RESUMO
Pandemic management requires reliable and efficient dynamical simulation to predict and control disease spreading. The COVID-19 (SARS-CoV-2) pandemic is mitigated by several non-pharmaceutical interventions, but it is hard to predict which of these are the most effective for a given population. We developed the computationally effective and scalable, agent-based microsimulation framework PanSim, allowing us to test control measures in multiple infection waves caused by the spread of a new virus variant in a city-sized societal environment using a unified framework fitted to realistic data. We show that vaccination strategies prioritising occupational risk groups minimise the number of infections but allow higher mortality while prioritising vulnerable groups minimises mortality but implies an increased infection rate. We also found that intensive vaccination along with non-pharmaceutical interventions can substantially suppress the spread of the virus, while low levels of vaccination, premature reopening may easily revert the epidemic to an uncontrolled state. Our analysis highlights that while vaccination protects the elderly from COVID-19, a large percentage of children will contract the virus, and we also show the benefits and limitations of various quarantine and testing scenarios. The uniquely detailed spatio-temporal resolution of PanSim allows the design and testing of complex, specifically targeted interventions with a large number of agents under dynamically changing conditions.
Assuntos
COVID-19/terapia , Modelos Teóricos , Adolescente , Adulto , Idoso , Algoritmos , COVID-19/epidemiologia , COVID-19/virologia , Criança , Humanos , Pessoa de Meia-Idade , Pandemias , Quarentena , SARS-CoV-2/isolamento & purificação , Adulto JovemRESUMO
In this paper a modular model of the GnRH neuron is presented. For the aim of simplicity, the currents corresponding to fast time scales and action potential generation are described by an impulsive system, while the slower currents and calcium dynamics are described by usual ordinary differential equations (ODEs). The model is able to reproduce the depolarizing afterpotentials, afterhyperpolarization, periodic bursting behavior and the corresponding calcium transients observed in the case of GnRH neurons.
Assuntos
Potenciais de Ação/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Modelos Neurológicos , Neurônios/fisiologia , Potenciais de Ação/genética , Animais , Biofísica , Cálcio/metabolismo , Dendritos/fisiologia , Estimulação Elétrica , Hormônio Liberador de Gonadotropina/genética , Proteínas de Fluorescência Verde/genética , Hipotálamo/citologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Técnicas de Patch-Clamp , Compostos de Fósforo/farmacologia , Canais de Potássio/metabolismo , Potenciais Sinápticos/genética , Potenciais Sinápticos/fisiologiaRESUMO
In this paper the qualitative dynamic behavior of reaction kinetic models of G protein signaling is examined. A simplified basic G protein signaling structure is defined, which is extended to be able to take the effect of slow transmission, RGS mediated feedback regulation and ERK-phosphatase mediated feedback regulation into account. The resulting model gives rise to an acceptable qualitative approximation of the G protein dependent and independent ERK activation dynamics that is in good agreement with the experimentally observed behavior.
Assuntos
Arrestinas/metabolismo , Simulação por Computador , Proteínas de Ligação ao GTP/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Modelos Químicos , Animais , Retroalimentação Fisiológica , Modelos Biológicos , Fosforilação , beta-ArrestinasRESUMO
In this paper a simple one compartment Hodgkin-Huxley type electrophysiological model of GnRH neurons is presented, that is able to reasonably reproduce the most important qualitative features of the firing pattern, such as baseline potential, depolarization amplitudes, sub-baseline hyperpolarization phenomenon and average firing frequency in response to excitatory current. In addition, the same model provides an acceptable numerical fit of voltage clamp (VC) measurement results. The parameters of the model have been estimated using averaged VC traces, and characteristic values of measured current clamp traces originating from GnRH neurons in hypothalamic slices. The resulting parameter values show a good agreement with literature data in most of the cases. Applying parametric changes, which lead to the increase of baseline potential and enhance cell excitability, the model becomes capable of bursting. The effects of various parameters to burst length have been analyzed by simulation.