Recent advances of small molecule detection in nanopore sensing.

Due to its advantages of label-free and highly sensitive, the resistive pulse sensing with a nanopore has recently become even more potent for the discrimination of analytes in single molecule level. Generally, a transient interruption of ion current originated from the captured molecule passing through a nanopore will provide the rich information on the structure, charge and translocation dynamics of the analytes. Therefore, nanopore sensors have been widely used in the fields of DNA sequencing, protein recognition, and the portable detection of varied macromolecules and particles. However, the conventional nanopore devices are still lack of sufficient selectivity and sensitivity to distinguish more metabolic molecules involving ATP, glucose, amino acids and small molecular drugs because it is hard to receive a large number of identifiable signals with the fabricated pores comparable in size to small molecules for nanopore sensing. For all this, a series of innovative strategies developed in the past decades have been summarized in this review, including host-guest recognition, engineering alteration of protein channel, the introduction of nucleic acid aptamers and various delivery carriers integrating signal amplification sections based on the biological and solid nanopore platforms, to achieve the high resolution for the small molecules sensing in micro-nano environment. These works have greatly enhanced the powerful sensing capabilities and extended the potential application of nanopore sensors.

Procedural Data Processing for Single-Molecule Identification by Nanopore Sensors.

Nanopores are promising single-molecule sensing devices that have been successfully used for DNA sequencing, protein identification, as well as virus/particles detection. It is important to understand and characterize the current pulses collected by nanopore sensors, which imply the associated information of the analytes, including the size, structure, and surface charge. Therefore, a signal processing program, based on the MATLAB platform, was designed to characterize the ionic current signals of nanopore measurements. In a movable data window, the selected current segment was analyzed by the adaptive thresholds and corrected by multi-functions to reduce the noise obstruction of pulse signals. Accordingly, a set of single molecular events was identified, and the abundant information of current signals with the dwell time, amplitude, and current pulse area was exported for quantitative analysis. The program contributes to the efficient and fast processing of nanopore signals with a high signal-to-noise ratio, which promotes the development of the nanopore sensing devices in various fields of diagnosis systems and precision medicine.

Transitions in physiological coupling between heartbeat and pulse across sleep stages.

OBJECTIVE: The aim of this study is to investigate the coupling behavior between heartbeat and pulse of blood flow at different sleep stages, and to explore the feasibility of using this coupling strength for automatic sleep staging. APPROACH: The electrocardiogram and photoplethysmography signals are recorded during sleep, and R-wave-to-R-wave intervals (RRI) and pulse-to-pulse intervals (PPI) are extracted respectively. The detrended cross-correlation analysis (DCCA) is applied to quantify long-range cross correlations between the RRIs and PPIs across sleep stages. The DCCA scaling exponents are used as the indicator of coupling strength between heartbeat and pulse, and are compared with detrended fluctuation analysis (DFA) scaling exponents of RRIs and PPIs in the application of sleep stage discrimination. MAIN RESULTS: We find the DCCA scaling exponents between RRIs and PPIs decrease monotonously from wake, REM sleep to light and deep sleep, indicating that the coupling strength between heartbeat and pulse are reduced gradually when entering deep sleep. Statistical analysis shows that the DCCA scaling exponents possess better discrimination ability between wake/REM sleep and light/deep sleep, compared with DFA scaling exponents of RRIs and PPIs. SIGNIFICANCE: Our study reveals the coupling strength between heartbeat and pulse changes regularly across sleep stages, which may help understand the regulation mechanism underlying the cardiovascular system. The DCCA scaling exponents between RRIs and PPIs can be used as an indicator for measuring vigilance level and automatic sleep staging.

Model of the Dynamic Construction Process of Texts and Scaling Laws of Words Organization in Language Systems.

Scaling laws characterize diverse complex systems in a broad range of fields, including physics, biology, finance, and social science. The human language is another example of a complex system of words organization. Studies on written texts have shown that scaling laws characterize the occurrence frequency of words, words rank, and the growth of distinct words with increasing text length. However, these studies have mainly concentrated on the western linguistic systems, and the laws that govern the lexical organization, structure and dynamics of the Chinese language remain not well understood. Here we study a database of Chinese and English language books. We report that three distinct scaling laws characterize words organization in the Chinese language. We find that these scaling laws have different exponents and crossover behaviors compared to English texts, indicating different words organization and dynamics of words in the process of text growth. We propose a stochastic feedback model of words organization and text growth, which successfully accounts for the empirically observed scaling laws with their corresponding scaling exponents and characteristic crossover regimes. Further, by varying key model parameters, we reproduce differences in the organization and scaling laws of words between the Chinese and English language. We also identify functional relationships between model parameters and the empirically observed scaling exponents, thus providing new insights into the words organization and growth dynamics in the Chinese and English language.

Major component analysis of dynamic networks of physiologic organ interactions.

The human organism is a complex network of interconnected organ systems, where the behavior of one system affects the dynamics of other systems. Identifying and quantifying dynamical networks of diverse physiologic systems under varied conditions is a challenge due to the complexity in the output dynamics of the individual systems and the transient and non-linear characteristics of their coupling. We introduce a novel computational method based on the concept of time delay stability and major component analysis to investigate how organ systems interact as a network to coordinate their functions. We analyze a large database of continuously recorded multi-channel physiologic signals from healthy young subjects during night-time sleep. We identify a network of dynamic interactions between key physiologic systems in the human organism. Further, we find that each physiologic state is characterized by a distinct network structure with different relative contribution from individual organ systems to the global network dynamics. Specifically, we observe a gradual decrease in the strength of coupling of heart and respiration to the rest of the network with transition from wake to deep sleep, and in contrast, an increased relative contribution to network dynamics from chin and leg muscle tone and eye movement, demonstrating a robust association between network topology and physiologic function.

Modified permutation-entropy analysis of heartbeat dynamics.

Heart rate variability (HRV) contains important information about the modulation of the cardiovascular system. Various methods of nonlinear dynamics (e.g., estimating Lyapunov exponents) and complexity measures (e.g., correlation dimension or entropies) have been applied to HRV analysis. Permutation entropy, which was proposed recently, has been widely used in many fields due to its conceptual and computational simplicity. It maps a time series onto a symbolic sequence of permutation ranks. The original permutation entropy assumes the time series under study has a continuous distribution, thus equal values are rare and can be ignored by ranking them according to their order of emergence, or broken by adding small random perturbations to ensure every symbol in a sequence is different. However, when the observed time series is digitized with lower resolution leading to a greater number of equal values, or the equalities represent certain characteristic sequential patterns of the system, it may not be rational to simply ignore or break them. In the present paper, a modified permutation entropy is proposed that, by mapping the equal value onto the same symbol (rank), allows for a more accurate characterization of system states. The application of the modified permutation entropy to the analysis of HRV is investigated using clinically collected data. Results show that modified permutation entropy can greatly improve the ability to distinguish the HRV signals under different physiological and pathological conditions. It can characterize the complexity of HRV more effectively than the original permutation entropy.

Effects of coarse-graining on the scaling behavior of long-range correlated and anti-correlated signals.

We investigate how various coarse-graining (signal quantization) methods affect the scaling properties of long-range power-law correlated and anti-correlated signals, quantified by the detrended fluctuation analysis. Specifically, for coarse-graining in the magnitude of a signal, we consider (i) the Floor, (ii) the Symmetry and (iii) the Centro-Symmetry coarse-graining methods. We find that for anti-correlated signals coarse-graining in the magnitude leads to a crossover to random behavior at large scales, and that with increasing the width of the coarse-graining partition interval Δ, this crossover moves to intermediate and small scales. In contrast, the scaling of positively correlated signals is less affected by the coarse-graining, with no observable changes when Δ < 1, while for Δ > 1 a crossover appears at small scales and moves to intermediate and large scales with increasing Δ. For very rough coarse-graining (Δ > 3) based on the Floor and Symmetry methods, the position of the crossover stabilizes, in contrast to the Centro-Symmetry method where the crossover continuously moves across scales and leads to a random behavior at all scales; thus indicating a much stronger effect of the Centro-Symmetry compared to the Floor and the Symmetry method. For coarse-graining in time, where data points are averaged in non-overlapping time windows, we find that the scaling for both anti-correlated and positively correlated signals is practically preserved. The results of our simulations are useful for the correct interpretation of the correlation and scaling properties of symbolic sequences.

Effect of extreme data loss on long-range correlated and anticorrelated signals quantified by detrended fluctuation analysis.

Detrended fluctuation analysis (DFA) is an improved method of classical fluctuation analysis for nonstationary signals where embedded polynomial trends mask the intrinsic correlation properties of the fluctuations. To better identify the intrinsic correlation properties of real-world signals where a large amount of data is missing or removed due to artifacts, we investigate how extreme data loss affects the scaling behavior of long-range power-law correlated and anticorrelated signals. We introduce a segmentation approach to generate surrogate signals by randomly removing data segments from stationary signals with different types of long-range correlations. The surrogate signals we generate are characterized by four parameters: (i) the DFA scaling exponent alpha of the original correlated signal u(i) , (ii) the percentage p of the data removed from u(i) , (iii) the average length mu of the removed (or remaining) data segments, and (iv) the functional form P(l) of the distribution of the length l of the removed (or remaining) data segments. We find that the global scaling exponent of positively correlated signals remains practically unchanged even for extreme data loss of up to 90%. In contrast, the global scaling of anticorrelated signals changes to uncorrelated behavior even when a very small fraction of the data is lost. These observations are confirmed on two examples of real-world signals: human gait and commodity price fluctuations. We further systematically study the local scaling behavior of surrogate signals with missing data to reveal subtle deviations across scales. We find that for anticorrelated signals even 10% of data loss leads to significant monotonic deviations in the local scaling at large scales from the original anticorrelated to uncorrelated behavior. In contrast, positively correlated signals show no observable changes in the local scaling for up to 65% of data loss, while for larger percentage of data loss, the local scaling shows overestimated regions (with higher local exponent) at small scales, followed by underestimated regions (with lower local exponent) at large scales. Finally, we investigate how the scaling is affected by the average length, probability distribution, and percentage of the remaining data segments in comparison to the removed segments. We find that the average length mu_{r} of the remaining segments is the key parameter which determines the scales at which the local scaling exponent has a maximum deviation from its original value. Interestingly, the scales where the maximum deviation occurs follow a power-law relationship with mu_{r} . Whereas the percentage of data loss determines the extent of the deviation. The results presented in this paper are useful to correctly interpret the scaling properties obtained from signals with extreme data loss.

Levels of complexity in scale-invariant neural signals.

Many physical and physiological signals exhibit complex scale-invariant features characterized by 1/f scaling and long-range power-law correlations, indicating a possibly common control mechanism. Specifically, it has been suggested that dynamical processes, influenced by inputs and feedback on multiple time scales, may be sufficient to give rise to 1/f scaling and scale invariance. Two examples of physiologic signals that are the output of hierarchical multiscale physiologic systems under neural control are the human heartbeat and human gait. Here we show that while both cardiac interbeat interval and gait interstride interval time series under healthy conditions have comparable 1/f scaling, they still may belong to different complexity classes. Our analysis of the multifractal scaling exponents of the fluctuations in these two signals demonstrates that in contrast to the multifractal behavior found in healthy heartbeat dynamics, gait time series exhibit less complex, close to monofractal behavior. Further, we find strong anticorrelations in the sign and close to random behavior for the magnitude of gait fluctuations at short and intermediate time scales, in contrast to weak anticorrelations in the sign and strong positive correlation for the magnitude of heartbeat interval fluctuations-suggesting that the neural mechanisms of cardiac and gait control exhibit different linear and nonlinear features. These findings are of interest because they underscore the limitations of traditional two-point correlation methods in fully characterizing physiological and physical dynamics. In addition, these results suggest that different mechanisms of control may be responsible for varying levels of complexity observed in physiological systems under neural regulation and in physical systems that possess similar 1/f scaling.