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Ribosomes decode mRNA to synthesize proteins. Ribosomes, once considered static, executing machines, are now viewed as dynamic modulators of translation. Increasingly detailed analyses of structural ribosome heterogeneity led to a paradigm shift toward ribosome specialization for selective translation. As sessile organisms, plants cannot escape harmful environments and evolved strategies to withstand. Plant cytosolic ribosomes are in some respects more diverse than those of other metazoans. This diversity may contribute to plant stress acclimation. The goal of this thesis was to determine whether plants use ribosome heterogeneity to regulate protein synthesis through specialized translation. I focused on temperature acclimation, specifically on shifts to low temperatures. During cold acclimation, Arabidopsis ceases growth for seven days while establishing the responses required to resume growth. Earlier results indicate that ribosome biogenesis is essential for cold acclimation. REIL mutants (reil-dkos) lacking a 60S maturation factor do not acclimate successfully and do not resume growth. Using these genotypes, I ascribed cold-induced defects of ribosome biogenesis to the assembly of the polypeptide exit tunnel (PET) by performing spatial statistics of rProtein changes mapped onto the plant 80S structure. I discovered that growth cessation and PET remodeling also occurs in barley, suggesting a general cold response in plants. Cold triggered PET remodeling is consistent with the function of Rei-1, a REIL homolog of yeast, which performs PET quality control. Using seminal data of ribosome specialization, I show that yeast remodels the tRNA entry site of ribosomes upon change of carbon sources and demonstrate that spatially constrained remodeling of ribosomes in metazoans may modulate protein synthesis. I argue that regional remodeling may be a form of ribosome specialization and show that heterogeneous cytosolic polysomes accumulate after cold acclimation, leading to shifts in the translational output that differs between wild-type and reil-dkos. I found that heterogeneous complexes consist of newly synthesized and reused proteins. I propose that tailored ribosome complexes enable free 60S subunits to select specific 48S initiation complexes for translation. Cold acclimated ribosomes through ribosome remodeling synthesize a novel proteome consistent with known mechanisms of cold acclimation. The main hypothesis arising from my thesis is that heterogeneous/ specialized ribosomes alter translation preferences, adjust the proteome and thereby activate plant programs for successful cold acclimation.
The role of biogenic carbonate producers in the evolution of the geometries of carbonate systems has been the subject of numerous research projects. Attempts to classify modern and ancient carbonate systems by their biotic components have led to the discrimination of biogenic carbonate producers broadly into Photozoans, which are characterised by an affinity for warm tropical waters and high dependence on light penetration, and Heterozoans which are generally associated with both cool water environments and nutrient-rich settings with little to no light penetration. These broad categories of carbonate sediment producers have also been recognised to dominate in specific carbonate systems. Photozoans are commonly dominant in flat-topped platforms with steep margins, while Heterozoans generally dominate carbonate ramps. However, comparatively little is known on how these two main groups of carbonate producers interact in the same system and impact depositional geometries responding to changes in environmental conditions such as sea level fluctuation, antecedent slope, sediment transport processes, etc. This thesis presents numerical models to investigate the evolution of Miocene carbonate systems in the Mediterranean from two shallow marine domains: 1) a Miocene flat-topped platform dominated by Photozoans, with a significant component of Hetrozoans in the slope and 2) a Heterozoan distally steepened ramp, with seagrass-influenced (Photozoan) inner ramp. The overarching aim of the three articles comprising this cumulative thesis is to provide a numerical study of the role of Photozoans and Heterozoans in the evolution of carbonate system geometries and how these biotas respond to changes in environmental conditions. This aim was achieved using stratigraphic forward modelling, which provides an approach to quantitatively integrate multi-scale datasets to reconstruct sedimentary processes and products during the evolution of a sedimentary system.
In a Photozoan-dominated carbonate system, such as the Miocene Llucmajor platform in Western Mediterranean, stratigraphic forward modelling dovetailed with a robust set of sensitivity tests reveal how the geometry of the carbonate system is determined by the complex interaction of Heterozoan and Photozoan biotas in response to variable conditions of sea level fluctuation, substrate configuration, sediment transport processes and the dominance of Photozoan over Heterozoan production. This study provides an enhanced understanding of the different carbonate systems that are possible under different ecological and hydrodynamic conditions. The research also gives insight into the roles of different biotic associations in the evolution of carbonate geometries through time and space. The results further show that the main driver of platform progradation in a Llucmajor-type system is the lowstand production of Heterozoan sediments, which form the necessary substratum for Photozoan production.
In Heterozoan systems, sediment production is mainly characterised by high transport deposits, that are prone to redistribution by waves and gravity, thereby precluding the development of steep margins. However, in the Menorca ramp, the occurrence of sediment trapping by seagrass led to the evolution of distal slope steepening. We investigated, through numerical modelling, how such a seagrass-influenced ramp responds to the frequency and amplitude of sea level changes, variable carbonate production between the euphotic and oligophotic zone, and changes in the configuration of the paleoslope. The study reinforces some previous hypotheses and presents alternative scenarios to the established concepts of high-transport ramp evolution. The results of sensitivity experiments show that steep slopes are favoured in ramps that develop in high-frequency sea level fluctuation with amplitudes between 20 m and 40 m. We also show that ramp profiles are significantly impacted by the paleoslope inclination, such that an optimal antecedent slope of about 0.15 degrees is required for the Menorca distally steepened ramp to develop.
The third part presents an experimental case to argue for the existence of a Photozoan sediment threshold required for the development of steep margins in carbonate platforms. This was carried out by developing sensitivity tests on the forward models of the flat-topped (Llucmajor) platform and the distally steepened (Menorca) platform. The results show that models with Photozoan sediment proportion below a threshold of about 40% are incapable of forming steep slopes. The study also demonstrates that though it is possible to develop steep margins by seagrass sediment trapping, such slopes can only be stabilized by the appropriate sediment fabric and/or microbial binding. In the Photozoan-dominated system, the magnitude of slope steepness depends on the proportion of Photozoan sediments in the system. Therefore, this study presents a novel tool for characterizing carbonate systems based on their biogenic components.
The central gas in half of all galaxy clusters shows short cooling times. Assuming unimpeded cooling, this should lead to high star formation and mass cooling rates, which are not observed. Instead, it is believed that condensing gas is accreted by the central black hole that powers an active galactic nuclei jet, which heats the cluster. The detailed heating mechanism remains uncertain. A promising mechanism invokes cosmic ray protons that scatter on self-generated magnetic fluctuations, i.e. Alfvén waves. Continuous damping of Alfvén waves provides heat to the intracluster medium. Previous work has found steady state solutions for a large sample of clusters where cooling is balanced by Alfvénic wave heating. To verify modeling assumptions, we set out to study cosmic ray injection in three-dimensional magnetohydrodynamical simulations of jet feedback in an idealized cluster with the moving-mesh code arepo. We analyze the interaction of jet-inflated bubbles with the turbulent magnetized intracluster medium.
Furthermore, jet dynamics and heating are closely linked to the largely unconstrained jet composition. Interactions of electrons with photons of the cosmic microwave background result in observational signatures that depend on the bubble content. Those recent observations provided evidence for underdense bubbles with a relativistic filling while adopting simplifying modeling assumptions for the bubbles. By reproducing the observations with our simulations, we confirm the validity of their modeling assumptions and as such, confirm the important finding of low-(momentum) density jets.
