Control of scroll wave turbulence using resonant perturbations

Turbulence of scroll waves is a sort of spatio-temporal chaos that exists in three-dimensional excitable media. Cardiac tissue and the Belousov-Zhabotinsky reaction are examples of such media. In cardiac tissue, chaotic behaviour is believed to underlie fibrillation which, without intervention, precedes cardiac death. In this study we investigate suppression of the turbulence using stimulation of two different types, "modulation of excitability" and "extra transmembrane current". With cardiac defibrillation in mind, we used a single pulse as well as repetitive extra current with both constant and feedback controlled frequency. We show that turbulence can be terminated using either a resonant modulation of excitability or a resonant extra current. The turbulence is terminated with much higher probability using a resonant frequency perturbation than a non-resonant one. Suppression of the turbulence using a resonant frequency is up to fifty times faster than using a non-resonant frequency, in both the modulation of excitability and the extra current modes. We also demonstrate that resonant perturbation requires strength one order of magnitude lower than that of a single pulse, which is currently used in clinical practice to terminate cardiac fibrillation. Our results provide a robust method of controlling complex chaotic spatio-temporal processes. Resonant drift of spiral waves has been studied extensively in two dimensions, however, these results show for the first time that it also works in three dimensions, despite the complex nature of the scroll wave turbulence.Comment: 13 pages, 12 figures, submitted to Phys Rev E 2008/06/13. Last version: 2008/09/18, after revie

How to infer gene networks from expression profiles

Inferring, or ‘reverse-engineering', gene networks can be defined as the process of identifying gene interactions from experimental data through computational analysis. Gene expression data from microarrays are typically used for this purpose. Here we compared different reverse-engineering algorithms for which ready-to-use software was available and that had been tested on experimental data sets. We show that reverse-engineering algorithms are indeed able to correctly infer regulatory interactions among genes, at least when one performs perturbation experiments complying with the algorithm requirements. These algorithms are superior to classic clustering algorithms for the purpose of finding regulatory interactions among genes, and, although further improvements are needed, have reached a discreet performance for being practically useful

Elucidation of Directionality for Co-Expressed Genes: Predicting Intra-Operon Termination Sites

We present a novel framework for inferring regulatory and sequence-level information from gene co-expression networks. The key idea of our methodology is the systematic integration of network inference and network topological analysis approaches for uncovering biological insights. We determine the gene co-expression network of Bacillus subtilis using Affymetrix GeneChip time series data and show how the inferred network topology can be linked to sequence-level information hard-wired in the organism's genome. We propose a systematic way for determining the correlation threshold at which two genes are assessed to be co-expressed by using the clustering coefficient and we expand the scope of the gene co-expression network by proposing the slope ratio metric as a means for incorporating directionality on the edges. We show through specific examples for B. subtilis that by incorporating expression level information in addition to the temporal expression patterns, we can uncover sequence-level biological insights. In particular, we are able to identify a number of cases where (i) the co-expressed genes are part of a single transcriptional unit or operon and (ii) the inferred directionality arises due to the presence of intra-operon transcription termination sites.Comment: 7 pages, 8 figures, accepted in Bioinformatic

On the Integrability, B\"Acklund Transformation and Symmetry Aspects of a Generalized Fisher Type Nonlinear Reaction-Diffusion Equation

The dynamics of nonlinear reaction-diffusion systems is dominated by the onset of patterns and Fisher equation is considered to be a prototype of such diffusive equations. Here we investigate the integrability properties of a generalized Fisher equation in both (1+1) and (2+1) dimensions. A Painlev\'e singularity structure analysis singles out a special case ($m=2$) as integrable. More interestingly, a B\"acklund transformation is shown to give rise to a linearizing transformation for the integrable case. A Lie symmetry analysis again separates out the same $m=2$ case as the integrable one and hence we report several physically interesting solutions via similarity reductions. Thus we give a group theoretical interpretation for the system under study. Explicit and numerical solutions for specific cases of nonintegrable systems are also given. In particular, the system is found to exhibit different types of travelling wave solutions and patterns, static structures and localized structures. Besides the Lie symmetry analysis, nonclassical and generalized conditional symmetry analysis are also carried out.Comment: 30 pages, 10 figures, to appear in Int. J. Bifur. Chaos (2004

