Publications by authors named "Anthony S Wexler"

60 Publications

Expiratory aerosol particle escape from surgical masks due to imperfect sealing.

Sci Rep 2021 Jun 8;11(1):12110. Epub 2021 Jun 8.

Department of Chemical Engineering, University of California Davis, 1 Shields Ave., Davis, CA, 95616, USA.

Wearing surgical masks or other similar face coverings can reduce the emission of expiratory particles produced via breathing, talking, coughing, or sneezing. Although it is well established that some fraction of the expiratory airflow leaks around the edges of the mask, it is unclear how these leakage airflows affect the overall efficiency with which masks block emission of expiratory aerosol particles. Here, we show experimentally that the aerosol particle concentrations in the leakage airflows around a surgical mask are reduced compared to no mask wearing, with the magnitude of reduction dependent on the direction of escape (out the top, the sides, or the bottom). Because the actual leakage flowrate in each direction is difficult to measure, we use a Monte Carlo approach to estimate flow-corrected particle emission rates for particles having diameters in the range 0.5-20 μm. in all orientations. From these, we derive a flow-weighted overall number-based particle removal efficiency for the mask. The overall mask efficiency, accounting both for air that passes through the mask and for leakage flows, is reduced compared to the through-mask filtration efficiency, from 93 to 70% for talking, but from only 94-90% for coughing. These results demonstrate that leakage flows due to imperfect sealing do decrease mask efficiencies for reducing emission of expiratory particles, but even with such leakage surgical masks provide substantial control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91487-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187651PMC
June 2021

The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer's Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats.

Environ Health Perspect 2021 May 10;129(5):57005. Epub 2021 May 10.

Department of Molecular Biosciences, University of California Davis (UC Davis) School of Veterinary Medicine, Davis, California, USA.

Background: Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer's disease (AD). Preclinical data corroborating this association are largely from studies of male animals exposed acutely or subchronically to high levels of isolated fractions of TRAP. What remains unclear is whether chronic exposure to ambient TRAP modifies AD risk and the influence of sex on this interaction.

Objectives: This study sought to assess effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a preclinical model and to determine whether sex or genetic susceptibility influences outcomes.

Methods: Male and female TgF344-AD rats that express human AD risk genes and wildtype littermates were housed in a vivarium adjacent to a heavily trafficked tunnel in Northern California and exposed for up to 14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unchanged in real time. Refractive particles in the brain and AD phenotypes were quantified in 3-, 6-, 10-, and 15-month-old animals using hyperspectral imaging, behavioral testing, and neuropathologic measures.

Results: Particulate matter (PM) concentrations in TRAP exposure chambers fluctuated with traffic flow but remained below 24-h PM with aerodynamic diameter less than or equal to 2.5 micrometers () U.S. National Ambient Air Quality Standards limits. Ultrafine PM was a predominant component of TRAP. Nano-sized refractive particles were detected in the hippocampus of TRAP animals. TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, and greater cognitive deficits in an age-, genotype-, and sex-dependent manner. TRAP-exposed animals also had more microglial cell activation, but not astrogliosis.

Discussion: These data demonstrate that chronic exposure to ambient TRAP promoted AD phenotypes in wildtype and genetically susceptible rats. TRAP effects varied according to age, sex, and genotype, suggesting that AD progression depends on complex interactions between environment and genetics. These findings suggest current regulations are insufficient to protect the aging brain. https://doi.org/10.1289/EHP8905.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/EHP8905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110309PMC
May 2021

Pathological Cardiopulmonary Evaluation of Rats Chronically Exposed to Traffic-Related Air Pollution.

Environ Health Perspect 2020 12 4;128(12):127003. Epub 2020 Dec 4.

Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, Oregon, USA.

Background: Traffic-related air pollution (TRAP) is made up of complex mixtures of particulate matter, gases and volatile compounds. However, the effects of TRAP on the cardiopulmonary system in most animal studies have been tested using acute exposure to singular pollutants. The cardiopulmonary effects and molecular mechanisms in animals that are chronically exposed to unmodified air pollution as a whole have yet to be studied. Additionally, sex-dependent toxicity of TRAP exposure has rarely been evaluated.

Objectives: This study sought to assess the cardiopulmonary effect of chronic exposure to unmodified, real-world TRAP in both female and male rats.

Methods: Four-week-old male and female rats were exposed to TRAP or filtered air for 14 months in a novel facility drawing air from a major freeway tunnel system in Northern California. Inflammation and oxidative stress markers were examined in the lung, heart, spleen, and plasma, and TRAP deposits were quantified in the lungs of both male and female rats.

Results: Elemental analysis showed higher levels of eight elements in the female lungs and one element in the male lungs. Expression of genes related to fibrosis, aging, oxidative stress, and inflammation were higher in the rat hearts exposed to TRAP, with female rats being more susceptible than males. Enhanced collagen accumulation was found only in the TRAP-exposed female hearts. Plasma cytokine secretion was higher in both female and male rats, but inflammatory macrophages were higher only in TRAP-exposed male spleens.

