Thesis (MScMed)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: It has recently been observed that the application of multiple short cycles of reperfusion and ischaemia, at the onset of reperfusion, elicits cardioprotection against injury due to prior sustained ischaemia. This phenomenon has been termed “postconditioning” (postC) and is of special interest due to its clinical applicability. Although much work has been done to delineate the mechanism of protection, there is still controversy regarding the precise algorithm of postC, the importance of the reperfusion injury salvage kinases (RISK), as well as uncertainty about the possible role of p38 MAPK and the protein phosphatases in postC cardioprotection. The aims of this study were therefore: I. To develop and characterise a cardioprotective postC protocol in the ex vivo rat heart, using both the retrogradely perfused and working heart models. II. To characterise the profiles of PKB/Akt, ERK p42/p44 and p38 MAPK associated with the postC intervention. III. To investigate the possible role of the serine/threonine protein phosphatases type 1 and type 2A (PP1 and PP2A) in the mechanism of postC. Hearts from male Wistar rats were perfused in both the retrograde Langendorff (at a perfusion pressure of 100 cmH2O and diastolic pressure set between 1 and 10 mmHg) and working heart models (preload: 15 cmH20 and afterload: 100 cmH20). Several different postC protocols were tested for their cardioprotective effect, as analysed by infarct size (IFS; determined by triphenyltetrazolium chloride (TTC) staining) and functional recovery. Experimental parameters tested were the number of cycles (3,4 or 6), the duration of the cycles (10, 15, 20 or 30 seconds), the method of application (regional or global) and temperature during the intervention (36.5 or 37 °C). Different sustained ischaemic insults were also utilised: 35 minutes regional (RI) or 20, 25, 30 and 35 minutes global ischaemia (GI). Hearts treated with a cardioprotective postC intervention or standard reperfusion after sustained ischaemia, were freeze-clamped at 10 and 30 minutes reperfusion in both perfusion models. Tissue samples were then analyzed using Western blotting, probing for total and phosphorylated PKB/Akt, ERK p42/p44 and p38 MAPK. The contribution of PKB/Akt and ERK p42/p44 activation to cardioprotection was also investigated by administration of inhibitors (A6730 and PD098059 respectively) in the final 5 minutes of ischaemia and the first 10 minutes of reperfusion, in the presence and absence of the postC intervention. The effect of these inhibitors were analyzed in terms of IFS and kinase profiles. The possible role of the phosphatases in postC was investigated by observing the effect of cantharidin (a PP1 and PP2A inhibitor) treatment directly before sustained ischaemia (PreCanth) or in reperfusion (PostCanth), in the presence and absence of postC, on IFS and kinase profiles. A postC protocol of 6x10 seconds global reperfusion / ischaemia, at 37°C, was found to give the best and most consistent reduction in infarct size in both the Langendorff (IFS in NonPostC: 47.99±3.31% vs postC: 27.81±2.49%; p<0.0001) and working heart (IFS in NonPostC: 35.81±3.67% vs postC: 17.74±2.73%, p<0.001) models. It could however only improve functional recovery in the Langendorff model (after 30 minutes GI: rate pressure product (RPP) recovery: NonPostC = 12.27±2.63% vs postC = 24.61±2.53%, p<0.05; and after 35 minutes GI: left ventricular developed pressure (LVDP) recovery: NonPostC = 28.40±7.02% vs postC = 48.49±3.14%, p<0.05). This protection was associated with increased PKB/Akt (NonPostC: 0.88±0.26 