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Electrosynthesis and characterization of molecularly imprinted polymers for peptides and proteins
(2019)
This thesis covers the synthesis of conjugates of 2-Deoxy-D-ribose-5-phosphate aldolase (DERA) with suitable polymers and the subsequent immobilization of these conjugates in thin films via two different approaches.
2-Deoxy-D-ribose-5-phosphate aldolase (DERA) is a biocatalyst that is capable of converting acetaldehyde and a second aldehyde as acceptor into enantiomerically pure mono- and diyhydroxyaldehydes, which are important structural motifs in a number of pharmaceutically active compounds. Conjugation and immobilization renders the enzyme applicable for utilization in a continuously run biocatalytic process which avoids the common problem of product inhibition. Within this thesis, conjugates of DERA and poly(N-isopropylacrylamide) (PNIPAm) for immobilization via a self-assembly approach were synthesized and isolated, as well as conjugates with poly(N,N-dimethylacrylamide) (PDMAA) for a simplified and scalable spray-coating approach. For the DERA/PNIPAm-conjugates different synthesis routes were tested, including grafting-from and grafting-to, both being common methods for the conjugation. Furthermore, both lysines and cysteines were addressed for the conjugation in order to find optimum conjugation conditions. It turned out that conjugation via lysine causes severe activity loss as one lysine plays a key role in the catalyzing mechanism. The conjugation via the cysteines by a grafting-to approach using pyridyl disulfide (PDS) end-group functionalized polymers led to high conjugation efficiencies in the presence of polymer solubilizing NaSCN. The resulting conjugates maintained enzymatic activity and also gained high acetaldehyde tolerance which is necessary for their use later on in an industrial relevant process after their immobilization.
The resulting DERA/PNIPAm conjugates exhibited enhanced interfacial activity at the air/water interface compared to the single components, which is an important pre-requisite for the immobilization via the self-assembly approach. Conjugates with longer polymer chains formed homogeneous films on silicon wafers and glass slides while the ones with short chains could only form isolated aggregates. On top of that, long chain conjugates showed better activity maintenance upon the immobilization.
The crosslinking of conjugates, as well as their fixation on the support materials, are important for the mechanical stability of the films obtained from the self-assembly process. Therefore, in a second step, we introduced the UV-crosslinkable monomer DMMIBA to the PNIPAm polymers to be used for conjugation. The introduction of DMMIBA reduced the lower critical solution temperature (LCST) of the polymer and thus the water solubility at ambient conditions, resulting in lower conjugation efficiencies and in turn slightly poorer acetaldehyde tolerance of the resulting conjugates. Unlike the DERA/PNIPAm, the conjugates from the copolymer P(NIPAM-co-DMMIBA) formed continuous, homogenous films only after the crosslinking step via UV-treatment. For a firm binding of the crosslinked films, a functionalization protocol for the model support material cyclic olefin copolymer (COC) and the final target support, PAN based membranes, was developed that introduces analogue UV-reactive groups to the support surface. The conjugates immobilized on the modified COC films maintained enzymatic activity and showed good mechanical stability after several cycles of activity assessment. Conjugates with longer polymer chains, however, showed a higher degree of crosslinking after the UV-treatment leading to a pronounced loss of activity. A porous PAN membrane onto which the conjugates were immobilized as well, was finally transferred to a dead end filtration membrane module to catalyze the aldol reaction of the industrially relevant mixture of acetaldehyde and hexanal in a continuous mode. Mono aldol product was detectable, but yields were comparably low and the operational stability needs to be further improved
Another approach towards immobilization of DERA conjugates that was followed, was to generate the conjugates in situ by simply mixing enzyme and polymer and spray coat the mixture onto the membrane support. Compared to the previous approach, the focus was more put on simplicity and a possible scalability of the immobilization. Conjugates were thus only generated in-situ and not further isolated and characterized. For the conjugation, PDMAA equipped with N-2-thiolactone acrylamide (TlaAm) side chains was used, an amine-reactive comonomer that can react with the lysine residues of DERA, as well as with amino groups introduced to a desired support surface. Furthermore disulfide formation after hydrolysis of the Tla groups causes a crosslinking effect. The synthesized copolymer poly(N,N-Dimethylacrylamide-co-N-2-thiolactone acrylamide) (P(DMAA-co-TlaAm)) thus serves a multiple purpose including protein binding, crosslinking and binding to support materials. The mixture of DERA and polymer could be immobilized on the PAN support by spray-coating under partial maintenance of enzymatic activity. To improve the acetaldehyde tolerance, the polymer in used was further equipped with cysteine reactive PDS end-groups that had been used for the conjugation as described in the first part of the thesis. The generated conjugates indeed showed good acetaldehyde tolerance and were thus used to be coated onto PAN membrane supports. Post treatment with a basic aqueous solution of H2O2 was supposed to further crosslink the spray-coated film hydrolysis and oxidation of the thiolactone groups. However, a washing off of the material was observed. Optimization is thus still necessary.
Der Betrieb gewerblicher Art
(2019)
Die Arbeit untersucht die Grundlagen der Besteuerung der öffentlichen Hand, hier insbesondere die geschichtliche Entwicklung des Betriebs gewerblicher Art und die seit 2009 geltende Querverbundsystematik. Es wird die Entwicklung der einzelnen Tatbestände bis hin zur tatbestandsmäßigen Zusammenfassung einzelner Betriebe gewerblicher Art untersucht. Dabei stehen immer wieder die Wettbewerbssystematik und der steuerliche Gleichbehandlungsgrundsatz im Diskussionsmittelpunkt. Nachstehend schließt sich ein Vergleich zwischen dem horizontalen und vertikalen Querverbund an, der die grundlegenden Rechtsfolgen und die dauerdefizitären Betätigungen umfasst. Das Ergebnis zeigt auf, dass die öffentliche Hand mit ihrem wahlweisen horizontalen Querverbund und der fehlenden Gewinnerzielungsabsicht erhebliche Vorteile gegenüber privatrechtlich geführten Unternehmensformen genießt und somit erhebliches Steuersparpotential generiert.