Discussion: Our results in rats suggest pathological consequences from chronic TRAP exposure, including sex differences indicating females may be more susceptible to TRAP-induced cardiac fibrosis. https://doi.org/10.1289/EHP7045.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/EHP7045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717845PMC
December 2020

Efficacy of masks and face coverings in controlling outward aerosol particle emission from expiratory activities.

Sci Rep 2020 09 24;10(1):15665. Epub 2020 Sep 24.

Department of Chemical Engineering, University of California Davis, 1 Shields Ave, Davis, CA, 95616, USA.

The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air. Here, we measured outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities while wearing different types of medical-grade or homemade masks. Both surgical masks and unvented KN95 respirators, even without fit-testing, reduce the outward particle emission rates by 90% and 74% on average during speaking and coughing, respectively, compared to wearing no mask, corroborating their effectiveness at reducing outward emission. These masks similarly decreased the outward particle emission of a coughing superemitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average. In contrast, shedding of non-expiratory micron-scale particulates from friable cellulosic fibers in homemade cotton-fabric masks confounded explicit determination of their efficacy at reducing expiratory particle emission. Audio analysis of the speech and coughing intensity confirmed that people speak more loudly, but do not cough more loudly, when wearing a mask. Further work is needed to establish the efficacy of cloth masks at blocking expiratory particles for speech and coughing at varied intensity and to assess whether virus-contaminated fabrics can generate aerosolized fomites, but the results strongly corroborate the efficacy of medical-grade masks and highlight the importance of regular washing of homemade masks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72798-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518250PMC
September 2020

Influenza A virus is transmissible via aerosolized fomites.

Nat Commun 2020 08 18;11(1):4062. Epub 2020 Aug 18.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.

Influenza viruses are presumed, but not conclusively known, to spread among humans by several possible routes. We provide evidence of a mode of transmission seldom considered for influenza: airborne virus transport on microscopic particles called "aerosolized fomites." In the guinea pig model of influenza virus transmission, we show that the airborne particulates produced by infected animals are mainly non-respiratory in origin. Surprisingly, we find that an uninfected, virus-immune guinea pig whose body is contaminated with influenza virus can transmit the virus through the air to a susceptible partner in a separate cage. We further demonstrate that aerosolized fomites can be generated from inanimate objects, such as by manually rubbing a paper tissue contaminated with influenza virus. Our data suggest that aerosolized fomites may contribute to influenza virus transmission in animal models of human influenza, if not among humans themselves, with important but understudied implications for public health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17888-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435178PMC
August 2020

Effects of early life exposure to traffic-related air pollution on brain development in juvenile Sprague-Dawley rats.

Transl Psychiatry 2020 05 27;10(1):166. Epub 2020 May 27.

Molecular Biosciences, UC Davis School of Veterinary Medicine, Davis, CA, USA.

Epidemiological studies link traffic-related air pollution (TRAP) to increased risk for various neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship between TRAP and adverse neurodevelopmental outcomes. Moreover, much of the preclinical literature reports effects of concentrated ambient particles or diesel exhaust that do not recapitulate the complexity of real-world TRAP exposures. To assess the developmental neurotoxicity of more realistic TRAP exposures, we exposed male and female rats during gestation and early postnatal development to TRAP drawn directly from a traffic tunnel in Northern California and delivered to animals in real-time. We compared NDD-relevant neuropathological outcomes at postnatal days 51-55 in TRAP-exposed animals versus control subjects exposed to filtered air. As indicated by immunohistochemical analyses, TRAP significantly increased microglial infiltration in the CA1 hippocampus, but decreased astrogliosis in the dentate gyrus. TRAP exposure had no persistent effect on pro-inflammatory cytokine levels in the male or female brain, but did significantly elevate the anti-inflammatory cytokine IL-10 in females. In male rats, TRAP significantly increased hippocampal neurogenesis, while in females, TRAP increased granule cell layer width. TRAP had no effect on apoptosis in either sex. Magnetic resonance imaging revealed that TRAP-exposed females, but not males, also exhibited decreased lateral ventricular volume, which was correlated with increased granule cell layer width in the hippocampus in females. Collectively, these data indicate that exposure to real-world levels of TRAP during gestation and early postnatal development modulate neurodevelopment, corroborating epidemiological evidence of an association between TRAP exposure and increased risk of NDDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-020-0845-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264203PMC
May 2020

Reconciling Measurement and Prediction of Free and Solvated Water in Solution.

ACS Omega 2020 Apr 9;5(15):8754-8765. Epub 2020 Apr 9.

School of Energy and Environment, City University of Hong Kong, Kowloon, Hong Kong, China.

