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Automotive brake-wear emissions are increasingly important in on-road particulate matter (PM) emission inventory. Previous studies reported a high level of PM emissions from the friction materials of light/medium-duty vehicles, but there are few data available from heavy-duty (HD) vehicles equipped with drum brakes despite their popularity (â¼85% in HD vehicle fleet). This study developed a novel tracer-gas-integrated method for brake-wear PM emission measurements and evaluated four HD vehicles on a chassis dynamometer that complied with regulatory exhaust emission testing requirements. Three class-6 vehicles with a similar test weight demonstrated repeatability, with the coefficient of variation in the range of 9-36%. Braking events increased PM concentrations by 3 orders of magnitude above the background level. Resuspension of brake-wear PM also occurred during acceleration and contributed to 8-31% of the total PM2.5 mass. The class-6 vehicles had PM2.5 emissions from a single brake (0.7-1.5 mg/km/brake), generally similar to the level of tail-pipe exhaust PM emissions (0.7-1.5 mg/km/vehicle) of each vehicle. A class-8 vehicle exhibited brake-wear PM2.5 emissions (2.4-3.4 mg/km/brake) significantly higher than the tail-pipe exhaust PM emissions (â¼1.3 mg/km/vehicle). This article reports an exceptionally high level of brake-wear PM emissions measured directly from the drum brakes of HD vehicles.
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Contaminantes Atmosféricos , Material Particulado , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Emisiones de Vehículos/análisis , Vehículos a MotorRESUMEN
An electronic cigarette (e-cig) generates aerosols by vaporizing the e-liquid, which mainly consists of propylene glycol (PG), vegetable glycerin (VG), and nicotine. Understanding the effects of e-liquid main compositions on e-cig aerosols is important for exposure assessment. This study investigated how the PG/VG ratio and nicotine content affect e-cig aerosol emissions and dynamics. A tank-based e-cig device with 10 different flavorless e-liquid mixtures (e.g., PG/VG ratios of 0/100, 10/90, 30/70, 50/50, and 100/0 with 0.0% or 2.4% nicotine) was used to puff aerosols into a 0.46 m3 stainless steel chamber for 0.5 h. Real-time measurements of particle number concentration (PNC), fine particulate matter (PM2.5), and particle size distributions were conducted continuously throughout the puffing and the following 2-h decay period. During the decay period, particle loss rates were determined by a first-order log-linear regression and used to calculate the emission factor. The addition of nicotine in the e-liquid significantly decreased the particle number emission factor by 33%. The PM2.5 emission factor significantly decreased with greater PG content in the e-liquid. For nicotine-free e-liquids, increasing the PG/VG ratio resulted in increased particle loss rates measured by PNC and PM2.5. This pattern was not observed with nicotine in the e-liquids. The particle loss rates, however, were significantly different with and without nicotine especially when the PG/VG ratios were greater than 30/70. Compared with nonvolatile diethyl-hexyl subacute (DEHS) aerosols, e-cig particle concentration decayed faster inside the chamber, presumably due to evaporation. These results have potential implications for assessing human exposure to e-cig aerosols.
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AIMS: Histology-based tumour microenvironment (TME) scores are useful in predicting the prognosis of gastrointestinal cancer. However, their prognostic roles in distal bile duct cancer (DBDC) have not been previously studied. This study aimed to evaluate the prognostic significance of the TME scores using the Klintrup-Mäkinen (KM) grade, tumour stroma percentage (TSP) and the Glasgow microenvironment score (GMS) in resected DBDC. METHODS AND RESULTS: Eighty-one patients with DBDC who underwent curative resection were enrolled. DBDC was graded according to KM grade, TSP and GMS. A high KM grade was found in 19 patients (24%) and a high TSP was found in 47 patients (58%). A high TSP was significantly correlated with a low KM grade (P < 0.001). The distribution of the GMS, which was developed by combining the KM grade and TSP, was as follows: 0 (n = 19, 24%), 1 (n = 19, 24%) and 2 (n = 43, 52%). A low KM grade, high TSP and high GMS were significantly associated with short overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P < 0.001). Furthermore, multivariate analysis showed that a low KM grade [hazard ratio (HR) = 3.826; confidence interval (CI) = 1.650-8.869; P = 0.014], high TSP (HR = 2.193; CI = 1.173-4.100, P = 0.002) and high GMS (HR = 7.148; CI = 2.811-18.173) were independent prognostic factors for short RFS; a low KM grade (HR = 4.324; CI = 1.594-11.733) and high GMS (HR = 6.332; CI = 2.743-14.594) were independent prognostic factors for short OS. CONCLUSION: Histology-based TME scores, including the KM grade, TSP and GMS, are useful for predicting the survival of patients with resected DBDC.
