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- Moreau, V., et al.
(författare)
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Pool CFD modelling : lessons from the SESAME project
- 2019
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Ingår i: Nuclear Engineering and Design. - : ELSEVIER SCIENCE SA. - 0029-5493 .- 1872-759X. ; 355
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Tidskriftsartikel (refereegranskat)abstract
- The current paper describes the Computational Fluid-Dynamics (CFD) modelling of Heavy Liquid Metal (HLM) flows in a pool configuration and in particular how this is approached within the Horizon 2020 SESAME project. SESAME's work package structure, based on a systematic approach of redundancy and diversification, is explained along with its motivation. The main achievements obtained and the main lessons learned during the project are illustrated. The paper focuses on the strong coupling between the experimental activities and CFD simulations performed within the SESAME project. Two different HLM fluids are investigated: pure lead and Lead-Bismuth Eutectic. The objective is to make CFD a valid instrument used during the design of safe and innovative Gen-IV nuclear plants. Some effort has also been devoted to Proper Orthogonal Decomposition with Galerkin projection modelling (POD-Galerkin), a reduced order model suited for Uncertainty Quantification that operates by post-processing CFD results. Assessment of Uncertainty highly improves the reliability of CFD simulations. Dedicated experimental campaigns on heavily instrumented facilities have been conceived with the specific objective to build a series of datasets suited for the calibration and validation of the CFD modelling. In pool configuration, the attention is focused on the balance between conductive and convective heat transfer phenomena, on transient test-cases representative of incidental scenarios and on the possible occurrence of solidification phenomena. Four test sections have been selected to generate the datasets: (i) the CIRCE facility from ENEA, (ii) the TALL-3D pool test section from KTH, (iii) the TALL-3D Solidification Test Section (STS) from KTH and (iv) the SESAME Stand facility from CVR. While CIRCE and TALL-3D were existing facilities, the STS and SESAME Stand facility have been conceived, built and operated within the project, heavily relying on the use of CFD support. Care has been taken to ensure that almost all tasks were performed by at least two partners. Specific examples are given on how this strategy has allowed to uncover flaws and overcome pitfalls. Furthermore, an overview of the performed work and the achieved results is presented, as well as remaining or new uncovered issues. Finally, the paper is concluded with a description of one of the main goals of the SESAME project: the construction of the Gen-IV ALFRED CFD model and an investigation of its general circulation.
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- Simonds, Erin F., et al.
(författare)
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Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
- 2021
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Glioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.Methods We used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.Results ICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.Conclusions Our data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.
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- Mendoza-Revilla, Javier, et al.
(författare)
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Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
- 2022
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 39:4
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Tidskriftsartikel (refereegranskat)abstract
- Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
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- Reynolds-Cuellar, Pedro, et al.
(författare)
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Para Cima y Pa' Abajo : Building Bridges Between HCI Research in Latin America and in the Global North
- 2023
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Ingår i: PROCEEDINGS OF THE 2023 CHI CONFERENCE ON HUMAN FACTORS IN COMPUTING SYSTEMS (CHI 2023). - : Association for Computing Machinery (ACM).
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Konferensbidrag (refereegranskat)abstract
- The Human-computer Interaction (HCI) community has the opportunity to foster the integration of research practices across the Global South and North to begin overcoming colonial relationships. In this paper, we focus on the case of Latin America (LATAM), where initiatives to increase the representation of HCI practitioners lack a consolidated understanding of the practices they employ, the factors that infuence them, and the challenges that practitioners face. To address this knowledge gap, we employ a mixed-methods approach, comprising a survey (66 respondents) and in-depth interviews (19 interviewees). Our analyses characterize a set of research perspectives on how HCI is practiced in/about LATAM; a set of driving forces and tensions with a heavy reliance on diasporic dynamics; and a set of professional demands and associated structural limitations. We also ofer a roadmap towards building connections across HCI communities, in an attempt to rebuild HCI as a pluriverse.
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