52 research outputs found

    Stability of explicit radiation-material coupling in radiative transfer calculations

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    a b s t r a c t We show that explicit radiation-material coupling, which is essentially always stable for infrared radiative transfer is conditionally stable in the high energy density regime. A linearized stability analysis is first performed for a simple infinite-medium problem that yields both a criterion for unconditional stability, a time-step restriction that applies for conditional stability, and a time-step criterion that always applies for nonoscillatory solutions. This analysis is then extended to include space dependence with the result that the system is always conditionally stable, but with a time step restriction somewhat different from the infinite-medium case. Nonetheless, the time step restriction for non-oscillatory solutions remains the same. Computations are presented that confirm the predictions of our analysis, and conclusions are given

    Preconditioning a mixed discontinuous finite element method for radiation diffusion

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    We propose a multilevel preconditioning strategy for the iterative solution of large sparse linear systems arising from a finite element discretization of the radiation diffusion equations. In particular, these equations are solved using a mixed finite element scheme in order to make the discretization discontinuous, which is imposed by the application in which the diffusion equation will be embedded. The essence of the preconditioner is to use a continuous finite element discretization of the original, elliptic diffusion equation for preconditioning the discontinuous equations. We have found that this preconditioner is very effective and makes the iterative solution of the discontinuous diffusion equations practical for large problems. This approach should be applicable to discontinuous discretizations of other elliptic equations. We show how our preconditioner is developed and applied to radiation diffusion problems on unstructured, tetrahedral meshes and show numerical results that illustrate its effectiveness. Published in 2004 by John Wiley & Sons, Ltd

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Approximate Schur Complement Preconditioning Of The Lowest Order Nodal Discretizations

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    Certain classes of nodal methods and mixed-hybrid finite element methods lead to equivalent, robust and accurate discretizations of 2nd order elliptic PDEs. However, widespread popularity of these discretizations has been hindered by the awkward linear systems which result. The present work overcomes this awkwardness and develops preconditioners which yield solution algorithms for these discretizations with an efficiency comparable to that of the multigrid method for standard discretizations. Our approach exploits the natural partitioning of the linear system obtained by the mixed-hybrid finite element method. By eliminating different subsets of unknowns, two Schur complements are obtained with known structure. Replacing key matrices in this structure by lumped approximations we define three optimal preconditioners. Central to the optimal performance of these preconditioners is their sparsity structure which is compatible with standard finite difference discretizations and hence tre..
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