Suchergebnisse

Gender in Plato's thought is examined in terms of his depiction of the nature of wisdom and philosophizing, the relation of philosophy to power and the 'politics' of the Republic. The guiding thread is Plato's personification of truth and philosophy as female. (JLN)

We present a spectroscopic survey of 230 white dwarf candidates within 40 pc of the Sun from the William Herschel Telescope and Gran Telescopio Canarias. All candidates were selected from Gaia Data Release 2 (DR2) and in almost all cases, had no prior spectroscopic classifications. We find a total of 191 confirmed white dwarfs and 39 main-sequence star contaminants. The majority of stellar remnants in the sample are relatively cool (Teff = 6200 K), showing either hydrogen Balmer lines or a featureless spectrum, corresponding to 89 DA and 76 DC white dwarfs, respectively. We also recover two DBA white dwarfs and 9–10 magnetic remnants. We find two carbon-bearing DQ stars and 14 new metal-rich white dwarfs ; The research leading to these results has received funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme no. 677706 (WD3D). This article is based on observations made in the Observatorios de Canarias del IAC with the WHT operated on the island of La Palma by the Isaac Newton Group of Telescopes in the Observatorio del Roque de los Muchachos. Based on observations made with the Gran Telescopio Canarias (GTC), installed at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrof´ısica de Canarias, in the island of La Palma. This work presents results from the European Space Agency (ESA) space mission Gaia. Gaia data are being processed by the Gaia Data Processing and Analysis Consortium (DPAC). Funding for the DPAC is provided by national institutions, in particular the institutions participating in the Gaia MultiLateral Agreement (MLA). BTG was supported by the UK STFC grants ST/P000495 and ST/T000406/1. ARM acknowledges support from the MINECO under the Ramon y Cajal ´ programme (RYC-2016-20254), the AYA2017-86274-P grant, and the AGAUR grant SGR-661/2017. MRS thanks for support from Fondecyt (grant 1181404). DdM acknowledges financial support from 0:funding-source 3:href="http://dx.doi.org/10.13039/501100 003981"ASI/0:funding-source-INAF I/037/12/0 and ASI-INAF no. 2017-14-H.0 and from INAF "INAF main streams", Presidential Decree 43/2018. RR has received funding from the postdoctoral fellowship programme Beatriu de Pinos, funded by the Secretary ´ of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Maria Skłodowska-Curie grant agreement no. 801370. ; Postprint (published version)

Objectives To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-Associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. Methods Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. Results Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4 + CXC-motif chemokine receptor 5 (CXCR5) + programmed cell death protein 1 (PD1) + ICOS + Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4 + CD45RO + ICOS + PD1 + cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5 + CD4 + PD1 + ICOS + Foxp3-Tfh-cells and a uniquely expanded population of CXCR5-CD4 + PD1 hi ICOS + Foxp3-Tph-cells displayed frequent IL-21/interferon-γdouble-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). Conclusions Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.