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Proteine sind an praktisch allen Prozessen in lebenden Zellen maßgeblich beteiligt. Auch in der Biotechnologie werden Proteine in vielfältiger Weise eingesetzt.
Ein Protein besteht aus einer Kette von Aminosäuren. Häufig lagern sich mehrere dieser Ketten zu größeren Strukturen und Funktionseinheiten, sogenannten Proteinkomplexen,
zusammen. Kürzlich wurde gezeigt, dass eine Proteinkomplexbildung bereits während der Biosynthese der Proteine (co-translational) stattfinden kann
und nicht stets erst danach (post-translational) erfolgt. Da Fehlassemblierungen von Proteinen zu Funktionsverlusten und adversen Effekten führen, ist eine präzise und verlässliche Proteinkomplexbildung sowohl für zelluläre Prozesse als auch für biotechnologische Anwendungen essenziell. Mit experimentellen Methoden lassen sich zwar u.a. die Stöchiometrie und die Struktur von Proteinkomplexen bestimmen,
jedoch bisher nicht die Dynamik der Komplexbildung auf unterschiedlichen Zeitskalen. Daher sind grundlegende Mechanismen der Proteinkomplexbildung noch nicht vollständig verstanden. Die hier vorgestellte, auf experimentellen Erkenntnissen aufbauende, computergestützte Modellierung der Proteinkomplexbildung erlaubt eine umfassende Analyse des Einflusses physikalisch-chemischer Parameter
auf den Assemblierungsprozess. Die Modelle bilden möglichst realistisch die experimentellen Systeme der Kooperationspartner (Bar-Ziv, Weizmann-Institut, Israel; Bukau und Kramer, Universität Heidelberg) ab, um damit die Assemblierung von Proteinkomplexen einerseits in einem quasi-zweidimensionalen synthetischen Expressionssystem (in vitro) und andererseits im Bakterium Escherichia coli (in vivo) untersuchen zu können. Mit Hilfe eines vereinfachten Expressionssystems, in dem die Proteine nur an die Chip-Oberfläche, aber nicht aneinander binden können, wird das theoretische Modell parametrisiert. In diesem vereinfachten in-vitro-System durchläuft die Effizienz der Komplexbildung drei Regime – ein bindedominiertes Regime, ein Mischregime und ein produktionsdominiertes Regime. Ihr Maximum erreicht die Effizienz dabei kurz nach dem Übergang vom bindedominierten ins Mischregime und fällt anschließend monoton ab. Sowohl im nicht-vereinfachten in-vitro- als auch im in-vivo-System koexistieren je zwei konkurrierende Assemblierungspfade: Im in-vitro-System erfolgt die Komplexbildung entweder spontan in wässriger Lösung (Lösungsassemblierung) oder aber in einer definierten Schrittfolge an der Chip-Oberfläche (Oberflächenassemblierung); Im in-vivo-System konkurrieren hingegen die co- und die post-translationale Komplexbildung. Es zeigt sich, dass die Dominanz der Assemblierungspfade im in-vitro-System zeitabhängig ist und u.a. durch die Limitierung und Stärke der Bindestellen auf der Chip-Oberfläche beeinflusst werden kann. Im in-vivo-System hat der räumliche Abstand zwischen den Syntheseorten der beiden Proteinkomponenten nur dann einen Einfluss auf die Komplexbildung, wenn die Untereinheiten schnell degradieren. In diesem Fall dominiert die co-translationale Assemblierung auch auf kurzen Zeitskalen deutlich, wohingegen es bei stabilen Untereinheiten zu einem Wechsel von der Dominanz der post- hin zu einer geringen Dominanz der co-translationalen Assemblierung kommt. Mit den in-silico-Modellen lässt sich neben der Dynamik u.a. auch die Lokalisierung der Komplexbildung und -bindung darstellen, was einen Vergleich der theoretischen Vorhersagen mit experimentellen Daten und somit eine Validierung der Modelle ermöglicht. Der hier präsentierte in-silico Ansatz ergänzt die experimentellen Methoden, und erlaubt so, deren Ergebnisse zu interpretieren und neue Erkenntnisse davon abzuleiten.
