Development and validation of computational models of cellular interaction

In this paper we take the view that computational models of biological systems should satisfy two conditions – they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of software issues

Agent-based computational modeling of wounded epithelial cell monolayers

Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures

An agent-based model of anoikis in the colon crypt displays novel emergent behaviour consistent with biological observations

Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth. Model simulations yield previously unseen emergent phenomena, such as localization of cell death to a small region of the crypt mouth which corresponds with that observed in vivo. A mechanism emerges in the model for regulation of crypt cellularity in response to changes in either cell proliferation rates or membrane adhesion strengths. We show that cell shape assumptions influence this behaviour, with cylinders recapitulating biology better than spheres. Potential applications of the model include determination of roles of mutations in neoplasia and exploring factors for altered crypt morphodynamics

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

The VPH Hypermodelling framework for cancer multiscale models in the clinical practice

The VPH Hypermodelling framework is a collaborative computational platform providing a complete Problem Solving Environment to execute, on distributed computational architectures, sophisticated predictive models involving patient medical data or specialized repositories. In the CHIC' project, it will be enhanced to support clinicians in providing prompt personalised cancer treatments. It supports several computational architectures with strict security policies

Interdisciplinary care to enhance mental health and social and emotional wellbeing

This chapter discusses and defines the difference between multidisciplinary and interdisciplinary/interprofessional care with a focus on interdisciplinary care as a model of practice which supports equality and interconnectedness of responsibility amongst team members when working in Aboriginal and Torres Strait Islander contexts. The chapter describes the various professional and para professional practitioners that comprise interdisciplinary teams working in mental health and wellbeing contexts and their roles. The focus is on an interdisciplinary team approach to providing health and wellbeing care as its ethos of equal relationships and interdependent collaboration is more encompassing of social and emotional wellbeing values. Identification of the issues and limitations of interdisciplinary practice and the means to addressing them are explored within the context of how interdisciplinary care fits into mental health best practice and human rights

Three point SUSY Ward identities without Ghosts

We utilise a non-local gauge transform which renders the entire action of SUSY QED invariant and respects the SUSY algebra modulo the gauge-fixing condition, to derive two- and three-point ghost-free SUSY Ward identities in SUSY QED. We use the cluster decomposition principle to find the Green's function Ward identities and then takes linear combinations of the latter to derive identities for the proper functions.Comment: 20 pages, no figures, typos correcte

Use of soil testing to predict nitrogen fertilizer needs of barley and rapeseed in Alberta

Non-Peer Reviewe

A cellular based model of the colon crypt suggests novel effects forApc phenotype in colorectal carcinogenesis

Colorectal cancer (CRC) is a major cause of cancer mortality; loss of the Apc gene is an early step in the formation of CRC. A new computational model of the colonic crypt has been developed to simulate the effects of Apc loss. The model includes a region of flat mucosa, which has not previously been considered in the context of Apc loss. The model suggests that Apc loss confers a survival advantage at the crypt mouth which may be a previously unknown method of mutation fixation