Na/K pump regulation of cardiac repolarization: Insights from a systems biology approach

The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the Systems Biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most\ud important ionic mechanisms in regulating key properties of cardiac repolarization and its rate-dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies

A non-parametric analysis of convergence in ICT industries

The purpose of this article is to explore the relative merits of capital accumulation and efficiency catch-up in the convergence patterns of labor productivity in theICT (Information and Communication Technologies) sector in a set of developed countries. It is the first convergence analysis of ICT carried out from the non-parametric kernel approach and using an intertemporal data envelopment analysis (DEA) to estimate the efficiency of the analyzed countries. Special care has been paid to the dataset construction, using hedonic prices and unit value ratios because of the nature of the industry. The appropriate technology theory extended with non-immediate spillovers is the theoretical framework used to interpret the obtained results. These show thatlabor productivity, technology and efficiency have moved from a unimodal towards a bimodal distribution over time, beginning the 21th century with two convergence clubs of countries. The conclusions obtained from these results show that while capital intensification offer opportunities to benefit from new knowledge developed by the leaders, assimilation of this knowledge is not immediate and its speed depends upon the social and technological capabilities of the followers. Policy decision-makers should be aware that the choice of the technology has to be complemented with the development of other actives to benefit from all its potentialities

Apodized pupil Lyot coronagraphs for arbitrary apertures. V. Hybrid Shaped Pupil designs for imaging Earth-like planets with future space observatories

We introduce a new class of solutions for Apodized Pupil Lyot Coronagraphs (APLC) with segmented aperture telescopes to remove broadband diffracted light from a star with a contrast level of $10^{10}$. These new coronagraphs provide a key advance to enabling direct imaging and spectroscopy of Earth twins with future large space missions. Building on shaped pupil (SP) apodization optimizations, our approach enables two-dimensional optimizations of the system to address any aperture features such as central obstruction, support structures or segment gaps. We illustrate the technique with a design that could reach $10^{10}$ contrast level at 34\,mas for a 12\,m segmented telescope over a 10\% bandpass centered at a wavelength $\lambda_0=$500\,nm. These designs can be optimized specifically for the presence of a resolved star, and in our example, for stellar angular size up to 1.1\,mas. This would allow probing the vicinity of Sun-like stars located beyond 4.4\,pc, therefore fully retiring this concern. If the fraction of stars with Earth-like planets is \eta_{\Earth}=0.1, with 18\% throughput, assuming a perfect, stable wavefront and considering photon noise only, 12.5 exo-Earth candidates could be detected around nearby stars with this design and a 12\,m space telescope during a five-year mission with two years dedicated to exo-Earth detection (one total year of exposure time and another year of overheads). Our new hybrid APLC/SP solutions represent the first numerical solution of a coronagraph based on existing mask technologies and compatible with segmented apertures, and that can provide contrast compatible with detecting and studying Earth-like planets around nearby stars. They represent an important step forward towards enabling these science goals with future large space missions.Comment: 9 pages, 6 figures, ApJ accepted on 01/04/201

Calcium-Activated Potassium Channels Inhibition in Autonomically Stimulated Human Atrial Myocytes

The autonomic nervous system has been reported to play a major role in the generation and maintenance of atrial fibrillation. Various investigations have suggested small-conductance calcium-activated potassium (SK) channels as potential targets for more effective pharmacological therapies. In this study, we used in silico modeling and simulation to investigate the effects of SK channel inhibition on the action potential (AP) of autonomically stimulated human atrial cardiomyocytes. The Grandi AP model, with a new formulation for the ISK current, was used to represent human atrial electrophysiology. Choliner-gic stimulation by different concentrations of acetylcholine (ACh) hyperpolarized the AP and shortened the AP duration (APD) in a dose-dependent manner, with up to 7 mV resting membrane potential elevation and >200 ms APD shortening for 1 µM ACh at 1 Hz pacing frequency. Additional ß-adrenergic stimulation by 1 µM Isoproterenol (Iso) partially attenuated the effects of cholinergic stimulation by prolonging the APD by 41.6%. ISK inhibition was able to reverse the effects of cholinergic activation, but only for moderate ACh doses and when combined with 1 µM Iso, leading to 58.3% prolongation of the AP stimulated with 0.01 µM ACh. In conclusion, ISK inhibition combined with ß-adrenergic stimulation can be effective in antagonizing cholinergic effects on human atrial myocytes