In addition, the velocity and magnetic field structure of the intracluster medium have profound consequences for bubble evolution and heating processes. As velocity and magnetic fields are physically coupled, we demonstrate that numerical simulations can help link and thereby constrain their respective observables. Finally, we implement the currently preferred accretion model, cold accretion, into the moving-mesh code arepo and study feedback by light jets in a radiatively cooling magnetized cluster. While self-regulation is attained independently of accretion model, jet density and feedback efficiencies, we find that in order to reproduce observed cold gas morphology light jets are preferred.
Background: The characteristics of osteoporosis are decreased bone mass and destruction towards the microarchitecture of bone tissue, which raises the risk of fracture. Psychosocialstress and osteoporosis are linked by sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and other endocrine factors. Psychosocial stress causes a series of effects on the organism, and this long-term depletion at the cellular level is considered to be mitochondrial allostatic load, including mitochondrial dysfunction and oxidative stress. Extracellular vesicles (EVs) are involved in the mitochondrial allostatic load process and may as biomarkers in this setting. As critical participants during cell-to-cell communications, EVs serve as transport vehicles for nucleic acid and proteins, alter the phenotypic and functional characteristics of their target cells, and promote cell-to-cell contact. And hence, they play a significant role in the diagnosis and therapy of many diseases, such as osteoporosis.
Aim: This narrative review attempts to outline the features of EVs, investigate their involvement in both psychosocial stress and osteoporosis, and analyze if EVs can be potential mediators between both.
Methods: The online database from PubMed, Google Scholar, and Science Direct were searched for keywords related to the main topic of this study, and the availability of all the selected studies was verified. Afterward, the findings from the articles were summarized and synthesized.
Results: Psychosocial stress affects bone remodeling through increased neurotransmitters such as glucocorticoids and catecholamines, as well as increased glucose metabolism. Furthermore, psychosocial stress leads to mitochondrial allostatic load, including oxidative stress, which may affect bone remodeling. In vitro and in vivo data suggest EVs might involve in the link between psychosocial stress and bone remodeling through the transfer of bioactive substances and thus be a potential mediator of psychosocial stress leading to osteoporosis.
Conclusions: According to the included studies, psychosocial stress affects bone remodeling, leading to osteoporosis. By summarizing the specific properties of EVs and the function of EVs in both psychosocial stress and osteoporosis, respectively, it has been demonstrated that EVs are possible mediators of both, and have the prospects to be useful in innovative research areas.
Im Rahmen dieser Dissertation wurden die erstmaligen Totalsynthesen der Arylnaphthalen-Lignane Alashinol D, Vitexdoin C, Vitrofolal E, Noralashinol C1 und Ternifoliuslignan E vorgestellt. Der Schlüsselschritt der entwickelten Methode, basiert auf einer regioselektiven intramolekularen Photo-Dehydro-Diels-Alder (PDDA)-Reaktion, die mittels UV-Strahlung im Durchflussreaktor durchgeführt wurde. Bei der Synthese der PDDA-Vorläufer (Diarylsuberate) wurde eine Synthesestrategie nach dem Baukastenprinzip verfolgt. Diese ermöglicht die Darstellung asymmetrischer komplexer Systeme aus nur wenigen Grundbausteinen und die Totalsynthese einer Vielzahl an Lignanen. In systematischen Voruntersuchungen konnte zudem die klare Überlegenheit der intra- gegenüber der intermolekularen PDDA-Reaktion aufgezeigt werden. Dabei stellte sich eine Verknüpfung der beiden Arylpropiolester über einen Korksäurebügel, in para-Position, als besonders effizient heraus. Werden asymmetrisch substituierte Diarylsuberate, bei denen einer der endständigen Estersubstituenten durch eine Trimethylsilyl-Gruppe oder ein Wasserstoffatom ersetzt wurde, verwendet, durchlaufen diese Systeme eine regioselektive Cyclisierung und als Hauptprodukt werden Naphthalenophane mit einem Methylester in 3-Position erhalten. Mit Hilfe von umfangreichen Experimenten zur Funktionalisierung der 4-Position, konnte zudem gezeigt werden, dass die Substitution der nucleophilen Cycloallen-Intermediate, während der PDDA-Reaktion, generell durch die Zugabe von N-Halogen-Succinimiden möglich ist. In Anbetracht der geringen Ausbeuten haben diese intermolekularen Abfangreaktionen, jedoch keinen präparativen Nutzen für die Totalsynthesen von Lignanen. Mit dem Ziel die allgemeinen photochemischen Reaktionsbedingungen zu optimieren, wurde erstmalig die triplettsensibilisierte PDDA-Reaktion vorgestellt. Durch die Verwendung von Xanthon als Sensibilisator wurde der Einsatz von effizienteren UVA-Lichtquellen ermöglicht, wodurch die Gefahr einer Photozersetzung durch Überbestrahlung minimiert wurde. Im Vergleich zur direkten Anregung mit UVB-Strahlung, konnten die Ausbeuten mit indirekter Anregung durch einen Photokatalysator signifikant gesteigert werden. Die grundlegenden Erkenntnisse und die entwickelten Synthesestrategien dieser Arbeit, können dazu beitragen zukünftig die Erschließung neuer pharmakologisch interessanter Lignane voranzutreiben.
1 Bisher ist nur die semisynthetische Darstellung von Noralashinol C ausgehend von Hydroxymatairesinol literaturbekannt.
In recent decades, astronomy has seen a boom in large-scale stellar surveys of the Galaxy. The detailed information obtained about millions of individual stars in the Milky Way is bringing us a step closer to answering one of the most outstanding questions in astrophysics: how do galaxies form and evolve? The Milky Way is the only galaxy where we can dissect many stars into their high-dimensional chemical composition and complete phase space, which analogously as fossil records can unveil the past history of the genesis of the Galaxy. The processes that lead to large structure formation, such as the Milky Way, are critical for constraining cosmological models; we call this line of study Galactic archaeology or near-field cosmology.
At the core of this work, we present a collection of efforts to chemically and dynamically characterise the disks and bulge of our Galaxy. The results we present in this thesis have only been possible thanks to the advent of the Gaia astrometric satellite, which has revolutionised the field of Galactic archaeology by precisely measuring the positions, parallax distances and motions of more than a billion stars. Another, though not less important, breakthrough is the APOGEE survey, which has observed spectra in the near-infrared peering into the dusty regions of the Galaxy, allowing us to determine detailed chemical abundance patterns in hundreds of thousands of stars. To accurately depict the Milky Way structure, we use and develop the Bayesian isochrone fitting tool/code called StarHorse; this software can predict stellar distances, extinctions and ages by combining astrometry, photometry and spectroscopy based on stellar evolutionary models. The StarHorse code is pivotal to calculating distances where Gaia parallaxes alone cannot allow accurate estimates.
We show that by combining Gaia, APOGEE, photometric surveys and using StarHorse, we can produce a chemical cartography of the Milky way disks from their outermost to innermost parts. Such a map is unprecedented in the inner Galaxy. It reveals a continuity of the bimodal chemical pattern previously detected in the solar neighbourhood, indicating two populations with distinct formation histories. Furthermore, the data reveals a chemical gradient within the thin disk where the content of 𝛼-process elements and metals is higher towards the centre. Focusing on a sample in the inner MW we confirm the extension of the chemical duality to the innermost regions of the Galaxy. We find stars with bar shape orbits to show both high- and low-𝛼 abundances, suggesting the bar formed by secular evolution trapping stars that already existed. By analysing the chemical orbital space of the inner Galactic regions, we disentangle the multiple populations that inhabit this complex region. We reveal the presence of the thin disk, thick disk, bar, and a counter-rotating population, which resembles the outcome of a perturbed proto-Galactic disk. Our study also finds that the inner Galaxy holds a high quantity of super metal-rich stars up to three times solar suggesting it is a possible repository of old super-metal-rich stars found in the solar neighbourhood.
