Grantee Research Project Results

Final Report: Rochester PM Center: Source-Specific Health Effects of Ultrafine/Fine Particles

EPA Grant Number: R832415
Center: Rochester PM Center
Center Director: Oberdörster, Günter
Title: Rochester PM Center: Source-Specific Health Effects of Ultrafine/Fine Particles
Investigators: Oberdörster, Günter , Hopke, Philip K. , Frampton, Mark W. , Utell, Mark J. , Finkelstein, Jacob N. , Peters, Annette
Institution: University of Rochester , Clarkson University , GSF-National Research Center for Environment and Health
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
Project Amount: $8,000,000
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

Introduction:

The Rochester Center on "Source-Specific Health Effects of Ultrafine/Fine Particles" focused on the fine (PM_2.5) fraction of ambient PM which includes the ultrafine particle (UFP) fraction. The studies were designed to identify health hazards of source-specific physicochemical components of fine PM (e.g., UFP; organics) in epidemiological, controlled clinical, animal, and in vitro studies; with a new main focus being on sources and on pathophysiological mechanisms by which ambient ultrafine (UF)/fine PM trigger cardiovascular adverse health effects and effects in the central nervous system (CNS). A specific emphasis was on events leading to endothelial dysfunction.

The objective of our Center's multidisciplinary research was to conduct well-coordinated studies covering several aspects of the Source-Exposure-Dose-Response paradigm. Our main focus regarding health effects was not only the respiratory tract but extrapulmonary organ systems, such as the vascular system, the heart and also the CNS. This focus was based on epidemiological and experimental findings, including our own, of PM effects and an awareness of newer results related to the pathophysiology of endothelial dysfunction and thrombus formation associated with cardiac events in susceptible parts of the population.

Approach

The Rochester Center consisted of five Research Cores to test specific hypotheses in order to answer questions of the correlation between the physicochemical makeup of ambient fine ( including UF) particles and effects on blood coagulation, thrombus formation and cardiac events. A multidisciplinary team of atmospheric scientists, chemists, epidemiologists, pulmonary, vascular and cardiac physicians and scientists, inhalation-, neuro-, cellular- and molecular- toxicologists, and immunologists were involved in the following five Research Cores:

Studies in Research Core 1 (Characterization & Source Apportionment) were designed to measure and characterize UF and fine PM to understand the link between physicochemical properties (EC/OC; inorganics, surface reactive oxygen species, EPR), sources, and health effects. Research Core 2 (Epidemiological Studies) investigated real-world PM exposure of susceptible populations, including diabetics, MI (myocardial infarction) patients, and patients with genetic susceptibility, to understand the mechanisms and genetic determinants of susceptibility and to identify the PM components responsible for these effects. Research Core 3 (Clinical Studies) performed controlled exposures of healthy and diabetic subjects with concentrated UF/fine PM to understand the mechanisms of vascular function and cardiac effects. Furthermore, the influence of ambient fine and ultrafine PM exposure on cardiac response parameters in patients with coronary artery disease in an active cardiac rehabilitation program was evaluated. Research Core 4 (Animal Models) used rodent models exposed to concentrated ambient UF/fine particles and on-road highway UF/fine particles to investigate cardiovascular and CNS effects. In addition, the impact of early life (neonatal) exposure to UFP on the respiratory and central nervous system and altered responses later in life was investigated in a mouse model. Research Core 5 (In Vitro Studies) exposed epithelial and endothelial cells and macrophages to PM fractions to study mechanisms of particle-induced injury. Toxicity ranking of PM samples from different sources was verified in in vivo animal studies.

RESEARCH CORE 1: Characterization and Source Apportionment

One objective of the research was to greatly expand the understanding of the chemical composition and impact of specific sources of ultrafine particles on human health, as determined in our epidemiological, clinical and toxicological studies. Another was to develop new sampling methods coupling ATOFMS with high volume cascade impactors such that samples will be collected that represent material primarily from well defined specific sources.

RESEARCH CORE 2: Epidemiological studies on extra pulmonary effects of fresh and aged urban aerosols from different sources

The objective of the epidemiological study in Augsburg, Germany, was to examine the effects of fine and ultrafine particles on systemic responses, endothelial, and cardiac function. Furthermore, we aimed to assess the health effects of air temperature and noise.

RESEARCH CORE 3: Clinical Studies

The overall objective of our studies was to determine the pulmonary and cardiovascular effects of exposure to ultrafine and fine particulate matter (PM). The clinical studies in healthy humans and susceptible individuals in this research core focused on the effects of ambient ultrafine and fine particles on three major determinants of adverse cardiac events: 1) blood coagulation induced by effects on platelets and circulating microparticles; 2) cardiac output; and 3) cardiac rhythm and repolarization. Healthy human subjects, diabetics and asthmatics were exposed for 2hours to either concentrated ambient ultrafine and fine particles or to laboratory generated elemental carbon ultrafine particles.

Title: Ultrafine Particles and Cardiac Responses: Evaluation in a Cardiac Rehabilitation Center

The objectives of the study were to assess the effects of ambient ultrafine and fine particle exposure on biomarkers of pathophysiologic mechanisms thought to underlie previous reports of PM mediated cardiovascular morbidity, in a panel of patients with coronary artery disease.

RESEARCH CORE 4: Animal Models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics

The animal studies were designed to be complementary to the epidemiological and clinical studies and further test hypotheses derived from those studies, but also to explore novel areas of PM research such as effects on the brain, on the developing organism, or the impact of using cleaner fuel on diesel exhaust-induced health effects. Thus, response measurements took into account endpoints determined in the epidemiological (Core 2) and clinical (Core 3) studies. In addition, based on our earlier findings of translocation of inhaled UFP from nasal deposits to the brain, effects on the CNS were also assessed.

RESEARCH CORE 5: In vitro studies

Experiments in this core were designed to provide a mechanistic link and biological plausibility for the whole animal and controlled clinical (human) exposures. Our ability to use defined populations of cells and well characterized particles allows us to test specific hypothesis that arise from the in vivo studies described elsewhere. Endothelial cells as a potential target for translocated ultrafine particles were used to compare different effects of several particulate materials with those of ambient concentrated particles. Results showed that induction of IL-6 gene expression and production of nitrate is regulated by independent mechanisms and simply invoking particle-induced oxidative stress is insufficient to our understanding of the process.

Summary/Accomplishments (Outputs/Outcomes):

RESEARCH CORE 1: Characterization and Source Apportionment

Examples of the core's activity are the development of a Field Deployable ROS Monitor. The Core previously developed a laboratory version of a continuous monitor for particle-bound reactive oxygen species (ROS) (Venkatachari and Hopke, 2008a). This work demonstrated that it is possible to automate the use of dichlorofluorescin (DCFH) as a non-specific indicator of the oxidative capacity of particle surfaces. To move this system into the field to permit routine monitoring of particle-bound ROS, a number of problems had to be resolved, including sensitivity, user-friendly operation, reproducibility, and stability. The result has led to changes in the ROS continuous system. Further testing of the system continues with the expectation that it will be deployed at the NYS DEC site in Rochester where it will operate for at least one year. The improvements we have made appear to work, so it may be possible to operate the system continuously over an entire year.

Research on the characterization of urban ultrafine and accumulation mode particles allows composition and size analysis in real time of single particles using aerosol time-of-flight mass spectrometry (ATOFMS) that was further improved by this Core. One objective of the research was to greatly expand the understanding of the chemical composition and impact of specific sources of ultrafine particles on human health, as determined in our epidemiological, clinical and toxicological studies. Another was to develop new sampling methods coupling ATOFMS with high volume cascade impactors such that samples will be collected that represent material primarily from well defined specific sources. These samples permit improved characterization of the PM from specific sources as well as providing material for in vitro and in vivo testing of their toxicity in Cores 4 and 5. Also, a new method for collecting size-resolved samples of ultrafine PM from ambient air directly into an aqueous solution has been developed. This method gets around issues required with sample collection on filters, where PM species have been determined to be difficult to extract. By growing ambient ultrafine particles with a growth tube (by condensation) they can be detected by ATOFMS and samples can be collected via impinging in fluids. A newly developed growth tube was used to collect samples in close proximity to ships and a local highway. The first growth tube had limited applicability due to its low flow rate, and a new design has been tested to collect higher masses. The final goal is to collect and study a broad range of aerosol sources for chemical analyses and subsequent in vitro cell culture studies.

A method for detection and characterization of ROS was developed to preserve these radicals for a sufficiently long time to permit analyses, using spin-trapping techniques. The formation of α-pinene/ozone first generation products resulting in a number of intermediate species was determined. Based on tandem mass spectrometry results, chemical structures of radicals from these reactions were identified. The structures of these radicals and the formation mechanisms have been revealed and showed radicals that have not been reported previously.

These results showed that the reactions of ozone with monoterpenes proceed via the formation of multiple oxygen- and carbon-centered free radical species. These radical species are highly reactive and thus, have generally not been measureable. A method for their detection and characterization was needed to preserve these radicals for a sufficiently long time to permit analyses to be performed. Radical-addition reactions, also called spin trapping techniques, allow the detection of short-lived radicals. This approach has been applied to products from the α-pinene/ozone reaction. Secondary organic aerosol (SOA) from a reaction chamber was collected on quartz fiber filters and extracted. The extracts were then reacted with either 5,5-dimethyl-1- pyrroline-N-oxide (DMPO) or diethyl-(2-methyl-1-oxido-3,4-dihydro-2H-pyrrol-2-yl) phosphonate (DEPMPO) followed by analysis with ion-trap tandem mass spectrometry (MSn) using electrospray ionization (ESI) in the positive scan mode.

At the suggestion of the Center's Science Advisory Committee, we have examined the ROS associated with main and side stream tobacco smoke (Zhao and Hopke, 2012). Both research and commercially available cigarettes were tested using mainstream and sidestream smoke generated by a Single Cigarette Smoking Machine. For mainstream smoke from regular and light cigarettes, the total quantities of ROS were 120-150 nmol and 90-110 nmol, respectively. For sidestream smoke, the values were 60-90 nmol and 30-70 nmol for regular and light cigarettes, respectively. The effects of the cigarette filter on the emissions were to reduce the particle mass and particle-phase ROS in the mainstream smoke.

The ROS concentrations could be converted to the ROS amount inhaled by human breath per hour (also shown in the table). Combined with the data from this study, we can estimate the length of human exposure to ambient air that is equivalent to smoking or being exposed to the sidestream smoke of a Marlboro (red) cigarette. Thus, if one were to continuously breathe ambient air for a total of 2 to 3 days, the resulting ROS exposure would be equivalent to smoking one Marlboro (red) cigarette. Air heavily impacted by traffic is more polluted, and one day of continuous ambient air exposure is equivalent to smoking one cigarette.

Significance to the field: This work provides a clearer picture of the nature of some short-lived but highly reactive species that are associated with freshly formed secondary organic aerosol. The work provides a better understanding of the mechanism of formation of SOA and ROS and the nature of the reactive species to which humans are exposed. It also indicates that ROS is associated with cigarette smoking and provides a basis for looking at the relative influence of ambient air on ROS exposure in units of cigarettes smoked.

Relationship to the overall Center goals: We hypothesized that particle-bound ROS might be an important contributor to the health effects resulting from oxidative stress. Thus, understanding the nature of the ROS components, their formation and their reactivity provides a better basis for understanding their potential role in inducing adverse effects. Also being able to put ambient ROS exposure into the context of a known human health threat (cigarette smoke), further emphasizes the need to reduce exposure to ambient PM.

Relevance to the Agency's mission: Understanding this oxidative chemistry is important to a fuller understanding of the formation of SOA and associated ROS in the ambient atmosphere. It helps to provide additional insights into the role composition might play in inducing adverse health effects and provides additional information regarding the implications of controlling ozone, a criterion air pollutant.

Potential practical applications: If ROS associated with biogenic SOA is a driver of adverse health effects, then regulatory action would need to focus more on ozone control as a basis for controlling secondary particulate matter.