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Hyperactivity of the parasympathetic nervous system has been linked to the development of paroxysmal atrial fibrillation (AF). The parasympathetic neurotransmitter acetylcholine (ACh) causes a reduction in action potential (AP) duration (APD) and an increase in resting membrane potential (RMP), both of which contribute to enhance the risk for reentry. Research suggests that small-conductance calcium activated potassium (SK) channels may be an effective target for treating AF. Therapies targeting the autonomic nervous system, either alone or in combination with other drugs, have been explored and have been shown to decrease the incidence of atrial arrhythmias. This study uses computational modeling and simulation to examine the impact of SK channel block (SKb) and β-adrenergic stimulation through Isoproterenol (Iso) on countering the negative effects of cholinergic activity in human atrial cell and 2D tissue models. The steady-state effects of Iso and/or SKb on AP shape, APD at 90% repolarization (APD90) and RMP were evaluated. The ability to terminate stable rotational activity in cholinergically-stimulated 2D tissue models of AF was also investigated. A range of SKb and Iso application kinetics, which reflect varying drug binding rates, were taken into consideration. The results showed that SKb alone prolonged APD90 and was able to stop sustained rotors in the presence of ACh concentrations up to 0.01 μM. Iso terminated rotors under all tested ACh concentrations, but resulted in highly-variable steady-state outcomes depending on baseline AP morphology. Importantly, the combination of SKb and Iso resulted in greater APD90 prolongation and showed promising anti-arrhythmic potential by stopping stable rotors and preventing re-inducibility

Palaeohydrology of the Mulhouse Basin: are fluid inclusions in halite tracers of past seawater composition?

Brine reactions processes were the most important factors controlling the major-ion evolution in the Oligocene, Mulhouse Basin (France) evaporite basin. The combined analysis of fluid inclusions in primary textures in halite by Cryo-SEM-EDS with sulfate-δ34S, δ18O and 87Sr/86Sr isotope ratios reveals hydrothermal inputs and recycling of Permian evaporites, particularly during advanced stages of evaporation in the Salt IV member which ended with sylvite formation. The lower part of the Salt IV evolved from an originally marine input. Sulfate-δ34S shows Oligocene marine-like signatures at the base of the member (Fig.1). However, enriched sulfate-δ18O reveals the importance of re-oxidation processes. As evaporation progressed other non-marine or marine-modified inputs from neighbouring basins became more important. This is demonstrated by an increase in K concentrations in brine inclusions, Br in halite and variations in sulfate isotopes trends and 87Sr/86Sr ratios. The recycling of previously precipitated evaporites was increasingly important with evaporation. Therefore, regardless of the apparent marine sequence (gypsum, halite, potassic salts), the existence of diverse inputs and the consequent chemical changes to the brine preclude the use of trapped brine inclusions in direct reconstruction of Oligocene seawater chemistry.European Association for Geochemistry; Geochemical Societ

CLIPSwarm: Converting text into formations of robots

We present CLIPSwarm, an algorithm to generate robot swarm formations from natural language descriptions. CLIPSwarm receives an input text and finds the position of the robots to form a shape that corresponds to the given text. To do so, we implement a variation of the Montecarlo particle filter to obtain a matching formation iteratively. In every iteration, we generate a set of new formations and evaluate their Clip Similarity with the given text, selecting the best formations according to this metric. This metric is obtained using Clip, [1], an existing foundation model trained to encode images and texts into vectors within a common latent space. The comparison between these vectors determines how likely the given text describes the shapes. Our initial proof of concept shows the potential of this solution to generate robot swarm formations just from natural language descriptions and demonstrates a novel application of foundation models, such as CLIP, in the field of multi-robot systems. In this first approach, we create formations using a Convex-Hull approach. Next steps include more robust and generic representation and optimization steps in the process of obtaining a suitable swarm formation.Comment: Please cite this article as "P. Pueyo, E. Montijano, A. C. Murillo, and M. Schwager, CLIPSwarm: Converting text into formations of robots. ICRA 2023 Workshop on Multi-Robot Learning

CineTransfer: Controlling a Robot to Imitate Cinematographic Style from a Single Example

This work presents CineTransfer, an algorithmic framework that drives a robot to record a video sequence that mimics the cinematographic style of an input video. We propose features that abstract the aesthetic style of the input video, so the robot can transfer this style to a scene with visual details that are significantly different from the input video. The framework builds upon CineMPC, a tool that allows users to control cinematographic features, like subjects' position on the image and the depth of field, by manipulating the intrinsics and extrinsics of a cinematographic camera. However, CineMPC requires a human expert to specify the desired style of the shot (composition, camera motion, zoom, focus, etc). CineTransfer bridges this gap, aiming a fully autonomous cinematographic platform. The user chooses a single input video as a style guide. CineTransfer extracts and optimizes two important style features, the composition of the subject in the image and the scene depth of field, and provides instructions for CineMPC to control the robot to record an output sequence that matches these features as closely as possible. In contrast with other style transfer methods, our approach is a lightweight and portable framework which does not require deep network training or extensive datasets. Experiments with real and simulated videos demonstrate the system's ability to analyze and transfer style between recordings, and are available in the supplementary video