2008 Progress Report: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)

EPA Grant Number: R832414
Center: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Center Director: Wexler, Anthony S.
Title: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Investigators: Wexler, Anthony S. , Pinkerton, Kent E.
Institution: University of California - Davis
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: October 1, 2007 through September 30,2008
Project Amount: $7,999,767
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Particulate Matter , Air

Objective:

The overall mission of the San Joaquin Valley Aerosol Health Effects Research Center (SAHERC) is to provide a mechanistic link between ambient particles and the health effects that they elicit. This entails two goals: (1) Understanding the metabolic response of tissue and organs when they are exposed to particulate pollutants and (2) understanding the characteristics of the particulate pollutants and their gaseous co-pollutants that elicit these responses. To forward these goals, the center is divided into five complementary and cooperating projects, supported by a like number of cores. The projects explore metabolic response of pulmonary and cardiovascular tissues to pollutant exposure, whole animal effects of exposure, transport of particles from the airways to other organs and tissues, and disruption of juvenile airway development in response to particle exposure. Thus, the projects take top down approaches, identifying particle characteristics that elicit health responses, and bottom up approaches, examining the health effects that the particles elicit. Our field studies take place in the San Joaquin Valley of California, one of the most polluted airsheds in the country. SAHERC activities also extend beyond the direct exploration of health effects to sponsoring conferences and outreach to the community, and educating graduate students and post-doctoral fellows. SAHERC has sponsored scientific conferences that forward air quality research and complement our mission, including an annual meeting on aviation and the environment (300 attendees), an annual meeting on agricultural emissions of air pollutants (130 attendees), a biennial meeting on photochemical mechanisms in air quality models (100 attendees) and a biennial meeting on modeling aerosol dynamics (100 attendees). SAHERC has sponsored an outreach program whereby female air quality faculty and research staff mentor Girl Scouts on science careers. SAHERC investigators also work together on a training grant that educates PhD students in atmospheric aerosols and health from science, engineering, sociological, economic and policy viewpoints.

SAHERC is in its first funding cycle, so initial efforts were focused more on methods, infrastructure development and screening studies, although substantial research results have also been obtained.

Progress Summary:

Project 1: Pulmonary Metabolic Response.

This project is motivated by elevated susceptibility to polycyclic aromatic hydrocarbons (PAHs) in the young as well as national increases in juvenile and adult asthma. We hypothesize that exposure to PAHs on PM during lung development leads to oxidant stress and increased airway inflammation, and that repeated cycles of injury and repair predispose the lung to a more responsive, asthmatic phenotype. We further hypothesize that these alterations and responses will differ in fundamental ways between neonates and adults. To explore these hypotheses, we have developed novel exposure strategies using custom laboratory generated PM +/- PAHs in collaboration with the center’s PM generation core. We are applying site-specific approaches, developed at UC Davis, to study airway level specific responses to PM.

Our results show that particles with and without PAHs have unique cytokine signatures in the lung with particles containing the PAH 1-nitronaphthalene (1-NN) causing the greatest increase in a number of cytokines associated with inflammation. We have also found that neonatal and adult rat airways metabolize 1-NN differently leading to age-dependent adduction of different cellular proteins. Exposure to low PAH flame generated soot causes the temporal pattern of increases in circulating and migratory PMNs to differ between neonates and adults and increases cytokine expression and elevates markers of oxidant stress including hemeoxygenase-1 and enzymes involved in GSH synthesis. These responses occur in the absence of frank cellular toxicity or morphologic changes.

Project 2: Cardiovascular Metabolic Response.

This project investigates mechanisms whereby particulate matter elicits acute cardiovascular effects. The focus is on endothelial cell responses to particulates and the interaction between pulmonary inflammation and systemic vascular responses. We use cultured human endothelium and airway epithelium to determine the gene, protein and signaling responses to collected ambient particulate matter. We use gene array analysis to identify patterns of altered transcription in response to PM collected from differing sites and seasons in collaboration with the field studies managed by Project 3. Results of these studies drive mechanistic evaluation of PM specific signaling pathways. To extend these results in vivo, we use mice exposed as part of Project 3’s field studies to determine whether pulmonary and systemic endothelial activation occurs and whether this leads to alterations in circulating markers of inflammation or coagulation.

