Campylobacter jejuni and C. coli in Finnish poultry production

Campylobacter, mainly Campylobacter jejuni and C. coli, are worldwide recognized as a major cause of bacterial food-borne gastroenteritis. Epidemiological studies have shown handling or eating of poultry to be significant risk factors for human infections. Campylobacter contamination can occur at all stages of a poultry meat production cycle. The aim of this thesis was to study the occurrence and diversity of Campylobacter in broiler and turkey production in Finland. In summer 1999, 2.9 % of slaughtered broiler flocks were Campylobacter-positive. From the isolated strains 94 % were C. jejuni and 6% were C. coli. During years 2005-2006 one turkey parent flock, the hatchery, six different commercial turkey farms and different stages of the slaughterhouse were monitored during one and the half year. No Campylobacter were detected in either of the samples from the turkey parent flock or from the hatchery using the culture method. Instead PCR detected DNA of Campylobacter from the turkey parent flock and samples from the hatchery. Six out of 12 commercial turkey flocks were found negative at the farm level but only two of those were negative at slaughter. Campylobacter-positive samples within the flock at slaughter were detected between 0% and 94% with evisceration and chilling water being the most critical stages for contamination. All of Campylobacter isolates were shown to be C. jejuni. Campylobacter-positive turkey flocks were colonized by a limited number of Campylobacter genotypes both at the farm and slaughter level. In conclusion, in our first study in 1999 a low prevalence of Campylobacter in Finnish broiler flocks was detected and it has remained at a low level during the study period until the present. In the turkey meat production, we found that flocks which were negative at the farm became contaminated with Campylobacter at the slaughter process. These results suggest that proper and efficient cleaning and disinfection of slaughter and processing premises are needed to avoid cross-contamination. Prevention of colonization at the farm by a high level of biosecurity control and hygiene may be one of the most efficient ways to reduce the amount of Campylobacter-positive poultry meat in Finland. With a persistent low level of Campylobacter-positive flocks, it could be speculated that the use of logistic slaughtering, according to Campylobacter status at farm, might have be advantageous in reducing Campylobacter contamination of retail poultry products. However, the significance of the domestic poultry meat for human campylobacteriosis in Finland should be evaluated.

Disabled Revolutionary War Veterans and the Construction of Disability in the Early United States, c. 1776-1840

This thesis addresses the following broad research question: what did it mean to be a disabled Revolutionary War veteran in the early United States during the period from 1776 to roughly 1840? The study approaches the question from two angles: a state-centred one and an experiential one. In both cases, the theoretical framework employed comes from disability studies. Consequently, disability is regarded as a sociocultural phenomenon rather than a medical condition. The state-centred dimension of the study explores the meaning of disability and disabled veterans to the early American state through an examination of the major military pension laws of the period. An analysis of this legislation, particularly the invalid pension acts of 1793 and 1806, indicates that the early United States represents a key period in the development of the modern disability category. The experiential approach, in contrast, shifts the focus of attention away from the state towards the lived experiences of disabled veterans. It seeks to address the issue of whether or not the disabilities of disabled veterans had any significant material impact on their everyday lives. It does this through a comparison of the situation of 153 disabled veterans with that of an equivalent number of nondisabled veterans. The former group received invalid pensions while the latter did not. In comparing the material conditions of disabled and nondisabled veterans, a wide range of primary sources from military records to memoirs and letters are used. The most important sources in this regard are the pension application papers submitted by veterans in the early nineteenth century. These provide us with a unique insight into the everyday lives of veterans. Looking at the issue of experience through the window of the pension files reveals that there was not much difference in the broad contours of disabled and nondisabled veteran life. This finding has implications for the theorisation of disability that are highlighted and discussed in the thesis. The main themes covered in this study are: the wartime experiences of injured American soldiers, the military pension establishment of the early United States and the legal construction of disability, and the post-war working and family lives of disabled veterans. Keywords: disability, early America, veterans, military pensions, disabled people, Revolutionary War, United States, disability theory.

"Do Not Celebrate Your Feast without Your Neighbours" : A Study of References to Feasts and Festivals in Non-Literary Documents from Ramesside Period Deir el-Medina

This dissertation is a study of the forms and functions of feasts and feasting in the ancient Egyptian village of Deir el-Medina in Thebes (modern Luxor). This particular village, during the New Kingdom (c. 1550 1069 BC), was inhabited by the men (and their families) who constructed the Royal Tombs in the Valley of the Kings and the Valley of the Queens. The royal artisans were probably more literate than the average Egyptians and the numerous Ramesside Period (c. 1295 1069 BC) non-literary texts found in the excavations of the village and its surroundings form the source material for this study. In this study, the methods used are mainly Egyptological and the references to feasts and feasting are considered in view of what is known of New Kingdom Egypt, Thebes, and Deir el-Medina. Nevertheless, it is the use of the methodological concept local vernacular religion that has resulted in the division of the research findings into two sections, i.e., references to feasts celebrated both in and outside the community and other references to feasts and feasting in the village. When considering the function of the feasts celebrated at Deir el-Medina, a functional approach to feasts introduced by anthropologists and archaeologists is utilized. The Deir el-Medina feasts which were associated with the official religion form a festival calendar of feasts celebrated annually on the same civil calendar day. The reconstructed festival calendar of Deir el-Medina reflects the feasts celebrated around Thebes or, at least, in Western Thebes. The function of the nationally and regionally observed feasts (which, at least at Deir el-Medina, resulted in a work-free day) may have been to keep people content so that they would continue to work which was to the advantage of the king and the elite surrounding him. Local feasts appear to have been observed more irregularly at Deir el-Medina or perhaps according to the lunar calendar. Feasts celebrated by the community as a whole served to maintain the unity of the group. In addition to feasts celebrated by the entire community, the inhabitants of Deir el-Medina could mark their own personal feasts and organize small gatherings during public feasts. Through such feasts, an individual man might form alliances and advance his chances of a favourable marriage or of acquiring a position on the work crew.

Deus vult: Images of crusader violence c. 1095-1100.

This study sets out to provide new information about the interaction between abstract religious ideas and actual acts of violence in the early crusading movement. The sources are asked, whether such a concept as religious violence can be sorted out as an independent or distinguishable source of aggression at the moment of actual bloodshed. The analysis concentrates on the practitioners of sacred violence, crusaders and their mental processing of the use of violence, the concept of the violent act, and the set of values and attitudes defining this concept. The scope of the study, the early crusade movement, covers the period from late 1080 s to the crusader conquest of Jerusalem in 15 July 1099. The research has been carried out by contextual reading of relevant sources. Eyewitness reports will be compared with texts that were produced by ecclesiastics in Europe. Critical reading of the texts reveals both connecting ideas and interesting differences between them. The sources share a positive attitude towards crusading, and have principally been written to propagate the crusade institution and find new recruits. The emphasis of the study is on the interpretation of images: the sources are not asked what really happened in chronological order, but what the crusader understanding of the reality was like. Fictional material can be even more crucial for the understanding of the crusading mentality. Crusader sources from around the turn of the twelfth century accept violent encounters with non-Christians on the grounds of external hostility directed towards the Christian community. The enemies of Christendom can be identified with either non-Christians living outside the Christian society (Muslims), non-Christians living within the Christian society (Jews) or Christian heretics. Western Christians are described as both victims and avengers of the surrounding forces of diabolical evil. Although the ideal of universal Christianity and gradual eradication of the non-Christian is present, the practical means of achieving a united Christendom are not discussed. The objective of crusader violence was thus entirely Christian: the punishment of the wicked and the restoration of Christian morals and the divine order. Meanwhile, the means used to achieve these objectives were not. Given the scarcity of written regulations concerning the use of force in bello, perceptions concerning the practical use of violence were drawn from a multitude of notions comprising an adaptable network of secular and ecclesiastical, pre-Christian and Christian traditions. Though essentially ideological and often religious in character, the early crusader concept of the practise of violence was not exclusively rooted in Christian thought. The main conclusion of the study is that there existed a definable crusader ideology of the use of force by 1100. The crusader image of violence involved several levels of thought. Predominantly, violence indicates a means of achieving higher spiritual rewards; eternal salvation and immortal glory.