AU (arbitrary unit) vs postC: 1.65±0.06 AU; p<0.05) and ERK p42 (NonPostC: 2.03±0.2 AU vs postC: 3.13±0.19 AU; p<0.05) phosphorylation. Inhibition of PKB/Akt activation with A6730 (2.5 μM) abrogated the infarct sparing effect of postC. Administration of cantharidin, either before of after ischaemia, in the absence of postC, conferred an infarct sparing effect (IFS in PreCanth: 15.42±1.80%, PostCanth: 21.60±2.79%; p<0.05) associated with an increase in the phosphorylation of MAPK p38 (administration before ischaemia: NonCanth: 1.52±0.26 AU vs PreCanth: 2.49±0.17 AU, p<0.05; and administration after ischaemia: NonCanth: 5.64±1.17 AU vs PostCanth: 10.69±1.29 AU, p<0.05) and ERK p42 (when administered in reperfusion; NonCanth: 2.24±0.21 AU vs PostCanth: 3.34±0.37 AU; p<0.05). Cantharidin treatment combined with the postC intervention did not elicit an additive infarct sparing effect (postC: 17.74±2.72%, PreCanth-postC: 13.30±3.46% and PostCanth-postC: 15.39±2.67%). In conclusion: a postC protocol of 6x10 seconds global ischaemia / reperfusion, at 37°C, confers the best infarct sparing effect in both the Langendorff and working rat heart models. This protection is associated with ERK p42 and PKB/Akt phosphorylation, although only PKB/Akt is necessary for cardioprotection. We could not find evidence for PP1 and PP2A involvement in postC, although inhibition of these phosphatases per se does elicit an infarct sparing effect. The latter observation suggests that phosphatase activation during ischaemia / reperfusion is potentially harmful. / AFRIKAANSE OPSOMMING: Dit is onlangs waargeneem dat toediening van meervoudige siklusse herperfusie / iskemie, met die aanvang van herperfusie, die hart teen iskemie / herperfusie beskadiging beskerm. Hierdie verskynsel, bekend as postkondisionering (postC), geniet tans baie aandag vanweë die kliniese toepaslikheid van die ingreep. Ten spyte van intensiewe navorsing om die betrokke meganisme van beskerming vas te stel, is daar steeds kontroversie oor die presiese algoritme van die ingreep, asook die betrokkenheid van die sogenaamde iskemie herperfusie oorlewings kinases (RISK). Daar bestaan ook onsekerheid oor die rol van die stres-kinase, p38 MAPK, asook die proteïen fosfatases in die meganisme van beskerming teen iskemiese besering. Hierdie studie het dus drie doelstellings gehad: I. Ontwikkeling van ‘n postC protokol wat beskerming ontlok in die rothart ex vivo, deur gebruik te maak van beide die retrograad geperfuseerde ballon model, asook die werkhart model. II. Analiese van die profiele van die kinases PKB/Akt, ERK p42/p44 en p38 MAPK tydens herperfusie van postC en kontrole (NonPostC) harte. III. Ondersoek na die moontlike rol van die serien / treonien proteïen fosfatases tipe 1 en tipe 2A (PP1 en PP2A) in die meganisme van postC beskerming. Harte van manlike Wistar rotte is geperfuseer in beide die retrograad geperfuseerde ballon (d.i. die Langendorff) model (teen ‘n konstante perfusie druk van 100 cmH20 en ‘n diastoliese druk gestel tussen 1 en 10 mmHg), asook die werkhart model (teen ‘n voorbelading van 15 cmH20 en ‘n nabelading van 100 cmH20). Verskeie moontlike postC protokolle is getoets vir hul vermoë om kardiobeskerming te ontlok, in terme van funksionele herstel en infarktgrootte (IFS), soos bepaal deur trifenieltetrazolium chloried (TTC) kleuring. Die eksperimentele veranderlikes tydens die postC protokol wat ondersoek is, sluit in: die aantal siklusse (3, 4 of 6), die duur van die siklusse (10, 15, 20 of 30 sekondes), die wyse van postC toediening (streeks of globaal) en laastens die temperatuur tydens die ingreep (36.5 of 37 °C). Daar is ook gebruik