| 1. |
- Scott, Jacob G, et al.
(författare)
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A filter-flow perspective of haematogenous metastasis offers a non-genetic paradigm for personalised cancer therapy
- 2014
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 50:17, s. 3068-3075
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Tidskriftsartikel (refereegranskat)abstract
- Research into mechanisms of haematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of ‘seed–soil’ relationships. Preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulation. Patterns of metastatic spread have been previously quantified using the metastatic efficiency index, a measure quantifying metastatic incidence for a given primary-target organ pair and the relative blood flow between them. We extend this concept to take into account the reduction in CTCs which occurs in organ capillary beds connected by a realistic vascular network topology. Application to a dataset of metastatic incidence reveals that metastatic patterns depend strongly on assumptions about the existence and location of micrometastatic disease which governs CTC dynamics on the network, something which has heretofore not been considered – an oversight which precludes our ability to predict metastatic patterns in individual patients.
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| 2. |
- Anderson, Alexander, et al.
(författare)
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Evolution, regulation and disruption of homeostasis and its role in carcinogenesis
- 2010
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Ingår i: Multiscale Cancer Modeling. - : CRC Press. - 9781439814406 ; , s. 1-30
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Homeostasis is a critical property of living beings that involves the ability to self-regulate in response to changes in the environment in order to maintain a certain dynamic balance aecting form and/or function. Homeostasis is of particular importance in multicellular organisms, where it is intertwined with development [2,3]. Organisms have evolved intricate control mechanisms that ensure developmental processes achieve their end points and stabilize (e.g., dierentiate) as well as allow for a degree of adaptability to a range of conditions (e.g., stress or damage induced by wounding). is allows for the emergence of a more robust system that can tolerate both external and internal perturbations [4]. However, there are limitations to this tolerance, and oen it is the rare events that cause the most disruption [5]; think of the extinction of dinosaurs for an example. From an evolutionary point of view, this is a viable trade-o between the energetic cost of homeostasis versus the tness benet it would provide. In practical terms, homeostasis of living multicellular organisms is constrained in terms of the amount of disruption they can cope with and in terms of the amount of time they will remain homeostatic.
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| 3. |
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| 4. |
- Bengmark, Samuel, 1965, et al.
(författare)
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Combining engineering and teacher education – ideas and experiences from Chalmers University of Technology
- 2021
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Ingår i: Bidrag från 8:e Utvecklingskonferensen för Sveriges ingenjörsutbildningar. - 9789178672714
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Konferensbidrag (refereegranskat)abstract
- In response to the lack of STEM teachers in Sweden, Chalmers University of Technology offers a double degree program in engineering and education. This article investigates which ideas behind the program’s design have been of particular value in implementing the program and their added value. The five main ideas are: involve skilled schoolteachers called master teachers in the education, having many entrances to the program but only one exit, using interviews as part of the admission process, using a competency model to ensure coherence in the education, focusing on concrete work skills at the beginning of the education and later move on to theory and further development. We invite other universities to consider double degree programs in engineering and education and be inspired by these five ideas in their implementation.
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| 5. |
- Bernhardsson, Sebastian, et al.
(författare)
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Structural correlations in bacterial metabolic networks
- 2011
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 11:20
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Tidskriftsartikel (refereegranskat)abstract
- Background Evolution of metabolism occurs through the acquisition and loss of genes whose products acts as enzymes in metabolic reactions, and from a presumably simple primordial metabolism the organisms living today have evolved complex and highly variable metabolisms. We have studied this phenomenon by comparing the metabolic networks of 134 bacterial species with known phylogenetic relationships, and by studying a neutral model of metabolic network evolution. Results We consider the 'union-network' of 134 bacterial metabolisms, and also the union of two smaller subsets of closely related species. Each reaction-node is tagged with the number of organisms it belongs to, which we denote organism degree (OD), a key concept in our study. Network analysis shows that common reactions are found at the centre of the network and that the average OD decreases as we move to the periphery. Nodes of the same OD are also more likely to be connected to each other compared to a random OD relabelling based on their occurrence in the real data. This trend persists up to a distance of around five reactions. A simple growth model of metabolic networks is used to investigate the biochemical constraints put on metabolic-network evolution. Despite this seemingly drastic simplification, a 'union-network' of a collection of unrelated model networks, free of any selective pressure, still exhibit similar structural features as their bacterial counterpart. Conclusions The OD distribution quantifies topological properties of the evolutionary history of bacterial metabolic networks, and lends additional support to the importance of horizontal gene transfer during bacterial metabolic evolution where new reactions are attached at the periphery of the network. The neutral model of metabolic network growth can reproduce the main features of real networks, but we observe that the real networks contain a smaller common core, while they are more similar at the periphery of the network. This suggests that natural selection and biochemical correlations can act both to diversify and to narrow down metabolic evolution.
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| 6. |
- Borgqvist, Johannes, 1990, et al.
