designed epidemiologic studies of environmental chemical exposures and kidney disease outcomes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet

Highlights: • Exposure to vehicle emissions alters BBB permeability in high-fat-fed C57BL/6 mice. • Vehicle emission exposures exacerbate oxLDL levels in animals on a high-fat diet. • Alterations in neurovascular integrity are associated with increased oxLDL receptors. • Exposures result in reduced TJ protein expression associated with MMP-2/9 activity. Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100 PM/m{sup 3} vehicle emissions mixture: 30 µg PM/m{sup 3} gasoline engine + 70 µg PM/m{sup 3} diesel engine emissions; median size ~ 60 nm; particle mass size distribution median of ~ 1 µm (range: < 0.5–20 µm)] for 6 h/d, 7d/wk, for 30d. Using sodium fluorescein as a tracer, we observed a significant increase in BBB permeability in both HF + MVE exposed and HF + FA animals, compared to LF + FA controls. Exposure to HF + MVE also led to a significant increase plasma ox-LDL and ox-LDL scavenger receptors (LOX-1 and CD-36) expression in the cerebral vasculature. Histological analysis revealed decreased expression of TJ protein, claudin-5, associated with increased matrix metalloproteinase (MMP)−9 activity and oxidative stress in the cerebral vasculature of HF + MVE mice, compared to LF + MVE. Such findings indicate that inhalation exposure to traffic-generated pollutants, coupled with a HF diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors

Highlights: • DNA was extracted from breast tumor tissue and methylation of nine genes was measured. • Total suspended particulates and traffic exposures throughout life were considered. • Exposure to TSP of a woman's first birth was associated with higher methylation of SYK and lower methylation of SCGB3A1. • Traffic exposure was associated with methylation of certain genes. • Our observed associations were not statistically significant after adjustment for multiple comparisons. We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1999

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗
NASA NTRSDate not supplied

Using A Guided Interview to Create an Individual Exposure Profile for The Lifetime Surveillance of Astronaut Health (LSAH)

BACKGROUND To support NASA’s Lifetime Surveillance of Astronaut Health (LSAH) project, Individual Exposure Profiles (IEPs) were developed to record an astronaut’s pre-, in-, and post-NASA exposures. NASA astronauts were invited to participate in a one-time guided interview to review known hazard exposures and medical history documented in NASA records and to add new information not otherwise reported. The purpose of the IEP project was to determine if any significant information was gained from these interviews and identify potential trends in long-term health. METHODOLOGY The pre-filled exposure profile data was extracted from several sources including medical records, biographies, and LSAH records. The information that was pre-filled before the interview included occupational exposures prior to selection to the Astronaut Corps, during active astronaut career (e.g., EVA and ground-based training, on-orbit exposures), and after active career. The IEPs also contained relevant medical history (e.g., audiometry, illnesses, injuries) and significant non-occupational exposures. 189 interviews were conducted from 2012-2014. A Microsoft Access database was created to store the information collected in the IEPs before and after the interviews. The database houses the information from the IEPs to track the updates made to the original data. By analyzing which astronauts supplied additional information and which kinds of data were consistently added, potential gaps and trends in missing data may be identified. In designing the database, an efficient structure was implemented for ease of inputting data and to create variables that would generate quantifiable data. Creating standardized variables within the structure helped ease the process of inputting, organizing data, and analyzing data. Additional updates/data were denoted and were categorized by type of update. The categories identified were “Confirmed”, “Confirmed & Supplemented”, “Supplemented”, “Denied”, “Denied & Supplemented”, and “Other”. STATISTICAL ANALYSIS AND RESULTS To assess frequency of exposure updates, descriptive statistics will be generated and stratified by relevant factors such as astronaut selection decade, age at selection, and program/era. Hypothesis testing will be performed to understand the associations between updates to exposure information and population characteristics.

Astronaut health↗
DOE OSTI2024

Private, public, and bottled drinking water: Shared contaminant-mixture exposures and effects challenge

Background: Humans are primary drivers of environmental–contaminant exposures worldwide, including in drinking-water (DW). In the United States, point-of-use DW (POU–DW) is supplied via private tapwater (TW), public-supply TW, and bottled water (BW). Differences in management, monitoring, and messaging and lack of directly–intercomparable exposure data influence the actual and perceived quality and safety of different DW supplies and directly impact consumer decision–making. Objectives: The purpose of this paper is to provide a meta-analysis (quantitative synthesis) of POU–DW contaminant–mixture exposures and corresponding potential human–health effects of private-TW, public-TW, and BW by aggregating exposure results and harmonizing apical–health–benchmark–weighted and bioactivity–weighted effects predictions across previous studies by this research group. Discussion: Simultaneous exposures to multiple inorganic and organic contaminants of known or suspected human-health concern are common across all three DW supplies, with substantial variability observed in each and no systematic difference in predicted cumulative risk between supplies. Differences in contaminant or contaminant–class exposures, with important implications for DW–quality improvements, were observed and attributed to corresponding differences in regulation and compliance monitoring. Conclusion: The results indicate that human-health risks from contaminant exposures are common to and comparable in all three DW–supplies, including BW. Importantly, this study’s target analytical coverage, which exceeds that currently feasible for water purveyors or homeowners, nevertheless is a substantial underestimation of the breadth of contaminant mixtures in the environment and potentially present in DW. Thus, the results emphasize the need for improved understanding of the adverse human-health implications of long-term exposures to low–level inorganic–/organic–contaminant mixtures across all three distribution pipelines and do not support commercial messaging of BW as a systematically safer alternative to public-TW. Regardless of the supply, increased public engagement in source-water protection and drinking–water treatment is necessary to reduce risks associated with long-term DW–contaminant exposures, especially in vulnerable populations, and to reduce environmental waste and plastics contamination.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerning inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2012

Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically different, the two MWCNTs induced a similar systemic acute phase response. • We found a close correlation between plasma SAA levels and pulmonary Saa3 transcription levels. • Similar changes in plasma lipid levels and in the hepatic transcriptome were observed. • Our results indicate a link between pulmonary exposure to MWCNTs with risk of cardiovascular disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. • The nicotine-induced secondary motoneuron axonal pathfinding errors can occur independent of any muscle fiber alterations. • Nicotine exposure primarily affects dorsal projecting secondary motoneurons axons. • Nicotine-induced primary motoneuron axon pathfinding errors can influence secondary motoneuron axon morphology.

60 APPLIED LIFE SCIENCES↗