New Perspectives on the Roman Coinage on the Eastern Limes in the Late Republican and Roman Imperial Period

The Ph.D. thesis discusses the monetary development in Roman Syria and Judaea in the Late Republican and the Early Imperial Period, from a numismatic, archaeological and historical point of view. In effect, the work focuses on the 1st century B.C. to the 1st century A.D., that is, the assumed time of introduction of Roman denarii to the region. The work benefits from the silver coin hoards of Khirbet Qumran recently published by the author. Though discovered as early as 1955 at Qumran, where the famous Dead Sea Scrolls had been found prior to that in 1947, most hoards remained unpublished until 2007. A second important source utilized is the so-called Tax Law from Palmyra in Syria. Its significance lies in the fact that Palmyra used to be one of the most important cities on the Silk Road, along which luxury goods were transported into the Roman Empire and Rome itself. During the research conducted, studies of the provincial coinage of Judaea (A.D. 6-66) shed new light on the authority of the Roman governors in economic and monetary matters in eastern Mediterranean regions. Furthermore, a new suggestion as to the length of the mandate period of Pontius Pilate is made. The extent of Emperor Augustus monetary reforms as well as the military history of Judaea are discussed in the light of new analytical studies, which show that the production of Roman base metal coins appears to have been a highly controlled process, contrary to popular opinion. Statistical calculations related to the coin alloy revealed striking similarities with Roman and other local metalwork found in Israel; a fact previously unknown. Results indicate that both Roman and local metalwork consisted of outstandingly systematized practises and may have exploited the same metal sources. Information: Kenneth Lönnqvist (*25.7.1962) has studied at the University of Helsinki since 1981. Furthermore, Lönnqvist has lived in the Mediterranean countries and the Near East, and made research there at various scientific institutions and universities for ca. 7 years. Contact and sales of thesis: kenneth.lonnqvist@helsinki.fi

VEGF-C and angiopoietins in lymphangiogenesis

Angiogenesis and lymphangiogenesis occur during development as the result of tightly coordinated signalling programs to generate two hierarchically organised vascular systems. All tissues and organs are dependent on a functional blood vasculature for oxygen and nutrients, whereas the lymphatic vasculature functions to collect excess tissue fluid, passing it through lymph nodes for immune surveillance, and returning it to the blood circulation. Effectors that control developmental angiogenesis and lymphangiogenesis are also involved in pathological settings, and therefore potential targets for therapy. Vascular endothelial growth factor (VEGF) and angiopoietin (Ang) growth factors, signalling through endothelial VEGFR and Tie receptors, have been established as key regulators of angiogenic and lymphangiogenic processes in development and disease. In this study, we aimed to obtain a clearer understanding of the vascular effects of stimulation by VEGF-C, Ang1 and Ang2, all known to be involved in lymphangiogenesis. In cell culture models, we found that both intrinsic and microenvironmental regulatory mechanisms are involved in the regulation of endothelial cell phenotypes, and distinct responses to VEGF signalling are induced by specific receptor pathways in different endothelial cell types. Surprisingly, we also found that Ang1 induces sprouting lymphangiogenesis in vivo by a VEGFR-3 dependent mechanism, establishing Ang1 as a novel lymphangiogenic factor. Using inducible transgenic mouse models, we found that VEGF-C-induced lymphatic hyperplasia persisted independently of the growth factor, indicating that short pro-lymphangiogenic therapy could lead to lasting improvements in tissue oedema. While VEGF-C had blood vessel effects in embryos, no angiogenic side effects were observed in adult tissues. Furthermore, inducible transgenic expression of Ang2 during embryonic development confirmed Ang2 as an important regulator of lymphatic remodelling and mural cell contacts. The unexpected similarity of the lymphatic maturation defects caused by excess Ang2 to those observed in Ang2 deficient mice demonstrated that correct doses of Ang2 are crucial for the control of lymphatic development. Unlike Ang1, Ang2 did not induce lymphatic sprouting. Although Ang1 has been shown to be able to substitute for Ang2 during developmental lymphangiogenesis, their lymphatic effects are not identical. These findings further our understanding of the basic mechanisms of angiogenesis and lymphangiogenesis, important for the future development of targeted therapies for vascular diseases such as cancer, inflammation, lymphoedema and ischemia. VEGF-C and Ang1 especially emerged as promising candidates for pro-lymphangiogenic therapy.