The development of speaking competence is widely regarded as a central aspect of second language (L2) learning. It may be questioned, however, if the currently predominant ways of conceptualising the term fully satisfy the complexity of the construct: Although there is growing recognition that language primarily constitutes a tool for communication and participation in social life, as yet it is rare for conceptualisations of speaking competence to incorporate the ability to inter-act and co-construct meaning with co-participants. Accordingly, skills allowing for the successful accomplishment of interactional tasks (such as orderly speaker change, and resolving hearing and understanding trouble) also remain largely unrepresented in language teaching and assessment. As fostering the ability to successfully use the L2 within social interaction should arguably be a main objective of language teaching, it appears pertinent to broaden the construct of speaking competence by incorporating interactional competence (IC). Despite there being a growing research interest in the conceptualisation and development of (L2) IC, much of the materials and instruments required for its teaching and assessment, and thus for fostering a broader understanding of speaking competence in the L2 classroom, still await development. This book introduces an approach to the identification of candidate criterial features for the assessment of EFL learners’ L2 repair skills. Based on a corpus of video-recorded interaction between EFL learners, and following conversation-analytic and interactional-linguistic methodology as well as drawing on basic premises of research in the framework of Conversation Analysis for Second Language Acquisition, differences between (groups of) learners in terms of their L2 repair conduct are investigated through qualitative and inductive analyses. Candidate criterial features are derived from the analysis results. This book does not only contribute to the operationalisation of L2 IC (and of L2 repair skills in particular), but also lays groundwork for the construction of assessment scales and rubrics geared towards the evaluation of EFL learners’ L2 interactional skills.
A decade ago, it became feasible to store multi-terabyte databases in main memory. These in-memory databases (IMDBs) profit from DRAM's low latency and high throughput as well as from the removal of costly abstractions used in disk-based systems, such as the buffer cache. However, as the DRAM technology approaches physical limits, scaling these databases becomes difficult. Non-volatile memory (NVM) addresses this challenge. This new type of memory is persistent, has more capacity than DRAM (4x), and does not suffer from its density-inhibiting limitations. Yet, as NVM has a higher latency (5-15x) and a lower throughput (0.35x), it cannot fully replace DRAM.
IMDBs thus need to navigate the trade-off between the two memory tiers. We present a solution to this optimization problem. Leveraging information about access frequencies and patterns, our solution utilizes NVM's additional capacity while minimizing the associated access costs. Unlike buffer cache-based implementations, our tiering abstraction does not add any costs when reading data from DRAM. As such, it can act as a drop-in replacement for existing IMDBs. Our contributions are as follows:
(1) As the foundation for our research, we present Hyrise, an open-source, columnar IMDB that we re-engineered and re-wrote from scratch. Hyrise enables realistic end-to-end benchmarks of SQL workloads and offers query performance which is competitive with other research and commercial systems. At the same time, Hyrise is easy to understand and modify as repeatedly demonstrated by its uses in research and teaching.
(2) We present a novel memory management framework for different memory and storage tiers. By encapsulating the allocation and access methods of these tiers, we enable existing data structures to be stored on different tiers with no modifications to their implementation. Besides DRAM and NVM, we also support and evaluate SSDs and have made provisions for upcoming technologies such as disaggregated memory.
(3) To identify the parts of the data that can be moved to (s)lower tiers with little performance impact, we present a tracking method that identifies access skew both in the row and column dimensions and that detects patterns within consecutive accesses. Unlike existing methods that have substantial associated costs, our access counters exhibit no identifiable overhead in standard benchmarks despite their increased accuracy.
(4) Finally, we introduce a tiering algorithm that optimizes the data placement for a given memory budget. In the TPC-H benchmark, this allows us to move 90% of the data to NVM while the throughput is reduced by only 10.8% and the query latency is increased by 11.6%. With this, we outperform approaches that ignore the workload's access skew and access patterns and increase the query latency by 20% or more.
Individually, our contributions provide novel approaches to current challenges in systems engineering and database research. Combining them allows IMDBs to scale past the limits of DRAM while continuing to profit from the benefits of in-memory computing.
Moderne Technologien befähigen die beteiligten Akteure eines Produktionsprozesses die Informationsaufnahme, Entscheidungsfindung und -ausführung selbstständig auszuführen. Hierarchische Kontrollbeziehungen werden aufgelöst und die Entscheidungsfindung auf eine Vielzahl von Akteuren verteilt. Positive Folgen sind unter anderem die Nutzung lokaler Kompetenzen und ein schnelles Handeln vor Ort ohne (zeit-)aufwändige prozessübergreifende Planungsläufe durch eine zentrale Steuerungsinstanz. Die Bewertung der Dezentralität des Prozesses hilft beim Vergleich verschiedener Steuerungsstrategien und trägt so zur Beherrschung komplexerer Produktionsprozesse bei.
