The influence of porosity changes in human epidermal membrane during iontophoresis on the permeability enhancement of a model peptide

Purpose: We tested the hypothesis that the increases in the porosity of the skin during iontophoresis would not significantly increase the transport of peptides due to the small size of electrically induced pores. To investigate this mechanistically, we used human epidermal membrane under constant voltage conditions, applying the Nernst–Planck equation to the transport of a small ionic solute, tetraethylammonium bromide (TEAB), and a model peptide, luteinizing hormone releasing hormone. Methods: Steady-state flux of the drugs was determined under passive conditions and also during iontophoresis using constant DC voltages applied across side-by-side diffusion cells. Electrical conductance measurements were used to monitor the porosity changes that occur during electrical field application. Results: Porosity increases observed in the membrane substantially increased the permeability enhancement of the small ionic solute TEAB. The permeability enhancement was well described by Nernst–Planck model predictions after porosity changes in the membrane were taken into account. Enhancement of luteinizing hormone releasing hormone under identical conditions was much less than TEAB. The porosity increases induced by iontophoresis had little or no effect on the permeability enhancement of the larger molecule. Conclusions: These findings closely parallel those reports that have found electrically induced pores to be significantly smaller than preexisting pores in the human epidermal membrane. The data obtained also support the view that iontophoresis-induced pores, alone, may provide limited benefit for macromolecule transport across the skin.     

Philosophy of the M<Emphasis Type="SmallCaps">ini</Emphasis>Z<Emphasis Type="SmallCaps">inc</Emphasis> challenge

MiniZinc arose as a response to the extended discussion at CP2006 of the need for a standard modelling language for CP. This is a challenging problem, and we believe MiniZinc makes a good attempt to handle the most obvious obstacle: there are hundreds of potential global constraints, most handled by few or no systems. A standard input language for solvers gives us the capability to compare different solvers. Hence, every year since 2008 we have run the MiniZinc Challenge comparing different solvers that support MiniZinc. In this report we discuss the philosophy behind the challenge, why we do it, how we do it, and why we do it that way.     

Imperfection for realistic image synthesis

Creating objects with surface imperfections is accomplished through texture specification and generation techniques. Based on fractal subdivision techniques and relatively simple distribution models, a wide class of surface imperfections may be generated, combined and rendered. The surface effects include scratches, splotches, smudges, corrosion, mould, stains and rust. A rule-based system is used to position the various surface imperfections on the texture map, and a simple natural language interface is used to specify the kinds of imperfections and their generative parameters through adverbs and prepositional phrases. Results along some of the imperfection dimensions are illustrated.