Deutschland und Frankreich benötigen stetige Metallimporte, um ihr Wirtschaftsmodell aufrechtzuerhalten. Internationale Kooperation ist unerlässlich, damit diese Importe zuverlässig und nachhaltig verlaufen. Doch welche Potenziale bieten sich in diesem Bereich, welche Grenzen sind dabei zu erkennen? Dieser Frage geht Yann Wernert durch einen Fallstudienvergleich mit prozessanalytischen Methoden und auf der theoretischen Grundlage des neoliberalen Institutionalismus nach. Er zeigt, dass beide Länder ihre Bemühungen als reaktive Mittelmächte gestalten. Sie wollen durch staatliche Rohstoffstrategien wirtschaftliche, strategische und Nachhaltigkeitsziele erreichen. Während die Analyse durchaus Kooperationspotenziale ausmacht, fallen diese je nach Ländergruppe und Politikbereich sehr unterschiedlich aus.
The present dissertation investigates profit-maximizing behavior in different phases of the negotiation process. Over the last decades, research dealt in detail with behavior of negotiation actors with the aim of identifying performance enhancing factors. The majority of those studies focused on behavior within the main negotiation phase. This work, however, considers phases which are, so far, underrepresented in research but show an impact on the negotiation process and outcome. Those phases are the pre-negotiation, the first offer, and the main negotiation phase which is further divided by breaks into several rounds. Within these phases, traits of behavior are analyzed that can be used strategically in order to impact the negotiation outcome. The dissertation contains three papers, each one dealing with a specific strategy within one phase. The first paper investigates communication behavior in the pre-negotiation phase. Content analysis of a negotiation experiment shows that the employment of positive communication elements such as the generation of enthusiasm for an upcoming project results in an increase of agreements on entering a negotiation and also leads to a higher willingness to make concessions. The second paper explores the impact of a semantic first anchor, which does not contain a specific number but only gives a numerical direction, on the opponent’s concession behavior and the final outcome. By means of two scenario-based questionnaires and a negotiation experiment it is demonstrated that semantic offers reveal an anchoring effect and lead to better negotiation outcomes. The third paper deals with the introduction of breaks and their effect on the following negotiation process. Therefore, content and outcome of another negotiation experiment are investigated. The analysis shows that breaks evoke a dominant impression but can negatively impact the atmosphere and thereby also the outcome. Finally, the gathered insights are brought together and discussed. The dissertation closes with implications for practice, limitations of the work, and ideas for future research.
Berlin, Leipziger Straße 3-4
(2019)
In der Leipziger Straße 3–4 in Berlin, in der seit Herbst 2000 der Deutsche Bundesrat residiert, waren seit jeher bedeutende Institutionen angesiedelt.
1904 errichtet für das Preußische Herrenhaus, wurde das Gebäude nach dem Ersten Weltkrieg von den Arbeiter- und Soldatenräten genutzt. In der Weimarer Republik teilten sich der Preußische Staatsrat und das Preußische Wohlfahrtsministerium das Haus. Im Nationalsozialismus arbeiteten hier u. a. das Reichskirchenministerium und die Reichsstelle für Raumordnung.
Bartek Wardecki bietet eine vollständige Darstellung der Geschichte dieser berühmten Adresse sowie eine Übersicht über annähernd 1000 Veranstaltungen, die hier ausgerichtet wurden.
Die deutschen Wirtschaftsverbände geraten zunehmend unter Konkurrenzdruck. Immer mehr Verbände werben um dieselbe Mitgliederklientel und haben einen ähnlichen Themenzuschnitt. Darüber hinaus betreiben immer mehr Mitgliedsunternehmen eigene politische Interessenvertretung. Die vorliegende Studie untersucht auf der Grundlage des aus der Evolutionsbiologie stammenden Population Ecology-Ansatzes, wie die Verbände mit dieser Konkurrenz umgehen.
Determining the relationship between genotype and phenotype is the key to understand the plasticity and robustness of phenotypes in nature. While the directly observable plant phenotypes (e.g. agronomic, yield and stress resistance traits) have been well-investigated, there is still a lack in our knowledge about the genetic basis of intermediate phenotypes, such as metabolic phenotypes. Dissecting the links between genotype and phenotype depends on suitable statistical models. The state-of-the-art models are developed for directly observable phenotypes, regardless the characteristics of intermediate phenotypes. This thesis aims to fill the gaps in understanding genetic architecture of intermediate phenotypes, and how they tie to composite traits, namely plant growth. The metabolite levels and reaction fluxes, as two aspects of metabolic phenotypes, are shaped by the interrelated chemical reactions formed in genome-scale metabolic network. Here, I attempt to answer the question: Can the knowledge of underlying genome-scale metabolic network improve the model performance for prediction of metabolic phenotypes and associated plant growth? To this end, two projects are investigated in this thesis. Firstly, we propose an approach that couples genomic selection with genome-scale metabolic network and metabolic profiles in Arabidopsis thaliana to predict growth. This project is the first integration of genomic data with fluxes predicted based on constraint-based modeling framework and data on biomass composition. We demonstrate that our approach leads to a considerable increase of prediction accuracy in comparison to the state-of-the-art methods in both within and across environment predictions. Therefore, our work paves the way for combining knowledge on metabolic mechanisms in the statistical approach underlying genomic selection to increase the efficiency of future plant breeding approaches. Secondly, we investigate how reliable is genomic selection for metabolite levels, and which single nucleotide polymorphisms (SNPs), obtained from different neighborhoods of a given metabolic network, contribute most to the accuracy of prediction. The results show that the local structure of first and second neighborhoods are not sufficient for predicting the genetic basis of metabolite levels in Zea mays. Furthermore, we find that the enzymatic SNPs can capture most the genetic variance and the contribution of non-enzymatic SNPs is in fact small. To comprehensively understand the genetic architecture of metabolic phenotypes, I extend my study to a local Arabidopsis thaliana population and their hybrids. We analyze the genetic architecture in primary and secondary metabolism as well as in growth. In comparison to primary metabolites, compounds from secondary metabolism were more variable and show more non-additive inheritance patterns which could be attributed to epistasis. Therefore, our study demonstrates that heterozygosity in local Arabidopsis thaliana population generates metabolic variation and may impact several tasks directly linked to metabolism. The studies in this thesis improve the knowledge of genetic architecture of metabolic phenotypes in both inbreed and hybrid population. The approaches I proposed to integrate genome-scale metabolic network with genomic data provide the opportunity to obtain mechanistic insights about the determinants of agronomically important polygenic traits.