Obwohl die Kommunikationsstruktur der an der Entscheidungsfindung beteiligten Akteure zunehmend an Bedeutung gewinnt, existiert keine Methode, welche diese als Grundlage für die Operationalisierung der Dezentralität verwendet. Hier setzt diese Arbeit an. Es wird ein dreistufiges Bewertungsmodell entwickelt, dass die Dezentralität eines Produktionsprozesses auf Basis der Kommunikations- und Entscheidungsstruktur der am Prozess beteiligten, autonomen Akteure ermittelt.
Aufbauend auf einer Definition von Dezentralität von Produktionsprozessen werden Anforderungen an eine Kennzahl erhoben und - auf Basis der Kommunikationsstruktur - eine die strukturelle Autonomie der Akteure bestimmenden Kenngröße der sozialen Netzwerkanalyse ermittelt. Die Notwendigkeit der zusätzlichen Berücksichtigung der Entscheidungsstruktur wird basierend auf der Möglichkeit der Integration von Entscheidungsfindung und -ausführung begründet.
Die Differenzierung beider Faktoren bildet die Grundlage für die Klassifikation der Akteure; die Multiplikation beider Werte resultiert in dem die Autonomie eines Akteurs beschreibenden Kennwert tatsächliche Autonomie, welcher das Ergebnis der ersten Stufe des Modells darstellt. Homogene Akteurswerte charakterisieren eine hohe Dezentralität des Prozessschrittes, welcher Betrachtungsobjekt der zweiten Stufe ist. Durch einen Vergleich der vorhandenen mit der maximal möglichen Dezentralität der Prozessschritte wird auf der dritten Stufe der Autonomie Index ermittelt, welcher die Dezentralität des Prozesses operationalisiert.
Das erstellte Bewertungsmodell wird anhand einer Simulationsstudie im Zentrum Industrie 4.0 validiert. Dafür wird das Modell auf zwei Simulationsexperimente - einmal mit einer zentralen und einmal mit einer dezentralen Steuerung - angewendet und die Ergebnisse verglichen. Zusätzlich wird es auf einen umfangreichen Produktionsprozess aus der Praxis angewendet.
Bio-sourced adsorbing poly(2-oxazoline)s mimicking mussel glue proteins for antifouling applications
(2022)
Nature developed countless systems for many applications. In maritime environments, several organisms established extra-ordinary mechanisms to attach to surfaces. Over the past years, the scientific interest to employ those mechanisms for coatings and long-lasting adhering materials gained significant attention.
This work describes the synthesis of bio-inspired adsorbing copoly(2-oxazoline)s for surface coatings with protein repelling effects, mimicking mussel glue proteins. From a set of methoxy substituted phenyl, benzyl, and cinnamyl acids, 2-oxazoline monomers were synthesized. All synthesized 2-oxazolines were analyzed by FT-IR spectroscopy, NMR spectroscopy, and EI mass spectrometry. With those newly synthesized 2-oxazoline monomers and 2-ethyl-2-oxazoline, kinetic studies concerning homo- and copolymerization in a microwave reactor were conducted. The success of the polymerization reactions was demonstrated by FT-IR spectroscopy, NMR spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography (SEC). The copolymerization of 2-ethyl-2-oxazoline with a selection of methoxy-substituted 2-oxazolines resulted in water-soluble copolymers. To release the adsorbing catechol and cationic units, the copoly(2-oxazoline)s were modified. The catechol units were (partially) released by a methyl aryl ether cleavage reaction. A subsequent partial acidic hydrolysis of the ethyl unit resulted in mussel glue protein-inspired catechol and cation-containing copolymers. The modified copolymers were analyzed by NMR spectroscopy, UV-VIS spectroscopy, and SEC. The catechol- and cation-containing copolymers and their precursors were examined by a Quartz Crystal Microbalance with Dissipation (QCM-D), so study the adsorption performance on gold, borosilicate, iron, and polystyrene surfaces. An exemplary study revealed that a catechol and cation-containing copoly(2-oxazoline)-coated gold surface exhibits strong protein repelling properties.
Carbohydrates are found in every living organism, where they are responsible for numerous, essential biological functions and processes. Synthetic polymers with pendant saccharides, called glycopolymers, mimic natural glycoconjugates in their special properties and functions. Employing such biomimetics furthers the understanding and controlling of biological processes. Hence, glycopolymers are valuable and interesting for applications in the medical and biological field. However, the synthesis of carbohydrate-based materials can be very challenging. In this thesis, the synthesis of biofunctional glycopolymers is presented, with the focus on aqueous-based, protecting group free and short synthesis routes to further advance in the field of glycopolymer synthesis.
