Role of ryanodine receptor cooperativity in Ca-wave-mediated triggered activity in cardiomyocytes.

Ca waves are known to trigger delayed after-depolarizations that can cause malignant cardiac arrhythmias. However, modelling Ca waves using physiologically realistic models has remained a major challenge. Existing models with low Ca sensitivity of ryanodine receptors (RyRs) necessitate large release currents, leading to an unrealistically large Ca transient amplitude incompatible with the experimental observations.

E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (I) and corresponding channel proteins.

Genome-wide association studies have reported a correlation between a SNP of the RING finger E3 ubiquitin protein ligase rififylin (RFFL) and QT interval variability in humans (Newton-Cheh et al., 2009). Previously, we have shown that RFFL downregulates expression and function of the human-like ether-a-go-go-related gene potassium channel and corresponding rapidly activating delayed rectifier potassium current (I) in adult rabbit ventricular cardiomyocytes.

Solidification furnace for in situ observation of bulk transparent systems and image analysis methods.

This paper aims to describe the experimental framework of the Directional Solidification Insert, installed onboard the International Space Station, dedicated to the in situ and real-time characterization of the dynamic selection of the solid-liquid interface morphology in bulk samples of transparent materials under diffusive growth conditions. The in situ observation of the solid-liquid interface is an invaluable tool for gaining knowledge on the time evolution of the interface pattern because the initial morphological instability evolves nonlinearly and undergoes a reorganization process. The result of each experiment, characterized by the sample concentration, a thermal gradient, and a pulling rate, is a large number of images.

Scaling laws for two-dimensional dendritic crystal growth in a narrow channel.

We investigate analytically and computationally the dynamics of two-dimensional needle crystal growth from the melt in a narrow channel. Our analytical theory predicts that, in the low supersaturation limit, the growth velocity V decreases in time t as a power law V∼t^{-2/3}, which we validate by phase-field and dendritic-needle-network simulations. Simulations further reveal that, above a critical channel width Λ≈5l_{D}, where l_{D} is the diffusion length, needle crystals grow with a constant V View Article and Find Full Text PDF

Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.

Discordant alternans, the spatially out-of-phase alternation of the durations of propagating action potentials in the heart, has been linked to the onset of fibrillation, a major cardiac rhythm disorder. The sizes of the regions, or domains, within which these alternations are synchronized are critical in this link. However, computer models employing standard gap junction-based coupling between cells have been unable to reproduce simultaneously the small domain sizes and rapid action potential propagation speeds seen in experiments.

Ephaptic Coupling as a Resolution to the Paradox of Action Potential Wave Speed and Discordant Alternans Spatial Scales in the Heart.

Previous computer simulations have suggested that existing models of action potential wave propagation in the heart are not consistent with observed wave propagation behavior. Specifically, computer models cannot simultaneously reproduce the rapid wave speeds and small spatial scales of discordant alternans patterns measured experimentally in the same simulation. The discrepancy is important, because discordant alternans can be a key precursor to the development of abnormal and dangerous rapid rhythms in the heart.

Hierarchical structure formation by crystal growth-front instabilities during ice templating.

Directional solidification of aqueous solutions and slurries in a temperature gradient is widely used to produce cellular materials through a phase separation of solutes or suspended particles between growing ice lamellae. While this process has analogies to the directional solidification of metallurgical alloys, it forms very different hierarchical structures. The resulting honeycomb-like porosity of freeze-cast materials consists of regularly spaced, lamellar cell walls which frequently exhibit unilateral surface features of morphological complexity reminiscent of living forms, all of which are unknown in metallurgical structures.

Cell invasion during competitive growth of polycrystalline solidification patterns.

Spatially extended cellular and dendritic array structures forming during solidification processes such as casting, welding, or additive manufacturing are generally polycrystalline. Both the array structure within each grain and the larger scale grain structure determine the performance of many structural alloys. How those two structures coevolve during solidification remains poorly understood.

Microstructural Pattern Formation during Far-from-Equilibrium Alloy Solidification.

We introduce a new phase-field formulation of rapid alloy solidification that quantitatively incorporates nonequilibrium effects at the solid-liquid interface over a very wide range of interface velocities. Simulations identify a new dynamical instability of dendrite tip growth driven by solute trapping at velocities approaching the absolute stability limit. They also reproduce the formation of the widely observed banded microstructures, revealing how this instability triggers transitions between dendritic and microsegregation-free solidification.

Topological control of liquid-metal-dealloyed structures.

The past few years have witnessed the rapid development of liquid metal dealloying to fabricate nano-/meso-scale porous and composite structures with ultra-high interfacial area for diverse materials applications. However, this method currently has two important limitations. First, it produces bicontinuous structures with high-genus topologies for a limited range of alloy compositions.

Fracture toughness of bone at the microscale.

