285 research outputs found

    MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells

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    We have recently shown that the E3 ubiquitin ligase midline 1 (MID1) is upregulated in murine cytotoxic lymphocytes (CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out (MID1-/- ) mice have a 25-30% reduction in exocytosis of lytic granules and cytotoxicity compared to CTL from wild-type (WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1-/- CTL. Here, we showed that MID2, like MID1, is upregulated in activated murine T cells. Furthermore, MID1-/- CTL upregulated MID2 two-twenty-fold stronger than CTL from WT mice, suggesting that MID2 might compensate for MID1. In agreement, transfection of MID2 into MID1-/- CTL completely rescued exocytosis of lytic granules in MID1-/- CTL, and vice versa, knock-down of MID2 inhibited exocytosis of lytic granules in both WT and MID1-/- CTL, demonstrating that both MID1 and MID2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID1 and MID2 in CTL

    Midline 1 controls polarization and migration of murine cytotoxic T cells

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    Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims of the present study were to determine the localization of MID1 in migrating CTLs, and to investigate whether MID1 affects CTL polarization and migration. We found that MID1 mainly localizes to the uropod of migrating CTLs and that it has a substantial impact on CTL polarization and migration in vitro. Furthermore, analysis of contact hypersensitivity responses supported that MID1 controls effector functions of CTLs in hapten-challenged skin in vivo. These results provide significant new knowledge on the role of MID1 in CTL biology

    ERP software system comparison between Odoo and Microsoft Dynamics NAV

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    The purpose of the thesis was to compare the two ERP software systems Odoo and Microsoft Dynamics NAV. The thesis sought to find out if Odoo can replace the existing Microsoft Dynamics core functionalities. The commissioner is Lasse Seppänen, a principal lecturer at HAMK (Häme University of Applied Sciences) in Finland. The university currently uses Microsoft Dynamics NAV to teach students about business information systems. The thesis explores the Microsoft Dynamics NAV system’s current features and asks how Odoo meets these requirements. The objective is also to determine which ERP system serves the university best. First, the thesis explains central concepts related to ERP systems. In order to compare the two ERP systems evaluation criteria investigated through literary research. The thesis proceeds by discussing the current ERP requirements. Based on this data Odoo and Microsoft Dynamics were analyzed. The research compares the two ERP solutions. The outcome of the analysis shows that Odoo is an alternative in comparison to Microsoft Dynamics NAV. The author recommends that the university implement Odoo through the Odoo Education platform

    Fictionality and Literature: Core Concepts Revisited

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    Author / Henrik Zetterberg-Nielsen -- Narrator / Sylvie Patron -- Plot / Wendy Veronica Xin -- Character / H. Porter Abbott -- Consciousness / Maria Mäkelä -- Metaphor / Greta Olson -- Paratext / Louise Brix Jacobsen -- Intertextuality / Rikke Andersen Kraglund -- Metafiction and metalepsis / Richard Walsh -- The novel / Catherine Gallagher and Simona Zetterberg-Nielsen -- Poetry / Lasse R. Gammelgaard -- Literary nonfiction / James Phelan -- Ethics / Jakob Lothe -- Social justice / Susan S. Lanser.Item embargoed for five year

    The Rating Game: Sentiment Rating Reproducibility from Text

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    Sentiment analysis models often use rat-ings as labels, assuming that these rat-ings reflect the sentiment of the accom-panying text. We investigate (i) whether human readers can infer ratings from re-view text, (ii) how human performance compares to a regression model, and (iii) whether model performance is affected by the rating “source ” (i.e. original author vs. annotator). We collect IMDb movie reviews with author-provided ratings, and have them re-annotated by crowdsourced and trained annotators. Annotators re-produce the original ratings better than a model, but are still far off in more than 5 % of the cases. Models trained on annotator-labels outperform those trained on author-labels, questioning the useful-ness of author-rated reviews as training data for sentiment analysis.

    Optimal high-dimensional and nonparametric distributed testing under communication constraints

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    We derive minimax testing errors in a distributed framework where the data is split over multiple machines and their communication to a central machine is limited to bb bits. We investigate both the dd- and infinite-dimensional signal detection problem under Gaussian white noise. We also derive distributed testing algorithms reaching the theoretical lower bounds. Our results show that distributed testing is subject to fundamentally different phenomena that are not observed in distributed estimation. Among our findings, we show that testing protocols that have access to shared randomness can perform strictly better in some regimes than those that do not. We also observe that consistent nonparametric distributed testing is always possible, even with as little as 11-bit of communication and the corresponding test outperforms the best local test using only the information available at a single local machine. Furthermore, we also derive adaptive nonparametric distributed testing strategies and the corresponding theoretical lower bounds.Comment: 53 page

    Finn Søeborg - a forgotten welfare voice

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    This thesis examines popular Danish author Finn Søeborg’s relation to the public literary andhistorical debate surrounding the idea and consequences of the Danish welfare state during itsfoundation and heyday around 1950 to 1970. Through a thematic reading of all nine Søeborgnovelsthe thesis aims to clarify his specific contribution if any and present an educated guessas to why he has largely been passed over by previous research – has this been warranted?The broad themes chosen for the readings are materialism, conformism and bureaucracy, sochosen because they are believed to be concurrent and important within the debateindependently of the author himself. Any contribution is worth considering since currentresearch into Søeborg is scarce. The thematic readings are then cross-referenced with literaryhistoricalresearch by Lasse Horne Kjældgaard and Søren Schou among others, as well asprominent welfare state-commentary and fiction from that period. The studies find thatSøeborg did in fact write fully within the welfare-fiction framework and used the themesoutlined above and related welfare-tropes to weigh in.He writes fiction to further a moralistic anti-conformity and anti-state agenda where thosewho resist the onslaught of historicist conformity are elevated. Apart from these few themasses are an unfree, sorry lot and the future looks gloomy. Søeborg shares existentialistattitudes with Hans Jørgen Lembourn and anarchist attitudes with Johan Fjord Jensen –prominent welfare-commentators. He is different from them both however, in that he refusesall power-structures making literary alliances, recognition and categorization very difficult.The thesis concludes that Søeborg was a forerunner in terms of exploring in fiction some ofthe negative lifestyle effects resulting from the welfare state’s materialistic and bureaucraticexcesses, and should be held in higher regard historically for that reason; but his obstinatemoralism, mostly copying subject matter from the 1930s literature and not being able to fullyexpress his insights before they were displayed in a better way by others, is to his historicaland literary detriment

    Optimal Distributed Composite Testing in High-Dimensional Gaussian Models With 1-Bit Communication

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    In this paper we study the problem of signal detection in Gaussian noise in a distributed setting where the local machines in the star topology can communicate a single bit of information. We derive a lower bound on the Euclidian norm that the signal needs to have in order to be detectable. Moreover, we exhibit optimal distributed testing strategies that attain the lower bound. </p
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