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Adenocarcinoma/patología , Neoplasias de los Conductos Biliares/patología , Clasificación del Tumor/métodos , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Objective: Since the introduction in 2004, global usage of e-cigarettes (ECs) has risen exponentially. However, the risks of ECs on oral health are uncertain. The purpose of this study is to understand if EC aerosol exposure impacts the gene pathways of normal human oral keratinocytes (NHOKs), particularly the unfolded protein response (UPR) pathway. Materials and methods: EC aerosols were generated reproducibly with a home-made puffing device and impinged into the culture medium for NHOKs. DNA microarrays were used to profile the gene expression changes in NHOKs treated with EC aerosols, and the Ingenuity Pathway Analysis (IPA) was used to reveal signaling pathways altered by the EC aerosols. Quantitative PCR was used to validate the expression changes of significantly altered genes. Results: DNA microarray profiling followed by IPA revealed a number of signaling pathways, such as UPR, cell cycle regulation, TGF-ß signaling, NRF2-mediated oxidative stress response, PI3K/AKT signaling, NF-κB signaling, and HGF signaling, activated by EC aerosols in NHOKs. The UPR pathway genes, C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), X box binding protein 1 (XBP1), and inositol-requiring enzyme 1 alpha (IRE1α) were all significantly up-regulated in EC aerosol-treated NHOKs whereas immunoglobulin heavy-chain binding protein (BIP) and PRKR-like ER kinase (PERK) were slightly up-regulated. qPCR analysis results were found to be well correlated with those from the DNA microarray analysis. The most significantly changed genes in EC aerosol-treated NHOKs versus untreated NHOKs were CHOP, ATF4, XBP1, IRE1α and BIP. Meanwhile, Western blot analysis confirmed that CHOP, GRP78 (BIP), ATF4, IRE1α and XBP1s (spliced XBP1) were significantly up-regulated in NHOKs treated with EC aerosols. Conclusion: Our results indicate that EC aerosols up-regulate the UPR pathway genes in NHOKs, and the induction of UPR response is mediated by the PERK - EIF2α - ATF4 and IRE1α - XBP1 pathways.
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Pollutants in tailpipe emissions can be highly elevated around roadways, and in early mornings the pollution plume can extend hundreds of meters into surrounding neighborhoods. Solid sound walls and vegetation barriers are commonly used to mitigate noise, but they also help mitigate near-road air pollution. Here we assess the effectiveness of barriers consisting of vegetation only and of a combination of vegetation and a solid sound wall (combination barrier) in reducing pollution concentrations downwind of roads, under stable atmospheric stability and calm to light wind conditions. Because there was no practical (no barrier) control site in the area, we primarily compare the two barrier types to each other and explore the importance of atmospheric conditions. Using measurements collected with a mobile platform, we develop concentration decay profiles of ultrafine and fine particles, oxides of nitrogen (NO and NO2) and carbon monoxide downwind of a freeway in California with different barrier configurations and meteorological conditions. Diurnally averaged data collected with passive samplers indicate that pollution from morning rush hour has about equal impact as the entire remainder of the day, because of differences in atmospheric dispersion as the day progresses. Under calm and stable atmospheric conditions (wind speed <0.6â¯m/s); a vegetation-only barrier was more effective than a combination barrier with a total height that was somewhat lower than the vegetation-only barrier, by 10-24% in the first 160â¯m downwind. Under light winds (above ~ 0.6 but below 3â¯m/s) and stable conditions, the combination barrier was more effective than the vegetation barrier alone, by 6-33%, in the first 160â¯m from the barrier. The average particle size downwind of the vegetation-only barrier was larger than downwind of the combination barrier, indicating that particle deposition plays an important role in the reductions observed downwind of vegetation. Our results are consistent with the notion that at low wind speeds, vegetation acts as an effective barrier. Overall, adding vegetation alone or to an existing solid barrier results in lower downwind pollution concentrations, especially under low wind speeds when concentrations can be high.
