High-dimensional switches and the modeling of cellular differentiation

Many genes have been identified as driving cellular differentiation, but because of their complex interactions, the understanding of their collective behaviour requires mathematical modelling. Intriguingly, it has been observed in numerous developmental contexts, and particularly hematopoiesis, that genes regulating differentiation are initially co-expressed in progenitors despite their antagonism, before one is upregulated and others downregulated. We characterise conditions under which 3 classes of generic "master regulatory networks", modelled at the molecular level after experimentally-observed interactions (including bHLH protein dimerisation), and including an arbitrary number of antagonistic components, can behave as a "multi-switch", directing differentiation in an all-or-none fashion to a specific cell-type chosen among more than 2 possible outcomes. bHLH dimerisation networks can readily display coexistence of many antagonistic factors when competition is low (a simple characterisation is derived). Decision-making can be forced by a transient increase in competition, which could correspond to some unexplained experimental observations related to Id proteins; the speed of response varies with the initial conditions the network is subjected to, which could explain some aspects of cell behaviour upon reprogramming.The coexistence of antagonistic factors at low levels, early in the differentiation process or in pluripotent stem cells, could be an intrinsic property of the interaction between those factors, not requiring a specific regulatory system

Structural Sensitivity of Neural and Genetic Networks

International audienceThis paper aims at giving new results on the structural sensitivity of biological networks represented by threshold Boolean networks and ruled by Hopfield-like evolution laws classically used in the context of neural and genetic networks. Indeed, the objective is to present how certain changes and/or perturbations in such networks can modify signicantly their asymptotic behaviour. More precisely, this work has been focused on three diferent kinds of what we think to be relevant in the biological area of robustness (in both theoretical and applied frameworks): the boundary sensitivity (external fields, hormone flows, ...), the state sensitivity (axonal or somatic modulations, microRNAs actions, ...) and the updating sensitivity

A Novel Low-Cost Sensor Prototype for Nocturia Monitoring in Older People

Indexación: Scopus.This work was supported in part by CORFO - CENS 16CTTS-66390 through the National Center on Health Information Systems, in part by the National Commission for Scientific and Technological Research (CONICYT) through the program STIC-AMSUD 17STIC-03: ‘‘e-MONITOR âĂŞ Chronic Disease: Ambient Assisted Living and vital teleMONOTORing for e-health,’’ FONDEF ID16I10449 ‘‘Sistema inteligente para la gestión y análisis de la dotación de camas en la red asistencial del sector público,’’ and MEC80170097 ‘‘Red de colaboración científica entre universidades nacionales e internacionales para la estructuración del doctorado y magister en informática médica en la Universidad de Valparaíso.’’ The work of V. H. C. de Albuquerque was supported by the Brazilian National Council for Research and Development (CNPq) under Grant #304315/2017-6.Nocturia is frequently defined as the necessity to get out of bed at least one time during the night to urinate, with each of these episodes being preceded and continued by sleep. Several studies suggest that an increase of nocturia is seen with the onset of age, occurring in around 70% of adults over the age of 70. Its appearance is associated with detrimental quality of life for those who present nocturia, since it leads to daytime sleepiness, cognitive dysfunction, among others. Currently, a voiding diary is necessary for nocturia assessment; these are prone to bias due to their inherent subjectivity. In this paper, we present the design of a low-cost device that automatically detects micturition events. The device obtained 73% in sensibility and 81% in specificity; these results show that systems such as the proposed one can be a valuable tool for the medical team when evaluating nocturia. © 2013 IEEE.https://ieeexplore.ieee.org/document/845445