In 2019, Wexler showed that, by applying Raoult's law rigorously to aqueous solutions and properly accounting for hydration of solutes, equations can be derived that accurately describe solute and solvent activity over the full range of concentrations from infinitely dilute to pure solutes. One feature of this theory is that it also predicts the amount of water that is free and the amount that is bound to the solute. In 2004 and 2005, Choi and co-workers used an electrodynamic balance to measure (i) the concentration of a range of organic and electrolyte solutes as a function of water activity and (ii) the amount of free and bound water in these solutions using the fluorescence of pyranine as a probe. In the current work, we compare the predictions of Wexler's theory to the measurements of Choi. After the adjustments to the amount of free water obtained by these measurements, the predictions of Wexler's theory match the measurements of Choi. The potential reasons for the adjustments are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178779PMC
April 2020

The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?

Aerosol Sci Technol 2020 3;0(0):1-4. Epub 2020 Apr 3.

Department of Chemical Engineering, Davis College of Engineering, University of California, Davis, California, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02786826.2020.1749229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157964PMC
April 2020

Effect of voicing and articulation manner on aerosol particle emission during human speech.

PLoS One 2020 27;15(1):e0227699. Epub 2020 Jan 27.

Dept. of Chemical Engineering, University of California Davis, Davis, California, United States of America.

Previously, we demonstrated a strong correlation between the amplitude of human speech and the emission rate of micron-scale expiratory aerosol particles, which are believed to play a role in respiratory disease transmission. To further those findings, here we systematically investigate the effect of different 'phones' (the basic sound units of speech) on the emission of particles from the human respiratory tract during speech. We measured the respiratory particle emission rates of 56 healthy human volunteers voicing specific phones, both in isolation and in the context of a standard spoken text. We found that certain phones are associated with significantly higher particle production; for example, the vowel /i/ ("need," "sea") produces more particles than /ɑ/ ("saw," "hot") or /u/ ("blue," "mood"), while disyllabic words including voiced plosive consonants (e.g., /d/, /b/, /g/) yield more particles than words with voiceless fricatives (e.g., /s/, /h/, /f/). These trends for discrete phones and words were corroborated by the time-resolved particle emission rates as volunteers read aloud from a standard text passage that incorporates a broad range of the phones present in spoken English. Our measurements showed that particle emission rates were positively correlated with the vowel content of a phrase; conversely, particle emission decreased during phrases with a high fraction of voiceless fricatives. Our particle emission data is broadly consistent with prior measurements of the egressive airflow rate associated with the vocalization of various phones that differ in voicing and articulation. These results suggest that airborne transmission of respiratory pathogens via speech aerosol particles could be modulated by specific phonetic characteristics of the language spoken by a given human population, along with other, more frequently considered epidemiological variables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227699PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984704PMC
April 2020

Raoult Was Right After All.

Authors:
Anthony S Wexler

ACS Omega 2019 Jul 30;4(7):12848-12852. Epub 2019 Jul 30.

Air Quality Research Center and Departments of Mechanical and Aerospace Engineering, Civil and Environmental Engineering and Land, Air and Water Resources, University of California, Davis, California 95616, United States.

Raoult's law, published in 1887, is taught in chemistry and chemical engineering fields as a first approximation to the vapor pressure and activity of solutes and solvents in mixtures. In ideal solutions, it is exact but many solutions are known to have substantial deviations from Raoult's law as conventionally interpreted. In 1908, Callendar showed that water hydrated to the solute can explain some of the departures from Raoult's law in aqueous solution. Here, we show that by simply assuming equilibria between the free water in solution and its hydrated forms, Raoult's law and Callendar's extension are valid over the full range of concentrations, while also showing how water and solutes interact in solution. This model of solutions has importance in highly concentrated solutions common in atmosphere aerosols relevant to climate change and air quality, and in numerous industrial processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b01707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682120PMC
July 2019

Aerosol emission and superemission during human speech increase with voice loudness.

Sci Rep 2019 02 20;9(1):2348. Epub 2019 Feb 20.

Department of Chemical Engineering, University of California Davis, 1 Shields Ave, Davis, CA, 95616, USA.

Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as "speech superemitters," consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-38808-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382806PMC
February 2019

Statistical Mechanics of Multilayer Sorption: Surface Concentration Modeling and XPS Measurement.

J Phys Chem Lett 2018 Mar 8;9(6):1461-1464. Epub 2018 Mar 8.

Mechanical and Aerospace Engineering , University of California , Davis , California 95616 , United States.

The concentration of solute molecules at the surface of a liquid is a factor in heterogeneous reactions, surface tension, and Marangoni-effect-driven surface flows. Increasingly, X-ray photoelectron spectroscopy (XPS) has enabled surface concentrations to be measured. In prior work, we employed statistical mechanics to derive expressions for surface tension as a function of solute activity in a binary solution. Here we use a Gibbs relation to derive concomitant expressions for surface concentration. Surface tension data from the literature for five alcohols are used to identify parameters in the surface tension equation. These parameters are then used in the surface concentration equation to predict surface concentrations. Comparison of these predictions to those measured with XPS shows a factor of three difference between measured and predicted surface concentrations. Potential reasons for the discrepancy are discussed, including lack of surface-bulk equilibrium in the measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.8b00332DOI Listing
March 2018

Comparison of Manual and Automated Measurements of Tracheobronchial Airway Geometry in Three Balb/c Mice.