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Contaminantes Atmosféricos/análisis , Conservación de los Recursos Naturales/métodos , Monitoreo del Ambiente , Emisiones de Vehículos/análisis , Contaminación del Aire/análisis , California , Tamaño de la Partícula , Material Particulado/análisis , VientoRESUMEN
Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30-35 and 190-240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers. In summary, we developed an aerosol system that can produce clinically relevant chronic intermittent nicotine exposure in unanesthetized, unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for understanding the health effects of chronic intermittent nicotine exposure such as with tobacco cigarettes and electronic cigarettes for studies of behavior, pharmacology and toxicology, nicotine addiction, tobacco-related diseases, and teratogenicity, and for the discovery of therapeutics. NEW & NOTEWORTHY We developed a lung alveolar region-targeted aerosol method and a system that provides chronic intermittent nicotine exposure in freely moving rodents. The method produces in rodents clinically relevant nicotine exposure with the route and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health impacts of chronic nicotine exposures such as with tobacco cigarettes and electronic cigarettes, for studying nicotine pharmacology, toxicology, addiction, and tobacco-related diseases, and for the discovery of therapeutics.
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Ritmo Circadiano , Nicotina/administración & dosificación , Aerosoles , Animales , Cámaras de Exposición Atmosférica , Cotinina/sangre , Sistemas de Liberación de Medicamentos , Masculino , Modelos Animales , Nicotina/sangre , Nicotina/farmacocinética , Ratas , Ratas Sprague-DawleyRESUMEN
Particle emissions from heavy-duty vehicles (HDVs) have significant environmental and public health impacts. This study measured total particle number emission factors (PNEFs) from six newly certified HDVs powered by diesel and compressed natural gas totaling over 6800 miles of on-road operation in California. Distance-, fuel- and work-based PNEFs were calculated for each vehicle. Distance-based PNEFs of vehicles equipped with original equipment manufacturer (OEM) diesel particulate filters (DPFs) in this study have decreased by 355-3200 times compared to a previous retrofit DPF dynamometer study. Fuel-based PNEFs were consistent with previous studies measuring plume exhaust in the ambient air. Meanwhile, on-road PNEF shows route and technology dependence. For vehicles with OEM DPFs and Selective Catalytic Reduction Systems, PNEFs under highway driving (i.e., 3.34 × 1012 to 2.29 × 1013 particles/mile) were larger than those measured on urban and drayage routes (i.e., 5.06 × 1011 to 1.31 × 1013 particles/mile). This is likely because a significant amount of nucleation mode volatile particles were formed when the DPF outlet temperature reached a critical value, usually over 310 °C, which was commonly achieved when vehicle speed sustained over 45 mph. A model year 2013 diesel HDV produced approximately 10 times higher PNEFs during DPF active regeneration events than nonactive regeneration.
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Contaminantes Atmosféricos , Gas Natural , Emisiones de Vehículos , California , Catálisis , Humanos , Vehículos a Motor , Tamaño de la PartículaRESUMEN
An increasing number of studies have reported deleterious health effects of vehicle-emitted particulate matter (PM), including PM2.5 (aerodynamic diameter≤2.5 µm), black carbon (BC), and ultrafine particles (UFPs, diameter≤100 nm). When commuting inside school buses, children are exposed to high level of these pollutants due to emissions from both school bus itself and other on-road vehicles. This study developed an on-board high efficiency cabin air (HECA) filtration system for reducing children's exposure inside school buses. Six school buses were driven on two typical routes to evaluate to what extent the system reduces particulate pollutant levels inside the buses. The testing routes included freeways and major arterial roadways in Los Angeles, CA. UFP number concentrations and size distributions as well as BC and PM2.5 concentrations were monitored concurrently inside and outside of each bus. With the HECA filtration system on, in-cabin UFP and BC levels were reduced by 88±6% and 84±5% on averages across all driving conditions, respectively. The system was less effective for PM2.5 (55±22%) but successfully kept its levels below 12 µg/m3 inside all the buses. For all three types of particulate pollutants, in-cabin reductions were higher on freeways than on arterial roadways.