A novel monitoring system for fall detection in older people

Indexación: Scopus.This work was supported in part by CORFO - CENS 16CTTS-66390 through the National Center on Health Information Systems, in part by the National Commission for Scientific and Technological Research (CONICYT) through the Program STIC-AMSUD 17STIC-03: ‘‘MONITORing for ehealth," FONDEF ID16I10449 ‘‘Sistema inteligente para la gestión y análisis de la dotación de camas en la red asistencial del sector público’’, and in part by MEC80170097 ‘‘Red de colaboración científica entre universidades nacionales e internacionales para la estructuración del doctorado y magister en informática médica en la Universidad de Valparaíso’’. The work of V. H. C. De Albuquerque was supported by the Brazilian National Council for Research and Development (CNPq), under Grant 304315/2017-6.Each year, more than 30% of people over 65 years-old suffer some fall. Unfortunately, this can generate physical and psychological damage, especially if they live alone and they are unable to get help. In this field, several studies have been performed aiming to alert potential falls of the older people by using different types of sensors and algorithms. In this paper, we present a novel non-invasive monitoring system for fall detection in older people who live alone. Our proposal is using very-low-resolution thermal sensors for classifying a fall and then alerting to the care staff. Also, we analyze the performance of three recurrent neural networks for fall detections: Long short-term memory (LSTM), gated recurrent unit, and Bi-LSTM. As many learning algorithms, we have performed a training phase using different test subjects. After several tests, we can observe that the Bi-LSTM approach overcome the others techniques reaching a 93% of accuracy in fall detection. We believe that the bidirectional way of the Bi-LSTM algorithm gives excellent results because the use of their data is influenced by prior and new information, which compares to LSTM and GRU. Information obtained using this system did not compromise the user's privacy, which constitutes an additional advantage of this alternative. © 2013 IEEE.https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=842305

On the complexity of acyclic modules in automata networks

Modules were introduced as an extension of Boolean automata networks. They have inputs which are used in the computation said modules perform, and can be used to wire modules with each other. In the present paper we extend this new formalism and study the specific case of acyclic modules. These modules prove to be well described in their limit behavior by functions called output functions. We provide other results that offer an upper bound on the number of attractors in an acyclic module when wired recursively into an automata network, alongside a diversity of complexity results around the difficulty of deciding the existence of cycles depending on the number of inputs and the size of said cycle.Comment: 21 page

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally

Description of Fischer Clusters Formation in Supercooled Liquids Within Framework of Continual Theory of Defects

Liquid is represented as complicated system of disclinations according to defect description of liquids and glasses. The expressions for the linear disclination field of an arbitrary form and energy of inter-disclination interaction are derived in the framework of gauge theory of defects. It allows us to describe liquid as a disordered system of topological moments and reduce this model to the Edwards--Anderson model with large-range interaction. Within the framework of this approach vitrifying is represented as a "hierarchical" phase transition. The suggested model allows us to explain the process of the Fischer clusters formation and the slow dynamics in supercooled liquids close to the liquid--glass transition point

Non-maximal sensitivity to synchronism in periodic elementary cellular automata: exact asymptotic measures

In [11] and [13] the authors showed that elementary cellular automata rules 0, 3, 8, 12, 15, 28, 32, 34, 44, 51, 60, 128, 136, 140, 160, 162, 170, 200 and 204 (and their conjugation, reflection, reflected-conjugation) are not maximum sensitive to synchronism, i.e. they do not have a different dynamics for each (non-equivalent) block-sequential update schedule (defined as ordered partitions of cell positions). In this work we present exact measurements of the sensitivity to synchronism for these rules, as functions of the size. These exhibit a surprising variety of values and associated proof methods, such as the special pairs of rule 128, and the connection to the bissection of Lucas numbers of rule 8

Boolean dynamics revisited through feedback interconnections

Boolean models of physical or biological systems describe the global dynamics of the system and their attractors typically represent asymptotic behaviors. In the case of large networks composed of several modules, it may be difficult to identify all the attractors. To explore Boolean dynamics from a novel viewpoint, we will analyse the dynamics emerging from the composition of two known Boolean modules. The state transition graphs and attractors for each of the modules can be combined to construct a new asymptotic graph which will (1) provide a reliable method for attractor computation with partial information; (2) illustrate the differences in dynamical behavior induced by the updating strategy (asynchronous, synchronous, or mixed); and (3) show the inherited organization/structure of the original network’s state transition graph.publishe

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

. Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.Using a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.Theoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled