Bakterien der Gattung Shigella sind die Erreger der bakteriellen Ruhr beim Menschen. Der wesent-liche Virulenzfaktor der Shigellen ist ihre Fähigkeit zur Invasion. Die Invasion in Epithel-zellen ist Ausdruck des erregerspezifischen Infektionsprozesses, der gekennzeichnet ist durch eine vom Bakterium induzierte zelluläre Aufnahme über einen Phagozytose-ähnlichen Mechanismus. In dessen Verlauf führt die charakteristische Reorganisation des Zytoskeletts der Zelle zur Ausbildung einer blütenartigen Membranstruktur an der bakteriellen Eintrittsstelle. Als essentielles Glied der Signalisationskaskade vom Bakterium zum zellulären Zytoskelett erwies sich das kleine G-Protein Rho. Es wurde gezeigt, daß Rho als Regulator der Veränderungen des Zytoskeletts selbst an den bakteriellen Invasionslocus rekrutiert wird. Diese Rekrutierung umfaßt drei Isoformen von Rho: RhoA, RhoB und RhoC. Trotz hoher Sequenzhomologie der Isoformen untereinander ( 85% ) existiert ein unterschiedliches Rekrutierungsmuster dieser Isoproteine an der Eintrittsstelle von Shigella flexneri. RhoA akkumuliert vorwiegend um die eindringenden Bakterien herum. Demgegenüber werden RhoB und RhoC in die bakterieninduzierten zellulären Protrusionen rekrutiert. Der Mechanismus dieser isoformspezifischen Rekrutierung ist nicht bekannt. Anhand unserer Experimente konnten wir zeigen, daß das allen kleinen G-Proteinen gemeinsame C-terminale Peptid-Motiv CAAX ( C = Cystein, A = aliphatische Aminosäure, X = Leucin ) eine wesentliche Voraussetzung für die Rekrutierung von Rho darstellt, sich die isoformspezifische Rekrutierung jedoch nicht anhand des CAAX-Motivs erklären läßt. Bedeutsam für die differentielle Rekrutierung der Isoproteine ist vielmehr die präterminale Region des Moleküls. Diese Beobachtung hat weitreichende Konsequenzen für die funktionelle Rolle von Rho bei der Epithelzellinvasion durch Shigella. / Shigella is the etiologic agent of human bacillary, an infectious large bowel disease. A major feature of Shigella's pathogenic potential is the capacity to invade epithelial cells. Shigella entry into epithelial cells is considered a parasite-induced internalization requiring cytosceletal rearrangements; Shigella entry induces a blossom-like membrane structure at the bacterial entry site. This membrane folding process is dependent on the small GTPase rho. It has been shown that three rho isoforms rhoA, rhoB and rhoC are recruited into bacterial entry sites with different localization relative to the membrane structures. While rhoA preferentially accumulates in close vicinity to entering bacteria, rhoB and rhoC are recruited into the tips of Shigella-induced cellular protrusions. We could show that the C-terminal CAAX-region of rho is a prerequisite for recruitment, but not sufficient for different recruitment of rho isoforms. Additional information for differential recruitment patterns seems to come from the preterminal region of rho proteins. This result is of great importance for the functional role of rho during Shigella-invasion into epithelial cells.

