Accuracy analysis for explicit-implicit finite volume schemes on cut cell meshes

The solution of time-dependent hyperbolic conservation laws on cut cell meshes causes the small cell problem: standard schemes are not stable on the arbitrarily small cut cells if an explicit time stepping scheme is used and the time step size is chosen based on the size of the background cells. In [J. Sci. Comput. 71, 919-943 (2017)], the mixed explicit implicit approach in general and MUSCL-Trap in particular have been introduced to solve this problem by using implicit time stepping on the cut cells. Theoretical and numerical results have indicated that this might lead to a loss in accuracy when switching between the explicit and implicit time stepping. In this contribution we examine this in more detail and will prove in one dimension that the specific combination MUSCL-Trap of an explicit second-order and an implicit second-order scheme results in a fully second-order mixed scheme. As this result is unlikely to hold in two dimensions, we also introduce two new versions of mixed explicit implicit schemes based on exchanging the explicit scheme. We present numerical tests in two dimensions where we compare the new versions with the original MUSCL-Trap scheme

Molecular techniques for identifying North Sea fauna

Accelerated biodiversity assessment is the key to understanding the relationship between biodiversity and ecosystem functioning, especially in times of rapid climate change and habitat destruction. For the marine fauna of the North Sea, morphological species identification is impaired by the small size of many taxa, morphological convergence, intraspecific variation and larval stages which often elude morphological identification. Accordingly, the use of molecular methods presents highly promising tools for fast and accurate species identification. The aim of the new established research group “molecular taxonomy of marine organisms” at the German Centre of Marine Biodiversity Research is to test and develop molecular methods for the identification of the marine fauna of the North Sea, aiding efforts to monitor biodiversity patterns and changes. The research will focus on the analysis and identification of specimens using DNA barcodes, and environmental samples, in particular zooplankton, using next-generation DNA sequencing techniques. In addition it is planned to develop molecular methods for a fast and routine identification of larvae of selected invertebrate and vertebrate taxa of economic value

Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3

AIMS: Clinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). beta-Adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease. METHODS AND RESULTS: We studied effects of autonomic modulation on arrhythmias in vivo and in vitro and quantified sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (DeltaKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice). Cholinergic stimulation by carbachol provoked bigemini and TdP in freely roaming LQT3 mice. No arrhythmias were provoked by physical stress, mental stress, isoproterenol, or atropine. In isolated, beating hearts, carbachol did not prolong action potentials per se, but caused bradycardia and rate-dependent action potential prolongation. The muscarinic inhibitor AFDX116 prevented effects of carbachol on heart rate and arrhythmias. beta-Adrenoceptor stimulation suppressed arrhythmias, shortened rate-corrected action potential duration, increased rate, and minimized difference in late sodium current between genotypes. beta-Adrenoceptor density was reduced in LQT3 hearts. Acute beta-adrenoceptor blockade by esmolol, propranolol or chronic propranolol in vivo did not suppress arrhythmias. Chronic flecainide pre-treatment prevented arrhythmias (all P < 0.05). CONCLUSION: Cholinergic stimulation provokes arrhythmias in this model of LQT3 by triggering bradycardia. beta-Adrenoceptor density is reduced, and beta-adrenoceptor blockade does not prevent arrhythmias. Sodium channel blockade and beta-adrenoceptor stimulation suppress arrhythmias by shortening repolarization and minimizing difference in late sodium current.status: publishe

Knock-in gain-of-function sodium channel mutation prolongs atrial action potentials and alters atrial vulnerability

BACKGROUND Patients with long QT syndrome (LQTS) are at increased risk not only for ventricular arrhythmias but also for atrial pathology including atrial fibrillation (AF). Some patients with "lone" AF carry Na(+)-channel mutations. OBJECTIVE The purpose of this study was to determine the mechanisms underlying atrial pathology in LQTS. METHODS In mice with a heterozygous knock-in long QT syndrome type 3 (LQT3) mutant of the cardiac Na(+) channel (Delta KPQ-SCN5A) and wild-type (WT) littermates, atrial size, function, and electrophysiologic parameters were measured in intact Langendorff-perfused hearts, and histologic analysis was performed. RESULTS Atrial action potential duration, effective refractory period, cycle length, and PQ interval were prolonged in Delta KPQ-SCN5A hearts (all P &lt;.05). Flecainide (1 mu M) reversed atrial action potential duration prolongation and induced postrepolarization refractoriness (P &lt;.05). Arrhythmias were infrequent during regular rapid atrial rate in both WT and Delta KPQ-SCN5A but were inducible in 15 (38%) of 40 Delta KPQ-SCN5A and 8 (29%) of 28 WT mice upon extrastimulation. Pacing protocols generating rapid alterations in rate provoked atrial extrasystoles and arrhythmias in 6 66%) of 9 Delta KPQ-SCN5A but in 0 (0%) of 6 WT mice (P &lt;.05). Atrial diameter was increased by nearly 10% in Delta KPQ-SCN5A mice &gt; 5 months old without increase in fibrotic tissue. CONCLUSION Murine hearts bearing an LQT3 mutation show abnormalities in atrial electrophysiology and subtle changes in atrial dimension, including an atrial arrhythmogenic phenotype on provocation. These results support clinical data suggesting that LQTS mutations can cause atrial pathology and arrhythmogenesis and indicate that murine sodium channel LQTS models may be useful for exploring underlying mechanisms

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention