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Freie Univ., Diss.--Berlin, 2005.

Au cours de cette thèse on étude deux des plus populaires systèmes de nano-échelle, nano fil et points quantiques (quantum dots), dans le cadre d'une approximation basé sur des premiers principes. Afin d'atteindre cet objectif, nous avons utilisé et développé des théories plus sophistiquées qui nous ont permis d'avoir un meilleur aperçu de la façon dont les systèmes se comportent. Un aspect commun qui limite ces deux types de systèmes (nano fil et points quantiques) est la souplesse de contrôler les propriétés électroniques et optiques. Cette accordabilité des propriétés électroniques et optiques les dote d'un grand intérêt technologique, et elle est la raison de sa popularité / In this thesis we studied two of the most popular nano-scale systems, nano-wires and quantum dots, via a first-principles approach. In order to achieve this objective we have used and developed state-of-the-art theories that allowed us to have a greater insight into the the way this systems behave. One common aspect that bounds this two class of systems (nano-wires and quantum dots) is the flexibility to control their electronic and optical properties. This tunability of their electronic and optical properties, endows them of great technological interest, and is the reason behind their popularity

Knapp 25 Jahre nach dem ersten Auftreten der bovinen spongiformen Enzephalopathie (BSE) in Europa, bleibt die Entfernung und unschädliche Beseitigung des sogenannten spezifizierten Risikomaterials (SRM) eine der wichtigsten Maßnahmen zur Reduzierung des humanen oralen BSE-Expositionsrisikos. Angesichts des Rückgangs der BSE-Inzidenzen in Europa hat sich die Europäische Kommission (EC) in ihrer „TSE Roadmap“ das Ziel gesetzt, die Auflistung und/oder die Alters-grenzen für das SRM schrittweise zu modifizieren. In diesem Sinne hat die EC die Europäische Behörde für Lebensmittelsicherheit (EFSA) mehrfach aufgefordert, das BSE-Risiko anhand aktueller Daten neu zu bewerten, insbesondere das, welches von Rindernaturdärmen für den Verbraucher ausgeht. Die wissenschaftliche Bewertung des humanen BSE-Expositionsrisikos ist jedoch bis heute mit großen Unsicherheiten verbunden und deshalb sollten erfassbare Varianzeinflüsse so weit wie möglich reduziert werden. Nachdem experimentell BSE-Infektiosität im distalen Ileum demonstriert wurde, erfolgte vorsorglich die Einstufung des gesamten bovinen Darmes (Duodenum bis Rektum, einschließlich des Mesenteriums) als SRM. Eine der wesentlichen Eingangsgrößen bei der wissenschaftlichen Bewertung des Expositionsrisikos ist die Masse des in die Nahrungskette eingebrachten potentiell infektiösen Materials. Alle bis zum heutigen Zeitpunkt durchgeführten Risikobewertungen legten eine Masse von 800 g für das bovine Ileum zugrunde. Die eigenen Untersuchungen hatten das Ziel die Gewichtsangabe des bovinen Ileums zu validieren, die Effizienz des SRM-Verbotes zur Reduktion des humanen oralen BSE-Infektionsrisikos sowie das Infektionspotential nach der Bearbeitung des Darmes im Hinblick auf seine Einstufung als SRM einzuschätzen. Von 129 Schlachtrindern wurde das Ileum unter kontrollierten Bedingungen entnommen und in der Folge der technologischen Bearbeitung vermessen. Zudem wurden 13 bovine Ilea und 11 Jejuna jeweils vor und nach der manuellen Bearbeitung histologisch auf das Vorkommen von lymphatischem Gewebe untersucht. Das lymphatische Gewebe des Darmes stellt wahrscheinlich den Ort der Erregeraufnahme nach einer oralen BSE-Infektion dar. Wesentliches Ergebnis ist ein mittleres Gewicht für das bovine Ileum im entleerten und bearbeiteten Zustand von 57 g (Spannweite: 23,1 bis 135,8 g). Dieser Wert liegt im