869 resultados para Pre-history Regional
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The technological constraints of early British television encouraged drama productions which emphasised the immediate, the enclosed and the close-up, an approach which Jason Jacobs described in the title of his seminal study as 'the intimate screen'. While Jacobs' book showed that this conception of early British television drama was only part of the reality, he did not focus on the role that special effects played in expanding the scope of the early television screen. This article will focus upon this role, showing that special effects were not only of use in expanding the temporal and spatial scope of television, but were also considered to be of interest to the audience as a way of exploring the new medium, receiving coverage in the popular press. These effects included pre-recorded film inserts, pre-recorded narration, multiple sets, model work and animation, combined with the live studio performances. Drawing upon archival research into television production files and scripts as well as audience responses and periodical coverage of television at the time of broadcast, this article will focus on telefantasy. This genre offered particular opportunities for utilising effects in ways that seemed appropriate for the experimentation with the form of television and for the drama narratives. This period also saw a variety of shifts within television as the BBC sought to determine a specific identity and understand the possibilities for the new medium.
This research also incorporates the BBC's own research and internal dialogue concerning audiences and how their tastes should best be met, at a time when the television audience was not only growing in terms of number but was also expanding geographically and socially beyond the moneyed Londoners who could afford the first television sets and were within range of the Alexandra Palace transmissions. The primary case study for this article will be the 1949 production of H.G.Wells’ The Time Machine, which incorporated pre-recorded audio and film inserts, which expanded the narrative out of the live studio performance both temporally and spatially, with the effects work receiving coverage in the popular magazine Illustrated. Other productions considered will be the 1938 and 1948 productions of RUR, the 1948 production of Blithe Spirit, and the 1950 adaptation of The Strange Case of Dr Jekyll and Mr Hyde. Despite the focus on telefantasy, this article will also include examples from other genres, both dramatic and factual, showing how the BBC's response to the changing television audience was to restrict drama to a more 'realistic' aesthetic and to move experimentation with televisual form to non-drama productions such as variety performances.
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Background: Outwith clinical trials, patient outcomes specifically related to SACT (systemic anti-cancer therapy) are not well reported despite a significant proportion of patients receiving active treatment at the end of life. The NCEPOD reviewing deaths within 30 days of SACT found SACT caused or hastened death in 27% of cases.
Method: Across the Northern Ireland cancer network, 95 patients who died within 30 days of SACT for solid tumours were discussed at the Morbidity and Mortality monthly meeting during 2013. Using a structured template, each case was independently reviewed, with particular focus on whether SACT caused or hastened death.
Results: Lung, GI and breast cancers were the most common sites. Performance status was recorded in 92% at time of final SACT cycle (ECOG PS 0-2 89%).
In 57% the cause of death was progressive disease. Other causes included thromboembolism (13%) and infection (5% neutropenic sepsis, 6% non-neutropenic sepsis). In 26% with death from progressive disease, the patient was first cycle of first line treatment for metastatic disease. In the majority discussion regarding treatment aims and risks was documented. Only one patient was receiving SACT with curative intent, who died from appropriately managed neutropenic sepsis.
A definitive decision regarding SACT's role in death was made in 60%: in 49% SACT was deemed non-contributory and in 11% SACT was deemed the cause of death. In 40% SACT did not play a major role, but a definitive negative association could not be made.
Conclusion: Development of a robust review process of 30-day mortality after SACT established a benchmark for SACT delivery for future comparisons and identified areas for SACT service organisation improvement. Moreover it encourages individual practice reflection and highlights the importance of balancing patients' needs and concerns with realistic outcomes and risks, particularly in heavily pre-treated patients or those of poor performance status.
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How much does the antiquity of states, and the sometimes arbitrary nature of colonial boundaries, explain the modern degree of ethnic diversity? It is shown that states with greater historical legitimacy (more continuity between the pre-colonial and post-colonial state) have less ethnic diversity. Historical legitimacy is more strongly correlated with ethnic diversity than are the antiquity of states, genetic diversity or the duration of human settlement. Although historical legitimacy is particularly pertinent to Africa, the correlation also holds outside Africa.