The usage of mobile devices is rapidly growing with Android being the most prevalent mobile operating system. Thanks to the vast variety of mobile applications, users are preferring smartphones over desktops for day to day tasks like Internet surfing. Consequently, smartphones store a plenitude of sensitive data. This data together with the high values of smartphones make them an attractive target for device/data theft (thieves/malicious applications).
Unfortunately, state-of-the-art anti-theft solutions do not work if they do not have an active network connection, e.g., if the SIM card was removed from the device. In the majority of these cases, device owners permanently lose their smartphone together with their personal data, which is even worse.
Apart from that malevolent applications perform malicious activities to steal sensitive information from smartphones. Recent research considered static program analysis to detect dangerous data leaks. These analyses work well for data leaks due to inter-component communication, but suffer from shortcomings for inter-app communication with respect to precision, soundness, and scalability.
This thesis focuses on enhancing users' privacy on Android against physical device loss/theft and (un)intentional data leaks. It presents three novel frameworks: (1) ThiefTrap, an anti-theft framework for Android, (2) IIFA, a modular inter-app intent information flow analysis of Android applications, and (3) PIAnalyzer, a precise approach for PendingIntent vulnerability analysis.
ThiefTrap is based on a novel concept of an anti-theft honeypot account that protects the owner's data while preventing a thief from resetting the device.
We implemented the proposed scheme and evaluated it through an empirical user study with 35 participants. In this study, the owner's data could be protected, recovered, and anti-theft functionality could be performed unnoticed from the thief in all cases.
IIFA proposes a novel approach for Android's inter-component/inter-app communication (ICC/IAC) analysis. Our main contribution is the first fully automatic, sound, and precise ICC/IAC information flow analysis that is scalable for realistic apps due to modularity, avoiding combinatorial explosion: Our approach determines communicating apps using short summaries rather than inlining intent calls between components and apps, which requires simultaneously analyzing all apps installed on a device.
We evaluate IIFA in terms of precision, recall, and demonstrate its scalability to a large corpus of real-world apps. IIFA reports 62 problematic ICC-/IAC-related information flows via two or more apps/components.
PIAnalyzer proposes a novel approach to analyze PendingIntent related vulnerabilities. PendingIntents are a powerful and universal feature of Android for inter-component communication. We empirically evaluate PIAnalyzer on a set of 1000 randomly selected applications and find 1358 insecure usages of PendingIntents, including 70 severe vulnerabilities.
Bei der Arbeit mit literarischen Texten spielen Kontexte für das Verstehen naturgemäß eine herausgehobene Rolle. Lehrerinnen und Lehrer sind dabei mit vielfältigen Problemen konfrontiert: Welche Kontexte sind in welchen Jahrgangsstufen sinnvoll und ergiebig? Wann überfrachtet die Anreicherung mit Kontexten einen Verstehensprozess, wann ist sie unumgänglich? Wie gelingt es, dass Lernende Kontexte nicht nur schematisch, sondern flexibel für das Verstehen einsetzen? Wie können die Forderungen der Bildungsstandards und Lehrpläne nach einer intensiven Kontextualisierung im Unterricht konkret umgesetzt werden? Der vorliegende Band gibt auf diese Fragen anwendungsorientierte Antworten. Dies geschieht auf drei Ebenen: Zum einen wird über einen analytischen Zugang der Kontextbegriff systematisiert (mit den Kontextbereichen Gattung, Literaturgeschichte, Autorbiografie und Intertextualität), zum anderen wird in einer empirischen Studie die Wirksamkeit reflektierter Kontextnutzung für das Textverstehen verdeutlicht. Drittens werden erprobte Modelle für den konkreten Einsatz im Unterricht vorgestellt und diskutiert. So können Kontexte als ein ergiebiges Werkzeug für den Unterricht bereitgestellt werden.
Dieses Buch befasst sich mit der Anteilsübertragung von Kommanditanteilen, die von der Rechtsprechung zwar längst anerkannt ist, jedoch vom Gesetzgeber bislang nicht geregelt wurde. Bei der Eintragung einer solchen Anteilsübertragung in das Handelsregister unterlaufen in der Praxis häufig Fehler, deren jeweilige haftungsrechtliche Konsequenz die Autorin eingehend untersucht. Im Zentrum der Arbeit steht die These, dass die Nichteintragung des Sonderrechtsnachfolgevermerkes zu keiner doppelten Haftung von Neu- und Altkommanditist führt.
Giuseppe Prezzolini
(2019)
Der Journalist Giuseppe Prezzolini (1882–1982) gehört zu den prägenden italienischen Intellektuellen des 20. Jahrhunderts. Die von ihm begründete Kulturzeitschrift »La Voce« bot einflussreichen Stimmen der Zeit eine Bühne, darunter Giovanni Gentile, Benedetto Croce oder Benito Mussolini. Durch seine publizistische Arbeit avancierte er zu einem festen intellektuellen Bezugspunkt konservativer Kreise Italiens. Seine Forderungen u. a. nach einer Neugründung des italienischen Konservatismus abseits neofaschistischer Ideen begründeten seinen umstrittenen Ruf als Antikonformist.