Anat Rec (Hoboken) 2017 Nov 5;300(11):2046-2057. Epub 2017 Jul 5.

Mechanical and Aerospace Engineering, University of California, Davis, California.

Mammalian lungs are comprised of large numbers of tracheobronchial airways that transition from the trachea to alveoli. Studies as wide ranging as pollutant deposition and lung development rely on accurate characterization of these airways. Advancements in CT imaging and the value of computational approaches in eliminating the burden of manual measurement are providing increased efficiency in obtaining this geometric data. In this study, we compare an automated method to a manual one for the first six generations of three Balb/c mouse lungs. We find good agreement between manual and automated methods and that much of the disagreement can be attributed to method precision. Using the automated method, we then provide anatomical data for the entire tracheobronchial airway tree from three Balb/C mice. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2046-2057, 2017. © 2017 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ar.23624DOI Listing
November 2017

Architecture of the rat nephron-arterial network: analysis with micro-computed tomography.

Am J Physiol Renal Physiol 2017 Aug 19;313(2):F351-F360. Epub 2017 Apr 19.

Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.

Among solid organs, the kidney's vascular network stands out, because each nephron has two distinct capillary structures in series and because tubuloglomerular feedback, one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each generates a self-sustained periodic oscillation and an oscillating electrical signal that propagates upstream along arterioles. Similar electrical signals from other nephrons interact, allowing nephron synchronization. Experimental measurements show synchronization over fields of a few nephrons; simulations based on a simplified network structure that could obscure complex interactions predict more widespread synchronization. To permit more realistic simulations, we made a cast of blood vessels in a rat kidney, performed micro-computed tomography at 2.5-μm resolution, and recorded three-dimensional coordinates of arteries, afferent arterioles, and glomeruli. Nonterminal branches of arcuate arteries form treelike structures requiring two to six bifurcations to reach terminal branches at the tree tops. Terminal arterial structures were either paired branches at the tops of the arterial trees, from which 52.6% of all afferent arterioles originated, or unpaired arteries not at the tree tops, yielding the other 22.9%; the other 24.5% originated directly from nonterminal arteries. Afferent arterioles near the corticomedullary boundary were longer than those farther away, suggesting that juxtamedullary nephrons have longer afferent arterioles. The distance separating origins of pairs of afferent arterioles varied randomly. The results suggest an irregular-network tree structure with vascular nodes, where arteriolar activity and local blood pressure interact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00092.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582900PMC
August 2017

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung.

Crit Care Med 2017 Apr;45(4):687-694

1European Synchrotron Radiation Facility, ID17 Biomedical Beamline, Grenoble, France.2Department of Pediatric Pulmonology, Université de Picardie Jules Verne, Inserm U1105 & Amiens University Hospital, Amiens, France.3Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.4Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.5Department of Physics, University of Helsinki, Helsinki, Finland.6Helsinki University Central Hospital, Helsinki, Finland.7Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil.8Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.9Department of Mechanical Engineering and Environmental Quality Laboratory, University of California Davis, Davis, CA.10Respiratory Division, University Hospital UZ Brussel, Brussels, Belgium.11Department of Medicine, University of Vermont, Burlington, VT.

Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model.

Design: Experimental animal study.

Setting: International synchrotron radiation laboratory.

Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode.

Interventions: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points.

Measurements And Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O.

Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000002234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702254PMC
April 2017

Pulmonary inflammatory effects of source-oriented particulate matter from California's San Joaquin Valley.

Atmos Environ (1994) 2015 Oct;119:174-181

Center for Health and the Environment, University of California, Davis, One Shields Avenue, Davis, California, 95616 USA.

The EPA regulates ambient particulate matter (PM) because substantial associations have been established between PM and health impacts. Presently, regulatory compliance involves broad control of PM emission sources based on mass concentration rather than chemical composition, although PM toxicity is likely to vary depending upon PM physicochemical properties. The overall objective of this study was to help inform source-specific PM emission control regulations. For the first time, source-oriented PM was collected from the atmosphere in Fresno, CA, onto 38 source/size substrates. Mice were exposed via oropharyngeal aspiration to equivalent mass doses [50 μg] of two size fractions: ultrafine (Dp < 0.17μm) and submicron fine (0.17 < Dp < 1 μm) during summer and winter seasons. At 24 hours post-exposure, cellular and biochemical indicators of pulmonary inflammation were evaluated in the bronchoalveolar lavage fluid. Significant inflammatory responses were elicited by vehicle, regional background, and cooking PM sources that were dependent on season and particle size. This is the first study of source-oriented toxicity of atmospheric PM and supports source-specific emissions control strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atmosenv.2015.08.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639935PMC
October 2015

Growth of Ammonium Bisulfate Clusters by Adsorption of Oxygenated Organic Molecules.

