Mathematical Modelling of Chemical Diffusion through Skin using Grid-based PSEs

A Problem Solving Environment (PSE) with connections to remote distributed Grid processes is developed. The Grid simulation is itself a parallel process and allows steering of individual or multiple runs of the core computation of chemical diffusion through the stratum corneum, the outer layer of the skin. The effectiveness of this Grid-based approach in improving the quality of the simulation is assessed

Micro-Fluidic Diffusion Coefficient Measurement

A new method for diffusion coefficient measurement applicable to micro-fluidics is pre- sented. The method Iltilizes an analytical model describing laminar dispersion in rect- anglllar ~llicro_channe]s. The Illethod ~vas verified throllgh measllremen~ of fllloresceill diffusivity in water and aqueolls polymer solutions of differing concentration. The diffll- sivity of flllorescein was measlmed as 0.64 x 10-gm2/s in water, 0.49 x 10-gm2/s in the 4 gm/dl dextran solution and 0.38 x 10-9n12/s in the 8 gnl/dl dextran solution

LTA/Poly(1-trimethylsilyl-1-propyne) mixed-matrix membranes for high-temperature CO2/N2 separation

Mixed-matrix membranes (MMM) consisting of poly(1-trimethylsilyl-1-propyne) (PTMSP) as continuous matrix and small-pore LTA-framework zeolites with Si/Al ratios from 1 (commercial zeolite A) to ¥ (ITQ-29) as dispersed phase were prepared by solution casting. The thermal stability of the MMM is as high as that of glassy PTMSP polymer, whose high permeability is maintained even at increasing temperature. The effect of the Si/Al ratio in the zeolite fillers on the membrane performance is observed by the increasing CO2/N2 permselectivity of low-Si/Al ratio zeolite A-based membranes, in comparison with pure silica ITQ-29. The performance of the LTA-type zeolite-PTMSP MMM was adjusted to the modified Maxwell model by estimating the chain immobilization factor and the interphase thickness as a function of temperature, Si/Al ratio, and zeolite loading.Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under project CTQ2012-31229 at the Universidad de Cantabria is gratefully acknowledged. A.F.B. and C.C.C. also thank the MINECO for the Early Stage Researcher (BES2013-064266) and “Ramón y Cajal” (RYC2011-0855) grants, respectively. M.P. and S.V. also gratefully acknowledge the financial support from the Spanish Government (MAT2012-38567-C02-01, Consolider Ingenio 2010-Multicat CSD-2009-00050 and Severo Ochoa SEV-2012-0267)

Formation and aging of incipient thin film wax-oil gels

A fundamental study of the deposition and aging of a thin incipient wax-oil gel that is formed during the flow of waxy oils in cooled pipes was performed. The solubility of high molecular weight paraffins in naphthenic, aromatic or paraffinic solvents is very low and decreases rapidly with decreasing temperature. This property of the paraffins leads to the formation of gels of complex morphology that deposit on the cold walls of the subsea pipelines during the flow of waxy crudes. This deposition reduces the pipe diameter and decreases the flow capacity of the pipe. These wax-oil gels contain a large fraction of oil trapped in a 3-D network structure of the wax crystals that behaves as a porous medium. After the incipient gel is formed, wax molecules continue to diffuse into this structure, thereby increasing its wax content. A model system of wax and oil mixture was used to understand the aging process of the wax-oil gels, which hardens the wax deposit with time. To understand the physics of the aging process for incipient thin-film deposits, a series of laboratory flow loop experiments was performed. The aging process was a counterdiffusion phenomenon with a critical carbon number above which wax molecules diffuse into the gel deposit and below which oil molecules diffuse out of the deposit. The aging rate of the gel deposit depends on the oil flow rate and the wall temperature. A mathematical model developed predicted the growth and wax content of the gel deposit on externally cooled pipe walls. The theory agreed with experiments excellently for thin gels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34241/1/690460517_ftp.pd

Morphological evolution of thick wax deposits during aging

The presence of waxes in crude oil can lead to the formation of wax deposits on the walls of cold subsea pipelines, which restricts flow and can lead to plugging of the pipelines. This problem has recently become more significant as the production wells move further offshore causing the oil to be cooled below the cloud point before reaching shore. Wax deposition was studied in the laboratory under conditions simulating the deposition in a subsea pipeline. Wax deposition is initiated by the precipitation of wax directly on the pipe wall and the formation of a network of' wax crystals (wax-oil gel) with significant amounts of oil trapped in it. Radial diffusion of the wax molecules from the bulk solution to the gel deposit causes it to simultaneously grow and age with time. The wax molecules diffusing into the gel deposit precipitate near the interface resulting in a faster aging rate of the deposit new the interface than that near the wall. This nonuniform aging of the wax deposit causes the evolution of complex morphologies of the wax deposits. The diffusion of wax molecules into the gel matrix was analyzed theoretically during the growth of the wax deposit. This mathematical model predicted the radial variation of the morphology of the wax deposit observed in the laboratory flow loop experiments along with the deposit thickness as a function of time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34242/1/690470103_ftp.pd