Vergleich zu der bisher verwendeten Eingangsgröße um eine Größenordnung niedriger. Im Hinblick auf die Effizienz des SRM-Verbots zur Risikoreduktion in der Lebensmittelkette ergibt sich mit den neuen Daten ein Anstieg von 95% auf 99% für das zentrale Nervensystem (ZNS) und das ZNS-nahe periphere Nervensystem. In den histologischen Untersuchungen konnte lymphatisches Gewebe nur bei einer der bearbeiteten Ileumproben (7.7%) und zwei der bearbeite-ten Jejunumproben (18,2%) gefunden werden. Dies zeigt, dass durch die Bearbeitung der Rinderdärme der größte Teil des lymphatischen Gewebes entfernt wird. Die vorliegenden Ergebnisse stützen die Aussage anderer Studien, dass durch die Reinigung der Därme signifikante Mengen an lymphatischem Gewebe entfernt werden. Aufgrund des niedrigen Ileumgewichtes und der effektiven Entfernung des lymphatischen Gewebes kann der Anteil des Ileums an der gesamten Infektiosität, bei einem klinisch an BSE erkrankten Rind, als sehr gering eingestuft werden. Das bovine Ileum ist nach vorliegender Untersuchung lediglich mit 1 % an der Gesamtinfektiosität beteiligt und nicht, wie bisher angenommenen, mit 3,3 % bzw. 9,6 %. Angesichts dieser Ergebnisse, der aktuellen BSE-Inzidenzen in Europa, der Verteilung und Höhe der BSE-Infektiosität im bovinen Darm wird, wie auch von einer Reihe anderer Autoren, die Übertragung von BSE durch Rinderdärme als ein vernachlässigbares Risiko angesehen. Vor diesem Hintergrund sollte der SRM-Status der Rinderdärme erneut geprüft und bewertet werden.:INHALTSVERZEICHNIS 1 EINLEITUNG 1 2 LITERATURÜBERSICHT 4 2.1 Transmissible spongiforme Enzephalopathien 4 2.1.1 Transmissible spongiforme Enzephalopathien beim Tier 5 2.1.1.1 Scrapie 6 2.1.1.2 Bovine spongiforme Enzephalopathie 9 2.1.2 Transmissible spongiforme Enzephalopathien beim Menschen 16 2.1.2.1 Klassische Formen der CJD 16 2.1.2.2 Neue Variante der CJD 19 2.2 Lymphatisches Gewebe des Rinderdarms 24 2.2.1 Bestandteile 25 2.2.2 Embryonale Entwicklung 26 2.2.3 Morphologie der Peyer’schen-Platten 27 2.2.3.1 Lymphfollikel 28 2.2.3.2 \"dome\" 29 2.2.3.3 Follikelassoziiertes Epithel 29 2.2.3.4 M-Zellen 29 2.2.3.5 Interfollikuläre Zone 31 2.2.4 Verteilung und Lage 32 2.2.4.1 Solitärfollikel 32 2.2.4.2 Peyer’sche-Platten 33 2.2.4.3 Lymphoglanduläre Komplexe 34 2.2.5 Involution 34 2.2.5.1 Involution der Peyer’schen-Platten 35 2.2.5.2 Involution der Solitärfollikel und des lymphatischen Gewebes des Dickdarms 36 2.3 Naturdarm 36 2.3.1 Gewinnung und Bearbeitung 38 2.3.1.1 Manuelle Bearbeitung 39 2.3.1.2 Maschinelle Bearbeitung 40 2.3.2 Einsatzmöglichkeiten 41 2.3.3 Wirtschaftliche Bedeutung 42 2.4 Risikoanalyse 43 2.4.1 Risikobewertung 44 2.4.1.1 BSE-Risikobewertung 45 2.4.2 Risikomanagement 49 2.4.2.1 Überwachungsmaßnahmen 50 2.4.2.2 Verfütterungsverbote 53 2.4.2.3 Spezifizierte Risikomaterialien 54 2.4.3 Risikokommunikation 56 3 TIERE, MATERIAL UND METHODEN 57 3.1 Gewichts- und Längenbestimmung der Ilea 57 3.1.1 Auswahl der Tiere 57 3.1.2 Entnahme der Ilea 58 3.1.3 Bearbeitung der Ilea 59 3.1.4 Bestimmung des Gewichtes und der Länge 60 3.2 Histologische Untersuchungen 60 3.2.1 Ileum 60 3.2.1.1 Auswahl der Tiere 61 3.2.1.2 Entnahme der Ilea 61 3.2.1.3 Bearbeitung der Ileumabschnitte 61 3.2.1.4 Vorbereitung und Anfertigung der Schnitte 63 3.2.1.5 Auswertung der Schnitte und Dokumentation 64 3.2.2 Jejunum 65 3.2.2.1 Auswahl der Tiere 65 3.2.2.2 Entnahme der Jejuna 65 3.2.2.3 Bearbeitung der Jejunumabschnitte 65 3.2.2.4 Vorbereitung und Anfertigung der Schnitte 66 3.2.2.5 Auswertung der Schnitte und Dokumentation 67 3.3 Untersuchung auf Peyer’sche-Platten 67 3.4 Gewichtsreduktion durch die Bearbeitung 68 4 ERGEBNISSE 69 4.1 Gewicht und der Länge der Ilea 69 4.2 Histologische Untersuchung der Ilea 73 4.3 