Intelligente Drug-Delivery-Systeme zur Vermeidung Implantat-assoziierter Infektionen

All medical devices and implants are made of synthetic or natural, but usually not endogenous, materials. Implantation of such devices, into living tissue, is therefore subject to the risk of nosocomial infections, biofilm formation and may cause implant-associated infections. Microorganisms (including bacteria) that grow in biofilms and cause chronic inflammation are the typical source of these infections. Subsequently, they can lead to implant failure, requiring further surgical treatments. To prevent this, this study investigated and presented enzymatically degradable drug delivery systems that enable encapsulation and targeted release of an antibacterial agent triggered by an infection. To achieve this, the dissertation focused on the fabrication, characterization of suitable nanocarriers and their immobilization on implant surfaces such as titanium. To build a stable and degradable encapsulation system, different steps were established: 1) the integration of an enzyme-labile model peptide into two different polymer-based systems 2) generation of particles 3) coating of titanium surfaces with the particles 4) investigation of stability and degradability of those systems 5) the release of ciprofloxacin as a model substance. For this, two approaches have been tested. The first approach included the synthesis of chitosan‐g‐[peptide‐poly‐L‐caprolactone] and its self‐assembly into polymeric vesicles by the solvent shift method. For the second approach, nanogels dispersions were prepared by ionotropic gelation of the alginate with the poly-L-lysine, which was conjugated with ciprofloxacin via a copper-free 1,3-dipolar cycloaddition (click reaction).Alle medizinischen Geräte und Implantate bestehen aus synthetischen oder natürlichen, jedoch in der Regel aus nicht endogenen Materialien. Die Implantation solcher Geräte in lebendes Gewebe unterliegt daher dem Risiko nosokomialer Infektionen und der Bildung von Biofilmen und kann implantatassoziierte Infektionen verursachen. Mikroorganismen (einschließlich Bakterien), die in Biofilmen wachsen und chronische Entzündungen verursachen, sind die typische Quelle dieser Infektionen. Anschließend können sie zu einem Implantatversagen führen, was weitere chirurgische Behandlungen erforderlich macht. Um dies zu verhindern, untersuchte und ergab diese Studie enzymatisch abbaubare Arzneimittelabgabesysteme, die die Einkapselung und gezielte Freisetzung eines durch eine Infektion ausgelösten antibakteriellen Mittels ermöglichen. Um dies zu erreichen, konzentrierte sich die Dissertation auf die Herstellung und Charakterisierung geeigneter Nanoträger sowie deren Immobilisierung auf Implantatoberflächen wie Titan. Um ein stabiles und abbaubares Einkapselungssystem aufzubauen, wurden verschiedene Schritte festgelegt: 1) Integration eines enzymlabilen Modellpeptids in zwei verschiedene Systeme auf Polymerbasis 2) Erzeugung von Partikeln 3) Beschichtung von Titanoberflächen mit den Partikeln 4) Untersuchung von Stabilität und Abbaubarkeit dieser Systeme 5) Freisetzung von Ciprofloxacin als Modellsubstanz. Hierzu wurden zwei Ansätze getestet. Der erste Ansatz umfasste die Synthese von Chitosan-g-[Peptid-Poly-ε-Caprolacton] und dessen Selbstorganisation zu polymeren Vesikeln durch das Lösungsmittel-Verschiebungsverfahren. Für den zweiten Ansatz wurden Nanogeldispersionen durch ionotrope Gelierung des Alginats mit dem Poly-L-Lysin hergestellt, das über eine kupferfreie 1,3-dipolare Cycloaddition (Klickreaktion) mit Ciprofloxacin konjugiert wurde

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An incremental prototyping methodology for distributed systems based on formal specifications

This thesis presents a new incremental prototyping methodology for formally specified distributed systems. The objective of this methodology is to fill the gap which currently exists between the phase where a specification is simulated, generally using some sequential logical inference tool, and the phase where the modeled system has a reliable, efficient and maintainable distributed implementation in a main-stream object-oriented programming language. This objective is realized by application of a methodology we call Mixed Prototyping with Object-Orientation (in short: OOMP). This is an extension of an existing approach, namely Mixed Prototyping, that we have adapted to the object-oriented paradigm, of which we exploit the flexibility and inherent capability of modeling abstract entities. The OOMP process proceeds as follows. First, the source specifications are automatically translated into a class-based object-oriented language, thus providing a portable and high-level initial implementation. The generated class hierarchy is designed so that the developer may independently derive new sub-classes in order to make the prototype more efficient or to add functionalities that could not be specified with the given formalism. This prototyping process is performed incrementally in order to safely validate the modifications against the semantics of the specification. The resulting prototype can finally be considered as the end-user implementation of the specified software. The originality of our approach is that we exploit object-oriented programming techniques in the implementation of formal specifications in order to gain flexibility in the development process. Simultaneously, the object paradigm gives the means to harness this newly acquired freedom by allowing automatic generation of test routines which verify the conformance of the hand-written code with respect to the specifications. We demonstrate the generality of our prototyping scheme by applying it to a distributed collaborative diary program within the frame of CO-OPN (Concurrent Object-Oriented Petri Nets), a very powerful specification formalism which allows expressing concurrent and non-deterministic behaviours, and which provides structuring facilities such as modularity, encapsulation and genericity. An important effort has also been accomplished in the development or adaptation of distributed algorithms for cooperative symbolic resolution. These algorithms are used in the run-time support of the generated CO-OPN prototypes

Occupy: A People Yet To Come

The term Occupy represents a belief in the transformation of the capitalist system through a new heterogenic world of protest and activism that cannot be conceived in terms of liberal democracy, parliamentary systems, class war or vanguard politics. These conceptualisations do not articulate where power is held, nor from where transformation may issue. This collection of essays by world-leading scholars of Deleuze and Guattari examines how capitalism can be understood as a global abstract machine whose effects pervade all of life and how Occupy can be framed as a response to this as a heterogenic movement based on new tactics, revitalised democratic processes and nomadic systems of organisation. Seeing the question as a political tactic aimed at delegitimizing their protest, Occupiers refused to answer the question ‘what do you want?’, produce manifestos, elect leaders or act as a vanguard. Occupy: A People Yet to Come goes some considerable way towards providing the terms upon which this refusal can be understood within a changed landscape of political activism and the rewriting of the conventions of political protest. Including essays by Claire Colebrook, Giuseppina Mecchia, John Protevi, Rodrigo Nunes, Verena Andermatt Conley, Nicholas Thoburn, Ian Buchanan, David Burrows, Eugene Holland and Andrew Conio, the volume examines the economic predicates of capitalist economics: liberal democracy and its alternatives, the conjugation of protest and aesthetics, how occupy experiments with different types of leadership and how power, hierarchies and resistance might be understood using Deleuze and Guattari’s radical conceptualizations of debt; subjectivity, the minor and the molecular, occupation, dispersed leadership, territory, smooth space and the war machine

Covid Conspiracy Theories in Global Perspective

Covid Conspiracy Theories in Global Perspective examines how conspiracy theories and related forms of misinformation and disinformation about the Covid-19 pandemic have circulated widely around the world. Covid conspiracy theories have attracted considerable attention from researchers, journalists, and politicians, not least because conspiracy beliefs have the potential to negatively affect adherence to public health measures. While most of this focus has been on the United States and Western Europe, this collection provides a unique global perspective on the emergence and development of conspiracy theories through a series of case studies. The chapters have been commissioned by recognized experts on area studies and conspiracy theories. The chapters present case studies on how Covid conspiracism has played out (some focused on a single country, others on regions), using a range of methods from a variety of disciplinary perspectives, including history, politics, sociology, anthropology, and psychology. Collectively, the authors reveal that, although there are many narratives that have spread virally, they have been adapted for different uses and take on different meanings in local contexts. This volume makes an important contribution to the rapidly expanding field of academic conspiracy theory studies, as well as being of interest to those working in the media, regulatory agencies, and civil society organizations, who seek to better understand the problem of how and why conspiracy theories spread

