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In this paper, a method to study how the design of indoor spaces and people's movement within them affect disease spread is proposed by integrating computer-aided modeling, multi-agent movement simulation, and airborne viral transmission modeling. Topologicpy spatial design and analysis software is used to model indoor environments, connect spaces, and construct a navigation graph. Pathways for agents, each with unique characteristics such as walking speed, infection status, and activities, are computed using this graph. Agents follow a schedule of events with specific locations and times. The software calculates "time-to-leave" based on walking speed and event start times, and agents are moved along the shortest path within the navigation graph, accurately considering obstacles, doorways, and walls. Precise distance calculations between agents are enabled by this setup. Viral aerosol concentration is then computed and visualized using a reaction-diffusion equation, and each agent's infection risk is determined with an extension of the Wells-Riley ansatz. Infection risk simulations are improved by this spatio-temporal and topological approach, incorporating realistic human behavior and spatial dynamics. The resulting software is designed as a rapid decision-support tool for policymakers, facility managers, stakeholders, architects, and engineers to mitigate disease spread in existing buildings and inform the design of new ones. The software's effectiveness is demonstrated through a comparative analysis of cellular and open commercial office plan layouts.

A Viral Infection Risk Indoor Simulator (VIRIS) has been developed to quickly assess and compare mitigations for airborne disease spread. This agent-based simulator combines people movement in an indoor space, viral transmission modelling and detailed architectural design, and it is powered by topologicpy, an open-source Python library. VIRIS generates very fast predictions of the viral concentration and the spatiotemporal infection risk for individuals as they move through a given space. The simulator is validated with data from a courtroom superspreader event. A sensitivity study for unknown parameter values is also performed. We compare several non-pharmaceutical interventions (NPIs) issued in UK government guidance, for two indoor settings: a care home and a supermarket. Additionally, we have developed the user-friendly VIRIS web app that allows quick exploration of diverse scenarios of interest and visualisation, allowing policymakers, architects and space managers to easily design or assess infection risk in an indoor space.

We incorporate local ventilation effects into a spatially dependent generalisation of the Wells--Riley model of airborne viral transmission. Aerosol production and removal through ventilation (global and local), biological deactivation, and gravitational settling as well as transport around a recirculating air-conditioning flow and turbulent mixing are modelled using an advection--diffusion--reaction equation. The local ventilation effects are compared with the equivalent global ventilation and we find that the streamlines of the airflow provide insight into when the global ventilation model is a good approximation. When the agreement between ventilation models is poor, we find that the global ventilation model generally overestimates the infection risk., Comment: 10 pages, 4 figures, submitted to the Journal of Fluid Mechanics as a Rapids article

During In Vitro Fertilisation (IVF), combining time-lapse contrast microscopy with suitable image processing techniques could facilitate non-invasive classification of oocyte health, driving oocyte selection to maximise success rates. One image processing technique, Differential Dynamic Microscopy (DDM), has been used in a variety of microscopy settings including bright field, dark field and fluorescence. However, in some applications, effects stemming from the choice of microscopy may invalidate underlying assumptions of DDM. Here, we study the DDM analysis of differential interference contrast (DIC) microscopy movies. DIC exhibits a characteristic shadowing effect that gives the illusion of a 3D appearance, which we show causes deformation of the output DDM matrix. We present a mathematical description of this deformation, and conclude that, when studying isotropic motion, no account of the DIC shadow needs to be considered during DDM analysis. We validate our conclusions with simulated particle data, and with DIC images of colloidal dispersions. Although this conclusion does not generally extend to anisotropic motion, we demonstrate that for directed advection and diffusion behaviour, parameter fitting invariance still holds. These results validate the current practice of applying DDM to DIC, and are a foundation for further exploration of DDM in other phase-contrast image datasets.

In embryogenesis, epithelial cells, acting as individual entities or as coordinated aggregates in a tissue, exhibit strong coupling between chemical signalling and mechanical responses to internally or externally applied stresses. Intercellular communication in combination with such coordination of morphogenetic movements can lead to drastic modifications in the calcium distribution in the cells. In this paper we extend the recent mechanochemical model in [K. Kaouri, P.K. Maini, P.A. Skourides, N. Christodoulou, S.J. Chapman. J. Math. Biol., 78 (2019) 2059--2092], for an epithelial continuum in one dimension, to a more realistic multi-dimensional case. The resulting parametrised governing equations consist of an advection-diffusion-reaction system for calcium signalling coupled with active-stress linear viscoelasticity and equipped with pure Neumann boundary conditions. We implement a mixed finite element method for the simulation of this complex multiphysics problem. Special care is taken in the treatment of the stress-free boundary conditions for the viscoelasticity in order to eliminate rigid motions from the space of admissible displacements. The stability and solvability of the continuous weak formulation is shown using fixed-point theory. We investigate numerically the solutions of this system and show that solitary waves and periodic wavetrains of calcium propagate through the embryonic epithelial sheet. We analyse the bifurcations of the system guided by the bifurcation analysis of the one-dimensional model. We also demonstrate the nucleation of calcium sparks into synchronous calcium waves coupled with contraction. This coupled model can be employed to gain insights into recent experimental observations in the context of embryogenesis, but also in other biological systems such as cancer cells, wound healing, keratinocytes, or white blood cells., Comment: 29 pages