A practical and versatile precursor for glycopolymers are glycosylamines. To maintain biofunctionality of the saccharides after their amination, regioselective functionalization was performed. This frequently performed synthesis was optimized for different sugars. The optimization was facilitated using a design of experiment (DoE) approach to enable a reduced number of necessary experiments and efficient procedure. Here, the utility of using DoE for optimizing the synthesis of glycosylamines is discussed.
The glycosylamines were converted to glycomonomers which were then polymerized to yield biofunctional glycopolymers. Here, the glycopolymers were aimed to be applicable as layer-by-layer (LbL) thin film coatings for drug delivery systems. To enable the LbL technique, complimentary glycopolymer electrolytes were synthesized by polymerization of the glycomonomers and subsequent modification or by post-polymerization modification. For drug delivery, liposomes were embedded into the glycopolymer coating as potential cargo carriers. The stability as well as the integrity of the glycopolymer layers and liposomes were investigated at physiological pH range.
Different glycopolymers were also synthesized to be applicable as anti-adhesion therapeutics by providing advanced architectures with multivalent presentations of saccharides, which can inhibit the binding of pathogene lectins. Here, the synthesis of glycopolymer hydrogel particles based on biocompatible poly(N-isopropylacrylamide) (NiPAm) was established using the free-radical precipitation polymerization technique. The influence of synthesis parameters on the sugar content in the gels and on the hydrogel morphology is discussed. The accessibility of the saccharides to model lectins and their enhanced, multivalent interaction were investigated.
At the end of this work, the synthesis strategies for the glycopolymers are generally discussed as well as their potential application in medicine.
Synthetische Transkriptionsfaktoren bestehen wie natürliche Transkriptionsfaktoren aus einer DNA-Bindedomäne, die sich spezifisch an die Bindestellensequenz vor dem Ziel-Gen anlagert, und einer Aktivierungsdomäne, die die Transkriptionsmaschinerie rekrutiert, sodass das Zielgen exprimiert wird. Der Unterschied zu den natürlichen Transkriptionsfaktoren ist, sowohl dass die DNA-Bindedomäne als auch die Aktivierungsdomäne wirtsfremd sein können und dadurch künstliche Stoffwechselwege im Wirt, größtenteils chemisch, induziert werden können. Optogenetische synthetische Transkriptionsfaktoren, die hier entwickelt wurden, gehen einen Schritt weiter. Dabei ist die DNA-Bindedomäne nicht mehr an die Aktivierungsdomäne, sondern mit dem Blaulicht-Photorezeptor CRY2 gekoppelt. Die Aktivierungsdomäne wurde mit dem Interaktionspartner CIB1 fusioniert. Unter Blaulichtbestrahlung dimerisieren CRY2 und CIB1 und damit einhergehend die beiden Domänen, sodass ein funktionsfähiger Transkriptionsfaktor entsteht. Dieses System wurde in die Saccharomyces cerevisiae genomisch integriert. Verifiziert wurde das konstruierte System mit Hilfe des Reporters yEGFP, welcher durchflusszytometrisch detektiert werden konnte. Es konnte gezeigt werden, dass die yEGFP Expression variabel gestaltet werden kann, indem unterschiedlich lange Blaulichtimpulse ausgesendet wurden, die DNA-Bindedomäne, die Aktivierungsdomäne oder die Anzahl der Bindestellen, an dem sich die DNA-Bindedomäne anlagert, verändert wurden. Um das System für industrielle Anwendungen attraktiv zu gestalten, wurde das System vom Deepwell-Maßstab auf Photobioreaktor-Maßstab hochskaliert. Außerdem erwies sich das Blaulichtsystem sowohl im Laborstamm YPH500 als auch im industriell oft verwendeten Hefestamm CEN.PK als funktional. Des Weiteren konnte ein industrierelevante Protein ebenso mit Hilfe des verifizierten Systems exprimiert werden. Schlussendlich konnte in dieser Arbeit das etablierte Blaulicht-System erfolgreich mit einem Rotlichtsystem kombiniert werden, was zuvor noch nicht beschrieben wurde.
The index theorem for elliptic operators on a closed Riemannian manifold by Atiyah and Singer has many applications in analysis, geometry and topology, but it is not suitable for a generalization to a Lorentzian setting.