Dieses Buch liefert überblicksartig Befunde einer Wirkungsforschung im Fach Sport und behandelt Determinanten und Konsequenzen von Leistungen von Schülern und Schülerinnen im Sportunterricht. Ausgehend vom Angebot-Nutzen-Modell (nach Helmke, 2010) analysiert Sara Seiler distale und proximale Merkmale des Lehr-Lern-Prozesses in ihrer Einflussnahme auf Lernleistungen von Schülern und Schülerinnen in einem Mehrebenenmodell. Entgegen einer Reduzierung auf kognitive Lernleistungen werden motorische, motivationale, volitionale und personale Aspekte als Lernleistungen im Sport diskutiert.
The Italian Army’s participation in Hitler’s war against the Soviet Union has remained unrecognized and understudied. Bastian Matteo Scianna offers a wide-ranging, in-depth corrective. Mining Italian, German and Russian sources, he examines the history of the Italian campaign in the East between 1941 and 1943, as well as how the campaign was remembered and memorialized in the domestic and international arena during the Cold War. Linking operational military history with memory studies, this book revises our understanding of the Italian Army in the Second World War.
Im Mittelpunkt dieser Arbeit standen Analysen zur Charakterisierung der periplasmatischen Aldehyd Oxidoreduktase aus E. coli. Kinetische Untersuchungen mit Ferricyanid als Elektronenakzeptor unter anaeroben Bedingungen zeigten für dieses Enzym eine höhere Aktivität als unter aeroben Bedingungen. Die getroffene Hypothese, dass PaoABC fähig ist Elektronen an molekularen Sauerstoff weiter zu geben, konnte bestätigt werden. Für den Umsatz aromatischer Aldehyde mit molekularem Sauerstoff wurde ein Optimum von pH 6,0 ermittelt. Dies steht im Gegensatz zur Reaktion mit Ferricyanid, mit welchem ein pH-Optimum von 4,0 gezeigt wurde. Die Reaktion von PaoABC mit molekularem Sauerstoff generiert zwar Wasserstoffperoxid, die Produktion von Superoxid konnte dagegen nicht beobachtet werden. Dass aerobe Bedingungen einen Einfluss auf das Auslösen der Expression von PaoABC haben, wurde in dieser Arbeit ebenfalls ermittelt.
Im Zusammenhang mit der Produktion von ROS durch PaoABC wurde die Funktion eines kürzlich in Elektronentransfer-Distanz zum FAD identifizierten [4Fe4S]-Clusters untersucht. Ein Austausch der für die Bindung des Clusters zuständigen Cysteine führte zur Instabilität der Proteinvarianten, weswegen für diese keine weiteren Untersuchungen erfolgten. Daher wird zumindest ein struktur-stabilisierender Einfluss des [4Fe4S]-Clusters angenommen. Zur weiteren Untersuchung der Funktion dieses Clusters, wurde ein zwischen FAD und [4Fe4S]-Cluster lokalisiertes Arginin gegen ein Alanin ausgetauscht. Diese Proteinvariante zeigte eine reduzierte Geschwindigkeit der Reaktion gegenüber dem Wildtyp. Die Bildung von Superoxid konnte auch hier nicht beobachtet werden. Die Vermutung, dass dieser Cluster einen elektronen-sammelnden Mechanismus unterstützt, welcher die Radikalbildung verhindert, kann trotz allem nicht ausgeschlossen werden. Da im Umkreis des Arginins weitere geladene und aromatische Aminosäuren lokalisiert sind, können diese den notwendigen Elektronentransfer übernehmen.
Neben der Ermittlung eines physiologischen Elektronenakzeptors und dessen Einfluss auf die Expression von PaoABC zeigt diese Arbeit auch, dass die Chaperone PaoD und MocA während der Reifung des MCD-Kofaktor eine gemeinsame Bindung an PaoABC realisieren. Es konnte im aktiven Zentrum von PaoABC ein Arginin beschrieben werden, welches auf Grund der engen Nachbarschaft zum MCD-Kofaktor und zum Glutamat (PaoABC-EC692) am Prozess der Substratbindung beteiligt ist. Im Zusammenhang mit dem Austausch dieses Arginins gegen ein Histidin oder ein Lysin wurden die Enzymspezifität und der Einfluss physiologischer Bedingungen, wie pH und Ionenstärke, auf die Reaktion des Enzyms untersucht. Gegenüber dem Wildtyp zeigten die Varianten mit molekularem Sauerstoff eine geringere Affinität zum Substrat aber auch eine höhere Geschwindigkeit der Reaktion. Vor allem für die Histidin-Variante konnte im gesamten pH-Bereich ein instabiles Verhalten bestimmt werden. Der Grund dafür wurde durch das Lösen der Struktur der Histidin-Variante beschreiben. Durch den Austausch der Aminosäuren entfällt die stabilisierende Wirkung der delokalisierten Elektronen des Arginins und es kommt zu einer Konformationsänderung im aktiven Zentrum.
Neben der Reaktion von PaoABC mit einer Vielzahl aromatischer Aldehyde konnte auch der Umsatz von Salicylaldehyd zu Salicylsäure durch PaoABC in einer Farbreaktion bestimmt werden. Durch Ausschluss von molekularem Sauerstoff als terminaler Elektronenakzeptor, in einer enzym-gekoppelten Reaktion, erfolgte ein Elektronentransport auf Ferrocencarboxylsäure. Die Kombination aus beiden Methoden ermöglichte eine Verwendung von Ferrocen-Derivaten zur Generierung einer enzym-gekoppelten Reaktion mit PaoABC.
Die Untersuchungen zu PaoABC zeigen, dass die Vielfalt der durch das Enzym katalysierten Rektionen weitere Möglichkeiten der enzymatischen Bestimmung biokatalytischer Prozesse bietet.
STERILE APETALA (SAP) is known to be an essential regulator of flower development for over 20 years. Loss of SAP function in the model plant Arabidopsis thaliana is associated with a reduction of floral organ number, size and fertility. In accordance with the function of SAP during early flower development, its spatial expression in flowers is confined to meristematic stages and to developing ovules. However, to date, despite extensive research, the molecular function of SAP and the regulation of its spatio-temporal expression still remain elusive.