Bone's hierarchical arrangement of collagen and mineral generates a confluence of toughening mechanisms acting at every length scale from the molecular to the macroscopic level. Molecular defects, disease, and age alter bone structure at different levels and diminish its fracture resistance. However, the inability to isolate and quantify the influence of specific features hampers our understanding and the development of new therapies.

Oscillatory-nonoscillatory transitions for inclined cellular patterns in three-dimensional directional solidification.

The oscillatory behavior of cellular patterns produced by directional solidification of a transparent alloy under microgravity conditions was recently observed to depend on the misorientation of the main crystal axis with respect to the direction of the imposed thermal gradient [Pereda et al., Phys. Rev.

Experimental characterization and theoretical analysis of cell tip oscillations in directional solidification.

Experiments performed in DECLIC-DSI on board the International Space Station evidenced oscillatory modes during the directional solidification of a bulk sample of succinonitrile-based transparent alloy. The interferometric data acquired during a reference experiment, V_{p}=1 μm/s and G=19 K/cm, allowed us to reconstruct the cell shape and thus measure the cell tip position, radius, and growth velocity evolution, in order to quantify the dynamics of the oscillating cells. This study completes our previous reports [Bergeon et al.

Crack path selection in orientationally ordered composites.

While cracks in isotropic homogeneous materials propagate straight, perpendicularly to the tensile axis, cracks in natural and synthetic composites deflect from a straight path, often increasing the toughness of the material. Here we combine experiments and simulations to identify materials properties that predict whether cracks propagate straight or kink on a macroscale larger than the composite microstructure. Those properties include the anisotropy of the fracture energy, which we vary several fold by increasing the volume fraction of orientationally ordered alumina (Al_{2}O_{3}) platelets inside a polymer matrix, and a microstructure-dependent process zone size that is found to modulate the additional stabilizing or destabilizing effect of the nonsingular stress acting parallel to the crack.

Late I Blocker GS967 Supresses Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long QT Type 2.

Background: Long QT syndrome has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (I) may counterbalance the reduced repolarization reserve in long QT syndrome and prevent EADs and PVTs.

Methods: We tested the effects of the selective I blocker GS967 on PVT induction in a transgenic rabbit model of long QT syndrome type 2 using intact heart optical mapping, cellular electrophysiology and confocal Ca imaging, and computer modeling.

LITAF (Lipopolysaccharide-Induced Tumor Necrosis Factor) Regulates Cardiac L-Type Calcium Channels by Modulating NEDD (Neural Precursor Cell Expressed Developmentally Downregulated Protein) 4-1 Ubiquitin Ligase.

Background: The turnover of cardiac ion channels underlying action potential duration is regulated by ubiquitination. Genome-wide association studies of QT interval identified several single-nucleotide polymorphisms located in or near genes involved in protein ubiquitination. A genetic variant upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor) gene prompted us to determine its role in modulating cardiac excitation.

Universality and Stability Phase Diagram of Two-Dimensional Brittle Fracture.

The two-dimensional oscillatory crack instability, experimentally observed in a class of brittle materials under strongly dynamic conditions, has been recently reproduced by a nonlinear phase-field fracture theory. Here, we highlight the universal character of this instability by showing that it is present in materials exhibiting widely different near crack tip elastic nonlinearity, and by demonstrating that the oscillations wavelength follows a universal master curve in terms of dissipation-related and nonlinear elastic intrinsic length scales. Moreover, we show that upon increasing the driving force for fracture, a high-velocity tip-splitting instability emerges, as experimentally demonstrated.

The Ca transient as a feedback sensor controlling cardiomyocyte ionic conductances in mouse populations.

Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new conceptual approach to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca transient without any constraint on the action potential.

NCX-Mediated Subcellular Ca Dynamics Underlying Early Afterdepolarizations in LQT2 Cardiomyocytes.

Long QT syndrome type 2 (LQT2) is a congenital disease characterized by loss of function mutations in hERG potassium channels (I). LQT2 is associated with fatal ventricular arrhythmias promoted by triggered activity in the form of early afterdepolarizations (EADs). We previously demonstrated that intracellular Ca handling is remodeled in LQT2 myocytes.

Transient Outward K Current (I) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

Background: Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1.

Methods: Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits.

The modular socket system in a rural setting in Indonesia.

Background: Prosthetic services are inaccessible to people living in rural areas. Systems like the modular socket system have the potential to be fabricated outside of the prosthetic workshop.

Objectives: This study aimed to evaluate the patient's performance and satisfaction with the use of the modular socket system, and the technical feasibility of its implementation in a rural setting.

Experimental observation of oscillatory cellular patterns in three-dimensional directional solidification.

We present a detailed analysis of oscillatory modes during three-dimensional cellular growth in a diffusive transport regime. We ground our analysis primarily on in situ observations of directional solidification experiments of a transparent succinonitrile 0.24wt% camphor alloy performed in microgravity conditions onboard the International Space Station.