We develop a spatially dependent generalisation to the Wells-Riley model and its extensions applied to COVID-19, that determines the infection risk due to airborne transmission of viruses. We assume that the concentration of infectious particles is governed by an advection-diffusion-reaction equation with the particles advected by airflow, diffused due to turbulence, emitted by infected people and removed due to the room ventilation, inactivation of the virus and gravitational settling. We consider one asymptomatic or presymptomatic infectious person who breathes or talks, with or without a mask and model a quasi-3D setup that incorporates a recirculating air-conditioning flow. A semi-analytic solution is available and this enables fast simulations. We quantify the effect of ventilation and particle emission rate on the particle concentration, infection risk and the `time to probable infection' (TTPI). Good agreement with CFD models is achieved. Furthermore, we derive power laws that quantify the effect of ventilation, emission rate and infectiousness of the virus on the TTPI. The model can be easily updated to take into account modified parameter values. This work paves the way for establishing `safe occupancy times' at any location and has direct applicability in mitigating the spread of the COVID-19 pandemic., Comment: 25 pages, 14 figures. Version v3 substantially revises v1. (v3 same as v2 but with a more compact layout, hence fewer pages.) Compared to v1 the model has been extended to determine the spatiotemporal infection risk and recast as an extension of the Wells-Riley model. Another author has been added. The underlying model and domain linked to the semi-analytic solution are now explained in detail

Cancer cells exhibit increased motility and proliferation, which are instrumental in the formation of tumours and metastases. These pathological changes can be traced back to malfunctions of cellular signalling pathways, and calcium signalling plays a prominent role in these. We formulate a new model for cancer cell movement which for the first time explicitly accounts for the dependence of cell proliferation and cell-cell adhesion on calcium. At the heart of our work is a non-linear, integro-differential (non-local) equation for cancer cell movement, accounting for cell diffusion, advection and proliferation. We also employ an established model of cellular calcium signalling with a rich dynamical repertoire that includes experimentally observed periodic wave trains and solitary pulses. The cancer cell density exhibits travelling fronts and complex spatial patterns arising from an adhesion-driven instability (ADI). We show how the different calcium signals and variations in the strengths of cell-cell attraction and repulsion shape the emergent cellular aggregation patterns, which are a key component of the metastatic process. Performing a linear stability analysis, we identify parameter regions corresponding to ADI. These regions are confirmed by numerical simulations, which also reveal different types of aggregation patterns and these patterns are significantly affected by \ca. Our study demonstrates that the maximal cell density decreases with calcium concentration, while the frequencies of the calcium oscillations and the cell density oscillations are approximately equal in many cases. Furthermore, as the calcium levels increase the speed of the travelling fronts increases, which is related to a higher cancer invasion potential. These novel insights provide a step forward in the design of new cancer treatments that may rely on controlling the dynamics of cellular calcium., Comment: 27 pages; 8 figures

This report summarises the work and results produced at the 146th European Study Group with Industry/co-creation event with society on the challenge \textit{Breaking barriers for women in Science}. The aim of this challenge, proposed by the Cyprus-based non-profit AIPFE Cyprus-Women of Europe, was to quantify the barriers that women face in science so that eventually policy changes can take place in Cyprus and elsewhere. Two distinct but related challenges were considered. The first challenge was to quantify the wage gap between men and women in 28 European countries. In this connection, we analysed Eurostat data and developed a mathematical model quantifying how probable it is for countries to decrease their wage gap. Secondly, we analysed data provided by the University of Cyprus and determined the percentage of women and men in STEM (Science, Technology, Engineering and Mathematics) departments as they move up the academic ladder, starting from the undergraduate level. Studying the latter challenge is a first step in studying the wage gap in all Cypriot universities and in other universities abroad. This work was supported financially by the EU project SciShops.eu, the EU Mathematics for Industry Network (MI-NET) and several other organisations.

We consider the management of sloping, long and thin, coastal aquifers. We first develop a simple mathematical model, based on Darcy flow for porous media, which gives the water table height, and the flow velocity as a function of the underground seepage rate, the recharge rates and the extraction rates, neglecting sea water intrusion. We then validate the model with recent data from the Germasogeia aquifer which caters for most of the water demand in the area of Limassol, Cyprus. The data is provided over a three year period by the Cyprus Water Development Department (WDD), the governmental department managing the aquifer. Furthermore, based on our model, we subsequently develop an optimised recharge strategy and identify the optimal recharge rates for a desired extracted water volume while the water table height is maintained at the acceptable level. We study several scenarios of practical interest and we find that we can achieve considerable water savings, compared to the current empirical strategy followed by WDD. Additionally, we model the transport of pollutants in the aquifer in the case of accidental leakage, using an advection-diffusion equation. We find that in the case of an undetected and unhindered contamination (worst case scenario) the aquifer would get polluted in about three years. Also, we find that double recharge rates flush the pollutant out of the aquifer faster. Finally, to incorporate the possibility of sea water intrusion, which can render aquifers unusable, we develop a new, transient two-dimensional model of groundwater flow based on the Darcy-Brinkman equations, and determine the position of the water table and the seawater-freshwater interface for conditions of drought, moderate rainfall and flooding. The validation of the new seawater intrusion modelling approach has been carried out via comparison with a widely-accepted code., Comment: 25 pages

Calcium (Ca2+) signalling is one of the most important mechanisms of information propagation in the body. In embryogenesis the interplay between Ca2+ signalling and mechanical forces is critical to the healthy development of an embryo but poorly understood. Several types of embryonic cells exhibit calcium-induced contractions and many experiments indicate that Ca2+ signals and contractions are coupled via a two-way mechanochemical coupling. We present a new analysis of experimental data that supports the existence of this coupling during Apical Constriction in Neural Tube Closure. We then propose a mechanochemical model, building on early models that couple Ca2+ dynamics to cell mechanics and replace the bistable Ca2+ release with modern, experimentally validated Ca2+ dynamics. We assume that the cell is a linear viscoelastic material and model the Ca2+-induced contraction stress with a Hill function saturating at high Ca2+ levels. We also express, for the first time, the "stretch-activation" Ca2+ flux in the early mechanochemical models as a bottom-up contribution from stretch-sensitive Ca2+ channels on the cell membrane. We reduce the model to three ordinary differential equations and analyse its bifurcation structure semi-analytically as the $IP_3$ concentration, and the "strength" of stretch activation, $\lambda$ vary. The Ca2+ system ($\lambda=0$, no mechanics) exhibits relaxation oscillations for a certain range of $IP_3$ values. As $\lambda$ is increased the range of $IP_3$ values decreases, the oscillation amplitude decreases and the frequency increases. Oscillations vanish for a sufficiently high value of $\lambda$. These results agree with experiments in embryonic cells that also link the loss of Ca2+ oscillations to embryo abnormalities. The work addresses a very important and understudied question on the coupling of chemical and mechanical signalling in embryogenesis., Comment: 37 pages (this is the revised version after being accepted with minor revisions at the Journal of Mathematical Biology)

Most of the calcium in the body is stored in bone. The rest is stored elsewhere, and calcium signalling is one of the most important mechanisms of information propagation in the body. Yet, many questions remain open. In this work, we initially consider the mathematical model proposed in Atri et al. \cite{ atri1993single}. Omitting diffusion, the model is a system of two nonlinear ordinary differential equations (ODEs) for the calcium concentration, and the fraction of $IP_3$ receptors that have not been inactivated by the calcium. We analyse in detail the system as the $IP_3$ concentration, the \textit{bifurcation parameter}, increases presenting some new insights. We analyse asymptotically the relaxation oscillations of the model by exploiting a separation of timescales. Furthermore, motivated by experimental evidence that cells release calcium when mechanically stimulated and that, in turn, calcium release affects the mechanical behaviour of cells, we propose an extension of the Atri model to a 3D nonlinear ODE mechanochemical model, where the additional equation, derived consistently from a full viscoelastic \emph{ansatz}, models the evolution of cell/tissue dilatation. Furthermore, in the calcium dynamics equation we introduce a new "stretch-activation" source term that induces calcium release and which involves a new bifurcation parameter, the "strength" of the source. Varying the two bifurcation parameters, we analyse in detail the interplay of the mechanical and the chemical effects, and we find that as the strength of the mechanical stimulus is increased, the $IP_3$ parameter range for which oscillations emerge decreases, until oscillations eventually vanish at a critical value. Finally, we analyse the model when the calcium dynamics are assumed faster than the dynamics of the other two variables., Comment: 38 pages, 14 figures. Submitted to the Journal of Mathematical Biology. Keywords: calcium modelling, mechanochemical model, dynamical systems, bifurcations, asymptotic methods, excitable systems PACS: 87.10.Ed, 87.10.Pq, 87.10.Ca, 87.10.Vg