RESEARCH CORE 2: Epidemiological studies on extra pulmonary effects of fresh and aged urban aerosols from different sources

Methods

Between March 2007 and December 2008, we enrolled 275 participants in three panels consisting of 1) 83 participants with type 2 diabetes mellitus (T2D), 2) 104 participants with impaired glucose tolerance (IGT) and 3) 88 participants with a potential genetic susceptibility (gen. susc.) on the detoxification or inflammation pathways. In total, 1780 visits of all individuals were available with a mean of 6.5 visits per participant which were scheduled every 4-6 weeks on the same weekday and at the same time of the day. At each visit a blood sample was drawn and the blood markers high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), myeloperoxidase (MPO), high sensitivity soluble CD40Ligand (sCD40L), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen were determined. Air pollution and meteorological parameters were measured at a central measurement site in Augsburg throughout the complete study period. In addition, for a subgroup of 112 participants (33 with T2D, 33 with IGT, 46 with gen. susc.) personal measurements of ultrafine particles using a portable condensation particle counter (CPC) as well as air temperature, relative humidity and noise were conducted in 385 visits. Furthermore, cardiac function characterized by electrocardiogram (ECG) measures as well as blood pressure (BP) and endothelial function were assessed in this subset.

Results

Blood markers & air pollutants. Associations between air pollutants and blood markers showed clear differences between persons with T2D or IGT and gen susc. individuals. Associated with increases in air pollution levels we observed significant immediate and lagged increases in hsCRP (range of %-changes of mean across all lags: e.g. 8.9 to 22.9% for PM_2.5 effects), significant increases in MPO (e.g. %-change of mean: 4.9 and 5.0% for effects of lag1 and the five-day average of PM_2.5, respectively; PM10 effects were even more clearly for lag0 to lag3: 4.4 to 5.5%) in gen. susc. individuals. Furthermore, we observed immediate decreases in sCD40L (e.g. -5.2% for PM_2.5 effect) and PAI-1 (e.g. -6.2% for PM_2.5 effect) in the same group. We found nearly no significant air pollution effects in persons with metabolic disorder, except for fibrinogen which showed small delayed increases in persons with IGT associated with almost all air pollutants (e.g. 1.0 to 1.3% for PM_2.5 effects).

Blood markers & air temperature. We observed immediate, lagged and cumulative increases in fibrinogen (0.6% to 0.8%) and PAI-1 (6.0% to 10.1%) in association with a 5°C temperature decrement in participants with T2D or IGT. Participants with a body mass index (BMI) above 30 kg/m² as well as females showed particularly strong effects on fibrinogen. In gen. susc. persons, 5°C decreases in the 5-day average of temperature led to a change of 8.0% [95% confidence interval: 0.5%;16.2%] in IL-6 and of -8.4% [-15.8%;-0.3%] in hsCRP, the latter driven by physically active individuals.

Endothelial function, blood pressure & air temperature. Our analyses of air pollution effects on markers of endothelial dysfunction showed conflicting associations across the analyzed parameters and only weak associations with blood pressure (BP). However, decreases in air temperature were associated with an increase in systolic and diastolic BP and pulse pressure (PP) in individuals with T2D. For example, a 5°C decrease in ambient air temperature led to an immediate increase in systolic BP of 5 mmHg [2.5 mmHg; 7.3 mmHg]. Effects of personally measured air temperature were slightly stronger. Temperature effects were more pronounced in men, in obese (BMI≥30kg/m2) or elderly (age≥60years) individuals, and in those taking no antihypertensive medication or spending most of their time indoors (>70%).

ECG measures & air pollutants. In our analyses of the effects of personally measured particle number concentration (PNC) on ECG measures we observed a concurrent decrease in 5-minute averages of the standard deviation of all normal-to-normal intervals (SDNN) of -0.56% [-1.02; -0.09%] with an increase in PNC of 16000 per cm³. Furthermore, an increase in heart rate (HR) of 0.23 % [0.11; 0.36%] five minutes after the same increase in PNC was noted. One-hour average concentrations of PM_2.5 measured at the central monitoring site were associated with decreases in 1-hour averages of SDNN of -3.38% [-6.01; -0.75%] and in 1- hour averages of the root mean square of successive normal-to-normal interval differences (RMSSD) of -7.65% [-12.64; -2.38%] per 12.4 µg/m³ PM_2.5.

The analyses of effect modifications by single nucleotide polymorphisms (SNP) in persons with T2D or IGT showed concurrent and lagged decreases in the SDNN by about 25% in association with all centrally measured air pollutants. These effects were especially strong in participants with at least one minor allele of rs332229. Increases in PM_2.5 were associated with 4-hour lagged decreases of -6.6% [-10.6; -2.6%] and -13.0% [-20.7; -5.1%] in SDNN in individuals with one or two minor alleles, respectively. We observed a -7.2% [-12.2; -1.8%] reduction in RMSSD associated with concurrent increases in PM_2.5. Individuals with at least one minor allele of rs2096767 or at most one minor allele of rs2745967 exhibited stronger PM_2.5 effects.

Furthermore, we observed concurrent and 1- to 4-hour lagged increases in (HR) of 0.5-0.7% for each 20 mg/m³ increase in ozone. These effects were stronger (1.0-1.2%) when participants were outdoors during the summer. We detected in all participants a concurrent (-1.31% [-2.19;-0.42%]) and 1-hour lagged (-1.32% [-2.19; -0.45%]) T-wave flattening. Elevated ozone levels were associated with 1-hour (2.12% [0.81; 3.52%]) and 2- hour lagged (1.89% [0.55%; 3.26%]) increases in T-wave complexity. However, no effects were seen for the Bazett-corrected QT-interval. Ozone effects were generally more pronounced in individuals with metabolic disorders than in persons with a potential genetic predisposition.

ECG measures & noise. When noise levels where below 65 dB(A) over a 5-minute period we observed an increases in HR (1.5% [1.4; 1.6%]) and in the ratio of low frequency (LF) to high frequency (HF) power (4.9% [3.5; 6.4%]) as well as decreases in LF (-3.9% [-5.6; -2.1%]) and HF (-8.7% [-10.4; -6.9%]) power. SDNN increased concurrently with noise levels below 65 dB(A) (5.6% [5.0; 6.2]) but also showed 5- to 15-minute delayed decreases (-0.6% to -0.7%). For increases in noise levels above 65 dB(A), associations with cardiac function were less pronounced partly showing opposite signs.

RESEARCH CORE 3: Clinical Studies

Results from these studies were: UFCP (ultrafine carbon particles) at 20 µg/ml alone significantly increased platelet p-selectin expression (p = 0.04), but did not further enhance p-selectin expression in the presence of agonists. UFCP at 20 µg/ml also significantly reduced platelet count in the presence of all agonists except thrombin. There was no significant increase in platelet aggregates or microparticles. Conclusions: UFCP alone at 20 µg/ml activated platelet in vitro. Prior exposure to UFCP significantly reduced platelet count in response to platelet agonists in vitro. This may reflect the formation of platelet-leukocyte conjugates. Ten- fold lower UFC concentration did not induce these effects.

Compared with air, ultrafine carbon particle exposure of diabetics increased platelet expression of CD40 ligand (CD40L) and the number of platelet-leukocyte conjugates 3.5 hr after exposure. Soluble CD40L decreased with UFCP exposure. Plasma von Willebrand factor increased immediately after exposure. There were no effects of particles on plasma tissue factor, coagulation factors VII or IX, or D-dimer.

Increases in ambient UFP were associated with decreases in surface expression of platelet activation markers. The number of platelet-leukocyte conjugates decreased by -80 (95% confidence interval (CI) -123 to -37, p = 0.001) on the first lag day (20-44 h prior to the blood draw) and by -85 (CI -139 to -31, p = 0.005) on combined lag days 1 to 5, per interquartile range (IQR) increase in UFP particle number (2482). However, levels of soluble CD40L increased 104 (CI 3 to 205, p = 0.04) pg/ml per IQR increase in UFP on lag day 1, a finding consistent with prior platelet activation.

Healthy non-smoking subjects were exposed to ambient concentrated ultrafine particles. The mean particle number was 24.7±13.3 x 104 particles/cm3 (10.5 times higher than outside), with a mass concentration of 158.0±84.6 µg/m3. The particle count mean diameter was 94.14±7.90 nm, with a geometric standard deviation of 1.60. None of the subjects experienced exposure-related symptoms. The diastolic and mean blood pressure increased 0.5 hour after exposure to UFP vs air (mean blood pressure 97.6±2.2 vs 92.6±3.0 mmHg respectively, p = 0.04), and returned to baseline 3 hours after exposure. 24 hours after UFP exposure, the FEV1 decreased 2.0% and the maximum mid-expiratory flow rate decreased 6.5%, significantly different from air exposure (p = 0.01 and p = 0.02, respectively). There were no significant changes in heart rate, Vc, or FMD.

Exposure of asthmatics to concentrated UFP was well-tolerated, and did not alter the FEV1 or airway NO kinetics. Expression of CD40 was significantly reduced on CD14+ monocytes 3 hours after UFP exposure compared to filtered air (p = 0.03). The numbers of lin- cells decreased significantly 3 hours after UFP but not filtered air (p = 0.02), but this was not reflected by changes in the frequencies or activation of mDC1, mDC2, or pDC subsets, although expression of CD40 tended to be lower on mDC1. Inducible expression of CD40 also tended to be lower on DC differentiated from CD14+ precursors obtained 3 hours after UFP exposure compared to filtered air. The number of blood eosinophils increased 24 hours after UFP exposure relative to air (p=0.02). None of these results were significantly affected by GSTM1 genotype.

Healthy subjects were exposed to ultrafine elemental carbon particles. We identified 1713 genes (UFCP 24 h vs. FA 0 and 24 h, P < 0.05, false discovery rate of 0.01). The top 10 upregulated genes (fold) were CDKN1C (1.86), ZNF12 (1.83), SRGAP2 (1.82), FYB (1.79), LSM14B (1.79), CD93 (1.76), NCSTN (1.70), DUSP6 (1.69), TACC1 (1.68), and H2AFY (1.68). Upregulation of CDKN1C and SRGAP2 was confirmed by real-time-PCR. We entered 1020 genes with a ratio >1.1 or <−1.1 into the Ingenuity Pathway Analysis and identified pathways related to inflammation, tissue growth and host defense against environmental insults, such as, insulin growth factor 1 signaling, insulin receptor signaling and NF-E2-related factor-2-mediated oxidative stress response pathway.

Healthy non-smoking subjects were exposed to elemental ultrafine carbon particles to study effects on electrocardiogram (ECG) recordings. Observed responses to UFCP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFCP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFCP in comparison to air exposure.

Title: Ultrafine Particles and Cardiac Responses: Evaluation in a Cardiac Rehabilitation Center

Patients were offered enrollment in the study as they entered the Cardiac Rehabilitation program. A population of 76 subjects referred by their cardiologist to the University of Rochester Cardiac Rehabilitation Center (Center) after having a recent coronary event (MI or unstable angina) were included in the study. The project assessed the following specific hypotheses: (1) Elevated levels of ambient ultrafine and fine particles are associated with changes in autonomic nervous system function measured by heart rate variability parameters, and myocardial substrate and myocardial vulnerability measured by QRS duration, QT interval, ST segment changes and T wave abnormalities; (2) Elevated levels of ambient ultrafine and fine particles are associated with changes in biomarkers of enhanced cardiovascular risk, including systemic inflammation (C-reactive protein) and hypercoagulability (fibrinogen); and (3) Elevated levels of ambient ultrafine and fine particles are associated with slower and compromised rehabilitation.

Our findings revealed that the peak of ultrafine particles in the 10 - 50 nm size range is primarily related to traffic sources during the morning rush hour (7 to 9 AM). In contrast, the peak of ultrafine particles in the 50 to 100 nm size range were more correlated with the evening rush-hour (6 to 7 PM), while fine particles (100 to 500 nm) were marginally related to the traffic during both the morning and evening periods. In addition, we found that a second pattern of particle distribution follows the morning rush-hour peak, where large numbers of very small (approximately 10 nm) particles appeared just after noon. These particles grew rapidly through the early afternoon into particles in the 50 to 75 nm size range. This growth resulted from frequent nucleation events, which were most evident during the summer when photochemical processes were more intense.

Results: Mean (and standard deviation) HRV and repolarization and heart rate turbulence levels in both the pre-exercise resting period and across the whole session, as well as diastolic and systolic blood pressure, white blood cell count, CRP, and fibrinogen levels were analyzed. There was no clear pattern of response to any pollutant for MeanNN or SDNN in the pre-exercise resting period, although we did observe a significant (p < 0.05) 2.67 ms increase in SDNN associated with each IQR increase in PM_2.5 72-95 hours before the clinic visit. However, IQR increases in AMP (accumulation mode particles) in both the previous 6 and 24 hours were associated with significant 3.65 and 4.33 ms decreases in rMSSD, respectively. Although not statistically significant, decreases in rMSSD were also associated with UFP and PM_2.5 at the same lag times.

