Implementierung eines parallelen vorkonditionierten Schur-Komplement CG-Verfahrens in das Programmpaket FEAP

A parallel realisation of the Conjugate Gradient Method with Schur-Complement preconditioning, based on a domain decomposition approach, is described in detail. Special kinds of solvers for the resulting interiour and coupling systems are presented. A large range of numerical results is used to demonstrate the properties and behaviour of this solvers in practical situations

Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter

AbstractInterleukin-17A (IL-17A) is the signature cytokine produced by Th17 CD4+ T cells and has been tightly linked to autoimmune pathogenesis. In particular, the transcription factors NFAT and RORγt are known to activate Il17a transcription, although the detailed mechanism of action remains incompletely understood. Here, we show that the nuclear orphan receptor NR2F6 can attenuate the capacity of NFAT to bind to critical regions of the Il17a gene promoter. In addition, because NR2F6 binds to defined hormone response elements (HREs) within the Il17a locus, it interferes with the ability of RORγt to access the DNA. Consistently, NFAT and RORγt binding within the Il17a locus were enhanced in Nr2f6-deficient CD4+ Th17 cells but decreased in Nr2f6-overexpressing transgenic CD4+ Th17 cells. Taken together, our findings uncover an example of antagonistic regulation of Il17a transcription through the direct reciprocal actions of NR2F6 versus NFAT and RORγt

Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells

All memory T cells mount an accelerated response on antigen reencounter, but significant functional heterogeneity is present within the respective memory T-cell subsets as defined by CCR7 and CD45RA expression, thereby warranting further stratification. Here we show that several surface markers, including KLRB1, KLRG1, GPR56, and KLRF1, help define low, high, or exhausted cytokine producers within human peripheral and intrahepatic CD4+ memory T-cell populations. Highest simultaneous production of TNF and IFN-γ is observed in KLRB1+KLRG1+GPR56+ CD4 T cells. By contrast, KLRF1 expression is associated with T-cell exhaustion and reduced TNF/IFN-γ production. Lastly, TCRβ repertoire analysis and in vitro differentiation support a regulated, progressive expression for these markers during CD4+ memory T-cell differentiation. Our results thus help refine the classification of human memory T cells to provide insights on inflammatory disease progression and immunotherapy development

Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study

Abstract Background Immune monitoring by flow cytometry is a fast and highly informative way of studying the effects of novel therapeutics aimed at reducing transplant rejection or treating autoimmune diseases. The ONE Study consortium has recently initiated a series of clinical trials aimed at using different cell therapies to promote tolerance to renal allografts. To compare the effectiveness of different cell therapies, the consortium developed a robust immune monitoring strategy, including procedures for whole blood (WB) leukocyte subset profiling by flow cytometry. Methods Six leukocyte profiling panels computing 7- to 9-surface marker antigens for monitoring the major leukocyte subsets as well as characteristics of T cell, B cell, and dendritic cell (DC) subsets were designed. The precision and variability of these panels were estimated. The assay was standardized within eight international laboratories using Flow-Set Pro beads for mean fluorescence intensity target definition and the flow cytometer setup procedure. Standardization was demonstrated by performing inter-site comparisons. Results Optimized methods for sample collection, storage, preparation, and analysis were established, including protocols for gating target subsets. WB specimen age testing demonstrated that staining must be performed within 4 hours of sample collection to keep variability low, meaning less than or equal to 10% for the majority of defined leukocyte subsets. Inter-site comparisons between all participating centers testing shipped normal WB revealed good precision, with a variability of 0.05% to 30% between sites. Intra-assay analyses revealed a variability of 0.05% to 20% for the majority of subpopulations. This was dependent on the frequency of the particular subset, with smaller subsets showing higher variability. The intra-assay variability performance defined limits of quantitation (LoQ) for subsets, which will be the basis for assessing statistically significant differences achieved by the different cell therapies. Conclusions Local performance and central analysis of the ONE Study flow cytometry panel yields acceptable variability in a standardized assay at multiple international sites. These panels and procedures with WB allow unmanipulated analysis of changes in absolute cell numbers of leukocyte subsets in single- or multicenter clinical trials. Accordingly, we propose the ONE Study panel may be adopted as a standardized method for monitoring patients in clinical trials enrolling transplant patients, particularly trials of novel tolerance promoting therapies, to facilitate fair and meaningful comparisons between trials. </jats:sec

Hierarchically preconditioned parallel CG-solvers with and without coarse-matrix-solvers inside FEAP

After some remarks on the parallel implementation of the Finite Element package FEAP, our realisation of the parallel CG-algorithm is sketched. From a technical point of view, a hierarchical preconditioner with and without additional global crosspoint preconditioning is presented. The numerical properties of this preconditioners are discussed and compared to a Schur-complement-preconditioning, using a wide range of data from computations on technical and academic examples from elasticity

Implementierung eines parallelen vorkonditionierten Schur-Komplement CG-Verfahrens in das Programmpaket FEAP

A parallel realisation of the Conjugate Gradient Method with Schur-Complement preconditioning, based on a domain decomposition approach, is described in detail. Special kinds of solvers for the resulting interiour and coupling systems are presented. A large range of numerical results is used to demonstrate the properties and behaviour of this solvers in practical situations

Some remarks to large deformation elasto-plasticity (continuum formulation)

The continuum theory of large deformation elasto-plasticity is summarized as far as it is necessary for the numerical treatment with the Finite-Element-Method. Using the calculus of modern differential geometry and functional analysis, the fundamental equations are derived and the proof of most of them is shortly outlined. It was not our aim to give a contribution to the development of the theory, rather to show the theoretical background and the assumptions to be made in state of the art elasto-plasticity

RASSA-Stakeholderprozess

Das Projekt bereitet die Entwicklung einer Smart Grids Referenzarchitektur für Österreich unter Einbindung aller relevanten Akteure auf. Aus den technisch-wissenschaftlichen Grundlagen wird ein Prozess erarbeitet, der die Anforderungen vom Infrastrukturbetreiber, der Industrie bis zu Bedarfsträgern abholt und zu einer national akzeptierten und international ausgerichteten Referenzarchitektur abstimmt.The project works out the development of a smart grids reference architecture for Austria under involvement of all actors. Based on technological-scientific elements a process will be worked out, which meets the requirements of stakeholders like operators of infrastructure, industry and also public agencies to achieve a national accepted and international orientated reference architecture

Definition einer Referenzarchitektur für sichere Smart Grids in Österreich

Der RASSA-Stakeholderprozess hat die Entwicklung einer Smart-Grids-Referenzarchitektur für Österreich unter Einbindung relevanter Akteure aufbereitet. Aus technisch-wissenschaftlichen Grundlagen wurde ein Prozess erarbeitet, der Anforderungen vom Infrastrukturbetreiber, der Industrie bis zu Bedarfsträgern abholt und zu einer national akzeptierten und international ausgerichteten Referenzarchitektur abstimmt