In this work, amino acid sequence analysis and homology modeling revealed that SAP belongs to the rare class of plant F-box proteins with C-terminal WD40 repeats. In opisthokonts, this type of F-box proteins constitutes the substrate binding subunit of SCF complexes, which catalyze the ubiquitination of proteins to initiate their proteasomal degradation. With LC-MS/MS-based protein complex isolation, the interaction of SAP with major SCF complex subunits was confirmed. Additionally, candidate substrate proteins, such as the growth repressor PEAPOD 1 and 2 (PPD1/2), could be revealed during early stages of flower development. Also INDOLE-3-BUTYRIC ACID RESPONSE 5 (IBR5) was identified among putative interactors. Genetic analyses indicated that, different from substrate proteins, IBR5 is required for SAP function. Protein complex isolation together with transcriptome profiling emphasized that the SCFSAP complex integrates multiple biological processes, such as proliferative growth, vascular development, hormonal signaling and reproduction. Phenotypic analysis of sap mutant and SAP overexpressing plants positively correlated SAP function with plant growth during reproductive and vegetative development.
Furthermore, to elaborate on the transcriptional regulation of SAP, publicly available ChIP-seq data of key floral homeotic proteins were reanalyzed. Here, it was shown that the MADS-domain transcription factors APETALA 1 (AP1), APETALA 3 (AP3), PISTILLATA (PI), AGAMOUS (AG) and SEPALLATA 3 (SEP3) bind to the SAP locus, which indicates that SAP is expressed in a floral organ-specific manner. Reporter gene analyses in combination with CRISPR/Cas9-mediated deletion of putative regulatory regions further demonstrated that the intron contains major regulatory elements of SAP in Arabidopsis thaliana.
In conclusion, these data indicate that SAP is a pleiotropic developmental regulator that acts through tissue-specific destabilization of proteins. The presumed transcriptional regulation of SAP by the floral MADS-domain transcription factors could provide a missing link between the specification of floral organ identity and floral organ growth pathways.
Untersuchungen zur Entwicklung und Synthese neuartiger Gelenkstäbe basierend auf Oligospiroketalen
(2019)
Totalsynthese benzoannellierter Sauerstoffheterocyclen durch Mikrowellen induzierte Tandem-Sequenzen
(2019)
The business model has emerged as a construct to understand how firms drive innovation through emerging technologies. It is defined as the ‘architecture of the firm’s value creation, delivery and appropriation mechanisms’ (Foss & Saebi, 2018, p. 5). The architecture is characterized by complex functional interrelations between activities that are conducted by various actors, some within and some outside of the firm. In other words, a firm’s value architecture is embedded within a wider system of actors that all contribute to the output of the value architecture.
The question of what drives innovation within this system and how the firm can shape and navigate this innovation is an essential question within innova- tion management research. This dissertation is a compendium of four individual research articles that examine how the design of a firm’s value architecture can fa- cilitate system-wide innovation in the context of Artificial Intelligence and Block- chain Technology. The first article studies how firms use Blockchain Technology to design a governance infrastructure that enables innovation within a platform ecosystem. The findings propose a framework for blockchain-enabled platform ecosystems that address the essential problem of opening the platform to allow for innovation while also ensuring that all actors get to capture their share of the value. The second article analyzes how German Artificial Intelligence startups design their business models. It identifies three distinct types of startup with dif- ferent underlying business models. The third article aims to understand the role of a firm’s value architecture during the socio-technical transition process of Arti- ficial Intelligence. It identifies three distinct ways in which Artificial Intelligence startups create a shared understanding of the technology. The last article exam- ines how corporate venture capital units configure value-adding services for their venture portfolios. It derives a taxonomy of different corporate venture capital types, driven by different strategic motivations.
Ultimately, this dissertation provides novel empirical insights into how a firm’s value architecture determines it’s role within a wider system of actors and how that role enables the firm to facilitate innovation. In that way, it contributes to both business model and innovation management literature.
The facilitation of species coexistence has been a central theme in ecological research for years, highlighting two key aspects: ecological niches and competition between species. According to the competitive exclusion principle, the overlap of species niches predicts the amount of shared resources and therefore competition between species, determining their ability to coexist. Only if niches of two species are sufficiently different, thus niche overlap is low, competition within species is higher than competition between species and stable coexistence is possible. Thereby, differences in species mean traits are focused on and conspecific individuals are assumed to be interchangeable. This approach might be outdated since behaviour, as a key aspect mediating niche differentiation between species, is individual based. Individuals from one species consistently differ across time and situations in their behavioural traits. Causes and consequences of consistent behavioural differences have been thoroughly investigated stimulating their recent incorporation into ecological interactions and niche theory. Spatial components have so far been largely overlooked, although animal movement is strongly connected to several aspects of ecological niches and interactions between individuals. Furthermore, numerous movement aspects haven been proven to be crucially influenced by consistent individual differences. Considering spatial parameters could therefore crucially broaden our understanding of how individual niches are formed and ecological interactions are shaped. Furthermore, extending established concepts on species interactions by an individual component could provide new insights into how species coexistence is facilitated and local biodiversity is maintained.
The main aim of this thesis was to test whether consistent inter-individual differences can facilitate the coexistence of ecological similar species. Therefore, the effects of consistent inter-individual differences on the spatial behaviour of two rodent species, the bank vole (Myodes glareolus) and the striped field mouse (Apodemus agrarius), were investigated and put in the context of: (i) individual spatial niches, (ii) interactions between species, and (iii) the importance of different levels of behavioural variation within species for their interactions. Consistent differences of study animals in boldness and exploration were quantified with the same tests in all presented studies and always combined with observations of movement and space use via automated VHF radio telemetry. Consequently, results are comparable throughout the thesis and the methods provide a common denominator for all chapters. The first two chapters are based on observations of free-ranging rodents in natural populations, while chapter III represents an experimental approach under semi-natural conditions.
Chapter I focusses on the effect of consistent differences in boldness and exploration on movement and space use of bank voles and their contribution to individual spatial niche separation. Results show boldness to be the dominating predictor for spatial parameters in bank voles. Irrespective of sex, bolder individuals had larger home ranges, moved longer distances, had less spatial interactions with conspecifics and occupied different microhabitats compared to shy individuals. The same boldness-dependent spatial patterns could be observed in striped field mice which is reported in chapter II. Therefore, both study species showed individual spatial niche occupation.