There was no clear pattern of response of MeanNN or deceleration capacity to any pollutant across the whole session (pre and post-exposure). However, each IQR increase in UFP 24-47 hours before the clinic session was associated with a 2.19 ms decrease in SDNN. rMSSD also decreased significantly with the same IQR increase in UFP within the previous 48 hours (lag hour 0-5, 0-23, and 24-47), with the largest change (-3.19 ms) observed with the UFP count in the 6 hours before the exercise session. Each IQR increase in AMP 72-95 hours before the clinic session was also associated with a significant 0.67 ms/RR reduction in heart rate turbulence.

There were statistically significant 0.89 and 0.94 mmHg increases in SBP (systolic blood pressure) associated with IQR increases in UFP lagged 24-47 hours and PM_2.5 lagged 0-5 hours, respectively, but little change in DBP (diastolic blood pressure). However, each IQR increase in UFP lagged 96-119 hours was associated with significantly decreased DBP. White blood cell counts did not respond to any lagged pollutant concentration, but IQR increases in UFP, AMP, and PM_2.5 concentrations were associated with increases in CRP and fibrinogen at most lags, although not all were statistically significant.

RESEARCH CORE 4: Animal Models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics

Several studies were done using JCR rats, a model of type II diabetes. Although these rats are not hyperglycemic, the JCR cp/cp rats are obese, hyperlipidemic, hyperinsulinemic, and have atherosclerotic and ischemic lesions that are hallmark features of human type II diabetes. These rats were either exposed to realistic ultrafine diesel exhaust aerosols in a mobile exposure laboratory on a highway, or exposed in the laboratory to concentrated ambient ultrafine particles in parallel to the controlled clinical studies.

Exposures (6 hr/day; 1 or 4 days in a row) to low- and ultralow-sulfur Diesel fuel exhaust emission aerosols were conducted in compartmentalized whole-body chambers while the mobile laboratory was driven between Rochester and Utica (NY I-90). There was an obvious effect of obesity and insulin resistance on baseline lavage inflammatory parameters, namely that the JCR cp/cp (obese) rats had higher total cell numbers, percentages of PMNs, and lavage fluid protein content and LDH and β-glucuronidase activities than their lean litter mates. However, the emission aerosols did not have any consistent effects on these parameters. We also measured several parameters in serum and lavage fluid related to inflammation (PAI-1, IL-1β, IL-6, MCP-1, TNF-α) and metabolism (insulin, leptin) using bead array technology (rat adipokine panel, Luminex detector system). There was a lot of variability in the results, more so in the JCR cp/cp than in +/? rats, but the obese rats had higher levels for most of the parameters we measured. There was a trend that JCR cp/cp rats had lower levels of GFAP in sampled brain regions (olfactory bulb, olfactory tract, cortex, striatum, cerebellum, hippocampus), there was no consistent pattern of response of this protein to the exhaust emission aerosols.

Exposure of the JCR rats to concentrated ambient UFP also showed that many baseline parameters were elevated in the obese, insulin-resistant rats (JCR cp/cp) as compared to the lean controls (JCR +/?). The parameters that were elevated in cp/cp as compared to +/? JCR rats included total lavage cell number; lavage fluid protein concentration and LDH and β-glucuronidase activities; plasma fibrinogen; total white blood cell number; and the number of blood leukocyte aggregates.

After three days of exposure, we found statistically significant increases in lavage fluid protein concentration and LDH activity in the HUCAPS-exposed JCR cp/cp rats as compared to filtered air-exposed and +/? rats. These changes occurred in the absence of increases in the percentage of lavage fluid PMNs. These changes were not observed following 4 weeks of exposure. An intriguing piece of data from the 3-day exposure was that aortic mtDNA amplification was blunted in HUCAPS-exposed JCR cp/cp rats relative to air- exposed controls and +/? rats, suggesting that oxidative DNA damage had occurred. However, this finding could not be confirmed with samples from the 4-week study, as the long fragment from the extracted mtDNA was degraded due to technical issues. We also examined brain tissues for GFAP protein content and inflammatory cytokine/chemokines message levels. As we had seen in the on-road studies, the GFAP levels in all of the brain regions tended to be lower in the JCR cp/cp rats as compared to the +/? rats. However, there were no changes in the levels of GFAP protein or TNF-α or MCP-1 mRNA levels that were related to exposure atmosphere.

Studies in neonatal and young mice involved inhalation exposures to concentrated ambient UFP. Following 6 weeks of exposures of transgenic Huntington Disease model mice, statistical analyses revealed that, unlike non-transgenic mice, the Rotarod performance of the transgenic mice declined over time. For those mice exposed to HUCAPS aerosols, the performance was significantly lower by the third week of testing, whereas for filtered air-exposed mice, performance did not drop significantly until the fourth testing week. Serial coronal sections of brain tissue were evaluated for striatal atrophy and huntingtin protein (Htt) expression and aggregation. There were no significant differences between filtered air and HUCAPs exposed mice.

Twelve day exposure to inhaled Mn-oxide particles using a transgenic Alzheimer's disease mouse model at 4 months of age revealed heightened activation of Iba1-expressing microglia in the hippocampus and dentate gyrus one days following Mn oxide aerosol exposure alone or in combination with LPS. Quantitative image analysis of staining intensities for GFAP indicated that astrocyte activation was similarly enhanced. These results indicate enhanced activation of the innate immune system in brain regions that are relevant to the pathology of AD and raise the possibility that disease severity could be accelerated with inhaled pollutant exposures. These changes in inflammatory cell activation state persisted through two months post-exposure.

Effects of early life exposure to ambient ultrafine particles and ozone mixtures on the early and late pulmonary responses of mice re-challenged with ovalbumin, including an assessment of nanoparticle translocation to the brain. Gold nanoparticles were detected in lung, liver, kidney, spleen and the brain, demonstrating that nanoparticle translocation occurs during the postnatal lung growth period.

Enhanced staining intensity of GFAP could be seen throughout the ventral midbrain in mice that were exposed to UFP neonatally and kept until 56 days of age. The astrocytes were hypertrophied with thickened processes, indicative of glial activation. A remarkable feature of this response is its persistence from early-life exposure to adulthood. These observations demonstrate that astroglial activation is present in the adult ventral midbrain following HUCAPS exposure during the neonatal period. We also observed increased numbers of microglial cells and enhanced Iba-1 staining in all layers of the dentate gyrus. These cells also exhibited a more ameboid morphology and increased intensity of Iba-1 staining, which are features consistent with microglial activation.

A separate group of neonatally UFP + ozone exposed mice was intranasally infected on day 178 with 120 hemagglutination units (HAU) of influenza virus A/HKx31 (H3N2) in order to study the impact of viral respiratory tract infection on ultrafine particle induced effects. This study showed that early life ultrafine particle and ozone inhalation sensitizes the lung to later life environmental and viral challenges. There was no lethality in any of the mock flu infected groups; however, there was approximately a 25% lethality in the sham, HUCAPS and HUCAPS + ozone groups with influenza infection. The ozone only group had approximately 50% lethality 14 days post infection.

Another mouse study tested the hypothesis that early life postnatal exposure to concentrated ambient ultrafine particles would sensitize the CNS to subsequent adult challenge with paraquat + maneb (PQ+MB), a well-established pesticide-based model of the Parkinsons disease phenotype (PDP). Mice exposed postnatally to concentrated ambient ultrafine particles were significantly more sensitive to the locomotor-reducing effects of PQ+MB than sham controls, or those exposed to UFP alone or PQ+MB alone. UFP and PQ+MB significantly altered catecholamine levels in both the nigrostriatal and mesocortical dopamine pathways. UFP had a particular influence on striatum, increasing NE, DOPAC, and DA turnover (DOPAC/DA) levels, while PQ+MB generally impacted midbrain, decreasing 5HT, DOPAC and dopamine turnover. An interaction between UFP and PQ+MB on cortical 5-HT levels was evidenced as a significant 5-HT decrease in PQ+MB treated animals compared to both sham controls and UFP +PQ+MB treated mice. Cortical DA was also increased in PQ+MB treated animals.

RESEARCH CORE 5: In vitro studies

A particular focus of the in vitro studies was to identify mechanisms that may be involved in the enhanced susceptibility of cells from diabetics. Our in vitro studies were designed to model this under controlled conditions. One of the hallmarks of the diabetic is the increased blood glucose and we have shown that culture of vascular endothelial cells in high glucose alters both the basal and particle induced cytokine responses. Using this model we studied the response of pulmonary cells to particles collected by a high volume sampler in Rochester. These are similar to PM used in animal and human clinical studies carried out using the Harvard ultrafine particle concentrator. Human respiratory epithelial cells exposed to collected ultrafine particles responded through increased production of IL-6. In contrast to previous work that focused only on the production of NO and endothelium epithelial cells maintained under conditions of hyperglycemia actually produced increased amounts of IL-6. This was in contrast to results where HUVEC were cultured under similar conditions. It was also evident that the ambient samples showed a somewhat different response in these cells for this marker.

In vitro studies were designed to model the diabetic condition and thereby altered cellular responses to PM by culturing vascular endothelial cells in high glucose. This altered both the basal and particle-induced cytokine response. We showed that the normally increased production of NO in ultrafine particle exposed endothelial cells is reduced under these hyperglycemic culture conditions. We found also that particulate matter from different sites show significant differences in their ability to induce NO production, suggesting to reflect differences in PM composition.

One question raised in our studies is the role of PM induced oxidative stress in the generation of cytokine or NO (Nitric Oxide) responses. The human clinical studies have been measuring vascular reactivity as a measure of response to inhaled PM. Included in that battery of outcomes was IL-6 and plasma Nitric Oxide (NO). To examine this response in a mechanistic manner we measured changes in both of these outcomes in cells that have had their antioxidant status altered by culturing with exogenous antioxidants.

Emphasis in these studies shifted to vascular cells to examine specific mechanistic pathways that complement results of the cardiovascular in vivo endpoints. Endothelial cell monolayer as well as epithelial-endothelial cell co-cultures were established. Exposures to different ultrafine particle types or "as positive control LPS" showed that measurement of induced IL-6 has best predictive value. The co-culture model used the epithelial A549 cell on the top of a transwell insert with HUVEC cells in the lower chamber. Adding a stimulus to the upper chamber stimulated directly the epithelial cells, while dosing the lower chamber stimulated the apical side of the endothelial cells. Results with ultrafine particles show specificity in terms of oxidative stress induction observed only after particle addition to the upper but not to the lower chamber. Use of collected ambient ultrafine particles for in vitro cell culture studies did experience problems in that it was not possible to separate the particles from the filter substrate.

We have focused on developing approaches that could be used to measure cellular responses to collected and fractionated sample of ambient ultrafine PM. PM samples obtained from various sources were tested in a novel growth tube device that would increase the yield of ultrafine PM material available for testing. Each sample was adjusted to the same final concentration and evaluated in our indicator A549 cell line. Physical and chemical ambient measurements of the samples collected between the ports of Long Beach and Los Angeles showed that the major sources of the particles were marine diesel combustion, local diesel pollution, nearby freeway pollution, biomass burning, and transport of pollution from California's Central Valley. The results indicate that ambient aerosol containing ultrafine PM from marine diesel engines are significantly more reactive inducing oxidative stress than ultrafine TiO2 particles that were used as control PM. However, the yield of the growth tube device was insufficient for obtaining enough ultrafine PM sample to establish dose-response relationships. Efforts to increase the yield of the collecting system were not successful. We were experiencing problems with collecting source-specific ambient ultrafine particles using a new growth tube/impinger system for studying potential responses in vitro. A larger model of the growth tube had been developed to be used for collecting source-specific ultrafine particles but was still not able to supply sufficient ultrafine PM material to carry out meaningful in vitro studies.

Conclusions:

RESEARCH CORE 1: Characterization and Source Apportionment

Better insights have been gained on the formation of endogenous ROS through the formation of secondary organic aerosol (SOA).
We have been able to show that it is possible to capture and characterize organic free radical species formed in the oxidation of common biogenic VOCs.
We have shown that the ambient aerosol can induce levels of exposure to particle-bound oxidants similar to exposure to cigarette smoke.
We have been able to collect highly source impacted samples to provide characterization of particles from specific sources.

