Parameter Sensitivity and Experimental Validation for Fractional-Order Dynamical Modeling of Neurovascular Coupling

Goal: Neurovascular coupling is a fundamental mechanism linking neural activity to cerebral blood flow (CBF) response. Modeling this coupling is very important to understand brain functions, yet challenging due to the complexity of the involved phenomena. One key feature that different studies have reported is the time delay that is inherently present between the neural activity and cerebral blood flow, which has been described by adding a delay parameter in standard models. An alternative approach was recently proposed where the framework of fractional-order modeling is employed to characterize the complex phenomena underlying the neurovascular. Thanks to its nonlocal property, a fractional derivative is suitable for modeling delayed and power-law phenomena. Methods: In this study, we analyzed and validated an effective fractional-order for the effective modeling and characterization of the neurovascular coupling mechanism. To show the added value of the fractional order parameters of the proposed model, we perform a parameter sensitivity analysis of the fractional model compared to its integer counterpart. Moreover, the model was validated using neural activity-CBF data related to both event and block design experiments that were acquired using electrophysiology and laser Doppler flowmetry recordings, respectively. Results: The validation results show the aptitude and flexibility of the fractional-order paradigm in fitting a more comprehensive range of well-shaped CBF response behaviors while maintaining a low model complexity. Comparison with the standard integer-order models shows the added value of the fractional-order parameters in capturing various key determinants of the cerebral hemodynamic response, e.g., post-stimulus undershoot. Conclusions: This investigation authenticates the ability and adaptability of the fractional-order framework to characterize a wider range of wellshaped cerebral blood flow responses while preserving low model complexity through a series of unconstrained and constrained optimizations

Finite-time simultaneous estimation of aortic blood flow and differentiation order for fractional-order arterial Windkessel model calibration

A fractional-order vascular model representation for emulating arterial hemody-namics has been recently presented as an alternative to the well-known integer-order arterial Windkessel. The model uses a fractional-order capacitor (FOC) to describe the complex and frequency-dependent arterial compliance. This paper presents a two-stage algorithm based on modulating functions for finite-time simultaneous estimation of the model’s input and the fractional differentiation order. The proposed approach is validated using in-silico human data. Results show the prominent potential of this method for calibrating arterial models and enhancing cardiovascular mechanics research as well as clinical practice

aWCluster: A novel integrative network-based clustering of multiomics for subtype analysis of cancer data

The remarkable growth of multi-platform genomic profiles has led to the challenge of multiomics data integration. In this study, we present a novel network-based multiomics clustering founded on the Wasserstein distance from optimal mass transport. This distance has many important geometric properties making it a suitable choice for application in machine learning and clustering. Our proposed method of aggregating multiomics and Wasserstein distance clustering (aWCluster) is applied to breast carcinoma as well as bladder carcinoma, colorectal adenocarcinoma, renal carcinoma, lung non-small cell adenocarcinoma, and endometrial carcinoma from The Cancer Genome Atlas project. Subtypes were characterized by the concordant effect of mRNA expression, DNA copy number alteration, and DNA methylation of genes and their neighbors in the interaction network. aWCluster successfully clusters all cancer types into classes with significantly different survival rates. Also, a gene ontology enrichment analysis of significant genes in the low survival subgroup of breast cancer leads to the well-known phenomenon of tumor hypoxia and the transcription factor ETS1 whose expression is induced by hypoxia. We believe aWCluster has the potential to discover novel subtypes and biomarkers by accentuating the genes that have concordant multiomics measurements in their interaction network, which are challenging to find without the network inference or with single omics analysis

Long-term p21 and p53 trends regulate the frequency of mitosis events and cell cycle arrest

Radiation exposure of healthy cells can halt cell cycle temporarily or permanently. In this work, two single cell datasets that monitored the time evolution of p21 and p53, one subjected to gamma irradiation and the other to x-ray irradiation, are analyzed to uncover the dynamics of this process. New insights into the biological mechanisms were found by decomposing the p53 and p21 signals into transient and oscillatory components. Through the use of dynamic time warping on the oscillatory components of the two signals, we found that p21 signaling lags behind its lead signal, p53, by about 3.5 hours with oscillation periods of around 6 hours. Additionally, through various quantification methods, we showed how p21 levels, and to a lesser extent p53 levels, dictate whether the cells are arrested in their cell cycle and how fast these cells divide depending on their long-term trend in these signals

Periodicity Scoring of Time Series Encodes Dynamical Behavior of the Tumor Suppressor p53

In this paper we analyze the dynamical behavior of the tumor suppressor protein p53, an essential player in the cellular stress response, which prevents a cell from dividing if severe DNA damage is present. When this response system is malfunctioning, e.g. due to mutations in p53, uncontrolled cell proliferation may lead to the development of cancer. Understanding the behavior of p53 is thus crucial to prevent its failing. It has been shown in various experiments that periodicity of the p53 signal is one of the main descriptors of its dynamics, and that its pulsing behavior (regular vs. spontaneous) indicates the level and type of cellular stress. In the present work, we introduce an algorithm to score the local periodicity of a given time series (such as the p53 signal), which we call Detrended Autocorrelation Periodicity Scoring (DAPS). It applies pitch detection (via autocorrelation) on sliding windows of the entire time series to describe the overall periodicity by a distribution of localized pitch scores. We apply DAPS to the p53 time series obtained from single cell experiments and establish a correlation between the periodicity scoring of a cell’s p53 signal and the number of cell division events. In particular, we show that high periodicity scoring of p53 is correlated to a low number of cell divisions and vice versa. We show similar results with a more computationally intensive state-of-the-art periodicity scoring algorithm based on topology known as Sw1PerS. This correlation has two major implications: It demonstrates that periodicity scoring of the p53 signal is a good descriptor for cellular stress, and it connects the high variability of p53 periodicity observed in cell populations to the variability in the number of cell division events

Multiple model iterative learning control of FES electrode arrays

Stroke is a common cause of hand and upper limb disability, but current rehabilitation approaches do not adequately support successful recovery. Functional electrical stimulation (FES) is the most widely used assistive technology, and is able to support accurate hand and wrist motion when applied using multi-element electrode arrays. However, accurate movements have only been possible using an iterative learning control (ILC) approach involving many repeated model identification tests. This lengthy process limits wide-spread use. This paper presents a solution for FES electrode array control using estimation-based multiple-model ILC (EM-MILC), in which a set of parameterised models is used to automatically update the stimulation applied to each array element every time a task is carried out. This removes the need for model identification, significantly improving system usability whilst maintaining high performance. Experimental results demonstrate that EM-MILC reduces the average number of tests from 16 to 3, compared to the most accurate existing approach

Initialization of fractional order systems for the joint estimation of parameters and fractional differentiation orders

International audienc

A new discrete-time interval estimator for vehicle side-slip angle estimation

International audienceThe information about vehicle side-slip angle is essential given its relation to lateral stability and its importance for active safety control systems. Since direct measurement of the side-slip angle is expensive, developing efficient indirect techniques to extract this information from available sensor measurements is essential. This paper proposes a novel, cost-effective indirect strategy for the robust estimation of the side-slip angle using a state observer that relies on a discrete-time Linear Parameter Varying (LPV) lateral vehicle dynamic model. The proposed algorithm relies on a finite-time interval LMI-based observer, which accounts for the uncertainties on the model parameters (cornering stiffness) with known upper and lower uncertainty bounds. The simulation results show the effective and robust estimation performance of the proposed observer under various changes in system parameters. Moreover, comparison results with H∞ set-membership observer for discrete-time LPV systems show the effectiveness of the developed observer