In the case where a boundary is present Atiyah, Patodi and Singer provide an index theorem for compact Riemannian manifolds by introducing non-local boundary conditions obtained via the spectral decomposition of an induced boundary operator, so called APS boundary conditions. Bär and Strohmaier prove a Lorentzian version of this index theorem for the Dirac operator on a manifold with boundary by utilizing results from APS and the characterization of the spectral flow by Phillips. In their case the Lorentzian manifold is assumed to be globally hyperbolic and spatially compact, and the induced boundary operator is given by the Riemannian Dirac operator on a spacelike Cauchy hypersurface. Their results show that imposing APS boundary conditions for these boundary operator will yield a Fredholm operator with a smooth kernel and its index can be calculated by a formula similar to the Riemannian case.
Back in the Riemannian setting, Bär and Ballmann provide an analysis of the most general kind of boundary conditions that can be imposed on a first order elliptic differential operator that will still yield regularity for solutions as well as Fredholm property for the resulting operator. These boundary conditions can be thought of as deformations to the graph of a suitable operator mapping APS boundary conditions to their orthogonal complement.
This thesis aims at applying the boundary conditions found by Bär and Ballmann to a Lorentzian setting to understand more general types of boundary conditions for the Dirac operator, conserving Fredholm property as well as providing regularity results and relative index formulas for the resulting operators. As it turns out, there are some differences in applying these graph-type boundary conditions to the Lorentzian Dirac operator when compared to the Riemannian setting. It will be shown that in contrast to the Riemannian case, going from a Fredholm boundary condition to its orthogonal complement works out fine in the Lorentzian setting. On the other hand, in order to deduce Fredholm property and regularity of solutions for graph-type boundary conditions, additional assumptions for the deformation maps need to be made.
The thesis is organized as follows. In chapter 1 basic facts about Lorentzian and Riemannian spin manifolds, their spinor bundles and the Dirac operator are listed. These will serve as a foundation to define the setting and prove the results of later chapters.
Chapter 2 defines the general notion of boundary conditions for the Dirac operator used in this thesis and introduces the APS boundary conditions as well as their graph type deformations. Also the role of the wave evolution operator in finding Fredholm boundary conditions is analyzed and these boundary conditions are connected to notion of Fredholm pairs in a given Hilbert space.
Chapter 3 focuses on the principal symbol calculation of the wave evolution operator and the results are used to proof Fredholm property as well as regularity of solutions for suitable graph-type boundary conditions. Also sufficient conditions are derived for (pseudo-)local boundary conditions imposed on the Dirac operator to yield a Fredholm operator with a smooth solution space.
In the last chapter 4, a few examples of boundary conditions are calculated applying the results of previous chapters. Restricting to special geometries and/or boundary conditions, results can be obtained that are not covered by the more general statements, and it is shown that so-called transmission conditions behave very differently than in the Riemannian setting.
Plant metabolism is the main process of converting assimilated carbon to different crucial compounds for plant growth and therefore crop yield, which makes it an important research topic. Although major advances in understanding genetic principles contributing to metabolism and yield have been made, little is known about the genetics responsible for trait variation or canalization although the concepts have been known for a long time. In light of a growing global population and progressing climate change, understanding canalization of metabolism and yield seems ever-more important to ensure food security. Our group has recently found canalization metabolite quantitative trait loci (cmQTL) for tomato fruit metabolism, showing that the concept of canalization applies on metabolism. In this work two approaches to investigate plant metabolic canalization and one approach to investigate yield canalization are presented.
In the first project, primary and secondary metabolic data from Arabidopsis thaliana and Phaseolus vulgaris leaf material, obtained from plants grown under different conditions was used to calculate cross-environment coefficient of variations or fold-changes of metabolite levels per genotype and used as input for genome wide association studies. While primary metabolites have lower CV across conditions and show few and mostly weak associations to genomic regions, secondary metabolites have higher CV and show more, strong metabolite to genome associations. As candidate genes, both potential regulatory genes as well as metabolic genes, can be found, albeit most metabolic genes are rarely directly related to the target metabolites, suggesting a role for both potential regulatory mechanisms as well as metabolic network structure for canalization of metabolism.
In the second project, candidate genes of the Solanum lycopersicum cmQTL mapping are selected and CRISPR/Cas9-mediated gene-edited tomato lines are created, to validate the genes role in canalization of metabolism. Obtained mutants appeared to either have strong aberrant developmental phenotypes or appear wild type-like. One phenotypically inconspicuous mutant of a pantothenate kinase, selected as candidate for malic acid canalization shows a significant increase of CV across different watering conditions. Another such mutant of a protein putatively involved in amino acid transport, selected as candidate for phenylalanine canalization shows a similar tendency to increased CV without statistical significance. This potential role of two genes involved in metabolism supports the hypothesis of structural relevance of metabolism for its own stability.
