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The emerging threat of antibiotic-resistant bacteria has become a global challenge in the last decades, leading to a rising demand for alternative treatments for bacterial infections. One approach is to target the bacterial cell envelope, making understanding its biophysical properties crucial. Specifically, bacteriophages use the bacterial envelope as an entry point to initiate infection, and they are considered important building blocks of new antibiotic strategies against drug-resistant bacteria.. Depending on the structure of the cell wall, bacteria are classified as Gram-negative and Gram-positive. Gram-negative bacteria are equipped with a complex cell envelope composed of two lipid membranes enclosing a rigid peptidoglycan layer. The synthesis machinery of the Gram-negative cell envelope is the target of antimicrobial agents, including new physical sanitizing procedures addressing the outer membrane (OM). It is therefore very important to study the biophysical properties of the Gram-negative bacterial cell envelope. The high complexity of the Gram-negative OM sets the demand for a model system in which the contribution of individual components can be evaluated separately. In this respect, giant unilamellar vesicles (GUVs) are promising membrane systems to study membrane properties while controlling parameters such as membrane composition and surrounding medium conditions.
The aim of this work was to develop methods and approaches for the preparation and characterization of a GUV-based membrane model that mimics the OM of the Gram-negative cell envelope. A major component of the OM is the lipopolysaccharide (LPS) on the outside of the OM heterobilayer. The vesicle model was designed to contain LPS in the outer leaflet and lipids in the inner leaflet. Furthermore, the interaction of the prepared LPS-GUVs with bacteriophages was tested. LPS containing GUVs were prepared by adapting the inverted emulsion technique to meet the challenging properties of LPS, namely their high self-aggregation rate in aqueous solutions. Notably, an additional emulsification step together with the adaption of solution conditions was employed to asymmetrically incorporate LPS containing long polysaccharide chains into the artificial membranes. GUV membrane asymmetry was verified with a fluorescence quenching assay. Since the necessary precautions for handling the quenching agent sodium dithionite are often underestimated and poorly described, important parameters were tested and identified to obtain a stable and reproducible assay. In the context of varied LPS incorporation, a microscopy-based technique was introduced to determine the LPS content on individual GUVs and to directly compare vesicle properties and LPS coverage. Diffusion coefficient measurements in the obtained GUVs showed that increasing LPS concentrations in the membranes resulted in decreased diffusivity.
Employing LPS-GUVs we could demonstrate that a Salmonella bacteriophage bound with high specificity to its LPS receptor when presented at the GUV surface, and that the number of bound bacteriophages scaled with the amount of presented LPS receptor. In addition to binding, the bacteriophages were able to eject their DNA into the vesicle lumen. LPS-GUVs thus provide a starting platform for bottom-up approaches for the generation of more complex membranes, in which the effects of individual components on the membrane properties and the interaction with antimicrobial agents such as bacteriophages could be explored.
Shape change is a fundamental process occurring in biological tissues during embryonic development and regeneration of tissues and organs. This process is regulated by cells that are constrained within a complex environment of biochemical and physical cues. The spatial constraint due to geometry has a determining role on tissue mechanics and the spatial distribution of force patterns that, in turn, influences the organization of the tissue structure. An understanding of the underlying principles of tissue organization may have wide consequences for the understanding of healing processes and the development of organs and, as such, is of fundamental interest for the tissue engineering community.
This thesis aims to further our understanding of how the collective behaviour of cells is influenced by the 3D geometry of the environment. Previous research studying the role of geometry on tissue growth has mainly focused either on flat surfaces or on substrates where at least one of the principal curvatures is zero. In the present work, tissue growth from MC3T3-E1 pre-osteoblasts was investigated on surfaces of controlled mean curvature.
One key aspect of this thesis was the development of substrates of controlled mean curvature and their visualization in 3D. It was demonstrated that substrates of controlled mean curvature suitable for cell culture can be fabricated using liquid polymers and surface tension effects.
Using these substrates, it was shown that the mean surface curvature has a strong impact on the rate of tissue growth and on the organization of the tissue structure. It was thereby not only demonstrated that the amount of tissue produced (i.e. growth rates) by the cells depends on the mean curvature of the substrate but also that the tissue surface behaves like a viscous fluid with an equilibrium shape governed by the Laplace-Young-law. It was observed that more tissue was formed on highly concave surfaces compared to flat or convex surfaces.
Motivated by these observations, an analytical model was developed, where the rate of tissue growth is a function of the mean curvature, which could successfully describe the growth kinetics. This model was also able to reproduce the growth kinetics of previous experiments where tissues have been cultured in straight-sided prismatic pores.
A second part of this thesis focuses on the tissue structure, which influences the mechanical properties of the mature bone tissue. Since the extracellular matrix is produced by the cells, the cell orientation has a strong impact on the direction of the tissue fibres. In addition, it was recently shown that some cell types exhibit collective alignment similar to liquid crystals.
Based on this observation, a computational model of self-propelled active particles was developed to explore in an abstract manner how the collective behaviour of cells is influenced by 3D curvature. It was demonstrated that the 3D curvature has a strong impact on the self-organization of active particles and gives, therefore, first insights into the principles of self-organization of cells on curved surfaces.
"Wortabruf im Handumdrehen"?