We have determined that collected ambient PM stimulates transcription of xenobiotoic metabolizing enzymes in both endothelium and airway epithelium. We demonstrate PM induced signaling by the aryl hydrocarbon receptor system that leads to up regulation of several of these enzymes. Additional gene pathways emphasize inflammatory activities including e-selectin. We have developed antibody probes for e-selectin in fixed tissues and are evaluating lungs from field exposures. Our field exposure evaluations had demonstrated activation of pro-inflammatory, myelopoetic and pro-coagulant activites in exposed mice. We demonstrated that an increase in the number of blood platelets in exposed animals was correlated with an increase in platelet aggregation and secretion suggesting platelet activation could be an important contributor to PM induced cardiovascular effects.

Project 3: Inhalation Exposure Assessment of San Joaquin Valley Aerosol.

This project examines the health effects elicited in mice due to real-time exposure to ambient particles present in urban and rural locations of the San Joaquin Valley during summer and winter seasons. Animals are examined to determine respiratory and cardiovascular responses and their correlation to particle concentration, size and composition for each location and season. The hypothesis is that particle size and composition, differentiated by location and season, elicit different health effects.

Both location and season significantly affect particle mass, size and composition. Our urban site in Fresno has demonstrated higher particle mass concentrations than present in our rural Westside location. The summer season in both urban and rural sites typically have higher particle mass concentrations compared with the winter season, but this may also be due to periods of rain that reduced particle mass during the winter season. To date the most significant biological effects of particle exposure have been observed at our rural site, compared with our urban site for both summer and winter seasons. Significant increases in the proportion and number of neutrophils recovered from the lungs by bronchoalveolar lavage have been observed, as well as alterations in systemic measures of platelet activation conducted under Project 2. Also noted have been significant increases in the levels of several circulating pro-inflammatory cytokines during the winter season in rural Westside. Heart rate variability studies at the Fresno urban site have yielded inconclusive findings, due to the presence of arrhythmias in both control and particle-exposed mice. However, a significant reduction in heart rate variability has been noted following exposure to concentrated ambient particles in Davis, CA.

Project 4: Transport and Fate of Particles.

This project uses a combined in vitro and in vivo approach to determining the nature and extent of transport of inhaled PM. Our hypothesis is that inhaled fine and ultrafine particles translocate to the circulation and localize to other tissues, mediating the adverse health effects observed outside of the respiratory system. We use size specific synthetic particles with either fluorescent, electron dense or radioisotopic labeling to study mechanisms of transport across cellular barriers in vitro with fluorescence and confocal and electron microscopy. Our in vivo studies use positron emission tomography (PET) to study transport from the lung to other organs after intratracheal instillation of radioisotope labeled (64Cu) PM in live mice.

Our in vitro findings suggest that transport of ultrafine PM across endothelial barriers occurs through vesiculocaveolar transport. Cultured bronchial epithelial cells create a barrier that is relatively impermeable to ultrafine PM. Our in vivo results demonstrate that PET is a powerful tool for visualizing the deposition pattern and subsequent migration of PM. Studies in normal animals show increased levels of PM in the heart after deposition. Studies in an animal model with pre-existing disease show accumulation of PM in the vessel wall at sites of atherosclerosis.

Project 5: Architecture Development and Particle Deposition.

This project is motivated by national increases in juvenile and adult asthma. We hypothesize that exposure to PM during lung development leads to altered airway architecture and function, and concomitant particle deposition. To explore this hypothesis, we developed a method for identifying the entire airway tree down to the terminal bronchioles, and along with Project 1 and the PM generation core, we have developed a flame generated soot exposure facility. Methods are also under development for measuring bolus dispersion and airway-by-airway particle deposition in the rat.