RESEARCH CORE 2: Epidemiological studies on extra pulmonary effects of fresh and aged urban aerosols from different sources

Our analyses of associations between air pollutants and blood markers confirmed the hypothesis that oxidative stress plays a role in the mechanism linking air pollution and cardiovascular disease.
Results substantially differed between persons with type 2 diabetes or impaired glucose tolerance and genetically susceptible participants, indicating that there might be different biological mechanisms ongoing.
Effects were mostly seen for PM_2.5 and less for ultrafine particles, and most clearly for inflammatory markers. One can assume that the reason for this is the inflammatory potential of particulate mass, which possibly derives from secondary organic aerosols.
We observed differing temperature effects on blood markers in persons with metabolic disorder and genetically susceptible individuals which again probably indicates different underlying biological mechanisms with regard to systematic responses.
We observed associations between decreases in air temperature and increases in blood pressure as well as in pulse pressure mainly in persons with type 2 diabetes, possibly due to vascular abnormalities like endothelial dysfunction which are very common in these individuals.
Our study showed changes in ECG measures associated with personally measured particle number concentration and centrally monitored air pollutants suggesting that both freshly emitted traffic particles as well as aged aerosol in urban areas are associated with changes in cardiac rhythm.
Our results suggested that certain polymorphisms in persons with type 2 diabetes or impaired glucose tolerance make them potentially more susceptible to air pollutants with regard to changes in heart rate variability.
Individual day-time noise exposure was associated with immediate changes in heart rate variability. Thereby, noise at lower levels led to a parasympathetic withdrawal while changes in high noise levels were rather associated with a sympathetic activation in terms of a "fight-or-flight" response.

RESEARCH CORE 3: Clinical Studies

UF carbon particles activate platelets in vitro at high concentration.
Inhalation of UF carbon particles activate platelets in type 2 diabetics.
Ambient UFP exposure activate circulating platelets in type 2 diabetics.
Concentrated ambient UFP transiently increase blood pressure and reduce pulmonary function 24 hrs. after exposure in healthy people.
Concentrated ambient UFP alters circulating eosinophils, monocytes, myeloid dendritic cells and their precursors in asthmatic subjects.
Exposure of healthy subjects to UF carbon particles induced gene expression changes in circulating mononuclear cells.
Exposure of healthy young subjects to UF carbon particles did not induce significant changes in ECG- derived parameters; trends in some subjects indicating autonomic modulation of the heart and repolarization of ventricular myocardium.
Exposure to concentrated UFP non-significantly increased nitrite arterial-venous gradients without effects on vascular function.

Title: Ultrafine Particles and Cardiac Responses: Evaluation in a Cardiac Rehabilitation Center

Major Findings:

The major objective of the panel study in cardiac rehabilitation patients was to determine if elevated levels of ambient ultrafine and fine particles were associated with adverse changes in autonomic nervous system function measured by heart rate variability parameters as well as in myocardial substrate and myocardial vulnerability measured by QRS duration, QT interval, ST segment changes and T wave abnormalities.

Significant adverse changes were observed in most outcomes associated with increased UFP, AMP, and PM_2.5 within the previous 5 days using repeated measures analysis of variance.
The largest changes were decreased rMSSD (square root of the mean of the sum of the squared differences between adjacent NN intervals) associated with UFP in the previous 6 hours.
Increased TpTe (Time from peak to end of T-wave) was associated with AMP lagged 72-95 hours.
Decreased heart rate turbulence was associated with AMP lagged 72-95 hours.
Increased systolic blood pressure was associated with PM_2.5 in the previous 6 hours.
Increased fibrinogen was associated with all three particulate air pollutant size fractions lagged 24-47 hours.
There was little evidence of an air pollution effect on subjects self-perceived exertion during the exercise sessions.
In these cardiac rehabilitation patients, particles were associated with asymptomatic and subclinical decreases in parasympathetic modulation, prolongation of late repolarization duration, increased blood pressure, and systemic inflammation, factors predisposing to increased risk of arrhythmic events and sudden death in post-infarction patients.

RESEARCH CORE 4: Animal Models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics

Six-hour exposure of obese diabetic and lean control rats to diesel exhaust (low and ultralow sulfur fuel) in a mobile lab on highway induced significant decreases in serum leptin; non-significant trend of higher levels in serum and lung lavage, of inflammatory cytokines; trend of lower GFAP level in brain regions and higher levels of inflammatory cytokines in olfactory bulb (non-significant.
Four-week exposure of obese diabetic and lean rats to concentrated ambient UFP showed increased lung lavage protein and LDH levels at 3 days of exposure but not at the end of 4-week exposure, indicating potential adaptive mechanisms. Platelet number decreased in both rat types at the end of 4-week exposure. The obese diabetic rats are not more sensitive than their lean litter mates.
Four-week exposure to concentrated ambient UFP resulted in a disruption of iron homeostasis in obese diabetic rats indicting higher baseline levels of oxidative stress.
Obese diabetic rats have higher leptin levels in serum and lavage fluid.
Concentrated UF particle exposure in an early onset neurodegeneration mouse model may accelerate decline in locomotor function.
Twelve-day ultrafine Mn-oxide exposure in a mouse model of Alzheimer's Disease induced enhanced activation of the innate immune system in hippocampus and dentate gyrus which persisted through two months post-exposure.
Neonatal mice inhalation exposure to gold nanoparticles confirmed their translocation to extrapulmonary tissues, including the olfactory bulb of the CNS.
Eight days of neonatal mouse inhalation exposure to concentrated ambient UF particles induced microglial activation in the dentate gyrus of the hippocampus, which was still present in adulthood.
Neonatal mouse inhalation exposure to concentrated ambient UF particles in combination with ozone sensitizes the lung to later life viral challenges.
Early life exposure of mice with a pesticide-based Parkinson's disease phenotype to concentrated UFP enhances locomotor reduction with concurrent damage to striatum and midbrain.

RESEARCH CORE 5: In vitro studies

Elevated glucose, as a model for diabetes, caused enhanced cytokine production by endothelial cells when cultured with collected ambient samples of PM.
No production was significantly affected by PM composition and ongoing oxidative stress in cultured endothelial cells.
Modeling endothelial cell responses to PM was enhanced in a co-culture model where both epithelial cells and endothelial cells were exposed to PM.
Source-specific PM can be used in vitro as a potential model to examine the role of specific PM components.
Marine diesel PM showed the greatest oxidative stress potential in vitro.

