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Philip M. Cook - One of the best experts on this subject based on the ideXlab platform.
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Quantitative structure-mesothelioma potency model optimization for complex mixtures of Elongated Particles in rat pleura: A retrospective study.
Journal of Toxicology and Environmental Health-part B-critical Reviews, 2016Co-Authors: Philip M. Cook, Joseph Swintek, Timothy D. Dawson, Mathew A. Etterson, David Chapman, Dale J HoffAbstract:ABSTRACTCancer potencies of mineral and synthetic Elongated Particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of Elongated Particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual Elongated Particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the Elongated Particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin Elongated particl...
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Quantitative structure-mesothelioma potency model optimization for complex mixtures of Elongated Particles in rat pleura: A retrospective study.
Journal of Toxicology and Environmental Health Part B, 2016Co-Authors: Philip M. Cook, Joseph Swintek, Timothy D. Dawson, Mathew A. Etterson, David Chapman, Dale J HoffAbstract:Cancer potencies of mineral and synthetic Elongated Particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of Elongated Particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual Elongated Particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the Elongated Particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin Elongated Particles significantly degrades the resultant Particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of Elongated Particles with aspect ratios less than 8 and lengths greater than 80 µm. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short Elongated Particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short Elongated Particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio Elongated Particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence.
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In vitro determinants of asbestos fiber toxicity: effect on the relative toxicity of Libby amphibole in primary human airway epithelial cells
Particle and Fibre Toxicology, 2014Co-Authors: Kelly E Duncan, Stephen H. Gavett, Philip M. Cook, Lisa A Dailey, Ron K Mahoney, Andrew J Ghio, Victor L. Roggli, Robert B DevlinAbstract:Background An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative Particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples. Methods Primary human airway epithelial cells (HAEC) were exposed to two different LA samples as well as standard amphibole reference samples. Analysis of the samples included a complete Particle size distribution analysis, calculation of surface area by electron microscopy and by gas adsorption and quantification of surface-conjugated iron and hydroxyl radical production by the fibers. Interleukin-8 mRNA levels were quantified by qRT-PCR to measure relative pro-inflammatory response induced in HAEC in response to amphibole fiber exposure. The relative contribution of key physicochemical determinants on the observed pro-inflammatory response were also evaluated. Results The RTI amosite reference sample contained the longest fibers and demonstrated the greatest potency at increasing IL-8 transcript levels when evaluated on an equal mass basis. The two LA samples and the UICC amosite reference sample consisted of similar Particle numbers per milligram as well as similar Particle size distributions and induced comparable levels of IL-8 mRNA. A strong correlation was observed between the Elongated Particle (aspect ratio ≥3:1) dose metrics of length and external surface area. Expression of the IL-8 data with respect to either of these metrics eliminated the differential response between the RTI amosite sample and the other samples that was observed when HAEC were exposed on an equal mass basis. Conclusions On an equal mass basis, LA is as potent as the UICC amosite reference sample at inducing a pro-inflammatory response in HAEC but is less potent than the RTI amosite sample. The results of this study show that the Particle length and Particle surface area are highly correlated metrics that contribute significantly to the toxicological potential of these amphibole samples with respect to the inflammogenic response induced in airway epithelial cells.
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morphological and chemical mechanisms of Elongated mineral Particle toxicities
Journal of Toxicology and Environmental Health-part B-critical Reviews, 2011Co-Authors: Ann E Aust, Philip M. Cook, Ronald F DodsonAbstract:Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable Elongated mineral Particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos Particle toxicity involve two facets for each Particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/Elongated Particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable Elongated mineral Particles.
Yasutaro Uesaka - One of the best experts on this subject based on the ideXlab platform.
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computer simulation of magnetization reversal of cubic thin and Elongated Particles effect of method of calculating demagnetizing field
Journal of Magnetism and Magnetic Materials, 1995Co-Authors: Yasutaro Uesaka, Yoshinobu Nakatani, N HayashiAbstract:Abstract Computer simulation was used to investigate the dependence of the switching fields and magnetization reversal mechanisms of cubic, thin and Elongated Particles on the angle of applied fields. In the simulation, the Particles were divided or not divided into cells. The Particles switch mostly in the coherent rotation mode. However, the switching field of the thin or Elongated Particle obtained by dividing the Particle into cells does not coincide with the switching field of the Particle obtained without dividing the Particle into cells, except when a field is applied in the largest plane of a thin Particle with the intrinsic uniaxial easy axis in the plane. The non-coincidence of the switching fields is due to the improper calculation method of the demagnetizing field. If the average demagnetizing fields, which are obtained by dividing the Particles into cubic cells, are used in the undivided Particle cases, the switching fields of the undivided Particles coincide with the switching fields of the divided Particles.
