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Mathematical models are critical to understand the spread of pathogens in a population and evaluate the effectiveness of non-pharmaceutical interventions (NPIs). A plethora of optimal strategies has been recently developed to minimize either the infected peak prevalence ( I P P ) or the epidemic final size ( E F S ). While most of them optimize a simple cost function along a fixed finite-time horizon, no consensus has been reached about how to simultaneously handle the I P P and the E F S , while minimizing the intervention's side effects. In this work, based on a new characterization of the dynamical behaviour of SIR-type models under control actions (including the stability of equilibrium sets in terms of herd immunity), we study how to minimize the E F S while keeping the I P P controlled at any time. A procedure is proposed to tailor NPIs by separating transient from stationary control objectives: the potential benefits of the strategy are illustrated by a detailed analysis and simulation results related to the COVID-19 pandemic.
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Mathematical models describing SARS-CoV-2 dynamics and the corresponding immune responses in patients with COVID-19 can be critical to evaluate possible clinical outcomes of antiviral treatments. In this work, based on the concept of virus spreadability in the host, antiviral effectiveness thresholds are determined to establish whether or not a treatment will be able to clear the infection. In addition, the virus dynamic in the host - including the time-to-peak and the final monotonically decreasing behavior - is characterized as a function of the time to treatment initiation. Simulation results, based on nine patient data, show the potential clinical benefits of a treatment classification according to patient critical parameters. This study is aimed at paving the way for the different antivirals being developed to tackle SARS-CoV-2.
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While many epidemiological models were proposed to understand and handle COVID-19 pandemic, too little has been invested to understand human viral replication and the potential use of novel antivirals to tackle the infection. In this work, using a control theoretical approach, validated mathematical models of SARS-CoV-2 in humans are characterized. A complete analysis of the main dynamic characteristic is developed based on the reproduction number. The equilibrium regions of the system are fully characterized, and the stability of such regions is formally established. Mathematical analysis highlights critical conditions to decrease monotonically SARS-CoV-2 in the host, as such conditions are relevant to tailor future antiviral treatments. Simulation results show the aforementioned system characterization.
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p53 regulates the cellular response to genotoxic damage and prevents carcinogenic events. Theoretical and experimental studies state that the p53-Mdm2 network constitutes the core module of regulatory interactions activated by cellular stress induced by a variety of signaling pathways. In this paper, a strategy to control the p53-Mdm2 network regulated by p14ARF is developed, based on the pinning control technique, which consists into applying local feedback controllers to a small number of nodes (pinned ones) in the network. Pinned nodes are selected on the basis of their importance level in a topological hierarchy, their degree of connectivity within the network, and the biological role they perform. In this paper, two cases are considered. For the first case, the oscillatory pattern under gamma-radiation is recovered; afterward, as the second case, increased expression of p53 level is taken into account. For both cases, the control law is applied to p14ARF (pinned node based on a virtual leader methodology), and overexpressed Mdm2-mediated p53 degradation condition is considered as carcinogenic initial behavior. The approach in this paper uses a computational algorithm, which opens an alternative path to understand the cellular responses to stress, doing it possible to model and control the gene regulatory network dynamics in two different biological contexts. As the main result of the proposed control technique, the two mentioned desired behaviors are obtained.
RESUMO
Bacteria control the expression of specific genes by Quorum Sensing (QS). This works using small signaling molecules called Autoinducers (AIs), for example, the Autoinducer-2 (AI-2). In this work, we present a mathematical model that represents the AI-2 dynamics on Escherichia coli, which is linked to the cell growth and the lsr operon expression. The model is adjusted using experimental data. Our results suggest that the extracellular AI-2 activity level depends on the cell growth rate, and this activity depends on the cell exponential growth phase. The model was adapted to simulate the interference of QS mechanisms in a co-culture of two E. coli strains: a wild type strain and a knock out strain that detects AI-2 but does not produce it. Co-culture simulations unveiled two conditions to avoid the QS on the wild strain: when the knock out takes control of the growth medium and overcomes the wild strain, or when is pre-cultured to its mid-exponential phase and then added to the wild strain culture. Model simulations unveiled new insights about the interference of bacterial communication and offer new tools for QS control.