Oxidation resistance of nano-reinforced PC-refractories modified with phenol formaldehyde resin. Part 4. Thermodynamic evaluation of phase formation within Mg–O–C–Al, Mg–O–C–Ni and МgO‒Al₂O₃‒NiO‒SiO₂ systems using SiC + Al + Ni (NiO) complex antioxidant

Results are given for the synthesis and co-existence of phases formed from components of complex organic- inorganic antioxidant formed during modification of phenol-formaldehyde resin (PFR) and graphite with silica alkoxide and inorganic or organic nickel precursors. Thermodynamic analysis is given for the Mg–Al–C and Mg–O–Ni–C systems. It is shown that the periclase and carbon can coexist with aluminum and nickel, and also that oxidized antioxidants Al₂O₃ and NiO can interact respectively with the periclase and with the synthesized SiC formed during modification of PFR with silica. In considering the NiO‒MgO‒Al₂O₃‒SiO₂ system it is established that during service noble spinel will be synthesized from the complex antioxidant components, facilitating an increase in PC-refractory durability in service

GENETIC POLYMORPHISM OF INFLAMMATORY FACTORS IS ASSOCIATED WITH THROMBOEMBOLIC COMPLICATIONS OF ATRIAL FIBRILLATION

Aim. To reveal the association of hereditary specifics of inflammatory factors with the adverse risk in atrial fibrillation (AF).Material and methods. Totally 258 patients studied (68,5±0,67 y. o.) with nonvalvular AF, recording the events as ischemic stroke, myocardial infarction, venous and arterial thromboembolism. Mean follow-up was 455±11,71 days.Results. Factors that are independently associated with ischemic stroke development in patients not receiving anticoagulants (n=101), were the allele C of polymorphic marker rs2228145(А/С) of gene IL-6 receptor (OR 13,25 CI 1,57112,18, р=0,018), age ?75 y. o. (OR 1,1, CI 1,008-1,2, р=0,032) and EF LV (OR 0,97 CI 0,94-0,99 р=0,027), with a “thrombotic endpoint” development — DM (OR 4,3 CI 1,46-12,45 р=0,008), EF LV (OR 0,96 CI 0,94-0,98, р<0,0001) and carriage of allele C of polymorphic marker rs2228145(А/С) of receptor to IL-6 gene (OR 4,03 CI 1,0715,26, р=0,04). There was no association with adverse outcomes in genes IL-6 polymorphisms as (G(-174)C and G(-572)C), ИЛ-10 (C(-819)T), ФНО (G(-238)A, G(-308)A and ФНО? rs180630). In those receiving adequate anticoagulant therapy (n=157) there was no significant association of IL-6 receptor gene polymorphism with adverse outcomes.Conclusion. Therefore, the carriage of allele C of polymorphic marker rs2228145(А/С) of the IL-6 receptor gene might be an independent risk marker for adverse outcome in non-valvular AF, potentially, being a selection tool for those patients not having enough high risk according to common scores

Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone

Abnormal electrical activity from the boundaries of ischemic cardiac tissue is recognized as one of the major causes in generation of ischemia-reperfusion arrhythmias. Here we present theoretical analysis of the waves of electrical activity that can rise on the boundary of cardiac cell network upon its recovery from ischaemia-like conditions. The main factors included in our analysis are macroscopic gradients of the cell-to-cell coupling and cell excitability and microscopic heterogeneity of individual cells. The interplay between these factors allows one to explain how spirals form, drift together with the moving boundary, get transiently pinned to local inhomogeneities, and finally penetrate into the bulk of the well-coupled tissue where they reach macroscopic scale. The asymptotic theory of the drift of spiral and scroll waves based on response functions provides explanation of the drifts involved in this mechanism, with the exception of effects due to the discreteness of cardiac tissue. In particular, this asymptotic theory allows an extrapolation of 2D events into 3D, which has shown that cells within the border zone can give rise to 3D analogues of spirals, the scroll waves. When and if such scroll waves escape into a better coupled tissue, they are likely to collapse due to the positive filament tension. However, our simulations have shown that such collapse of newly generated scrolls is not inevitable and that under certain conditions filament tension becomes negative, leading to scroll filaments to expand and multiply leading to a fibrillation-like state within small areas of cardiac tissue.Comment: 26 pages, 13 figures, appendix and 2 movies, as accepted to PLoS ONE 2011/08/0

Buckling of scroll waves

A scroll wave in a sufficiently thin layer of an excitable medium with negative filament tension can be stable nevertheless due to filament rigidity. Above a certain critical thickness of the medium, such scroll wave will have a tendency to deform into a buckled, precessing state. Experimentally this will be seen as meandering of the spiral wave on the surface, the amplitude of which grows with the thickness of the layer, until a break-up to scroll wave turbulence happens. We present a simplified theory for this phenomenon and illustrate it with numerical examples.Comment: 4 pages main text + 5 pages appendix, 4+2 figures and a movie, as accepted by Phys Rev Letters 2012/09/2

Анкилозирующий спондилоартрит в ревматологической практике Карелии

The paper describes the pathological aspects of an inflammatory process in ankylosing spondyloarthritis (AS), the role of muscle spasm in maintaining the intensity of pain syndrome and stiffness, the need for the early diagnosis of AS, and the significance of the early use of nonster-oidal anti-inflammatory drugs in these patients. The results of clinical trials and the authorsX data demonstrate the high efficacy and good tolerance of nimesulide (nise) in AS.Представлены патоморфологические аспекты воспалительного процесса при анкилозирующем спондилоартрите (АС), роль мышечного спазма в поддержании интенсивности болевого синдрома и скованности, необходимость ранней диагностики АС, значение раннего применения нестероидных противовоспалительных препаратов у таких пациентов. Результаты клинических исследований и собственные данные авторов демонстрируют высокую эффективность и хорошую переносимость нимесулида (найз) при АС

LinkEHR-Ed: A multi-reference model archetype editor based on formal semantics

Purpose To develop a powerful archetype editing framework capable of handling multiple reference models and oriented towards the semantic description and standardization of legacy data. Methods The main prerequisite for implementing tools providing enhanced support for archetypes is the clear specification of archetype semantics. We propose a formalization of the definition section of archetypes based on types over tree-structured data. It covers the specialization of archetypes, the relationship between reference models and archetypes and conformance of data instances to archetypes. Results LinkEHR-Ed, a visual archetype editor based on the former formalization with advanced processing capabilities that supports multiple reference models, the editing and semantic validation of archetypes, the specification of mappings to data sources, and the automatic generation of data transformation scripts, is developed. Conclusions LinkEHR-Ed is a useful tool for building, processing and validating archetypes based on any reference model.This work was supported in part by the Spanish Ministry of Education and Science under grant TS12007-66S7S-C02; by the Generalitat Valenciana under grant APOSTD/2007/055 and by the program PAID-06-07 de la Universidad Politecnica de Valencia.Maldonado Segura, JA.; Moner Cano, D.; Boscá Tomás, D.; Fernandez Breis, JT.; Angulo Fernández, C.; Robles Viejo, M. (2009). LinkEHR-Ed: A multi-reference model archetype editor based on formal semantics. International Journal of Medical Informatics. 78(8):559-570. https://doi.org/10.1016/j.ijmedinf.2009.03.006S55957078