63 research outputs found
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
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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
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