J Phys Chem A 2015 Nov 30;119(45):11191-8. Epub 2015 Oct 30.

Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.

Quantum chemical calculations were employed to model the interactions of the [(NH4(+))4(HSO4(-))4] ammonium bisulfate cluster with one or more molecular products of monoterpene oxidation. A strong interaction was found between the bisulfate ion of this cluster and a carboxylic acid, aldehyde, or ketone functionality of the organic molecule. Free energies of adsorption for carboxylic acids were in the -70 to -73 kJ/mol range, while those for aldehydes and ketones were in the -46 to -50 kJ/mol range. These values suggest that a small ambient [(NH4(+))4(SO4(-))4]cluster is able to adsorb an oxygenated organic molecule. While adsorption of the first molecule is highly favorable, adsorption of subsequent molecules is less so, suggesting that sustained uptake of organic molecules does not occur, and thus is not a pathway for continuing growth of the cluster. This result is consistent with ambient measurements showing that particles below ∼1 nm grow slowly, while those above 1 nm grow at an increasing rate presumably due to a lower surface energy barrier enabling the uptake of organic molecules. This work provides insight into the molecular level interactions which affect sustained cluster growth by uptake of organic molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.5b07744DOI Listing
November 2015

Isotherm-based thermodynamic model for electrolyte and nonelectrolyte solutions incorporating long- and short-range electrostatic interactions.

J Phys Chem A 2015 Apr 11;119(13):3244-52. Epub 2015 Mar 11.

†Department of Mechanical Engineering, University of Minnesota, Twin Cities, 111 Church Street SE, Minneapolis, Minnesota 55455, United States.

The activities of solutes and solvents in solutions govern numerous physical phenomena in a wide range of practical applications. In prior work, we used statistical mechanics and multilayer adsorption isotherms to develop a transformative model for capturing thermodynamic properties of multicomponent aqueous solutions over the entire concentration range (Dutcher et al. J. Phys. Chem. 2011, 2012, 2013). That model needed only a few adsorption energy values to represent the solution thermodynamics of each solute. In the current work, we posit that the adsorption energies are due to dipole-dipole electrostatic forces in solute-solvent and solvent-solvent interactions. This hypothesis was tested in aqueous solutions on (a) 37 1:1 electrolytes, over a range of cation sizes, from H(+) to tetrabutylammonium, for common anions including Cl(-), Br(-), I(-), NO3(-), OH(-), ClO4(-), and (b) 20 water-soluble organic molecules including alcohols and polyols. For both electrolytes and organic solutions, the energies of adsorption can be calculated with the dipole moments of the solvent, molecular size of the solvent and solute, and the solvent-solvent and solvent-solute intermolecular bond lengths. Many of these physical properties are available in the literature, with the exception of the solute-solvent intermolecular bond lengths. For those, predictive correlations developed here enable estimation of solute and solvent solution activities for which there are little or no activity data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jp512646kDOI Listing
April 2015

Allergic airway inflammation is differentially exacerbated by daytime and nighttime ultrafine and submicron fine ambient particles: heme oxygenase-1 as an indicator of PM-mediated allergic inflammation.

J Toxicol Environ Health A 2015 ;78(4):254-66

a Center for Health and the Environment , University of California , Davis , California , USA.

Ambient particulate matter (PM) originates from a range of sources and differs in composition with respect to season, time of day, and particle size. In this study, ambient PM samples in the ultrafine and submicrometer fine range were tested for the potential to exacerbate a murine model of allergic airway inflammation when exposure occurs solely during allergic sensitization, but not during subsequent allergen challenge. Temporally resolved and size-segregated PM samples were used to understand how summer or winter, day or night, and ambient ultrafine and submicrometer fine particle size influence PM's ability to exacerbate allergic inflammation. PM was collected in urban Fresno, CA. BALB/c mice were exposed to PM and house dust mite allergen (HDM) via intranasal aspiration on d 1, 3, and 5. HDM challenge occurred on d 12-14, with inflammation assessed 24 h following final challenge. While season or particle size did not predict allergic inflammation, daytime ultrafine and submicrometer fine particles significantly increased total cellular inflammation, specifically lymphocyte and eosinophil infiltration, compared to allergic controls. Further studies examined PM-mediated changes within the lung during the period where allergen sensitization occurred by measuring direct effects of PM on pulmonary oxidative stress and inflammation. Pulmonary levels of heme oxygenase-1 (HO-1), a biomarker of oxidative stress, but not cellular inflammation, demonstrated a remarkable correlation with the degree of allergic inflammation in animals sensitized to allergen and PM concomitantly, suggesting acute PM-mediated HO-1 levels may serve as a predictive indicator of a particle's ability to exacerbate allergic airway inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15287394.2014.959627DOI Listing
April 2015

Biological dose response to PM2.5: effect of particle extraction method on platelet and lung responses.