gemaak van verskillende periodes iskemie: 35 minute streeks iskemie (RI), asook 20, 25, 30 en 35 minute globale iskemie (GI). Na 10 of 30 minute herperfusie is harte wat blootgestel is aan ‘n kardiobeskermende postC ingreep of gewone standaard herperfusie na iskemie, in beide perfusie modelle, gevriesklamp. Die weefsel proteïen-inhoud is verder geanaliseer deur van die Western blot tegniek gebruik te maak vir bepaling van die totale en fosforileerde vlakke van PKB/Akt, ERK p42/p44 en p38 MAPK. Die funksionele belang van PKB/Akt en ERK p42/p44 is verder ondersoek deur die effek van ‘n geskikte inhibitor (onderskeidelik A6730 en PD098059, toegedien tydens die laaste 5 minute van iskemie en die eerste 10 minute van herperfusie), in die teenwoordigheid en afwesigheid van die postC ingreep, op infarktgrootte en kinase aktiwiteit te monitor. Die moontlike rol van proteïen fosfatases in postC is ondersoek deur die effek van cantharidin (‘n PP1 en PP2A inhibitor) op infarktgrootte en kinase profiele te ondersoek. Cantharidin is óf onmiddelik voor iskemie óf tydens herperfusie toegedien, in die aan – en afwesigheid van die postC ingreep. Daar is bevind dat ‘n postC protokol van 6x10 sekondes globale iskemie / herperfusie, teen 37°C, die mees effektiewe en konstante verlaging in infarktgrootte teweeg gebring het in beide die ballon model (IFS in NonPostC: 47.99±3.31% vs postC: 27.81±2.49%; p<0.0001), asook die werkhart (IFS in NonPostC: 35.81±3.67% vs postC: 17.74±2.73%, p<0.001). Funksionele herstel kon egter slegs ontlok word in die ballon model (na 30 minute GI: tempo druk produk (RPP) herstel: NonPostC = 12.27±2.63% vs postC = 24.61±2.53%, p<0.05; en na 35 minute GI: linker ventrikulêre ontwikkelde druk (LVDP) herstel: NonPostC = 28.40±7.02% vs postC = 48.49±3.14%, p<0.05). Die infarkt-besparende effek van postC was geassosieer met ‘n toename in die fosforilasie van beide PKB/Akt (NonPostC: 0.88±0.26 AU (arbitrêre eenhede) vs postC: 1.65±0.06 AU; p<0.05) en ERK p42 (NonPostC: 2.03±0.2 AU vs postC: 3.13±0.19 AU; p<0.05). Inhibisie van PKB/Akt met A6730 (2.5 μM) het die infarkt-besparende effek van postC opgehef. Inhibisie van PP1 en PP2A opsigself, deur toediening van cantharidin óf voor óf na iskemie (in die afwesigheid van postC), het ‘n infarkt-besparende effek ontlok (IFS in PreCanth: 15.42±1.80%, PostCanth: 21.60±2.79%; p<0.05). Hierdie kardiobeskerming was geassosieer met ‘n toename in die fosforilasie van beide p38 MAPK (met toediening voor iskemie: NonCanth: 1.52±0.26 AU vs PreCanth: 2.49±0.17 AU, p<0.05; en toediening na iskemie: NonCanth: 5.64±1.17 AU vs PostCanth: 10.69±1.29 AU, p<0.05), asook ERK p42, indien cantharidin toegedien is tydens herperfusie (NonCanth: 2.24±0.21 AU vs PostCanth: 3.34±0.37 AU; p<0.05). Kombinasie van cantharidin behandeling met postC toediening kon egter nie ‘n kumulatiewe infarkt-besparende effek uitlok nie (postC: 17.74±2.72%, PreCanth-postC: 13.30±3.46% en PostCanth-postC: 15.39±2.67%). In samevatting: ‘n PostC protokol van 6x10 sekondes globale iskemie / herperfusie, teen 37°C, ontlok die mees effektiewe infarkt-besparende effek in beide die ballon, sowel as die werkhart modelle. Alhoewel hierdie beskerming geassosieer is met ‘n toename in die fosforilasie van beide PKB/Akt en ERK p42/p44 tydens herperfusie, is dit slegs PKB/Akt wat van funksionele belang is in die meganisme van kardiobeskerming. Ons kon geen bewyse vind vir die betrokkenheid van PP1 en PP2A in postC beskerming nie, alhoewel inhibisie van hierdie fosfatases opsigself infarkt-besparend is. Laasgenoemde waarneming toon dat fosfatase aktivering tydens iskemie / herperfusie skadelike gevolge mag hê.