Shigellen sind Erreger der bakteriellen Dysenterie beim Menschen. Ein notwendiger Schritt bei der Pathogenese der Shigellose ist die Invasion von Darmepithelzellen durch das Bakterium. Der Mikroorganismus löst dabei in der Wirtszelle Veränderungen des Aktinzytoskeletts aus, die zur Bildung einer blütenähnlichen Membranstruktur und schließlich zur Internalisierung des Pathogens führen. Diese Umbauvorgänge am Zytoskelett sind abhängig von einem Wirtszellprotein, der kleinen GTPase Rho. Drei Isoformen von Rho (A, B und C) sind beschrieben, deren Aminosäuresequenzen zu etwa 90% identisch sind. Während der Zellinvasion durch Shigella akkumulieren verschiedene Rho-Isoformen an unterschiedlichen Lokalisationen des Invasionskomplexes. Dabei werden RhoA vorwiegend um die eindringenden Bakterienherum, RhoB und RhoC hingegen hauptsächlich in die bakterieninduzierten zellulären Protrusionen rekrutiert. Durch Untersuchung von Rho-Hybridkonstrukten konnte gezeigt werden, daß ein prä-C-terminales, acht Aminosäuren umfassendes Modul die Rekrutierungsmuster von RhoA bzw. RhoC bestimmt. Der Austausch zweier Aminosäuren innerhalb des Moduls führte zu einer Konversion des Rekrutierungsmusters von RhoA. Wir konnten zeigen, daß die Rekrutierung von RhoA vom Funktionszustand der GTPase (Bindung von GTP/GDP) sowie von der Phosphorylierung durch die Proteinkinase A unabhängig ist. Schließlich wurde hier nachgewiesen, daß auch RhoD, das zu RhoA, B und C auf der Primärstrukturebene nur zu etwa 50% homolog ist, an die Bakterieneintrittsstelle rekrutiert werden kann. RhoD folgt dabei dem Rekrutierungsmuster von RhoB und RhoC. / Shigella causes bacillary dysentery in humans. Bacterial invasion of enterocytes is an essential step in the pathogenesis of shigellosis. Pathogen-triggered rearrangements of the host cell actin cytoskeleton induce a blossom-like membrane structure for internalisation of the microorganism. Actin remodeling requires activity of the host cell small GTPase rho. Three highly homologous rho isoforms (A, B and C) have been described with amino acid identities of about 90%. During Shigella invasion these rho isoforms accumulate at different sites of the invasion complex. While rhoA is chiefly recruited around entering bacteria, rhoB and rhoC are essentially translocated to the bacteria-induced cellular protrusions. Using a variety of rho hybrid constructs in a HeLa cell transfection-infection assay we were able to show that a pre-C-terminal stretch of eight amino acids determines the recruitment patterns of rhoA and rhoC. Exchange of two amino acids was sufficient for conversion of the rhoA recruitment pattern into a rhoC-like pattern. We could demonstrate that rhoA recruitment is independent of its functional state (GDP- or GTP-bound) or phosphorylation by the proteinkinase A (PKA). Finally, we have shown that rhoD, another member of the rho family which shares only 50% of its primary structure with rhoA, B or C, is also recruited to the bacterial entry site exhibiting a rhoB/C-like pattern of distribution.

Cette thèse s'inscrit dans le cadre des grappes dans le projet Grid'5000 (Projet Français pour les grilles). Grid'5000 est une plate-forme expérimentale qui offre la possibilité aux chercheurs de soumettre aux gestionnaires de ressource des programmes (travaux) et d'associer pour chaque requête un environnement. Une grappe est un ensemble de noeuds de calcul, connectés entre eux via un réseau dédié. Le processus de déploiement d'environnement sur les noeuds de calcul n'est pas sans conséquence. Un des problèmes que l'on rencontre est la défaillance des machines. Le démarrage excessif lors de de la phase déploiement peut causer un endomagement de celles-ci. Nous avons ainsi modélisé ce problème sous forme d'un problème d'ordonnancement bicritère. Le premier critère à minimiser comptabilise pour chaque machine (processeur) le nombre de déploiements effectués. Il permet ainsi permet de définir le nombre total de déploiements sur toutes les machines. Nous avons également considéré un second critère à minimiser, le makespan. Nous avons défini un algorithme Groups List Scheduling, basé sur une approche budget, avec un relâchement des contraintes d'optimalité. Cette approche nous a permis de définir une solution (alpha, beta)-budget-relaxée-approchée pour un problème d'optimisation bicritère. Dans le cadre du problème d'ordonnancement bicritère avec déploiement, l'algorithme GLS donne ainsi une solution (4,2)-budget-approchée-relaxée. Nous avons ensuite abordé ce problème d'ordonnancement bicritère avec déploiement en utilisant l'approche «courbe de Pareto». Nous avons défini un algorithme polynômial, qui permet de construire une courbe de Pareto (4+epsilon, 2)-approchée, à partir des solutions fournies par l'algorithme GLS. Une analyse expérimentale nous a permis d'évaluer les performances de l'algorithme GLS et de valider ainsi les rapports