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Computer simulation of magnetization reversal: The effect of shape and uniaxial crystalline anisotropy
Journal of Applied Physics, 1991Co-Authors: Geoffrey W. D. Spratt, Yoshinobu Nakatani, Yasutaro Uesaka, Nobuo HayashiAbstract:The Landau–Lifshitz–Gilbert equation has been used to compare the hysteresis loops and magnetization‐reversal mechanisms of a cubic Particle, with uniaxial crystalline anisotropy, and a 2:1‐aspect‐ratio Elongated Particle. The switching fields of these Particles were 700 Oe. The cubic Particle exhibited a square hysteresis loop, but the Elongated Particle had a nonsquare hysteresis loop due to the tilting of spins in the surface layers. Magnetization reversal for the Elongated Particle was initiated at the surface layers. For the cubic Particle the reversal was initiated at an edge of the Particle and spread through to the central elements. Differences between the hysteresis loops and reversal mechanisms, for the different Particles, are attributed to the different nature of the magnetic anisotropies.
N Hayashi - One of the best experts on this subject based on the ideXlab platform.
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computer simulation of magnetization reversal of cubic thin and Elongated Particles effect of method of calculating demagnetizing field
Journal of Magnetism and Magnetic Materials, 1995Co-Authors: Yasutaro Uesaka, Yoshinobu Nakatani, N HayashiAbstract:Abstract Computer simulation was used to investigate the dependence of the switching fields and magnetization reversal mechanisms of cubic, thin and Elongated Particles on the angle of applied fields. In the simulation, the Particles were divided or not divided into cells. The Particles switch mostly in the coherent rotation mode. However, the switching field of the thin or Elongated Particle obtained by dividing the Particle into cells does not coincide with the switching field of the Particle obtained without dividing the Particle into cells, except when a field is applied in the largest plane of a thin Particle with the intrinsic uniaxial easy axis in the plane. The non-coincidence of the switching fields is due to the improper calculation method of the demagnetizing field. If the average demagnetizing fields, which are obtained by dividing the Particles into cubic cells, are used in the undivided Particle cases, the switching fields of the undivided Particles coincide with the switching fields of the divided Particles.
Dale J Hoff - One of the best experts on this subject based on the ideXlab platform.
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Quantitative structure-mesothelioma potency model optimization for complex mixtures of Elongated Particles in rat pleura: A retrospective study.
Journal of Toxicology and Environmental Health-part B-critical Reviews, 2016Co-Authors: Philip M. Cook, Joseph Swintek, Timothy D. Dawson, Mathew A. Etterson, David Chapman, Dale J HoffAbstract:ABSTRACTCancer potencies of mineral and synthetic Elongated Particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of Elongated Particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual Elongated Particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the Elongated Particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin Elongated particl...
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Quantitative structure-mesothelioma potency model optimization for complex mixtures of Elongated Particles in rat pleura: A retrospective study.
Journal of Toxicology and Environmental Health Part B, 2016Co-Authors: Philip M. Cook, Joseph Swintek, Timothy D. Dawson, Mathew A. Etterson, David Chapman, Dale J HoffAbstract:Cancer potencies of mineral and synthetic Elongated Particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of Elongated Particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual Elongated Particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the Elongated Particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin Elongated Particles significantly degrades the resultant Particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of Elongated Particles with aspect ratios less than 8 and lengths greater than 80 µm. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short Elongated Particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short Elongated Particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio Elongated Particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence.
Yoshinobu Nakatani - One of the best experts on this subject based on the ideXlab platform.
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computer simulation of magnetization reversal of cubic thin and Elongated Particles effect of method of calculating demagnetizing field
Journal of Magnetism and Magnetic Materials, 1995Co-Authors: Yasutaro Uesaka, Yoshinobu Nakatani, N HayashiAbstract:Abstract Computer simulation was used to investigate the dependence of the switching fields and magnetization reversal mechanisms of cubic, thin and Elongated Particles on the angle of applied fields. In the simulation, the Particles were divided or not divided into cells. The Particles switch mostly in the coherent rotation mode. However, the switching field of the thin or Elongated Particle obtained by dividing the Particle into cells does not coincide with the switching field of the Particle obtained without dividing the Particle into cells, except when a field is applied in the largest plane of a thin Particle with the intrinsic uniaxial easy axis in the plane. The non-coincidence of the switching fields is due to the improper calculation method of the demagnetizing field. If the average demagnetizing fields, which are obtained by dividing the Particles into cubic cells, are used in the undivided Particle cases, the switching fields of the undivided Particles coincide with the switching fields of the divided Particles.
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Computer simulation of magnetization reversal: The effect of shape and uniaxial crystalline anisotropy
Journal of Applied Physics, 1991Co-Authors: Geoffrey W. D. Spratt, Yoshinobu Nakatani, Yasutaro Uesaka, Nobuo HayashiAbstract:The Landau–Lifshitz–Gilbert equation has been used to compare the hysteresis loops and magnetization‐reversal mechanisms of a cubic Particle, with uniaxial crystalline anisotropy, and a 2:1‐aspect‐ratio Elongated Particle. The switching fields of these Particles were 700 Oe. The cubic Particle exhibited a square hysteresis loop, but the Elongated Particle had a nonsquare hysteresis loop due to the tilting of spins in the surface layers. Magnetization reversal for the Elongated Particle was initiated at the surface layers. For the cubic Particle the reversal was initiated at an edge of the Particle and spread through to the central elements. Differences between the hysteresis loops and reversal mechanisms, for the different Particles, are attributed to the different nature of the magnetic anisotropies.