5,038 research outputs found
Modelling the effects of disopyramide on short QT syndrome variant 1 in the human ventricles
The short QT syndrome (SQTS) is a recently identified genetic disorder associated with ventricular and/or atrial arrhythmias and increased risk of sudden cardiac death. The SQTS variant 1 (SQT1) N588K mutation to the hERG gene causes a gain-of-function to IKr which shortens the ventricular effective refractory period (ERP), as well as reducing the potency of several drugs which block the hERG channel. This study used computational modelling to assess the effects of disopyramide (DISO), a class 1a anti-arrhythmic agent, on human ventricular electro-physiology in SQT1. The O'Hara Rudy dynamic (ORd) model of the human ventricle action potential (AP) was modified to incorporate a Markov chain model of IKr/hERG including formulations for wild type (WT) and SQT1 N588K mutant hERG channels. The blocking effects of DISO on IKr, INa, ICaL, and Ito were modelled using IC50 and Hill coefficient values from the literature. The ability of DISO to prolong the QT interval was evaluated using a 1D model of human ventricular cells with transmural heterogeneities and the corresponding pseudo-ECG. At a clinically-relevant concentration of 10 μM DISO, the action potential duration (APD) at the single cell level was increased significantly through inhibition of mutant SQT1-hERG channels. The corrected QT interval in tissue was prolonged. This study provides further evidence that DISO is a suitable treatment for hERG-mediated SQTS
Modelling the effects of disopyramide on short QT syndrome variant 1 in the human ventricles
The short QT syndrome (SQTS) is a recently identified genetic disorder associated with ventricular and/or atrial arrhythmias and increased risk of sudden cardiac death. The SQTS variant 1 (SQT1) N588K mutation to the hERG gene causes a gain-of-function to IKr which shortens the ventricular effective refractory period (ERP), as well as reducing the potency of several drugs which block the hERG channel. This study used computational modelling to assess the effects of disopyramide (DISO), a class 1a anti-arrhythmic agent, on human ventricular electro-physiology in SQT1. The O'Hara Rudy dynamic (ORd) model of the human ventricle action potential (AP) was modified to incorporate a Markov chain model of IKr/hERG including formulations for wild type (WT) and SQT1 N588K mutant hERG channels. The blocking effects of DISO on IKr, INa, ICaL, and Ito were modelled using IC50 and Hill coefficient values from the literature. The ability of DISO to prolong the QT interval was evaluated using a 1D model of human ventricular cells with transmural heterogeneities and the corresponding pseudo-ECG. At a clinically-relevant concentration of 10 μM DISO, the action potential duration (APD) at the single cell level was increased significantly through inhibition of mutant SQT1-hERG channels. The corrected QT interval in tissue was prolonged. This study provides further evidence that DISO is a suitable treatment for hERG-mediated SQTS
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An Overview of the Use of Neural Networks for Data Mining Tasks
In the recent years the area of data mining has experienced a considerable demand for technologies that extract knowledge from large and complex data sources. There is a substantial commercial interest as well as research investigations in the area that aim to develop new and improved approaches for extracting information, relationships, and patterns from datasets. Artificial Neural Networks (NN) are popular biologically inspired intelligent methodologies, whose classification, prediction and pattern recognition capabilities have been utilised successfully in many areas, including science, engineering, medicine, business, banking, telecommunication, and many other fields. This paper highlights from a data mining perspective the implementation of NN, using supervised and unsupervised learning, for pattern recognition, classification, prediction and cluster analysis, and focuses the discussion on their usage in bioinformatics and financial data analysis tasks
Aharonov-Bohm interferences from local deformations in graphene
One of the most interesting aspects of graphene is the tied relation between
structural and electronic properties. The observation of ripples in the
graphene samples both free standing and on a substrate has given rise to a very
active investigation around the membrane-like properties of graphene and the
origin of the ripples remains as one of the most interesting open problems in
the system. The interplay of structural and electronic properties is
successfully described by the modelling of curvature and elastic deformations
by fictitious gauge fields that have become an ex- perimental reality after the
suggestion that Landau levels can form associated to strain in graphene and the
subsequent experimental confirmation. Here we propose a device to detect
microstresses in graphene based on a scanning-tunneling-microscopy setup able
to measure Aharonov-Bohm inter- ferences at the nanometer scale. The
interferences to be observed in the local density of states are created by the
fictitious magnetic field associated to elastic deformations of the sample.Comment: Some bugs fixe
Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea
Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes
QCD with Chemical Potential in a Small Hyperspherical Box
To leading order in perturbation theory, we solve QCD, defined on a small
three sphere in the large N and Nf limit, at finite chemical potential and map
out the phase diagram in the (mu,T) plane. The action of QCD is complex in the
presence of a non-zero quark chemical potential which results in the sign
problem for lattice simulations. In the large N theory, which at low
temperatures becomes a conventional unitary matrix model with a complex action,
we find that the dominant contribution to the functional integral comes from
complexified gauge field configurations. For this reason the eigenvalues of the
Polyakov line lie off the unit circle on a contour in the complex plane. We
find at low temperatures that as mu passes one of the quark energy levels there
is a third-order Gross-Witten transition from a confined to a deconfined phase
and back again giving rise to a rich phase structure. We compare a range of
physical observables in the large N theory to those calculated numerically in
the theory with N=3. In the latter case there are no genuine phase transitions
in a finite volume but nevertheless the observables are remarkably similar to
the large N theory.Comment: 44 pages, 18 figures, jhep3 format. Small corrections and
clarifications added in v3. Conclusions cleaned up. Published versio
The magnetic nature of disk accretion onto black holes
Although disk accretion onto compact objects - white dwarfs, neutron stars,
and black holes - is central to much of high energy astrophysics, the
mechanisms which enable this process have remained observationally elusive.