In the third project, a mutant for a putative disulfide isomerase, important for thylakoid biogenesis, is characterized by a multi-omics approach. The mutant was characterized previously in a yield stability screening and showed a variegated leaf phenotype, ranging from green leaves with wild type levels of chlorophyll over differently patterned variegated to completely white leaves almost completely devoid of photosynthetic pigments. White mutant leaves show wild type transcript levels of photosystem assembly factors, with the exception of ELIP and DEG orthologs indicating a stagnation at an etioplast to chloroplast transition state. Green mutant leaves show an upregulation of these assembly factors, possibly acting as overcompensation for partially defective disulfide isomerase, which seems sufficient for proper chloroplast development as confirmed by a wild type-like proteome. Likely as a result of this phenotype, a general stress response, a shift to a sink-like tissue and abnormal thylakoid membranes, strongly alter the metabolic profile of white mutant leaves. As the severity and pattern of variegation varies from plant to plant and may be effected by external factors, the effect on yield instability, may be a cause of a decanalized ability to fully exploit the whole leaf surface area for photosynthetic activity.
Digital transformation (DT) has not only been a major challenge in recent years, it is also supposed to continue to enormously impact our society and economy in the forthcoming decade. On the one hand, digital technologies have emerged, diffusing and determining our private and professional lives. On the other hand, digital platforms have leveraged the potentials of digital technologies to provide new business models. These dynamics have a massive effect on individuals, companies, and entire ecosystems. Digital technologies and platforms have changed the way persons consume or interact with each other. Moreover, they offer companies new opportunities to conduct their business in terms of value creation (e.g., business processes), value proposition (e.g., business models), or customer interaction (e.g., communication channels), i.e., the three dimensions of DT. However, they also can become a threat for a company's competitiveness or even survival. Eventually, the emergence, diffusion, and employment of digital technologies and platforms bear the potential to transform entire markets and ecosystems.
Against this background, IS research has explored and theorized the phenomena in the context of DT in the past decade, but not to its full extent. This is not surprising, given the complexity and pervasiveness of DT, which still requires far more research to further understand DT with its interdependencies in its entirety and in greater detail, particularly through the IS perspective at the confluence of technology, economy, and society. Consequently, the IS research discipline has determined and emphasized several relevant research gaps for exploring and understanding DT, including empirical data, theories as well as knowledge of the dynamic and transformative capabilities of digital technologies and platforms for both organizations and entire industries.
Hence, this thesis aims to address these research gaps on the IS research agenda and consists of two streams. The first stream of this thesis includes four papers that investigate the impact of digital technologies on organizations. In particular, these papers study the effects of new technologies on firms (paper II.1) and their innovative capabilities (II.2), the nature and characteristics of data-driven business models (II.3), and current developments in research and practice regarding on-demand healthcare (II.4). Consequently, the papers provide novel insights on the dynamic capabilities of digital technologies along the three dimensions of DT. Furthermore, they offer companies some opportunities to systematically explore, employ, and evaluate digital technologies to modify or redesign their organizations or business models.
The second stream comprises three papers that explore and theorize the impact of digital platforms on traditional companies, markets, and the economy and society at large. At this, paper III.1 examines the implications for the business of traditional insurance companies through the emergence and diffusion of multi-sided platforms, particularly in terms of value creation, value proposition, and customer interaction. Paper III.2 approaches the platform impact more holistically and investigates how the ongoing digital transformation and "platformization" in healthcare lastingly transform value creation in the healthcare market. Paper III.3 moves on from the level of single businesses or markets to the regulatory problems that result from the platform economy for economy and society, and proposes appropriate regulatory approaches for addressing these problems. Hence, these papers bring new insights on the table about the transformative capabilities of digital platforms for incumbent companies in particular and entire ecosystems in general.
Altogether, this thesis contributes to the understanding of the impact of DT on organizations and markets through the conduction of multiple-case study analyses that are systematically reflected with the current state of the art in research. On this empirical basis, the thesis also provides conceptual models, taxonomies, and frameworks that help describing, explaining, or predicting the impact of digital technologies and digital platforms on companies, markets and the economy or society at large from an interdisciplinary viewpoint.