Journal Articles: 144 Displayed | Download in RIS Format

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Other center views:	All 191 publications	157 publications in selected types	All 144 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Azadniv M, Torres A, Boscia J, Speers DM, Frasier LM, Utell MJ, Frampton MW. Neutrophils in lung inflammation: which reactive oxygen species are being measured? Inhalation Toxicology 2001;13(6):485-495.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R826781 (2001) R826781 (Final) R827354 (2004) R827354 (Final) R827354C003 (2001) R827354C003 (2002) R827354C003 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Beckett WS, Chalupa DF, Pauly-Brown A, Speers DM, Stewart JC, Frampton MW, Utell MJ, Huang L-S, Cox C, Zareba W, Oberdorster G. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults:a human inhalation study. American Journal of Respiratory and Critical Care Medicine 2005;171(10):1129-1135.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (2004) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ATS Journals - Full Text HTML Exit Abstract: ATS Journals - Abstract Exit Other: ATS Journals - Full Text PDF Exit
Journal Article	Berger A, Zareba W, Schneider A, Ruckerl R, Ibald-Mulli A, Cyrys J, Wichmann HE, Peters A. Runs of ventricular and supraventricular tachycardia triggered by air pollution in patients with coronary heart disease. Journal of Occupational and Environmental Medicine 2006;48(11):1149-1158.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Abstract from PubMed Full-text: JOEM - Full Text HTML Exit Abstract: JOEM - Abstract Exit
Journal Article	Bernard JJ, Seweryniak KE, Koniski AD, Spinelli SL, Blumberg N, Francis CW, Taubman MB, Palis J, Phipps RP. Foxp3 regulates megakaryopoiesis and platelet function. Arteriosclerosis, Thrombosis, and Vascular Biology 2009;29(11):1874-1882.	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ATVB-Full Text HTML Exit Other: ATVB-Full Text PDF Exit
Journal Article	Bezemer GFG, Bauer SM, Oberdorster G, Breysse PN, Pieters RHH, Georas SN, Williams MA. Activation of pulmonary dendritic cells and Th2-type inflammatory responses on instillation of engineered, environmental diesel emission source or ambient air pollutant particles in vivo. Journal of Innate Immunity 2011;3(2):150-166.	R832415 (Final) R832139 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Karger-Full Text PDF Exit Abstract: Karger-Abstract Exit
Journal Article	Breitner S, Stolzel M, Cyrys J, Pitz M, Wolke G, Kreyling W, Kuchenhoff H, Heinrich J, Wichmann H-E, Peters A. Short-term mortality rates during a decade of improved air quality in Erfurt, Germany. Environmental Health Perspectives 2009;117(3):448-454.	R832415 (2010) R832415 (Final) R832415C002 (2010) R832415C002 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
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.	R832415 (Final) R832413 (Final) R832414 (Final) R832416 (Final) R834798 (2013) R834798 (2014) R834798 (2015) R834798 (Final) R834798C001 (2013) R834798C001 (2014)	Abstract: Springer-Abstract Exit Other: ResearchGate-Abstract Exit
Journal Article	Bruske I, Hampel R, Socher MM, Ruckerl R, Schneider A, Heinrich J, Oberdorster G, Wichmann H-E, Peters A. Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease. Inhalation Toxicology 2010;22(3):245-252.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C002 (2010) R832415C002 (2011) R832415C004 (2010) R832415C004 (2011) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: Taylor&Francis-Abstract Exit
Journal Article	Bruske I, Hampel R, Baumgartner Z, Ruckerl R, Greven S, Koenig W, Peters A, Schneider A. Ambient air pollution and lipoprotein-associated phospholipase A2 in survivors of myocardial infarction. Environmental Health Perspectives 2011;119(7):921-926.	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text HTML Abstract: EHP-Abstract Other: EHP-Full Text PDF
Journal Article	Cass GR, Hughes LA, Bhave P, Kleeman MJ, Allen JO, Salmon LG. The chemical composition of atmospheric ultrafine particles. Philosophical Transactions of the Royal Society of London Series A-Mathematical Physical & Engineering Sciences 2000;358(1775):2581-2592.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (2004) R827354 (Final) R827354C001 (1999) R827354C001 (2000) R827354C001 (Final)	Abstract: Royal Society Publishing-Abstract Exit
Journal Article	Chalupa DC, Morrow PE, Oberdorster G, Utell MJ, Frampton MW. Ultrafine particle deposition in subjects with asthma. Environmental Health Perspectives 2004;112(8):879-882.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (2004) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Couderc JP, Elder ACP, Cox C, Zareba W, Oberdorster G. Limitations of power-spectrum and time-domain analysis of heart rate variability in short-term ECG recorded using telemetry in unrestrained rats. Computers in Cardiology 2002;29:589-592.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R828046 (Final)	Full-text: CINC-Full Text PDF Exit Abstract: IEEE-Abstract Exit
Journal Article	Cyrys J, Heinrich J, Peters A, Kreyling WG, Wichmann H-E. Emissionen, immission und messungen feiner und ultrafeiner partikel (Immission, emissions, and measurements of fine and ultrafine particles). Umweltmedizin in Forschung und Praxis 2002;7(2):67-77.	R832415 (2010) R832415 (Final) R832415C002 (2011)	Abstract: Research Gate-Abstract Exit
Journal Article	Cyrys J, Peters A, Soentgen J, Wichmann HE. Low emission zones reduce PM10 mass concentrations and diesel soot in German cities. Journal of the Air & Waste Management Association 2014;64(4):481-487.	R832415 (Final)	Abstract from PubMed Full-text: Taylor and Francis-Full Text HTML Exit Abstract: Taylor and Francis-Abstract Exit Other: Taylor and Francis-Full Text PDF Exit
Journal Article	Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdorster G, Utell MJ, Frampton MW. Ultrafine particle deposition in humans during rest and exercise. Inhalation Toxicology 2003;15(6):539-552.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826781 (2001) R826781 (Final) R827354 (2004) R827354 (Final) R827354C003 (1999) R827354C003 (2000) R827354C003 (2001) R827354C003 (2002) R827354C003 (2003) R827354C003 (2004) R827354C003 (Final) R827354C004 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Deffner V, Kuechenhoff H, Maier V, Pitz M, Cyrys J, Breitner S, Schneider A, Gu J, Geruschkat U, Peters A. Personal exposure to ultrafine particles: two-level statistical modeling of background exposure and time-activity patterns during three seasons. Journal of Exposure Science and Environmental Epidemiology 2016;26(1):17-25.	R832415 (Final)	Abstract from PubMed Abstract: Nature-Abstract Exit
Journal Article	Deffner V, Keuschenoff H, Breitner S, Schneider A, Cyrys J, Peters A. Mixtures of Berkson and classical covariate measurement error in the linear mixed model: Bias analysis and application to a study on ultrafine particles. BIOMETRICAL JOURNAL 2018;60(3):480-497	R832415 (Final)	Abstract from PubMed Abstract: Wiley- Abstract HTML Exit
Journal Article	Dillner AM, Schauer JJ, Christensen WF, Cass GR. A quantitative method for clustering size distributions of elements. Atmospheric Environment 2005;39(8):1525-1537.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (2004) R827354 (Final) R827354C001 (Final) R827355 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Elder ACP, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic interactions between inhaled ultrafine particles and endotoxin. Annals of Occupational Hygiene 2002;46(Suppl 1):231-234.	R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826784 (Final) R827354 (Final) R827354C003 (Final) R827354C004 (Final) R828046 (Final)	Full-text: Oxford Journals-Full Text PDF Exit Abstract: Oxford Journals-Abstract Exit
Journal Article	Elder ACP, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. Inhalation Toxicology 2004;16(6-7):461-471.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R832415C005 (2011) R826784 (Final) R827354 (Final) R827354C003 (Final) R827354C004 (2003) R827354C004 (Final) R827354C005 (Final) R828046 (Final)	Abstract from PubMed Abstract: Taylor&Francis-Abstract Exit
Journal Article	Elder ACP, Gelein R, Oberdorster G, Finkelstein J, Notter R, Wang Z. Efficient depletion of alveolar macrophages using intratracheally inhaled aerosols of liposome-encapsulated clodronate. Experimental Lung Research 2004;30(2):105-120.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R832415C005 (2011) R827354 (Final) R827354C003 (Final) R827354C004 (2003) R827354C004 (Final) R827354C005 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Elder A, Gelein R, Finkelstein J, Phipps R, Frampton M, Utell M, Kittelson DB, Watts WF, Hopke P, Jeong C-H, Kim E, Liu W, Zhao W, Zhuo L, Vincent R, Kumarathasan P, Oberdorster G. On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicology 2004;16(Suppl 1):41-53.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R832415C005 (2011) R827354 (Final) R827354C003 (Final) R827354C004 (2003) R827354C004 (Final) R827354C005 (Final) R828046 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdorster G. Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Experimental Lung Research 2005;31(6):527-546.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R832415C005 (2011) R827354 (Final) R827354C004 (Final) R827354C005 (Final) R828046 (Final)	Abstract from PubMed Abstract: Taylor&Francis-Abstract Exit
Journal Article	Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdorster G. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental Health Perspectives 2006;114(8):1172-1178.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R832415C005 (2011) R827354 (Final) R827354C004 (Final) R827354C005 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Elder A, Couderc J-P, Gelein R, Eberly S, Cox C, Xia X, Zareba W, Hopke P, Watts W, Kittelson D, Frampton M, Utell M, Oberdorster G. Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats. Inhalation Toxicology 2007;19(1):1-12.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2006) R832415C004 (2011) R827354 (Final) R827354C001 (Final) R827354C003 (Final) R827354C004 (Final) R828046 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit Other: University of Minnesota-Abstract Exit
Journal Article	Fanning EW, Froines JR, Utell MJ, Lippmann M, Oberdorster G, Frampton M, Godleski J, Larson TV. Particulate Matter (PM) Research Centers (1999-2005) and the role of interdisciplinary center-based research. Environmental Health Perspectives 2009;117(2):167-174.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R832415C005 (2011) R827351 (Final) R827352 (Final) R827353 (Final) R827354 (Final) R827355 (Final) R832416 (2009) R832416C003 (2009)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
Journal Article	Fensterer V, Kuchenhoff H, Maier V, Wichmann HE, Breitner S, Peters A, Gu JW, Cyrys J. Evaluation of the impact of low emission zone and heavy traffic ban in Munich (Germany) on the reduction of PM10 in ambient air. International Journal of Environmental Research and Public Health 2014;11(5):5094-5112.	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: MDPI-Full Text HTML & PDF Exit
Journal Article	Frampton MW. Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans. Environmental Health Perspectives 2001;109(Suppl 4):529-532.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R826781 (2001) R826781 (Final) R827354 (Final) R827354C003 (2001) R827354C003 (2002) R827354C003 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Frampton MW, Stewart JC, Oberdorster G, Morrow PE, Chalupa D, Pietropaoli AP, Frasier LM, Speers DM, Cox C, Huang L-S, Utell MJ. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environmental Health Perspectives 2006;114(1):51-58.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826781 (Final) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Frampton MW. Does inhalation of ultrafine particles cause pulmonary vascular effects in humans? Inhalation Toxicology 2007;19(Suppl 1):75-79.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R826781 (Final) R827354 (Final) R827354C003 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Frampton MW, Bausch J, Chalupa D, Hopke PK, Little EL, Oakes D, Stewart JC, Utell MJ. Effects of outdoor air pollutants on platelet activation in people with type 2 diabetes. Inhalation Toxicology 2012;24(12):831-838.	R832415 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Gu J, Pitz M, Breitner S, Birmili W, von Klot S, Schneider A, Soentgen J, Reller A, Peters A, Cyrys J. Selection of key ambient particulate variables for epidemiological studies--applying cluster and heatmap analyses as tools for data reduction. Science of the Total Environment 2012;435-436:541-550.	R832415 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Hampel R, Schneider A, Bruske I, Zareba W, Cyrys J, Ruckerl R, Breitner S, Korb H, Sunyer J, Wichmann HE, Peters A. Altered cardiac repolarization in association with air pollution and air temperature among myocardial infarction survivors. Environmental Health Perspectives 2010;118(12):1755-1761.	R832415 (Final) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
Journal Article	Hampel R, Breitner S, Ruckerl R, Frampton MW, Koenig W, Phipps RP, Wichmann HE, Peters A, Schneider A. Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season. Occupational & Environmental Medicine 2010;67(6):408-416.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C002 (2011) R832415C003 (2011)	Abstract from PubMed Abstract: BMJ Group-Abstract Exit
Journal Article	Hampel R, Breitner S, Schneider A, Zareba W, Kraus U, Cyrys J, Geruschkat U, Belcredi P, Muller M, Wichmann HE, Peters A, Cooperative Health Research in the Region of Augsburg (KORA) Study Group. Acute air pollution effects on heart rate variability are modified by SNPs involved in cardiac rhythm in individuals with diabetes or impaired glucose tolerance. Environmental Research 2012;112:177-185.	R832415 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Hampel R, Breitner S, Zareba W, Kraus U, Pitz M, Geruschkat U, Belcredi P, Peters A, Schneider A, Cooperative Health Research in the Region of Augsburg Study Group. Immediate ozone effects on heart rate and repolarisation parameters in potentially susceptible individuals. Occupational and Environmental Medicine 2012;69(6):428-436.	R832415 (Final)	Abstract from PubMed Abstract: BMJ-Abstract Exit
