Paul J. Bryce

The WIMS/PANTHER Embedded Supercell Method (ESM) provides a significant improvement in prediction accuracy in radial power distributions for pressurised water reactors compared to the standard “two-step” approach, without the need for a significant increase in computational resource.A companion paper presents validation of the ESM as previously presented, using PANTHER pin-by-pin diffusion to correct interface errors arising from the standard two-step approach. However, in principle any reference method can be used to solve the embedded supercells and correct the basic solution – this is a significant advantage of the ESM.A paper presented at PHYSOR 2016 demonstrated that use of diffusion theory introduces significant error relative to transport theory only in the high energy range, due to the discontinuous fission source when modelling the interface between two types of pincell.This paper investigates further improvement of the PANTHER solution through use of simplified PN in the fast energy groups. This solution method can be implemented without the need for any significant change to the calculation route and further improves agreement with a transport reference for a small computational cost.The remaining error in the solution is examined by derivation of an effective diffusion coefficient from a heterogeneous transport reference. This suggests a simple characterisation of the discrepancy, which can be easily corrected.Results are presented in comparison to WIMS for supercells and the KAIST benchmark. For the KAIST small core benchmark assembly power errors relative to a WIMS fine group transport reference are shown to be less than 0.5 %. Results are also presented in comparison to Monte Carlo for the Watts Bar benchmark.

The WIMS/PANTHER Embedded Supercell Method (ESM) provides a significant improvement in prediction accuracy for radial power distributions for PWR reactors compared to the standard “two-step” approach, without the need for a significant increase in computational resource. Recent papers at PHYSOR conferences have outlined the details of the method and demonstrated its operation, and the accuracy improvements possible, by means of benchmarking calculations.This paper applies the method to a 4-loop PWR in the U.K, and three PWRs (3-loop and 2-loop) in Belgium. Comparisons are made against measured data from the start-of-cycle physics testing performed for each cycle, and power-shape measurements collected during the cycle using a conventional “two-step” nodal reactor solution, and with the ESM. All results will be presented with the JEF2.2 nuclear data library, for ease of comparison between the methods and previously reported results, although the effects of more modern evaluations will be commented upon.The benchmark calculations referred to above studied a challenging MOX/UO2 benchmark core akin to an SMR. The four reactors studied here include conventional UO2 only core designs and cycles with UO2/MOX mixed cores. A variety of boron-and gadolinium-based burnable absorbers are also present. The data is used to show that the method both operates successfully for real reactor problems, and delivers improvements in the prediction accuracy of measured parameters.

The pore-forming protein perforin-2 facilitates IL-33 release from dendritic cells.

IgE-primed mast cells in peripheral tissues, including the skin, lung, and intestine, are key initiators of allergen-triggered edema and inflammation. Particularly in severe forms of allergy, this inflammation becomes strongly neutrophil dominated, and yet how mast cells coordinate this type of response is unknown. We and others have reported that activated mast cells––a hematopoietic cell type––can produce IL-33, a cytokine known to participate in allergic responses but generally considered as being of epithelial origin and driving Type 2 immune responses (e.g., ILC2 and eosinophil activation). Using models of skin anaphylaxis, our data reveal that mast cell-derived IL-33 also initiates neutrophilic inflammation. We demonstrate a cellular crosstalk mechanism whereby activated mast cells crosstalk to IL-33 receptor–bearing basophils, driving these basophils to adopt a unique response signature rich in neutrophil-associated molecules. We further establish that basophil expression of CXCL1 is necessary for IgE-driven neutrophilic inflammation. Our findings thus unearth a new mechanism by which mast cells initiate local inflammation after antigen triggering and might explain the complex inflammatory phenotypes observed in severe allergic diseases. Moreover, our findings (i) establish a functional link from IL-33 to neutrophilic inflammation that extends IL-33–mediated biology well beyond that of Type 2 immunity, and (ii) demonstrate the functional importance of hematopoietic cell–derived IL-33 in allergic pathogenesis.

