Pancheri, Francesco Q.; Dorfmann, Luis(Rubber Chemistry and Technology, Rubber Division, ACS, 2014-03)[Article]
We present a new experimental method and provide data showing the response of 40A natural rubber in uniaxial, pure shear, and biaxial tension. Real-time biaxial strain control allows for independent and automatic variation of the velocity of extension and retraction of each actuator to maintain the preselected deformation rate within the gage area of the specimen. Wealso focus on the Valanis-Landel hypothesis that is used to verify and validate the consistency of the data.Weuse a threeterm Ogden model to derive stress-stretch relations to validate the experimental data. The material model parameters are determined using the primary loading path in uniaxial and equibiaxial tension. Excellent agreement is found when the model is used to predict the response in biaxial tension for different maximum in-plane stretches. The application of the Valanis-Landel hypothesis also results in excellent agreement with the theoretical prediction.
Jain, Harsh Vardhan; Richardson, Alan; Meyer-Hermann, Michael; Byrne, Helen M.(PLoS ONE, Public Library of Science (PLoS), 2014-01-06)[Article]
Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.
Goriely, Alain; Moulton, Derek(New Trends in the Physics and Mechanics of Biological Systems, Oxford University Press (OUP), 2011-10-11)[Book Chapter]
This chapter is concerned with the modelling of growth processes in the framework of continuum mechanics and nonlinear elasticity. It begins by considering growth and deformation in a one-dimensional setting, illustrating the key relationship between growth, the elastic response of the material, and the generation of residual stresses. The general three-dimensional theory of morphoelasticity is then developed from conservation of mass and momentum balance equations. In the formulation, the multiplicative decomposition of the deformation tensor, the standard approach in morphoelasticity, is derived in a new way. A discussion of continuous growth is also included. The chapter concludes by working through a sample problem of a growing cylindrical tube. A stability analysis is formulated, and the effect of growth on mucosal folding, a commonly seen instability in biological tubes, is demonstrated.
Mirams, Gary R; Arthurs, Christopher J; Bernabeu, Miguel O; Bordas, Rafel; Cooper, Jonathan; Corrias, Alberto; Davit, Yohan; Dunn, Sara-Jane; Fletcher, Alexander G; Harvey, Daniel G; Marsh, Megan E; Osborne, James M.; Pathmanathan, Pras; Pitt-Francis, Joe; Southern, James; Zemzemi, Nejib; Gavaghan, David J(PLoS Computational Biology, Public Library of Science (PLoS), 2013-03-14)[Article]
Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to 're-invent the wheel' with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials.
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