PSExplorer: whole parameter space exploration for molecular signaling pathway dynamics

Motivation: Mathematical models of biological systems often have a large number of parameters whose combinational variations can yield distinct qualitative behaviors. Since it is intractable to examine all possible combinations of parameters for non-trivial biological pathways, it is required to have a systematic strategy to explore the parameter space in a computational way so that dynamic behaviors of a given pathway are estimated

Turbulence near cyclic fold bifurcations in birhythmic media

We show that at the onset of a cyclic fold bifurcation, a birhythmic medium composed of glycolytic oscillators displays turbulent dynamics. By computing the largest Lyapunov exponent, the spatial correlation function, and the average transient lifetime, we classify it as a weak turbulence with transient nature. Virtual heterogeneities generating unstable fast oscillations are the mechanism of the transient turbulence. In the presence of wavenumber instability, unstable oscillations can be reinjected leading to stationary turbulence. We also find similar turbulence in a cell cycle model. These findings suggest that weak turbulence may be universal in biochemical birhythmic media exhibiting cyclic fold bifurcations.Comment: 14 pages 10 figure

Mechanisms of tricuspid regurgitation in patients with hypoplastic left heart syndrome undergoing tricuspid valvuloplasty

ObjectivesTricuspid regurgitation (TR) remains a risk factor for morbidity and mortality through staged palliation in patients with hypoplastic left heart syndrome (HLHS). Reports on the mechanisms associated with TR in patients with HLHS are limited. Thus, we sought to describe our experience with tricuspid valve (TV) repair in these patients, focusing on the mechanisms of TR and corresponding surgical techniques.MethodsWe performed a retrospective single-center review (January 2000 to December 2012) of patients with HLHS undergoing TV repair and completing Fontan circulation. We evaluated the pre- and postoperative echocardiograms, intraoperative findings, and surgical techniques used.ResultsA total of 53 TV repairs were performed in 35 patients with HLHS completing staged palliation. TV repairs were performed at stage II in 15, between stage II and III in 4, at stage III in 27, and after stage III in 7. The surgical techniques for valvuloplasty included annuloplasty (38%), anteroseptal (AS) commissuroplasty (66%), anterior papillary muscle repositioning (11%), multiple commissuroplasties (9%), septal-posterior commissuroplasty (9%), and fenestration closure (4%). The predominant jet of TR emanated along the AS commissure in 68% of the cases. All patients survived the procedure and were discharged. Preoperative echocardiography showed a dilated TV annulus on the lateral dimension, anteroposterior dimension, and area that was significantly reduced after TV repair (P < .0001). The preoperative mean TR, as assessed by lateral (P = .002) and anteroposterior (P = .005) vena contracta, was also significantly reduced after TV repair. TV repair did not significantly affect right ventricular systolic function immediately after surgery (P = .17) or at the most recent follow-up visit (P = .52). Patients with anterior leaflet prolapse were at increased risk of worse outcomes, including moderate or greater right ventricular dysfunction (P = .02). Patients requiring reoperation for TV repair were younger (6.3 vs 28.1 months, P < .0001) at the initial operation. One patient died of heart failure. Freedom from TV replacement and transplant-free survival were both 97% at the most recent follow-up point.ConclusionsTR in patients with HLHS commonly emanates from the AS commissure. The associated mechanisms are often annular dilatation and anterior leaflet prolapse. Preoperative anterior leaflet prolapse was associated with worse outcomes. Annuloplasty, closure of the AS commissure, and repositioning of the anterior papillary muscle are effective in addressing TR in the short- and mid-term in this challenging population