Eukaryotic cells are populated by membrane-enclosed organelles possessing discrete molecular and biochemical properties. Communication between organelles is established by shuttling vesicles that transport proteins and other molecules. Vesicles bud from a donor organelle, travel in the cytosol, and are delivered to a target organelle. All these steps are regulated to ensure that cargoes are transported in a specific and directed manner. The focus of this thesis is on the last part of the journey of a vesicle: the process of vesicle targeting. Two phases can be distinguished in this process: vesicle tethering, defined as the first interaction between the shuttling vesicle and the target membrane, and membrane fusion, which is the mixing of the lipid bilayers and of lumen content. Both phases are mediated by a minimal set of molecular components that include one member of the family of Rab GTPases, a vesicle tethering factor, a phosphoinositide lipid, and four SNAREs together with their regulatory proteins. While many studies have investigated the molecular details of how SNAREs mediate membrane fusion, the process of vesicle tethering is less well understood. The overall scope of my study is to describe the molecular details of vesicle tethering and how they can contribute to the general process of vesicle targeting. To address this question I developed an in vitro assay where I reconstitute in vitro the process of vesicle tethering. This bottom-up approach allows the molecular dissection of cellular processes outside of the complex context of the cell. With this assay I have characterized the vesicle tethering abilities of individual proteins involved in vesicle tethering on early endosomes. I show that a minimal vesicle tethering machinery can be formed by the concomitant interaction between one vesicle tethering factor and a phosphoinositide on the membrane of one vesicle, and by a vesicle tethering factor and a Rab GTPase on the membrane of another vesicle. These results provide an explanation for how vesicle tethering contributes to the specificity of vesicle targeting and to the directionality of cargo transport. In particular, specificity of vesicle targeting can arise from the specific interaction between a Rab and a vesicle tethering factor that is an effector of the Rab. I show that the asymmetric distribution of binding sites in the structure of a vesicle tethering factor can generate a heterotypic vesicle tethering reaction that can account for the directionality of cargo transport. The outcome of this thesis emphasizes the role that vesicle tethering factors have in the self-organized system of vesicle trafficking of eukaryotic cells. To identify novel Rab5 effectors implicated in vesicle tethering, I carried out a Rab5-chromatography on mouse liver. Amongst other novel Rab5 effectors, I identify a multi-subunit vesicle tethering complex that was not previously characterized in mammalian cells. The complex, named CORVET, is conserved from yeast to humans and plays a major role in cell physiology since its removal causes embryonic death in mice. I define its subunits composition, determine its subcellular localization, and elucidate its role in cargo transport. This finding reconciles a disharmony between findings in mammals and yeast regarding the molecular machinery responsible for the conversion from early to late endosomes. I also show that the newly identified subunit of the mammalian CORVET complex is the only Rab5 effector to localize to autophagosomes. I hypothesise that it is through the CORVET complex that Rab5 is involved in the formation and maturation of autophagosomes.

Background: Schizophrenia first appears in adolescence, in boys at an earlier age than girls. The interpretation of this key epidemiological finding crucially depends on whether similar age-related sex differences exist in the expression of associated, subclinical psychosis-like experiences. Methods: Findings are based on a population sample of 2548 adolescents and young adults aged 17–28. Subjects were assessed with the core psychosis sections on delusions and hallucinations of the Munich- Composite International Diagnostic Interview. Results: The risk of subclinical psychotic experiences was significantly higher for males in the younger half of the cohort (17–21 years), but similar in the older half (22–28 years). Conclusions: These findings suggest that normal maturational changes in adolescence with differential age of onset in boys and girls cause the expression of psychosis, the extreme of which is schizophrenia.

The aim of this study was to investigate Meteorological Fire Danger Indices for Turkey. A number of internationally implemented fire danger indices were calculated with Fire Danger Processing software and their performances were tested with Mandallaz and Ye&rsquo / s Performance Score Method. As a result, among other meteorological fire danger indices that have been applied by several fire fighting administrations and services, the U.S. National Fire Danger Rating System, Mc.Arthur&rsquo / s Fuel Moisture Model and Forest Fire Weather Index, BEHAVE Fine Fuel Moisture Model and Keetch Byram Drought Index, the Canadian Fire Weather Index was selected as the best performing fire danger index for Turkey. Calibrated with monthly fire history data of the last 5 years&rsquo / records, the results during the determined fire season were integrated with vegetation cover data for Turkey, derived from GLC 2000 global land cover data. Besides, daily performance of the Canadian Fire Weather Index was observed by three consecutive days in August 2006 and the outcomes were evaluated with the information about fire events compiled from newspaper archives. The study is a first attempt for further fire related analysis at the national scale / an attempt to establish an early warning system and a spatial base for mitigation effort for the wild fire phenomenon in Turkey.