Mechanisms that regulate the tolerance to dietary proteins or the loss of this and subsequent development of disease are poorly understood. In food allergy, there is growing awareness of the urgency in understanding these events to aid in the development of next-generation therapies and interventions. This review focuses on the accumulating evidence related to food allergy that develops after transplantation. This intriguing immunological phenomenon has been described in several different types of transplant settings and to variety of different foods. We outline these studies and the evidence from them that support transplant-acquired food allergy being a process regulated by both the donor allergic status and the recipient genetics and treatments. A number of key risk factors seem prevalent throughout transplant-acquired food allergy and include type of transplant, age and general health of the recipient, modality of immunosuppression and potentially the genetics of both donor and recipient. Importantly, these studies provide a window into better general understanding of food allergy, and facilitate clearer understanding of the critical immunological and epidemiological factors needed to allow the adoptive transfer of a food-specific allergic disease from one individual to another.

Mast cells and basophils are developmentally related cells whose activation is a hallmark of allergy. Functionally, mast cells and basophils overlap in their ability to produce several mediators, including histamine and granule proteases, but studies have increasingly demonstrated nonredundant roles. To characterize the transcriptional heterogeneity of mast cells and basophils upon their activation, we performed large-scale comparative microarrays of murine bone marrow–derived mast cells and bone marrow–derived basophils (BMBs) at rest, upon an adaptive-type activation (IgE cross-linking), or upon an innate-type activation (IL-33 stimulation). Hierarchical clustering demonstrated that bone marrow–derived mast cells and BMBs shared specific activation-associated transcriptional signatures but differed in other signatures both between cell type and between activation mode. In bone marrow–derived mast cells, IgE cross-linking upregulated 785 genes, including Egr2, Ccl1, and Fxyd6, whereas IL-33 stimulation induced 823 genes, including Ccl1, Egr2, and Il1b. Focused bioinformatics pathway analysis demonstrated that IgE activation aligned with processes such as oxidative phosphorylation, angiogenesis, and the p53 pathway. The IL-33–activated transcriptome was enriched in genes commonly altered by NF-κB in response to TNF, by IL-6 via STAT3, and in response to IFN-γ. Furthermore, BMBs activated via IgE cross-linking selectively induced immune response genes Ccl1, Il3, and Il2 compared with IL-33–stimulated BMBs. Principal-component analysis revealed key cell- and activation-specific clustering. Overall, our data demonstrate that mast cells and basophils have cell- and activation-specific transcriptional responses and suggest that context-specific gene networks and pathways may shape how the immune system responds to allergens and innate cytokines.

Over the last decade, significant interest in the contribution of three “epithelial-derived cytokines,” thymic stromal lymphopoietin (TSLP), Interleukin 25 (IL-25), and Interleukin 33 (IL-33) has developed. These cytokines have been strongly linked to the early events that occur during allergen exposures and how they contribute to the subsequent type 2 immune response. Of these three cytokines, IL-33 has proven particularly interesting because of the strong associations found between both it and its receptor, ST2, in several genome wide association studies (GWAS) of allergic diseases. Further work has demonstrated clear mechanisms through which this cytokine might orchestrate allergic inflammation, including activation of several key effector cells that possess high ST2 levels, including mast cells, basophils, innate lymphoid cells, and eosinophils. Despite this, controversies surrounding IL-33 seem to suggest the biology of this cytokine might not be as simple as current dogmas suggest including: the relevant cellular sources of IL-33, with significant evidence for inducible expression in some hematopoietic cells; the mechanistic contributions of nuclear localization versus secretion; secretion and processing mechanisms; and the biological consequences of IL-33 exposure on different cell types. In this review, we will address the evidence for IL-33 and ST2 regulation over eosinophils and how this may contribute to allergic diseases. In particular, we focus on the accumulating evidence for a role of IL-33 in regulating hematopoiesis and how this relates to eosinophils as well as how this may provide new concepts for how the progression of allergy is regulated.