Effect of vehicle pretreatment on the flux, retention, and diffusion of topically applied penetrants in vitro

Purpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log K-oct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm(3))(1/2). Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log K-oct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

A reduced load approximation accounting for link interactions in a loss network

This paper is concerned with evaluating the performance of loss networks. Accurate determination of loss network performance can assist in the design and dimen- sioning of telecommunications networks. However, exact determination can be difficult and generally cannot be done in reasonable time. For these reasons there is much interest in developing fast and accurate approximations. We develop a reduced load approximation that improves on the famous Erlang fixed point approximation (EFPA) in a variety of circumstances. We illustrate our results with reference to a range of networks for which the EFPA may be expected to perform badly.

Surface diffusion of strongly adsorbing vapors in activated carbon by a differential permeation method

Conventional methods to determine surface diffusion of adsorbed molecules are proven to be inadequate for strongly adsorbing vapors on activated carbon. Knudsen diffusion permeability (B-k) for strongly adsorbing vapors cannot be directly estimated from that of inert gases such as helium. In this paper three models are considered to elucidate the mechanism of surface diffusion in activated carbon. The transport mechanism in all three models is a combination of Knudsen diffusion, viscous flow and surface diffusion. The collision reflection factor f (which is the fraction of molecules undergoing collision to the solid surface over reflection from the surface) of the Knudsen diffusivity is assumed to be a function of loading. It was found to be 1.79 in the limit of zero loading, and decreases as loading increases. The surface diffusion permeability increases sharply at very low pressures and then starts to decrease after it has reached a maximum (B(mum)s) at a threshold pressure. The initial rapid increase in the total permeability is mainly attributed to surface diffusion. Interestingly the B(mum)s for all adsorbates appear at the same volumetric adsorbed phase concentration, suggesting that the volume of adsorbed molecules may play an important role in the surface diffusion mechanism in activated carbon. (C) 2003 Elsevier Ltd. All rights reserved.

Hydrodynamic origin of diffusion in nanopores

We study the transport of a subcritical Lennard-Jones fluid in a cylindrical nanopore, using a combination of equilibrium and nonequilibrium as well as dual control volume grand canonical molecular dynamics methods. We show that all three techniques yield the same value of the transport coefficient for diffusely reflecting pore walls, even in the presence of viscous transport. We also demonstrate that the classical Knudsen mechanism is not manifested, and that a combination of viscous flow and momentum exchange at the pore wall governs the transport over a wide range of densities.

Automatic segmentation and 3D feature extraction of protein aggregates in Caenorhabditis Elegans

In the last years, it has become increasingly clear that neurodegenerative diseases involve protein aggregation, a process often used as disease progression readout and to develop therapeutic strategies. This work presents an image processing tool to automatic segment, classify and quantify these aggregates and the whole 3D body of the nematode Caenorhabditis Elegans. A total of 150 data set images, containing different slices, were captured with a confocal microscope from animals of distinct genetic conditions. Because of the animals’ transparency, most of the slices pixels appeared dark, hampering their body volume direct reconstruction. Therefore, for each data set, all slices were stacked in one single 2D image in order to determine a volume approximation. The gradient of this image was input to an anisotropic diffusion algorithm that uses the Tukey’s biweight as edge-stopping function. The image histogram median of this outcome was used to dynamically determine a thresholding level, which allows the determination of a smoothed exterior contour of the worm and the medial axis of the worm body from thinning its skeleton. Based on this exterior contour diameter and the medial animal axis, random 3D points were then calculated to produce a volume mesh approximation. The protein aggregations were subsequently segmented based on an iso-value and blended with the resulting volume mesh. The results obtained were consistent with qualitative observations in literature, allowing non-biased, reliable and high throughput protein aggregates quantification. This may lead to a significant improvement on neurodegenerative diseases treatment planning and interventions prevention

Modeling the Diffusion of Energy Performance Contracting

The Portuguese Energy Policy considers the development of a commercially viable and competitive market for energy performance contracting (EPC) as a main mechanism to achieve the objectives of energy efficiency improvement. This paper proposes a study to investigate how to achieve widespread adoption of energy performance contracting by means of system dynamics modelling and simulation. To explore and gather insights on this question, a system dynamics model representing the system of the Portuguese EPC market at industry level will be created. The simulation of that model will provide a helpful basis for analysing and explaining the development of key variables, and accelerating learning on the managerial, organizational and political adaptation processes that foster the diffusion of EPC adoption. The first phase of this research project aims at identifying and analysing the key factors and critical cause-effect relations that drive the adoption of EPC. With this purpose, a qualitative content analysis on relevant documents was performed and a set of interviews was conducted. That data was analysed to capture the critical variables and its interrelation to formulate a preliminary representation of the system structure as stock and flow diagrams.