Cilien und eukariotische Flagellen sind lange, dünne Fortsaetze von Zellen. Sie enthalten eine Struktur namens Axonem. Die wesentlichen Komponenten des Axonems sind die Filamente und Motorproteine namens Mikrotubuli und Dynein. Die Motoren forcieren die Filamente, sich in oszillierender Weise gegeneinander zu verschieben, was zu einem Schlagmuster entlang des Axonemes fuehrt. Wie diese Motoren koordiniert werden und wie dieses Phaenomen quantitativ beschrieben werden kann, ist nicht verstanden. Wir studierten die Wellenformen an Spermienschwaenzen, welche ein solches Axonem enthalten, unter verschiedenen Bedingungen mit einer Hochgeschwindigkeitskamera. Wir entwickelten eine automatisierte Bildanalyse-Software, die es erlaubt, lange Zeitreihen solcher Wellenformen von Filmen zu extrahieren. In einer anschließenden Fourieranalyse erzielten wir eine gemittelte Wellenform mit erhoehter Präzision. Ein Vergleich von unseren Daten mit den Vorhersagen einer Theorie (Camalet, Julicher et al. 1999) führte zu einer Diskrepanz. Entsprechend schlugen wir eine Erweiterung der Theorie vor, indem wir annahmen, daß an der Basis des Axonems ein viskos-elastisches Element existiert. Dies führte zu einer zufrieden stellenden Übereinstimmung zwischen Theorie und Experiment. Abschließend diskutieren wir offene Fragen und zukünftige Experimente. Als ein Nebenprodukt entdeckten wir ein neues Phaenomen, bei welchem Spermien Anordnungen von dynamischen Strudeln (Vortices) bilden. Wir beschrieben dieses Phaenomen im Detail und führten einen neuen Ordnungsparameter ein, mit dem die Ordnung zwischen vielen Objekten quantifiziert werden kann. Mittels dieses Ordnungsparameters konnten wir zeigen, daß dieses Muster sich erst ab einer kritischen Dichte herausbildet. Wir schlugen ein Model vor, um den Ursprung des Musters zu erklären. Die Simulation des Models zeigte volle Uebereinstimmung mit den wesentlichen Eigenschaften dieses Musters. Weiterhin schaetzten wir die typische Wechselwirkungskraft zwischen aktiven Axonemen mit 0.1 pN ab. Abschließend ziehen wir Schlußfolgerungen über die kollektive Wirkung von Axonemen im Allgemeinen mit Hinblick auf Spermienkooperation und metachronale Cilienwellen. - Die Druckexemplare enthalten jeweils eine CD-ROM als Anlagenteil: QuickTimeMovies (ca. 65 MB) Nutzung: PLAY32 - Übersicht über Inhalte siehe Dissertation S. 108 - 109 / Cilia and eukaryotic flagella are long, thin extensions of cells that contain a structure known as axoneme. The key components of the axoneme are microtubule filaments and the motor proteins dynein. These dynein motors force the microtubules to slide in an oscillatory fashion leading to a wave pattern along the axoneme. How these motors are coordinated and how this phenomenon can be described quantitatively is not understood. I therefore studied the waveforms of sperm tails that contain such an axoneme. I observed these waveforms under different conditions with a high-speed camera and developed an automated image analysis tool allowing the extraction of long time series of this waveform. In a subsequent Fourier analysis I increased the precision by obtaining an averaged waveform. I then compared the data to the predictions of a theoretical framework (Camalet, Julicher et al. 1999) and found that they do not agree. I suggested extending this theoretical framework by considering a visco-elastic element at the base of the axoneme, which leads to a satisfactory agreement. This project leaves open questions hence further work is discussed. As a side finding, I discovered a new phenomenon on how spermatozoa form dynamic vortex arrays. I described this pattern in detail and introduced a novel order parameter to quantify the order among many particles. I showed that the array only forms above a critical sperm density. I suggested a model to explain the origin of the pattern and showed by simulation that the model can account for the main features of the pattern. Finally I estimated the typical interaction force between beating axonemes to be 0.1 pN and drew conclusions about their collective action in general that might be relevant for sperm cooperation or metachronal waves of cilia.

