320 research outputs found
External calibration with Drosophila whole-cell spike-ins delivers absolute mRNA fold changes from human RNA-Seq and qPCR data
No full textGene expression measurements are typically performed on a fixed-weight aliquot of RNA, which assumes that the total number of transcripts per cell stays nearly constant across all conditions. In cases where this assumption does not hold (e.g., when comparing cell types with different cell sizes) the expression data provide a distorted view of cellular events. Assuming constant numbers of total transcripts, increases in expression of some RNAs must be compensated for by decreases in expression of others. Therefore, we propose calibrating gene expression data to an external reference point, the number of cells in the sample, using whole-cell spike-ins. In a systematic dilution experiment, we mixed varying numbers of human cells with fixed numbers of Drosophila melanogaster cells and scaled the expression levels of the human genes relative to those of the Drosophila genes. This approach restored the original gene expression ratios generated by the dilutions. We then used Drosophila whole-cell spike-ins to uncover non-symmetric gene expression changes, in this case much larger numbers of induced than repressed genes, under perturbations of the human cell line P493-6. Drosophila whole-cell spike-ins are an experimentally and computationally easy and low-priced method to derive mRNA fold changes of absolute abundances from RNA sequencing (RNA-Seq) and quantitative real-time PCR (qPCR) data
Modeling MYC-dependent regulation of gene expression and cell metabolism in B-cell lymphomas
No full textThe oncogene MYC plays an important role in B cell lymphoma pathogenesis. Despite more than 30 years of MYC research there are still open questions concerning its function and how to target MYC in lymphomagenesis. Thus, this work aims to examine the causal relationships between MYC and the transcriptome and metabolome in a B cell lymphoma cell line by computational methods. The data set covers RNA-seq and mass spectrometry measurements of the same cell line. The underlying data is purely observational, no intervention is needed since causal inference techniques enable virtual experiments in theory. The first part of this thesis addresses three issues: First, the analysis of the RNA-seq data from cells with overexpressed MYC is challenging since MYC is a transcriptional amplifier. There is no de novo activation of genes by the elevated MYC, but an amplification of all presently expressed genes. This behavior is accompanied with an increase in cell size and an increase of RNA amount. Thus, the comparison of lymphoma cells with a high MYC expression with normal B cells by RNA-seq standard pipelines is difficult, since current normalization methods require a constant RNA amount across samples. I present a method that uses Drosophila melanogaster cells as a spike-in to calibrate the data to the number of cells in the sample (Taruttis et al., 2017). I demonstrate that, in case of transcriptional amplification in the B cell lymphoma cell line the use of an external spike-in is mandatory to observe the global gene expression changes. Furthermore, the Drosophila melanogaster spike-in normalization outperforms other calibration methods, including the use of the commercially available ERCC spike-ins. Second, Maathuis et al. (2010) presented the first high throughput analysis of virtual intervention experiments. Their ground-breaking IDA method (Maathuis et al., 2009) will have a lasting effect on the field of systems biology. Further developments of the IDA method recommended a subsampling strategy for the estimation of causal effects from observational data (Stekhoven et al., 2012). I extend IDA and its extension CStaR by analyzing the distribution of causal effects and call the method Accumulation IDA (aIDA) (Taruttis et al., 2015). aIDA improves the prediction of causal effects in comparison to Maathuis et al. (2009) and (Stekhoven et al., 2012). Third, causal structure learning by the PC algorithm (Spirtes and Glymour, 1991; Kalisch and Bühlmann, 2007), the first step of both IDA and aIDA, assumes that the underlying structure is sparse. However, the application of the spike-in methods to B cell lymphoma data sets with MYC overexpression results in highly correlated data. Thus, the underlying causal structure is highly likely not sparse. I assume that this is a consequence of the global role of Myc in gene expression (Lin et al., 2012; Nie et al., 2012). Thus, we observe no technical artifact but a real biological process. I show that using the MMHC algorithm instead