204 research outputs found

    Antiferromagnetism at T > 500 K in the Layered Hexagonal Ruthenate SrRu2O6

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    We report an experimental and computational study of magnetic and electronic properties of the layered Ru(V) oxide SrRu2O6 (hexagonal, P-3 1m), which shows antiferromagnetic order with a N\'eel temperature of 563(2) K, among the highest for 4d oxides. Magnetic order occurs both within edge-shared octahedral sheets and between layers and is accompanied by anisotropic thermal expansivity that implies strong magnetoelastic coupling of Ru(V) centers. Electrical transport measurements using focused ion beam induced deposited contacts on a micron-scale crystallite as a function of temperature show p-type semiconductivity. The calculated electronic structure using hybrid density functional theory successfully accounts for the experimentally observed magnetic and electronic structure and Monte Carlo simulations reveals how strong intralayer as well as weaker interlayer interactions are a defining feature of the high temperature magnetic order in the material.Comment: Physical Review B 2015 accepted for publicatio

    MAIT cells come to the rescue in cancer immunotherapy?

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    Recent progress in immunobiology has led to the observation that, among cells classically categorized as the typical representatives of the adaptive immune system, i.e., T cells, some possess the phenotype of innate cells. Invariant T cells are characterized by T cell receptors recognizing a limited range of non-peptide antigens, presented only in the context of particular molecules. Mucosal-associated invariant T cells (MAIT cells) are an example of such unconventional cells. In humans, they constitute between 1% and 8% of the peripheral blood T lymphocytes and are further enriched in mucosal tissues, mesenteric lymph nodes, and liver, where they can account for even 40% of all the T cells. MAIT cells recognize antigens in the context of major histocompatibility complex class I-related protein (MR1). Upon activation, they instantly release pro-inflammatory cytokines and mediate cytolytic function towards bacterially infected cells. As such, they have been a rapidly evolving research topic not only in the field of infectious diseases but also in the context of many chronic inflammatory diseases and, more recently, in immuno-oncology. Novel findings suggest that MAIT cells function could also be modulated by endogenous ligands and drugs, making them an attractive target for therapeutic approaches. In this review, we summarize the current understanding of MAIT cell biology, their role in health and disease and discuss their future potential in cancer immunotherapy. This is discussed through the prism of knowledge and experiences with invariant natural killer T cells (iNKT)—another prominent unconventional T cell subset that shares many features with MAIT cells

    Linear Inequality Concepts and Social Welfare

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    The paper presents an abstract definition of linear inequality concepts leading to linearly invariant inequality measures and characterizes the class of linear concepts completely. Two general methods of deriving ethical measures are proposed. They imply an Atkinson-Kolm-Sen index and a new dual index reflecting the inequality of living standard. Then all separable social welfare orderings which generate linearly invariant measures are characterized. The measures are presented and their general properties discussed. Dual measures prove to be additively decomposable. Linear welfare orderings defined on rank-ordered income vectors are examined. They are consistent with all linear inequality and yield an inequality ordering for every concept.inequality concept, ethical inequality measures, decomposability, social welfare

    Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells

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    Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3–500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human MR1, forms MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. These antigens also induce MAIT cell accumulation in mouse lungs after administration with a co-stimulant. These chemical and immunological findings provide new insights into antigen properties and MAIT cell activation

    Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection

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    Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial innate-like T cells that have been characterized in human blood, liver, lungs, and intestine. Here, we investigated, for the first time, the presence of MAIT cells in the stomach of children, adults, and the elderly undergoing routine endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori – Hp), a major gastric pathogen. We observed that MAIT cells are present in the lamina propria compartment of the stomach and display a similar memory phenotype to blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able to recognize H. pylori. We found that CD8(+) and CD4(−)CD8(−) (double negative) MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1 restrictive manner by producing cytokines (IFN-γ, TNF-α, IL-17A) and exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell frequency in Hp(+ve) individuals was significantly lower than in Hp(−ve) individuals. However, gastric MAIT cell frequency was not significantly different between Hp(+ve) and Hp(−ve) individuals, demonstrating a dichotomy between blood and gastric tissues. Further, we observed that the majority of gastric MAIT cells (>80%) expressed tissue-resident markers (CD69(+) CD103(+)), which were only marginally present on PBMC MAIT cells (<3%), suggesting that gastric MAIT cells are readily available to respond quickly to pathogens. These results contribute important new information to the understanding of MAIT cells function on peripheral and mucosal tissues and its possible implications in the host response to H. pylori
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