Toxicol Sci 2015 Feb 11;143(2):349-59. Epub 2014 Nov 11.

*Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, Center for Health and the Environment, Air Quality Research Center, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine and Departments of Mechanical and Aerospace Engineering, Civil and Environmental Engineering, and Land, Air and Water Resources, University of California, Davis, California 95616-8732 *Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, Center for Health and the Environment, Air Quality Research Center, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine and Departments of Mechanical and Aerospace Engineering, Civil and Environmental Engineering, and Land, Air and Water Resources, University of California, Davis, California 95616-8732.

Particulate matter (PM) exposure contributes to respiratory diseases and cardiopulmonary mortality. PM toxicity is related to sources and composition, such as abundance of polycyclic aromatic hydrocarbons (PAHs). We exposed adult male BALB/c mice, via oropharyngeal aspiration, to a range of doses of PM2.5 collected during the winter in downtown Sacramento near a major freeway interchange (SacPM). Two preparation methods (spin-down and multi-solvent extraction) were tested to remove particles from collection filters. Three doses were analyzed 24 h after treatment for (1) leukocytes and total protein in bronchoalveolar lavage fluid (BALF), (2) airway-specific and whole lobe expression of PAH-sensitive genes (CYP1B1 and CYP1A1) and IL-1 b, (3) lung histology, and (4) platelet function. Both extraction methods stimulated biological responses, but the spin-down method was more robust at producing IL-1 b and CYP1B1 gene responses and the multi-solvent extraction induced whole lung CYP1A1. Neutrophils in the BALF were increased 5- to 10-fold at the mid and high dose for both preparations. Histopathology scores indicated dose-dependent responses and increased pathology associated with spin-down-derived PM exposure. In microdissected airways, spin-down PM increased CYP1B1 gene expression significantly, but multi-solvent extracted PM did not. Platelet responses to the physiological agonist thrombin were approximately twice as potent in the spin-down preparation as in the multi-solvent extract. We conclude (1) the method of filter extraction can influence the degree of biological response, (2) for SacPM the minimal effective dose is 27.5-50 µg based on neutrophil recruitment, and (3) P450s are upregulated differently in airways and lung parenchyma in response to PAH-containing PM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfu230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306718PMC
February 2015

Turbulent dispersion via fan-generated flows.

Phys Fluids (1994) 2014 May 30;26(5):055114. Epub 2014 May 30.

Department of Chemical Engineering and Materials Science, University of California Davis, Davis, California 95616, USA.

Turbulent dispersion of passive scalar quantities has been extensively studied in wind tunnel settings, where the flow is carefully conditioned using flow straighteners and grids. Much less is known about turbulent dispersion in the "unconditioned" flows generated by fans that are ubiquitous in indoor environments, despite the importance of these flows to pathogen and contaminant transport. Here, we demonstrate that a point source of scalars released into an airflow generated by an axial fan yields a plume whose width is invariant with respect to the fan speed. The results point toward a useful simplification in modeling of disease and pollution spread via fan-generated flows.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/1.4879256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039734PMC
May 2014

Statistical Mechanics of Multilayer Sorption: Surface Tension.

J Phys Chem Lett 2013 May 7;4(10):1723-6. Epub 2013 May 7.

Air Quality Research Center, University of California, Davis, California 95616, United States.

Mathematical models of surface tension as a function of solute concentration are needed for predicting the behavior of surface processes relevant to the environment, biology, and industry. Current aqueous surface tension-activity models capture either solutions of electrolytes or those of nonelectrolytes, but a single equation has not yet been found that represents both over the full range of compositions. In prior work, we developed an accurate model of the activity-concentration relationship in solutions over the full range of compositions by extending the BET (Brunauer, Emmett, Teller) and GAB (Guggenheim, Anderson, de Boer) isotherms to multiple monolayers of solvent molecules sorbed to solutes. Here, we employ similar statistical mechanical tools to develop a simple equation for the surface tension-activity relationship that differs remarkably from prior formulations in that it (1) works equally well for nonelectrolyte and electrolyte solutes and (2) is accurate over the full range of concentrations from pure solvent to pure solute.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jz400725pDOI Listing
May 2013

An isotherm-based thermodynamic model of multicomponent aqueous solutions, applicable over the entire concentration range.

J Phys Chem A 2013 Apr 8;117(15):3198-213. Epub 2013 Apr 8.

Air Quality Research Center, University of California at Davis, Davis, California 95616, USA.