of the PC algorithm together with my accumulation method outperforms aIDA for highly correlated datasets. However, the MMHC-aIDA method breaks down, too, when the density of the underlying causal structure becomes too high. The second part of the thesis presents a causal inference analysis of a B cell lymphoma cell line. We decided for the P493-6 cell line due to its doxycycline-dependent promoter to switch MYC on or off, which allows for an examination of the causal relationships of MYC under the same epigenetic conditions. RNA-seq and mass spectrometry data are measurements of the transcriptome and the metabolome of the cell line and are the input of the causal inference analysis. I show that the selection of the method to estimate the causal effects highly depends on the data structure. While the highly correlated RNA seq dataset shows the best results with the MMHC-aIDA method, the mass spectrometry data performs well with aIDA. The analysis of RNA-seq data shows that MYC upregulates most of genes in the dataset. MYC further shows a positive causal effect on most of the metabolites. These findings are in line with the hypothesis that MYC is a transcriptional amplifier. Some of the causal effects of MYC on the transcriptome and metabolome are already known, others can be high priority candidates for future wet lab experiments
Synergy of interleukin 10 and toll-like receptor 9 signalling in B cell proliferation: Implications for lymphoma pathogenesis
No full textA network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, alpha-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression. Combination of CpG and IL10 led to a strong synergistic activation of cell proliferation (S-phase/doubling of total cell number) comparable to cells with high MYC expression. A synergistic up-regulation of CDK4, CDK6 and CCND3 expression by IL10 and CpG treatment was causal for this proliferative effect as shown by qRT-PCR analysis and inhibition of the CDK4/6 complex by PD0332991. Furthermore, treatment of stimulated MYC deprived cells with MLN120b, ACHP, Pyridone 6 or Ruxolitinib showed that IL10/CpG induced proliferation and CDK4 expression were JAK/STAT3 and IKK/NF-jB dependent. This was further supported by STAT3 and p65/RELA knockdown experiments, showing strongest effects on cell proliferation and CDK4 expression after double knockdown. Additionally, chromatin immunoprecipitation revealed a dual binding of STAT3 and p65 to the proximal promotor of CDK4 after IL10/CpG treatment. Therefore, the observed synergism of IL10R and TLR9 signalling was able to induce proliferation in a comparable way as aberrant MYC and might play a role in B cell homeostasis or transformation
Triumphe des Heidentums: Bildende Kunst in Frank Wedekinds "Franziska"
No full textFrank Wedekinds ,Denken in Bildern‘ lässt sich im späten Stück Franziska (1911) besonders gut verfolgen. Zum einen manifestiert sich die Visualisierungstendenz in der tableauartigen Szenen-Choreographie, zum anderen in zahlreichen Bildzitaten, mit denen der Autor zum zeitgenössischen Kunstdiskurs Stellung bezieht. Die kunstgeschichtlichen Bezüge umfassen die breite Palette von der Renaissance, über die Präraffaeliten bis zur Kunst der 10er Jahre des 20. Jahrhunderts, womit ein reichhaltiges Bildarchiv mit u.a. Faust-, Helena-, Mignon-, Eva- und Maria-Figurationen eröffnet wird. Die visuellen Zitate fungieren als ein ironisches Korrektiv der christlichen Tradition, womit sich Wedekind als Sensualist in der Nachfolge der Antike profiliert.Frank Wedekind’s visual thinking can be studied particularly clearly in his late drama Franziska (1911). The tendency to visualize is on the one hand visible in the tableau-style choreography and on the other – in numerous references to art history, through which the author takes a position in contemporary art discourse. The references range from Renaissance through Pre-Raphaelite painting to contemporary art, opening up a wide archive of images, among them the figures of Faust, Helena, Mignon, Eve, Saint Mary and others. These “optical allusions” form an ironic corrective to the Christian tradition, and allow the author to inscribe his work among the ‘sensualists’ in the heritage of antiquity.Franka Wedekinda ,myślenie obrazami‘ szczególnie dobrze prześledzić można w jego późnym dramacie Franziska (1911). Tendencja wizualizacyjna przejawia się tu z jednej strony w zdjęciowej choreografii scenicznej, z drugiej w licznych odniesieniach do historii sztuki, poprzez które autor zabiera głos we współczesnym mu dyskursie. Cytaty obejmują szeroki okres od renesansu, poprzez prerafaelitów aż po sztukę współczesną, co otwiera bogate archiwum obrazów z figuracjami Fausta, Heleny, Mignon, Ewy, Maryi i innych. Cytaty optyczne pełnią funkcje ironicznej korekty tradycji chrześcijańskiej, dzięki czemu autor wpisuje się w sensualistyczne dziedzictwo antyku
Stigmatization, discrimination and illness
No full textSoftcover, 17x24, 119 S.: 24,00 €Softcover, 17x24“She was given her own plate, her own cup, everything of her own, even when she just touched a cloth then nobody wanted to touch it again.” (Halima, HIV-seropositive) The book sheds light on the profound influence of an HIV-seropositive diagnosis on the lives of women and their social environment in the United Republic of Tanzania. The author, a medical doctor and social anthropologist, tells the story of six Tanzanian HIV-seropositive women, focusing on their negotiation and perception of illness and disease. Furthermore, the high levels of discrimination and stigmatization in the context of HIV-seropositivity that they experience are presented in detail, weaving together the impacts of an HIV-seropositive diagnosis with results analyzed both from a Medical Anthropology and Public Health perspective. Despite a new era of antiretroviral treatment, available in Tanzania free of cost, that has given cause for hope in a change in how the disease is perceived, the book impressively underlines that being HIV-seropositive remains a great challenge and heavy burden for women in Tanzania
Rezension: "Erzählen im Imperativ. Zur strukturellen Agonalität von Rollenspielen und mittelhochdeutschen Epen" von Franziska Ascher
No full textDie zeitliche und mediale Kluft zwischen mittelhochdeutschen Epen auf der einen und Computerrollenspielen auf der anderen Seite lässt einen Vergleich beider Gegenstände auf den ersten Blick schwierig erscheinen. Dafür, dass ein zweiter Blick sich lohnen könnte, plädiert Franziska Ascher – derzeit Dozentin an der Universität Innsbruck und Mitherausgeberin der Zeitschrift für Computerspielforschung PAIDA – in ihrer neu erschienen Dissertationsschrift. In Erzählen im Imperativ beleuchtet die Autorin aus medien- und kulturwissenschaftlicher Perspektive strukturelle Ähnlichkeiten zwischen Computerrollenspielen und mittelalterlicher Heldenepik.At first glance, a comparison of Middle High German epics and computer role-playing games seems, to say the least, hardly feasible. In her newly published dissertation, Franziska Ascher – currently lecturer at the University of Innsbruck and co-editor of the magazine for computer game research PAIDA – argues that a second look might be worthwhile. In Erzählen im Imperativ, the author illuminates structural similarities between computer role-playing games and medieval heroic epics from a media and cultural studies perspective
Unter besonderer Berücksichtigung der Blankoeinwilligung und der Zulässigkeit weiterer Kontrollvarianten
No full textSoftcover, 17x24Die klinische Prüfung von Arzneimitteln am Menschen bedeutet eine Gratwanderung zwischen dem Schutz des Studienteilnehmers und der Wahrung seiner Würde auf der einen sowie dem Streben nach medizinischem Fortschritt auf der anderen Seite. Dies gilt ebenso für die Kontrolle der Studie. Denn zu Recht wird in Deutschland kein Medikament ohne die Testung in einer kontrollierten Studie zugelassen. Gleichzeitig bestehen hier bedenkliche Regelungslücken, hat doch der Gesetzgeber den Umgang mit der Kontrollgruppe in der Humanforschung bisher gesetzlich nicht reglementiert. Vor dem Hintergrund dieser ungeklärten Rechtslage werden die sich ergebenden Problemfelder in der aktuellen Forschungspraxis grundlegend wie kritisch analysiert und interessengerechte Lösungsvorschläge entwickelt. Denn nur die Schaffung rechtlicher Klarheit über den Umgang mit der Kontrollgruppe vermag in diesem Spannungsfeld aus Ethik, Medizin und Recht Sicherheit für Ärzte und Studienteilnehmer zu gewährleisten. Ebendiese Schaffung von rechtlicher Sicherheit und Angemessenheit muss in einem solchen Bereich, der als medizinrechtliche Thematik die Grundfesten von Persönlichkeits- und Selbstbestimmungsrecht berührt, als höchste Priorität gelten.Clinical trials of medicinal products on human subjects are a balancing act between the protection of the study participant and the preservation of his dignity on the one hand and the constant striving for medical progress on the other hand. This applies likewise to the control group as an essential part of every clinical testing of pharmaceuticals without which no drug will receive marketing authorisation in Germany by the competent authorities. Nevertheless, significant gaps in the German legislation concerning this matter still remain as the German legislator has yet to implement any specific rules with regard to the handling and management of the control group in clinical trials. In view of this unsettled legal situation, the author critically analyses the core of the problem areas in this field’s current research practice and creates solutions reflecting the interests of the study participant as well as the practical needs of medical research. Only legal clarity regarding the control group can provide for the safety that is crucial in this field of tension between ethics, medicine and the law