Four publications have resulted from this work to date. The first presents a model of airway architecture development that successfully reproduces the human airway tree from a few simple reproduction rules. The second demonstrates that evolution optimizes airway architecture to maximize peak performance. The third describes the method for automatically obtaining airway architecture in rats and other mammals with similar thoracic volumes and the fourth uses this method to characterize airway architecture and its variability in 6 normal rats. We have exposed rats to ozone during development, finding insignificant alterations in their architecture, but significant alterations in their lung capacity and compliance. The first PM exposures have been completed and are being analyzed.  


Journal Articles: 64 Displayed | Download in RIS Format

Other center views: All 128 publications 71 publications in selected types All 64 journal articles
Type Citation Sub Project Document Sources
Journal Article Aung HH, Lame MW, Gohil K, He G, Denison MS, Rutledge JC, Wilson DW. Comparative gene responses to collected ambient particles in vitro:endothelial responses. Physiological Genomics 2011;43(15):917-929. R832414 (Final)
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  • Journal Article Bein KJ, Zhao Y, Wexler AS. Conditional sampling for source-oriented toxicological studies using a single particle mass spectrometer. Environmental Science & Technology 2009;43(24):9445-9452. R832414 (Final)
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  • Journal Article Bein KJ, Wexler AS. A high-efficiency, low-bias method for extracting particulate matter from filter and impactor substrates. Atmospheric Environment 2014;90:87-95. R832414 (Final)
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  • Journal Article Bein KJ, Zhao Y, Wexler AS. Retrospective source attribution for source-oriented sampling. Atmospheric Environment 2015;119:228-239. R832414 (Final)
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  • Journal Article Breysse PN, Delfino RJ, Dominici F, Elder ACP, Frampton MW, Froines JR, Geyh AS, Godleski JJ, Gold DR, Hopke PK, Koutrakis P, Li N, Oberdorster G, Pinkerton KE, Samet JM, Utell MJ, Wexler AS. US EPA particulate matter research centers: summary of research results for 2005–2011. Air Quality, Atmosphere & Health 2013;6(2):333-355. R832414 (Final)
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  • Journal Article Chan JKW, Fanucchi MV, Anderson DS, Abid AD, Wallis CD, Dickinson DA, Kumfer BM, Kennedy IM, Wexler AS, Van Winkle LS. Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs. Toxicological Sciences 2011;124(2):472-486. R832414 (Final)
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  • Journal Article Chan JKW, Charrier JG, Kodani SD, Vogel CF, Kado SY, Anderson DS, Anastasio C, Van Winkle LS. Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs. Particle and Fibre Toxicology 2013;10:34. R832414 (Final)
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  • Journal Article Chan JKW, Kodani SD, Charrier JG, Morin D, Edwards PC, Anderson DS, Anastasio C, Van Winkle LS. Age-specific effects on rat lung glutathione and antioxidant enzymes after inhaling ultrafine soot. American Journal of Respiratory Cell and Molecular Biology 2013;48(1):114-124. R832414 (Final)
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  • Journal Article Chen C-Y, Chow D, Chiamvimonvat N, Glatter KA, Li N, He Y, Pinkerton KE, Bonham AC. Short-term secondhand smoke exposure decreases heart rate variability and increases arrhythmia susceptibility in mice. American Journal of Physiology-Heart and Circulatory Physiology 2008;295(2):H632-H639. R832414 (Final)
    R831918 (Final)
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  • Journal Article Day KC, Plopper CG, Fanucchi MV. Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult rats. American Journal of Physiology-Lung Cellular and Molecular Physiology 2006;291(1):L75-L83. R832414 (2009)
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  • Journal Article den Hartigh LJ, Lame MW, Ham W, Kleeman MJ, Tablin F, Wilson DW. Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species.Toxicology In Vitro 2010;24(7):1993-2002. R832414 (2010)
    R832414 (Final)
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  • Journal Article Donaldson K, Borm PJA, Oberdorster G, Pinkerton KE, Stone V, Tran CL. Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region. Inhalation Toxicology 2008;20(1):53-62. R832414 (Final)