Journal Article	Hampel R, Ruckerl R, Yli-Tuomi T, Breitner S, Lanki T, Kraus U, Cyrys J, Belcredi P, Bruske I, Laitinen TM, Timonen K, Wichmann HE, Peters A, Schneider A. Impact of personally measured pollutants on cardiac function. International Journal of Hygiene and Environmental Health 2014;217(4-5):460-464.	R832415 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: EuropePMC-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, Finkelstein JN, Elder A, Oberdorster G. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology 2011;287(1-3):99-104.	R832415 (2011) R832415 (Final) R832415C004 (2011) R832415C005 (2011)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Han X, Corson N, Wade-Mercer P, Gelein R, Jiang J, Sahu M, Biswas P, Finkelstein JN, Elder A, Oberdorster G. Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data. Toxicology 2012;297(1-3):1-9.	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Science Direct-Full Text HTML Exit Abstract: Science Direct-Abstract Exit Other: Science Direct-Full Text PDF Exit
Journal Article	Henneberger A, Zareba W, Ibald-Mulli A, Ruckerl R, Cyrys J, Couderc J-P, Mykins B, Woelke G, Wichmann H-E, Peters A. Repolarization changes induced by air pollution in ischemic heart disease patients. Environmental Health Perspectives 2005;113(4):440-446.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (2003) R827354C002 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Hildebrandt K, Ruckerl R, Koenig W, Schneider A, Pitz M, Heinrich J, Marder V, Frampton M, Oberdorster G, Wichmann HE, Peters A. Short-term effects of air pollution: a panel study of blood markers in patients with chronic pulmonary disease. Particle and Fibre Toxicology 2009;6:25.	R832415 (2009) R832415 (2010) R832415 (2011) R832415 (Final) R832415C002 (2009) R832415C002 (2010) R832415C002 (2011) R832415C003 (2010) R832415C003 (2011) R832415C004 (2010) R832415C004 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BioMed Central-Full Text HTML Exit Abstract: BioMed Central-Abstract Exit Other: BioMed Central-Full Text PDF Exit
Journal Article	Hopke PK, Ito K, Mar T, Christiansen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Liu H, Neas L, Pinto J, Stolzel M, Suh H, Paatero P, Thurston GD. PM source apportionment and health effects:1. Intercomparison of source apportionment results. Journal of Exposure Science & Environmental Epidemiology 2006;16(3):275-286.	R832415 (2010) R832415 (2011) R832415 (Final) R827351 (Final) R827351C001 (Final) R827353 (Final) R827353C017 (Final) R827354 (Final) R827354C001 (Final) R827355 (Final) R827355C008 (Final)	Abstract from PubMed Full-text: Nature-Full Text HTML Exit Abstract: Nature-Abstract Exit Other: Nature-Full Text PDF Exit
Journal Article	Ibald-Mulli A, Wichmann HE, Kreyling W, Peters A. Epidemiological evidence on health effects of ultrafine particles. Journal of Aerosol Medicine 2002;15(2):189-201.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (2001) R827354C002 (2003) R827354C002 (Final)	Abstract from PubMed Abstract: Mary Ann Liebert, Inc Publishers - Abstract Exit
Journal Article	Ito K, Christensen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Neas L, Hopke PK, Thurston GD. PM source apportionment and health effects: 2. An investigation of intermethod variability in associations between source-apportioned fine particle mass and daily mortality in Washington, DC. Journal of Exposure Science & Environmental Epidemiology 2006;16(4):300-310.	R832415 (2010) R832415 (2011) R832415 (Final) R827351 (Final) R827351C001 (Final) R827353C015 (Final) R827354 (Final) R827354C001 (Final) R827355 (Final) R827355C008 (Final) R827997 (Final)	Abstract from PubMed Full-text: JESEE-Full Text HTML Exit Other: JESEE-Full Text PDF Exit
Journal Article	Jeong C-H, Hopke PK, Chalupa D, Utell M. Characteristics of nucleation and growth events of ultrafine particles measured in Rochester, NY. Environmental Science & Technology 2004;38(7):1933-1940.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R827354 (Final) R827354C001 (2003) R827354C001 (Final) R827354C003 (Final)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Jeong C-H, Lee D-W, Kim E, Hopke PK. Measurement of real-time PM2.5 mass, sulfate, and carbonaceous aerosols at the multiple monitoring sites. Atmospheric Environment 2004;38(31):5247-5256.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (2003) R827354C001 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Jeong C-H, Hopke PK, Kim E, Lee D-W. The comparison between thermal-optical transmittance elemental carbon and Aethalometer black carbon measured at multiple monitoring sites. Atmospheric Environment 2004;38(31):5193-5204.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (2003) R827354C001 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Jeong C-H, Evans GJ, Hopke PK, Chalupa D, Utell MJ. Influence of atmospheric dispersion and new particle formation events on ambient particle number concentration in Rochester, United States, and Toronto, Canada. Journal of the Air & Waste Management Association 2006;56(4):431-443.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R827354 (Final) R827354C001 (Final) R827354C003 (Final)	Abstract from PubMed Full-text: Taylor & Francis Online - Full Text PDF Exit Abstract: Taylor & Francis Online - Abstract Exit
Journal Article	Kim E, Larson TV, Hopke PK, Slaughter C, Sheppard LE, Claiborn C. Source identification of PM2.5 in an arid Northwest U.S. city by positive matrix factorization. Atmospheric Research 2003;66(4):291-305.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final) R827355 (2004) R827355 (Final) R827355C008 (2002) R827355C008 (Final) R827355C009 (2003) R828678C010 (2003) R828678C010 (2004) R828678C010 (2005) R828678C010 (2006) R828678C010 (2007) R828678C010 (Final)	Full-text: ScienceDirect-Full Text PDF Exit Abstract: ScienceDirect-Abstract and Full Text HTML Exit Other: ResearchGate - Abstract & Full Text PDF Exit
Journal Article	Kim E, Hopke PK, Larson TV, Maykut NN, Lewtas J. Factor analysis of Seattle fine particles. Aerosol Science and Technology 2004;38(7):724-738.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final) R827355 (2004) R827355 (Final) R827355C004 (2003) R827355C008 (2003) R827355C008 (Final)	Full-text: Taylor&Francis-Full Text HTML Exit Abstract: Taylor&Francis-Abstract Exit Other: Tayor&Francis-Full Text PDF Exit
Journal Article	Kim E, Hopke PK, Larson TV, Covert DS. Analysis of ambient particle size distributions using Unmix and positive matrix factorization. Environmental Science & Technology 2004;38(1):202-209.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final) R827354C002 (2004) R827355 (2004) R827355 (Final) R827355C004 (2003) R827355C008 (2002) R827355C008 (2003) R827355C008 (Final)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Kittelson DB, Watts WF, Johnson JP, Remerowki ML, Ische EE, Oberdorster G, Gelein RM, Elder A, Hopke PK, Kim E, Zhao W, Zhou L, Jeong C-H. On-road exposure to highway aerosols. 1. Aerosol and gas measurements. Inhalation Toxicology 2004;16(Suppl 1):31-39.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C001 (Final) R827354C004 (2003) R827354C004 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Kraus U, Breitner S, Schnelle-Kreis J, Cyrys J, Lanki T, Ruckerl R, Schneider A, Bruske I, Gu J, Devlin R, Wichmann H-E, Zimmermann R, Peters A. Particle-associated organic compounds and symptoms in myocardial infarction survivors. Inhalation Toxicology 2011;23(7):431-447.	R832415 (Final) R832415C002 (2011)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdorster G, Ziesenis A. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. Journal of Toxicology and Environmental Health-Part A 2002;65(20):1513-1530.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C004 (2001) R827354C004 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Lagudu UR, Raja S, Hopke PK, Chalupa DC, Utell MJ, Casuccio G, Lersch TL, West RR. Heterogeneity of coarse particles in an urban area. Environmental Science & Technology 2011;45(8):3288-3296.	R832415 (2011) R832415 (Final) R832415C001 (2011) R832415C003 (2011)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Lanzinger S, Hampel R, Breitner S, Ruckerl R, Kraus U, Cyrys J, Geruschkat U, Peters A, Schneider A. Short-term effects of air temperature on blood pressure and pulse pressure in potentially susceptible individuals. International Journal of Hygiene and Environmental Health 2014;217(7):775-784.	R832415 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Lippmann M, Frampton M, Schwartz J, Dockery D, Schlesinger R, Koutrakis P, Froines J, Nel A, Finkelstein J, Godleski J, Kaufman J, Koenig J, Larson T, Luchtel D, Liu L-JS, Oberdorster G, Peters A, Sarnat J, Sioutas C, Suh H, Sullivan J, Utell M, Wichmann E, Zelikoff J. The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. Environmental Health Perspectives 2003;111(8):1074-1092.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827351 (2002) R827351 (Final) R827352 (Final) R827352C002 (Final) R827352C014 (Final) R827353 (Final) R827353C006 (Final) R827353C015 (Final) R827354 (Final) R827355 (Final)	Full-text from PubMed Abstract from PubMed Abstract: EBSCO Host-Abstract Exit
Journal Article	Ljungman P, Bellander T, Nyberg F, Lampa E, Jacquemin B, Kolz M, Lanki T, Mitropoulos J, Muller M, Picciotto S, Pistelli R, Ruckerl R, Koenig W, Peters A, AIRGENE Study Group. DNA variants, plasma levels and variability of Interleukin-6 in myocardial infarction survivors: results from the AIRGENE study. Thrombosis Research 2009;124(1):57-64.	R832415 (2010) R832415 (Final) R832415C002 (2010) R832415C002 (2011)	Abstract from PubMed Abstract: ScienceDirect-Abstract Exit
Journal Article	Mar TF, Ito K, Koenig JQ, Larson TV, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Neas L, Stolzel M, Paatero P, Hopke PK, Thurston GD. PM source apportionment and health effects. 3. Investigation of inter-method variations in associations between estimated source contributions of PM2.5 and daily mortality in Phoenix, AZ. Journal of Exposure Science & Environmental Epidemiology 2006;16(4):311-320.	R832415 (2010) R832415 (2011) R832415 (Final) R827351 (Final) R827353 (Final) R827353C015 (Final) R827354 (Final) R827354C001 (Final) R827355 (Final) R827355C002 (Final) R827355C008 (Final)	Abstract from PubMed Full-text: JESEE-Full Text HTML Exit Abstract: JESEE-Abstract Exit Other: JESEE-Full Text PDF Exit
Journal Article	Moffet RC, Shields LG, Berntsen J, Devlin RB, Prather KA. Characterization of an ambient coarse particle concentrator used for human exposure studies: aerosol size distributions, chemical composition, and concentration enrichment. Aerosol Science and Technology 2004;38(11):1123-1137.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (2003) R827354C001 (Final)	Full-text: IngentaConnect-Full Text PDF Exit Abstract: IngentaConnect-Abstract Exit
Journal Article	Oberdorster G. Pulmonary effects of inhaled ultrafine particles. International Archives of Occupational and Environmental Health 2001;74(1):1-8.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R826784 (Final) R827354 (Final) R827354C004 (2000) R827354C004 (2001) R827354C004 (Final)	Abstract from PubMed Full-text: Precaution.org-Full Text PDF Exit Abstract: SpringerLink-Abstract Exit
Journal Article	Oberdorster G, Utell MJ. Ultrafine particles in the urban air:to the respiratory tract—and beyond? Environmental Health Perspectives 2002;110(8):A440-A441.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826784 (Final) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed
Journal Article	Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. Journal of Toxicology and Environmental Health, Part A: Current Issues 2002;65(20):1531-1543.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R826784 (Final) R827354 (Final) R827354C004 (2001) R827354C004 (Final)	Abstract from PubMed Full-text: UMN-Full Text PDF Exit Abstract: Taylor & Francis-Abstract Exit
Journal Article	Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology 2004;16(6-7):437-445.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C004 (2003) R827354C004 (Final)	Abstract from PubMed Full-text: SemanticsScholar-Full Text PDF Exit Abstract: Taylor and Francis-Abstract Exit
Journal Article	Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology:an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 2005;113(7):823-839.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Oberdorster G, Stone V, Donaldson K. Toxicology of nanoparticles: a historical perspective. Nanotoxicology 2007;1(1):2-25.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2006) R832415C004 (2007) R832415C004 (2010) R832415C004 (2011)	Full-text: ResearchGate-Full Text PDF Exit Abstract: Taylor and Francis-Abstract Exit
Journal Article	Oberdorster G, Elder A, Rinderknecht A. Nanoparticles and the brain: cause for concern? Journal of Nanoscience and Nanotechnology 2009;9(8):4996-5007.	R832415 (2009) R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2009) R832415C004 (2010) R832415C004 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: ResearchGate-Abstract Exit
Journal Article	Oberdorster G. Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. Journal of Internal Medicine 2010;267(1):89-105.	R832415 (2009) R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2009) R832415C004 (2010) R832415C004 (2011)	Abstract from PubMed Full-text: Wiley Online-Full Text HTML Exit Abstract: Wiley Online-Abstract Exit Other: Wiley Online-Full Text PDF Exit
Journal Article	Ogulei D, Hopke PK, Chalupa DC, Utell MJ. Modeling source contributions to submicron particle number concentrations measured in Rochester, New York. Aerosol Science and Technology 2007;41(2):179-201.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2011) R832415C003 (2011) R827354 (Final) R827354C001 (Final) R827354C003 (Final) R831078 (Final)	Full-text: Taylor&Francis-Full Text HTML Exit Abstract: Taylor&Francis-Abstract Exit Other: Taylor&Francis-Full Text PDF Exit
Journal Article	Pavlovic J, Hopke PK. Technical note: detection and identification of radical species formed from α-pinene/ozone reaction using DMPO spin trap. Atmospheric Chemistry and Physics Discussions 2009;9(6):23695-23717.	R832415 (2009) R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2009) R832415C001 (2010) R832415C001 (2011)	Full-text: ACP-Full Text PDF Exit Abstract: ACP-Abstract Exit
Journal Article	Pavlovic J, Hopke PK. Detection of radical species formed by the ozonolysis of α-pinene. Journal of Atmospheric Chemistry 2010;66(3):137-155.	R832415 (2011) R832415 (Final) R832415C001 (2011)	Abstract: SpringerLink-Abstract Exit
Journal Article	Pavlovic J, Hopke PK. Chemical nature and molecular weight distribution of the water-soluble fine and ultrafine PM fractions collected in a rural environment. Atmospheric Environment 2012;59:264-271.	R832415 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Pekkanen J, Peters A, Hoek G, Tiittanen P, Brunekreef B, de Hartog J, Heinrich J, Ibald-Mulli A, Kreyling WG, Lanki T, Timonen KL, Vanninen E. Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease:the Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) study. Circulation 2002;106(8):933-938.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (2001) R827354C002 (2002) R827354C002 (2003) R827354C002 (Final)	Abstract from PubMed Full-text: Circulation - Full Text HTML Exit Abstract: Circulation - Abstract Exit Other: Circulation - Full Text PDF Exit
