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Tras la presentación de los objetivos, se discute los principales retos encontrados en Proyecto Humboldt Digital: sesgos de la digitalización, selección de documentos, Covid-19, embargo estadounidense, software libre, alianzas poscustodiales; asimismo se presentan los avances principales: flujo de trabajo, digitalización, adaptación de herramientas, documentación de criterios, edición de fuentes históricas, construcción de sitios web, exposición y actividades de difusión.

Modifications of nucleic acids comply different functions and are involved in genome or-ganization, cell differentiation, silencing, structure stability and enzyme recognition. Modi-fication abundances can be regulated intrinsically, like the incorporation of cap modifica-tions on viral RNA to evade the host immune response, but also extrinsically as a cause of damage, which can result in mutations or translational defects. Either way, modifications are highly dynamic. It is of great importance to trace and quantify these changes in order to understand the underlying mechanisms, which may offer a more divers applica-bility of RNA therapeutics and even facilitate the establishment of personalized medicine. Mass Spectrometry is a common technique to examine nucleic acids. However, mass spectrometry per se offers solely a static insight into the versatile dynamics of nucleic acid modifications. In order to circumvent this obstacle, Nucleic Acid Isotope Labeling coupled Mass Spectrometry (NAIL-MS) was developed. This powerful technique allows for absolute quantification on the one hand and on the other hand for examination of modification dynamics originating from endogenous or exogenous actuators. In 2010, the stress-induced reprogramming of tRNA modification in S. cerevisiae was reported. However, the underlying mechanisms remained to be elucidated. Few years later, the dynamics of RNA modifications and mechanisms like dilution, degradation and (de-)modification could be identified by the application of NAIL-MS. The first part of my dissertation deals with the examination of the extent of damage-induced alterations on nucleic acids. Therefore, a novel biosynthetically produced stable isotope labeled internal standard (SILIS) was established, to avoid the interference of signals with isotopologues generated in the stable isotope labeled pulse-chase experiments. Furthermore, the L-methionine-[2H3]-methyl labeling in S. cerevisiae was optimized to achieve full efficient labeling and thus again avoiding signal interferences with isotopologues due to inefficient labeling. Additionally, the tandem size exclusion chromatography was developed, allowing the time efficient purification of 28S/25S, 18S rRNA and tRNA in a single step. The appli-cation of improved stable isotope labeling and the facilitated purification of RNA popula-tions allowed for the examination of the stress-induced alterations in the RNA modifica-tion profile of S. cerevisiae. Thereby, the knowledge on stress-induced reprogramming of tRNA modifications in yeast could be expanded. Original and new transcripts could be discerned and in addition endogenous methylation could be differentiated from damage induced methylation. It was shown, that stress-induced alterations occur on original tRNA transcripts, whereas new transcripts were not affected. Moreover, the fast decrease of damage-induced methylations on 25S, 18S rRNA and tRNA in S. cerevisiae was demon-strated. Additionally, the formation of base damage on 2’-O-methylated nucleosides in rRNA upon methyl methanesulfonate (MMS) exposure were detected and thereby novel damage products of MMS could be identified. Furthermore, the application of NAIL-MS was expanded to study the endogenous and damage-induced methylome on the genomic levels in S. cerevisiae and E. coli. In parallel to the aforementioned findings, the fast dis-appearance of damage-induced methylations in the genome and transcriptome of S. cerevisiae and E. coli was shown. Apart from that, m7dG and m7G could be identified as the main damage products in the genome and transcriptome of both organisms. In parallel to prokaryotes and eukaryotes, the modifications in viral RNA are highly dy-namic. RNA viruses have high mutation rates and their modification abundances can vary during infection. So, several mutants and variants of the RNA virus SARS-CoV-2 emerged since 2019. It is necessary to understand the characteristics of the viral genome and the differences in mutants and variants in order to identify novel drug targets and optimize the application of available therapeutics and vaccines. Our previous work on absolute quantification of nucleic acid modifications in various organisms showed the strength of our LC-MS based approach. In the course of this study it was aimed at inves-tigating the viral RNA modification profile in the different mutants and variants of SARS-CoV-2. The absolute quantification of RNA modifications and the comparison to pub-lished reports lead to the assumption that observed modification densities are highly de-pendent on the cultivation and infection conditions as well as the purification method and verification of sample integrity is crucial for valid analysis. As outlined above, less is known about the genome of SARS-CoV-2 in terms of internal modifications. While the cap modification of the 5’ end of the SARS-CoV-2 genome is confirmed from many sides and is ascribed to regulate the host innate immune response and the viral replication. Hence, a better understanding of the viral capping mechanism is required in order to limit its contagiousness. Besides the interest in biological capping processes, the investigations on cap modifications become more relevant nowadays be-cause of mRNA therapeutics. The cap modification on engineered mRNA is necessary to prevent immunogenicity, improve intercellular stability and translation efficiency. Thus, therapeutic mRNA is engineered to resemble mature and processed eukaryotic mRNA, including the 5’ cap and the 3’ poly A tail. Currently, there are only a few published LC-MS methods for detection of cap modifications. Nevertheless, these methods include labor intensive sample preparation, long analyses times and have moderate sensitivity. In the course of my dissertation, the development and optimization of a time efficient and highly sensitive LC-MS method for absolute quantification of cap modifications is pre-sented. It includes an extensive method development, optimizing chromatographic and mass spectrometric parameters under consideration of short analysis time, low detection and quantification limits. For absolute quantification of cap modifications, an in vitro tran-scribed cap-SILIS was generated. Furthermore, limits of detection and quantification as well as the dynamic range for size and amount of macromolecules to be analyzed were determined. The high sensitivity allows for the analysis of RNA from synthetic but also from biological sources. The time efficiency is aspirational for ecologic and economic rea-sons, thus making this method suitable for high throughput analyses and industry. The identification and quantification of RNA modifications is getting more important with the significance of RNA therapeutics. In this work, efficient LC-MS based tools to study the extent of nucleic acid modifications are described. Insight into the stress-dependent regulation of the genome and transcriptome of common model organisms is given and a powerful method to quantify cap modifications is presented. These techniques can be used to study nucleic acid dynamics in clinical studies but also for quality control of RNA therapeutics.

The European Capital of Culture is an initiative by the European Union to highlight the richness and diversity of cultures across Europe. Cities are designated for a period of one calendar year during which they organize a series of cultural events. In July 2016 Galway was awarded the Irish designation for European Capital of Culture for 2020. Over 1900 events across 154 projects had been planned throughout the year. The Wave Makers volunteer programme was created to help with the delivery of the event. However, the outbreak of COVID-19 and the subsequent restrictions imposed by the Irish government, required Galway 2020 to postpone events. The event was later ‘reimagined’ to run from September 2020-April 2021, with most of the events taking place either online or in person under strict social distancing rules. This case study demonstrates how the Wave Makers programme adapted in line with these COVID-19 restrictions.

The COVID-19 pandemic brought along an “infodemic” which has been amplified in the digital world. We intend to discuss the harmful content onTwitter during the COVID-19 pandemic and the approaches to solve theproblem taken by different sides. We first lay out how disinformation and misinformation have become problems negatively affecting society. We then present solutions and roles by three organisational clusters, namely the platform Twitter itself, governing bodies in the EU and Germany, and civil society such, as the news media and NGOs. Firstly, Twitter’s response can be found in their guidelines against harmful content during this pandemic. Secondly, we analyse Germany’s Network Enforement Act and the EU’s Digital Services Act (DSA). Thirdly, we present criticism from civil society such as “netzpolitik.org” and “HateAid”. In conclusion, the paper finds it important to have all three clusters working together to form an effective system against harmful content online, which is in fact advocated by the EU’s DSA.The COVID-19 pandemic brought along an “infodemic” which has been amplified in the digital world. We intend to discuss the harmful content on Twitter during the COVID-19 pandemic and the approaches to solve the problem taken by different sides. We first lay out how disinformation and misinformation have become problems negatively affecting society. We then present solutions and roles by three organisational clusters, namely the platform Twitter itself, governing bodies in the EU and Germany, and civil society such, as the news media and NGOs. Firstly, Twitter’s response can be found in their guidelines against harmful content during this pandemic. Secondly, we analyse Germany’s Network Enforement Act and the EU’s Digital Services Act (DSA). Thirdly, we present criticism from civil society such as “netzpolitik.org” and “HateAid”. In conclusion, the paper finds it important to have all three clusters working together to form an effective system against harmful content online, which is in fact advocated by the EU’s DSA.

Die Lehre an Hochschulen in Deutschland befindet sich gegenwärtig im Umbruch. Die Maßnahmen zur Eindämmung der COVID-19-Pandemie haben dazu geführt, dass die Lehre an Hochschulen in Deutschland seit dem Sommersemester 2020 häufig nicht in der gewohnten Form von Präsenzveranstaltungen stattfinden konnte. Die Hochschulen haben mittlerweile eine große Bandbreite lokaler Lösungen für die notwendig gewordene Umstellung auf digitale Lehre umgesetzt. Für die weitere Zukunft der universitären Lehre stellen sich Fragen, die sowohl die methodischdidaktische wie insbesondere auch die fachliche Ausgestaltung hybrider Lehrkonzepte berühren: Welche Chancen und Potenziale, aber auch Herausforderungen sind mit zunehmend hybrider Hochschullehre verbunden? Inwieweit können Präsenzveranstaltungen sinnvoll durch digitale Formate, weitere Lernorte und informelle Lernprozesse ergänzt werden? Welche Implikationen lassen sich aus den empirischen Daten für die hybride Hochschullehre in den Fächern und im Lehramt und deren jeweiligen Spezifika ableiten? Gegenstand dieses Hrsg.-Bandes sind Einblicke in digitale, aber auch hybride Lehre, die Anlässe zur Reflexion der Förderung spezifisch fachlicher und/oder lehramtsbezogener Kompetenzentwicklungen bieten.