3D calculation of the lambda eigenvalues and eigenmodes of the two-group neutron diffusion equation by coarse-mesh nodal methods

[EN] This paper shows the development and roots of the lambda eigenvector and eigenmodes calculation by coarse-mesh finite difference nodal methods. In addition, this paper shows an inter-comparison of the eigenvalues and power profiles obtained by different 3D nodal methods with two neutron energy groups. The methods compared are: the nodal collocation method (Verdú et al., 1998, 1993; Hebert, 1987) with different orders of the Legendre expansions, the modified coarse-mesh nodal method explained in this paper, and the method implemented in the PARCS code by Wysocki et al. (2014, 2015). In this paper we have developed a program NODAL-LAMBDA that uses a two-group modified coarse-mesh finite difference method with albedo boundary conditions. Some of the approximations performed originally by Borressen (1971) have been discarded and more exact expressions have been used. We compare for instance the eigenvalues and power profiles obtained with Borressen original approach of 1.5 group and with 2 groups. Also, some improvements in the albedo boundary conditions suggested by (Turney 1975; Chung et al., 1981) have been incorporated to the code as an option. The goal is to obtain the eigenvalues and the sub-criticalities (ki¿k0) of the harmonic modes that can be excited during an instability event in a fast way and with an acceptable precision.The authors of this paper are indebted to IBERDROLA generacion nuclear for provide support and funding to perform this work.Muñoz-Cobo, J.; Miró Herrero, R.; Wysocki, A.; Soler Domingo, A. (2019). 3D calculation of the lambda eigenvalues and eigenmodes of the two-group neutron diffusion equation by coarse-mesh nodal methods. Progress in Nuclear Energy. 110:393-409. https://doi.org/10.1016/j.pnucene.2018.10.008S39340911

Crispr/Cas Mediated Deletion of PTPN22 in Jurkat T Cells Enhances TCR Signaling and Production of IL-2

A single nucleotide polymorphism, C1858T, in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) results in one of the strongest genetic traits associated with autoimmune disease outside of the Major Histocompatibility Complex (MHC) genes. However, the consequences of this polymorphism, which introduces an arginine to tryptophan substitution at amino acid 620, for the function of PTPN22 protein is unclear and conflicting results have been obtained in human compared to mouse cells expressing this variant phosphatase. In mouse the variant appears to be a loss-of-function allele resembling a milder form of the null allele, while studies in human cells have reported it to be a gain-of-function mutation. To address whether the phosphatase has distinct functions in mouse vs. human T cells, we used CRISPR gene-editing to generate the first example of human PTPN22-KnockOut (KO) T cells. By comparing isogenic human T cells which express or lack PTPN22, we showed that PTPN22 KO T cells displayed enhanced expression of IL-2 and CD69 upon stimulation with cognate antigen. PTPN22 KO cells also showed increased Erk phosphorylation upon stimulation with weak antigen, but the difference was diminished in response to strong antigen, indicating that PTPN22 plays a more critical role in regulating weak-antigen responses. These data are in keeping with a role for PTPN22 in determining the threshold of stimulation required to activate T cells, a critical function of autoimmune pathogenesis. Our data indicate that PTPN22 has comparable functions in mouse and human T cells, and that the conflicting results in the literature regarding the impact of the point mutation are not due to differences in the activity of PTPN22 itself, but may be related to interactions with other proteins or splice variation

CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) initiate immune responses through their direct interaction with effector cells. However, the mechanism by which DC activity is regulated is not well defined. Previous studies have shown that CTLA4 on T cells regulates DCs function by "cross-talk". We investigated whether there is an intrinsic regulatory mechanism in DCs, with CTLA4 as a candidate regulator.</p> <p>Results</p> <p>We confirmed via RT-PCR and flow cytometry the natural expression of CTLA4 on mature DCs derived from human monocytes. Approximately 8% CD1a-positive cells express CTLA4 both on surface and intracellular, whereas 10% CD1a-negative cells express CTLA4 intracellularly, but little expression was observed on the cell surface. The cross-linking of CTLA4 inhibits DCs maturation and antigen presentation in vitro, but does not inhibit endocytosis.</p> <p>Conclusions</p> <p>CTLA4 is expressed by DCs and plays an inhibitory role. CTLA4-expressing DCs may represent a group of regulatory DCs. Because of its wide distribution on different cell types, CTLA4 may play a general role in regulating immune responses.</p

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

The Economic Character of Education : The Swedish Primary Education System and the Freedom of Establishment

The education systems of the EU Member States have, following the principles of thecase Humbel, long been considered non-economic in character, and thus excepted frominternal market law. But since Humbel, the CJEU has increasingly applied the freemovement provisions, including the freedom of establishment, on public welfare. Thisalso on educational activities, when these have been economic in character, which posesa challenge the Humbel principles. Moreover, in Sweden, one of the most debated issuesis the economic character of the education system, especially the existence of private forprofit education providers. A reform of the education system aimed at the private schools,which is to be expected, would then have to comply with the freedom of establishment,if the private schools perform economic activities. In this light, this thesis studies the position of education under the freedom of establishment, to examine generally when aneducational activity is considered economic in character, and specifically if the Swedish education system entails economic activities.The thesis finds that the Humbel principles still stand but have seen their scope ofapplication reduced through the case-law of the CJEU. Tracing the development ofeducational activities in the free movement case-law from the 1980s to present-day, thethesis proposes a reformulation of the Humbel principles as two cumulative criteria basedon funding and purpose: educational activities which are funded from the public budgetand carry out the State’s task in the educational field, are not economic in character, andthus excepted from the freedom of establishment. These criteria are then applied to privateprimary schools of the Swedish education system. The result from this is that the privateprimary schools perform economic activities under the freedom of establishment. Thethesis accordingly concludes that the freedom of establishment is applicable to theSwedish education system, forcing a possible education reform to comply with saidfreedom. It is remarked that the freedom of establishment will not necessarily hinder aneducation reform, but that reform proposals will have to be tailored in a way which iscompatible with the requirements of the freedom of establishment. Finally, the thesisacknowledges that also other educational activities than those at the centre of this studyrisk falling under internal market law