VEGF-C/VEGFR-3 and PDGF-B/PDGFR-b pathways in embryonic lymphangiogenesis

The circulatory system comprises the blood vascular system and the lymphatic vascular system. These two systems function in parallel. Blood vessels form a closed system that delivers oxygen and nutrients to the tissues and removes waste products from the tissues, while lymphatic vessels are blind-ended tubes that collect extravasated fluid and cells from the tissues and return them back to blood circulation. Development of blood and lymphatic vascular systems occurs in series. Blood vessels are formed via vasculogenesis and angiogenesis whereas lymphatic vessels develop via lymphangiogenesis, after the blood vascular system is already functional. Members of the vascular endothelial growth factor (VEGF) family are regulators of both angiogenesis and lymphangiogenesis, while members of the platelet-derived growth factor (PDGF) family are major mitogens for pericytes and smooth muscle cells and regulate formation of blood vessels. Vascular endothelial growth factor C (VEGF-C) is the major lymphatic growth factor and signaling through its receptor vascular endothelial growth factor receptor 3 (VEGFR-3) is sufficient for lymphangiogenesis in adults. We studied the role of VEGF-C in embryonic lymphangiogenesis and showed that VEGF-C is absolutely required for the formation of lymph sacs from embryonic veins. VEGFR-3 is also required for normal development of the blood vascular system during embryogenesis, as Vegfr3 knockout mice die at mid-gestation due to failure in remodeling of the blood vessels. We showed that sufficient VEGFR-3 signaling in the embryo proper is required for embryonic angiogenesis and in a dosage-sensitive manner for embryonic lymphangiogenesis. Importantly, mice deficient in both VEGFR-3 ligands, Vegfc and Vegfd, developed a normal blood vasculature, suggesting VEGF-C- and VEGF-D- independent functions for VEGFR-3 in the early embryo. Platelet-derived growth factor B (PDGF-B) signals via PDGFR-b and regulates formation of blood vessels by recruiting pericytes and smooth muscle cells around nascent endothelial tubes. We showed that PDGF-B fails to induce lymphangiogenesis when overexpressed in adult mouse skin using adenoviral vectors. However, mouse embryos lacking Pdgfb showed abnormal lymphatic vessels, suggesting that PDGF-B plays a role in lymphatic vessel maturation and separation from blood vessels during embryogenesis. Lymphatic vessels play a key role in immune surveillance, fat absorption and maintenance of fluid homeostasis in the body. However, lymphatic vessels are also involved in various diseases, such as lymphedema and tumor metastasis. These studies elucidate the basic mechanisms of embryonic lymphangiogenesis and add to the knowledge of lymphedema and tumor metastasis treatments by giving novel insights into how lymphatic vessel growth could be induced (in lymphedema) or inhibited (in tumor metastasis).

A quantum chemical investigation of the metal centres in cytochrome c oxidase

Quantum effects are often of key importance for the function of biological systems at molecular level. Cellular respiration, where energy is extracted from the reduction of molecular oxygen to water, is no exception. In this work, the end station of the electron transport chain in mitochondria, cytochrome c oxidase, is investigated using quantum chemical methodology. Cytochrome c oxidase contains two haems, haem a and haem a3. Haem a3, with its copper companion, CuB, is involved in the final reduction of oxygen into water. This binuclear centre receives the necessary electrons from haem a. Haem a, in turn, receives its electrons from a copper ion pair in the vicinity, called CuA. Density functional theory (DFT) has been used to clarify the charge and spin distributions of haem a, as well as changes in these during redox activity. Upon reduction, the added electron is shown to be evenly distributed over the entire haem structure, important for the accommodation of the prosthetic group within the protein. At the same time, the spin distribution of the open-shell oxidised state is more localised to the central iron. The exact spin density distribution has been disputed in the literature, however, different experiments indicating different distributions of the unpaired electron. The apparent contradiction is shown to be due to the false assumption of a unit amount of unpaired electron density; in fact, the oxidised state has about 1.3 unpaired electrons. The validity of the DFT results have been corroborated by wave function based coupled cluster calculations. Point charges, for use in classical force field based simulations, have been parameterised for the four metal centres, using a newly developed methodology. In the procedure, the subsystem for which point charges are to be obtained, is surrounded by an outer region, with the purpose of stabilising the inner region, both electronically and structurally. Finally, the possibility of vibrational promotion of the electron transfer step between haem a and a3 has been investigated. Calculating the full vibrational spectra, at DFT level, of a combined model of the two haems, revealed several normal modes that do shift electron density between the haems. The magnitude of the shift was found to be moderate, at most. The proposed mechanism could have an assisting role in the electron transfer, which still seems to be dominated by electron tunnelling.