Chapter II builds on findings from the first chapter, investigating the effect of boldness driven individual spatial niche occupation on the interactions between species. Irrespective of species and sex, bolder individuals had more interspecific spatial interactions, but less intraspecific interactions, compared to shy individuals. Due to individual niches occupation the competitive environment individuals experience is not random. Interactions are restricted to individuals of similar behavioural type with presumably similar competitive ability, which could balance differences on the species level and support coexistence.
In chapter III the experimental populations were either comprised of only shy or only bold bank voles, while striped field mice varied, creating either a shy- or bold-biased competitive community. Irrespective of behavioural type, striped field mice had more intraspecific interactions in bold-biased competitive communities. Only in a shy-biased competitive community, bolder striped field mice had less interspecific interactions compared to shy individuals. Bank voles showed no difference in intra- or interspecific interactions between populations. Chapter III highlights, that not only consistent inter-individual differences per se are important for interactions within and between species, but also the amount of behavioural variation within coexisting species.
Overall, this thesis highlights the importance of considering consistent inter-individual differences in a spatial context and their connection to individual spatial niche occupation, as well as the resulting effects on interactions within and between species. Individual differences are discussed in the context of similarity of individuals, individual and species niche width, and individual and species niche overlap. Thereby, this thesis makes one step further from the existing research on individual niches towards integrating consistent inter-individual differences into the larger framework of species coexistence.
Infection on the move
(2019)
Movement plays a major role in shaping population densities and contact rates among individuals, two factors that are particularly relevant for disease outbreaks. Although any differences in movement behaviour due to individual characteristics of the host and heterogeneity in landscape structure are likely to have considerable consequences for disease dynamics, these mechanisms are neglected in most epidemiological studies. Therefore, developing a general understanding how the interaction of movement behaviour and spatial heterogeneity shapes host densities, contact rates and ultimately pathogen spread is a key question in ecological and epidemiological research.
In my thesis, I address this gap using both theoretical and empirical modelling approaches. In the theoretical part of my thesis, I investigated bottom-up effects of individual movement behaviour and landscape structure on host density, contact rates, and ultimately disease dynamics. I extended an established agent-based model that simulates ecological and epidemiological key processes to incorporate explicit movement of host individuals and landscape complexity. Neutral landscape models are a powerful basis for spatially-explicit modelling studies to imitate the complex characteristics of natural landscapes. In chapter 2, the first study of my thesis, I introduce two complementary R packages, NLMR and landscapetools, that I have co-developed to simplify the workflow of simulation and customization of such landscapes. To demonstrate the use of the packages I present a case study using the spatially explicit eco-epidemiological model and show that landscape complexity per se increases the probability of disease persistence. By using simple rules to simulate explicit host movement, I highlight in chapter 3 how disease dynamics are affected by population-level properties emerging from different movement rules leading to differences in the realized movement distance, spatiotemporal host density, and heterogeneity in transmission rates. As a consequence, mechanistic movement decisions based on the underlying landscape or conspecific competition led to considerably higher probabilities than phenomenological random walk approaches due directed movement leading to spatiotemporal differences in host densities. The results of these two chapters highlight the need to explicitly consider spatial heterogeneity and host movement behaviour when theoretical approaches are used to assess control measures to prevent outbreaks or eradicate diseases.
In the empirical part of my thesis (chapter 4), I focus on the spatiotemporal dynamics of Classical Swine Fever in a wild boar population by analysing epidemiological data that was collected during an outbreak in Northern Germany persisting for eight years. I show that infection risk exhibits different seasonal patterns on the individual and the regional level. These patterns on the one hand show a higher infection risk in autumn and winter that may arise due to onset of mating behaviour and hunting intensity, which result in increased movement ranges. On the other hand, the increased infection risk of piglets, especially during the birth season, indicates the importance of new susceptible host individuals for local pathogen spread. The findings of this chapter underline the importance of different spatial and temporal scales to understand different components of pathogen spread that can have important implications for disease management.
Taken together, the complementary use of theoretical and empirical modelling in my thesis highlights that our inferences about disease dynamics depend heavily on the spatial and temporal resolution used and how the inclusion of explicit mechanisms underlying hosts movement are modelled. My findings are an important step towards the incorporation of spatial heterogeneity and a mechanism-based perspective in eco-epidemiological approaches. This will ultimately lead to an enhanced understanding of the feedbacks of contact rates on pathogen spread and disease persistence that are of paramount importance to improve predictive models at the interface of ecology and epidemiology.
Selenite pseudomorphs
(2019)
Collagen is the most abundant protein in mammals. In many tissues, collagen molecules assemble to form a hierarchical structure. In the smallest supramolecular unit, named fibril, each molecule is displaced in the axial direction with respect to its neighbors. This staggering creates a periodic gap and overlap regions, where the gap regions exhibit 20% less density. These fibril-forming collagens play an essential role in the strength of connective tissues. Despite much effort, directed at understanding collagen function and regulation, the influence of the chemical environment on the local structural and mechanical properties remains poorly understood. Recent studies, aimed at elucidating the effect of osmotic pressure, showed that collagen contracts upon water removal. This observation highlights the importance of water for the stabilization and mechanics of the collagen molecule.
Using collagen mimetic peptides (CMPs), which fold into triple helical structures reminiscent of natural collagen, the primary goal of this work was to investigate the effect of the osmotic pressure on specific collagen-mimetic sequences. CMPs were used as the model system as they provide sequence control, which is essential for discriminating local from global structural changes and for relating the observed effects to existing knowledge about the full-length collagen molecule. Of specific interest was the structure of individual collagen triple helices as well as their organization into self-assembled higher order structures. These key structural features were monitored with infrared spectroscopy (IR) and synchrotron X-ray scattering, while varying the osmotic pressure. For controlling the osmotic pressure, CMP powder samples were incubated in air of defined relative humidity, ranging from dry conditions to highly “humid”. In addition, to obtain more biologically relevant conditions, the CMPs were measured in ultrapure water and in solutions containing small molecule osmolytes.