Microscopic Theory of Anchoring Transitions at the Surfaces of Pure Liquid-Crystals and their Mixtures .1. The Fowler Approximation

We have generalized earlier work on anchoring of nematic liquid crystals by Sullivan, and Sluckin and Poniewierski, in order to study transitions which may occur in binary mixtures of nematic liquid crystals as a function of composition. Microscopic expressions have been obtained for the anchoring energy of (i) a liquid crystal in contact with a solid aligning surface; (ii) a liquid crystal in contact with an immiscible isotropic medium; (iii) a liquid crystal mixture in contact with a solid aligning surface. For (iii), possible phase diagrams of anchoring angle versus dopant concentration have been calculated using a simple liquid crystal model. These exhibit some interesting features including re-entrant conical anchoring, for what are believed to be realistic values of the molecular parameters. A way of relaxing the most drastic approximation implicit in the above approach is also briefly discussed.

Radiatively induced Lorentz and CPT violation in Schwinger constant field approximation

The Schwinger proper-time method is an effective calculation method, explicitly gauge-invariant and nonperturbative. We make use of this method to investigate the radiatively induced Lorentz- and CPT-violating effects in quantum electrodynamics when an axial-vector interaction term is introduced in the fermionic sector. The induced Lorentz- and CPT-violating Chern-Simons term coincides with the one obtained using a covariant derivative expansion but differs from the result usually obtained in other regularization schemes. A possible ambiguity in the approach is also discussed. (C) 2001 Published by Elsevier Science B.V.

A class of singular first order differential equations with applications in reaction-diffusion

Agências Financiadoras: FCT e MIUR

Influence of network effects on the diffusion of information systems: the case of open source

Doutoramento em Gestão

Effects of international diffusion of a general purpose technology on wage inequality

This paper studies the effects of the diffusion of a General Purpose Technology (GPT) that spreads first within the developed North country of its origin, and then to a developing South country. In the developed general equilibrium growth model, each final good can be produced by one of two technologies. Each technology is characterized by a specific labor complemented by a specific set of intermediate goods, which are enhanced periodically by Schumpeterian R&D activities. When quality reaches a threshold level, a GPT arises in one of the technologies and spreads first to the other technology within the North. Then, it propagates to the South, following a similar sequence. Since diffusion is not even, neither intra- nor inter-country, the GPT produces successive changes in the direction of technological knowledge and in inter- and intra-country wage inequality. Through this mechanism the different observed paths of wage inequality can be accommodated.

Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

Optimal approximation of fractional derivatives through discrete-time fractions using genetic algorithms

This study addresses the optimization of rational fraction approximations for the discrete-time calculation of fractional derivatives. The article starts by analyzing the standard techniques based on Taylor series and Padé expansions. In a second phase the paper re-evaluates the problem in an optimization perspective by tacking advantage of the flexibility of the genetic algorithms.

Travelling wave profiles in some models with nonlinear diffusion

We study some properties of the monotone solutions of the boundary value problem (p(u'))' - cu' + f(u) = 0, u(-infinity) = 0, u(+infinity) = 1, where f is a continuous function, positive in (0, 1) and taking the value zero at 0 and 1, and P may be an increasing homeomorphism of (0, 1) or (0, +infinity) onto [0, +infinity). This problem arises when we look for travelling waves for the reaction diffusion equation partial derivative u/partial derivative t = partial derivative/partial derivative x [p(partial derivative u/partial derivative x)] + f(u) with the parameter c representing the wave speed. A possible model for the nonlinear diffusion is the relativistic curvature operator p(nu)= nu/root 1-nu(2). The same ideas apply when P is given by the one- dimensional p- Laplacian P(v) = |v|(p-2)v. In this case, an advection term is also considered. We show that, as for the classical Fisher- Kolmogorov- Petrovski- Piskounov equations, there is an interval of admissible speeds c and we give characterisations of the critical speed c. We also present some examples of exact solutions. (C) 2014 Elsevier Inc. All rights reserved.

Fractional control of heat diffusion systems

The concept of differentiation and integration to non-integer order has its origins in the seventeen century. However, only in the second-half of the twenty century appeared the first applications related to the area of control theory. In this paper we consider the study of a heat diffusion system based on the application of the fractional calculus concepts. In this perspective, several control methodologies are investigated and compared. Simulations are presented assessing the performance of the proposed fractional-order algorithms.