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  • Journal Article Enright HA, Bratt JM, Bluhm AP, Kenyon NJ, Louie AY. Tracking retention and transport of ultrafine polystyrene in an asthmatic mouse model using positron emission tomography. Experimental Lung Research 2013;39(7):304-313. R832414 (Final)
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  • Journal Article Ge X, Zhang Q, Sun Y, Ruehl CR, Setyan A. Effect of aqueous-phase processing on aerosol chemistry and size distributions in Fresno, California, during wintertime. Environmental Chemistry 2012;9(3):221-235. R832414 (Final)
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  • Journal Article Ge X, Setyan A, Sun Y, Zhang Q. Primary and secondary organic aerosols in Fresno, California during wintertime: results from high resolution aerosol mass spectrometry. Journal of Geophysical Research-Atmospheres 2012;117:15. R832414 (Final)
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  • Journal Article Gojova A, Lee JT, Jung HS, Guo B, Barakat AI, Kennedy IM. Effect of cerium oxide nanoparticles on inflammation in vascular endothelial cells. Inhalation Toxicology 2009;21(Suppl 1):123-130. R832414 (Final)
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  • Journal Article Greeley MA, Van Winkle LS, Edwards PC, Plopper CG. Airway trefoil factor expression during naphthalene injury and repair. Toxicological Sciences 2010;113(2):453-467. R832414 (Final)
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  • Journal Article Ham WA, Herner JD, Green PG, Kleeman MJ. Size distribution of health-relevant trace elements in airborne particulate matter during a severe winter stagnation event: implications for epidemiology and inhalation exposure studies. Aerosol Science and Technology 2010;44(9):753-765. R832414 (2010)
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  • Journal Article Ham WA, Kleeman MJ. Size-resolved source apportionment of carbonaceous particulate matter in urban and rural sites in central California. Atmospheric Environment 2011;45(24):3988-3995. R832414 (Final)
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  • Journal Article Ham WA, Ruehl CR, Kleeman MJ. Seasonal variation of airborne particle deposition efficiency in the human respiratory system. Aerosol Science and Technology 2011;45(7):795-804. R832414 (Final)
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  • Journal Article Kennedy IM. The health effects of combustion-generated aerosols. Proceedings of the Combustion Institute 2007;31(2):2757-2770. R832414 (2009)
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  • Journal Article Kleeman MJ, Riddle SG, Jakober CA. Size distribution of particle-phase molecular markers during a severe winter pollution episode. Environmental Science & Technology 2008;42(17):6469-6475. R832414 (2009)
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  • Journal Article Kleeman MJ, Riddle SG, Robert MA, Jakober CA, Fine PM, Hays MD, Schauer JJ, Hannigan MP. Source apportionment of fine (PM1.8) and ultrafine (PM0.1) airborne particulate matter during a severe winter pollution episode. Environmental Science & Technology 2009;43(2):272-279. R832414 (2010)
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  • Journal Article Lee DY, Wexler AS, Fanucchi MV, Plopper CG. Expiration rate drives human airway design. Journal of Theoretical Biology 2008;253(2):381-387. R832414 (2009)
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  • Journal Article Lee DY, Wallis C, Wexler AS, Schelegle ES, Van Winkle LS, Plopper CG, Fanucchi MV, Kumfer B, Kennedy IM, Chan JKW. Small particles disrupt postnatal airway development. Journal of Applied Physiology 2010;109(4):1115-1124. R832414 (Final)
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  • Journal Article Lee DY, Wallis CD, Van Winkle LS, Wexler AS. Disruption of tracheobronchial airway growth following postnatal exposure to ozone and ultrafine particles. Inhalation Toxicology 2011;23(9):520-531. R832414 (Final)
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  • Journal Article Lee DY, Wexler AS. Simulated annealing implementation with shorter Markov chain length to reduce computational burden and its application to the analysis of pulmonary airway architecture. Computers in Biology and Medicine 2011;41(8):707-715. R832414 (Final)
