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    Overexpression of primary microRNA 221/222 in acute myeloid leukaemia

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    Diplomarbeit - Veterinärmedizinische Universität Wien - 2021Bei der akuten myeloischen Leukämie (AML) handelt es sich um eine hämatologische, maligne Erkrankung, welche, insbesondere bei älteren Menschen, mit einer schlechten Prognose korreliert. Die Pathogenese der AML umfasst sowohl konsekutive Mutationen als auch Veränderungen im Genexpressionsmuster, welche auch Gene, die in nicht kodierende RNAs transkribiert werden, etwa Micro RNAs (miRNAs), betreffen. Um ein besseres Verständnis der deregulierten miRNA Expressionsmuster bei der AML zu erlangen, wurden 52 Proben von AML Patienten sowie 13 Proben von gesunden Individuen mittels „locked nucleic acid“ (LNA) Technologie hinsichtlich ihrer miRNA Expression analysiert. Von 636 analysierten humanen miRNAs waren 64 statistisch signifikant in AML Patienten dereguliert. Für weitere Analysen wurde die geclusterte miRNA 221/222 herangezogen, welche in anderen malignen Erkrankungen bereits als Onkogen identifiziert worden war. Es bestätigte sich eine gesteigerte Expression der miRNA 221/222 in AML-Proben, und zugleich konnte eine noch höhere Expression der Vorläufer-miRNA „primary-MiRNA (pri-miR)“ ermittelt werden. Das Expressionsniveau der pri-miR 221/222 in AML Patientenproben konnte zuverlässig das Krankheitsstadium widerspiegeln (Zeitpunkte: Diagnose, Remission und Rezidiv). Diese Ergebnisse, ergänzt durch Daten, die nach Expression der pre-miR-221/222 in humanen AML-Zelllinien erhalten wurden, legen den Schluss nahe, dass humane AML Zellen eine Defizienz in der Prozessierung von gesteigerten priMir Transkriptmengen aufweisen. Darüber hinaus könnte die pri-miR 221/222 einen neuen Biomarker in der AML darstellen und möglicherweise in dieser Krankheit auch als Onkogen fungieren.Diploma thesis - University of Veterinary Medicine Vienna - 2021Acute Myeloid Leukaemia (AML) is a haematological malignancy with a poor prognosis, especially in the elderly. Its pathogenesis includes consecutive mutations as well as gene expression changes, which also affect genes transcribed into non-coding RNAs, like microRNAs (miRNAs). In order to gain a better understanding of leukaemia associated miRNA misexpression, 52 AML patient samples and 13 healthy control samples were analysed via locked nucleic acid (LNA) microarray technology, thereby comparing 636 human miRNAs. 64 miRNAs were found to be significantly deregulated in AML patients. The expression of the miR-221/222 cluster, known to act as an oncogene in other malignancies, was further analysed. The obtained results confirmed overexpression of miR 221/222 and additionally revealed an even stronger upregulation of primary miRNA (pri-miR) 221/222 in primary AML patient samples. Pri-miR 221/222 levels in AML patient samples, obtained at diagnosis, remission and relapse, reliably reflected the disease stage. These results, together with data obtained after overexpression of pre-miR-221/222 in human AML cell lines, indicate a deficiency of human AML cells in processing an elevated rate of miR 221/222 precursor transcripts. Moreover, pri-miR 221/222 is an interesting candidate for a new biomarker in AML and may additionally represent a putative oncogene in this disorder

    MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)

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    The MECOM locus in chromosome band 3q26.2 gives rise to two major mRNA and protein species, EVI1 and MDS1/EVI1, of which the former has been characterized far more extensively. EVI1 has been implicated in the maintenance and expansion of normal hematopoietic stem cells. In addition, it plays a role as an oncogene in myeloid leukemia and in certain solid tumors, its overexpression being associated with a dismal prognosis in several of these malignancies. EVI1 exerts its biological effects mainly by regulating gene transcription, and does so by acting as a sequence specific transcription factor, by modulating the activity of other sequence specific transcription factors, and by regulating promoter CpG island methylation

    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

    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

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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