Step-like contrast structure of singularly perturbed optimal control problem

In this paper, the existence of step-like contrast structure for a class of singularly perturbed optimal control problem is shown by the contrast structure theory. By means of direct scheme of boundary function method, we construct the uniformly valid asymptotic solution for the singularly perturbed optimal control problem. Finally, an example is presented to show the result

Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue

We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanicalmyofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of the mechano-electrical feedback in facilitating and promoting atrial fibrillation

ECG Imaging to Detect the Site of Ventricular Ischemia Using Torso Electrodes: A Computational Study

Electrocardiography provides some information useful for ischemic diagnosis. However, more recently there has been substantial growth in the area of ECG imaging, which by solving the inverse problem of electrocardiography aims to produce high-resolution mapping of the electrical and magnetic dynamics of the heart. Most inverse studies use the full resolution of the body surface potential (BSP) to reconstruct the epicardial potentials, however using a limited number of torso electrodes to interpolate the BSP is more clinically relevant and has an important effect on the reconstruction which must be quantified. A circular ischemic lesion on the right ventricle lateral wall 27 mm in radius is reconstructed using three Tikhonov methods along with 6 different electrode configurations ranging from 32 leads to 1,024 leads. The 2nd order Tikhonov solution performed the most accurately (~80% lesion identified) followed by the 1st (~50% lesion identified) and then the 0 order Tikhonov solution performed the worst with a maximum of ~30% lesion identified regardless of how many leads were used. With an increasing number of leads the solution produces less error, and the error becomes more localised around the lesion for all three regularisation methods. In noisy conditions, the relative performance gap of the 1st and 2nd order Tikhonov solutions was reduced, and determining an accurate regularisation parameter became relatively more difficult. Lesions located on the left ventricle walls were also able to be identified but comparatively to the right ventricle lateral wall performed marginally worse with lesions located on the interventricular septum being able to be indicated by the reconstructions but not successfully identified against the error. The quality of reconstruction was found to decrease as the lesion radius decreased, with a lesion radius of <20 mm becoming difficult to correctly identify against the error even when using >512 torso electrodes

Fabrication of VO 2

VO2 (B) nanobelts have been successfully synthesized via a simple hydrothermal route. The products were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and Raman spectrum. These nanobelts are of rectangular cross-section with mean length about 1 μm, mean width about 80 nm, and mean thickness about 50 nm. The as-synthesized VO2 nanobelts were assembled as the cathode electrodes of lithium ion batteries. Their electrochemical properties were studied by conventional charge/discharge tests, which show an initial discharge capacity of 321 mAh g−1 with voltage plateau near 2.5 V. These results indicated that such hydrothermally synthesized VO2 (B) nanobelts could be an ideal candidate of cathode material for lithium ion battery

Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome:Insights from virtual human atria

Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF

A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research

In cardiac electrophysiology, there exist many sources of inter- and intra-personal variability. These include variability in conditions and environment, and genotypic and molecular diversity, including differences in expression and behavior of ion channels and transporters, which lead to phenotypic diversity (e.g., variable integrated responses at the cell, tissue, and organ levels). These variabilities play an important role in progression of heart disease and arrhythmia syndromes and outcomes of therapeutic interventions. Yet, the traditional in silico framework for investigating cardiac arrhythmias is built upon a parameter/property-averaging approach that typically overlooks the physiological diversity. Inspired by work done in genetics and neuroscience, new modeling frameworks of cardiac electrophysiology have been recently developed that take advantage of modern computational capabilities and approaches, and account for the variance in the biological data they are intended to illuminate. In this review, we outline the recent advances in statistical and computational techniques that take into account physiological variability, and move beyond the traditional cardiac model-building scheme that involves averaging over samples from many individuals in the construction of a highly tuned composite model. We discuss how these advanced methods have harnessed the power of big (simulated) data to study the mechanisms of cardiac arrhythmias, with a special emphasis on atrial fibrillation, and improve the assessment of proarrhythmic risk and drug response. The challenges of using in silico approaches with variability are also addressed and future directions are proposed