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  • Journal Article Lee DY, Willits N, Wexler AS. Detecting alterations in pulmonary airway development with airway-by-airway comparison. Annals of Biomedical Engineering 2011;39(6):1805-1814. R832414 (Final)
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  • Journal Article Lee DY, Srirama PK, Wallis C, Wexler AS. Postnatal growth of tracheobronchial airways of Sprague-Dawley rats. Journal of Anatomy 2011;218(6):717-725. R832414 (Final)
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  • Journal Article Lee DY, Wexler AS. Particle deposition in juvenile rat lungs: a model study. Journal of Aerosol Science 2011;42(9):567-579. R832414 (Final)
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  • Journal Article Lee D, Park SS, Ban-Weiss GA, Fanucchi MV, Plopper CG, Wexler AS. Bifurcation model for characterization of pulmonary architecture. Anatomical Record 2008;291(4):379-389. R832414 (2009)
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  • Journal Article Lee D, Fanucchi MV, Plopper CG, Fung J, Wexler AS. Pulmonary architecture in the conducting regions of six rats. Anatomical Record 2008;291(8):916-926. R832414 (2009)
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  • Journal Article Madl AK, Pinkerton KE. Health effects of inhaled engineered and incidental nanoparticles. Critical Reviews in Toxicology 2009;39(8):629-658. R832414 (2010)
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  • Journal Article Madl AK, Teague SV, Qu Y, Masiel D, Evans JE, Guo T, Pinkerton KE. Aerosolization system for experimental inhalation studies of carbon-based nanomaterials. Aerosol Science and Technology 2012;46(1):94-107. R832414C003 (Final)
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  • Journal Article Nakayama Wong LS, Lame MW, Jones AD, Wilson DW. Differential cellular responses to protein adducts of naphthoquinone and monocrotaline pyrrole. Chemical Research in Toxicology 2010;23(9):1504-1513. R832414 (2010)
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  • Journal Article Nakayama Wong LS, Aung HH, Lame MW, Wegesser TC, Wilson DW. Fine particulate matter from urban ambient and wildfire sources from California's San Joaquin Valley initiate differential inflammatory, oxidative stress, and xenobiotic responses in human bronchial epithelial cells. Toxicology In Vitro 2011;25(8):1895-1905. R832414 (Final)
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  • Journal Article Ngo MA, Pinkerton KE, Freeland S, Geller M, Ham W, Cliff S, Hopkins LE, Kleeman MJ, Kodavanti UP, Meharg E, Plummer L, Recendez JJ, Schenker MB, Sioutas C, Smiley-Jewell S, Haas C, Gutstein J, Wexler AS. Airborne particles in the San Joaquin Valley may affect human health. California Agriculture 2010;64(1):12-16. R832414 (2010)
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  • Journal Article Palko HA, Fung JY, Louie AY. Positron emission tomography:a novel technique for investigating the biodistribution and transport of nanoparticles. Inhalation Toxicology 2010;22(8):657-688. R832414 (Final)
    R832414C004 (Final)
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  • Journal Article Pham H, Bonham AC, Pinkerton KE, Chen CY. Central neuroplasticity and decreased heart rate variability after particulate matter exposure in mice. Environmental Health Perspectives 2009;117(9):1448-1453. R832414 (2010)
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  • Journal Article Pinkerton KE, Joad JP. Influence of air pollution on respiratory health during perinatal development. Clinical and Experimental Pharmacology and Physiology 2006;33(3):269-272. R832414 (2009)
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  • Journal Article Plummer LE, Smiley-Jewell S, Pinkerton KE. Impact of air pollution on lung inflammation and the role of Toll-like receptors. International Journal of Interferon, Cytokine and Mediator Research 2012;4:43-57. R832414 (Final)
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  • Journal Article Plummer LE, Ham W, Kleeman MJ, Wexler A, Pinkerton KE. Influence of season and location on pulmonary response to California's San Joaquin Valley airborne particulate matter. Journal of Toxicology and Environmental Health-Part A 2012;75(5):253-271. R832414 (Final)
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  • Journal Article Riddle SG, Robert MA, Jakober CA, Hannigan MP, Kleeman MJ. Size-resolved source apportionment of airborne particle mass in a roadside environment. Environmental Science & Technology 2008;42(17):6580-6586. R832414 (2009)