Using the sequences (Pro-Pro-Gly)10, (Pro-Hyp-Gly)10 and (Hyp-Hyp-Gly)10, it was shown that CMPs with different degrees of proline hydroxylation (Hyp = hydroxyproline) exhibit a sequence-specific response to osmotic pressure. IR spectroscopy revealed that osmotic pressure changes affect the strength of the triple helix stabilizing, interchain hydrogen bond and that the extent of this change depends on the degree of hydroxylation. X-ray scattering experiments further showed that changes in osmotic pressure affect both the molecular length as well as the higher order organization of CMPs. Starting from a pseudo-hexagonal packing in the dry state, all three CMPs showed isotropic swelling when increasing the water content to approximately 1.2 water molecules per amino acid, again to different extents depending on the degree of hydroxylation. When increasing the water content further, this pseudo-hexagonal arrangement breaks down. In the fully hydrated state, each CMP is characterized by its own specific and more complex packing geometry.
While these changes in the lateral packing arrangement suggest swelling upon hydration, an overall decrease of the molecular length (i.e. contraction) was observed in the axial direction. Also for this structural feature, a strong dependency on the specific amino acid sequence was found. Interestingly, the observed contraction is the opposite of what has been reported for natural collagen. As (Pro-Pro-Gly)n, (Pro-Hyp-Gly)n and (Hyp-Hyp-Gly)n repeat units are found in collagen with a relatively high abundance, this suggests that other collagen sequence fragments need to respond to hydration in the opposite way to obtain a net elongation of the full-length collagen molecule.
To test this hypothesis, sequences predicted to be sensitive to osmotic pressure were considered. One such sequence, consisting of two repeat units (Ala-Arg-Gly-Ser-Asp-Gly), was inserted as a guest into a (Pro-Pro-Gly) host. When compared to the canonical CMP sequences investigated earlier, the lateral helix packing follows a similar trend with increasing hydration; however, the host-guest CMP axially elongates with increasing water content. This behavior is more similar to what has been found for natural collagen and suggests that different sequences do determine the molecular length of collagen sequences differently. Interestingly, the canonical sequences are more abundant in the overlap region while the guest sequence is found in the gap region. This allows to speculate that sequences in the gap and overlap regions possess a specifically fine-tuned local response to osmotic pressure changes. Clearly, more experiments with additional sequences are needed to confirm this.
In conclusion, the results obtained in this work indicate a highly sequence specific interaction between collagen and water. Osmotic pressure-induced conformational changes mostly originate from local geometries and bonding patterns and affect both the structure of individual triple helices as well as higher order assemblies. One key remaining question is how these conformational changes affect the local mechanical properties of the collagen molecule. As a first step, the stiffness (persistence length) of full-length collagen was determined using atomic force microscopy. In the future, experimental strategies need to be developed that allow for investigating the mechanical properties of specific collagen sequences, e.g. performing single-molecule force spectroscopy of CMPs.
Alexander Rhode investigates performance-oriented measures of Contracting Authorities in public tenders conducted within the EU. He finds that Contracting Authorities can improve their performance and attract more suppliers by publishing (as precise as possible) starting prices in the beginning of a tender. First, he reports that compared with private-sector negotiations, starting prices do not create entry barriers in public procurement. Second, he finds that increased numerical precision of starting prices is linearly correlated with better performance and a higher number of bids. In public procurement, suppliers tend to attribute increased credibility to precise starting prices which reduces their (perceived) entry risks.
ATP-binding cassette (ABC) transporters are present in all kingdoms of life and enable active transport of various different molecules across biological membranes. They all share an overall architecture of two lipophilic transmembrane spanning domains (TMDs) traversing the membrane and two hydrophilic nucleotide binding domains (NBDs) usually lacking sequence identity. The multiplicity in transported molecules is accompanied by extreme diversity in TMDs. Human mitochondria harbor four ABC transporters, namely ABCB6, ABCB7, ABCB8 and ABCB10 with functional homologues in yeast and plants. Except the ones found in Rickettsiae and related bacteria mitochondrial ABC transporters are absent in bacteria. In addition to converting energy mitochondria are important platforms for biosynthesizing various cofactors as iron sulfur clusters, molybdenum cofactor (Moco) or heme. ABCB7 (Atm1 in yeast) has been shown to connect mitochondrial with cytosolic iron sulfur cluster assembly by exporting a yet unknown sulfur containing molecule. In addition, TMDs of Atm1 display a glutathione binding pocket accessible from the matrix which has been identified in all ABCB7-like transporters and also exists in a bacterial ABC transporter homologue of Atm1 in Novosphingobium aromaticivorans. In addition, ATM3, a plant mitochondrial homologous ABC transporter to human ABCB7, has been associated with biosynthesizing Moco.
In this study we used the α-proteobacterium Rhodobacter capsulatus as a model organism to characterize mitochondrial ABC transporter homologues. R. capsulatus contains two homologues to mitochondrial ABC transporters with the corresponding gene loci rcc03139 and rcc02305. They share 38 to 47 % sequence identities to human mitochondrial ABC transporters ABCB8/ABCB10 and ABCB7/ABCB6, respectively. We created interposon mutants lacking either rcc03139 or rcc02305, analyzed the physiological effects on R. capsulatus and compared the findings especially to eukaryotic deletion studies. A viable bacterial double mutant strain lacking both mitochondrial ABC transporters was constructed to investigate possible overlapping functions. Both R. capsulatus single mutants showed a severe accumulation of intracellular reactive oxygen species (ROS) in comparison to ∆nifDK which revealed to be additive in the double mutant. In the proteome of ∆rcc03139I abundancies of tetrapyrrole related proteins were significantly increased in comparison to the proteome of parental strain, which was further validated by reduced amounts of tetrapyrrole intermediates in ∆rcc03139. In contrast, in ∆rcc02305I total glutathione (GSH) was elevated when endogenous GSH biosynthesis was inhibited. In conjunction with proteomic studies we uncovered misbalanced sulfur distribution in ∆rcc02305I. Furthermore, strains lacking Rcc02305 accumulated cyclic pyranopterin monophosphate (cPMP), an intermediate of Moco biosynthesis, as it was already shown for the deletion strain of the eukaryotic counterpart ATM3 in plants. In contrast single mutant strain Δrcc03139I neither accumulated cPMP nor glutathione.