Journal Article	Peters A, Heinrich J, Wichmann H-E. Gesundheitliche Wirkungen von Feinstaub: Epidemiologie der Kurzzeiteffekte (Health impact of exposure to fine particles: epidemiology of short-term effects). Umweltmedizin in Forschung und Praxis 2002;7(2):101-115.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (2001) R827354C002 (2002) R827354C002 (2003) R827354C002 (Final)	Full-text: Schwerpunktthema Feinstäube - Full Text (English and German) Exit Abstract: Ecomed - Abstract (English and German) Exit
Journal Article	Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, Wichmann HE, Lowel H, Cooperative Health Research in the Region of Augsburg Study Group. Exposure to traffic and the onset of myocardial infarction. New England Journal of Medicine 2004;351(17):1721-1730.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (Final)	Abstract from PubMed Full-text: NEJM - Full Text HTML Exit Abstract: NEJM - Abstract Exit Other: NEJM - Full Text PDF Exit
Journal Article	Peters A. Particulate matter and heart disease:evidence from epidemiological studies. Toxicology and Applied Pharmacology 2005;207(2-Suppl):477-482.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (Final)	Abstract from PubMed Full-text: ScienceDirect - Full Text HTML Exit Abstract: ScienceDirect - Abstract Exit Other: ScienceDirect - Full Text PDF Exit
Journal Article	Peters A, Greven S, Heid IM, Baldari F, Breitner S, Bellander T, Chrysohoou C, Illig T, Jacquemin B, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Ruckerl R, Stefanadis C, Schneider A, Sunyer J, Wichmann HE, AIRGENE Study Group. Fibrinogen genes modify the fibrinogen response to ambient particulate matter. American Journal of Respiratory and Critical Care Medicine 2009;179(6):484-491.	R832415 (2009) R832415 (2010) R832415 (Final) R832415C002 (2009) R832415C002 (2010) R832415C002 (2011)	Abstract from PubMed Full-text: AJRCCM-Full Text HTML Exit Abstract: AJRCCM-Abstract Exit Other: AJRCCM-Full Text PDF Exit
Journal Article	Peters A. Air quality and cardiovascular health:smoke and pollution matter. Circulation 2009;120(11):924-927.	R832415 (2010) R832415 (Final) R832415C002 (2010) R832415C002 (2011)	Abstract from PubMed Full-text: Circulation-Full Text HTML Exit Abstract: Circulation-Abstract Exit Other: Circulation-Full Text PDF Exit
Journal Article	Peters A, Hampel R, Cyrys J, Breitner S, Geruschkat U, Kraus U, Zareba W, Schneider A. Elevated particle number concentrations induce immediate changes in heart rate variability: a panel study in individuals with impaired glucose metabolism or diabetes. Particle and Fibre Toxicology 2015;12:7 (11 pp.).	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BMC-Full Text HTML Exit Other: BMC-Full Text PDF Exit
Journal Article	Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberdorster G, Cox C, Speers DM, Frasier LM, Chalupa DC, Huang L-S, Utell MJ. Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhalation Toxicology 2004;16(Suppl 1):59-72.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826781 (Final) R827354 (Final) R827354C003 (2003) R827354C003 (Final) R827354C004 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit Other: Utah State University-Prepublication Full Text PDF Exit
Journal Article	Pitz M, Birmili W, Schmid O, Peters A, Wichmann HE, Cyrys J. Quality control and quality assurance for particle size distribution measurements at an urban monitoring station in Augsburg, Germany. Journal of Environmental Monitoring 2008;10(9):1017-1024.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (Final) R832415C002 (2006) R832415C002 (2008) R832415C002 (2010) R832415C002 (2011)	Abstract from PubMed Abstract: RSC Publishing-Abstract Exit
Journal Article	Pui DYH, Qi C, Stanley N, Oberdorster G, Maynard A. Recirculating air filtration significantly reduces exposure to airborne nanoparticles. Environmental Health Perspectives 2008;116(7):863-866.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2006) R832415C004 (2010) R832415C004 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Reemtsma T, These A, Venkatachari P, Xia X, Hopke PK, Springer A, Linscheid M. Identification of fulvic acids and sulfated and nitrated analogues in atmospheric aerosol by electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. Analytical Chemistry 2006;78(24):8299-8304.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Rich DQ, Zareba W, Beckett W, Hopke PK, Oakes D, Frampton MW, Bisognano J, Chalupa D, Bausch J, O’Shea K, Wang Y, Utell MJ. Are ambient ultrafine, accumulation mode, and fine particles associated with adverse cardiac responses in patients undergoing cardiac rehabilitation? Environmental Health Perspectives 2012;120(8):1162-1169.	R832415 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Riesenfeld E, Chalupa D, Gibb FR, Oberdo G, Gelein R, Morrow PE, Utell MJ, Frampton MW. Ultrafine particle concentrations in a hospital. Inhalation Toxicology 2000;12(Suppl 2):83-94.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R826781 (2000) R826781 (2001) R826781 (Final) R827354 (Final) R827354C003 (2000) R827354C003 (2001) R827354C003 (2002) R827354C003 (Final) R827354C004 (2000) R827354C004 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. American Journal of Respiratory and Critical Care Medicine 2006;173(4):432-441.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R827354 (Final) R827354C002 (2003) R827354C002 (Final) R827354C003 (Final) R827354C004 (Final)	Abstract from PubMed Full-text: ATS Journals - Full Text HTML Exit Abstract: ATS Journals - Abstract Exit Other: ATS Journals - Full Text PDF Exit
Journal Article	Ruckerl R, Phipps RP, Schneider A, Frampton M, Cyrys J, Oberdorster G, Wichmann HE, Peters A. Ultrafine particles and platelet activation in patients with coronary heart disease – results from a prospective panel study. Particle and Fibre Toxicology 2007;4:1.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C002 (2011) R832415C003 (2011) R832415C004 (2011) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BioMed Central-Full Text HTML Exit Abstract: BioMed Central-Abstract Exit Other: BioMed Central-Full Text PDF Exit
Journal Article	Ruckerl R, Hampel R, Breitner S, Cyrys J, Kraus U, Carter J, Dailey L, Devlin RB, Diaz-Sanchez D, Koenig W, Phipps R, Silbajoris R, Soentgen J, Soukup J, Peters A, Schneider A. Associations between ambient air pollution and blood markers of inflammation and coagulation/fibrinolysis in susceptible populations. Environment International 2014;70:32-49.	R832415 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Ruckerl R, Schneider A, Hampel R, Breitner S, Cyrys J, Kraus U, Gu J, Soentgen J, Koenig W, Peters A. Association of novel metrics of particulate matter with vascular markers of inflammation and coagulation in susceptible populations--results from a panel study. Environmental Research 2016;150:337-347.	R832415 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, Han X, Gelein R, Finkelstein J, Oberdorster G. Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. Journal of Toxicology and Environmental Health, Part A 2010;73(5-6):445-461.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2010) R832415C004 (2011) R832415C005 (2010) R832415C005 (2011)	Abstract from PubMed Abstract: Taylor & Francis-Abstract Exit
Journal Article	Schauble CL, Hampel R, Breitner S, Ruckerl R, Phipps R, Diaz-Sanchez D, Devlin RB, Carter JD, Soukup J, Silbajoris R, Dailey L, Koenig W, Cyrys J, Geruschkat U, Belcredi P, Kraus U, Peters A, Schneider AE. Short-term effects of air temperature on blood markers of coagulation and inflammation in potentially susceptible individuals. Occupational and Environmental Medicine 2012;69(9):670-678.	R832415 (Final)	Abstract from PubMed Full-text: University of Muenchen-Full Text PDF Exit Abstract: BMJ-Abstract Exit
Journal Article	Schneider A, Neas L, Herbst MC, Case M, Williams RW, Cascio W, Hinderliter A, Holguin F, Buse JB, Dungan K, Styner M, Peters A, Devlin RB. Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Environmental Health Perspectives 2008;116(12):1666-1674.	R832415 (2008) R832415 (2010) R832415 (Final) R832415C002 (2010) R832415C002 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
Journal Article	Schneider A, Neas LM, Graff DW, Herbst MC, Cascio WE, Schmitt MT, Buse JB, Peters A, Devlin RB. Association of cardiac and vascular changes with ambient PM2.5 in diabetic individuals. Particle and Fibre Toxicology 2010;7:14.	R832415 (2010) R832415 (Final) R832415C002 (2010) R832415C002 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BioMed Central-Full Text HTML Exit Abstract: BioMed Central-Abstract Exit Other: Partcle and Fibre Toxicology-Full Text PDF Exit
Journal Article	Schneider A, Hampel R, Ibald-Mulli A, Zareba W, Schmidt G, Schneider R, Ruckerl R, Couderc JP, Mykins B, Oberdorster G, Wolke G, Pitz M, Wichmann H-E, Peters A. Changes in deceleration capacity of heart rate and heart rate variability induced by ambient air pollution in individuals with coronary artery disease. Particle and Fibre Toxicology 2010;7:29 (12 pp.).	R832415 (2011) R832415 (Final) R832415C002 (2011) R832415C004 (2011) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BioMed Central-Full Text HTML Exit Abstract: BioMed Central-Abstract Exit Other: BioMed Central-Full Text PDF Exit
Journal Article	Schneider A, Alexis NE, Diaz-Sanchez D, Neas LM, Harder S, Herbst MC, Cascio WE, Buse JB, Peters A, Devlin RB. Ambient PM2.5 exposure up-regulates the expression of costimulatory receptors on circulating monocytes in diabetic individuals. Environmental Health Perspectives 2011;119(6):778-783.	R832415 (Final) R832415C002 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
Journal Article	Semmler-Behnke M, Takenaka S, Fertsch S, Wenk A, Seitz J, Mayer P, Oberdorster G, Kreyling WG. Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium. Environmental Health Perspectives 2007;115(5):728-733.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2006) R832415C004 (2007) R832415C004 (2010) R832415C004 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Shah AP, Pietropaoli AP, Frasier LM, Speers DM, Chalupa DC, Delehanty JM, Huang L-S, Utell MJ, Frampton MW. Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects. Environmental Health Perspectives 2008;116(3):375-380.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2006) R832415C003 (2010) R832415C003 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Silva VM, Corson N, Elder A, Oberdorster G. The rat ear vein model for investigating in vivo thrombogenicity of ultrafine particles (UFP). Toxicological Sciences 2005;85(2):983-989.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C004 (2003) R827354C004 (Final)	Abstract from PubMed Full-text: Oxford Journals-Full Text HTML Exit Abstract: Oxford Journals-Abstract Exit Other: Oxford Journals-Full Text PDF Exit
Journal Article	Singal M, Finkelstein JN. Use of indicator cell lines for determining inflammatory gene changes and screening the inflammatory potential of particulate and non-particulate stimuli. Inhalation Toxicology 2005;17(9):415-425.	R832415 (2010) R832415 (Final) R832415C005 (2011) R827354 (Final) R827354C005 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Singal M, Finkelstein JN. Amorphous silica particles promote inflammatory gene expression through the redox sensitive transcription factor, AP-1, in alveolar epithelial cells. Experimental Lung Research 2005;31(6):581-597.	R832415 (2010) R832415 (Final) R832415C005 (2011) R827354 (Final) R827354C005 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Spencer MT, Prather KA. Using ATOFMS to determine OC/EC mass fractions in particles. Aerosol Science and Technology 2006;40(8):585-594.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final) R831083 (Final)	Full-text: Taylor & Francis-Full Text HTML Exit Abstract: Taylor & Francis-Abstract Exit Other: Taylor & Francis-Full Text PDF Exit
Journal Article	Spencer MT, Shields LG, Sodeman DA, Toner SM, Prather KA. Comparison of oil and fuel particle chemical signatures with particle emissions from heavy and light duty vehicles. Atmospheric Environment 2006;40(27):5224-5235.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Spencer MT, Shields LG, Prather KA. Simultaneous measurement of the effective density and chemical composition of ambient aerosol particles. Environmental Science & Technology 2007;41(4):1303-1309.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2006) R832415C001 (2010) R832415C001 (2011) R827354 (Final) R831083 (Final)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Stewart JC, Villasmil ML, Frampton MW. Changes in fluorescence intensity of selected leukocyte surface markers following fixation. Cytometry Part A 2007;71A(6):379-385.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2006) R832415C003 (2010) R832415C003 (2011)	Abstract from PubMed Full-text: Wiley Online-Full Text HTML Exit Abstract: Wiley Online-Abstract Exit Other: Wiley Online-Full Text PDF Exit
Journal Article	Stewart JC, Chalupa DC, Devlin RB, Frasier LM, Huang LS, Little EL, Lee SM, Phipps RP, Pietropaoli AP, Taubman MB, Utell MJ, Frampton MW. Vascular effects of ultrafine particles in persons with type 2 diabetes. Environmental Health Perspectives 2010;118(12):1692-1698.	R832415 (2011) R832415 (Final) R832415C003 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Stolzel M, Breitner S, Cyrys J, Pitz M, Wolke G, Kreyling W, Heinrich J, Wichmann H-E, Peters A. Daily mortality and particulate matter in different size classes in Erfurt, Germany. Journal of Exposure Science & Environmental Epidemiology 2007;17(5):458-467.	R832415 (2010) R832415 (Final) R832415C002 (2011) R827354 (Final) R827354C002 (Final)	Abstract from PubMed Full-text: Nature Publishing - Full Text HTML Exit Abstract: Nature Publishing - Abstract Exit Other: Nature Publishing - Full Text PDF Exit
Journal Article	Su Y, Sipin MF, Furutani H, Prather KA. Development and characterization of an aerosol time-of-flight mass spectrometer with increased detection efficiency. Analytical Chemistry 2004;76(3):712-719.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (2003) R827354C001 (Final)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Su Y, Sipin MF, Prather KA, Gelein RM, Lunts A, Oberdorster G. ATOFMS characterization of individual model aerosol particles used for exposure studies. Aerosol Science and Technology 2005;39(5):400-407.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final) R827354C001 (2003) R827354C001 (Final) R827354C004 (Final)	Full-text: Taylor & Francis-Full Text PDF Exit Abstract: Taylor & Francis-Abstract Exit