Histologische Untersuchung der Jejuna 79 4.4 Untersuchung des Rinderdünndarmes auf sichtbares lymphatisches Gewebe 82 4.5 Gewichtsreduktion durch die Bearbeitung 84 5 DISKUSSION 85 5.1 Gewicht und Länge der Ilea 85 5.2 Histologische Untersuchung der Ilea und Jejuna 88 6 ZUSAMMENFASSUNG 95 7 SUMMARY 97 8 LITERATURVERZEICHNIS 99 ANHANG 135 DANKSAGUNG 148 / Nearly two and a half decades after the emergence of a new transmissible spongiform encephalopathy (TSE) in bovines (BSE) in Europe the ban on so called specified risk material (SRM) remains the most important measure to reduce any potential oral human BSE exposition risk from the food chain. In view of the overall and constant reduction of the frequency of bovine TSE cases in Europe the European Commission expressed in its “TSE-road map” the need for a future lifting of the SRM-ban and the European Food Safety Authority has been repeatedly asked by the European Commission to re-assess the BSE risk for the consumer on the basis of current data, amongst others the risk associated with natural bovine sausage casings. However, the scientific evaluation of the human BSE exposition risk is impeded by great uncertainties and ascertainable variances should be reduced as far as possible. After BSE-infectivity was demonstrated experimentally for the distal bovine ileum, the whole bovine intestine from duodenum to rectum including mesentery was categorized as specified risk material (SRM).The weight of potential infective material brought into the food chain is a major influencing variable in this context. All subsequent studies concerning the human BSE exposure risk have been based on an ileum weight of 800 g per adult cattle. The aim of the own studies was to validate the existing measurement of bovine ileum and its infectivity after processing with respect to the efficiency of the SRM ban for a risk reduction in the food chain. 129 ilea were removed from slaughtered cattle and weighted during subsequent technical processing. In parallel, 13 bovine ileum and 11 jejunum samples were analyzed histologically before and after manual processing in order to detect lymphatic tissue which is presumed to be the point of entry for the infective agent. The mean weight for the whole empty and processed ileum was 57 g ranging from 23.1 g to 135.8 g. This is one order of magnitude lower than the input level used to date. Residues of lymphatic tissue were detected in one of the processed ileum samples (7.7%) and two of the jejunum samples (18.2%). This means that the major part of lymphatic tissue is removed from the bovine intestine during the different processing steps. Our results are backed up by a number of studies made by other researchers who showed that significant quantities of lymphatic tissues are removed from the bovine intestine by cleaning.The ileum has to be recognized as only a minor fraction of the total infective load per animal due to its weight and the removal of most lymphatic tissue during processing. Contrary to previous assumptions that ileum amounts to 3.3 and 9.6% respectively of the total infective tissues this study clearly shows that this premise has to be corrected to 1%. Regarding these results in combination with the decreasing BSE incidences in Europe, the distribution and the amount of the BSE infectiosity the potential BSE-infectivity represented by the bovine intestine can be considered negligible. This assessment is shared by numerous authors. A possible amendment of the current SRM status of bovine intestine should be re-assessed.:INHALTSVERZEICHNIS 1 EINLEITUNG 1 2 LITERATURÜBERSICHT 4 2.1 Transmissible spongiforme Enzephalopathien 4 2.1.1 Transmissible spongiforme Enzephalopathien beim Tier 5 2.1.1.1 Scrapie 6 2.1.1.2 