A least-squares implicit RBF-FD closest point method and applications to PDEs on moving surfaces

The closest point method (Ruuth and Merriman, J. Comput. Phys. 227(3):1943-1961, [2008]) is an embedding method developed to solve a variety of partial differential equations (PDEs) on smooth surfaces, using a closest point representation of the surface and standard Cartesian grid methods in the embedding space. Recently, a closest point method with explicit time-stepping was proposed that uses finite differences derived from radial basis functions (RBF-FD). Here, we propose a least-squares implicit formulation of the closest point method to impose the constant-along-normal extension of the solution on the surface into the embedding space. Our proposed method is particularly flexible with respect to the choice of the computational grid in the embedding space. In particular, we may compute over a computational tube that contains problematic nodes. This fact enables us to combine the proposed method with the grid based particle method (Leung and Zhao, J. Comput. Phys. 228(8):2993-3024, [2009]) to obtain a numerical method for approximating PDEs on moving surfaces. We present a number of examples to illustrate the numerical convergence properties of our proposed method. Experiments for advection-diffusion equations and Cahn-Hilliard equations that are strongly coupled to the velocity of the surface are also presented

An RBF-FD closest point method for solving PDEs on surfaces

Partial differential equations (PDEs) on surfaces appear in many applications throughout the natural and applied sciences. The classical closest point method (Ruuth and Merriman, J. Comput. Phys. 227(3):1943-1961, [2008]) is an embedding method for solving PDEs on surfaces using standard finite difference schemes. In this paper, we formulate an explicit closest point method using finite difference schemes derived from radial basis functions (RBF-FD). Unlike the orthogonal gradients method (Piret, J. Comput. Phys. 231(14):4662-4675, [2012]), our proposed method uses RBF centers on regular grid nodes. This formulation not only reduces the computational cost but also avoids the ill-conditioning from point clustering on the surface and is more natural to couple with a grid based manifold evolution algorithm (Leung and Zhao, J. Comput. Phys. 228(8):2993-3024, [2009]). When compared to the standard finite difference discretization of the closest point method, the proposed method requires a smaller computational domain surrounding the surface, resulting in a decrease in the number of sampling points on the surface. In addition, higher-order schemes can easily be constructed by increasing the number of points in the RBF-FD stencil. Applications to a variety of examples are provided to illustrate the numerical convergence of the method.NSERC Canada (RGPIN 227823), Hong Kong Research Grant Council GRF Grant (HKBU 11528205), Hong Kong Baptist University FRG Grant

A least-squares implicit RBF-FD closest point method and applications to PDEs on moving surfaces

The closest point method (Ruuth and Merriman, J. Comput. Phys. 227(3):1943-1961, [2008]) is an embedding method developed to solve a variety of partial differential equations (PDEs) on smooth surfaces, using a closest point representation of the surface and standard Cartesian grid methods in the embedding space. Recently, a closest point method with explicit time-stepping was proposed that uses finite differences derived from radial basis functions (RBF-FD). Here, we propose a least-squares implicit formulation of the closest point method to impose the constant-along-normal extension of the solution on the surface into the embedding space. Our proposed method is particularly flexible with respect to the choice of the computational grid in the embedding space. In particular, we may compute over a computational tube that contains problematic nodes. This fact enables us to combine the proposed method with the grid based particle method (Leung and Zhao, J. Comput. Phys. 228(8):2993-3024, [2009]) to obtain a numerical method for approximating PDEs on moving surfaces. We present a number of examples to illustrate the numerical convergence properties of our proposed method. Experiments for advection-diffusion equations and Cahn-Hilliard equations that are strongly coupled to the velocity of the surface are also presented.NSERC Canada Grant (RGPIN 2016-04361), Hong Kong Research Grant Council GRF Grant, Hong Kong Baptist University FRG Gran

YopN and TyeA Hydrophobic Contacts Required for Regulating Ysc-Yop Type III Secretion Activity by Yersinia pseudotuberculosis

Yersinia bacteria target Yop effector toxins to the interior of host immune cells by the Ysc-Yop type III secretion system. A YopN-TyeA heterodimer is central to controlling Ysc-Yop targeting activity. A + 1 frameshift event in the 3-prime end of yopN can also produce a singular secreted YopN-TyeA polypeptide that retains some regulatory function even though the C-terminal coding sequence of this YopN differs greatly from wild type. Thus, this YopN C-terminal segment was analyzed for its role in type III secretion control. Bacteria producing YopN truncated after residue 278, or with altered sequence between residues 279 and 287, had lost type III secretion control and function. In contrast, YopN variants with manipulated sequence beyond residue 287 maintained full control and function. Scrutiny of the YopN-TyeA complex structure revealed that residue W 279 functioned as a likely hydrophobic contact site with TyeA. Indeed, a YopN W 279 G mutant lost all ability to bind TyeA. The TyeA residue F 8 was also critical for reciprocal YopN binding. Thus, we conclude that specific hydrophobic contacts between opposing YopN and TyeA termini establishes a complex needed for regulating Ysc-Yop activity

Lessons Learnt in Implementation of Coordinated Voltage Control Demonstration

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Influence of enzyme immobilization and skin-sensor interface on non-invasive glucose determination from interstitial fluid obtained by magnetohydrodynamic extraction

We integrated a magnetohydrodynamic fluid extractor with an amperometric glucose biosensor to develop a wearable device for non-invasive glucose monitoring. Reproducible fluid extraction through the skin and efficient transport of the extracted fluid to the biosensor surface are prerequisites for non-invasive glucose monitoring. We optimized the enzyme immobilization and the interface layer between the sensing device and the skin. The monitoring device was evaluated by extracting fluid through porcine skin followed by glucose detection at the biosensor. The biosensor featured a screen-printed layer of Prussian Blue that was coated with a layer containing glucose oxidase. Both physical entrapment of glucose oxidase in chitosan and tethering of glucose oxidase to electrospun nanofibers were evaluated. Binding of glucose oxidase to nanofibers under mild conditions provided a stable biosensor with analytical performance suitable for accurate detection of micromolar concentrations of glucose. Hydrogels of varying thickness (95-2000 mu m) as well as a thin (30 mu m) nanofibrous polycaprolactone mat were studied as an interface layer between the biosensor and the skin. The effect of mass transfer phenomena at the biosensor-skin interface on the analytical performance of the biosensor was evaluated. The sensing device detected glucose extracted through porcine skin with an apparent (overall) sensitivity of-0.8 mA/(M.cm(2)), compared to a sensitivity of-17 mA/(M.cm(2)) for measurement in solution. The amperometric response of the biosensor correlated with the glucose concentration in the fluid that had been extracted through porcine skin with the magnetohydrodynamic technique.Peer reviewe

Sampling of fluid through skin with magnetohydrodynamics for noninvasive glucose monitoring

Out of 463 million people currently with diabetes, 232 million remain undiagnosed. Diabetes is a threat to human health, which could be mitigated via continuous self-monitoring of glucose. In addition to blood, interstitial fluid is considered to be a representative sample for glucose monitoring, which makes it highly attractive for wearable on-body sensing. However, new technologies are needed for efficient and noninvasive sampling of interstitial fluid through the skin. In this report, we introduce the use of Lorentz force and magnetohydrodynamics to noninvasively extract dermal interstitial fluid. Using porcine skin as an ex-vivo model, we demonstrate that the extraction rate of magnetohydrodynamics is superior to that of reverse iontophoresis. This work seeks to provide a safe, effective, and noninvasive sampling method to unlock the potential of wearable sensors in needle-free continuous glucose monitoring devices that can benefit people living with diabetes.Peer reviewe

YopN and TyeA Hydrophobic Contacts Required for Regulating Ysc-Yop Type III Secretion Activity by Yersinia pseudotuberculosis

Yersinia bacteria target Yop effector toxins to the interior of host immune cells by the Ysc-Yop type III secretion system. A YopN-TyeA heterodimer is central to controlling Ysc-Yop targeting activity. A + 1 frameshift event in the 3-prime end of yopN can also produce a singular secreted YopN-TyeA polypeptide that retains some regulatory function even though the C-terminal coding sequence of this YopN differs greatly from wild type. Thus, this YopN C-terminal segment was analyzed for its role in type III secretion control. Bacteria producing YopN truncated after residue 278, or with altered sequence between residues 279 and 287, had lost type III secretion control and function. In contrast, YopN variants with manipulated sequence beyond residue 287 maintained full control and function. Scrutiny of the YopN-TyeA complex structure revealed that residue W-279 functioned as a likely hydrophobic contact site with TyeA. Indeed, a YopN(W279G) mutant lost all ability to bind TyeA. The TyeA residue F-8 was also critical for reciprocal YopN binding. Thus, we conclude that specific hydrophobic contacts between opposing YopN and TyeA termini establishes a complex needed for regulating Ysc-Yop activity

Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point