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    Human immune responses to SARS-Cov-2 and influenza A virus infection : from myeloid-derived suppressor cells and T cell functions to antibody responses

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    Acute respiratory viral infections are the most frequent reason for medical consultations in the world. They cause substantial illness and death every year, especially in young children, the immunocompromised and the elderly, with a large span of disease severity ranging from mild to fatal. This includes both seasonal and pandemic influenza viruses, as well as the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the ongoing corona virus disease 2019 (COVID-19) pandemic. Disease severity is likely influenced by immune responses directed against the virus, which are critical for clearance and protection but may also cause immunopathogenesis. Thus, understanding the dynamics and function of immune responses during respiratory viral infections is important to better understand and treat the disease.In this thesis, we studied longitudinal innate and adaptive immune responses in SARS-CoV-2 and influenza A virus (IAV) infected patients to investigate how they associate with and possibly predict disease severity. We also investigated the effects of a genetically engineered anti-viral lectin on the functionality of human immune cells during IAV infection in vitro.We found that innate monocytic myeloid-derived suppressor cells (M-MDSCs) were expanded in blood of both COVID-19 and influenza patients and strongly associated with disease severity. The MDSCs were functionally intact and potently suppressed T cell proliferation, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response (Paper I). Next, we observed that patients with moderate or severe COVID-19 disease generated higher levels of SARS-CoV-2-specific antibodies in both blood and airways compared to patients with mild symptoms (Paper II). Furthermore, we revealed the role of activated and virus-specific circulating T follicular helper (cTfh) cells in antibody production in response to SARS-CoV-2 infection.Importantly, we found that the generation of activated virus-specific cTfh cells was delayed during early infection in patients who already displayed or later developed severe disease. In turn, this was associated with delayed production of virus-neutralizing antibodies needed to combat infection at an early stage and likely contributed to progression to severe COVID-19 disease (Paper III). An aberrant cTfh cell response was also observed in IAV infected patients where older patients displayed delayed appearance of activated cTfh cells compared to younger patients during acute infection. This was associated with lower levels of virus-specific antibodies, which may contribute to poorer clinical outcome in older individuals (Paper IV).Finally, we found that the genetically engineered banana lectin (BanLec) H84T could inhibit IAV infection yet promote virus-specific CD8 T cell proliferation supported by dendritic cells, pointing to the potential benefit of H84T BanLec as an antiviral therapy (Paper V).In conclusion, the findings in this thesis provide perspectives on dysregulated immune responses and novel avenues for treatment to combat influenza and COVID-19 more efficiently.List of scientific papersI. Sara Falck-Jones, Sindhu Vangeti, Meng Yu, Ryan Falck-Jones, Alberto Cagigi, Isabella Badolati, Björn Österberg, Maximilian Julius Lautenbach, Eric Åhlberg, Ang Lin, Rico Lepzien, Inga Szurgot, Klara Lenart, Fredrika Hellgren, Holden Maecker, Jörgen Sälde, Jan Albert, Niclas Johansson, Max Bell, Karin Loré, Anna Färnert, Anna Smed-Sörensen. Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity. The Journal of Clinical Investigation. 2021, 131(6):e144734. https://doi.org/10.1172/JCI144734 II. Alberto Cagigi, Meng Yu, Björn Österberg, Julia Svensson, Sara Falck-Jones, Sindhu Vangeti, Eric Åhlberg, Lida Azizmohammadi, Anna Warnqvist, Ryan Falck-Jones, Pia C Gubisch, Mert Ödemis, Farangies Ghafoor, Mona Eisele, Klara Lenart, Max Bell, Niclas Johansson, Jan Albert, Jörgen Sälde, Deleah D Pettie, Michael P Murphy, Lauren Carter, Neil P King, Sebastian Ols, Johan Normark, Clas Ahlm, Mattias N Forsell, Anna Färnert, Karin Loré, Anna Smed-Sörensen. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination. The Journal of Clinical Investigation Insight. 2021, 6(22):e151463. https://doi.org/10.1172/jci.insight.151463 III. Meng Yu, Afandi Charles, Alberto Cagigi, Wanda Christ, Björn Österberg, Sara Falck-Jones, Lida Azizmohammadi, Eric Åhlberg, Ryan Falck-Jones, Julia Svensson, Mu Nie, Anna Warnqvist, Fredrika Hellgren, Klara Lenart, Rodrigo Arcoverde Cerveira, Sebastian Ols, Gustaf Lindgren, Ang Lin, Holden Maecker, Max Bell, Niclas Johansson, Jan Albert, Christopher Sundling, Paulo Czarnewski, Jonas Klingström, Anna Färnert, Karin Loré, Anna Smed-Sörensen. Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19. [Manuscript]IV. Meng Yu, Afandi Charles, Björn Österberg, Gustaf Lindgren, Ang Lin, Sara Falck-Jones, Lida Azizmohammadi, Eric Åhlberg, Christopher Sundling, Anna Färnert, Karin Loré, Anna Smed-Sörensen. Older patients display aberrant circulating T follicular helper cell activation and antibodies production in influenza A virus infection. [Manuscript]V. Meng Yu, Ang Lin, Shuijie Li, Evelyn Covés-Datson, Faezzah Baharom, Karl-Johan Malmberg, Susanne Schlisio, Karin Loré, David Markovitz, Anna Smed-Sörensen. A genetically engineered therapeutic lectin inhibits human influenza A virus infection yet promotes virus-specific CD8 T cell proliferation by dendritic cells. [Manuscript]</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    FIGURE 4 in Malaxis malipoensis (Malaxideae: Orchidaceae), a new species from Yunnan, China