Bovine spongiforme Enzephalopathie 9 2.1.2 Transmissible spongiforme Enzephalopathien beim Menschen 16 2.1.2.1 Klassische Formen der CJD 16 2.1.2.2 Neue Variante der CJD 19 2.2 Lymphatisches Gewebe des Rinderdarms 24 2.2.1 Bestandteile 25 2.2.2 Embryonale Entwicklung 26 2.2.3 Morphologie der Peyer’schen-Platten 27 2.2.3.1 Lymphfollikel 28 2.2.3.2 \"dome\" 29 2.2.3.3 Follikelassoziiertes Epithel 29 2.2.3.4 M-Zellen 29 2.2.3.5 Interfollikuläre Zone 31 2.2.4 Verteilung und Lage 32 2.2.4.1 Solitärfollikel 32 2.2.4.2 Peyer’sche-Platten 33 2.2.4.3 Lymphoglanduläre Komplexe 34 2.2.5 Involution 34 2.2.5.1 Involution der Peyer’schen-Platten 35 2.2.5.2 Involution der Solitärfollikel und des lymphatischen Gewebes des Dickdarms 36 2.3 Naturdarm 36 2.3.1 Gewinnung und Bearbeitung 38 2.3.1.1 Manuelle Bearbeitung 39 2.3.1.2 Maschinelle Bearbeitung 40 2.3.2 Einsatzmöglichkeiten 41 2.3.3 Wirtschaftliche Bedeutung 42 2.4 Risikoanalyse 43 2.4.1 Risikobewertung 44 2.4.1.1 BSE-Risikobewertung 45 2.4.2 Risikomanagement 49 2.4.2.1 Überwachungsmaßnahmen 50 2.4.2.2 Verfütterungsverbote 53 2.4.2.3 Spezifizierte Risikomaterialien 54 2.4.3 Risikokommunikation 56 3 TIERE, MATERIAL UND METHODEN 57 3.1 Gewichts- und Längenbestimmung der Ilea 57 3.1.1 Auswahl der Tiere 57 3.1.2 Entnahme der Ilea 58 3.1.3 Bearbeitung der Ilea 59 3.1.4 Bestimmung des Gewichtes und der Länge 60 3.2 Histologische Untersuchungen 60 3.2.1 Ileum 60 3.2.1.1 Auswahl der Tiere 61 3.2.1.2 Entnahme der Ilea 61 3.2.1.3 Bearbeitung der Ileumabschnitte 61 3.2.1.4 Vorbereitung und Anfertigung der Schnitte 63 3.2.1.5 Auswertung der Schnitte und Dokumentation 64 3.2.2 Jejunum 65 3.2.2.1 Auswahl der Tiere 65 3.2.2.2 Entnahme der Jejuna 65 3.2.2.3 Bearbeitung der Jejunumabschnitte 65 3.2.2.4 Vorbereitung und Anfertigung der Schnitte 66 3.2.2.5 Auswertung der Schnitte und Dokumentation 67 3.3 Untersuchung auf Peyer’sche-Platten 67 3.4 Gewichtsreduktion durch die Bearbeitung 68 4 ERGEBNISSE 69 4.1 Gewicht und der Länge der Ilea 69 4.2 Histologische Untersuchung der Ilea 73 4.3 Histologische Untersuchung der Jejuna 79 4.4 Untersuchung des Rinderdünndarmes auf sichtbares lymphatisches Gewebe 82 4.5 Gewichtsreduktion durch die Bearbeitung 84 5 DISKUSSION 85 5.1 Gewicht und Länge der Ilea 85 5.2 Histologische Untersuchung der Ilea und Jejuna 88 6 ZUSAMMENFASSUNG 95 7 SUMMARY 97 8 LITERATURVERZEICHNIS 99 ANHANG 135 DANKSAGUNG 148

Despite intensive research, the cellular and molecular mechanisms involved in human cellular susceptibility to prion infection remain poorly defined, in part due to the continuing lack of cultured human cells that are susceptible to infection with human prions. Such culture models would present distinct advantages including speed and expense compared with animal models, and would provide systems in which to investigate the interaction between PrPC and PrPSc, the basis of cellular susceptibility, the nature of the species barrier and the mechanism of prion propagation in situ. This study sought to examine whether non-neuronal cells might provide opportunities to establish human cell lines replicating human prions. A human follicular dendritic cell-like cell line (termed HK) was obtained, further characterised and then tested for its ability to support human prion replication. The mechanisms of internalisation, intracellular trafficking and the eventual fate of exogenous PrPSc taken up by these cells were also examined. This thesis similarly examined the cellular response of human embryonic stem cells (hESC) to acute exposure to human and animal prions. PrPC was found to be abundantly expressed by HK cells and HK cell extracts were found to support conversion to PrPSc in a cell-free conversion assay. However, HK cells exposed to infectious