Le domaine des énergies est au cœur des préoccupations technologiques, politiques et économiques de notre société moderne. Ce domaine nécessite une compréhension minimale du concept scientifique de l’énergie. Elle est selon nous essentielle à toute formation citoyenne. Nous avons dans un premier temps, à partir de considérations théoriques et pratiques, examiné pourquoi ce domaine si important dans notre société technologique est si peu abordé dans le cursus scolaire québécois? Pourquoi se contente-t-on d’un enseignement théorique et discursif de ce concept? Pourquoi, au contraire de tout enseignement scientifique, n’a-t-on pas envisagé de situations d’apprentissages en laboratoire pour l’étude des énergies? Dans un deuxième temps, nous avons proposé une idée de solution concrète et réaliste pour répondre à l’ensemble de ces questions. Une solution qui invite les élèves à s’investir de manière constructive dans des activités de laboratoire afin de s’approprier ces concepts. Pour ce faire, nous avons conçu des variables globales énergies qui ont permis aux élèves de les mesurer et d’expérimenter facilement des transformations énergétiques. Cette recherche de développement technologique en éducation consiste donc à profiter des nouveaux développements technologiques de l’informatique et de la micro-électronique pour concevoir, réaliser et mettre à l’essai un environnement informatisé d’apprentissage en laboratoire pour les sciences et la technologie. Par ce que l’énergie est au confluent de trois domaines, cet environnement a été conçu pour supporter dans une même activité l’apprentissage des mathématiques, des sciences et de la technologie. Cette intégration recommandée par les nouveaux programmes est, selon nous, essentielle à la compréhension des concepts liés à l’énergie et à ses transformations. Par cette activité d’apprentissage multidisciplinaire, nous voulons, via une approche empirique et concrète, aborder ces problèmes de transformations énergétiques afin de donner aux élèves la capacité de perfectionner les prototypes qu’ils construisent en technologie de manière à améliorer leurs performances. Nous avons montré que cette démarche technoscientifique, assimilable à la conception d’un schème expérimental en sciences, favorise la compréhension des concepts liés aux énergies et à leurs transformations. Ce développement, ouvert à l’investigation scientifique, apporte un bénéfice didactique, non seulement, pour des enseignants en exercices et des étudiants-maîtres, mais aussi pour des élèves de 5ème année du niveau secondaire, ce que nous avons démontré dans une mise à l’essai empirique. / The energy sector is at the heart of the concerns technological, political and economic modern society. This area requires a basic understanding of the scientific concept of energy. It is our opinion essential to any citizen training. We initially, from theoretical and practical considerations, examined why this area is so important in our technological society is so little discussed in the Quebec curriculum? Why do we merely a theoretical and discursive concept? Why, contrary to all scientific education, have we not considered learning situations in the laboratory for the study of energy? In a second step, we proposed an idea of practical and realistic solution to address all these questions. A solution that invites students to engage constructively in laboratory activities to appropriate these concepts. To do this, we have developed global variables energies that allowed students to experiment and measure energy transformations easily. This quest for technological development in education is therefore to take advantage of new technological developments in computing and microelectronics to design, build and test a computerized environment learning laboratory for science and technology. With this energy is at the confluence of three domains, this environment has been designed to support the same activity in the learning of mathematics, science and technology. This integration recommended by the new programs we believe is essential to the understanding of concepts related to energy and its transformations. For this learning activity multidisciplinary, we want, via an empirical and practical address these issues of energy transformations in order to give students the ability to develop the prototypes they build technology to improve their performance. We have shown that this approach techno, similar to the design of an experimental design in science, promotes understanding of concepts related to energy and their transformations. This educational development, open to scientific investigation, provides educational benefit, not only for practicing teachers and student teachers, but also for students from the fifth year of high school, we have shown in a setting tested empirically.

Le tube digestif héberge une communauté microbienne complexe, le microbiote intestinal, dont les capacités métaboliques sont plus riches et diversifiées que celles codées par le génome de l'hôte. L'implication du microbiote intestinal dans divers aspects de la physiologie de l'hôte, comme le métabolisme nutritionnel et l'immunité, est depuis longtemps étudiée. En revanche, l'action potentielle du microbiote sur le développement et le fonctionnement du cerveau constitue une nouvelle piste de recherche, encore peu explorée. Dans ce contexte, nous avons réalisé une première étude générale de l'action du microbiote intestinal sur le cerveau en comparant les fonctions sensori-motrices, le comportement de type anxieux, l'état d'activation de l'axe hypothalamo-hypophyso-surrénalien et le profil cérébral des monoamines de rats F344 axéniques et conventionnels. Les résultats révèlent que, chez cette lignée particulièrement sensible au stress, l'absence de microbiote intestinal exacerbe le comportement de type anxieux et la réponse hormonale au stress, et atténue le métabolisme dopaminergique cérébral. Afin d'étudier par quel moyen le microbiote peut agir sur le cerveau, une seconde étude a été menée, ciblant un métabolite