A two-dimensional mathematical model of percutaneous drug absorption

Background When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface. Methods Though a simple one-dimensional model is often useful to describe percutaneous drug absorption, it may be better represented by multi-dimensional models. A two-dimensional mathematical model is developed for percutaneous absorption of a drug, which may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. This model consists of a linear second-order parabolic equation with appropriate initial conditions and boundary conditions. These boundary conditions are of Dirichlet type, Neumann type or Robin type. A finite-difference method which maintains second-order accuracy in space along the boundary, is developed to solve the parabolic equation. Extrapolation in time is applied to improve the accuracy in time. Solution of the parabolic equation gives the concentration of the drug in the skin at a given time. Results Simulation of the numerical methods described is carried out with various values of the parameter r. The illustrations are given in the form of figures. Conclusion Based on the values of r, conclusions are drawn about (1) the flow rate of the drug, (2) the flux and the cumulative amount of drug eliminated into the receptor cell, (3) the steady-state value of the flux, (4) the time to reach the steady-state value of the flux and (5) the optimal value of r, which gives the maximum absorption of the drug. The paper gives valuable information which can be obtained by this two-dimensional model, that cannot be obtained with one-dimensional models. Thus this model improves upon the much simpler one-dimensional models. Some future directions of the work based on this model and the one-dimensional non-linear models that exist in the literature, are also discussed

β-Arrestin-2 regulates the development of allergic asthma

Asthma is a chronic inflammatory disorder of the airways that is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. Migration of Th2 cells to the lung is key to their inflammatory function and is regulated in large part by chemokine receptors, members of the seven-membrane-spanning receptor family. It has been reported recently that T cells lacking β-arrestin-2, a G protein-coupled receptor regulatory protein, demonstrate impaired migration in vitro. Here we show that allergen-sensitized mice having a targeted deletion of the β-arrestin-2 gene do not accumulate T lymphocytes in their airways, nor do they demonstrate other physiological and inflammatory features characteristic of asthma. In contrast, the airway inflammatory response to LPS, an event not coordinated by Th2 cells, is fully functional in mice lacking β-arrestin-2. β-arrestin-2-deficient mice demonstrate OVA-specific IgE responses, but have defective macrophage-derived chemokine-mediated CD4+ T cell migration to the lung. This report provides the first evidence that β-arrestin-2 is required for the manifestation of allergic asthma. Because β-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, novel therapies focused on this protein may prove useful in the treatment of asthma

In the Shadow of the Transiting Disk: Imaging epsilon Aurigae in Eclipse

Eclipses of the single-line spectroscopic binary star, epsilon Aurigae, provide an opportunity to study the poorly-defined companion. We used the MIRC beam combiner on the CHARA array to create interferometric images during eclipse ingress. Our results demonstrate that the eclipsing body is a dark disk that is opaque and tilted, and therefore exclude alternative models for the system. These data constrain the geometry and masses of the components, providing evidence that the F-star is not a massive supergiant star.Comment: As submitted to Nature. Published in Nature April 8, 2010

Experimental realisation of Shor's quantum factoring algorithm using qubit recycling

Quantum computational algorithms exploit quantum mechanics to solve problems exponentially faster than the best classical algorithms. Shor's quantum algorithm for fast number factoring is a key example and the prime motivator in the international effort to realise a quantum computer. However, due to the substantial resource requirement, to date, there have been only four small-scale demonstrations. Here we address this resource demand and demonstrate a scalable version of Shor's algorithm in which the n qubit control register is replaced by a single qubit that is recycled n times: the total number of qubits is one third of that required in the standard protocol. Encoding the work register in higher-dimensional states, we implement a two-photon compiled algorithm to factor N=21. The algorithmic output is distinguishable from noise, in contrast to previous demonstrations. These results point to larger-scale implementations of Shor's algorithm by harnessing scalable resource reductions applicable to all physical architectures.Comment: 7 pages, 3 figure

Stringy Stability of Charged Dilaton Black Holes with Flat Event Horizon

Electrically charged black holes with flat event horizon in anti-de Sitter space have received much attention due to various applications in Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence, from modeling the behavior of quark-gluon plasma to superconductor. Crucial to the physics on the dual field theory is the fact that when embedded in string theory, black holes in the bulk may become vulnerable to instability caused by brane pair-production. Since dilaton arises naturally in the context of string theory, we study the effect of coupling dilaton to Maxwell field on the stability of flat charged AdS black holes. In particular, we study the stability of Gao-Zhang black holes, which are locally asymptotically anti-de Sitter. We find that for dilaton coupling parameter $\alpha$ > 1, flat black holes are stable against brane pair production, however for 0 < $\alpha$ < 1, the black holes eventually become unstable as the amount of electrical charges is increased. Such instability however, behaves somewhat differently from that of flat Reissner-Nordstr\"om black holes. In addition, we prove that the Seiberg-Witten action of charged dilaton AdS black hole of Gao-Zhang type with flat event horizon (at least in 5-dimension) is always logarithmically divergent at infinity for finite values of $\alpha$, and is finite and positive in the case $\alpha$ tends to infinity . We also comment on the robustness of our result for other charged dilaton black holes that are not of Gao-Zhang type.Comment: Fixed some confusions regarding whether part of the discussions concern electrically charged hole or magnetically charged one. No changes to the result

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Human behaviour in emergency situations: comparisons between aviation and rail domains

This article presents a comparative review of the knowledge base regarding human behaviour in emergencies for both aviation and rail domains. Generic models of human behaviour in emergency situations are introduced and specific attention is then focussed on methods of behaviour prediction, exhibited behaviours in emergencies and methods of aiding evacuation across both modes of transport. Using established knowledge from the aviation domain, it has been possible to make observations and comparisons about the rail domain. Traditionally, the aviation domain has been a major focus of research attention and this is used to inform and interpret the rail domain. By drawing comparisons across these domains for human behaviour in emergency situations, the observations are discussed along with recommendations for future policies/planning for emergencies and future research areas

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease