4,675 research outputs found
Cardiac cell modelling: Observations from the heart of the cardiac physiome project
In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field
Obituary: Thomas Henry Kunz (1938–2020)
Dr. Thomas Henry Kunz, an internationally recognized expert on the ecology and behavior of bats and Professor at Boston University, passed away on April 13, 2020 in Dedham, Massachusetts, at the age of 81 as the result of complications from COVID-19. “Tom,” to his many friends and colleagues, was born on June 11, 1938 in Independence, Missouri, to William H. and Edna F. (Dornfeld) Kunz. He married Margaret Louise Brown on December 27, 1962 in Faucett, Missouri, Margaret’s hometown. Two children were born to Margaret and Tom—Pamela Kunz (Jeffrey Kwan) and David Kunz (Nicole, née D’Angelo), and five grandchildren.
As a faculty member at Boston University, Tom progressed through the academic ranks becoming an Associate Professor in 1977 and Professor in 1984 in the Department of Biology. Although Kunz made major scientific contributions through his research and administrative leadership, his greatest impact on the future of chiropterology and of science in America may well be through the students whom he trained. He published prolifically--a total of 347 items--including books, book chapters, journal articles, book reviews, project reports, and popular articles.
Includes lists of students trained, grants received, and a complete bibliography of published works, as well as a detailed description of his research program
Discordant Alternans Mechanism for Initiation of Ventricular Fibrillation In Vitro
Background: Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Methods and Results: Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block (P \u3c 1x10E-15, coefficient 44.36) and sustained ventricular fibrillation (P=0.0046, coefficient, 1.63) events. Conclusions: The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation
Arrhythmogenicity quantification of two genetic defects affecting IKr channel in AF patients
[EN] Atrial fibrillation (AF) is the most common cardiac arrhythmia
characterized by disorganized electrical activations of the upper
chambers of the heart, leading to uncoordinated contraction and
compromising the pumping action of the organ. AF risk factors
include cardiovascular pathologies, endocrine disorders,
advanced age, obesity, smoking and heritability. Genetic
mutations affecting gene encoding for ion channel protein
structures are in fact considered as cause of fibrillatory events in
individuals who do not present any other co-morbidities.
In this work, two genetic mutations found in literature and
affecting the alpha-subunit of the rapid delayed rectifier
potassium channel are modelled, by reparametrizing the IKr
current formulation and by fitting it to mutant experimental data.
The modified potassium current was then incorporated into the
Courtemanche-Ramirez-Nattel (CRN) model and single cell
simulations have been performed to study the mutationsÂż effects
on action potential and current traces, as well as, restitution
properties, in right and left atrium. Both mutations produced a
shortening of the action potential duration at 90% of
repolarization (APD90), a higher current peak and lower APD
values in the restitution curves. T895M yielded also to a reduction
in the maximum slope of restitution curve.
Tissue patch simulations revealed that T895M and T436M
provide a substrate to initiate and maintain re-entries during the
5 seconds of simulation. RotorÂżs meandering in T895M appears
more stable with a less extended area and more regular pattern
than in T436M. Investigation on 3D atria and torso models will
be necessary to provide further insights in understanding the
mechanisms behind these genetic mutations.I am grateful to the teams at GaTech, who helped me in the
realization of this work. This project has been funded by
the European Union's Horizon 2020 research and
innovation programme under the Marie Sklodowska-Curie
gran agreement No.766082 and by Generalitat Valenciana,
Prometeo programme 2020/043.Belletti, R.; MartĂnez Mateu, L.; Romero PĂ©rez, L.; Cherry, E.; Fenton, FH.; Saiz RodrĂguez, FJ. (2020). Arrhythmogenicity quantification of two genetic defects affecting IKr channel in AF patients. Sociedad Española de IngenierĂa BiomĂ©dica. 141-144. http://hdl.handle.net/10251/178268S14114
Direct measurement of antiferromagnetic domain fluctuations
Measurements of magnetic noise emanating from ferromagnets due to domain
motion were first carried out nearly 100 years ago and have underpinned much
science and technology. Antiferromagnets, which carry no net external magnetic
dipole moment, yet have a periodic arrangement of the electron spins extending
over macroscopic distances, should also display magnetic noise, but this must
be sampled at spatial wavelengths of order several interatomic spacings, rather
than the macroscopic scales characteristic of ferromagnets. Here we present the
first direct measurement of the fluctuations in the nanometre-scale spin-
(charge-) density wave superstructure associated with antiferromagnetism in
elemental Chromium. The technique used is X-ray Photon Correlation
Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that
serves as a "fingerprint" of a particular magnetic domain configuration. The
temporal evolution of the patterns corresponds to domain walls advancing and
retreating over micron distances. While the domain wall motion is thermally
activated at temperatures above 100K, it is not so at lower temperatures, and
indeed has a rate which saturates at a finite value - consistent with quantum
fluctuations - on cooling below 40K. Our work is important because it provides
an important new measurement tool for antiferromagnetic domain engineering as
well as revealing a fundamental new fact about spin dynamics in the simplest
antiferromagnet.Comment: 19 pages, 4 figure
Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study
Background
Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood.
Methods
We simulated a 150 Ă— 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution.
Results
Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms).
Conclusion
Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve
Overexpression of VEGF121, but not VEGF165 or FGF-1, improves oxygenation in MCF-7 breast tumours
Scroll waves in isotropic excitable media : linear instabilities, bifurcations and restabilized states
Scroll waves are three-dimensional analogs of spiral waves. The linear
stability spectrum of untwisted and twisted scroll waves is computed for a
two-variable reaction-diffusion model of an excitable medium. Different bands
of modes are seen to be unstable in different regions of parameter space. The
corresponding bifurcations and bifurcated states are characterized by
performing direct numerical simulations. In addition, computations of the
adjoint linear stability operator eigenmodes are also performed and serve to
obtain a number of matrix elements characterizing the long-wavelength
deformations of scroll waves.Comment: 30 pages 16 figures, submitted to Phys. Rev.
Approximate probabilistic verification of hybrid systems
Hybrid systems whose mode dynamics are governed by non-linear ordinary
differential equations (ODEs) are often a natural model for biological
processes. However such models are difficult to analyze. To address this, we
develop a probabilistic analysis method by approximating the mode transitions
as stochastic events. We assume that the probability of making a mode
transition is proportional to the measure of the set of pairs of time points
and value states at which the mode transition is enabled. To ensure a sound
mathematical basis, we impose a natural continuity property on the non-linear
ODEs. We also assume that the states of the system are observed at discrete
time points but that the mode transitions may take place at any time between
two successive discrete time points. This leads to a discrete time Markov chain
as a probabilistic approximation of the hybrid system. We then show that for
BLTL (bounded linear time temporal logic) specifications the hybrid system
meets a specification iff its Markov chain approximation meets the same
specification with probability . Based on this, we formulate a sequential
hypothesis testing procedure for verifying -approximately- that the Markov
chain meets a BLTL specification with high probability. Our case studies on
cardiac cell dynamics and the circadian rhythm indicate that our scheme can be
applied in a number of realistic settings
- …