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`Rainha Cláudia Verde' é uma antiga variedade da ameixeira europeia Prunus domestica L. que se encontra bem adaptada a uma zona restrita do Alto Alentejo. Esta variedade é utilizada para o consumo em fresco e na doçaria regional, onde se emprega na confecção das famosas 'Ameixas D'Elvas'. A confitagem é a técnica utilizada na confecção deste produto com denomicação de origem protegida, e que faz parte de um saber tradicional muito divulgado na região. As informações que resultam de evidências práticas mostram que nem todos os frutos reagem da mesma forma à fase da cozedura. Existem zonas específicas que produzem frutos que não se adequara processo da confitagem, apresentando uma textura imprópria após a cozedura. Recentemente, e com o aumento das áreas produtoras, verificou-se que os frutos destas regiões específicas para além de inadequados para a cozedura, também apresentavam uma menor capacidade de conservação em fresco. Assim durante a conservação estes frutos, quando comparados com os das outras regiões, apresentavam uma perda de firmeza mais rápida tornando-se mais difíceis de comercializar. Entre os factores culturais que contribuem para a qualidade pós-colheita dos frutos, o teor de cálcio presente no solo e nos frutos apresenta-se corno um dos mais importantes. O cálcio é um dos nutrientes que mais frequentemente é associado à manutenção da estrutura das paredes celulares das plantas, estando envolvido directamente na redução das perdas de textura dos frutos. Tendo em consideração os aspectos anteriormente referidos, foi delineado um trabalho que teve início com a selecção de dois pomares geograficamente distantes, e que tradicionalmente produziam frutos com diferentes comportamentos quer durante a conservação quer durante a confitagem. Associada ao conhecimento empírico, a prévia indicação de que estes pomares apresentavam concentrações cle cálcio foliar significativamente diferentes, contribuiu também para a sua selecção. O objectivo geral desta tese foi o de investigar o comportamento pós-colheita da `Rainha Cláudia Verde' particularmente a influência do cálcio na textura dos frutos. Definiram-se os seguintes objectivos específicos: (1) determinar a influência do porta-enxerto e do solo na concentração de cálcio dos frutos e as respectivas consequências, no seu comportamento pós-colheita; (2) seleccionar um método que permitisse avaliar a produção de etileno dos frutos e consequentemente a atribuição da designação de fruto climatérico ou não climatérico a esta variedade; (3) avaliar os e Feitos durante a conservação, de diferentes níveis de cálcio nos frutos; (4) quantificar nos frutos os níveis de cálcio da parede celular e avaliar a sua influência na firmeza dos frutos; (5) seleccionar as melhores temperaturas de conservação para os frutos desta variedade. Os resultados apresentados nesta tese indicam que a variedade 'Rainha Cláudia Verde' é uma variedade de frutos climatéricos que apresentam uma acentuada perda de textura após a colheita. Durante a conservação frigorífica os frutos apresentaram comportamentos diferentes, de acordo com a sua origem. Os frutos com origem no pomar que tradicionalmente não produz frutos aptos a serem confitados, apresentam simultaneamente uma mais rápida perda de firmeza quando comparados com os frutos dos outros pomares. Sendo que o menor teor de cálcio nos frutos leva a que a diminuição da firmeza da polpa ocorra mais rapidamente. No entanto à colheita não se observaram diferenças significativas da firmeza da polpa dos frutos. Esta informação parece indicar que outros factores, além do nível de cálcio dos frutos, poderão estar implicados na firmeza revelada à colheita. Por outro lado os frutos com epiderme revelaram diferenças de firmeza nos testes efectuados à colheita. O efeito da epiderme na firmeza dos frutos à colheita parece indicar que outros factores tais como o estado de hidratação dos frutos poderão contribuir para o aumento desta característica dos frutos. Apesar do teor de cálcio dos frutos melhorar o seu comportamento durante a conservação, a sua influência na emissão de etileno não foi evidente. O aumento do teor de cálcio nos frutos pode conseguir-se através de uma selecção adequada do porta-enxerto. Os porta-enxertos estudados induziram quantidades diferentes de cálcio nos frutos, aparentemente contribuindo o vigor do porta-enxerto para um efeito de diluição do cálcio na árvore. O estudo da influência do solo no teor do cálcio dos frutos revelou que os frutos com menor capacidade de conservação provinham de solos com maiores teores de cálcio, e que na sua constituição apresentavam uma menor concentração de cálcio na polpa. Apresenta-se ainda a hipótese de que o excesso de potássio presente nestes solos possa ter contribuído para um menor teor de cálcio nos frutos. De facto os frutos com uma razão Ca/K superior apresentaram também uma firmeza superior./ ABSTRACT - `Raínha Claudia Verde' is an old variety of Prunus domestica which is well adapted to a restrict zone of Alto Alentejo in the south region of Portugal. This variety is much appreciated either as a fresh fruit or as a sweet candy. The candying process is a widespread technique in this region with much empirical knowledge. There are practical evidences which indicate that fruits origin may influence the boiling process. Some fruits produced in specific areas in this region had an inadequate behaviour during boiling, becoming to soft and improper to use in canding. More recently it has been also observed that these specific areas produced fruits with a poor postharvest behaviour. During storage these fruits loose texture very quickly and became improper to commercialize. Many pre and postharvest factors may contribute to differences in fruit quality. calcium is one of most important nutrients which have a major effect on cell wall structure and membrane integrity. Studies on the role of calcium in fruits indicate its involvement in delaying changes associated with softening. Two orchards were selected because of their history of producing fruits with different characteristics either as a fresh or as a processed fruit, and because induced different calcium levels in the leaves. The main focus of this research work was to study the influence of the production region in fruit postharvest behaviour, specially the influence of calcium in fruit texture. The aims were: (1) to compare the rootstock and the soil influence on calcium fruit content, (2) to select a method- to measure the production of ethylene in fruits of 'Raínha Claudia Verde' (3) to evaluate the effects of different calcium fruit content in the postharvest behaviour of fruits (4) to evaluate the cell wall calcium content and its influence in fruit firmness, (5) and to select the best cold storage temperatures to this variety. It was found that 'Raínha Claudia Verde' is a climacteric variety and the studies on fruit firmness revealed a significant loss of fruit texture during ripening on or off the tree. During storage, fruits had a different behaviour depending on fruits origin. Usually fruits, which traditionally do not resist to boiling process, also exhibited an early softening, when compared to other fruits produced in adequate regions. The excessive fruit softening after harvest occurred in fruits with lower calcium content. However, at harvest, fruits from both orchards exhibited a similar firmness which may indicate that other factors besides calcium should be implicated in fruit firmness at harvest. In spite of a better postharvest behaviour of fruits with higher calcium content, it was not evident the calcium influence in the climacteric rise. The increase of calcium fruit content can be achieved with a proper rootstock selection. The rootstocks investigated in this study, induced different calcium fruit content, apparently vigorous rootstocks contributed to the dilution of calcium fruit level. The soil with higher calcium content induced a lower calcium fruit content, which may be due to the excess of potassium in this soil; in fact fruits with higher Ca/K ratio reached higher firmness values. It is also proposed a method to evaluate the calcium content in the fruit independently of fruit mass. The calcium fruit content is usually expressed as a percentage of dry mass, however during the course of fruit development there are a huge increment of fruit weight because of water and sugar mobilization into the fruit. Most of the total calcium in the plants is associated with the cell wall which means that calcium fruit content expressed as a percentage of cell wall fraction is a much more reliable method. Orchards with an excess of potassium in the soil produced fruits with a significant lower calcium fruit content. However it was not possible to prove the gradually firmness decrease during the harvest period as a consequence of calcium fruit loss. In fact, it was not evident a gradual decrease of calcium fruit content during the harvest dates thus it was impossible to find at harvest, a good correlation between fruit firmness and calcium fruit content. The analysis of cell wall polysaccharides evaluated during ripening in the tree showed a slight increase of more branched polysaccharides as ripening went. The small changes in pectic polysaccharides during the harvest season are in accordance with the small decrease in tissue firmness during this period. In this variety the usual storage period is about of 3-4weeks with a temperature of 1-2°C and 90% of relative humidity. However upon rewarming fruits held at 7°C, during 14 days, produced more ethylene at 20°C and exhibited also a higher firmness than fruits held at PC. The reduction of ethylene production and fruit firmness upon rewarming, after fruits being held at lower temperatures, may suggest some chilling injury in this variety.