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Contaminación del Aire Interior/prevención & control , Filtración/instrumentación , Vehículos a Motor , Emisiones de Vehículos , Contaminación del Aire Interior/efectos adversos , Niño , Exposición a Riesgos Ambientales/prevención & control , Diseño de Equipo , Filtración/métodos , Humanos , Los Angeles , Tamaño de la Partícula , Material Particulado/efectos adversos , Material Particulado/análisis , Hollín , Transportes , Emisiones de Vehículos/análisis , Emisiones de Vehículos/prevención & controlRESUMEN
Modern passenger vehicles are commonly equipped with cabin air filters but their filtration efficiency for ultrafine particle (UFP) is rather low. Although setting the vehicle ventilation system to recirculation (RC) mode can reduce in-cabin UFPs by â¼ 90%, passenger-exhaled carbon dioxide (CO2) can quickly accumulate inside the cabin. Using outdoor air (OA) mode instead can provide sufficient air exchange to prevent CO2 buildup, but in-cabin UFP concentrations would increase. To overcome this dilemma, we developed a simultaneous mitigation method for UFP and CO2 using high-efficiency cabin air (HECA) filtration in OA mode. Concentrations of UFP and other air pollutants were simultaneously monitored in and out of 12 different vehicles under 3 driving conditions: stationary, on local roadways, and on freeways. Under each experimental condition, data were collected with no filter, in-use original equipment manufacturer (OEM) filter, and two types of HECA filters. The HECA filters offered an average in-cabin UFP reduction of 93%, much higher than the OEM filters (â¼ 50% on average). Throughout the measurements, the in-cabin CO2 concentration remained in the range of 620-930 ppm, significantly lower than the typical level of 2500-4000 ppm observed in the RC mode.
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Filtros de Aire , Contaminación del Aire/prevención & control , Dióxido de Carbono/análisis , Exposición a Riesgos Ambientales/prevención & control , Vehículos a Motor , Tamaño de la Partícula , Contaminantes Atmosféricos/análisis , Conducción de Automóvil , Filtración , Material Particulado/análisis , Hollín/análisis , Factores de Tiempo , VentilaciónRESUMEN
Eon, S., Culard, F., Sy, D., Charlier, M. and Spotheim-Maurizot, M. Radiation Disrupts Protein-DNA Complexes through Damage to the Protein. The lac Repressor-Operator System. Radiat. Res. 156, 110-117 (2001). Binding of a protein to its cognate DNA sequence is a key step in the regulation of gene expression. If radiation damage interferes with protein-DNA recognition, the entire regulation process may be perturbed. We have studied the effect of gamma rays on a model regulatory system, the E. coli lactose repressor-operator complex. We have observed the disruption of the complex upon irradiation in aerated solution. The complex is completely restored by the addition of nonirradiated repressor, but not by the addition of nonirradiated DNA. Thus radiation disrupts the DNA-protein complex by affecting the binding ability of the protein. This interpretation is supported by the dramatic loss of binding ability of a free irradiated repressor toward nonirradiated DNA. Interestingly, the dose necessary for the disruption of the irradiated complex is higher than that for inducing the complete loss of the binding ability of the free irradiated repressor. This may be due to the protection of key amino acids by the bound DNA. As seen from calculations of the accessibility of amino acids to radiolytic OH(.), the protection is due to both masking and conformational effects.
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Proteínas Bacterianas/efectos de la radiación , ADN Bacteriano/química , ADN Bacteriano/efectos de la radiación , Proteínas Represoras/química , Proteínas Represoras/efectos de la radiación , Aminoácidos/química , Proteínas Bacterianas/química , Relación Dosis-Respuesta en la Radiación , Electroforesis en Gel de Poliacrilamida , Escherichia coli , Rayos gamma , Sustancias Macromoleculares , Modelos Moleculares , Unión Proteica/fisiología , Unión Proteica/efectos de la radiación , Estructura Secundaria de Proteína/fisiología , Estructura Terciaria de Proteína/fisiologíaRESUMEN
PURPOSE: To calculate the probability of radiation-induced frank strand breakage (FSB) at each nucleotide in the Escherichia coli lac repressor-lac operator system using a simulation procedure. To compare calculated and experimental results. To asses the contribution of DNA conformational changes and of the masking by the protein to DNA protection by the repressor. MATERIALS AND METHODS: Two structures of the complex were extracted from the PDB databank: crystallography- and NMR-based structures. Calculations were made of the accessibility of the atoms mainly involved in strand breakage (H4' and H5') to O&Hdot; and of the FSB probabilities, along: (1) DNA in the complex; (2) DNA in the complex depleted of the repressor; and (3) a linear DNA having the same sequence. An 80bp fragment bearing the operator was irradiated alone or in presence of the repressor. The relative probabilities of FSB at each nucleotide were determined using sequencing gel electrophoresis. RESULTS: Calculations predict modulation of the accessibility of H4' and H5' atoms and of the probabilities of FSB along the DNA fragments of complexes. This is due to the protein-induced conformational change and to masking by bound protein. The best agreement with the experimental FSB was observed for calculations that use the crystallography-based structure. CONCLUSIONS: For specific DNA-protein complexes, our calculations can predict the protein radiolytic footprints on DNA. They show the significant contribution of the protein-induced DNA conformational change to DNA protection.