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  • Journal Article Ruehl CR, Ham WA, Kleeman MJ. Temperature-induced volatility of molecular markers in ambient airborne particulate matter. Atmospheric Chemistry and Physics 2011;11(1):67-76. R832414 (2010)
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  • Journal Article Schenker MB, Pinkerton KE, Mitchell D, Vallyathan V, Elvine-Kreis B, Green FHY. Pneumoconiosis from agricultural dust exposure among young California farmworkers. Environmental Health Perspectives 2009;117(6):988-994. R832414 (2010)
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  • Journal Article Sekizawa Si, Joad JP, Pinkerton KE, Bonham AC. Distinct tachykinin NK1 receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure. British Journal of Pharmacology 2011;163(4):782-791. R832414 (Final)
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  • Full-text: Wiley-Full Text HTML
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  • Journal Article Sekizawa S-i, Joad JP, Pinkerton KE, Bonham AC. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates. Toxicology and Applied Pharmacology 2010;242(2):199-208. R832414 (2010)
    R832414C003 (2010)
    R832414C003 (Final)
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  • Full-text: Science Direct
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  • Journal Article Shen H, Barakat AI, Anastasio C. Generation of hydrogen peroxide from San Joaquin Valley particles in a cell-free solution. Atmospheric Chemistry and Physics 2011;11(2):753-765. R832414 (2010)
    R832414 (Final)
    R832414C002 (2010)
    R832414C002 (Final)
  • Full-text: ACP-Full Text PDF
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  • Abstract: ACP-Abstract
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  • Journal Article Shen H, Anastasio C. Formation of hydroxyl radical from San Joaquin Valley particles extracted in a cell-free surrogate lung fluid. Atmospheric Chemistry and Physics 2011;11(18):9671-9682. R832414 (Final)
    R832414C002 (Final)
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  • Journal Article Shen H, Anastasio C. A comparison of hydroxyl radical and hydrogen peroxide generation in ambient particle extracts and laboratory metal solutions. Atmospheric Environment 2012;46:665-668. R832414 (Final)
    R832414C002 (Final)
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  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Smith KR, Veranth JM, Kodavanti UP, Aust AE, Pinkerton KE. Acute pulmonary and systemic effects of inhaled coal fly ash in rats: comparison to ambient environmental particles. Toxicological Sciences 2006;93(2):390-399. R832414 (Final)
    R832414C003 (2006)
    R832414C003 (2007)
    R832414C003 (2008)
    R832414C003 (Final)
    R829215 (Final)
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  • Full-text: OUP-Full Text HTML
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  • Journal Article Srirama PK, Wallis CD, Lee DY, Wexler AS. Imaging extra-thoracic airways and deposited particles in laboratory animals. Journal of Aerosol Science 2012;45:40-49. R832414 (Final)
    R832414C005 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Sutherland KM, Combs TJ, Edwards PC, Van Winkle LS. Site-specific differences in gene expression of secreted proteins in the mouse lung: comparison of methods to show differences by location. Journal of Histochemistry and Cytochemistry 2010;58(12):1107-1119. R832414 (Final)
    R832414C001 (2010)
    R832414C001 (Final)
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  • Full-text: JHC-Full Text HTML
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  • Journal Article Sutherland KM, Edwards PC, Combs TJ, Van Winkle LS. Sex differences in the development of airway epithelial tolerance to naphthalene. American Journal of Physiology-Lung Cellular and Molecular Physiology 2012;302(1):L68-L81. R832414 (Final)
    R832414C001 (Final)
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  • Full-text: AJP-Full Text HTML
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  • Journal Article Tablin F, den Hartigh LJ, Aung HH, Lame MW, Kleeman MJ, Ham W, Norris JW, Pombo M, Wilson DW. Seasonal influences on CAPs exposures:differential responses in platelet activation, serum cytokines and xenobiotic gene expression. Inhalation Toxicology 2012;24(8):506-517. R832414 (Final)
