Modeling specific action potentials in the human atria based on a minimal reaction-diffusion model

We present an effective method to model empirical action potentials of specific patients in the human atria based on the minimal model of Bueno-Orovio, Cherry and Fenton adapted to atrial electrophysiology. In this model, three ionic are currents introduced, where each of it is governed by a characteristic time scale. By applying a nonlinear optimization procedure, a best combination of the respective time scales is determined, which allows one to reproduce specific action potentials with a given amplitude, width and shape. Possible applications for supporting clinical diagnosis are pointed out.Comment: 16 pages, 8 figure

Bridging between Load-Flow and Kuramoto-like Power Grid Models: A Flexible Approach to Integrating Electrical Storage Units

In future power systems, electrical storage will be the key technology for balancing feed-in fluctuations. With increasing share of renewables and reduction of system inertia, the focus of research expands towards short-term grid dynamics and collective phenomena. Against this backdrop, Kuramoto-like power grids have been established as a sound mathematical modeling framework bridging between the simplified models from nonlinear dynamics and the more detailed models used in electrical engineering. However, they have a blind spot concerning grid components, which cannot be modeled by oscillator equations, and hence do not allow to investigate storage-related issues from scratch. We remove this shortcoming by bringing together Kuramoto-like and algebraic load-flow equations. This is a substantial extension of the current Kuramoto framework with arbitrary grid components. Based on this concept, we provide a solid starting point for the integration of flexible storage units enabling to address current problems like smart storage control, optimal siting and rough cost estimations. For demonstration purpose, we here consider a wind power application with realistic feed-in conditions. We show how to implement basic control strategies from electrical engineering, give insights into their potential with respect to frequency quality improvement and point out their limitations by maximum capacity and finite-time response.Comment: 12 pages, 6 figure

Heterogeneities in electricity grids strongly enhance non-Gaussian features of frequency fluctuations under stochastic power input

Stochastic feed-in of fluctuating renewable energies is steadily increasing in modern electricity grids and this becomes an important risk factor for maintaining power grid stability. Here we study the impact of wind power feed-in on the short-term frequency fluctuations in power grids based on an IEEE test grid structure, the swing equation for the dynamics of voltage phase angles, and a series of measured wind speed data. External control measures are accounted for by adjusting the grid state to the average power feed-in on a time scale of one minute. The wind power is injected at a single node by replacing one of the conventional generator nodes in the test grid by a wind farm. We determine histograms of local frequencies for a large number of one-minute wind speed sequences taken from the measured data and for different injection nodes. These histograms exhibit a common type of shape, which can be described by a Gaussian distribution for small frequencies and a nearly exponentially decaying tail part. Non-Gaussian features become particularly pronounced for wind power injection at locations, which are weakly connected to the main grid structure. This effect is only present when taking into account the heterogeneities in transmission line and node properties of the grid, while it disappears upon homogenizing of these features. The standard deviation of the frequency fluctuations increases linearly with the average injected wind power.Comment: 9 pages, 7 figure

Internal Friction and Vulnerability of Mixed Alkali Glasses

Based on a hopping model we show how the mixed alkali effect in glasses can be understood if only a small fraction c_V ofthe available sites for the mobile ions is vacant. In particular, we reproduce the peculiar behavior of the internal friction and the steep fall (''vulnerability'') of the mobility of the majority ion upon small replacements by the minority ion. The single and mixed alkali internal friction peaks are caused by ion-vacancy and ion-ion exchange processes. If c_V is small, they can become comparable in height even at small mixing ratios. The large vulnerability is explained by a trapping of vacancies induced by the minority ions. Reasonable choices of model parameters yield typical behaviors found in experiments.Comment: 4 pages, 4 figure

Cis and trans effects differentially contribute to the evolution of promoters and enhancers

Background Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we use massively parallel reporter assays to directly measure the transcriptional outputs of thousands of individual regulatory elements in embryonic stem cells and measure cis and trans effects between human and mouse. Results Our approach reveals that cis effects are widespread across transcribed regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we find that trans effects are rare but stronger in enhancers than promoters and are associated with a subset of transcription factors that are differentially expressed between human and mouse. While we find that cis-trans compensation is common within promoters, we do not see evidence of widespread cis-trans compensation at enhancers. Cis-trans compensation is inversely correlated with enhancer redundancy, suggesting that such compensation may often occur across multiple enhancers. Conclusions Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.K.M. was a National Science Foundation Graduate Research Fellow under grant no. DGE1144152 during the majority of the project. M.M. was a Gilead Fellow of the Life Sciences Research Foundation during part of the project and is currently supported by the Spanish Ministry of Science and Innovation with a Ramon y Cajal grant (RYC-2017-22249). J.L.R. is an HHMI faculty scholar.Peer ReviewedPostprint (published version

Growth kinetics of racemic heptahelicene-2-carboxylic acid nanowires on calcite (104)

Einax M, Richter T, Nimmrich M, et al. Growth kinetics of racemic heptahelicene-2-carboxylic acid nanowires on calcite (104). Journal of Chemical Physics. 2016;145(13):134702.Molecular self-assembly of racemic heptahelicene-2-carboxylic acid on a dielectric substrate at room temperature can be used to generate wire-like organic nanostructures consisting of single and double molecular rows. By means of non-contact atomic force microscopy, we investigate the growth of the wire-like pattern after deposition by experimental and theoretical means. From analyzing the time dependence of the mean row length, two distinct regimes were found. At the early post-deposition stage, the mean length grows in time. Subsequently, a crossover to a second regime is observed, where the mean row length remains nearly constant. We explain these findings by a mean-field rate equation approach providing a comprehensive picture of the growth kinetics. As a result, we demonstrate that the crossover between the two distinct regimes is accomplished by vanishing of the homochiral single rows. At later stages only heterochiral double row structures remain. Published by AIP Publishing

A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus

The binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here we test the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~ 15 CTCF binding sites and located at the long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is invariant across evolution, tissues, and temporal dynamics of X-chromosome inactivation. We demonstrate that neither the deletion of this locus nor the ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter TADs in a sex-specific or allele-specific manner. In contrast, Firre’s deletion disrupts the chromatin super-loop formation of the inactive X-chromosome. Collectively, our findings suggest that apart from CTCF binding, additional mechanisms may play roles in establishing TAD boundary formation

Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage

Influence of adatom interactions on second layer nucleation

We develop a theory for the inclusion of adatom interactions in second layer nucleation occurring in epitaxial growth. The interactions considered are due to ring barriers between pairs of adatoms and binding energies of unstable clusters. The theory is based on a master equation, which describes the time development of microscopic states that are specified by cluster configurations on top of an island. The transition rates are derived by scaling arguments and tested against kinetic Monte-Carlo simulations. As an application we reanalyze experiments to determine the step edge barrier for Ag/Pt(111).Comment: 4 pages, 4 figure