brain homogenates failed to accumulate PrPSc or become infected in vitro. Exposed HK and hESC did display a readily detectable, time dependent uptake of PrPSc from medium spiked with prion-infected brain homogenates that was independent of the species, disease phenotype and PRNP codon 129 genotype of the human source and the recipient cells. The exposed cells showed intensely labelled intracellular accumulations of PrPSc with coarse granular morphology, largely in the juxtanuclear region of cytoplasm. However, when the brain-spiked medium was withdrawn and cells were given control medium, the intensity and extent of PrPSc immunostaining rapidly diminished. Co-localisation studies implicated caveolae-mediated endocytic uptake of exogenous PrPSc, apparently preceding uptake via clathrin coated pits in HK cells. Evidence suggesting that the endosomal recycling compartment and lysosomes are involved in intracellular trafficking and degradation of exogenous PrPSc was also found. Understanding the cell biology of these processes may help to explain why the majority of cultured cells are refractory to prion infection in vitro. Internalization of misfolded PrP and its subsequent degradation in the lysosomal compartment might function as a self-protective cellular mechanism, serving to eliminate non-native, presumably dysfunctional and potentially dangerous PrP conformers, whether generated endogenously or acquired through exposure to exogenous prion infectivity.

Each year more than 44,000 women are diagnosed with breast cancer and more than 12,000 of these die from the disease. These mortality rates are relatively high compared to the rest of Europe (Berrino et al., 2007; Mayor, 2003), which in part is due to the advanced stage of the disease at first presentation (McCready et al., 2005; Sant et al., 2003). Regular breast self-examination (BSE) can facilitate early detection (Cancer Research UK, 2008), yet it is not widespread. Identifying the motivational and contextual factors is likely to lead to the development of effective interventions as part of being ‘breast-aware’. This is particularly important given that mammography screening may not be effective (Crossing & Mansezewicz, 2003) or recommended for younger women (Cancer Research UK, 2008) and that BSE may be beneficial in offering women the opportunity to create a positive relationship with their body. This study considered the utility of a proposed Extended Health Belief Model (E-HBM) as a framework for understanding women’s knowledge, beliefs and behaviour. It sought to develop a new way to provide guidance and to encourage BSE by investigating the effect of autobiographical accounts of breast-cancer patients and a multimedia BSE support programme comparing video-enhanced or static guided instructions. The study adopted a 2x2 mixed methods design and 60 white British women aged between 19 and 67 participated. Analysis of Covariance revealed an interaction effect of autobiographical accounts and BSE support on BSE frequency and proficiency and regression analyses examined the utility of the E-HBM, with confidence being the main predictor. Moreover, thematic analysis elicited five themes; Previous Experience, BSE Irregularity, Perceived Susceptibility, Coping Style and The Usability of the 5 Step Model of BSE. The study concludes that the 5-step technique encourages BSE through creating a more pleasant experience, as women form an improved relationship with their breasts. Both the video-enhanced and static BSE supports are effective in terms of encouraging BSE and the effect of autobiographical accounts appears to be dependent on the type support. The practical implications and direction for future BSE interventions are discussed.