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Relatório da Prática de Ensino Supervisionada, Mestrado em Ensino de História e Geografia no 3º ciclo do Ensino Básico e no Ensino Secundário, Universidade de Lisboa, Instituto de Educação, 2015
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The genetic diversity of populations, which contributes greatly to their adaptive potential, is negatively affected by anthropogenic habitat fragmentation and destruction. However, continental-scale losses of genetic diversity also resulted from the population expansions that followed the end of the last glaciation, an element that is rarely considered in a conservation context. We addressed this issue in a meta-analysis in which we compared the spatial patterns of vulnerability of 18 widespread European amphibians in light of phylogeographic histories (glacial refugia and postglacial routes) and anthropogenic disturbances. Conservation statuses significantly worsened with distances from refugia, particularly in the context of industrial agriculture; human population density also had a negative effect. These findings suggest that features associated with the loss of genetic diversity in post-glacial amphibian populations (such as enhanced fixation load or depressed adaptive potential) may increase their susceptibility to current threats (e.g., habitat fragmentation and pesticide use). We propose that the phylogeographic status of populations (i.e., refugial vs. post-glacial) should be considered in conservation assessments for regional and national red lists.
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This investigation comprises three parts: (1) the source, mechanism of transport, and distribution of pollen, spores and other palynomorphs in Georgian Bay bottom sediments and a comparison of these data with the contemporary vegetation, (2) the relative significance of fluvial transportation of pollen and spores, and (3) the late- and postglacial history of vegetational and climatic changes in the Georgicin Bay region. Modem pollen and spore assemblages in Georgian Bay do reflect the surrovinding vegetation when preservation and pollen production by the different species are considered and accounted for. Relative pollen percentage and concentration isopoll patterns indicate that rivers contribute large quantities of pollen and spores to Georgian Bay. This is further substantiated by large amounts of pollen and spores which were caught in traps in the Moon, Muskoka, and Nottawasaga Rivers which flow into Georgian Bay. The majority of pollen and spores caught in these traps were washed into the rivers by surface water runoff and so reflect the vegetation of the watershed in a regional sense. In a 12.9 metre long sediment core from northeastern Georgian Bay the relative percentage and absolute pollen concentrations allow correlation of Georgian Bay Lake phases with climatic and forest history. Four distinct pollen zones are distinguished: zone GB IV which is the oldest, reflects the succession from open spruce woodland to boreal forest; zone GB III represents a period of pine-mixed hardwoods forests from about 10,000 to 7,500 years ago. A pine-maplehemlock association dominated in zone GB II, although during the culmination of postglacial warming about 4,000 to 5,000 years ago the Georgian Bay forests had a more deciduous character. Zone GB I clearly shows European man's disturbance of the forest by logging activities.
