5 research outputs found
Spatially Adaptive Stochastic Methods for Fluid-Structure Interactions Subject to Thermal Fluctuations in Domains with Complex Geometries
We develop stochastic mixed finite element methods for spatially adaptive
simulations of fluid-structure interactions when subject to thermal
fluctuations. To account for thermal fluctuations, we introduce a discrete
fluctuation-dissipation balance condition to develop compatible stochastic
driving fields for our discretization. We perform analysis that shows our
condition is sufficient to ensure results consistent with statistical
mechanics. We show the Gibbs-Boltzmann distribution is invariant under the
stochastic dynamics of the semi-discretization. To generate efficiently the
required stochastic driving fields, we develop a Gibbs sampler based on
iterative methods and multigrid to generate fields with computational
complexity. Our stochastic methods provide an alternative to uniform
discretizations on periodic domains that rely on Fast Fourier Transforms. To
demonstrate in practice our stochastic computational methods, we investigate
within channel geometries having internal obstacles and no-slip walls how the
mobility/diffusivity of particles depends on location. Our methods extend the
applicability of fluctuating hydrodynamic approaches by allowing for spatially
adaptive resolution of the mechanics and for domains that have complex
geometries relevant in many applications
Teagasc submission made in response to the Consultation Paper on Interim Review of Ireland’s Nitrates Derogation 2019
Teagasc SubmissionSubmission to governmentThis submission was made in response to the consultation process run jointly by the
Department of Housing, Planning, Community and Local Government (DHPCLG) and the
Department of Agriculture, Food and the Marine (DAFM) inviting views and comments on
proposals for the Interim Review of Ireland’s Nitrates Derogation Programme in 2019. It has
been prepared by Teagasc’s Water Quality Working Group in consultation with the Gaseous
Emissions Working Group. These working groups have members drawn from both the
Knowledge Transfer and Research Directorates of Teagasc. It was prepared following
consultation with colleagues across Teagasc using their collective knowledge and expertise
in agri-environmental science and practice and the implementation of the Good Agricultural
Practice (GAP) and Nitrates Derogation Regulations.https://www.teagasc.ie/publications/2019/teagasc-submission-made-in-response-to-the-consultation-paper-on-interim-review-of-irelands-nitrates-derogation-2019.ph
The role of platelet-derived ADP and ATP in promoting pancreatic cancer cell survival and gemcitabine resistance
Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal transition (EMT), an important step in metastasis. Markers of EMT are associated with chemotherapy resistance. However, the association between the development of chemoresistance, EMT, and the contribution of platelets to the process, is still unclear. Here we report that platelets regulate the expression of (1) human equilibrative nucleoside transporter 1 (hENT1) and (2) cytidine deaminase (CDD), markers of gemcitabine resistance in pancreatic cancer. Human ENT1 (hENT1) is known to enable cellular uptake of gemcitabine while CDD deactivates gemcitabine. Knockdown experiments demonstrate that Slug, a mesenchymal transcriptional factor known to be upregulated during EMT, regulates the expression of hENT1 and CDD. Furthermore, we demonstrate that platelet-derived ADP and ATP regulate Slug and CDD expression in pancreatic cancer cells. Finally, we demonstrate that pancreatic cancer cells express the purinergic receptor P2Y 12 , an ADP receptor found mainly on platelets. Thus ticagrelor, a P2Y 12 inhibitor, was used to examine the potential therapeutic effect of an ADP receptor antagonist on cancer cells. Our data indicate that ticagrelor negated the survival signals initiated in cancer cells by platelet-derived ADP and ATP. In conclusion, our results demonstrate a novel role of platelets in modulating chemoresistance in pancreatic cancer. Moreover, we propose ADP/ATP receptors as additional potential drug targets for treatment of pancreatic cancer. © 2017 by the authors