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Michael S Roberts - One of the best experts on this subject based on the ideXlab platform.
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Effect of Vehicles on the Maximum Transepidermal Flux of Similar Size Phenolic Compounds
Pharmaceutical Research, 2013Co-Authors: Qian Bo-zhang, David Liu, Peng Li, Michael S RobertsAbstract:PurposeIn principle, Maximum transepidermal Fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated Maximum Flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varying lipophilicity from polar and lipophilic vehicles.MethodsMaximum Flux and other skin transport parameters through human epidermis were obtained from lipophilic vehicles (mineral oil (MO) and isopropyl myristate (IPM)) and compared with values from water and propylene glycol (PG)-water solutions. Solvent uptake and changes in stratum corneum infrared spectroscopy and multiphoton microscopy imaging were also investigated.ResultsMaximum Fluxes for MO and water were similar but IPM has a higher value for more polar phenols due to a higher diffusivity and PG-water had a higher Flux due to higher solubility in the stratum corneum. Whereas Maximum Flux for various phenols was directly related to solubility in the stratum corneum independent of vehicle, increasing phenol lipophilicity increased and decreased permeability coefficient for aqueous solvents and lipophilic solvents, respectively.ConclusionThe Maximum Fluxes for phenols with a similar molecular size and varying lipophilicity were comparable between water and MO vehicles but higher for IPM and PG-water mixtures.
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Effect of vehicles on the Maximum transepidermal Flux of similar size phenolic compounds.
Pharmaceutical research, 2012Co-Authors: Qian Bo-zhang, David Liu, Michael S RobertsAbstract:Purpose In principle, Maximum transepidermal Fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated Maximum Flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varying lipophilicity from polar and lipophilic vehicles.
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Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules
Pharmaceutical research, 2009Co-Authors: Qian Bo-zhang, Jeffrey E. Grice, Owen G. Jepps, Guangji Wang, Michael S RobertsAbstract:Purpose The Maximum Flux of solutes penetrating the epidermis has been known to depend predominantly on solute molecular weight. Here we sought to establish the mechanistic dependence of Maximum Flux on other solute physicochemical parameters.
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molecular size as the main determinant of solute Maximum Flux across the skin
Journal of Investigative Dermatology, 2004Co-Authors: Beatrice M Magnusson, Yuri German Anissimov, Sheree E Cross, Michael S RobertsAbstract:One of the most important determinants of dermatological and systemic penetration after topical application is the delivery or Flux of solutes into or through the skin. The Maximum dose of solute able to be delivered over a given period of time and area of application is defined by its Maximum Flux (J max , mol per cm 2 per h) from a given vehicle. In this work, J max values from aqueous solution across human skin were acquired or estimated from experimental data and correlated with solute physicochemical properties. Whereas epidermal permeability coefficients (k p ) are optimally correlated to solute octanol–water partition coefficient (K ow ) and molecular weight (MW) was found to be the dominant determinant of J max for this literature data set: log J max =-3.90–0.0190MW (n=87, r 2 =0.847, p oc ) was also a determinant, but improvement in the regression by the addition of log S oc was small (r 2 increased to 0.856). Addition of other physicochemical parameters to MW by forward stepwise regression only marginally improved the regression with a melting point (Mpt) term (r 2 =0.879) and then hydrogen bonding acceptor capability (H a ) (r 2 =0.917) is significant. Validation of the equation above was carried with a number of other data sets: an aqueous vehicle with full- and split-thickness skin (r 2 =0.784, n=56), some pure solutes (r 2 =0.537, n=34), an aqueous vehicle with ionizable solutes (r 2 =0.282, n=54) and solutes from a propylene glycol vehicle (r 2 =0.484, n=36). An analysis of the entire database gave the equation log J max =-4.52–0.0141MW (n=278, r 2 =0.688, p a increasing r 2 to 0.760 (n=269). Separate analysis of full- and split-thickness skin data confirmed that the dermal resistance term had only a marginal effect on overall J max . Application of the latter model to an in vivo situation where the dermal capillary bed is slightly below the epidermal–dermal junction revealed that the dermal resistance term was unnecessary for in vivo predictions for most solutes.
Robert D. Skeel - One of the best experts on this subject based on the ideXlab platform.
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A minimization principle for transition paths of Maximum Flux for collective variables
Theoretical chemistry accounts, 2016Co-Authors: Robert D. Skeel, Ruijun Zhao, Carol Beth PostAbstract:Considered is the construction of transition paths of conformational changes for proteins and other macromolecules, using methods that do not require the generation of dynamics trajectories. Special attention is given to the use of a reduced set of collective variables for describing such paths. A favored way to define transition paths is to seek channels through the transition state having cross sections with a high reactive Flux (density of last hitting points of reactive trajectories). Given here is a formula for reactive Flux that is independent of the parameterization of “collective variable space.” This formula is needed for the principal curve of the reactive Flux (as in the revised finite temperature string method) and for the Maximum Flux transition (MaxFlux) path. Additionally, a resistance functional is derived for narrow tubes, which when minimized yields a MaxFlux path. A strategy for minimization is outlined in the spirit of the string method. Finally, alternative approaches based on determining trajectories of high probability are considered, and it is observed that they yield paths that depend on the parameterization of collective variable space, except in the case of zero temperature, where such a path coincides with a MaxFlux path.
