1,720,999 research outputs found
A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations
No full textA major goal of modern computational biology is to simulate the collective behaviour of large
cell populations starting from the intricate web of molecular interactions occurring at the
microscopic level. In this paper we describe a simplified model of cell metabolism, growth
and proliferation, suitable for inclusion in a multicell simulator, now under development
(Chignola R and Milotti E 2004 Physica A 338 261–6). Nutrients regulate the proliferation
dynamics of tumour cells which adapt their behaviour to respond to changes in the
biochemical composition of the environment. This modelling of nutrient metabolism and cell
cycle at a mesoscopic scale level leads to a continuous flow of information between the two
disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with
modern computers and tested experimentally
Bridging the gap between the micro- and the macro-world of tumors
No full textAt present it is still quite difficult to match the vast knowledge on the behavior of individual tumor cells with macroscopic measurements on clinical tumors. On the modeling side, we already know how to deal with many molecular pathways and cellular events, using systems of differential equations and other modeling tools, and ideally, we should be able to extend such a mathematical description up to the level of large tumor masses. An extended model should thus help us forecast the behavior of large tumors from our basic knowledge of microscopic processes. Unfortunately, the complexity of these processes makes it very difficult – probably impossible – to develop comprehensive analytical models. We try to bridge the gap with a simulation program which is based on basic biochemical and biophysical processes – thereby building an effective computational model – and in this paper we describe its structure, endeavoring to make the description sufficiently detailed and yet understandable
Fluctuations of Atmospheric Pressure and the Sound of Underground Karst Systems: The Antro del Corchia Case (Apuane Alps, Italy)
Full text linkMountains that contain subterranean voids can inhale fresh and clean air, and their breath is a fascinating natural phenomenon that speleologists know very well. Air flow through the entrances of underground systems is also an interesting geophysical problem. Basically, it is caused by temperature and pressure gradients between the internal and external atmospheres, but the dynamic interplay between these two driving forces is still not well understood. Our contribution dissects the physics of underground winds. Wind velocity, internal and external temperature and pressure have been measured synchronously at two entrances of a vast (∼64 km) underground system beneath the Mount Corchia, Apuane Alps, Italy. The data shows that, within time scales of minutes to days, pressure fluctuations of the external atmosphere primarily force air to flow underground, whereas temperature gradients play only a minor role. We modeled the cave as a system that takes the external atmospheric pressure as the input signal and outputs wind from its entrances. This wind, in turn, contains information about the system’s response, and hence on the structure of the subterranean voids. This information can be extracted using standard signal processing techniques and by using deconvolution methods we identify the same infrasound resonances in signals sampled at both entrances. These are the characteristic frequencies of the cave, and by using the Helmholtz resonance formalism it can be estimated that the explored volume of this important underground system is less than half of its probable real extension
Oxygen in the Tumor Microenvironment: Mathematical and Numerical Modeling
No full textThere are many reasons to try to achieve a good grasp of the distribution of oxygen in the tumor microenvironment. The lack of oxygen - hypoxia - is a main actor in the evolution of tumors and in their growth and appears to be just as important in tumor invasion and metastasis. Mathematical models of the distribution of oxygen in tumors which are based on reaction-diffusion equations provide partial but qualitatively significant descriptions of the measured oxygen concentrations in the tumor microenvironment, especially when they incorporate important elements of the blood vessel network such as the blood vessel size and spatial distribution and the pulsation of local pressure due to blood circulation. Here, we review our mathematical and numerical approaches to the distribution of oxygen that yield insights both on the role of the distribution of blood vessel density and size and on the fluctuations of blood pressure
Thresholds, long delays and stability from generalized allosteric effect in protein networks
No full text
Neighbor search algorithm for lattice-free simulations with short-range forces
No full textWe have recently developed a lattice-free simulation program in computational cell biology which needs the introduction and management of the biomechanical interactions of cells. These interactions are associated with short range forces which act on nearest-neighbors only. The forces act in the rearrangement of cells due to proliferation and cell growth and this requires a recalculation of the proximity relations at each time step. Here we describe the implementation of an algorithm to efficiently compute the proximity relations and designed to run on Graphics Processing Units (GPUs). The results of the first test runs on an NVidia Fermi GPU are encouraging: the algorithm has the potential to significantly boost the simulation program and to map the disordered lattice also on other multicore machines with hypercubic connectivity
Proliferation and Death in a Binary Environment : a Stochastic Model of Cellular Ecosystems
No full textThe activation, growth and death of animal cells are accompanied by changes in the chemical composition of the surrounding environment. Cells and their microscopic environment constitute therefore a cellular ecosystem whose
time-evolution determines processes of interest for either biology (e.g. animal development) and medicine (e.g. tumor spreading, immune response). In this paper, we consider a general stochastic model of the interplay between cells and environmental cellular niches. Niches may be either favourable or unfavourable in sustaining cell activation, growth and death, the state of the niches depending on the state of the cells. Under the hypothesis of random coupling between the state of the environmental niche and the state of the cell, the rescaled model reduces to a set of four non-linear differential equations. The biological meaning of the model is studied and illustrated by fitting experimental data on the growth of multicellular tumor spheroids. A detailed analysis of the stochastic model, of its deterministic
limit, and of normal fluctuations is provided
Interplay between distribution of live cells and growth dynamics of solid tumours
No full textExperiments show that simple diffusion of nutrients and waste molecules is not sufficient to explain the typical multilayered structure of solid tumours, where an outer rim of proliferating cells surrounds a layer of quiescent but viable cells and a central necrotic region. These experiments challenge models of tumour growth based exclusively on diffusion. Here we propose a model of tumour growth that incorporates the volume dynamics and the distribution of cells within the viable cell rim. The model is suggested by in silico experiments and is validated using in vitro data. The results correlate with in vivo data as well, and the model can be used to support experimental and clinical oncology
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