ЦИФРОВОЙ СТАБИЛИЗАТОР ЛАЗЕРНОГО ЛУЧА ТАНКОВОГО ПРИЦЕЛА-ДАЛЬНОМЕРА

The processes of the stabilization of the laser beam Tank rangefinder sight when using the digital indicator type stabilizer with digital low-pass filter. Algorithms stabilization implemented onboard digital computer, and delivers the accuracy of stabilization. It is shown that the best noise immunity of a closed system stability enables the use of digital filters Butterworth and Lanczos, operating on a series-parallel circuit. Bibl. 6, Fig. 1.Исследованы процессы стабилизации лазерного луча танкового прицела-дальномера при использовании цифрового стабилизатора индикаторного типа с цифровыми низкочастотными фильтрами. Предложены алгоритмы стабилизации, реализуемые бортовой цифровой вычислительной машиной и обеспечивающие необходимую точность стабилизации. Показано, что наилучшую помехозащищенность замкнутой системы стабилизации обеспечивает использование цифровых фильтров Баттеруорта и Ланцоша, функционирующих по последовательно-параллельной схеме. Библ. 6, рис. 1.Досліджені процеси стабілізації лазерного променя танкового прицілу-далекоміра при використанні цифрового стабілізатора індикаторного типа з цифровими низькочастотними фільтрами. Запропоновані алгоритми стабілізації, що реалізовуються бортовою цифровою обчислювальною машиною і що забезпечують необхідну точність стабілізації. Показано, що найкращу перешкодозахищену замкнутої системи стабілізації забезпечує використання цифрових фільтрів Баттеруорта і Ланцоша, що функціонують за послідовно-паралельною схемою. Бібл. 6, мал. 1

Stable stochastic dynamics in yeast cell cycle

Chemical reactions in cell are subject to intense stochastic fluctuations. An important question is how the fundamental physiological behavior of cell is kept stable against those noisy perturbations. In this paper a stochastic model of cell cycle of budding yeast is constructed to analyze the effects of noise on the cell cycle oscillation. The model predicts intense noise in levels of mRNAs and proteins, and the simulated protein levels explain the observed statistical tendency of noise in populations of synchronous and asynchronous cells. In spite of intense noise in levels of proteins and mRNAs, cell cycle is stable enough to bring the largely perturbed cells back to the physiological cyclic oscillation. The model shows that consecutively appearing fixed points are the origin of this stability of cell cycle.Comment: main text, 2 supporting texts, 3 supplementary table

Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch

<p>Abstract</p> <p>Background</p> <p>While biological systems have often been compared with digital systems, they differ by the strong effect of crosstalk between signals due to diffusivity in the medium, reaction kinetics and geometry. Memory elements have allowed the creation of autonomous digital systems and although biological systems have similar properties of autonomy, equivalent memory mechanisms remain elusive. Any such equivalent memory system, however, must silence the effect of crosstalk to maintain memory fidelity.</p> <p>Results</p> <p>Here, we present a system of enzymatic reactions that behaves like an RS latch (a simple memory element in digital systems). Using both a stochastic molecular simulator and ordinary differential equation simulator, we showed that crosstalk between two latches operating in the same spatial localization disrupts the memory fidelity of both latches. Crosstalk was reduced or silenced when simple reaction loops were replaced with multiple step or cascading reactions, showing that cascading signaling pathways are less susceptible to crosstalk.</p> <p>Conclusion</p> <p>Thus, the common biological theme of cascading signaling pathways is advantageous for maintaining the fidelity of a memory latch in the presence of crosstalk. The experimental implementation of such a latch system will lead to novel approaches to cell control using synthetic proteins and will contribute to our understanding of why cells behave differently even when given the same stimulus.</p

Information technologies for decision-making on the conditions of spatially distributed objects

The problem of depression is becoming one of the central problems in the medical practice. In doing so, it has a significant impact on socio-psychological and economic aspects of society. According to Who, depression more than 120 million people worldwide are affected. It is reported that approximately one in three people has had a depressive episode at least once in their lives. Depression only 40% of patients are diagnosed, who suffer from this disorder. Of these, only 10–15% are prescribed therapy with antidepressants. According to the WHO forecast, there will be depression by 2025 occupy the 2nd place after coronary heart disease among the diseases that lead to disability. In most patients experience a decrease in quality of life