(2017)
Participation has become an orthodoxy in the field of development, an essential element of projects and programmes. This book analyses participation in development interventions as an institutionalised expectation – a rationalized myth – and examines how organisations on different levels of government process it. At least two different objectives of participation are appropriate and legitimate for international organisations in the field: the empowerment of local beneficiaries and the achievement of programme goals. Both integrate participatory forums into the organisational logic of development interventions. Local administrations react to the institutionalised expectation with means-ends decoupling, where participatory forums are implemented superficially but de facto remain marginalised in local administrative processes and activities. The book furthermore provides a thick description of the organisationality of participation in development interventions. Participatory forums are shown to be a form of partial organisation. They establish an order in the relationship between administrations and citizens through the introduction of rules and the creation of a defined membership. At the same time, this order is found to be fragile and subject to criticism and negotiation.
"Vorübergehende" Leiharbeit
(2018)
Leiharbeit ist aus dem modernen Arbeitsleben nicht mehr wegzudenken. Von besonderer Bedeutung für Entleiher und Leiharbeitnehmer waren und sind seit jeher die zeitliche Limitierung von Leiharbeit. Die Unbestimmtheit des durch die Leiharbeitsrichtlinie eingeführten Merkmals der »vorübergehenden« Dauer von Leiharbeit hat in Literatur und Rechtsprechung viele Meinungen hervorgerufen. Rechtssicherheit haben all diese nicht gebracht. Der Autor widmet sich der Herkunft und Bedeutung des Begriffs der vorübergehenden Dauer und bietet ein grundrechts- und unionsrechtskonformes Lösungsmodell zum Verständnis und Umgang mit diesem Merkmal. Die gefundenen Ergebnisse überträgt er auf die AÜG-Novelle von 2017.
Anhand des religiösen Selbstverständnisses der Kirchen und des darauf beruhenden Begriffs der »Dienstgemeinschaft« untersucht der Autor Zulässigkeit und Grenzen der Leiharbeit in kirchlichen Einrichtungen. Er empfiehlt die Schaffung von Regelwerken zur Einhaltung kirchlicher Loyalitätspflichten.
"Seid mutig und aufrecht!"
(2016)
Der 'Centralverein deutscher Staatsbürger jüdischen Glaubens' (C.V.) wurde 1893 in Berlin gegründet. Sein Tätigkeitsschwerpunkt lag ursprünglich auf dem Gebiet des Rechtsschutzes gegen antisemitische Diskriminierungen. Eine zweite Säule seiner Arbeit war die Aufklärung der Nichtjuden über das 'wahre Wesen' des Judentums. Johann Nicolai analysiert in diesem Band unter Auswertung der Moskauer Archivbestände die Entwicklung des Vereins von 1933 bis zu seiner Auflösung im Jahr 1938. Im Mittelpunkt der Studie steht die Frage, wie der Centralverein die Fortsetzung seiner Arbeit gegenüber seinen Mitgliedern begründete, obwohl im Nationalsozialismus die grundlegenden Bürgerrechte für die deutschen Juden, die er ursprünglich verteidigen wollte, nicht mehr gewährleistet waren. Ein besonderer Fokus liegt auf der Wandlung des Centralvereins nach den Nürnberger Gesetzen und der darauf erfolgten Umbenennung und Umstrukturierung. Wesentlicher Bestandteil ist auch die Auseinandersetzung mit der jüdischen Emigration nach Übersee. Nicolai zeigt auf, dass es bis tief in die 1930er-Jahre hinein starke Spannungen im deutschen Judentum gab.
"Il Gattopardo" nella DDR
(2023)
Sulla base di materiale d'archivio inedito si ripercorre l'avvincente storia della prima edizione del Gattopardo nella DDR (1961). È qui analizzata la corsa ad ostacoli del romanzo tra congruenze ed eccezioni che assume i tratti di un giallo letterario. L'opera di un principe defunto scavalca il Muro grazie ad Alfred Kurella, potente funzionario della SED. Nella sua postfazione Il Gattopardo non è canto della decadenza, ma preannuncio di una nuova epoca, manifesto dello Stato in procinto di entrare nell'era socialista. La chiave di lettura è un unicum con una marcata impronta ideologica che ne determina prima la fortuna e poi l'isolamento. Al Gattopardo nella Germania Est Bernardina Rago dà per la prima volta voce.
"Der unterirdische Kampf"
(2016)
Die militärische Rüstungsbürokratie zwischen Niederlage des Deutschen Kaiserreiches und ›Totalem Krieg‹ der NS-Diktatur – in dieses Spannungsverhältnis begibt sich der Autor. Er untersucht, wie die Fachleute des Wehrwirtschafts- und Rüstungsamtes die Mobilisierung planten – und dabei scheiterten.
Bereits kurze Zeit nach der deutschen Niederlage von 1918 wurden die wirtschaftlichen Aspekte der Kriegführung wieder von einem kleinen, hochprofessionellen Offizierskreis diskutiert. Sie nahmen Gedanken aus der Zeit des Ersten Weltkrieges auf und forderten in der Reichswehr und noch stärker in der Wehrmacht die Steuerungshoheit des Militärs über die kriegsrelevante Wirtschaft. Ihre Planungen und Maßnahmen waren nicht nur im Offizierkorps selbst umstritten, sondern unterlagen letztlich auch den Widerständen der Privatwirtschaft und den Interessen von NS-Parteigrößen. Entlang dieser Fronten beschreibt der Autor eine militärische Organisation von ihrem Aufbau 1924 bis zu ihrer ›Zerschlagung‹ durch Albert Speer 1942. Dabei nimmt er auch das alles andere als eindeutige Verhalten des Führungspersonals im Amt in den Blick.