Accretion disks must transfer angular momentum for matter to travel radially
inward onto the compact object. Internal viscosity from magnetic processes and
disk winds can in principle both transfer angular momentum, but hitherto we
lacked evidence that either occurs. Here we report that an X-ray-absorbing wind
discovered in an observation of the stellar-mass black hole binary GRO J1655-40
must be powered by a magnetic process that can also drive accretion through the
disk. Detailed spectral analysis and modeling of the wind shows that it can
only be powered by pressure generated by magnetic viscosity internal to the
disk or magnetocentrifugal forces. This result demonstrates that disk accretion
onto black holes is a fundamentally magnetic process.Comment: 15 pages, 2 color figures, accepted for publication in Nature.
Supplemental materials may be obtained by clicking
http://www.astro.lsa.umich.edu/~jonmm/nature1655.p
Play dough as an educational tool for visualization of complicated cerebral aneurysm anatomy
BACKGROUND: Imagination of the three-dimensional (3D) structure of cerebral vascular lesions using two-dimensional (2D) angiograms is one of the skills that neurosurgical residents should achieve during their training. Although ongoing progress in computer software and digital imaging systems has facilitated viewing and interpretation of cerebral angiograms enormously, these facilities are not always available. METHODS: We have presented the use of play dough as an adjunct to the teaching armamentarium for training in visualization of cerebral aneurysms in some cases. RESULTS: The advantages of play dough are low cost, availability and simplicity of use, being more efficient and realistic in training the less experienced resident in comparison with the simple drawings and even angiographic views from different angles without the need for computers and similar equipment. The disadvantages include the psychological resistance of residents to the use of something in surgical training that usually is considered to be a toy, and not being as clean as drawings or computerized images. CONCLUSION: Although technology and computerized software using the patients' own imaging data seems likely to become more advanced in the future, use of play dough in some complicated cerebral aneurysm cases may be helpful in 3D reconstruction of the real situation
Strain- and Adsorption-Dependent Electronic States and Transport or Localization in Graphene
The chapter generalizes results on influence of uniaxial strain and
adsorption on the electron states and charge transport or localization in
graphene with different configurations of imperfections (point defects):
resonant (neutral) adsorbed atoms either oxygen- or hydrogen-containing
molecules or functional groups, vacancies or substitutional atoms, charged
impurity atoms or molecules, and distortions. To observe electronic properties
of graphene-admolecules system, we applied electron paramagnetic resonance
technique in a broad temperature range for graphene oxides as a good basis for
understanding the electrotransport properties of other active carbons. Applied
technique allowed observation of possible metal-insulator transition and
sorption pumping effect as well as discussion of results in relation to the
granular metal model. The electronic and transport properties are calculated
within the framework of the tight-binding model along with the Kubo-Greenwood
quantum-mechanical formalism. Depending on electron density and type of the
sites, the conductivity for correlated and ordered adsorbates is found to be
enhanced in dozens of times as compared to the cases of their random
distribution. In case of the uniaxially strained graphene, the presence of
point defects counteracts against or contributes to the band-gap opening
according to their configurations. The band-gap behaviour is found to be
nonmonotonic with strain in case of a simultaneous action of defect ordering
and zigzag deformation. The amount of localized charge carriers (spins) is
found to be correlated with the content of adsorbed centres responsible for the
formation of potential barriers and, in turn, for the localization effects.
Physical and chemical states of graphene edges, especially at a uniaxial strain
along one of them, play a crucial role in electrical transport phenomena in
graphene-based materials.Comment: 16 pages, 10 figure
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