Die vorliegende Ausgabe beschäftigt sich mit dem Thema der ökologischen und ökonomischen Bewertung von OP-Textilien. Die in dieser Ausgabe veröffentlichten Ergebnisse beruhen auf Seminararbeiten, die im Rahmen der Wissenschaftliche Begleitung eines Praxisprojekts an unserer Professur in Zusammenarbeit mit dem Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden erbracht wurden. Sie haben somit Fallstudiencharakter und erheben keinen Anspruch auf Vollständigkeit oder Repräsentativität, sondern geben in ihrem Umfang einen hervorragenden Einblick in das Betätigungsfeld der Betriebswirtschaftslehre im allgemeinen und der Betrieblichen Umweltökonomie im speziellen. Die in dieser Ausgabe dargestellten Ergebnisse stellen somit keinen Schlusspunkt für die Forschung dar, sondern bilden den Ausgangspunkt für weiterführende wissenschaftliche Untersuchungen.

In this thesis we have investigated the correlated ground state properties of polymers by applying wave-function-based ab-initio quantum-chemical methods such as the Hartree-Fock approach, the full configuration interaction method (FCI), coupled-cluster (CC) and Moller-Plesset second-order perturbation (MP2) theory. The polymers we have studied are the boron-nitrogen polymers, i.e., polyiminoborane (PIB) and polyaminoborane (PAB), the lithium hydride chain and the beryllium hydride polymer as well as the polymethineimine (PMI). The optimized structural parameters, cohesive energies, polymerization ernergies, relative stabilities of isomeric forms and some band structure results are presented. The results demonstrated that quantum chemical ab initio methods can be applied successfully to infinite systems like polymers, although such calculations are still far from being routine.

Prospective memory refers to the ability to remember to carry out delayed intentions, more precisely, to remember to initiate and execute an intended action at some point in the future. The development and progression of prospective memory across the lifespan is still heavily under debate. Only few studies have so far investigated prospective memory development in childhood, revealing an inconsistent pattern. In adulthood, studies in the laboratory and naturalistic studies showed paradoxical results with age deficits in the laboratory and age benefits in naturalistic tasks. Up to now, no conceptual model has been suggested to guide research on prospective memory development across the lifespan. Thus, the present work examined the effect of central factors from the multiprocess framework (McDaniel & Einstein, 2000) on the development of prospective memory in four different age-groups: pre-schoolers, school-age children, young and old adults. The first study explored the role of task motivation in age differences in prospective memory performance across the pre-school age-range. No main effect of age or motivation in prospective memory performance was found, yet a significant interaction, indicating that for younger children motivation or task importance may help allocating the available resources to the task elements of interest. Evidence from the second study indicated that 9-10 year old school children outperform 6-7 year old school children on a measure of prospective memory, and that retrieval-based factors (ongoing task absorption, cue salience, cue focality) systematically influenced performance. Of particular importance for possible developmental mechanisms was the finding of an age x cue focality interaction, suggesting that age effects may be modulated by cue focality. The third study examined the effect of task setting in a laboratory procedure and the effect of motivation in a naturalistic procedure on prospective memory performance in young and older adults. Results from the laboratory prospective memory procedure revealed significant age-related decline for irregular tasks but not for regular and focal tasks. In addition, in the naturalistic procedure, the age benefit was eliminated when young adults were motivated by incentives. Results from the present work indicated that already pre-school age children were able to remember to perform intended actions and this ability increased across school-age. In adulthood, the results revealed a decline with age on a pure performance level. Yet, older adults may be able to compensate for basic cognitive impairments if task conditions reduce the need for controlled attention. Furthermore, the present work suggest, that factors of the multiprocess framework may indeed affect age-differences in prospective memory performance throughout the lifespan, as cue focality and task importance were related to prospective memory development in children and adults. Thus, the multiprocess approach might serve as foundation for a lifespan theory of the development of prospective memory.