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Geochemical examination of the rock matrix and cements from core material extracted from four oil wells within southwestern Ontario suggest various stages of diagenetic alteration and preservation of the Trenton Group carbonates. The geochemical compositions of Middle Ordovician (LMC) brachiopods reflect the physicochemical water conditions of the ambient depositional environment. The sediments appear to have been altered in the presence of mixed waters during burial in a relatively open diagenetic microenvironment. Conodont CAl determination suggests that the maturation levels of the Trenton Group carbonates are low and proceeded at temperatures of about 30 - 50°C within the shallow burial environment. The Trenton Group carbonates are characterized by two distinct stages of dolomitization which proceeded at elevated temperatures. Preexisting fracture patterns, and block faulting controlled the initial dolomitization of the precursor carbonate matrix. Dolomitization progressed In the presence of warm fluids (60 75°C) with physicochemical conditions characteristic of a progressively depleted basinal water. The matrix is mostly Idiotopic-S and Idiotopic-E dolomite, with Xenotopic-A dolomite dominating the matrix where fractures occur. The second stage of dolomitization involved hydrothermal basinal fluid(s) with temperatures of about 60 - 70°C. These are the postulated source for the saddle dolomite and blocky calcite cements occurring in pore space and fractures. Rock porosity was partly occluded by Idiotopic-E type dolomite. Late stage saddle dolomite, calcite, anhydrite, pyrite, marcasite and minor sphalerite and celestite cements effectively fill any remaining porosity within specific horizons. Based on cathode luminescence, precipitation of the different diagenetic phases probably proceeded in open diagenetic systems from chemically homogeneous fluids. Ultraviolet fluorescence of 11 the matrix and cements demonstrated that hydrocarbons were present during the earliest formation of saddle dolomite. Oxygen isotope values of -7.6 to -8.5 %0 (PDB), and carbon isotope values of - 0.5 and -3.0 %0 (PDB) from the latest stage dog-tooth calcite cement suggest that meteoric water was introduced into the system during their formation. This is estimated to have occurred at temperatures of about 25 - 40°C. Specific facies associations within the Trenton Group carbonates exhibit good hydrocarbon generating potential based on organic carbon preservation (1-3.5%). Thermal maturation and Lopatin burial-history evaluations suggest that hydrocarbons were generated within the Trenton Group carbonates some time after 300 Ma . Progressively depleted vanadium trends measured from hydrocarbon samples within southwestern Ontario suggests its potential use as a hydrocarbon migration indicator on local (within an oilfield) and on regional scales.
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The Lincoln County Historical Council began meeting December 17,1960 under the advisement of the Publicity, Planning and Development Committee of Lincoln County. The group was composed of three members appointed from each of the four existing historical societies: one member appointed from the executive of the Women’s Institute, one member from Lincoln County Council, the Deputy-Clerk and Treasurer of the County and a member from the Niagara Editorial Bureau. The Welland County Historical Council was soon formed after this along the same lines. In the early 1960’s the Lincoln and Welland County historical councils began work on an inventory of historic buildings with the intent to emphasize the historical significance of this area. The information gathered by volunteers and a professional photographer and an architect was used to present a “brief” to the federal government in 1962 and the provincial government in 1963. This brief, An Area of Historical Interest in the Counties of Lincoln and Welland, Ontario was published in 1962 and revised and distributed to schools and libraries in the area in 1965. The Ontario Buildings Inventory Project became a provincial initiative spearheaded by the Department of Public Records and Archives, a branch of the Department of Tourism and Information, ca. 1966. Volunteers collected and photographed buildings of historical interest in Lincoln and Welland counties. This information was recorded on standardized survey forms for every township in the Niagara region. Niagara Regional Historical Council was created with the merger of Lincoln County Historical Council and Welland County Historical Council, at the time of the formation of Niagara Regional Government in 1970. The first meeting of the new council was held January 1970.