Psychosocial Interventions for Newly Arrived Adolescent Refugees: A Systematic Review
No full textThe article “Psychosocial Interventions for Newly Arrived Adolescent Refugees: A Systematic Review” written by Nora Hettich · Franziska Anna Seidel · Lydia Yao Stuhrmann was originally published Online First without Open Access. After publication in volume 5, issue 2, page 99–114 the author decided to opt for Open Choice and to make the article an Open Access publication.Gefördert im Rahmen des Projekts DEA
Rezension: "Besuch in der Hölle. Dantes Göttliche Komödie. Biographie eines Jahrtausendbuchs" von Franziska Meier
No full textFranziska Meiers vorliegende Studie stellt einen wichtigen Beitrag zur aktuellen wissenschaftlichen Erforschung von Dantes Divina Commedia dar. In ihrer Untersuchung erläutert sie nicht nur die grundlegenden Kontexte der Entstehungsgeschichte und die Biografie des schon zu Lebzeiten umstrittenen Verfassers. Vielmehr gelingt es Meier, auch linguistische Aspekte, Fragen der Übersetzung und der Rezeption außerhalb Europas schlüssig darzustellen. Die Autorin und Übersetzerin Lorena Pircher, selbst auch Romanistin, hat diese Studie für die Medienimpulse rezensiert.Franziska Meier\u27s study represents an important contribution to current scholarly research on Dante\u27s Divina Commedia. In her new book, she not only explains the fundamental contexts of the genesis of the Commedia and biography of the author, who was already controversial during his lifetime. Rather, Meier also succeeds in coherently presenting linguistic aspects, questions of translation and reception outside Europe. The author and translator Lorena Pircher, herself also a Romance scholar, reviewed this study for Medienimpulse
Identifying news coverage (Justice and Crime Coverage)
No full textContent analysis is often used to examine the extent to which the individual actors involved in the trial (especially the defendant) can be identified through the reporting, for example through full attribution of names, a detailed description of the person, his or her living circumstances and photos.
Field of application/theoretical foundation:
The variable “identifying new coverage” is of particular relevance in the context of debates on media ethics and legal philosophy. This variable is used to examine the extent to which personal rights provisions are respected in media coverage.
Example study:
Oehmer (work in progress)
Information on Oehmer (work in progress)
Author: Franziska Oehmer
Research interest: The research interest of the study focuses on three sets of questions concerning 1) the selection and representativeness of court reporting, 2) the information function of court reporting and 3) the presentation of court reporting.
Object of analysis: court coverage in Swiss newspapers (Tagesanzeiger, NZZ, Neue Luzerner Zeitung, Südostschweiz, Blick, Gratiszeitung, 20Minuten)
Time frame of analysis: January 2007 – December 2017
Info about variable
Variable name/definition: identifying news coverage [Identifizierende Berichterstattung über Opfer und Angeklagten]
Level of analysis: Actors in most covered court case in article
Values:
Keine identifizierende Berichterstattung. Indikator: alleinige Verwendung der Bezeichnungen Opfer, Angeklagter, ...
Mittlere identifizierende Berichterstattung: Aussage ist dazu geeignet, dass das unmittelbare Umfeld die Person identifizieren kann, Indikator: Nennung des Vornamens und des Anfangsbuchstabens.
Große identifizierende Berichterstattung: Aussage ist dazu geeignet, das Dritte die Person identifizieren können. Indikator: Nennung des vollen Namens, Nennung des Vornamens in Verbindung mit Nennung des Berufs, Wohnsitzes und Arbeitsplatzes, ...
Intercoder reliability: Holsti .73; Krippendorff’s Alpha: .57 (2 Coder)
Codebook: available (see attachment)
References
Oehmer, Franziska. Die dritte Gewalt in den Medien. Eine repräsentative quantitative Inhaltsanalyse der Gerichtsberichterstattung Schweizer Medien (work in progress). [Justice in the media. A representative quantitative content analysis of court reporting in the Swiss media]
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