(författare)
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Cell polarisation in a bulk-surface model can be driven by both classic and non-classic Turing instability
- 2021
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Ingår i: Npj Systems Biology and Applications. - : Springer Science and Business Media LLC. - 2056-7189. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The GTPase Cdc42 is the master regulator of eukaryotic cell polarisation. During this process, the active form of Cdc42 is accumulated at a particular site on the cell membrane called the pole. It is believed that the accumulation of the active Cdc42 resulting in a pole is driven by a combination of activation-inactivation reactions and diffusion. It has been proposed using mathematical modelling that this is the result of diffusion-driven instability, originally proposed by Alan Turing. In this study, we developed, analysed and validated a 3D bulk-surface model of the dynamics of Cdc42. We show that the model can undergo both classic and non-classic Turing instability by deriving necessary conditions for which this occurs and conclude that the non-classic case can be viewed as a limit case of the classic case of diffusion-driven instability. Using three-dimensional Spatio-temporal simulation we predicted pole size and time to polarisation, suggesting that cell polarisation is mainly driven by the reaction strength parameter and that the size of the pole is determined by the relative diffusion.
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| 7. |
- Borgqvist, Johannes, 1990, et al.
(författare)
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Turing pattern formation on the sphere is robust to the removal of a hole
- 2024
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Ingår i: JOURNAL OF MATHEMATICAL BIOLOGY. - : Springer Science+Business Media B.V.. - 0303-6812 .- 1432-1416. ; 88:2
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Tidskriftsartikel (refereegranskat)abstract
- The formation of buds on the cell membrane of budding yeast cells is thought to be driven by reactions and diffusion involving the protein Cdc42. These processes can be described by a coupled system of partial differential equations known as the Schnakenberg system. The Schnakenberg system is known to exhibit diffusion-driven pattern formation, thus providing a mechanism for bud formation. However, it is not known how the accumulation of bud scars on the cell membrane affect the ability of the Schnakenberg system to form patterns. We have approached this problem by modelling a bud scar on the cell membrane with a hole on the sphere. We have studied how the spectrum of the Laplace-Beltrami operator, which determines the resulting pattern, is affected by the size of the hole, and by numerically solving the Schnakenberg system on a sphere with a hole using the finite element method. Both theoretical predictions and numerical solutions show that pattern formation is robust to the introduction of a bud scar of considerable size, which lends credence to the hypothesis that bud formation is driven by diffusion-driven instability.
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| 8. |
- Gerlee, Philip, 1980, et al.
(författare)
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Autocrine signaling can explain the emergence of Allee effects in cancer cell populations
- 2022
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Ingår i: Plos Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- In many human cancers, the rate of cell growth depends crucially on the size of the tumour cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations from three patient-derived brain tumor cell lines grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy.
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| 9. |
- Gerlee, Philip, 1980, et al.
(författare)
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Bridging scales in cancer progression: Mapping genotype to phenotype using neural networks
- 2015
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 30, s. 30-41
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Tidskriftsartikel (refereegranskat)abstract
- In this review we summarise our recent efforts in trying to understand the role of heterogeneity in cancer progression by using neural networks to characterise different aspects of the mapping from a cancer cells genotype and environment to its phenotype. Our central premise is that cancer is an evolving system subject to mutation and selection, and the primary conduit for these processes to occur is the cancer cell whose behaviour is regulated on multiple biological scales. The selection pressure is mainly driven by the microenvironment that the tumour is growing in and this acts directly upon the cell phenotype. In turn, the phenotype is driven by the intracellular pathways that are regulated by the genotype. Integrating all of these processes is a massive undertaking and requires bridging many biological scales (i.e. genotype, pathway, phenotype and environment) that we will only scratch the surface of in this review. We will focus on models that use neural networks as a means of connecting these different biological scales, since they allow us to easily create heterogeneity for selection to act upon and importantly this heterogeneity can be implemented at different biological scales. More specifically, we consider three different neural networks that bridge different aspects of these scales and the dialogue with the micro-environment, (i) the impact of the micro-environment on evolutionary dynamics, (ii) the mapping from genotype to phenotype under drug-induced perturbations and (iii) pathway activity in both normal and cancer cells under different micro-environmental conditions.
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| 10. |
- Gerlee, Philip, 1980, et al.
(författare)
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Complexity and stability in growing cancer cell populations
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Evolutionary game theory (EGT) describes dynamics in populations in which individual fitness can change because of the interactions with others, called frequency-dependent selection (1). Interactions are driven by differences in phenotype. EGT has been proposed as a framework for evolutionary dynamics of tumors (2). An underlying assumption is that different cancer cell types within a tumor engage in different heritable behavior; thus, frequency-dependent selection acts. Until now there has been little direct empirical evidence for this. The study by Archetti et al. (3) demonstrates frequency-dependent growth rates of two phenotypically distinct cancer subclones. One clone produced the insulin-like growth factor (IGF)-II, the other did not. In a mix of producers and nonproducers, the growth rates of both clones varied with the frequency of producers. Because a similar effect was shown when varying the concentration of serum, the production of IGF-II could be viewed as a public goods game.
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