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Cette thèse s’intéresse aux effets de la conscience historique sur les négociations de l’ethnicité et la structuration des frontières intergroupes chez les enseignants d’histoire nationale au Québec. L’ambiguïté de dominance ethnique entre Francophones et Anglophones contextualise la façon dont les enseignants de ces groupes historicisent les significations du passé pour se connaître et s’orienter « ethniquement. » Selon leurs constructions des réalités intergroupes, ils peuvent promouvoir la compréhension intergroupe ou préserver une coexistence rigide. Le premier article théorise comment les capacités à historiciser le passé, ou à générer des formes de vie morales pour une orientation temporelle, soutiennent la construction de l’ethnicité. En développant un répertoire des tendances de conscience historique parallèles et égales afin de comprendre les fluctuations dans le maintien des frontières ethniques, l’article souligne l’importance de la volonté à reconnaître l’agentivité morale et historique des humains à rendre les frontières plus perméables. Le deuxième article discute d’une étude sur les attitudes intergroupes et les traitements mutuels entre des enseignants d’histoire Francophones et Anglophones. Alors que la plupart des répondants francophones sont indifférents aux réalités sociales et expériences historiques des Anglo-québécois, tous les répondants anglophones en sont conscients et enseignent celles des Franco-québécois. Cette divergence implique une dissemblance dans la manière dont les relations intergroupes passées sont historicisées. La non-reconnaissance de l’agentivité morale et historique des Anglo-québécois peut expliquer l’indifférence des répondants francophones. Le dernier article présente une étude sur la conscience historique des enseignants d’histoire francophone à l’égard des Anglo-québécois. En mettant le répertoire de conscience historique développé à l’épreuve, l’étude se concentre sur la manière dont les répondants historicisent le changement temporel dans leurs négociations de l’ethnicité et leurs structurations des frontières. Tandis que leurs opinions sur l’« histoire » et leurs historicisations des contextes différents les amènent à renforcer des différences ethnoculturelles et à ne pas reconnaître l’agentivité morale et historique de l’Autre, presque la moitié des répondants démontre une ouverture à apprendre et transmettre les réalités et expériences anglo-québécoises. La dépendance sur les visions historiques préétablies pour construire les réalités intergroupes souligne néanmoins l’exclusion de ce dernier groupe dans le développement d’une identité nationale.
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À l’aube du IXe siècle, les Carolingiens prétendent imposer à l’Occident l’unité dans la foi et le culte. Cet idéal domine les pensées des empereurs qui se conçoivent comme protecteurs, législateurs et juges, mais aussi vicaires du Christ et recteurs de l’Église. De telles ambitions stimulent l’élaboration d’un gouvernement original. Comme les conquêtes avaient composé une vaste mosaïque de populations, de cultures et d’intérêts, la concorde posait un grand défi. Pour y répondre, Charlemagne et Louis le Pieux ont fait des communications leur premier outil politique. Leur inventivité et leur efficience furent appréciables, mais elles n’ont pas suffi à leur gagner toutes les adhésions : la discorde s’est installée là où l’empereur ne parvenait pas à maintenir une relation forte avec les élites régionales. Les distances et les modalités des communications déterminaient la nature de leurs échanges, donc leurs limites et, de ce fait, le destin de l’Empire carolingien. L’enquête aborde un vaste éventail documentaire : actes, capitulaires, correspondances, monnaies... Elle s’intéresse particulièrement aux relations du pouvoir impérial avec les élites du sud-ouest de l’empire. Ses résultats dépendent d’un étayage complexe : dispositifs de représentation du pouvoir, conséquences politico-sociales des distances et des vitesses de déplacement, anthropologie de la rencontre et des relations à distance, étude des réseaux. Au-delà des considérations propres à l’histoire des VIIIe-IXe siècles, elle démontre l’intérêt d’aborder les réalités politiques prémodernes du point de vue des défis que présentent les distances géographiques, les rencontres et les communications.
