We examine the practical identifiability of parameters in a spatio-temporal reaction–diffusion model of a scratch assay. Experimental data involve fluorescent cell cycle labels, providing spatial information about cell position and temporal information about the cell cycle phase. Cell cycle labelling is incorporated into the reaction–diffusion model by treating the total population as two interacting subpopulations. Practical identifiability is examined using a Bayesian Markov chain Monte Carlo (MCMC) framework, confirming that the parameters are identifiable when we assume the diffusivities of the subpopulations are identical, but that the parameters are practically non-identifiable when we allow the diffusivities to be distinct. We also assess practical identifiability using a profile likelihood approach, providing similar results to MCMC with the advantage of being an order of magnitude faster to compute. Therefore, we suggest that the profile likelihood ought to be adopted as a screening tool to assess practical identifiability before MCMC computations are performed.

Let (G, P) be a quasi‐lattice ordered group, and let X be a product system over P of Hilbert bimodules. Under mild hypotheses, we associate to X a C*‐algebra which is co‐universal for injective Nica covariant Toeplitz representations of X which preserve the gauge coaction. Under appropriate amenability criteria, this co‐universal C*‐algebra coincides with the Cuntz‐Nica‐Pimsner algebra introduced by Sims and Yeend. We prove two key uniqueness theorems, and indicate how to use our theorems to realize a number of reduced crossed products as instances of our co‐universal algebras. In each case, it is an easy corollary that the Cuntz‐Nica‐Pimsner algebra is isomorphic to the corresponding full crossed product.

The fluorescent ubiquitination-based cell cycle indicator, also known as FUCCI, allows the visualization of the G1 and S/G2/M cell cycle phases of individual cells. FUCCI consists of two fluorescent probes, so that cells in the G1 phase fluoresce red and cells in the S/G2/M phase fluoresce green. FUCCI reveals real-time information about cell cycle dynamics of individual cells, and can be used to explore how the cell cycle relates to the location of individual cells, local cell density, and different cellular microenvironments. In particular, FUCCI is used in experimental studies examining cell migration, such as malignant invasion and wound healing. Here we present, to our knowledge, new mathematical models that can describe cell migration and cell cycle dynamics as indicated by FUCCI. The fundamental model describes the two cell cycle phases, G1 and S/G2/M, which FUCCI directly labels. The extended model includes a third phase, early S, which FUCCI indirectly labels. We present experimental data from scratch assays using FUCCI-transduced melanoma cells, and show that the predictions of spatial and temporal patterns of cell density in the experiments can be described by the fundamental model. We obtain numerical solutions of both the fundamental and extended models, which can take the form of traveling waves. These solutions are mathematically interesting because they are a combination of moving wavefronts and moving pulses. We derive and confirm a simple analytical expression for the minimum wave speed, as well as exploring how the wave speed depends on the spatial decay rate of the initial condition.

Abstract. We consider a family of dynamical systems (A, α, L) in which α is an endomorphism of a C * -algebra A and L is a transfer operator for α. We extend Exel's construction of a crossed product to cover non-unital algebras A, and show that the C * -algebra of a locally finite graph can be realised as one of these crossed products. When A is commutative, we find criteria for the simplicity of the crossed product, and analyse the ideal structure of the crossed product.

(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/238303 doi: bioRxiv preprint first posted online Dec. 21, 2017; extended models, which can take the form of travelling waves. These solutions are mathematically interesting because they are a combination of moving wavefronts and moving pulses. We derive and confirm a simple analytical expression for the minimum wave speed, as well as exploring how the wave speed depends on the spatial decay rate of the initial condition.2 All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

We present a suite of experimental data showing that cell proliferation assays, prepared using standard methods thought to produce asynchronous cell populations, persistently exhibit inherent synchronization. Our experiments use fluorescent cell cycle indicators to reveal the normally hidden cell synchronization, by highlighting oscillatory subpopulations within the total cell population. These oscillatory subpopulations would never be observed without these cell cycle indicators. On the other hand, our experimental data show that the total cell population appears to grow exponentially, as in an asynchronous population. We reconcile these seemingly inconsistent observations by employing a multi-stage mathematical model of cell proliferation that can replicate the oscillatory subpopulations. Our study has important implications for understanding and improving experimental reproducibility. In particular, inherent synchronization may affect the experimental reproducibility of studies aiming to investigate cell cycle-dependent mechanisms, including changes in migration and drug response.

In many scientific and technological contexts, we have only a poor understanding of the structure and details of appropriate mathematical models. We often, therefore, need to compare different models. With available data we can use formal statistical model selection to compare and contrast the ability of different mathematical models to describe such data. There is, however, a lack of rigorous methods to compare different models a priori . Here, we develop and illustrate two such approaches that allow us to compare model structures in a systematic way by representing models as simplicial complexes. Using well-developed concepts from simplicial algebraic topology, we define a distance between models based on their simplicial representations. Employing persistent homology with a flat filtration provides for alternative representations of the models as persistence intervals, which represent model structure, from which the model distances are also obtained. We then expand on this measure of model distance to study the concept of model equivalence to determine the conceptual similarity of models. We apply our methodology for model comparison to demonstrate an equivalence between a positional-information model and a Turing-pattern model from developmental biology, constituting a novel observation for two classes of models that were previously regarded as unrelated.

We introduce P -graphs, which are generalisations of directed graphs in which paths have a degree in a semigroup P rather than a length in N. We focus on semigroups P arising as part of a quasi-lattice ordered group (G, P ) in the sense of Nica, and on P -graphs which are finitely aligned in the sense of Raeburn and Sims. We show that each finitely aligned P -graph admits a C * -algebra C * min (Λ) which is co-universal for partial-isometric representations of Λ which admit a coaction of G compatible with the P -valued length function. We also characterise when a homomorphism induced by the co-universal property is injective. Our results combined with those of Spielberg show that every Kirchberg algebra is Morita equivalent C * min (Λ) for some (N 2 * N)-graph Λ.