Master of Agribusiness / Department of Agricultural Economics / Vincent Amanor-Boadu / The beef industry is a very important in the food sector of agriculture and over the past two decades the United States beef industry has faced many challenges. Over time the distribution of beef exports have changed due to food safety issues and government policies, not just in the U.S., but on a global scale forcing U.S. beef producers to diversify their export outputs to other countries that were not previously strong leaders in the export business. The U.S. must be strategic in their production decisions in order to continue to compete on a global level to avoid significant loss during adverse conditions. One of the major challenges that the U.S. industry has faced is the discovery of BSE in late 2003 in the state of Washington, which led to the closing of many borders to countries who had a significant impact on the beef industry in the U.S. Since U.S. beef is highly regarded by consumers for its quality worldwide, it is important to understand what changes have taken place in the past to have a full understanding of what changes need to be made in the future. The objective of this thesis is to look at how the distribution of the value, volume and price of U.S. beef exports have changed over the past two decades. By looking at how this has changed we will be able to see what countries are emerging as important customers and how others have declined. This is extremely important since some of the major importing countries have changed or put restrictions on the U.S. beef industry over the past two decades and the industry needs to understand these changes so that they can remain strong in the export sector. By analyzing the global trends of U.S. beef exports by value, volume and price across principal regions of the world, research will show us how to change for future changes. By assessing the effect of the discovery of BSE in the U.S on changes in the distribution of beef exports across the global regions, research will show who emerged when other countries declined. By using this research, the foregoing results will be helpful to inform the industry on what export market strategy can be developed for the U.S. beef industry. The results suggest that BSE had some negative effect on the U.S. beef industry in terms of the value and volume but did not have an impact on the price per pound of beef. Some regions had a larger impact than others when BSE was discovered, such as East Asia, but during this other regions, such as North America, came through and became the leaders in exports for U.S. beef. While there was some growth from the Rest of the World, there was not enough of an impact to compete with the foregoing countries.

Bovine Spongiform Encephalopathy (BSE) belongs to a group of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs) which affect many species. From 1986 more than 184,000 cattle in the UK have been confirmed to be infected with this disease, and in Canada total losses to the economy reached $6 billion. This study examines the gene expression in three major innate immunity components: complement system, toll-like receptors, interleukins, and selected proteins of their signaling pathways. Quantitative real time polymerase chain reaction analyses were performed on caudal medulla samples to identify differentially expressed genes between non-exposed and orally challenged animals. In general, immune genes were down-regulated in comparison to non-challenged animals during first 12 months of disease with a tendency to be up-regulated at terminal stage of BSE. The results from this study provide a basis for further research on the mechanisms modifying immune responses and altering progression of the disease. / Animal Science

In this study the dynamics of risk perceptions about BSE held by Canadian consumers and cow-calf operators are evaluated. Since the BSE outbreak in 2003, Canadian consumers and cow-calf operators may have had various different reactions to BSE. These reactions may be related to their different levels of risk perception about BSE, risk perceptions which may have evolved over time and may be affected by BSE media information. These reactions may also be the result of factors other than BSE. An analysis of behavioural models of consumers and cow-calf producers is required to reveal the impacts of both BSE risk perceptions and non-BSE related factors. In this study, the risk perceptions about BSE are specified applying a Social Amplification of Risk Framework (SARF) and a Prospective Reference Theory (PRT), and evaluated through market observed behaviour of Canadian consumers and cow-calf producers, an approach which is different than the traditional stated preference approach to eliciting risk perception measures. Parametric and non-parametric structural break tests associated with the BSE outbreak (May 2003) are employed to evaluate changes in consumers or cow-calf operators behaviour. The results show that SARF is supported by both panel data and time series data on Canadian consumers and cow-calf producers, suggesting that their risk perceptions about BSE are amplified by both the quantity and quality of BSE information. Risk perceptions about BSE have led to a decrease in beef demand and an increase in slaughter cow supply, which in turn, exacerbated losses in Canadian beef sector. Structural break tests related to the BSE outbreak in May 2003 confirm changes in both consumers and cow-calf producers behaviour. Consumers with different profiles had different levels of risk perceptions about BSE and different demand and substitution elasticities. Cow-calf producers from different regions also had different levels of risk perceptions about BSE and different supply elasticities, suggesting the need for more analysis of market segmentation. Simulation analyses over the North American beef sector further confirmed the impact of BSE risk perceptions of Canadian consumers and cow-calf producers in the North American beef and live cattle market. / Agricultural and Resource Economics

No description available.