Bioinformatic analysis of the amino acid sequence of Rcc02305 revealed a pyridoxal 5´phosphate (PLP) binding site which overlaps with Walker A within the NBDs of Rcc02305 and other ABCB7-like transporters. The PLP cofactor is well studied in C-DES (L-cysteine/cystine lyase from Synechocystis) for persulfide production and in L-cysteine desulfurases such as IscS and NFS1 for its role in formation of protein-bound persulfides. Based on our findings we are able to propose a new modality for the transport of the sulfur containing molecule: first of all, the transporter produces a highly reactive persulfide which is then subsequently trapped by glutathione polysulfide, already bound within the binding pocket in TMDs. Walker A becomes accessible for ATP and after hydrolysis the mixed polysulfide is released.
Based on our studies we are convinced that both mitochondrial ABC transporter homologues fulfil distinct roles in R. capsulatus: Rcc02305 is a representative of Atm1/ABCB7-like transporters and important for proper sulfur distribution by exporting persulfides. In contrast Rcc03139 is a representative of ABCB6/ABCB10 related transporters and involved in biosynthesizing tetrapyrroles.
Autour de 1990 en France et de 2005 en Allemagne, deux nouvelles catégories sont introduites dans le champ de la statistique de la population. Toutes deux, « immigré » et « Person mit Migrationshintergrund », font appel au registre de la migration pour qualifier un groupe de population. Notre analyse montre que ces deux événements sont révélateurs d’un changement de signification des catégorisations statistiques de la migration dans les deux pays, de la description de la mobilité vers l’observation de l’altérité de la population, changement lié au contexte de la politique publique dite d’« intégration » qui se développe en France et en Allemagne dans les années 1990-2000. La thèse interroge ainsi la manière dont la statistique rend la migration socialement pertinente pour construire l’altérité. Pour pouvoir comprendre le virage entrepris dans les nomenclatures statistiques et le resituer dans une perspective de longue durée, nous avons postulé qu’il fallait aller chercher dans l’histoire de la statistique ce qui avait tenu lieu de classification principale de la population, en lieu et place des nouvelles catégories inventées au tournant des XXe et XXIe siècles. Nous nous sommes donc interrogée sur la genèse et l’institutionnalisation des catégories de l’altérité et de la mobilité dans la période 1880-1914, alors que la France et l’Allemagne, à l’époque le Deutsches Kaiserreich, se constituent en États-nations et en empires coloniaux. Pour observer ces processus empiriquement, nous avons choisi de comparer les pratiques de catégorisation de l’altérité et la mobilité (1) en France et en Allemagne, (2) à deux périodes différentes, 1880-1914 et 1990-2010, et (3) dans le contexte métropolitain et colonial. L’analyse socio-historique comparée d’après la méthodologie de la comparaison en contexte a reposé sur une asymétrie assumée entre les deux périodes étudiées : tandis qu’il s’agissait de reconstruire la genèse des catégories « immigré » et « Person mit Migrationshintergrund » à deux moments distincts temporellement en France et en Allemagne, l’analyse de la période 1880-1914 a consisté à mettre au jour ruptures et continuités historiques des principes de classification sur l’ensemble de la période dans une perspective croisée. La démarche n’est ni chronologique ni rétrospective : elle contraste deux configurations historiques pour tenter d’identifier des ressemblances et des différences. Nos résultats montrent qu’entre 1880 et 1914, la catégorie de migration est majoritairement associée à un phénomène de mobilité dans les discours politiques et statistiques. À cette époque, la focale se porte sur l’émigration, redéfinie comme un déplacement géographique en dehors des frontières de la nation et de l’Empire. Le transport des « émigrants », catégorie de population qui nourrit le débat et les tableaux statistiques, fait l’objet des problématisations politiques. Les statistiques relatives à l’émigration comme mobilité étaient alors séparées de l’observation de la composition de la population, à travers le critère de la nationalité dans le contexte métropolitain et des schémas « raciaux » dans le contexte colonial. En 1990 en France et 2005 en Allemagne, le registre de la migration est mobilisé cette fois pour observer statistiquement la composition de la population. Nos résultats ont permis de mettre au jour trois principes de construction de l’altérité dans les deux pays et dans les deux périodes étudiées : un principe national, un principe colonial et un principe migratoire. La thèse développe ainsi une approche renouvelée des interactions entre observation statistique et politique publique, en testant empiriquement sur le terrain des statistiques relatives à la migration l’hypothèse de la « circularité du savoir et de l’action » mise au point par Alain Desrosières
Parlamentarier als Beruf
(2019)
Die politische Professionalisierung hat innerhalb der institutionellen Rahmenbedingungen zur Sozialfigur des Berufspolitikers geführt. Diese Entwicklung wird im theoretischen Teil der Arbeit hergeleitet und im empirischen Teil mit umfangreichen Daten belegt. Bemerkenswert ist, dass es dabei nicht zu erheblichen Veränderungen in den Rekrutierungsmustern und Karriereverläufen der Abgeordneten gekommen ist. Vielmehr erweisen sich die von Dietrich Herzog herausgearbeiteten Karrieretypen auch heute noch als gültig und mussten nur moderat angepasst werden. Es zeigt sich damit eine erstaunliche Kontinuität in der politischen Elitenbildung. Die in Deutschland sehr gefestigten institutionellen Rahmenbedingungen, die den Zugang und die Attraktivität politischer Karrieren determinieren, haben offensichtlich auch zu einer Stabilisierung der Karrieretypen geführt.