Synthesis and characterisation of MOF/ionic liquid/chitosan mixed matrix membranes for CO2/N2 separation

Mixed matrix membranes (MMMs) have been prepared by combining a small amount of highly absorbing non-toxic ionic liquid, [emim][Ac] (IL) (5 wt%), a biopolymer from renewable abundant natural resources, chitosan (CS), and nanometre-sized metal-organic framework (MOF) ZIF-8 or HKUST-1 particles to improve the selectivity of the IL-CS hybrid continuous polymer matrix. The TGA revealed that the thermal stability has been enhanced by the influence of both IL and ZIF-8 or HKUST-1 fillers, while keeping a water content of around 20 wt%, which suggests the potential of such materials for developing high temperature water resistant membranes for CO2 separation. The CO2 and N2 single gas permeation performance was tested at temperatures in the range of 25-50 C, to compare with the previously reported IL-CS hybrid membranes. The best CO2 permeability and CO2/N2 selectivity performance is obtained for 10 wt% ZIF-8 and 5 wt% HKUST-1/IL-CS membranes, as high as 5413 191 Barrer and 11.5, and 4754 1388 Barrer and 19.3, respectively. This is attributed to a better adhesion and smaller particle size of ZIF-8 than HKUST-1 nanoparticles with respect to the IL-CS continuous matrix, as interpreted by Hansen solubility parameters and Maxwell-based models, modified to account for rigidification, pore blockage and crystallinity of the CS matrix, with very accurate predictions.Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) for the project CTQ2012-31229 at the University of Cantabria, and MAT2013-40556-R, at the University of Zaragoza, is gratefully acknowledged. C.C.C. and A.F.B. also thank the MINECO for the Ramon y Cajal contract (RYC-2011-08550) and the post-graduate research grant (BES2013-064266), respectively, at the Universidad de Cantabria. Dr. Sara Sorribas is gratefully thanked for her technical assistance on the XRD, SEM and TEM analyses. The microscopy work was done at the Laboratorio de Microscopias Avanzadas of the Instituto de Nanociencia de Aragon (LMA-INA), and the XRD measurements were carried out at the Servicio General de Apoyo a la Investigacion (SAI) of the Universidad de Zaragoza

A novel approach to modelling water transport and drug diffusion through the stratum corneum

<p>Abstract</p> <p>Background</p> <p>The potential of using skin as an alternative path for systemically administering active drugs has attracted considerable interest, since the creation of novel drugs capable of diffusing through the skin would provide a great step towards easily applicable -and more humane- therapeutic solutions. However, for drugs to be able to diffuse, they necessarily have to cross a permeability barrier: the <it>stratum corneum </it>(SC), the uppermost set of skin layers. The precise mechanism by which drugs penetrate the skin is generally thought to be diffusion of molecules through this set of layers following a "tortuous pathway" around corneocytes, i.e. impermeable dead cells.</p> <p>Results</p> <p>In this work, we simulate water transport and drug diffusion using a three-dimensional porous media model. Our numerical simulations show that diffusion takes place through the SC regardless of the direction and magnitude of the fluid pressure gradient, while the magnitude of the concentrations calculated are consistent with experimental studies.</p> <p>Conclusions</p> <p>Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties.</p

Enhancement of Transport Selectivity through Nano-Channels by Non-Specific Competition

The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecular re-arrangements (such as transition from a ‘closed’ to an ‘open’ state) and do not require a direct input of metabolic energy during transport. Nevertheless, these ‘always open’ channels are highly selective and pass only their cognate molecules, while efficiently excluding all others; indeed, these channels can efficiently transport specific molecules even in the presence of a vast excess of non-specific molecules. Such biological transporters have inspired the creation of artificial nano-channels. These channels can be used as nano-molecular sorters, and can also serve as testbeds for examining modes of biological transport. In this paper, we propose a simple kinetic mechanism that explains how the selectivity of such ‘always open’ channels can be based on the exclusion of non-specific molecules by specific ones, due to the competition for limited space inside the channel. The predictions of the theory account for the behavior of the nuclear pore complex and of artificial nanopores that mimic its function. This theory provides the basis for future work aimed at understanding the selectivity of various biological transport phenomena

Impact of Sarcoplasmic Reticulum Calcium Release on Calcium Dynamics and Action Potential Morphology in Human Atrial Myocytes: A Computational Study

Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca2+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL) ion currents, accounts for the heterogeneity of intracellular Ca2+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR). Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca2+ dynamics: 1) the biphasic increment during the upstroke of the Ca2+ transient resulting from the delay between the peripheral and central SR Ca2+ release, and 2) the relative contribution of SL Ca2+ current and SR Ca2+ release to the Ca2+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca2+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca2+ release sites define the interface between Ca2+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca2+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca2+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca2+ signaling. Thus, the model provides a useful framework for future studies of excitation-contraction coupling in human atrial myocytes