A flux balance approach to integrate cell metabolism into multicelluar agent-based simulations

The study of multicellular systems such as tumors, tissues, or organoids is critical to improve our understanding of the complex dynamics exhibited by these systems. For instance, the emergence of resistant cancer cells is process that manifest at many different scales from the molecular, to the population level. Multicellular systems such as tumors are complex adaptive systems an thus are no reducible to classical analytical techniques. Nevertheless, multi-scale simulations can used study these systems by integrating models of processes taking place at these different scales. In this way, multi-scale model simulations provide a genotype-to-phenotype mapping framework, that allow the exploration of genetic variations and their interaction with changing environmental conditions. In the Computational Biology Group we are extending a multiscale modelling framework combining agent-based and models of signaling pathways (PhysiCell/PhysiBoSS), to link pathways’ activity and cells’ phenotypes to physical interactions among cells and with their environment. In this seminar, I will introduce the current status of our multi-scale framework, as well as the ongoing development of a novel extension to integrate metabolic models within the agent-based framework. This novel feature will allow to study the intersection between cell metabolism and their microenvironment, at the population

Evaluating the policy of closing bars and restaurants in Cataluña and its effects on mobility and COVID19 incidence

The world has gone through unprecedented changes since the global pandemic hit. During the early phase of the pandemic, the absence of known drugs or pharmaceutical treatments forced governments to introduce different policies in order to help reduce contagion rates and manage the economic consequences of the pandemic. This paper analyses the causal impact on mobility and COVID19 incidence from policy makers in Cataluña, Spain. We use anonymized phone-based mobility data together with reported incidence and apply a series of causal impact models frequently used in econometrics and policy evaluation in order to measure the policies impact. We analyse the case of Cataluña and the public policy decision of closing all bars and restaurants down for a 5 week period between 2020-16-10 and 2020-23-11. We find that this decision led to a significant reduction in mobility. It not only led to reductions in mobility but from a behavioural economics standpoint, we highlight how people responded to the policy decision. Moreover, the policy of closing bars and restaurants slowed the incidence rate of COVID19 after a time lag has been taken into account. These findings are significant since governments worldwide want to restrict movements of people in order to slow down COVID19 incidence without infringing on their rights directly.Peer ReviewedPostprint (published version

A Modelling and Reasoning Framework for Representing and Orchestrating Service Level Agreement Behaviour

This paper describes a new electronic Service Level Agreement model that is part of the DEN-ng information model. A new knowledge representation method is used to extract knowledge from the model and associate it with knowledge from ontologies, enabling a system to reason about how to best orchestrate behaviour to meet the terms and conditions of the Service Level Agreement, even if business, user, and/or environmental conditions change. Such intelligent automation can save significant operational expenditures and ensure that customers receive the services that they have contracted for, thereby reducing customer churn

Scenarios Designed for the Verification of Mobile IPv6 Enabling Technologies

Conveying the innovations of an infrastructural based technology such as Mobile IPv6 is not easy. The identification of an application scenario can be a beneficial way to guide the development of Mobile IPv6 enabling technologies and to assist the real life deployment of Mobile IPv6. Well defined scenarios can also become an important part of the final system integration and test bed deployment. This paper will first describe additional functional components for Mobile IPv6, particularly the ones that have been successfully integrated, i.e. MIPv6 bootstrapping based on EAP (with and without MIPv6 DHCPv6 extensions and DNS/IKEv2), AAA for MIPv6 bootstrapping, and HA load sharing. We will then highlight a methodology used in identifying an application scenario chosen to demonstrate the operational mobility service. We will briefly review the state of the art in the domain and seventeen scenarios in the “Mobile and Wireless Systems and Platforms beyond 3G” area. We will then show the process of defining one specific demonstrable scenario, which adequately verifies the technical and business requirements for the deployment of a Mobile IPv6 service

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Implementation of cellular transport models within a multiscale simulation software

Agent-based models (ABM) have been increasingly employed to study dynamics of biological systems. However, these mostly lack transport mechanisms that interface between the agents and their microenvironment. We considered a set of 5 general transport mechanisms (see Fig. 1), written as ODE models and built on top of Fick’s Second Law of Diffusion and R-MM kinetics, and their implementation within an ABM software. Unit testing of said models was performed on static, liposome-like agents. We also studied the effect of varying agent and microenvironment-related parameters on the dynamic. We then connected a few of these mechanisms to the agent phenotype, developing a toy example that emulates the experimental decreased tumorigenic growth dynamics of Cytochalasin β

Creating a distributed mobile networking testbed environment - through the Living Labs approach

Today, new ways of constructing and delivering complex wireless and mobile services require more elaborate and distributed prototyping, testing, and validation facilities. Testbeds are becoming an important tool for integrating technology components into the complex environment of the wireless world and end-users in their daily life. However technology in itself is no longer valid – benefits and usefulness for people in their daily life must be proven before the technology or service can be said to be a success

SEINIT Security for Heterogeneous Mobile Network Services

This paper presents a model for securing mobile services using heterogeneous access networks, and implementing sample solutions using this framework. This is a project that is defining new security models and policies to address the new issues of the pervasive computing world. The security models and policies are implemented over IPv6 infrastructures to cover various business cases and assessed against real life scenarios. SEINIT is developing a trusted and dependable security framework with the end-user as the focus

Securing mobile services

This paper reports on some initial findings of the EU IST SEINIT project with respect to the security of end-to-end services over the wireless access and fixed network and captures the state of the art in secure mobile services infrastructures

Optimizing dosage-specific treatments in a multi-Scale model of a tumor growth

The emergence of cell resistance in cancer treatment is a complex phenomenon that emerges from the interplay of processes that occur at different scales. For instance, molecular mechanisms and population-level dynamics such as competition and cell–cell variability have been described as playing a key role in the emergence and evolution of cell resistances. Multi-scale models are a useful tool for studying biology at very different times and spatial scales, as they can integrate different processes occurring at the molecular, cellular, and intercellular levels. In the present work, we use an extended hybrid multi-scale model of 3T3 fibroblast spheroid to perform a deep exploration of the parameter space of effective treatment strategies based on TNF pulses. To explore the parameter space of effective treatments in different scenarios and conditions, we have developed an HPC-optimized model exploration workflow based on EMEWS. We first studied the effect of the cells’ spatial distribution in the values of the treatment parameters by optimizing the supply strategies in 2D monolayers and 3D spheroids of different sizes. We later study the robustness of the effective treatments when heterogeneous populations of cells are considered. We found that our model exploration workflow can find effective treatments in all the studied conditions. Our results show that cells’ spatial geometry and population variability should be considered when optimizing treatment strategies in order to find robust parameter sets.This research has received funding from the Horizon 2020 INFORE Project, GA n° 825070 and the Horizon 2020 PerMedCoE Project, GA n° 951773.Peer ReviewedPostprint (published version