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Maximum Flux transition paths of conformational change
Journal of Chemical Theory and Computation, 2010Co-Authors: Ruijun Zhao, Juanfang Shen, Robert D. SkeelAbstract:Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the “center” of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor “foliates” the transition region into a set of isocommittors. The Maximum Flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. This path is based on the same principle as the minimum resistance path of Berkowitz et al (1983), but it has two advantages: (i) the path is invariant with respect to a change of coordinates in collective variable space and (ii) the differential equations that define the path are simpler. It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.
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Maximum Flux Transition Paths of Conformational Change
Journal of chemical theory and computation, 2010Co-Authors: Ruijun Zhao, Juanfang Shen, Robert D. SkeelAbstract:Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the "center" of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor "foliates" the transition region into a set of isocommittors. The Maximum Flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. (This path is different from that of the MaxFlux method of Huo and Straub.) It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.
Qian Bo-zhang - One of the best experts on this subject based on the ideXlab platform.
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Effect of Vehicles on the Maximum Transepidermal Flux of Similar Size Phenolic Compounds
Pharmaceutical Research, 2013Co-Authors: Qian Bo-zhang, David Liu, Peng Li, Michael S RobertsAbstract:PurposeIn principle, Maximum transepidermal Fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated Maximum Flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varying lipophilicity from polar and lipophilic vehicles.MethodsMaximum Flux and other skin transport parameters through human epidermis were obtained from lipophilic vehicles (mineral oil (MO) and isopropyl myristate (IPM)) and compared with values from water and propylene glycol (PG)-water solutions. Solvent uptake and changes in stratum corneum infrared spectroscopy and multiphoton microscopy imaging were also investigated.ResultsMaximum Fluxes for MO and water were similar but IPM has a higher value for more polar phenols due to a higher diffusivity and PG-water had a higher Flux due to higher solubility in the stratum corneum. Whereas Maximum Flux for various phenols was directly related to solubility in the stratum corneum independent of vehicle, increasing phenol lipophilicity increased and decreased permeability coefficient for aqueous solvents and lipophilic solvents, respectively.ConclusionThe Maximum Fluxes for phenols with a similar molecular size and varying lipophilicity were comparable between water and MO vehicles but higher for IPM and PG-water mixtures.
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Effect of vehicles on the Maximum transepidermal Flux of similar size phenolic compounds.
Pharmaceutical research, 2012Co-Authors: Qian Bo-zhang, David Liu, Michael S RobertsAbstract:Purpose In principle, Maximum transepidermal Fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated Maximum Flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varying lipophilicity from polar and lipophilic vehicles.
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Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules
Pharmaceutical research, 2009Co-Authors: Qian Bo-zhang, Jeffrey E. Grice, Owen G. Jepps, Guangji Wang, Michael S RobertsAbstract:Purpose The Maximum Flux of solutes penetrating the epidermis has been known to depend predominantly on solute molecular weight. Here we sought to establish the mechanistic dependence of Maximum Flux on other solute physicochemical parameters.
Lihe Chai - One of the best experts on this subject based on the ideXlab platform.
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a spatio temporal analysis of low carbon development in china s 30 provinces a perspective on the Maximum Flux principle
Ecological Indicators, 2018Co-Authors: Zhenni Chen, Guo Zhu Mao, Lihe ChaiAbstract:Abstract This study constructed a multidimensional indicator system to evaluate low carbon development of the whole country and 30 provinces in China from 2003 to 2013, based on the Maximum Flux principle, which reflects the dynamic evolutionary process of low carbon development. Then k-means cluster analysis was used to classify 30 provinces into three grades (highest, medium and lowest) according to their average low carbon development level. Finally, Moran’s I was used to investigate the spatial correlation of low carbon development in China. The simulation results show that the national low carbon development level increased with fluctuations from 2008 as the nation paid high attention to low carbon development, and the provincial low carbon development is unbalanced, which is closely related to the socioeconomic conditions, resources endowment and geographical locations. For each province, the development level of different evaluative dimension grows unequally. For each grade, the provinces of highest grade have good performance in energy and environmental dimensions and the provinces of medium grade have good performance in society or the economic dimension, but the provinces of lowest grade have a lower development level in all dimensions. There is significant positive spatial dependence and cluster characteristics in low carbon development in China. In general, high-level provinces are distributed in southern China while low-level provinces are mainly located in northern China. The high-level provinces should perform their demonstrating functions and promote low carbon development in their surrounding areas.
