Model selection is a chronic issue in computational science. The conventional approach relies heavily on human experience. However, gaining experience takes years and is severely inefficient.
View Article and Find Full Text PDFThe microbiota associated with the rhizosphere is responsible for crucial processes. Understanding how the plant and its bacterial community interact is of great importance to face the upcoming agricultural and viticultural challenges. The composition of the bacterial communities associated with the rhizosphere of grapevines is the result of the interaction between many drivers: biogeography, edaphic factors, soil management and plant genotype.
View Article and Find Full Text PDFThis work focuses on one component of a larger research effort to develop a simulation tool to model populations of flowing cells. Specifically, in this study a local model of the biochemical interactions between circulating melanoma tumor cells (TC) and substrate adherent polymorphonuclear neutrophils (PMN) is developed. This model provides realistic three-dimensional distributions of bond formation and attendant attraction and repulsion forces that are consistent with the time dependent Computational Fluid Dynamics (CFD) framework of the full system model which accounts local pressure, shear and repulsion forces.
View Article and Find Full Text PDFDrug Discov Today Dis Models
July 2015
Paced by advances in high performance computing, and algorithms for multi-physics and multi-scale simulation, a number of groups have recently established numerical models of flowing blood systems, where cell-scale interactions are explicitly resolved. To be biologically representative, these models account for some or all of: (1) fluid dynamics of the carrier flow, (2) structural dynamics of the cells and vessel walls, (3) interaction and transport biochemistry, and, (4) methods for scaling to physiologically representative numbers of cells. In this article, our interest is the modelling of the tumour micro-environment.
View Article and Find Full Text PDFTumor cell adhesion to the endothelium under shear flow conditions is a critical step that results in circulation-mediated tumor metastasis. This study presents experimental and computational techniques for studying the local hydrodynamic environment around adherent cells and how local shear conditions affect cell-cell interactions on the endothelium in tumor cell adhesion. To study the local hydrodynamic profile around heterotypic adherent cells, a side-view flow chamber assay coupled with micro particle imaging velocimetry (μPIV) technique was developed, where interactions between leukocytes and tumor cells in the near-endothelial wall region and the local shear flow environment were characterized.
View Article and Find Full Text PDFThe primary cause of cancer mortality is not attributed to primary tumor formation, but rather to the growth of metastases at distant organ sites. Tumor cell adhesion to blood vessel endothelium (EC) and subsequent transendothelial migration within the circulation are critical components of the metastasis cascade. Previous studies have shown polymorphonuclear neutrophils (PMNs) may facilitate melanoma cell adhesion to the EC and subsequent extravasation under flow conditions.
View Article and Find Full Text PDFExperimental models that mimic the flow conditions in microcapillaries have suggested that the local shear stresses and shear rates can mediate tumor cell and leukocyte arrest on the endothelium and subsequent sustained adhesion. However, further investigation has been limited by the lack of experimental models that allow quantitative measurement of the hydrodynamic environment over adherent cells. The purpose of this study was to develop a system capable of acquiring quantitative flow profiles over adherent cells.
View Article and Find Full Text PDFBackground: Early rejection of discordant porcine xenografts in primate recipients is initiated by the intragraft binding of either preformed (hyperacute xenograft rejection) or induced (acute vascular rejection) antiporcine recipient antibodies with subsequent complement activation via the classical pathway. We have investigated the efficacy of the supplemental administration of C1-inhibitor (C1-INH), a specific inhibitor of the classical complement activation pathway, for prophylaxis of xenograft rejection in a pig to primate kidney xenotransplantation setting.
Methods: Based on the results of pharmacokinetic studies performed in two nontransplanted monkeys, supplemental C1-INH therapy was administered daily to three Cynomolgus monkeys receiving a life-supporting porcine kidney transplant together with cyclophosphamide-induction/cyclosporine A/mycophenolat-mofetil/steroid immunosuppressive therapy.