SignificanceDespite the revolution in cancer therapy initiated by checkpoint inhibitors, durable clinical responses remain sporadic in many types of cancer, including ovarian cancer. Understanding which antigens are essentially presented by tumor cells and further able to be recognized by T cells provides a major step toward novel effective targeted immunotherapies. In this study, we comprehensively analyzed the immunopeptidomic landscape of ovarian carcinoma and compared it to variety of benign sources to identify antigens exclusively presented on tumor cells. With personalized therapies moving into the focus of clinical cancer therapy, we further present insights on how gene-expression analysis and immunohistochemistry can support antigen selection for individualized immunotherapy.

Abstract-Inflammatory processes involve both synthesis of inflammatory cytokines, such as interleukin-6 (IL-6), and the activation of their distinct signaling pathways, eg, the janus kinases (JAKs) and signal transducers and activators of transcription (STAT). Superoxide (O 2 Ϫ ) anions activate this signaling cascade, and the vasoconstrictor angiotensin II (Ang II) enhances the formation of O 2 Ϫ anions via the NAD(P)H oxidase system in rat aortic smooth muscle cells. Ang II activates the JAK/STAT cascade via its type 1 (AT 1 ) receptor and induces synthesis and release of IL-6. Therefore, we investigated the role of O 2 Ϫ anions generated by the NAD(P)H oxidase system on the Ang II activation of the JAK/STAT cascade and its impact on IL-6 synthesis. Ang II stimulation of rat aortic smooth muscle cells induced a rapid increase in O 2 Ϫ anions determined by laser fluoroscopy, which can be abolished by DPI, a flavoprotein inhibitor. Ang II-induced phosphorylation of JAK2, STAT1␣/␤, STAT3, and IL-6-synthesis can be abolished by DPI, as determined by immunoprecipitations and Northern blot analysis. Electroporation of neutralizing antisera targeted against p47 phox , a NAD(P)H oxidase subunit, abolished Ang II-induced JAK/STAT activation and IL-6 synthesis. Inhibition of JAK2 by its inhibitor AG490 (10 mol/L) blocked not only JAK2 activation but also IL-6 synthesis. These results suggest that stimulation of the JAK/STAT cascade by Ang II requires O 2 Ϫ anions generated by the NAD(P)H oxidase system, and O 2 Ϫ anion-dependent activation of the JAK/STAT cascade seems to be additionally involved in Ang II-induced IL-6 synthesis. Thus, Ang II-induced inflammatory effects seem to require O 2 Ϫ anions generated by the NAD(P)H oxidase system.

The potential of corpora for language learning and teaching has been widely acknowledged and their ready availability on the Web has facilitated access for a broad range of users, including language teachers and learners. However, the integration of corpora into general language learning and teaching practice has so far been disappointing. In this paper, I will argue that the shape of many existing corpora, designed with linguistic research goals in mind, clashes with pedagogic requirements for corpus design and use. Hence, a 'pedagogic mediation of corpora' is required (cf. Widdowson, 2003). I will also show that the realisation of this requirement touches on both the development of appropriate corpora and the ways in which they are exploited by learners and teachers. I will use a small English Interview Corpus (ELISA) to outline possible solutions for a pedagogic mediation. The major aspect of this is the combination of two approaches to the analysis and exploitation of a pedagogically relevant corpus: a corpus-based and a discourse-based approach.

Abstract. Rain recharges soil water storages and either percolates downward into aquifers and streams, or is returned to the atmosphere through evapotranspiration. Although it is commonly assumed that summer rainfall recharges plant-available water during the growing season, the seasonal origins of water used by plants have not been systematically explored. We characterize the seasonal origins of waters in soils and trees by comparing their mid-summer isotopic signatures (δ2H) to seasonal isotopic cycles in precipitation, using a new seasonal origin index. Across 182 Swiss forest sites, xylem water isotopic signatures show that summer rain was not the predominant water source for mid-summer transpiration in any of the three sampled tree species. Beech and oak mostly used winter precipitation, whereas spruce used water of more diverse seasonal origins. Even in the same plots, beech consistently used more winter precipitation than spruce, demonstrating consistent niche partitioning in the rhizosphere. All three species' xylem water isotopes indicate that trees used more winter precipitation in drier regions, potentially mitigating their vulnerability to summer droughts. The widespread occurrence of winter isotopic signatures in mid-summer xylem implies that growing-season rainfall may have minimally recharged the soil water storages that supply tree growth, even across diverse humid climates (690–2068-mm annual precipitation). Beyond these ecological and hydrological implications, our findings also imply that stable isotopes of δ18O and δ2H in plant tissues, which are often used in climate reconstructions, may not reflect water from growing-season climates. More broadly, these results conflict with common assumptions on tree water use and provide empirical support for developing more realistic concepts of how water flows through soils and is accessed by roots.

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This paper reports on an empirical case study conducted to investigate the overall conditions and challenges of integrating corpus materials and corpus-based learning activities into Englishlanguage classes at a secondary school in Germany. Starting from the observation that in spite of the large amount of research into corpus-based language learning, hands-on work with corpora has remained an exception in secondary schools, the paper starts by outlining a set of pedagogical requirements for corpus integration and the approach which has formed the basis for designing the case study. Then the findings of the study are reported and discussed. As a result of the methodological challenges identified in the study, the author argues for a move from 'data-driven learning' to needs-driven corpora, corpus activities and corpus methodologies.

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We investigated the effect of aldosterone on Src kinase. In the kidney cell line, M-1 aldosterone leads to a >2-fold transient activation of Src kinase seen as early as 2 min after aldosterone administration. Maximal Src kinase activation was measured at an aldosterone concentration of 1 nM. In parallel to activation, autophosphorylation at Tyr-416 of Src kinase increased. Src kinase activation was blocked by spironolactone. Aldosterone led to increased association of Src with HSP84. Furthermore, rapamycin blocked aldosterone-induced Src activation. We conclude that Src activation by aldosterone is mediated through the mineralocorticoid receptor and HSP84.