# Mathematical Biology

## Flattening the curve and the effect of atypical events on mitigation measures

On March 23rd and March 30th, 2020, the Mexican Federal government implemented social distancing measures to mitigate the COVID-19 epidemic. In this work a mathematical model is used to explore atypical transmission events within the confinement period, triggered by the timing and strength of short time perturbations of social distancing. Is shown that social distancing measures were successful in achieving a significant reduction of the epidemic curve growth rate in the early weeks of the intervention. However, “flattening the curve” had an undesirable effect, since the epidemic peak was delayed too far, almost to the government preset day for lifting restrictions (June 1st, 2020). If the peak indeed occurs in late May or early June, then the events of children's day and Mother’s Day may either generate a later peak (worst case scenario), a long plateau with relatively constant but high incidence (middle case scenario) or the same peak date as in the original baseline epidemic curve, but with a post-peak interval of slower decay.

## Implementation of quarantine measures accounting for Covid-19 hospital saturation

A SEIRS model was developed to describe the spread of COVID-19 in Mexico, assuming different quarantine scenarios as a function of the conditions of hospital shortage. The presented model takes into account the heterogeneity of the state of infection, that is, the groups of clinical variants that can occur when the disease is contracted. Finally, the model allows different policy options to be implemented in different sectors of population.

## Epidemiology CovidSimABM: An Agent-Based Model of Contagion

This is the prototype of an agent based model for a closed universe of a population experiencing a contagion-based epidemic, in which risk factors, movement, time of incubation and asymptomatic infection are all parameters. The model allows the operator to intervene at any step and change parameters, thus analytically visualizing the effect of policies like more testing, contract tracing, and shelter in place. Under current development, CovidSimMV is an ABM that supports a Multiverse of different environments, in which agents move from one to another according to ticket with stops. Each universe has its own characteristic mix of residents, transients and attached staff, and persons are able to adopt different roles and characteristics in different universes. The fundamental disease characteristics of incubation, asymptomatic infection, confirmed cases will be preserved. The Multiverse model will support a rich diversity of environments and interpersonal dynamics. These are JavaScript programs that can be run in a browser as HTML files. The code is open source, and available on github.com/ecsendmail.

## The Mathematics of Life: Making Diffusion Your Friend

Diffusion is the enemy of life. This is because diffusion is a ubiquitous feature of molecular motion that is constantly spreading things out, destroying molecular aggregates. However, all living organisms, whether single cell or multicellular have ways to use the reality of molecular diffusion to their advantage. That is, they expend energy to concentrate molecules and then use the fact that molecules move down their concentration gradient to do useful things. In this talk, I will show some of the ways that cells use diffusion to their advantage, to signal, to form structures and aggregates, and to make measurements of length and size of populations. Among the examples I will describe are signalling by nerves, cell polarization, bacterial quorum sensing, and regulation of flagellar molecular motors. In this way, I hope to convince you that living organisms have made diffusion their friend, not their enemy.