In previous studies (Dutcher et al. J. Phys. Chem. C 2011, 115, 16474-16487; 2012, 116, 1850-1864), we derived equations for the Gibbs energy, solvent and solute activities, and solute concentrations in multicomponent liquid mixtures, based upon expressions for adsorption isotherms that include arbitrary numbers of hydration layers on each solute. In this work, the long-range electrostatic interactions that dominate in dilute solutions are added to the Gibbs energy expression, thus extending the range of concentrations for which the model can be used from pure liquid solute(s) to infinite dilution in the solvent, water. An equation for the conversion of the reference state for solute activity coefficients to infinite dilution in water has been derived. A number of simplifications are identified, notably the equivalence of the sorption site parameters r and the stoichiometric coefficients of the solutes, resulting in a reduction in the number of model parameters. Solute concentrations in mixtures conform to a modified Zdanovskii-Stokes-Robinson mixing rule, and solute activity coefficients to a modified McKay-Perring relation, when the effects of the long-range (Debye-Hückel) term in the equations are taken into account. Practical applications of the equations to osmotic and activity coefficients of pure aqueous electrolyte solutions and mixtures show both satisfactory accuracy from low to high concentrations, together with a thermodynamically reasonable extrapolation (beyond the range of measurements) to extreme concentration and to the pure liquid solute(s).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jp310860pDOI Listing
April 2013

Predicting non-isometric fatigue induced by electrical stimulation pulse trains as a function of pulse duration.

J Neuroeng Rehabil 2013 Feb 2;10:13. Epub 2013 Feb 2.

Biomedical Engineering Program, University of California, Davis, CA 95616, USA.

Background: Our previous model of the non-isometric muscle fatigue that occurs during repetitive functional electrical stimulation included models of force, motion, and fatigue and accounted for applied load but not stimulation pulse duration. Our objectives were to: 1) further develop, 2) validate, and 3) present outcome measures for a non-isometric fatigue model that can predict the effect of a range of pulse durations on muscle fatigue.

Methods: A computer-controlled stimulator sent electrical pulses to electrodes on the thighs of 25 able-bodied human subjects. Isometric and non-isometric non-fatiguing and fatiguing knee torques and/or angles were measured. Pulse duration (170-600 μs) was the independent variable. Measurements were divided into parameter identification and model validation subsets.

Results: The fatigue model was simplified by removing two of three non-isometric parameters. The third remained a function of other model parameters. Between 66% and 77% of the variability in the angle measurements was explained by the new model.

Conclusion: Muscle fatigue in response to different stimulation pulse durations can be predicted during non-isometric repetitive contractions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-0003-10-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626903PMC
February 2013

Direct surface analysis of time-resolved aerosol impactor samples with ultrahigh-resolution mass spectrometry.

Anal Chem 2012 Nov 30;84(22):9858-64. Epub 2012 Oct 30.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

Aerosol particles in the atmosphere strongly influence the Earth's climate and human health, but the quantification of their effects is highly uncertain. The complex and variable composition of atmospheric particles is a main reason for this uncertainty. About half of the particle mass is organic material, which is very poorly characterized on a molecular level, and therefore it is challenging to identify sources and atmospheric transformation processes. We present here a new combination of techniques for highly time-resolved aerosol sampling using a rotating drum impactor (RDI) and organic chemical analysis using direct liquid extraction surface analysis (LESA) combined with ultrahigh-resolution mass spectrometry. This minimizes sample preparation time and potential artifacts during sample workup compared to conventional off-line filter or impactor sampling. Due to the high time resolution of about 2.5 h intensity correlations of compounds detected in the high-resolution mass spectra were used to identify groups of compounds with likely common sources or atmospheric history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/ac3020615DOI Listing
November 2012

Multinephron dynamics on the renal vascular network.

Am J Physiol Renal Physiol 2013 Jan 12;304(1):F88-F102. Epub 2012 Sep 12.

Dept. of Molecular Pharmacology, Physiology, and Biotechnology Brown Univ., Providence, RI 02912, USA.

Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each nephron to regulate blood flow and glomerular filtration rate. Both mechanisms are nonlinear, generate self-sustained oscillations, and interact as their signals converge on arteriolar smooth muscle, forming a regulatory ensemble. Ensembles may synchronize. Smooth muscle cells in the ensemble depolarize periodically, generating electrical signals that propagate along the vascular network. We developed a mathematical model of a nephron-vascular network, with 16 versions of a single nephron model containing representations of both mechanisms in the regulatory ensemble, to examine the effects of network structure on nephron synchronization. Symmetry, as a property of a network, facilitates synchronization. Nephrons received blood from a symmetric electrically conductive vascular tree. Symmetry was created by using identical nephron models at each of the 16 sites and symmetry breaking by varying nephron length. The symmetric model achieved synchronization of all elements in the network. As little as 1% variation in nephron length caused extensive desynchronization, although synchronization was maintained in small nephron clusters. In-phase synchronization predominated among nephrons separated by one or three vascular nodes and antiphase synchronization for five or seven nodes of separation. Nephron dynamics were irregular and contained low-frequency fluctuations. Results are consistent with simultaneous blood flow measurements in multiple nephrons. An interaction between electrical signals propagated through the network to cause synchronization; variation in vascular pressure at vessel bifurcations was a principal cause of desynchronization. The results suggest that the vasculature supplies blood to nephrons but also engages in robust information transfer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00237.2012DOI Listing
January 2013

A comprehensive breath plume model for disease transmission via expiratory aerosols.

