A unified theory of calcium alternans in ventricular myocytes.

Intracellular calcium (Ca2+) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca2+ cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca2+ alternans. Two mechanisms of Ca2+ alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca2+ release and uptake, and the other on refractoriness and other properties of Ca2+ sparks. Each of the two mechanisms can partially explain the experimental observations, but both have their inconsistencies with the experimental results. Here we developed an iterated map model that is composed of two coupled iterated maps, which unifies the two mechanisms into a single cohesive mathematical framework. The unified theory can consistently explain the seemingly contradictory experimental observations and shows that the two mechanisms work synergistically to promote Ca2+ alternans. Predictions of the theory were examined in a physiologically-detailed spatial Ca2+ cycling model of ventricular myocytes

Computational Modeling and Numerical Methods for Spatiotemporal Calcium Cycling in Ventricular Myocytes

Intracellular calcium (Ca) cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR), mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU) network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a variant of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5 × 5 × 5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100 × 20 × 10 CRUs, a 1-s heart time simulation takes about 10 min of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown

Temperature dependence of magnetic resonance probes for use as embedded sensors in constructed wetlands

Constructed wetlands are now accepted as an environmentally friendly means of wastewater treatment however, their effectiveness can be limited by excessive clogging of the pores within the gravel matrix, making this an important parameter to monitor. It has previously been shown that the clog state can be characterised using magnetic resonance (MR) relaxation parameters with permanent magnet based sensors. One challenge with taking MR measurements over a time scale on the order of years is that seasonal temperature fluctuations will alter both the way that the sensor operates as well as the relaxation times recorded. Without an understanding of how the sensor will behave under different temperature conditions, meaningful information about the clog state cannot be successfully extracted from a wetland. This work reports the effect of temperature on a permanent magnet based MR sensor to determine if the received signal intensity is significantly compromised as a result of large temperature changes, and whether meaningful relaxation data can be extracted over the temperature range of interest. To do this, the central magnetic field of the sensor was monitored as a function of temperature, showing an expected linear relationship. Signal intensity was measured over a range of temperatures (5 °C to 44 °C) for which deterioration at high and low temperatures compared to room temperature was observed. The sensor was still operable at the extremes of this range and the reason for the signal loss has been studied and explained. Spin-lattice relaxation time measurements using the sensor at different temperatures have also been taken on a water sample and seem to agree with literature values. Further to this, measurements have been taken in an operational wetland over the course of 203 days and have shown a linear dependence with temperature as would be expected. This work concluded that the sensor can perform the task of measuring the spin-lattice relaxation time over the required temperature range making it suitable for long-term application in constructed wetlands

Label-Free Optical Detection of Biomolecular Translocation through Nanopore Arrays

In recent years, nanopores have emerged as exceptionally promising single-molecule sensors due to their ability to detect biomolecules at subfemtomole levels in a label-free manner. Development of a high-throughput nanopore-based biosensor requires multiplexing of nanopore measurements. Electrical detection, however, poses a challenge, as each nanopore circuit must be electrically independent, which requires complex nanofluidics and embedded electrodes. Here, we present an optical method for simultaneous measurements of the ionic current across an array of solid-state nanopores, requiring no additional fabrication steps. Proof-of-principle experiments are conducted that show simultaneous optical detection and characterization of ssDNA and dsDNA using an array of pores. Through a comparison with electrical measurements, we show that optical measurements are capable of accessing equivalent transmembrane current information