No description available.

Diss. Univ. Freiburg im Breisgau, 2006. / Literaturverzeichnis: S. 332-343.

Univ., Diss.--München, 1997.

Thesis (doctoral)--Universiẗat, Bonn, 2005. / Includes bibliographical references (p. 393-420).

In dieser Arbeit wurde der Schwerpunkt auf die Erforschung der Immuncheckpointproteine PD-L2, VISTA und B7-H2 gelegt. Hierbei wurde unter anderem der Einfluss der Wachstumsfaktoren HGF und EGF mitbetrachtet, welchen eine wichtige Rolle bei der Tumorgenese zugeschrieben wird. Ein zentraler Punkt dieser Arbeit stellte der Einsatz und Vergleich von zweidimensionalen Zelllinien und dreidimensionalen Organoiden dar. Damit sollte das Spektrum des bisherigen Wissenstandes erweitert und eine Basis für folgende Forschungsprojekte geschaffen werden. Die Erforschung der betrachteten Immuncheckpointproteine erfolgte mittels in vitro- Versuchsreihen an sechs Zell- und zwei Organoidlinien von Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC). Zum Nachweis der Checkpointproteine sowie des Einflusses der Wachstumsfaktoren wurden Methoden wie die qPCR, Western Blots und die Durchflusszytometrie genutzt. Die untersuchten Immuncheckpointproteine sowie der Met-Rezeptor konnten mittels qPCR bei allen adhärenten Zelllinien und allen Organoiden (mit Ausnahme von PD-L2) nachgewiesen werden. Mittels Western-Blot und Durchflusszytometrie konnte PD-L2 bei den adhärenten Zelllinien unter HGF- und EGF-Stimulation vermehrt nachgewiesen werden, die Konzentration von VISTA und B7-H2 verringerte sich mit Stimulation. Bei den Organoiden konnte hingegen unter HGF-Stimulation nur B7-H2 verringert nachgewiesen werden, die VISTA-Konzentration blieb konstant. Insgesamt zeigen die vorliegenden Ergebnisse allerdings ein heterogenes Expressionsmuster für die untersuchten Checkpointproteine. Der Nachweis für PD-L2, VISTA und B7-H2 und die Beeinflussung mittels Wachstumsfaktoren bieten eine Chance, das Ansprechen einer potentiellen Immuncheckpoint-Therapie vorherzusagen. Durch die Inhibition weiterer Checkpointproteine, gegebenenfalls auch in Kombination mit derselben oder anderen Wirkstoffklassen, könnte die Ansprechrate einer Therapie erhöht werden. / This study focused on investigating the immune checkpoint proteins PD-L2, VISTA and B7-H2. It also considered the influence of the growth factors HGF and EGF, which are believed to play an important role in tumorigenesis. A central aspect of this work was the use and comparison of two-dimensional cell lines and three-dimensional organoids. This was intended to expand the current knowledge base and lay the groundwork for future research projects. The investigation of the immune checkpoint proteins was conducted through in vitro experiments on six cell lines and two organoid lines derived from squamous cell carcinomas of the head and neck region (HNSCC). Techniques such as qPCR, Western blotting, and flow cytometry were used to detect the checkpoint proteins and examine the influence of the growth factors. The examined immune checkpoint proteins, along with the met receptor, were detected by qPCR in all adherent cell lines and organoid samples (except for PD-L2). Western blotting and flow cytometry revealed an increased presence of PD-L2 in adherent cell lines under HGF and EGF stimulation, while the concentrations of VISTA and B7-H2 decreased with stimulation. In contrast, in the organoids, only B7-H2 was found to decrease under HGF stimulation, with the VISTA concentration remaining constant. Overall, the results show a heterogeneous expression pattern for the checkpoint proteins under investigation. The detection of PD-L2, VISTA and B7-H2, along with their modulation by growth factors, provides an opportunity to predict the response to potential immune checkpoint therapies. By inhibiting additional checkpoint proteins, possibly in combination with the same or other drug classes, the response rate for therapy could be increased.

Transgenic plants expressing a foreign gene are a suitable system for the production of relevant immunogens in high amounts that can be used for the development of a new generation of vaccines against a variety of infectious diseases. In the present study, the expression of the nucleocapsid (N) protein of hantavirus serotype Puumala in tobacco and potato plants was investigated. Transgenic tobacco and potato plants were generated and established. These transgenic plants expressed the N protein of Puumala virus strain CG-1820. No major differences were observed when the phenotype and growth rates of transgenic plants were compared to those of normal plants. However, it was found that the leaves of transgenic tobacco plants were more slender and the tubers of transgenic potato plants were smaller than those in normal plants. In order to investigate the distribution of the expression of the foreign gene in transgenic plants, the proteins of leaves and roots of the individual transgenic tobacco and potato plants were examined by Western blot analyses. It was found that all transgenic tobacco and potato plants expressed the N protein in the leaves, whereas transgenic potato plants are able to significantly express the viral proteins also in the tubers and roots. The antigens were expressed at a level of 1 ng of protein/5 μg of dried leaves. The hantaviral recombinant N proteins obtained from transgenic tobacco and potato plants were able to elicit specific humoral and mucosal immune responses when administered intraperitoneally or orally to rabbits and mice. The expression of viral proteins in plants has two major advantages compared to other expression systems: firstly, there is no risk of contamination with mammalian viruses or other pathogens, and secondly, the production of high amounts of antigens is cheap and therefore of great economic interest. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Zugl.: Berlin, Humboldt-Universiẗat, Habil.-Schr., 2004. / Angekündigt u.d.T.: Meuter, Norbert: Die Expressivität der menschlichen Existenz.

