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This paper explores memory mechanisms in complex socio-technical systems, using a mobility demand model as an example case. We simplified a large-scale agent-based mobility model into a Markov process and discover that the mobility decision process is non-Markovian. This is due to its dependence on the system’s history, including social structure and local infrastructure, which evolve based on prior mobility decisions. To make the process Markovian, we extend the state space by incorporating two history-dependent components. Although our model is a very much reduced version of the original one, it remains too complex for the application of usual analytic methods. Instead, we employ simulations to examine the functionalities of the two history-dependent components. We think that the structure of the analyzed stochastic process is exemplary for many socio-technical, -economic, -ecological systems. Additionally, it exhibits analogies with the framework of extended evolution, which has previously been used to study cultural evolution.
Collective variables (CVs) are low-dimensional projections of high-dimensional system states. They are used to gain insights into complex emergent dynamical behaviors of processes on networks. The relation between CVs and network measures is not well understood and its derivation typically requires detailed knowledge of both the dynamical system and the network topology. In this Letter, we present a data-driven method for algorithmically learning and understanding CVs for binary-state spreading processes on networks of arbitrary topology. We demonstrate our method using four example networks: the stochastic block model, a ring-shaped graph, a random regular graph, and a scale-free network generated by the Albert-Barabási model. Our results deliver evidence for the existence of low-dimensional CVs even in cases that are not yet understood theoretically.
We previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. The design process of NFEPP was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present an additional and novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels and their dependence on parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for the ligands NFEPP and fentanyl at different pH values and radical concentrations. We observe markedly reduced binding affinity and calcium channel inhibition for NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein activation but reduced ligand binding affinity. Assessing the different effects, the results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.
Initiated by mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands in normal versus diseased (inflamed) environments, we previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. Uniquely, this design recognised that GPCRs function differently under pathological versus healthy conditions.
We now present a novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels associated with parameters of inflamed tissue (pH, radicals). By means of molecular dynamics simulations, we also assessed qualitative changes of the reaction rates due to additional disulfide bridges inside the GPCR binding pocket and used these rates for stochastic simulations of the corresponding reaction jump process.
The modelling results were validated with in vitro experiments measuring calcium currents and G-protein activation.
We found markedly reduced G-protein dissociation and calcium channel inhibition induced by NFEPP at normal pH, and enhanced constitutive G-protein activation but lower probability of ligand binding with increasing radical concentrations.
These results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.
Modeling, simulation and analysis of interacting agent systems is a broad field of research, with existing approaches reaching from informal descriptions of interaction dynamics to more formal, mathematical models. In this paper, we study agent-based models (ABMs) given as continuous-time stochastic processes and their pathwise approximation by ordinary and stochastic differential equations (ODEs and SDEs, respectively) for medium to large populations. By means of an appropriately adapted transfer operator approach we study the behavior of the ABM process on long time scales. We show that, under certain conditions, the transfer operator approach allows to bridge the gap between the pathwise results for large populations on finite timescales, i.e., the SDE limit model, and approaches built to study dynamical behavior on long time scales like large deviation theory. The latter provides a rigorous analysis of rare events including the associated asymptotic rates on timescales that scale exponentially with the population size. We demonstrate that it is possible to reveal metastable structures and timescales of rare events of the ABM process by finite-length trajectories of the SDE process for large enough populations. This approach has the potential to drastically reduce computational effort for the analysis of ABMs.
This work explores a synchronization-like phenomenon induced by common noise for continuous-time Markov jump processes given by chemical reaction networks. Based on Gillespie’s stochastic simulation algorithm, a corresponding random dynamical system is formulated in a two-step procedure, at first for the states of the embedded discrete-time Markov chain and then for the augmented Markov chain including random jump times. We uncover a time-shifted synchronization in the sense that—after some initial waiting time—one trajectory exactly replicates another one with a certain time delay. Whether or not such a synchronization behavior occurs depends on the combination of the initial states. We prove this partial time-shifted synchronization for the special setting of a birth-death process by analyzing the corresponding two-point motion of the embedded Markov chain and determine the structure of the associated random attractor. In this context, we also provide general results on existence and form of random attractors for discrete-time, discrete-space random dynamical systems.
Our theoretical study concerns an urea-urease-based pH oscillator confined to giant lipid vesicles. Under suitable conditions, differential transport of urea and hydrogen ion across the unilamellar vesicle membrane periodically resets the pH clock that switches the system from acid to basic, resulting in self-sustained oscillations. We analyse the structure of the limit cycle, which controls the dynamics for giant vesicles and dominates the strongly stochastic oscillations in small vesicles of submicrometer size. To this end, we derive reduced models, amenable to analytic treatments, and show that the accuracy of predictions, including the period of oscillations, is highly sensitive to the choice of the reduction scheme. In particular, we suggest an accurate two-variable model and show its equivalence to a three-variable model that admits an interpretation in terms of a chemical reaction network. The accurate description of a single pH oscillator appears crucial for rationalizing experiments and understanding communication of vesicles and synchronization of rhythms.
This article addresses reaction networks in which spatial and stochastic effects are of crucial importance. For such systems, particle-based models allow us to describe all microscopic details with high accuracy. However, they suffer from computational inefficiency if particle numbers and density get too large. Alternative coarse-grained-resolution models reduce computational effort tremendously, e.g., by replacing the particle distribution by a continuous concentration field governed by reaction-diffusion PDEs. We demonstrate how models on the different resolution levels can be combined into hybrid models that seamlessly combine the best of both worlds, describing molecular species with large copy numbers by macroscopic equations with spatial resolution while keeping the stochastic-spatial particle-based resolution level for the species with low copy numbers. To this end, we introduce a simple particle-based model for the binding dynamics of ions and vesicles at the heart of the neurotransmission process. Within this framework, we derive a novel hybrid model and present results from numerical experiments which demonstrate that the hybrid model allows for an accurate approximation of the full particle-based model in realistic scenarios.