A Review of Mathematical Models for the Formation of\ud Vascular Networks

Mainly two mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former consists of the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter consists of the sprouting of new vessels from an existing capillary or post-capillary venule. Similar phenomena are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis.\ud \ud A number of mathematical approaches have analysed these phenomena. This paper reviews the different modelling procedures, with a special emphasis on their ability to reproduce the biological system and to predict measured quantities which describe the overall processes. A comparison between the different methods is also made, highlighting their specific features

Towards whole-organ modelling of tumour growth

Multiscale approaches to modelling biological phenomena are growing rapidly. We present here some recent results on the formulation of a theoretical framework which can be developed into a fully integrative model for cancer growth. The model takes account of vascular adaptation and cell-cycle dynamics. We explore the effects of spatial inhomogeneity induced by the blood flow through the vascular network and of the possible effects of p27 on the cell cycle. We show how the model may be used to investigate the efficiency of drug-delivery protocols

Quasispecies Spatial Models for RNA Viruses with Different Replication Modes and Infection Strategies

Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along time

Layered Cellular Automata

Layered Cellular Automata (LCA) extends the concept of traditional cellular automata (CA) to model complex systems and phenomena. In LCA, each cell's next state is determined by the interaction of two layers of computation, allowing for more dynamic and realistic simulations. This thesis explores the design, dynamics, and applications of LCA, with a focus on its potential in pattern recognition and classification. The research begins by introducing the limitations of traditional CA in capturing the complexity of real-world systems. It then presents the concept of LCA, where layer 0 corresponds to a predefined model, and layer 1 represents the proposed model with additional influence. The interlayer rules, denoted as f and g, enable interactions not only from adjacent neighboring cells but also from some far-away neighboring cells, capturing long-range dependencies. The thesis explores various LCA models, including those based on averaging, maximization, minimization, and modified ECA neighborhoods. Additionally, the implementation of LCA on the 2-D cellular automaton Game of Life is discussed, showcasing intriguing patterns and behaviors. Through extensive experiments, the dynamics of different LCA models are analyzed, revealing their sensitivity to rule changes and block size variations. Convergent LCAs, which converge to fixed points from any initial configuration, are identified and used to design a two-class pattern classifier. Comparative evaluations demonstrate the competitive performance of the LCA-based classifier against existing algorithms. Theoretical analysis of LCA properties contributes to a deeper understanding of its computational capabilities and behaviors. The research also suggests potential future directions, such as exploring advanced LCA models, higher-dimensional simulations, and hybrid approaches integrating LCA with other computational models.Comment: This thesis represents the culmination of my M.Tech research, conducted under the guidance of Dr. Sukanta Das, Associate Professor at the Department of Information Technology, Indian Institute of Engineering Science and Technology, Shibpur, West Bengal, India. arXiv admin note: substantial text overlap with arXiv:2210.13971 by other author

Common metrics for cellular automata models of complex systems

The creation and use of models is critical not only to the scientific process, but also to life in general. Selected features of a system are abstracted into a model that can then be used to gain knowledge of the workings of the observed system and even anticipate its future behaviour. A key feature of the modelling process is the identification of commonality. This allows previous experience of one model to be used in a new or unfamiliar situation. This recognition of commonality between models allows standards to be formed, especially in areas such as measurement. How everyday physical objects are measured is built on an ingrained acceptance of their underlying commonality. Complex systems, often with their layers of interwoven interactions, are harder to model and, therefore, to measure and predict. Indeed, the inability to compute and model a complex system, except at a localised and temporal level, can be seen as one of its defining attributes. The establishing of commonality between complex systems provides the opportunity to find common metrics. This work looks at two dimensional cellular automata, which are widely used as a simple modelling tool for a variety of systems. This has led to a very diverse range of systems using a common modelling environment based on a lattice of cells. This provides a possible common link between systems using cellular automata that could be exploited to find a common metric that provided information on a diverse range of systems. An enhancement of a categorisation of cellular automata model types used for biological studies is proposed and expanded to include other disciplines. The thesis outlines a new metric, the C-Value, created by the author. This metric, based on the connectedness of the active elements on the cellular automata grid, is then tested with three models built to represent three of the four categories of cellular automata model types. The results show that the new C-Value provides a good indicator of the gathering of active cells on a grid into a single, compact cluster and of indicating, when correlated with the mean density of active cells on the lattice, that their distribution is random. This provides a range to define the disordered and ordered state of a grid. The use of the C-Value in a localised context shows potential for identifying patterns of clusters on the grid

Dickkopf1 Regulates Fate Decision and Drives Breast Cancer Stem Cells to Differentiation: An Experimentally Supported Mathematical Model

BACKGROUND: Modulation of cellular signaling pathways can change the replication/differentiation balance in cancer stem cells (CSCs), thus affecting tumor growth and recurrence. Analysis of a simple, experimentally verified, mathematical model suggests that this balance is maintained by quorum sensing (QS). METHODOLOGY/PRINCIPAL FINDINGS: To explore the mechanism by which putative QS cellular signals in mammary stem cells (SCs) may regulate SC fate decisions, we developed a multi-scale mathematical model, integrating extra-cellular and intra-cellular signal transduction within the mammary tissue dynamics. Preliminary model analysis of the single cell dynamics indicated that Dickkopf1 (Dkk1), a protein known to negatively regulate the Wnt pathway, can serve as anti-proliferation and pro-maturation signal to the cell. Simulations of the multi-scale tissue model suggested that Dkk1 may be a QS factor, regulating SC density on the level of the whole tissue: relatively low levels of exogenously applied Dkk1 have little effect on SC numbers, whereas high levels drive SCs into differentiation. To verify these model predictions, we treated the MCF-7 cell line and primary breast cancer (BC) cells from 3 patient samples with different concentrations and dosing regimens of Dkk1, and evaluated subsequent formation of mammospheres (MS) and the mammary SC marker CD44(+)CD24(lo). As predicted by the model, low concentrations of Dkk1 had no effect on primary BC cells, or even increased MS formation among MCF-7 cells, whereas high Dkk1 concentrations decreased MS formation among both primary BC cells and MCF-7 cells. CONCLUSIONS/SIGNIFICANCE: Our study suggests that Dkk1 treatment may be more robust than other methods for eliminating CSCs, as it challenges a general cellular homeostasis mechanism, namely, fate decision by QS. The study also suggests that low dose Dkk1 administration may be counterproductive; we showed experimentally that in some cases it can stimulate CSC proliferation, although this needs validating in vivo

Modelling Early Transitions Toward Autonomous Protocells

This thesis broadly concerns the origins of life problem, pursuing a joint approach that combines general philosophical/conceptual reflection on the problem along with more detailed and formal scientific modelling work oriented in the conceptual perspective developed. The central subject matter addressed is the emergence and maintenance of compartmentalised chemistries as precursors of more complex systems with a proper cellular organization. Whereas an evolutionary conception of life dominates prebiotic chemistry research and overflows into the protocells field, this thesis defends that the 'autonomous systems perspective' of living phenomena is a suitable - arguably the most suitable - conceptual framework to serve as a backdrop for protocell research. The autonomy approach allows a careful and thorough reformulation of the origins of cellular life problem as the problem of how integrated autopoietic chemical organisation, present in all full-fledged cells, originated and developed from more simple far-from-equilibrium chemical aggregate systems.Comment: 205 Pages, 27 Figures, PhD Thesis Defended Feb 201