Transgenic plants expressing a foreign gene are a suitable system for the production of relevant immunogens in high amounts that can be used for the development of a new generation of vaccines against a variety of infectious diseases. In the present study, the expression of the nucleocapsid (N) protein of hantavirus serotype Puumala in tobacco and potato plants was investigated. Transgenic tobacco and potato plants were generated and established. These transgenic plants expressed the N protein of Puumala virus strain CG-1820. No major differences were observed when the phenotype and growth rates of transgenic plants were compared to those of normal plants. However, it was found that the leaves of transgenic tobacco plants were more slender and the tubers of transgenic potato plants were smaller than those in normal plants. In order to investigate the distribution of the expression of the foreign gene in transgenic plants, the proteins of leaves and roots of the individual transgenic tobacco and potato plants were examined by Western blot analyses. It was found that all transgenic tobacco and potato plants expressed the N protein in the leaves, whereas transgenic potato plants are able to significantly express the viral proteins also in the tubers and roots. The antigens were expressed at a level of 1 ng of protein/5 μg of dried leaves. The hantaviral recombinant N proteins obtained from transgenic tobacco and potato plants were able to elicit specific humoral and mucosal immune responses when administered intraperitoneally or orally to rabbits and mice. The expression of viral proteins in plants has two major advantages compared to other expression systems: firstly, there is no risk of contamination with mammalian viruses or other pathogens, and secondly, the production of high amounts of antigens is cheap and therefore of great economic interest. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Systems for selective dissemination of information (SDI) are used to efficiently filter, transform, and route incoming XML documents according to pre-registered XPath profiles to subscribers. Recent work focuses on the efficient implementation of the SDI core/filtering engine. Surprisingly, all systems are based on the best effort principle: The resulting XML document is delivered to the consumer as soon as the filtering engine has successfully finished. In this paper, we argue that a more specific Quality-of-Service consideration has to be applied to this scenario. We give a comprehensive motivation of quality of service in SDI-systems, discuss the two most critical factors of XML document size and shape and XPath structure and length, and finally outline our current prototype of a Quality-of-Service-based SDI-system implementation based on a real-time operating system and an extention of the XML toolkit.

Sowohl die öffentlichen wie die akademischen Auseinandersetzungen um Gehalt und Bedeutung der Menschenwürde werden bis heute von der Philosophie, den Rechtswissenschaften und der Theologie dominiert; Stimmen aus der Soziologie werden hierzu nur vereinzelt vernommen. Der Beitrag verfolgt zunächst das Ziel, unter Rückgriff auf ‚würdesensible‘ klassische Autoren Koordinaten eines genuin soziologischen Würdekonzepts zu entwickeln, das Probleme des menschlichen Ausdrucks und gesellschaftsstrukturelle Faktoren (u. a. städtische Öffentlichkeit, Arbeitsteilung, Rollenvielfalt) in strenger Weise zusammendenkt. Im ersten Kapitel (1) wird daher insbesondere auf Helmuth Plessners Grenzen der Gemeinschaft und Erving Goffmans Interaktionssoziologie Bezug genommen, um in einem eher induktiven, phänomenzentrierten Zugriff überhaupt erst diejenigen Situationen und die zugehörigen gesellschaftlichen Randbedingungen zu identifizieren, in denen das Problem der Würde in einem soziologisch distinkten Sinne akut wird. Das anschließende Kapitel (2) verfolgt mit Georg Simmel, Émile Durkheim und Niklas Luhmann zunächst eine rollentheoretische Präzisierung des Würdekonzeptes, die sich vor allem an der problematischen Annahme Peter L. Bergers abarbeitet, dass die vermeintlich bruchlose Ablösung von traditionellen Ehrvorstellungen durch den Würdekomplex gleichbedeutend wäre mit einer Bedeutungsminderung gesellschaftlicher Rollenerwartungen. Das letzte Kapitel (3) hält den systematischen Ertrag der vorangegangenen Überlegungen fest und widmet sich abschließend der Frage, in welchem Verhältnis dieser Ertrag zu dem normativ emphatischen Verständnis von Menschenwürde steht, wie es dem in Philosophie und Verfassungsrecht nach wie vor dominanten Unverlierbarkeitspostulat zugrunde liegt. / Both public and academic debates about the concept of human dignity are to date dominated by philosophical, legal and theological perspectives, while sociological contributions remain conspicuously scarce. This article aims at developing a genuine sociological concept of dignity, which binds together problems of human expression with socio-structural conditions of modernity (urban public sphere, division of labour, variety of roles, etc.). The argument unfolds in three steps: first, drawing upon the works of Helmuth Plessner, Erving Goffman and Niklas Luhmann, I identify those situations which allow us to distinguish problems of dignity from those associated with other expectational forms (particularly honour). Secondly, I turn to Simmel, Durkheim and Luhmann in order to pursue a role-theoretical clarification of the concept of dignity. Finally, I inquire into the question of how the systematic yield of these sociological considerations relates to the emphatic and heavily normative understanding of human dignity which pervades recent philosophical and juridical discourses.