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- ItemTiming cellular decision making under noise via cell-cell communication(San Francisco, CA : Public Library of Science (PLoS), 2009) Koseska, A.; Zaikin, A.; Kurths, J.; García-Ojalvo, J.Many cellular processes require decision making mechanisms, which must act reliably even in the unavoidable presence of substantial amounts of noise. However, the multistable genetic switches that underlie most decision-making processes are dominated by fluctuations that can induce random jumps between alternative cellular states. Here we show, via theoretical modeling of a population of noise-driven bistable genetic switches, that reliable timing of decision-making processes can be accomplished for large enough population sizes, as long as cells are globally coupled by chemical means. In the light of these results, we conjecture that cell proliferation, in the presence of cell-cell communication, could provide a mechanism for reliable decision making in the presence of noise, by triggering cellular transitions only when the whole cell population reaches a certain size. In other words, the summation performed by the cell population would average out the noise and reduce its detrimental impact.
- ItemAn electronic analog of synthetic genetic networks(San Francisco, CA : Public Library of Science (PLoS), 2011) Hellen, E.H.; Volkov, E.; Kurths, J.; Dana, S.K.An electronic analog of a synthetic genetic network known as the repressilator is proposed. The repressilator is a synthetic biological clock consisting of a cyclic inhibitory network of three negative regulatory genes which produces oscillations in the expressed protein concentrations. Compared to previous circuit analogs of the repressilator, the circuit here takes into account more accurately the kinetics of gene expression, inhibition, and protein degradation. A good agreement between circuit measurements and numerical prediction is observed. The circuit allows for easy control of the kinetic parameters thereby aiding investigations of large varieties of potential dynamics.
- ItemCardio-respiratory coordination increases during sleep apnea(San Francisco, CA : Public Library of Science (PLoS), 2014) Riedl, M.; Müller, A.; Kraemer, J.F.; Penzel, T.; Kurths, J.; Wessel, N.Cardiovascular diseases are the main source of morbidity and mortality in the United States with costs of more than $170 billion. Repetitive respiratory disorders during sleep are assumed to be a major cause of these diseases. Therefore, the understanding of the cardio-respiratory regulation during these events is of high public interest. One of the governing mechanisms is the mutual influence of the cardiac and respiratory oscillations on their respective onsets, the cardiorespiratory coordination (CRC). We analyze this mechanism based on nocturnal measurements of 27 males suffering from obstructive sleep apnea syndrome. Here we find, by using an advanced analysis technique, the coordigram, not only that the occurrence of CRC is significantly more frequent during respiratory sleep disturbances than in normal respiration (p-value<10-51) but also more frequent after these events (p-value<10-15). Especially, the latter finding contradicts the common assumption that spontaneous CRC can only be observed in epochs of relaxed conditions, while our newly discovered epochs of CRC after disturbances are characterized by high autonomic stress. Our findings on the connection between CRC and the appearance of sleep-disordered events require a substantial extension of the current understanding of obstructive sleep apneas and hypopneas.
- ItemSleep apnea-hypopnea quantification by cardiovascular data analysis(San Francisco, CA : Public Library of Science (PLoS), 2014) Camargo, S.; Riedl, M.; Anteneodo, C.; Kurths, J.; Penzel, T.; Wessel, N.Sleep disorders are a major risk factor for cardiovascular diseases. Sleep apnea is the most common sleep disturbance and its detection relies on a polysomnography, i.e., a combination of several medical examinations performed during a monitored sleep night. In order to detect occurrences of sleep apnea without the need of combined recordings, we focus our efforts on extracting a quantifier related to the events of sleep apnea from a cardiovascular time series, namely systolic blood pressure (SBP). Physiologic time series are generally highly nonstationary and entrap the application of conventional tools that require a stationary condition. In our study, data nonstationarities are uncovered by a segmentation procedure which splits the signal into stationary patches, providing local quantities such as mean and variance of the SBP signal in each stationary patch, as well as its duration L. We analysed the data of 26 apneic diagnosed individuals, divided into hypertensive and normotensive groups, and compared the results with those of a control group. From the segmentation procedure, we identified that the average duration 〈L〉, as well as the average variance 〈σ2〉, are correlated to the apnea-hypoapnea index (AHI), previously obtained by polysomnographic exams. Moreover, our results unveil an oscillatory pattern in apneic subjects, whose amplitude S∗ is also correlated with AHI. All these quantities allow to separate apneic individuals, with an accuracy of at least 79%. Therefore, they provide alternative criteria to detect sleep apnea based on a single time series, the systolic blood pressure.