Journal Article	Su Y, Sipin MF, Spencer MT, Qin X, Moffet RC, Shields LG, Prather KA, Venkatachari P, Jeong C-H, Kim E, Hopke PK, Gelein RM, Utell MJ, Oberdorster G, Berntsen J, Devlin RB, Chen LC. Real-time characterization of the composition of individual particles emitted from ultrafine particle concentrators. Aerosol Science and Technology 2006;40(6):437-455.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (Final) R827354C001 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text: Taylor & Francis - Full Text HTML Exit Abstract: Taylor & Francis - Abstract Exit Other: Taylor & Francis - Full Text PDF Exit
Journal Article	Thurston GD, Ito K, Mar T, Christensen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Liu H, Neas L, Pinto J, Stolzel M, Suh H, Hopke PK. Workgroup report: Workshop on source apportionment of particulate matter health effects—intercomparison of results and implications. Environmental Health Perspectives 2005;113(12):1768-1774.	R832415 (2010) R832415 (2011) R832415 (Final) R827351 (Final) R827351C001 (Final) R827353 (Final) R827353C015 (Final) R827354 (Final) R827354C001 (Final) R827355 (Final) R827355C008 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ResearchGate - Abstract & Full Text Exit
Journal Article	Thurston GD, Bekkedal MY, Roberts EM, Ito K, Pope III CA, Glenn BS, Ozkaynak H, Utell MJ. Use of health information in air pollution health research:past successes and emerging needs. Journal of Exposure Science and Environmental Epidemiology 2009;19(1):45-58.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2010) R832415C003 (2011)	Abstract from PubMed Full-text: Nature Publishing-Full Text PDF Exit Abstract: Nature Publishing-Abstract Exit
Journal Article	Toner SM, Shields LG, Sodeman DA, Prather KA. Using mass spectral source signatures to apportion exhaust particles from gasoline and diesel powered vehicles in a freeway study using UF-ATOFMS. Atmospheric Environment 2008;42(3):568-581.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2011) R827354 (Final) R827354C001 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Utell MJ, Frampton MW. Toxicologic methods: controlled human exposures. Environmental Health Perspectives 2000;108(Suppl 4):605-613.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R826781 (Final) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Utell MJ, Frampton MW. Acute health effects of ambient air pollution: the ultrafine particle hypothesis. Journal of Aerosol Medicine 2000;13(4):355-359.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R827354 (Final)	Abstract from PubMed Abstract: MaryAnnLiebert-Abstract Exit
Journal Article	Utell MJ, Frampton MW, Zareba W, Devlin RB, Cascio WE. Cardiovascular effects associated with air pollution:potential mechanisms and methods of testing. Inhalation Toxicology 2002;14(12):1231-1247.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R826781 (2001) R826781 (Final) R827354 (Final) R827354C003 (2001) R827354C003 (2002) R827354C003 (Final)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
Journal Article	Venkatachari P, Hopke PK, Grover BD, Eatough DJ. Measurement of particle-bound reactive oxygen species in rubidoux aerosols. Journal of Atmospheric Chemistry 2005;50(1):49-58.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (2003) R827354C001 (Final)	Abstract: SpringerLink-Abstract Exit Other: Environmental Expert-Full Text PDF Exit
Journal Article	Venkatachari P, Zhou L, Hopke PK, Felton D, Rattigan OV, Schwab JJ, Demerjian KL. Spatial and temporal variability of black carbon in New York City. Journal of Geophysical Research 2006;111(D10):D10S05 (9 pp.).	R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final)	Full-text: Wiley Online-Full Text Exit Abstract: Wiley Online-Abstract Exit Other: Wiley Online-Full Text PDF Exit
Journal Article	Venkatachari P, Zhou L, Hopke PK, Schwab JJ, Demerjian KL, Weimer S, Hogrefe O, Felton D, Rattigan O. An intercomparison of measurement methods for carbonaceous aerosol in the ambient air in New York City. Aerosol Science and Technology 2006;40(10):788-795.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final)	Full-text: Taylor & Francis-Full Text HTML Exit Abstract: Taylor & Francis-Abstract Exit Other: Taylor & Francis-Full Text PDF Exit
Journal Article	Venkatachari P, Hopke PK, Brune WH, Ren X, Lesher R, Mao J, Mitchell M. Characterization of wintertime reactive oxygen species concentrations in Flushing, New York. Aerosol Science and Technology 2007;41(2):97-111.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2011) R827354 (Final)	Full-text: Taylor & Francis-Full Text HTML Exit Abstract: Taylor & Francis-Abstract Exit Other: Taylor & Francis-Full Text PDF Exit
Journal Article	Venkatachari P, Hopke PK. Development and laboratory testing of an automated monitor for the measurement of atmospheric particle-bound reactive oxygen species (ROS). Aerosol Science and Technology 2008;42(8):629-635.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2008) R832415C001 (2010) R832415C001 (2011)	Full-text: Taylor & Francis-Full Text HTML Exit Abstract: Taylor & Francis-Abstract Exit Other: Taylor & Francis-Full Text PDF Exit
Journal Article	Venkatachari P, Hopke PK. Characterization of products formed in the reaction of ozone with α-pinene: case for organic peroxides. Journal of Environmental Monitoring 2008;10(8):966-974.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2011) R827354 (Final)	Abstract from PubMed Abstract: RSC-Abstract Exit
Journal Article	Venkatachari P, Hopke PK. Development and evaluation of a particle-bound reactive oxygen species generator. Journal of Aerosol Science 2008;39(2):168-174.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2011) R827354 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Veranth JM, Gelein R, Oberdorster G. Vaporization – condensation generation of ultrafine hydrocarbon particulate matter for inhalation toxicology studies. Aerosol Science and Technology 2003;37(7):603-609.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C004 (2011) R827354 (Final)	Full-text: Taylor & Francis-Full Text PDF Exit Abstract: Taylor & Francis-Abstract Exit
Journal Article	von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D'Ippoliti D, Elosua R, Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer J, Forastiere F. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation 2005;112(20):3073-3079.	R832415 (2010) R832415 (Final) R827354 (Final) R827354C002 (Final)	Abstract from PubMed Full-text: Circulation - Full Text HTML Exit Abstract: Circulation - Abstract Exit Other: Circulation - Full Text PDF Exit
Journal Article	von Klot S, Cyrys J, Hoek G, Kuhnel B, Pitz M, Kuhn U, Kuch B, Meisinger C, Hormann A, Wichmann HE, Peters A. Estimated personal soot exposure is associated with acute myocardial infarction onset in a case-crossover study. Progress in Cardiovascular Diseases 2011;53(5):361-368.	R832415 (Final)	Abstract from PubMed Full-text: PCD-Full Text PDF Exit Abstract: PCD-Full Text HTML Exit
Journal Article	Wang Y, Hopke PK, Chalupa DC, Utell MJ. Long-term study of urban ultrafine particles and other pollutants. Atmospheric Environment 2011;45(40):7672-7680.	R832415 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Wang Y, Hopke PK, Sun L, Chalupa DC, Utell MJ. Laboratory and field testing of an automated atmospheric particle-bound reactive oxygen species sampling-analysis system. Journal of Toxicology 2011;2011:419476 (9 pp).	R832415 (2011) R832415 (Final) R832415C003 (2011) R831078 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Hindawi-Full Text HTML and PDF Exit
Journal Article	Wang Y, Hopke PK, Chalupa DC, Utell MJ. Effect of the shutdown of a coal-fired power plant on urban ultrafine particles and other pollutants. Aerosol Science and Techology 2011;45(10):1245-1249.	R832415 (2011) R832415 (Final) R832415C001 (2011) R832415C003 (2011)	Full-text: Taylor & Francis-Full Text HTML Exit Abstract: Taylor & Francis-Abstract Exit Other: Taylor & Francis-Full Text PDF Exit
Journal Article	Wang Y, Hopke PK, Utell MJ. Urban-scale spatial-temporal variability of black carbon and winter residential wood combustion particles. Aerosol and Air Quality Research 2011;11(5):473-481.	R832415 (2011) R832415 (Final) R832415C003 (2011) R831078 (Final)	Full-text: AAQR-Full Text PDF Exit Abstract: AAQR-Abstract Exit
Journal Article	Wang Y, Hopke PK, Rattigan OV, Xia X, Chalupa DC, Utell MJ. Characterization of residential wood combustion particles using the two-wavelength aethalometer. Environmental Science & Technology 2011;45(17):7387-7393.	R832415 (2011) R832415 (Final) R832415C001 (2011) R832415C003 (2011)	Abstract from PubMed Full-text: ACS-Full Text HTML Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Wang Y, Hopke PK, Rattigan OV, Chalupa DC, Utell MJ. Multiple-year black carbon measurements and source apportionment using Delta-C in Rochester, New York. Journal of the Air & Waste Management Association 2012;62(8):880-887.	R832415 (Final)	Abstract from PubMed Full-text: ResearchGate-Full Text Exit Abstract: Taylor & Francis-Abstract Exit
Journal Article	Wang Y, Hopke PK, Xia X, Rattigan OV, Chalupa DC, Utell MJ. Source apportionment of airborne particulate matter using inorganic and organic species as tracers. Atmospheric Environment 2012;55:525-532.	R832415 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Wang Y, Hopke PK, Rattigan OV. A new indicator of fireworks emissions in Rochester, New York. Environmental Monitoring and Assessment 2012;184(12):7293-7297.	R832415 (Final)	Abstract from PubMed Abstract: SpringerLink-Abstract Exit
Journal Article	Yue W, Schneider A, Stolzel M, Ruckerl R, Cyrys J, Pan X, Zareba W, Koenig W, Wichmann H-E, Peters A. Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2007;621(1-2):50-60.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Yue W, Schneider A, Ruckerl R, Koenig W, Marder V, Wang S, Wichmann H-E, Peters A, Zareba W. Relationship between electrocardiographic and biochemical variables in coronary artery disease. International Journal of Cardiology 2007;119(2):185-191.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (Final)	Abstract from PubMed Abstract: Elsevier-Abstract Exit
Journal Article	Yue W, Stolzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann H-E, Peters A, Wang S, Hopke PK. Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany. Science of the Total Environment 2008;398(1-3):133-144.	R832415 (2007) R832415 (2008) R832415 (2010) R832415 (2011) R832415 (Final) R832415C001 (2008) R832415C001 (2010) R832415C001 (2011) R832415C002 (2006) R832415C002 (2008) R832415C002 (2010) R832415C002 (2011) R827354 (Final) R834797 (2016)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Zareba W, Nomura A, Couderc JP. Cardiovascular effects of air pollution:what to measure in ECG? Environmental Health Perspectives 2001;109(Suppl 4):533-538.	R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011) R827354 (Final) R827354C003 (Final) R827354C004 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: JSTOR - Full Text PDF Exit
Journal Article	Zareba W, Couderc JP, Oberdorster G, Chalupa D, Cox C, Huang L-S, Peters A, Utell MJ, Frampton MW. ECG parameters and exposure to carbon ultrafine particles in young healthy subjects. Inhalation Toxicology 2009;21(3):223-233.	R832415 (2008) R832415 (2009) R832415 (2010) R832415 (2011) R832415 (Final) R832415C002 (2010) R832415C002 (2011) R832415C003 (2010) R832415C003 (2011) R832415C004 (2009) R832415C004 (2010) R832415C004 (2011) R827354 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: Taylor and Francis-Abstract Exit
Journal Article	Zauscher MD, Moore MJK, Lewis GS, Hering SV, Prather KA. Approach for measuring the chemistry of individual particles in the size range critical for cloud formation. Analytical Chemistry 2011;83(6):2271-2278.	R832415 (Final)	Abstract: ACS-Abstract Exit
Journal Article	Zauscher MD, Wang Y, Moore MJK, Gaston CJ, Prather KA. Air quality impact and physicochemical aging of biomass burning aerosols during the 2007 San Diego Wildfires. Environmental Science and Technology 2013;47(14):7633-7643.	R832415 (Final)	Abstract from PubMed Exit Abstract: ACS-Abstract Exit
Journal Article	Zhao J, Hopke PK. Concentration of reactive oxygen species (ROS) in mainstream and sidestream cigarette smoke. Aerosol Science and Technology 2012;46(2):191-197.	R832415 (Final)	Abstract: Taylor & Francis-Abstract Exit
Journal Article	Zhao W, Hopke PK, Qin X, Prather KA. Predicting bulk ambient aerosol compositions from ATOFMS data with ART-2a and multivariate analysis. Analytica Chimica Acta 2005;549(1-2):179-187.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final) R831083 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Zhou L, Kim E, Hopke PK, Stanier C, Pandis SN. Mining airborne particulate size distribution data by positive matrix factorization. Journal of Geophysical Research 2005;110(D7):D07S19 (15 pp.).	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final)	Full-text: Wiley Online-Full Text HTML Exit Abstract: Wiley Online-Abstract Exit Other: University of Iowa-Full Text PDF Exit
Journal Article	Zhou L, Hopke PK, Venkatachari P. Cluster analysis of single particle mass spectra at Flushing, NY. Analytica Chimica Acta 2006;555(1):47-56.	R832415 (2010) R832415 (2011) R832415 (Final) R827354 (Final) R827354C001 (Final)	Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit

Supplemental Keywords:

analysis, asthma, cardiac, CNS, concentrator, diabetic, monitor, neonates, neurodegeneration, ROS, rat/mouse, rehabilitation, susceptibility, ultrafine particles, vascular, RFA, Scientific Discipline, Health, Air, particulate matter, Health Risk Assessment, Risk Assessments, Biochemistry, airway epithelial cells, atmospheric particles, cardiopulmonary responses, chemical characteristics, fine particles, human health effects, airborne particulate matter, animal model, airway disease, air pollution, pariculate matter, aerosol composition, human exposure, epidemiological studies, atmospheric chemistry

Progress and Final Reports:

Original Abstract

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832415C001 Characterization and Source Apportionment
R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

Grantee Research Project Results

Final Report: Rochester PM Center: Source-Specific Health Effects of Ultrafine/Fine Particles

Objective:

Summary/Accomplishments (Outputs/Outcomes):

Conclusions:

Supplemental Keywords:

Progress and Final Reports:

Project Research Results

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