23 research outputs found

    Lattice cleaving: a multimaterial tetrahedral meshing algorithm with guarantees

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    pre-printWe introduce a new algorithm for generating tetrahedral meshes that conform to physical boundaries in volumetric domains consisting of multiple materials. The proposed method allows for an arbitrary number of materials, produces high-quality tetrahedral meshes with upper and lower bounds on dihedral angles, and guarantees geometric fidelity. Moreover, the method is combinatoric so its implementation enables rapid mesh construction. These meshes are structured in a way that also allows grading, to reduce element counts in regions of homogeneity. Additionally, we provide proofs showing that both element quality and geometric fidelity are bounded using this approach

    Natural climate solutions

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    Our thanks for inputs by L. Almond, A. Baccini, A. Bowman, S. CookPatton, J. Evans, K. Holl, R. Lalasz, A. Nassikas, M. Spalding, M. Wolosin, and expert elicitation respondents. Our thanks for datasets developed by the Hansen lab and the NESCent grasslands working group (C. Lehmann, D. Griffith, T. M. Anderson, D. J. Beerling, W. Bond, E. Denton, E. Edwards, E. Forrestel, D. Fox, W. Hoffmann, R. Hyde, T. Kluyver, L. Mucina, B. Passey, S. Pau, J. Ratnam, N. Salamin, B. Santini, K. Simpson, M. Smith, B. Spriggs, C. Still, C. Strömberg, and C. P. Osborne). This study was made possible by funding from the Doris Duke Charitable Foundation. Woodbury was supported in part by USDA-NIFA Project 2011-67003-30205 Data deposition: A global spatial dataset of reforestation opportunities has been deposited on Zenodo (https://zenodo.org/record/883444). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710465114/-/DCSupplemental.Peer reviewedPublisher PD

    Natural climate solutions for the United States

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    © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517

    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
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