RESUMO
An innovative neurodynamical model of epidemics in social networks - the Neuro-SIR - is introduced. Susceptible-Infected-Removed (SIR) epidemic processes are mechanistically modeled as analogous to the activity propagation in neuronal populations. The workings of infection transmission from individual to individual through a network of social contacts, is driven by the dynamics of the threshold mechanism of leaky integrate-and-fire neurons. Through this approach a dynamically evolving landscape of the susceptibility of a population to a disease is formed. In this context, epidemics with varying velocities and scales are triggered by a small fraction of infected individuals according to the configuration of various endogenous and exogenous factors representing the individuals' vulnerability, the infectiousness of a pathogen, the density of a contact network, and environmental conditions. Adjustments in the length of immunity (if any) after recovery, enable the modeling of the Susceptible-Infected-Recovered-Susceptible (SIRS) process of recurrent epidemics. Neuro-SIR by supporting an impressive level of heterogeneities in the description of a population, contagiousness of a disease, and external factors, allows a more insightful investigation of epidemic spreading in comparison with existing approaches. Through simulation experiments with Neuro-SIR, we demonstrate the effectiveness of the #stayhome strategy for containing Covid-19, and successfully validate the simulation results against the classical epidemiological theory. Neuro-SIR is applicable in designing and assessing prevention and control strategies for spreading diseases, as well as in predicting the evolution pattern of epidemics.
RESUMO
Receptor activator of nuclear factor-κB ligand (RANKL) is critically involved in mammary gland pathophysiology, while its pharmaceutical inhibition is being currently investigated in breast cancer. Herein, we investigated whether the overexpression of human RANKL in transgenic mice affects hormone-induced mammary carcinogenesis, and evaluated the efficacy of anti-RANKL treatments, such as OPG-Fc targeting both human and mouse RANKL or Denosumab against human RANKL. We established novel MPA/DMBA-driven mammary carcinogenesis models in TgRANKL mice that express both human and mouse RANKL, as well as in humanized humTgRANKL mice expressing only human RANKL, and compared them to MPA/DMBA-treated wild-type (WT) mice. Our results show that TgRANKL and WT mice have similar levels of susceptibility to mammary carcinogenesis, while OPG-Fc treatment restored mammary ductal density, and prevented ductal branching and the formation of neoplastic foci in both genotypes. humTgRANKL mice also developed MPA/DMBA-induced tumors with similar incidence and burden to those of WT and TgRANKL mice. The prophylactic treatment of humTgRANKL mice with Denosumab significantly prevented the rate of appearance of mammary tumors from 86.7% to 15.4% and the early stages of carcinogenesis, whereas therapeutic treatment did not lead to any significant attenuation of tumor incidence or tumor burden compared to control mice, suggesting the importance of RANKL primarily in the initial stages of tumorigenesis. Overall, we provide unique genetic tools for investigating the involvement of RANKL in breast carcinogenesis, and allow the preclinical evaluation of novel therapeutics that target hormone-related breast cancers.
RESUMO
The interaction of social networks with the external environment gives rise to non-stationary activity patterns reflecting the temporal structure and strength of exogenous influences that drive social dynamical processes far from an equilibrium state. Following a neuro-inspired approach, based on the dynamics of a passive neuronal membrane, and the firing rate dynamics of single neurons and neuronal populations, we build a state-of-the-art model of the collective social response to exogenous interventions. In this regard, we analyze online activity patterns with a view to determining the transfer function of social systems, that is, the dynamic relationship between external influences and the resulting activity. To this end, first we estimate the impulse response (Green's function) of collective activity, and then we show that the convolution of the impulse response with a time-varying external influence field accurately reproduces empirical activity patterns. To capture the dynamics of collective activity when the generating process is in a state of statistical equilibrium, we incorporate into the model a noisy input convolved with the impulse response function, thus precisely reproducing the fluctuations of stationary collective activity around a resting value. The outstanding goodness-of-fit of the model results to empirical observations, indicates that the model explains human activity patterns generated by time-dependent external influences in various socio-economic contexts. The proposed model can be used for inferring the temporal structure and strength of external influences, as well as the inertia of collective social activity. Furthermore, it can potentially predict social activity patterns.
Assuntos
Redes Comunitárias , Modelos Teóricos , Redes Neurais de Computação , Rede Social , HumanosRESUMO
We develop and validate a model of the micro-level dynamics underlying the formation of macro-level information propagation patterns in online social networks. In particular, we address the dynamics at the level of the mechanism regulating a user's participation in an online information propagation process. We demonstrate that this mechanism can be realistically described by the dynamics of noisy spiking neurons driven by endogenous and exogenous, deterministic and stochastic stimuli representing the influence modulating one's intention to be an information spreader. Depending on the dynamically changing influence characteristics, time-varying propagation patterns emerge reflecting the temporal structure, strength, and signal-to-noise ratio characteristics of the stimulation driving the online users' information sharing activity. The proposed model constitutes an overarching, novel, and flexible approach to the modeling of the micro-level mechanisms whereby information propagates in online social networks. As such, it can be used for a comprehensive understanding of the online transmission of information, a process integral to the sociocultural evolution of modern societies. The proposed model is highly adaptable and suitable for the study of the propagation patterns of behavior, opinions, and innovations among others.