We also enter into the complicated task of deriving individual stellar ages. With StarHorse, we calculate the ages of main-sequence turn-off and sub-giant stars for several public spectroscopic surveys. We validate our results by investigating linear relations between chemical abundances and time since the 𝛼 and neutron capture elements are sensitive to age as a reflection of the different enrichment timescales of these elements. For further study of the disks in the solar neighbourhood, we use an unsupervised machine learning algorithm to delineate a multidimensional separation of chrono-chemical stellar groups revealing the chemical thick disk, the thin disk, and young 𝛼-rich stars. The thick disk is shown to have a small age dispersion indicating its fast formation contrary to the thin disk that spans a wide range of ages.
With groundbreaking data, this thesis encloses a detailed chemo-dynamical view of the disk and bulge of our Galaxy. Our findings on the Milky Way can be linked to the evolution of high redshift disk galaxies, helping to solve the conundrum of galaxy formation.
Cosmic rays (CRs) constitute an important component of the interstellar medium (ISM) of galaxies and are thought to play an essential role in governing their evolution. In particular, they are able to impact the dynamics of a galaxy by driving galactic outflows or heating the ISM and thereby affecting the efficiency of star-formation. Hence, in order to understand galaxy formation and evolution, we need to accurately model this non-thermal constituent of the ISM. But except in our local environment within the Milky Way, we do not have the ability to measure CRs directly in other galaxies. However, there are many ways to indirectly observe CRs via the radiation they emit due to their interaction with magnetic and interstellar radiation fields as well as with the ISM.
In this work, I develop a numerical framework to calculate the spectral distribution of CRs in simulations of isolated galaxies where a steady-state between injection and cooling is assumed. Furthermore, I calculate the non-thermal emission processes arising from the modelled CR proton and electron spectra ranging from radio wavelengths up to the very high-energy gamma-ray regime.
I apply this code to a number of high-resolution magneto-hydrodynamical (MHD) simulations of isolated galaxies, where CRs are included. This allows me to study their CR spectra and compare them to observations of the CR proton and electron spectra by the Voyager-1 satellite and the AMS-02 instrument in order to reveal the origin of the measured spectral features.
Furthermore, I provide detailed emission maps, luminosities and spectra of the non-thermal emission from our simulated galaxies that range from dwarfs to Milk-Way analogues to starburst galaxies at different evolutionary stages. I successfully reproduce the observed relations between the radio and gamma-ray luminosities with the far-infrared (FIR) emission of star-forming (SF) galaxies, respectively, where the latter is a good tracer of the star-formation rate. I find that highly SF galaxies are close to the limit where their CR population would lose all of their energy due to the emission of radiation, whereas CRs tend to escape low SF galaxies more quickly. On top of that, I investigate the properties of CR transport that are needed in order to match the observed gamma-ray spectra.
Furthermore, I uncover the underlying processes that enable the FIR-radio correlation (FRC) to be maintained even in starburst galaxies and find that thermal free-free-emission naturally explains the observed radio spectra in SF galaxies like M82 and NGC 253 thus solving the riddle of flat radio spectra that have been proposed to contradict the observed tight FRC.
Lastly, I scrutinise the steady-state modelling of the CR proton component by investigating for the first time the influence of spectrally resolved CR transport in MHD simulations on the hadronic gamma-ray emission of SF galaxies revealing new insights into the observational signatures of CR transport both spectrally and spatially.
Neue Wege ins Lehramt
(2023)
Bis zum Jahr 2035 fehlen nach neuesten Prognosen von Klemm (2022) in Deutschland ca. 127.000 Lehrkräfte. Diese große Lücke kann nicht mehr allein durch Lehrkräfte abge-deckt werden, die ein traditionelles Lehramtsstudium absolviert haben. Als Antwort auf den Lehrkräftemangel werden in Schulen in Deutschland daher vermehrt Personen ohne traditio-nelles Lehramtsstudium eingestellt, um die Unterrichtsversorgung zu gewährleisten (KMK, 2022). Nicht-traditionell ausgebildete Lehrkräfte durchlaufen vor ihrer Einstellung in den Schuldienst in der Regel ein alternatives Qualifizierungsprogramm. Diese Qualifizierungs-programme sind jedoch in ihrer zeitlichen und inhaltlichen Ausgestaltung sehr heterogen und setzen unterschiedliche Eingangsvoraussetzungen der Bewerber:innen voraus (Driesner & Arndt, 2020). Sie sind in der Regel jedoch deutlich kürzer als traditionelle Lehramtsstudien-gänge an Hochschulen und Universitäten, um einen schnellen Einstieg in den Schuldienst zu gewährleisten. Die kürzere Qualifizierung geht damit mit einer geringeren Anzahl an Lern- und Lehrgelegenheiten einher, wie sie in einem traditionellen Lehramtsstudium zu finden wäre. Infolgedessen kann davon ausgegangen werden, dass nicht-traditionell ausgebildete Lehrkräfte weniger gut auf die Anforderungen des Lehrberufs vorbereitet sind.
Diese Annahme wird auch oft in der Öffentlichkeit vertreten und die Kritik an alternati-ven Qualifizierungsprogrammen ist groß. So äußerte sich beispielsweise der Präsident des Deutschen Lehrerverbandes, Heinz-Peter Meidinger, im Jahr 2019 gegenüber der Zeitung „Die Welt“, dass die unzureichende Qualifizierung von Quereinsteiger:innen „ein Verbre-chen an den Kindern“ sei (Die Welt, 2019). Die Forschung im deutschsprachigen Raum, die in der Läge wäre, belastbare Befunde für die Unterstützung dieser Kritik liefern zu können, steht jedoch noch am Anfang. Erste Arbeiten weisen generell auf wenige Unterschiede zwi-schen traditionell und nicht-traditionell ausgebildeten Lehrkräften hin (Kleickmann & An-ders, 2011; Kunina-Habenicht et al., 2013; Oettinghaus, Lamprecht & Korneck, 2014). Ar-beiten, die Unterschiede finden, zeigen diese vor allem im Bereich des pädagogischen Wis-sens zuungunsten der nicht-traditionell ausgebildeten Lehrkräfte. Die Frage nach weiteren Unterschieden, beispielsweise in der Unterrichtsqualität oder im beruflichen Wohlbefinden, ist bislang jedoch für den deutschen Kontext nicht beantwortet worden.
Die vorliegende Arbeit hat zum Ziel, einen Teil dieser Forschungslücken zu schließen. Sie bearbeitet in diesem Zusammenhang im Rahmen von drei Teilstudien die Fragen nach Unterschieden zwischen traditionell und nicht-traditionell ausgebildeten Lehrkräften hin-sichtlich ihrer professionellen Kompetenz, Berufswahlmotivation, Wohlbefinden und Unter-richtsqualität. Die übergeordnete Fragestellung wird vor dem Hintergrund des theoretischen Modells zu den Determinanten und Konsequenzen der professionellen Kompetenz (Kunter, Kleickmann, Klusmann & Richter, 2011) bearbeitet. Dieses Modell wird auch für die theore-tische Aufarbeitung der bereits bestehenden nationalen und internationalen Forschungsarbei-ten zu Unterschieden zwischen traditionell und nicht-traditionell ausgebildeten Lehrkräften herangezogen.