PLoS One 2012 15;7(5):e37088. Epub 2012 May 15.

Department of Chemical Engineering and Materials Science, University of California Davis, Davis, California, United States of America.

The peak in influenza incidence during wintertime in temperate regions represents a longstanding, unresolved scientific question. One hypothesis is that the efficacy of airborne transmission via aerosols is increased at lower humidities and temperatures, conditions that prevail in wintertime. Recent work with a guinea pig model by Lowen et al. indicated that humidity and temperature do modulate airborne influenza virus transmission, and several investigators have interpreted the observed humidity dependence in terms of airborne virus survivability. This interpretation, however, neglects two key observations: the effect of ambient temperature on the viral growth kinetics within the animals, and the strong influence of the background airflow on transmission. Here we provide a comprehensive theoretical framework for assessing the probability of disease transmission via expiratory aerosols between test animals in laboratory conditions. The spread of aerosols emitted from an infected animal is modeled using dispersion theory for a homogeneous turbulent airflow. The concentration and size distribution of the evaporating droplets in the resulting "Gaussian breath plume" are calculated as functions of position, humidity, and temperature. The overall transmission probability is modeled with a combination of the time-dependent viral concentration in the infected animal and the probability of droplet inhalation by the exposed animal downstream. We demonstrate that the breath plume model is broadly consistent with the results of Lowen et al., without invoking airborne virus survivability. The results also suggest that, at least for guinea pigs, variation in viral kinetics within the infected animals is the dominant factor explaining the increased transmission probability observed at lower temperatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037088PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352828PMC
January 2013

Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs.

Toxicol Sci 2011 Dec 13;124(2):472-86. Epub 2011 Sep 13.

Center for Health and the Environment, University of California, Davis, Davis, California 95616, USA.

Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfr233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216412PMC
December 2011

Disruption of tracheobronchial airway growth following postnatal exposure to ozone and ultrafine particles.

Inhal Toxicol 2011 Aug 22;23(9):520-31. Epub 2011 Jul 22.

Department of Mechanical and Aerospace Engineering, University of California, Davis, CA 95616, USA.

This study examined airway structure changes in adult rats after a long recovery period due to sub-chronic juvenile exposure to ozone and ultrafine particles that have a high organic fraction. Neonatal male Sprague-Dawley rats were exposed during lung development to 3 cycles of 0.5 ppm ozone from postnatal day 7 through 25. Two different exposure patterns were used: 5-day exposure per week (Ozone52) or 2-day exposure per week (Ozone25) with or without co-exposure to ultrafine particles (OPFP5252, OPFP5225). Airway architecture was evaluated at 81 days of age, after 56 days of continued development beyond the exposure period in filtered air (FA). By analyzing CT images from lung airway casts, we determined airway diameter, length, branching angle, and rotation angle for most conducting airways. Compared with the FA control group, the Ozone52 group showed significant decreases in airway diameter in generations larger than 10 especially in the right diaphragmatic lobe and in airway length in distal generations, while changes in airway structure due to the Ozone25 exposure were not appreciable. Interaction effects of ozone and ultrafine particle exposures were not significant. These results suggest that airway alterations due to postnatal ozone exposure are not limited to the distal region but occur extensively from the middle to distal conducting airways. Further, alterations due to early ozone exposure do not recover nearly 2 months after exposure has ceased demonstrating a persistent airway structural change following an early life exposure to ozone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08958378.2011.591447DOI Listing
August 2011

Simulated annealing implementation with shorter Markov chain length to reduce computational burden and its application to the analysis of pulmonary airway architecture.

Comput Biol Med 2011 Aug 29;41(8):707-15. Epub 2011 Jun 29.

Department of Mechanical and Aerospace Engineering, One Shields Ave., University of California, Davis, CA 95616, USA.

A new way to implement the Simulated Annealing (SA) algorithm was developed and tested that improves computation performance by using shorter Markov chain length (inner iterations) and repeating the entire SA process until the final function value meets the solution criterion. The new approach coupled with the adaptive neighborhood method was tested on the Rosenbrock function in 4 and 13 dimensions. This implementation significantly improved the computation speed without degrading solution quality. The proposed implementation was used to characterize pulmonary architecture from micro CT image data demonstrating the algorithm's effectiveness especially for problems with high computational demand and when the solution quality requirement can be pre-specified. Using this implementation, detailed statistics of the morphometry of conducting airways from 12 male Sprague Dawley rats were obtained for each lobe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2011.06.006DOI Listing
August 2011