## Multiscale multicellular modeling of tissue function and disease using CompuCell3D

Multiscale multicellular models combine representations of subcellular biological networks, cell behaviors, tissue level effects and whole body effects to describe tissue outcomes during development, homeostasis and disease. I will briefly introduce these simulation methodologies, the CompuCell3D simulation environment and their applications, then focus on a multiscale simulation of an acute primary infection of an epithelial tissue infected by a virus like SARS-CoV-2, a simplified cellular immune response and viral and immune-induced tissue damage. The model exhibits four basic parameter regimes: where the immune response fails to contain or significantly slow the spread of viral infection, where it significantly slows but fails to stop the spread of infection, where it eliminates all infected epithelial cells, but reinfection occurs from residual extracellular virus and where it clears the both infected cells and extracellular virus, leaving a substantial fraction of epithelial cells uninfected. Even this simplified model can illustrate the effects of a number of drug therapy concepts. Inhibition of viral internalization and faster immune-cell recruitment promote containment of infection. Fast viral internalization and slower immune response lead to uncontrolled spread of infection. Existing antivirals, despite blocking viral replication, show reduced clinical benefit when given later during the course of infection. Simulation of a drug which reduces the replication rate of viral RNA, shows that a low dosage that provides only a relatively limited reduction of viral RNA replication greatly decreases the total tissue damage and extracellular virus when given near the beginning of infection. However, even a high dosage that greatly reduces the rate of RNA replication rapidly loses efficacy when given later after infection. Many combinations of dosage and treatment time lead to distinct stochastic outcomes, with some replicas showing clearance or control of the virus (treatment success), while others show rapid infection of all epithelial cells (treatment failure). This switch between a regime of frequent treatment success and frequent failure occurs is quite abrupt as the time of treatment increases. The model is open-source and modular, allowing rapid development and extension of its components by groups working in parallel.

## Binocular Rivalry; Modeling by Network Structure

Binocular rivalry explores the question of how the brain copes with contradictory information. A subject is shown two different pictures – one to each eye. What images does the subject perceive? Results from rivalry experiments usually lead to alternation of percepts and are often surprising. Hugh Wilson proposed modeling rivalry in the brain by using structured networks of differential equations. We use Wilson networks as modeling devices and equivariant Hopf bifurcation as a tool to both post-dict and predict experimentally observed percepts. This work is joint with Casey Diekman, Zhong-Lin Lu, Tyler McMillen, Ian Stewart, Yunjiao Wang, and Yukai Zhao.

## Gaps of saddle connection directions for some branched covers of tori

TBA

## Real-time modelling of the COVID-19 epidemic: perspectives from British Columbia

The COVID-19 global pandemic has led to unprecedented public interest in mathematical modelling as a tool to understand the dynamics of disease spread and predict the impact of public health interventions. In this pair of talks, we will describe how mathematical models are being used, with particular reference to the British Columbia epidemic.

In the first talk, Prof. Caroline Colijn (Dept. of Mathematics, Simon Fraser University) will outline the key features of the British Columbia data and focus on how modelling has allowed us to estimate the effectiveness of the provincial response. In the second talk, Prof. Daniel Coombs (Dept. of Mathematics and Inst. of Applied Mathematics, University of British Columbia) will describe forward-looking modelling approaches that can provide some guidance as the province moves towards partial de-escalation of measures. Each talk will be 30 mins in length and followed by a question and discussion period.

For more details on the group's work and to contact the team, please visit https://bccovid-19group.ca/

## What is epithelial-mesenchymal plasticity and why is it important for metastasis?

Until very recently most cancer biologists operated with the assumption that the most common route to metastasis involved cells of the primary tumor transforming to a motile single-cell phenotype via complete EMT (the epithelial-mesenchymal transition). This change allowed them to migrate individually to distant organs, eventually leading to clonal growths in other locations. But, a new more nuanced picture has been emerging, based on advanced measurements and on computational systems biology approaches. It has now been realized that cells can readily adopt states with hybrid properties, use these properties to move collectively and cooperatively, and reach distant niches as highly metastatic clusters. This talk will focus on the accumulating evidence for this revised perspective, the role of biological physics theory in instigating this whole line of investigation, and on open questions currently under investigation.

## Modeling strict age-targeted mitigation strategies for COVID-19

In this talk, we will use compartmental models to examine the power of age-targeted mitigation strategies for COVID-19. We will present evidence that, in the context of strategies which end with herd immunity, age-heterogeneous strategies are better for reducing direct mortalities across a wide parameter regime. And using a model which integrates empirical data on age-contact patterns in the United States and recent estimates of COVID-19 mortality and hospitalization rates, we will present evidence that age-targeted approaches have the potential to greatly reduce mortalities and ICU utilization for COVID-19, among strategies which ultimately end the epidemic by reaching herd immunity. This is joint work with Maria Chikina.