Teilstudie I untersucht zunächst Unterschiede in der professionellen Kompetenz zwi-schen traditionell und nicht-traditionell ausgebildeten Lehrkräften. Nach dem Kompetenz-modell nach Baumert und Kunter (2006) werden die beiden Gruppen in den vier Aspekten professioneller Kompetenz – Professionswissen, Überzeugungen, motivationale Orientierun-gen und selbstregulative Fähigkeiten – verglichen. Im Fokus dieser Arbeit stehen traditionell ausgebildete Lehramtsanwärter:innen und die sogenannten Quereinsteiger:innen während des Vorbereitungsdiensts. Mittels multivariater Kovarianzanalysen wurde eine Sekundärdaten-analyse des Projekts COACTIV-R durchgeführt und Unterschiede analysiert.
Teilstudie II beleuchtet sowohl Determinanten als auch Konsequenzen professioneller Kompetenz. Auf Seiten der Determinanten werden Unterschiede in der Berufswahlmotivati-on zwischen Lehrkräften mit und ohne traditionellem Lehramtsstudium untersucht. Ferner erfolgt die Analyse von Unterschieden im beruflichen Wohlbefinden (emotionale Erschöp-fung, Enthusiasmus) und die Intention, im Beruf zu verbleiben, als Konsequenz professionel-ler Kompetenz. Es erfolgte eine Analyse der Daten aus der Pilotierungsstudie aus dem Jahr 2019 für den Bildungstrend des Instituts für Qualitätsentwicklung im Bildungswesen (IQB). Unterschiede zwischen traditionell und nicht-traditionell ausgebildeten Lehrkräften wurden erneut mittels multivariater Kovarianzanalysen berechnet.
Abschließend erfolgte in Teilstudie III die Untersuchung von Unterschieden in der Un-terrichtsqualität zwischen traditionell und nicht-traditionell ausgebildeten Lehrkräften als Konsequenz professioneller Kompetenz. Hierzu wurden Daten des IQB-Bildungstrends 2018 im Rahmen einer Sekundäranalyse mithilfe doppelt-latenter Mehrebenenanalysen genutzt. Es wurden die Unterschiede in den Bereichen Abwesenheit von Störungen, kognitive Akti-vierung und Schüler:innenunterstützung betrachtet.
Im finalen Kapitel der vorliegenden Arbeiten werden die zentralen Befunde der drei Teilstudien zusammengefasst und diskutiert. Die Ergebnisse weisen darauf hin, dass sich traditionell und nicht-traditionell ausgebildete Lehrkräfte nur in wenigen der untersuchten Aspekte signifikant voneinander unterscheiden. Nicht-traditionell ausgebildete Lehrkräfte verfügen über weniger pädagogisches Wissen, haben bessere selbstregulative Fähigkeiten und unterscheiden sich nicht in ihren Berufswahlmotiven, ihrem Wohlbefinden und in der Unterrichtsqualität von traditionell ausgebildeten Lehrkräften. Die Ergebnisse öffnen die Tür für die Diskussion der Relevanz des traditionellen Lehramtsstudiums, bieten eine Grundlage bzgl. der Implikationen für weiterführende Forschungsarbeiten und die Bildungspolitik. Die Arbeiten werden abschließend hinsichtlich ihrer Grenzen bewertet.
In Forschungsprogrammen werden zahlreiche Akteure mit unterschiedlichen Hintergründen und fachlichen Expertisen in Einzel- oder Verbundvorhaben vereint, die jedoch weitestgehend unabhängig voneinander durchgeführt werden. Vor dem Hintergrund, dass gesamtgesellschaftliche Herausforderungen wie die globale Erwärmung zunehmend disziplinübergreifende Lösungsansätze erfordern, sollten Vernetzungs- und Transferprozesse in Forschungsprogrammen stärker in den Fokus rücken. Mit der Implementierung einer Begleitforschung kann dieser Forderung Rechnung getragen werden. Begleitforschung unterscheidet sich in ihrer Herangehensweise und ihrer Zielvorstellung von den „üblichen“ Projekten und kann in unterschiedlichen theoretischen Reinformen auftreten. Verkürzt dargestellt agiert sie entweder (1) inhaltlich komplementär zu den jeweiligen Forschungsprojekten, (2) auf einer Metaebene mit Fokus auf die Prozesse im Forschungsprogramm oder (3) als integrierende, synthetisierende Instanz, für die die Vernetzung der Projekte im Forschungsprogramm sowie der Wissenstransfer von Bedeutung sind. Zwar sind diese Formen analytisch in theoretische Reinformen trennbar, in der Praxis ergibt sich in der Regel jedoch ein Mix aus allen dreien.
In diesem Zusammenhang schließt die vorliegende Dissertation als ergänzende Studie an bisherige Ansätze zum methodischen Handwerkszeug der Begleitforschung an und fokussiert auf folgende Fragestellungen: Auf welcher Basis kann die Vernetzung der Akteure in einem Forschungsprogramm durchgeführt werden, um diese effektiv zusammenzubringen? Welche weiteren methodischen Elemente sollten daran ansetzen, um einen Mehrwert zu generieren, der die Summe der Einzelergebnisse des Forschungsprogrammes übersteigt? Von welcher Art kann dann ein solcher Mehrwert sein und welche Rolle spielt dabei die Begleitforschung?
Das erste methodische Element bildet die Erhebung und Aufbereitung einer Ausgangsdatenbasis. Durch eine auf semantischer Analyse basierenden Verschlagwortung projektbezogener Texte lässt sich eine umfassende Datenbasis aus den Inhalten der Forschungsprojekte generieren. Die Schlagwörter werden dabei anhand eines kontrollierten Vokabulars in einem Schlagwortkatalog strukturiert. Parallel dazu werden sie wiederum den jeweiligen Projekten zugeordnet, wodurch diese thematische Merkmale erhalten. Um thematische Überschneidungen zwischen Forschungsprojekten sichtbar und interpretierbar zu machen, beinhaltet das zweite Element Ansätze zur Visualisierung. Dazu werden die Informationen in einen Netzwerkgraphen transferiert, der sowohl alle im Forschungsprogramm involvierten Projekte als auch die identifizierten Schlagwörter in Relation zueinander abbilden kann. So kann zum Beispiel sichtbar gemacht werden, welche Forschungsprojekte sich auf Basis ihrer Inhalte „näher“ sind als andere. Genau diese Information wird im dritten methodischen Element als Planungsgrundlage für unterschiedliche Veranstaltungsformate wie Arbeitstagungen oder Transferwerkstätten genutzt. Das vierte methodische Element umfasst die Synthesebildung. Diese gestaltet sich als Prozess über den gesamten Zeitraum der Zusammenarbeit zwischen Begleitforschung und den weiteren Forschungsprojekten hinweg, da in die Synthese unter anderem Zwischen-, Teil- und Endergebnisse der Projekte einfließen, genauso wie Inhalte aus den unterschiedlichen Veranstaltungen. Letztendlich ist dieses vierte Element auch das Mittel, um aus den integrierten und synthetisierten Informationen Handlungsempfehlungen für zukünftige Vorhaben abzuleiten.
Die Erarbeitung der methodischen Elemente erfolgte im laufenden Prozess des Begleitforschungsprojektes KlimAgrar, welches der vorliegenden Dissertation als Fallbeispiel dient und dessen Hintergründe in der Thematik Klimaschutz und Klimaanpassung in der Landwirtschaft im Text ausführlich erläutert werden.
Creative intensive processes
(2023)
Creativity – developing something new and useful – is a constant challenge in the working world. Work processes, services, or products must be sensibly adapted to changing times. To be able to analyze and, if necessary, adapt creativity in work processes, a precise understanding of these creative activities is necessary. Process modeling techniques are often used to capture business processes, represent them graphically and analyze them for adaptation possibilities. This has been very limited for creative work. An accurate understanding of creative work is subject to the challenge that, on the one hand, it is usually very complex and iterative. On the other hand, it is at least partially unpredictable as new things emerge. How can the complexity of creative business processes be adequately addressed and simultaneously manageable? This dissertation attempts to answer this question by first developing a precise process understanding of creative work. In an interdisciplinary approach, the literature on the process description of creativity-intensive work is analyzed from the perspective of psychology, organizational studies, and business informatics. In addition, a digital ethnographic study in the context of software development is used to analyze creative work. A model is developed based on which four elementary process components can be analyzed: Intention of the creative activity, Creation to develop the new, Evaluation to assess its meaningfulness, and Planning of the activities arising in the process – in short, the ICEP model. These four process elements are then translated into the Knockledge Modeling Description Language (KMDL), which was developed to capture and represent knowledge-intensive business processes. The modeling extension based on the ICEP model enables creative business processes to be identified and specified without the need for extensive modeling of all process details. The modeling extension proposed here was developed using ethnographic data and then applied to other organizational process contexts. The modeling method was applied to other business contexts and evaluated by external parties as part of two expert studies. The developed ICEP model provides an analytical framework for complex creative work processes. It can be comprehensively integrated into process models by transforming it into a modeling method, thus expanding the understanding of existing creative work in as-is process analyses.
Insight by de—sign
(2023)
The calculus of design is a diagrammatic approach towards the relationship between design and insight. The thesis I am evolving is that insights are not discovered, gained, explored, revealed, or mined, but are operatively de—signed. The de in design neglects the contingency of the space towards the sign. The — is the drawing of a distinction within the operation. Space collapses through the negativity of the sign; the command draws a distinction that neglects the space for the form's sake. The operation to de—sign is counterintuitively not the creation of signs, but their removal, the exclusion of possible sign propositions of space. De—sign is thus an act of exclusion; the possibilities of space are crossed into form.
Many complex systems that we encounter in the world can be formalized using networks. Consequently, they have been in the focus of computer science for decades, where algorithms are developed to understand and utilize these systems.
Surprisingly, our theoretical understanding of these algorithms and their behavior in practice often diverge significantly. In fact, they tend to perform much better on real-world networks than one would expect when considering the theoretical worst-case bounds. One way of capturing this discrepancy is the average-case analysis, where the idea is to acknowledge the differences between practical and worst-case instances by focusing on networks whose properties match those of real graphs. Recent observations indicate that good representations of real-world networks are obtained by assuming that a network has an underlying hyperbolic geometry.
In this thesis, we demonstrate that the connection between networks and hyperbolic space can be utilized as a powerful tool for average-case analysis. To this end, we first introduce strongly hyperbolic unit disk graphs and identify the famous hyperbolic random graph model as a special case of them. We then consider four problems where recent empirical results highlight a gap between theory and practice and use hyperbolic graph models to explain these phenomena theoretically. First, we develop a routing scheme, used to forward information in a network, and analyze its efficiency on strongly hyperbolic unit disk graphs. For the special case of hyperbolic random graphs, our algorithm beats existing performance lower bounds. Afterwards, we use the hyperbolic random graph model to theoretically explain empirical observations about the performance of the bidirectional breadth-first search. Finally, we develop algorithms for computing optimal and nearly optimal vertex covers (problems known to be NP-hard) and show that, on hyperbolic random graphs, they run in polynomial and quasi-linear time, respectively.
Our theoretical analyses reveal interesting properties of hyperbolic random graphs and our empirical studies present evidence that these properties, as well as our algorithmic improvements translate back into practice.
Laser cutting is a fast and precise fabrication process. This makes laser cutting a powerful process in custom industrial production. Since the patents on the original technology started to expire, a growing community of tech-enthusiasts embraced the technology and started sharing the models they fabricate online. Surprisingly, the shared models appear to largely be one-offs (e.g., they proudly showcase what a single person can make in one afternoon). For laser cutting to become a relevant mainstream phenomenon (as opposed to the current tech enthusiasts and industry users), it is crucial to enable users to reproduce models made by more experienced modelers, and to build on the work of others instead of creating one-offs.
We create a technological basis that allows users to build on the work of others—a progression that is currently held back by the use of exchange formats that disregard mechanical differences between machines and therefore overlook implications with respect to how well parts fit together mechanically (aka engineering fit).
For the field to progress, we need a machine-independent sharing infrastructure.
In this thesis, we outline three approaches that together get us closer to this:
(1) 2D cutting plans that are tolerant to machine variations. Our initial take is a minimally invasive approach: replacing machine-specific elements in cutting plans with more tolerant elements using mechanical hacks like springs and wedges. The resulting models fabricate on any consumer laser cutter and in a range of materials.
(2) sharing models in 3D. To allow building on the work of others, we build a 3D modeling environment for laser cutting (kyub). After users design a model, they export their 3D models to 2D cutting plans optimized for the machine and material at hand. We extend this volumetric environment with tools to edit individual plates, allowing users to leverage the efficiency of volumetric editing while having control over the most detailed elements in laser-cutting (plates)
(3) converting legacy 2D cutting plans to 3D models. To handle legacy models, we build software to interactively reconstruct 3D models from 2D cutting plans. This allows users to reuse the models in more productive ways. We revisit this by automating the assembly process for a large subset of models.
The above-mentioned software composes a larger system (kyub, 140,000 lines of code). This system integration enables the push towards actual use, which we demonstrate through a range of workshops where users build complex models such as fully functional guitars. By simplifying sharing and re-use and the resulting increase in model complexity, this line of work forms a small step to enable personal fabrication to scale past the maker phenomenon, towards a mainstream phenomenon—the same way that other fields, such as print (postscript) and ultimately computing itself (portable programming languages, etc.) reached mass adoption.
In this work, binding interactions between biomolecules were analyzed by a technique that is based on electrically controllable DNA nanolevers. The technique was applied to virus-receptor interactions for the first time. As receptors, primarily peptides on DNA nanostructures and antibodies were utilized. The DNA nanostructures were integrated into the measurement technique and enabled the presentation of the peptides in a controllable geometrical order. The number of peptides could be varied to be compatible to the binding sites of the viral surface proteins.
Influenza A virus served as a model system, on which the general measurability was demonstrated. Variations of the receptor peptide, the surface ligand density, the measurement temperature and the virus subtypes showed the sensitivity and applicability of the technology. Additionally, the immobilization of virus particles enabled the measurement of differences in oligovalent binding of DNA-peptide nanostructures to the viral proteins in their native environment.
When the coronavirus pandemic broke out in 2020, work on binding interactions of a peptide from the hACE2 receptor and the spike protein of the SARS-CoV-2 virus revealed that oligovalent binding can be quantified in the switchSENSE technology. It could also be shown that small changes in the amino acid sequence of the spike protein resulted in complete loss of binding. Interactions of the peptide and inactivated virus material as well as pseudo virus particles could be measured. Additionally, the switchSENSE technology was utilized to rank six antibodies for their binding affinity towards the nucleocapsid protein of SARS-CoV-2 for the development of a rapid antigen test device.
The technique was furthermore employed to show binding of a non-enveloped virus (adenovirus) and a virus-like particle (norovirus-like particle) to antibodies. Apart from binding interactions, the use of DNA origami levers with a length of around 50 nm enabled the switching of virus material. This proved that the technology is also able to size objects with a hydrodynamic diameter larger than 14 nm.
A theoretical work on diffusion and reaction-limited binding interactions revealed that the technique and the chosen parameters enable the determination of binding rate constants in the reaction-limited regime.
Overall, the applicability of the switchSENSE technique to virus-receptor binding interactions could be demonstrated on multiple examples. While there are challenges that remain, the setup enables the determination of affinities between viruses and receptors in their native environment. Especially the possibilities regarding the quantification of oligo- and multivalent binding interactions could be presented.
Selenium (Se) is an essential trace element that is ubiquitously present in the environment in small concentrations. Essential functions of Se in the human body are manifested through the wide range of proteins, containing selenocysteine as their active center. Such proteins are called selenoproteins which are found in multiple physiological processes like antioxidative defense and the regulation of thyroid hormone functions. Therefore, Se deficiency is known to cause a broad spectrum of physiological impairments, especially in endemic regions with low Se content. Nevertheless, being an essential trace element, Se could exhibit toxic effects, if its intake exceeds tolerable levels. Accordingly, this range between deficiency and overexposure represents optimal Se supply. However, this range was found to be narrower than for any other essential trace element. Together with significantly varying Se concentrations in soil and the presence of specific bioaccumulation factors, this represents a noticeable difficulty in the assessment of Se
epidemiological status. While Se is acting in the body through multiple selenoproteins, its intake occurs mainly in form of small organic or inorganic molecular mass species. Thus, Se exposure not only depends on daily intake but also on the respective chemical form, in which it is present.
The essential functions of selenium have been known for a long time and its primary forms in different food sources have been described. Nevertheless, analytical capabilities for a comprehensive investigation of Se species and their derivatives have been introduced only in the last decades. A new Se compound was identified in 2010 in the blood and tissues of bluefin tuna. It was called selenoneine (SeN) since it is an isologue of naturally occurring antioxidant ergothioneine (ET), where Se replaces sulfur. In the following years, SeN was identified in a number of edible fish species and attracted attention as a new dietary Se source and potentially strong antioxidant. Studies in populations whose diet largely relies on fish revealed that SeN
represents the main non-protein bound Se pool in their blood. First studies, conducted with enriched fish extracts, already demonstrated the high antioxidative potential of SeN and its possible function in the detoxification of methylmercury in fish. Cell culture studies demonstrated, that SeN can utilize the same transporter as ergothioneine, and SeN metabolite was found in human urine.
Until recently, studies on SeN properties were severely limited due to the lack of ways to obtain the pure compound. As a predisposition to this work was firstly a successful approach to SeN synthesis in the University of Graz, utilizing genetically modified yeasts. In the current study, by use of HepG2 liver carcinoma cells, it was demonstrated, that SeN does not cause toxic effectsup to 100 μM concentration in hepatocytes. Uptake experiments showed that SeN is not bioavailable to the used liver cells.
In the next part a blood-brain barrier (BBB) model, based on capillary endothelial cells from the porcine brain, was used to describe the possible transfer of SeN into the central nervous system (CNS). The assessment of toxicity markers in these endothelial cells and monitoring of barrier conditions during transfer experiments demonstrated the absence of toxic effects from SeN on the BBB endothelium up to 100 μM concentration. Transfer data for SeN showed slow but substantial transfer. A statistically significant increase was observed after 48 hours following SeN incubation from the blood-facing side of the barrier. However, an increase in Se content was clearly visible already after 6 hours of incubation with 1 μM of SeN. While the transfer rate of SeN after application of 0.1 μM dose was very close to that for 1 μM, incubation with 10 μM of SeN resulted in a significantly decreased transfer rate. Double-sided application of SeN caused no side-specific transfer of SeN, thus suggesting a passive diffusion mechanism of SeN across the BBB. This data is in accordance with animal studies, where ET accumulation was observed in the rat brain, even though rat BBB does not have the primary ET transporter – OCTN1. Investigation of capillary endothelial cell monolayers after incubation with SeN and reference selenium compounds showed no significant increase of intracellular selenium concentration. Speciesspecific Se measurements in medium samples from apical and basolateral compartments, as good as in cell lysates, showed no SeN metabolization. Therefore, it can be concluded that SeN may reach the brain without significant transformation.
As the third part of this work, the assessment of SeN antioxidant properties was performed in Caco-2 human colorectal adenocarcinoma cells. Previous studies demonstrated that the intestinal epithelium is able to actively transport SeN from the intestinal lumen to the blood side and accumulate SeN. Further investigation within current work showed a much higher antioxidant potential of SeN compared to ET. The radical scavenging activity after incubation with SeN was close to the one observed for selenite and selenomethionine. However, the SeN effect on the viability of intestinal cells under oxidative conditions was close to the one caused by ET. To answer the question if SeN is able to be used as a dietary Se source and induce the activity of selenoproteins, the activity of glutathione peroxidase (GPx) and the secretion of selenoprotein P (SelenoP) were measured in Caco-2 cells, additionally. As expected, reference selenium compounds selenite and selenomethionine caused efficient induction of GPx activity. In contrast to those SeN had no effect on GPx activity. To examine the possibility of SeN being embedded into the selenoproteome, SelenoP was measured in a culture medium. Even though Caco-2 cells effectively take up SeN in quantities much higher than selenite or selenomethionine, no secretion of SelenoP was observed after SeN incubation.
Summarizing, we can conclude that SeN can hardly serve as a Se source for selenoprotein synthesis. However, SeN exhibit strong antioxidative properties, which appear when sulfur in ET is exchanged by Se. Therefore, SeN is of particular interest for research not as part of Se metabolism, but important endemic dietary antioxidant.
Non-local boundary conditions for the spin Dirac operator on spacetimes with timelike boundary
(2023)
Non-local boundary conditions – for example the Atiyah–Patodi–Singer (APS) conditions – for Dirac operators on Riemannian manifolds are rather well-understood, while not much is known for such operators on Lorentzian manifolds. Recently, Bär and Strohmaier [15] and Drago, Große, and Murro [27] introduced APS-like conditions for the spin Dirac operator on Lorentzian manifolds with spacelike and timelike boundary, respectively. While Bär and Strohmaier [15] showed the Fredholmness of the Dirac operator with these boundary conditions, Drago, Große, and Murro [27] proved the well-posedness of the corresponding initial boundary value problem under certain geometric assumptions.
In this thesis, we will follow the footsteps of the latter authors and discuss whether the APS-like conditions for Dirac operators on Lorentzian manifolds with timelike boundary can be replaced by more general conditions such that the associated initial boundary value problems are still wellposed.
We consider boundary conditions that are local in time and non-local in the spatial directions. More precisely, we use the spacetime foliation arising from the Cauchy temporal function and split the Dirac operator along this foliation. This gives rise to a family of elliptic operators each acting on spinors of the spin bundle over the corresponding timeslice. The theory of elliptic operators then ensures that we can find families of non-local boundary conditions with respect to this family of operators. Proceeding, we use such a family of boundary conditions to define a Lorentzian boundary condition on the whole timelike boundary. By analyzing the properties of the Lorentzian boundary conditions, we then find sufficient conditions on the family of non-local boundary conditions that lead to the well-posedness of the corresponding Cauchy problems. The well-posedness itself will then be proven by using classical tools including energy estimates and approximation by solutions of the regularized problems.
Moreover, we use this theory to construct explicit boundary conditions for the Lorentzian Dirac operator. More precisely, we will discuss two examples of boundary conditions – the analogue of the Atiyah–Patodi–Singer and the chirality conditions, respectively, in our setting. For doing this, we will have a closer look at the theory of non-local boundary conditions for elliptic operators and analyze the requirements on the family of non-local boundary conditions for these specific examples.
In the last two decades, process mining has developed from a niche
discipline to a significant research area with considerable impact on academia and industry. Process mining enables organisations to identify the running business processes from historical execution data. The first requirement of any process mining technique is an event log, an artifact that represents concrete business process executions in the form of sequence of events. These logs can be extracted from the organization's information systems and are used by process experts to retrieve deep insights from the organization's running processes. Considering the events pertaining to such logs, the process models can be automatically discovered and enhanced or annotated with performance-related information. Besides behavioral information, event logs contain domain specific data, albeit implicitly. However, such data are usually overlooked and, thus, not utilized to their full potential.
Within the process mining area, we address in this thesis the research gap of discovering, from event logs, the contextual information that cannot be captured by applying existing process mining techniques. Within this research gap, we identify four key problems and tackle them by looking at an event log from different angles. First, we address the problem of deriving an event log in the absence of a proper database access and domain knowledge. The second problem is related to the under-utilization of the implicit domain knowledge present in an event log that can increase the understandability of the discovered process model. Next, there is a lack of a holistic representation of the historical data manipulation at the process model level of abstraction. Last but not least, each process model presumes to be independent of other process models when discovered from an event log, thus, ignoring possible data dependencies between processes within an organization.
For each of the problems mentioned above, this thesis proposes a dedicated method. The first method provides a solution to extract an event log only from the transactions performed on the database that are stored in the form of redo logs. The second method deals with discovering the underlying data model that is implicitly embedded in the event log, thus, complementing the discovered process model with important domain knowledge information. The third method captures, on the process model level, how the data affects the running process instances. Lastly, the fourth method is about the discovery of the relations between business processes (i.e., how they exchange data) from a set of event logs and explicitly representing such complex interdependencies in a business process architecture.
All the methods introduced in this thesis are implemented as a prototype and their feasibility is proven by being applied on real-life event logs.
Die vorgelegte Dissertation befasst sich mit der frühen Wortsegmentierung im monolingualen und bilingualen Spracherwerb. Die Wortsegmentierung stellt eine der wesentlichen Herausforderungen für Säuglinge im Spracherwerb dar, da gesprochene Sprache kontinuierlich ist und Wortgrenzen nicht zuverlässig durch akustische Pausen markiert werden. Zahlreiche Studien konnten für mehrere Sprachen zeigen, dass sich Segmentierungsfähigkeiten von monolingualen Säuglingen zwischen dem 6. und 12. Lebensmonat herausbilden (z. B. Englisch: Jusczyk, Houston & Newsome, 1999; Französisch: Nazzi, Mersad, Sundara, Iakimova & Polka, 2014; Deutsch: Höhle & Weissenborn, 2003; Bartels, Darcy & Höhle, 2009). Frühe Wortsegmentierungsfähigkeiten sind sprachspezifisch (Polka & Sundara, 2012). Crosslinguistische Studien zeigten, dass eine sprachübergreifende Segmentierung für einsprachig aufwachsende Säuglinge nur erfolgreich bewältigt wird, wenn die nicht-native Sprache rhythmische Eigenschaften mit ihrer Muttersprache teilt (Houston, Jusczyk, Kuijpers, Coolen & Cutler, 2000; Höhle, 2002; Polka & Sundara, 2012).
In vier Studien dieser Dissertation wurden mit behavioralen (Headturn Preference Paradigma) und elektrophysiologischen Untersuchungen (Elektroenzephalografie) monolingual Deutsch aufwachsende und bilingual Deutsch-Französisch aufwachsende Säuglinge im Alter von 9 Monaten untersucht. Dabei wurde der Frage nachgegangen, ob monolingual Deutsch aufwachsende Säuglinge im Alter von 9 Monaten in der Lage sind, ihre Muttersprache Deutsch und die rhythmisch unähnliche Sprache Französisch zu segmentieren. Mit anderen Worten: Können monolinguale Säuglinge im Alter von 9 Monaten ihre Segmentierungsprozeduren modifizieren bzw. von ihrer bevorzugten Segmentierung abweichen, um auch nicht-muttersprachlichen Input erfolgreich zu segmentieren?
Bezogen auf die bilingualen Sprachlerner wurde der Frage nachgegangen, ob zweisprachig aufwachsende Säuglinge vergleichbare Segmentierungsfähigkeiten wie monolingual aufwachsende Säuglinge aufweisen und ob sich zudem ein Einfluss der Sprachdominanz auf die Entwicklung der Wortsegmentierungsfähigkeiten in einer bilingualen Population zeigt.
Durch die gewählten Methoden konnten sowohl Verhaltenskorrelate als auch elektrophysiologische Korrelate zur Beantwortung der Fragestellungen herangezogen werden. Darüber hinaus ermöglichte das EEG durch ereigniskorrelierte Potenziale (EKPs) einen Einblick in Lern- und Verarbeitungsprozesse, die mit Verhaltensmethoden nicht erfassbar waren.
Die Ergebnisse zeigen, dass monolingual Deutsch aufwachsende Säuglinge im Alter von 9 Monaten sowohl ihre Muttersprache als auch die nicht-native Sprache Französisch erfolgreich segmentieren. Die Fähigkeit zur Segmentierung der nicht-nativen Sprache Französisch wird jedoch beeinflusst von der Muttersprache: monolinguale Säuglinge, die mit Französisch zuerst getestet wurden, segmentierten sowohl das Französische als auch das im Anschluss präsentierte deutsche Sprachmaterial. Monolinguale Säuglinge die zuerst mit Deutsch und anschließend mit Französisch getestet wurden, segmentierten die deutschen Stimuli, jedoch nicht das französische Sprachmaterial.
Bilingual Deutsch-Französisch aufwachsende Säuglinge segmentieren im Alter von 9 Monaten beide Muttersprachen erfolgreich. Die Ergebnisse deuten zudem auf einen Einfluss der Sprachdominanz auf die Wortsegmentierungsfähigkeiten von zweisprachig aufwachsenden Säuglingen. Die balancierten Bilingualen segmentieren beide Muttersprachen erfolgreich, die unbalancierten Bilingualen zeigen nur für die jeweils dominante Sprache eine erfolgreiche Segmentierung.
Zusammenfassend liefert diese Arbeit erstmals Evidenz für eine erfolgreiche sprachübergreifende Segmentierung in prosodisch differenten Sprachen unterschiedlicher Rhythmusklassen in einer monolingualen Population. Darüber hinaus liefern die Studien dieser Arbeit Evidenz dafür, dass bilingual aufwachsende Säuglinge bezogen auf die Wortsegmentierungsfähigkeiten eine vergleichbare Entwicklung wie einsprachig aufwachsende Sprachlerner zeigen. Dieses Ergebnis erweitert die Datenlage bisheriger Studien, die für verschiedene Entwicklungsschritte im Spracherwerb keine Verzögerung, sondern eine zu monolingual aufwachsenden Säuglingen vergleichbare Entwicklung innerhalb einer bilingualen Population nachweisen konnten (Sprachdiskrimination: Byers-Heinlein, Burns & Werker, 2010; Bosch & Sebastian-Galles, 1997; Phonemdiskrimination: Albareda-Castellot, Pons & Sebastián-Gallés, 2011; Wahrnehmung rhythmischer Eigenschaften: Bijeljac-Babic, Höhle & Nazzi, 2016).
Hantaviruses (HVs) are a group of zoonotic viruses that infect human beings primarily through aerosol transmission of rodent excreta and urine samplings. HVs are classified geographically into: Old World HVs (OWHVs) that are found in Europe and Asia, and New World HVs (NWHVs) that are observed in the Americas. These different strains can cause severe hantavirus diseases with pronounced renal syndrome or severe cardiopulmonary system distress. HVs can be extremely lethal, with NWHV infections reaching up to 40 % mortality rate. HVs are known to generate epidemic outbreaks in many parts of the world including Germany, which has seen periodic HV infections over the past decade. HV has a trisegmented genome. The small segment (S) encodes the nucleocapsid protein (NP), the middle segment (M) encodes the glycoproteins (GPs) Gn and Gc which forms up to tetramers and primarily monomers \& dimers upon independent expression respectively and large segment (L) encodes RNA dependent RNA polymerase (RdRp). Interactions between these viral proteins are crucial in providing mechanistic insights into HV virion development. Despite best efforts, there continues to be lack of quantification of these associations in living cells. This is required in developing the mechanistic models for HV viral assembly. This dissertation focuses on three key questions pertaining to the initial steps of virion formation that primarily involves the GPs and NP.
The research investigations in this work were completed using Fluorescence Correlation Spectroscopy (FCS) approaches. FCS is frequently used in assessing the biophysical features of bio-molecules including protein concentration and diffusion dynamics and circumvents the requirement of protein overexpression. FCS was primarily applied in this thesis to evaluate protein multimerization, at single cell resolution.
The first question addressed which GP spike formation model proposed by Hepojoki et al.(2010) appropriately describes the evidence in living cells. A novel in cellulo assay was developed to evaluate the amount of fluorescently labelled and unlabeled GPs upon co-expression. The results clearly showed that Gn and Gc initially formed a heterodimeric Gn:Gc subunit. This sub-unit then multimerizes with congruent Gn:Gc subunits to generate the final GP spike. Based on these interactions, models describing the formation of GP complex (with multiple GP spike subunits) were additionally developed.
HV GP assembly primarily takes place in the Golgi apparatus (GA) of infected cells. Interestingly, NWHV GPs are hypothesized to assemble at the plasma membrane (PM). This led to the second research question in this thesis, in which a systematic comparison between OWHV and NWHV GPs was conducted to validate this hypothesis. Surprisingly, GP localization at the PM was congruently observed with OWHV and NWHV GPs. Similar results were also discerned with OWHV and NWHV GP localization in the absence of cytoskeletal factors that regulate HV trafficking in cells.
The final question focused on quantifying the NP-GP interactions and understanding their influence of NP and GP multimerization. Gc mutlimers were detected in the presence of NP and complimented by the presence of localized regions of high NP-Gc interactions in the perinuclear region of living cells. Gc-CT domain was shown to influence NP-Gc associations. Gn, on the other hand, formed up to tetrameric complexes, independent from the presence of NP.
The results in this dissertation sheds light on the initial steps of HV virion formation by quantifying homo and heterotypic interactions involving NP and GPs, which otherwise are very difficult to perform. Finally, the in cellulo methodologies implemented in this work can be potentially extended to understand other key interactions involved in HV virus assembly.
Este trabajo pretende demostrar que en la obra narrativa del escritor Tomás Carrasquilla Naranjo (1858 - 1940) hay un Wahrheitsgehalt (Benjamin, 2012), la concreción temporal de una idea, que se materializa a través de lo que aquí he denominado imagen de la religiosidad popular. Esto quiere decir que la obra del antioqueño estaría construida a la manera de un gran mosaico, en el que pese a los variados y disparejos elementos que la componen, la unión de todos produce una imagen (Bild). En dicha imagen se representa la experiencia histórica de lo moderno en los sectores populares, a partir de la unión fugaz entre los rezagos de tradiciones vetustas y las formas de vida más novedosas. Lejos de las convenciones de su época, donde la pregunta por la experiencia de lo moderno redunda en los ámbitos metropolitanos y el papel del artista, Carrasquilla se pregunta por lo que ocurre en los extensos ámbitos rurales o liminares entre lo citadino y lo rural, y sus respectivos entrecruzamientos. Los sujetos que habitan estos ámbitos, al carecer de herramientas conceptuales que les permita definir esta nueva “experiencia viviente”, esa nueva Structures and Feeling como la denomina Raymond Williams (2019); apelan a lo único que conocen, los vetustos saberes transmitidos oralmente para explicar su ahora.
En este sentido, es posible afirmar que Carrasquilla, valiéndose de esta imagen de la religiosidad popular, intentó establecer un diálogo en el campo de lo literario, desde el que postuló una idea de lo moderno diferencial. En varias ocasiones, el antioqueño manifestó que la literatura debía incorporar las experiencias locales al diálogo de lo universal. Ejemplo de esto es el símil de la literatura con el sistema planetario, pues, según él, las relaciones de jerarquía se establecen cuando los países que producen modas literarias, los planetas (Europa), relegan a los otros a ser simples satélites, es decir, a imitar (Carrasquilla, 1991). Hoy en día, se aprecia en aquella crítica dirigida a sus paisanos, los modernistas antioqueños, una reivindicación de la alteridad. Por lo que aquí se postula, que si bien dichas vivencias, no son similares a las que se dan en los nacientes ámbitos metropolitanos, donde las mercancías representan a los nuevos sustitutos de la fe; en esos extensos ámbitos, en apariencia provincianos y alejados del contacto con otras culturas y saberes, la imagen de religiosidad popular viene a desempeñar el mismo papel que aquellas. En otras palabras, “indem an Dingen ihr Gebrauchswert abstirbt” (utilidad o adoración), la subjetividad del personaje las carga con “Intentionen von Wunsch und Angst” (Benjamin, 2013a.), convirtiéndolas en objetos de contemplación, bien sea portándolas o coleccionándolas. De manera similar Carrasquilla se habría valido del cúmulo de saberes (Wissen) residuales de su hipotético público lector, heredado de diversas áreas culturales -durante el proceso de la colonización-, sus respectivos y heterogéneos tiempos y lenguas particulares (Ette, 2019), para aunarlos a las experiencias profanas actuales. Así, la obra (cuento o novela) representaría artísticamente “formas de vida” popular, a través de las cuales se “experimenta estéticamente” cómo se sobrevive (überleben) (Ette, 2015) a la modernidad en los sectores marginados. Es decir, solo desde lo vetusto y ruinoso de la religiosidad popular, otrora sagrado, es posible explicar la experiencia de lo moderno, su aquí y ahora.