    R832414C002 (Final)
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  • Abstract: Taylor and Francis-Abstract
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  • Journal Article Tebockhorst S, Lee D, Wexler AS, Oldham MJ. Interaction of epithelium with mesenchyme affects global features of lung architecture: a computer model of development. Journal of Applied Physiology 2007;102(1):294-305. R832414 (2009)
    R832414C005 (2007)
    R832414C005 (2008)
    R832414C005 (Final)
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  • Journal Article Van Winkle LS, Chan JK, Anderson DS, Kumfer BM, Kennedy IM, Wexler AS, Wallis C, Abid AD, Sutherland KM, Fanucchi MV. Age specific responses to acute inhalation of diffusion flame soot particles:cellular injury and the airway antioxidant response. Inhalation Toxicology 2010;22(Suppl 2):70-83. R832414 (Final)
    R832414C001 (2010)
    R832414C001 (Final)
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  • Journal Article Wang L, Green FHY, Smiley-Jewell SM, Pinkerton KE. Susceptibility of the aging lung to environmental injury. Seminars in Respiratory and Critical Care Medicine 2010;31(5):539-553. R832414 (Final)
    R829215 (Final)
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  • Abstract: SRCCM-Abstract
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  • Journal Article Wegesser TC, Pinkerton KE, Last JA. California wildfires of 2008: coarse and fine particulate matter toxicity. Environmental Health Perspectives 2009;117(6):893-897. R832414 (2010)
    R832414C003 (2009)
    R832414C003 (2010)
    R832414C003 (Final)
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  • Full-text: EHP
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  • Journal Article Wegesser TC, Franzi LM, Mitloehner FM, Eiguren-Fernandez A, Last JA. Lung antioxidant and cytokine responses to coarse and fine particulate matter from the great California wildfires of 2008. Inhalation Toxicology 2010;22(7):561-570. R832414 (Final)
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  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Wells MA, Abid A, Kennedy IM, Barakat AI. Serum proteins prevent aggregation of Fe2O3 and ZnO nanoparticles. Nanotoxicology 2012;6(8):837-846. R832414 (Final)
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  • Full-text: ResearchGate-Full Text PDF
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  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Wexler AS, Johnston MV. What have we learned from highly time-resolved measurements during EPA's Supersites Program and related studies? Journal of the Air & Waste Management Association 2008;58(2):303-319. R832414 (Final)
    R832414C005 (Final)
  • Abstract from PubMed
  • Full-text: Taylor&Francis-Full Text PDF
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  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Wilson DW, Aung HH, Lame MW, Plummer L, Pinkerton KE, Ham W, Kleeman M, Norris JW, Tablin F. Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation. Inhalation Toxicology 2010;22(4):267-276. R832414 (2010)
    R832414 (Final)
    R832414C002 (Final)
    R832414C003 (2010)
    R832414C003 (Final)
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  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Zhong C-Y, Zhou Y-M, Smith KR, Kennedy IM, Chen C-Y, Aust AE, Pinkerton KE. Oxidative injury in the lungs of neonatal rats following short-term exposure to ultrafine iron and soot particles. Journal of Toxicology and Environmental Health, Part A-Current Issues 2010;73(12):837-847. R832414 (2010)
    R832414C003 (2010)
    R832414C003 (Final)
    R829215 (Final)
  • Abstract from PubMed
  • Full-text: ResearchGate-Full Text PDF
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  • Abstract: Taylor&Francis-Abstract
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  • Supplemental Keywords:

    ambient air, ozone, exposure, health effects, human health, metabolism, sensitive populations, infants, children, PAH, metals, oxidants, agriculture, transportation,

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832414C001 Project 1 -- Pulmonary Metabolic Response
    R832414C002 Endothelial Cell Responses to PM—In Vitro and In Vivo
    R832414C003 Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
    R832414C004 Project 4 -- Transport and Fate Particles
    R832414C005 Project 5 -- Architecture Development and Particle Deposition