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La pratique du design industriel dans la province canadienne de l’Alberta est en pleine croissance. Ses activités sont principalement concentrées à Edmonton et à Calgary, qui sont les plus grandes villes de la province. On y trouve des studios de design de renom, des communautés de design complexes et des programmes universitaires de design bien établis. Cependant, la pratique du design industriel albertaine est sous-développée en comparaison avec celle du reste du Canada et il y a peu de recherches et de documentation sur le design industriel en Alberta. Dans ce projet de mémoire, la pratique du design industriel en Alberta a été explorée depuis une approche historique. Pour pallier le manque de documentation, la collecte de données a été faite par une recherche qualitative, des entretiens narratifs et une recherche quantitative statistique. Une base d’information historique sur le design industriel albertain a été établie puis située par rapport au développement de la pratique du design industriel ailleurs au Canada. Les facteurs, événements et tendances dans l’histoire de la pratique du design industriel en Alberta ont été identifiés. De plus, le développement de la pratique du design industriel de l’Alberta a été comparé à celui du Québec et de l’Ontario. Les retombées de cette étude indiquent que la pratique du design industriel en Alberta présente quatre domaines de spécialisations distincts se développant depuis les années 1980. La pratique du design industriel en Alberta est sous-développée en comparaison à celui du Québec et de l’Ontario, mais elle peut devenir plus compétitive, au niveau canadien, avec plus de soutien gouvernemental, de meilleures relations avec l’industrie manufacturière et les institutions académiques, une communauté de design plus unifiée et en portant une plus grande attention aux domaines les plus prometteurs de l’industrie. Ces informations supportent une meilleure compréhension de la pratique du design industriel en Alberta et pourront informer les praticiens, enseignants et administrateurs du domaine du design industriel dans la province. Finalement, le mémoire servira de base à d’autres projets de recherche sur les changements potentiels dans la pratique du design industriel en Alberta et l’étude du design canadien et des industries de design régionales.
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Problématique : Bien que le tabac et l’alcool soient les facteurs causaux principaux des cancers épidermoïdes de l’oropharynx, le virus du papillome humain (VPH) serait responsable de l’augmentation récente de l’incidence de ces cancers, particulièrement chez les patients jeunes et/ou non-fumeurs. La prévalence du VPH à haut risque, essentiellement de type 16, est passée de 20% à plus de 60% au cours des vingt dernières années. Certaines études indiquent que les cancers VPH-positifs ont un meilleur pronostic que les VPH- négatifs, mais des données prospectives à cet égard sont rares dans la littérature, surtout pour les études de phase III avec stratification basée sur les risques. Hypothèses et objectifs : Il est présumé que la présence du VPH est un facteur de bon pronostic. L’étude vise à documenter la prévalence du VPH dans les cancers de l’oropharynx, et à établir son impact sur le pronostic, chez des patients traités avec un schéma thérapeutique incluant la chimio-radiothérapie. Méthodologie : Les tumeurs proviennent de cas traités au CHUM pour des cancers épidermoïdes de la sphère ORL à un stade localement avancé (III, IVA et IVB). Elles sont conservées dans une banque tumorale, et les données cliniques sur l’efficacité du traitement et les effets secondaires, recueillies prospectivement. La présence du VPH est établie par biologie moléculaire déterminant la présence du génome VPH et son génotype. Résultats: 255 spécimens ont été soumis au test de génotypage Linear Array HPV. Après amplification par PCR, de l’ADN viral a été détecté dans 175 (68.6%) échantillons tumoraux ; le VPH de type 16 était impliqué dans 133 cas (52.25 %). Conclusion: Une proportion grandissante de cancers ORL est liée au VPH. Notre étude confirme que la présence du VPH est fortement associée à une amélioration du pronostic chez les patients atteints de cancers ORL traités par chimio-radiothérapie, et devrait être un facteur de stratification dans les essais cliniques comprenant des cas de cancers ORL.
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In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.
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Lecture 1: The Pioneers and History of Hypertext (pre-WWW) Contains Powerpoint Lecture slides and Hypertext Research Papers: Bush: As We may Think; Engelbart: NLS and A Framework for Augmenting Human Intelligence; Nelson: Xanalogical Structure; Conklin: A Survey of Hypertext; Halasz 1987: Reflections on NoteCards: Seven Issues for the Next Generation of Hypermedia Systems; Berners-Lee 1994 The World-Wide Web.