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    FIGURE 4. Pollen morphology of Malaxis malipoensis. A. Pollinium. B. Exine sculpturing. C. Outermost thick wall. D. Interior of pollinium.Published as part of Meng, Yu-Fang, Hu, Ai-Qun, Yi, Qi-Fei & Xing, Fu-Wu, 2014, Malaxis malipoensis (Malaxideae: Orchidaceae), a new species from Yunnan, China, pp. 195-200 in Phytotaxa 167 (2) on page 198, DOI: 10.11646/phytotaxa.167.2.6, http://zenodo.org/record/513871

    FIGURE 2 in Malaxis malipoensis (Malaxideae: Orchidaceae), a new species from Yunnan, China

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    FIGURE 2. Habitat and habit of Malaxis malipoensis (holotype locality). Photographed by Y. F. Meng.Published as part of Meng, Yu-Fang, Hu, Ai-Qun, Yi, Qi-Fei & Xing, Fu-Wu, 2014, Malaxis malipoensis (Malaxideae: Orchidaceae), a new species from Yunnan, China, pp. 195-200 in Phytotaxa 167 (2) on page 197, DOI: 10.11646/phytotaxa.167.2.6, http://zenodo.org/record/513871

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    [[alternative]]The Imprint of My Family--A Discourse on the Oil Painting Creative Works of Tsai Meng-Yu

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    [[abstract]]  本論文研究旨在探討「吾家印記」的繪畫創作方式與成果。創作理念主要來自於家庭生活經驗與家庭情感的累積,將家庭中人、事、物所構成日常生活的精彩片段轉化為觸動內心創作的主力,藉由創作實踐,讓原本存在於內心深處對於家的印記可以清晰的呈現出來。筆者以行動研究法和理論分析法,透過實際創作行動的實施執行和理論的探究,讓研究順利實踐並從中得到藝術專業知能。根據所擬定之創作目的,加以檢視後得到結論如下四點:一、完成以家為主題的創作題材,經由本創作研究的過程,以藝術形式表現家庭的溫馨與美好。二、蒐集與家的主題相關之藝術哲學觀點、藝術創作學說、藝術流派的文獻作為理論基礎,釐清本研究之理論脈絡,有助於論文之撰寫。三、完成以自身家庭的印記為主題的系列作品,從中獲得純熟的油畫表現技法,樹立屬於個人生命體驗之油畫風格。四、從創作研究的各個階段性過程中,汲取豐富的藝術知識,增進自己的藝術涵養,增廣自己的創作視野。[[abstract]]  This essay aims to unfold a working process and the final outcome for ‘The Imprint of My Family’. This project is originated from the assemblage of one’s own sentiments, emotions and experiences in family life; and through transforming those treasurable moments into art works by integrating people, events, and objects, this project reveals an inner impression towards memory and affection. The author explores the discourses on methodology and adopts the fashion of action research, in which praxis and theories are outlined in equal measure, to achieve an improved competence both intellectually and technically. As examining the goals set previously for this project, there are four notable points worth carrying into conclusion. Firstly, while this project is on the theme of home, it requires practices and researches to built up the feeling of warmth and intimacy, and furthermore conveys them through the form of art. Secondly, in order to unravel this essay logically for its working progress, it is helpful to seek for ideas in the fields of methodology on creative practices, philosophy, art theories, and those archives in different art movements. Thirdly, through a project like this, exploring the imprint of one’s own family, the acquisition is not only about an improved skill nor better expression on oil painting but also about establishing a painting style embedded with one’s own personal experiences of life. Last but not least, a richer collaboration of intellect and of insight towards art is generated by reviewing each stage in this project. It broadens one’s horizons on creative production
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