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A spatio-temporal analysis of low carbon development in China’s 30 provinces: A perspective on the Maximum Flux principle
Ecological Indicators, 2018Co-Authors: Zhenni Chen, Guo Zhu Mao, Lihe ChaiAbstract:Abstract This study constructed a multidimensional indicator system to evaluate low carbon development of the whole country and 30 provinces in China from 2003 to 2013, based on the Maximum Flux principle, which reflects the dynamic evolutionary process of low carbon development. Then k-means cluster analysis was used to classify 30 provinces into three grades (highest, medium and lowest) according to their average low carbon development level. Finally, Moran’s I was used to investigate the spatial correlation of low carbon development in China. The simulation results show that the national low carbon development level increased with fluctuations from 2008 as the nation paid high attention to low carbon development, and the provincial low carbon development is unbalanced, which is closely related to the socioeconomic conditions, resources endowment and geographical locations. For each province, the development level of different evaluative dimension grows unequally. For each grade, the provinces of highest grade have good performance in energy and environmental dimensions and the provinces of medium grade have good performance in society or the economic dimension, but the provinces of lowest grade have a lower development level in all dimensions. There is significant positive spatial dependence and cluster characteristics in low carbon development in China. In general, high-level provinces are distributed in southern China while low-level provinces are mainly located in northern China. The high-level provinces should perform their demonstrating functions and promote low carbon development in their surrounding areas.
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ICNC - Maximum Flux principle and simulation on urban sustainable development
2012 8th International Conference on Natural Computation, 2012Co-Authors: Hongxin Cheng, Xiaonan Wang, Long Wang, Xingshu Liu, Lihe ChaiAbstract:City is a complex, evolutionary and organic whole. The sustainable development problems of organic urban systems cannot be resolved just using modern science grounded upon reductionism, in which city seems to have to be gradually divided into many mechanical world reality as particles in physics or compound in chemistry. The new information reality for world is proposed in this paper, by which a universal ζ field dynamical equation is derived by Maximum Flux principle and new numerical method on sustainable development of organic urban system is then established, which can not only provide a new unified paradigm for urban systems, but also be instructive in rigorous practical evaluation, planning, regulation and control on urban engineering.
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An Etrophication Model for Lake Based on Maximum Flux Principle for Waihai of Dianchi Lake
Advanced Materials Research, 2011Co-Authors: Hong Mei Wang, Guo Zhu Mao, Shu Zhang, Hui Bin Du, Wei Dai, Lihe ChaiAbstract:The aquatic ecosystem of lake is a complex open systems, taking account of the shortcomings of available eutrophication models for water quality, this study based on the principles of Maximum Flux selects Waihai as the object, we apply complex systems analysis to construct eutropication model which is suitable for local conditions and select a larger time scale and control parameters to simulate the eutrophication status to find out the main factors and to put forward reasonable proposals for giving out optimal control techniques. This model can be expanded in time scale, spatial scale and the number of parameters, while the difficulty of calculation and analysis will not be increased.
Ruijun Zhao - One of the best experts on this subject based on the ideXlab platform.
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A minimization principle for transition paths of Maximum Flux for collective variables
Theoretical chemistry accounts, 2016Co-Authors: Robert D. Skeel, Ruijun Zhao, Carol Beth PostAbstract:Considered is the construction of transition paths of conformational changes for proteins and other macromolecules, using methods that do not require the generation of dynamics trajectories. Special attention is given to the use of a reduced set of collective variables for describing such paths. A favored way to define transition paths is to seek channels through the transition state having cross sections with a high reactive Flux (density of last hitting points of reactive trajectories). Given here is a formula for reactive Flux that is independent of the parameterization of “collective variable space.” This formula is needed for the principal curve of the reactive Flux (as in the revised finite temperature string method) and for the Maximum Flux transition (MaxFlux) path. Additionally, a resistance functional is derived for narrow tubes, which when minimized yields a MaxFlux path. A strategy for minimization is outlined in the spirit of the string method. Finally, alternative approaches based on determining trajectories of high probability are considered, and it is observed that they yield paths that depend on the parameterization of collective variable space, except in the case of zero temperature, where such a path coincides with a MaxFlux path.
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Maximum Flux transition paths of conformational change
Journal of Chemical Theory and Computation, 2010Co-Authors: Ruijun Zhao, Juanfang Shen, Robert D. SkeelAbstract:Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the “center” of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor “foliates” the transition region into a set of isocommittors. The Maximum Flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. This path is based on the same principle as the minimum resistance path of Berkowitz et al (1983), but it has two advantages: (i) the path is invariant with respect to a change of coordinates in collective variable space and (ii) the differential equations that define the path are simpler. It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.
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Maximum Flux Transition Paths of Conformational Change
Journal of chemical theory and computation, 2010Co-Authors: Ruijun Zhao, Juanfang Shen, Robert D. SkeelAbstract:Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the "center" of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor "foliates" the transition region into a set of isocommittors. The Maximum Flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. (This path is different from that of the MaxFlux method of Huo and Straub.) It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.