Covid Conspiracy Theories in Global Perspective

Covid Conspiracy Theories in Global Perspective examines how conspiracy theories and related forms of misinformation and disinformation about the Covid-19 pandemic have circulated widely around the world. Covid conspiracy theories have attracted considerable attention from researchers, journalists, and politicians, not least because conspiracy beliefs have the potential to negatively affect adherence to public health measures. While most of this focus has been on the United States and Western Europe, this collection provides a unique global perspective on the emergence and development of conspiracy theories through a series of case studies. The chapters have been commissioned by recognized experts on area studies and conspiracy theories. The chapters present case studies on how Covid conspiracism has played out (some focused on a single country, others on regions), using a range of methods from a variety of disciplinary perspectives, including history, politics, sociology, anthropology, and psychology. Collectively, the authors reveal that, although there are many narratives that have spread virally, they have been adapted for different uses and take on different meanings in local contexts. This volume makes an important contribution to the rapidly expanding field of academic conspiracy theory studies, as well as being of interest to those working in the media, regulatory agencies, and civil society organizations, who seek to better understand the problem of how and why conspiracy theories spread

Authoritarian Populism and the Rural World

The rise of authoritarian, nationalist forms of populism and the implications for rural actors and settings is one of the most crucial foci for critical agrarian studies today, with many consequences for political action. Authoritarian Populism and the Rural World reflects on the rural origins and consequences of the emergence of authoritarian and populist leaders across the world, as well as on the rise of multi-class mobilisation and resistance, alongside wider counter-movements and alternative practices, which together confront authoritarianism and nationalist populism. The book includes 20 chapters written by contributors to the Emancipatory Rural Politics Initiative (ERPI), a global network of academics and activists committed to both reflective analysis and political engagement. Debates about ‘populism’, ‘nationalism’, ‘authoritarianism’ and more have exploded recently, but relatively little of this has focused on the rural dimensions. Yet, wherever one looks, the rural aspects are key – not just in electoral calculus, but in understanding underlying drivers of authoritarianism and populism, and potential counter-movements to these. Whether because of land grabs, voracious extractivism, infrastructural neglect or lack of services, rural peoples’ disillusionment with the status quo has had deeply troubling consequences and occasionally hopeful ones, as the chapters in this book show. The chapters in this book were originally published in The Journal of Peasant Studies

Occupy: A people yet to come

The term Occupy represents a belief in the transformation of the capitalist system through a new heterogenic world of protest and activism that cannot be conceived in terms of liberal democracy, parliamentary systems, class war or vanguard politics. These conceptualisations do not articulate where power is held, nor from where transformation may issue. This collection of essays by world-leading scholars of Deleuze and Guattari examines how capitalism can be understood as a global abstract machine whose effects pervade all of life and how Occupy can be framed as a response to this as a heterogenic movement based on new tactics, revitalised democratic processes and nomadic systems of organisation. Seeing the question as a political tactic aimed at delegitimizing their protest, Occupiers refused to answer the question ‘what do you want?’, produce manifestos, elect leaders or act as a vanguard. Occupy: A People Yet to Come goes some considerable way towards providing the terms upon which this refusal can be understood within a changed landscape of political activism and the rewriting of the conventions of political protest.Including essays by Claire Colebrook, Giuseppina Mecchia, John Protevi, Rodrigo Nunes, Verena Andermatt Conley, Nicholas Thoburn, Ian Buchanan, David Burrows, Eugene Holland and Andrew Conio, the volume examines the economic predicates of capitalist economics: liberal democracy and its alternatives, the conjugation of protest and aesthetics, how occupy experiments with different types of leadership and how power, hierarchies and resistance might be understood using Deleuze and Guattari’s radical conceptualizations of debt; subjectivity, the minor and the molecular, occupation, dispersed leadership, territory, smooth space and the war machine