bactérien spécifique, l’indole, dont certains dérivés oxydés par le foie sont connus pour avoir des propriétés neuroactives. L'indole est un métabolite naturel du microbiote intestinal, dont la surproduction pourrait survenir lors d'une dysbiose du microbiote. Deux cas de surproduction ont été modélisés : chronique et aiguë. Dans les deux cas, des modifications importantes du comportement de l'hôte ont été observées. En situation de surproduction chronique, l'indole favorise des comportements de type anxieux et dépressif, tandis qu'une surproduction aiguë a un effet sédatif marqué. D'un point de vue mécanistique, nous confirmons que l’indole peut agir sur le système nerveux central par la voie sanguine impliquant les dérivés oxydés et montrons pour la première fois qu'il peut aussi agir en activant les noyaux cérébraux du nerf vague. / The gastro-intestinal tract hosts a complex microbial community, the gut microbiota, whose collective genome coding capacity vastly exceeds that of the host genome. The involvement of the gut microbiota in various aspects of the host physiology, such as the nutritional metabolism and the immunity, has long been studied. In contrast, the possible action of the gut microbiota on brain development and functioning is a new line of research, still poorly explored. In this context, we performed a first general study of the effect of gut microbiota on the brain by comparing the sensory-motor functions, the anxiety-like behaviour, the activation of the hypothalamic-pituitary-adrenal axis and the brain monoamine profile in germ-free and conventional F344 rats. The results show that, in this particularly stress-sensitive strain, absence of gut microbiota exacerbates the anxiety-like behaviour and neuroendocrine response to stress, and reduces brain dopamine metabolism. To investigate the means by which the microbiota can affect the brain, a second study was conducted, targeting a specific bacterial metabolite, indole, whose oxidative derivatives, produced by the liver, are known to have neuroactive properties. Indole is a natural metabolite of the gut microbiota, whoseoverproduction could occur during a microbiota dysbiosis. Two conditions of overproduction, namely chronic and acute, were modelled. In both cases, significant changes in the behaviour of the host were observed. In chronic overproduction, indole promotes anxiety- and depressive-like behaviours, while acute overproduction has a marked sedative effect. From a mechanistic point of view, we confirm that indole can act on the central nervous system through its oxidized derivatives and show for the first time that it can also act by activating the brain nuclei of the vagus nerve.

RésuméEn raison des bouleversements qui ont eu lieu dans la seconde moitié du XXe siècle, le monde a connu une accélération notable de l'histoire. Cette accélération s'est manifestée sur plusieurs fronts – l'historique, le scientifique, le technologique – mais aussi sur le front littéraire, changeant à jamais la façon dont nous représentons notre monde et notre passé. Cette thèse porte sur les nouveaux modes de représentation ou mimesis dans l'œuvre d'art. Comment les événements, qui se déroulent en dehors du roman, ont-ils affecté la forme même, la technique et la langue du roman contemporain ? Comment la violence qui a été infligée au monde extérieur s'est-elle reflétée dans le récit littéraire ? Du fait que la forme narrative est en soi un moyen de « rassembler » les événements dispersés et les incohérences de la réalité, la forme traditionnelle manipule violemment cette réalité dans le but de lui donner un sens, quand elle est souvent inexplicable. En mettant en question les conventions naturelles et données du récit, les romans expérimentaux du XXe siècle ont tenté de mettre en place des formes originales, en mesure de représenter des expériences différentes. Notre thèse traite principalement de ces nouvelles conceptions de la représentation dans le roman contemporain et de la manière dont, en dépit de leur fragmentation, de l'expérimentation et de la rupture violente avec les traditions du passé, ces romans innovants ont néanmoins réussi à produire des «représentations» de la réalité qui captent fidèlement notre histoire contemporaine, caractérisée par l'accélération et la fragmentation. Pour justifier cet argument, nous avons comparé les récits de fiction avec ceux des deux autres domaines à partir desquels nous tirons la connaissance de notre passé, à savoir l'histoire et la mémoire. Où est la place de la fiction aux côtés de ces deux piliers de connaissance souvent totalisants et totalitaires ? Enfin, que peut faire la littérature pour ces sujets de l'histoire, systématiquement exclus de l'écriture de l’histoire dominante ? En prenant la plume pour écrire leur version de l'histoire, ces «autres» du document historique dominant ont inscrit leur histoire particulière sur le palimpseste existant de l'histoire dominante et ont également obligé les canons littéraires, auxquels ils appartiennent, à développer leurs limites esthétiques et éthiques. / SummaryAs a result of the changes that have occurred in the latter half of the twentieth century, the world has witnessed a noticeable acceleration of history. This acceleration has manifested itself on many fronts – the historic, the scientific, the technological – but also on the literary front changing forever the way we represent our world and our place in it. This paper deals with the new modes of representation or mimesis in the work of art. How have the events happening outside the novel affected the very form, technique and the language of the contemporary novel? How has the violence that has been inflicted on the outside world being replicated and perhaps resolved in the literary narrative? Because narrative form is in itself a way of ordering and “bringing together” the fragmented events and incoherencies of reality, the very traditional form often violently manipulates this reality with the aim of giving meaning to an often inexplicable reality. By bringing into question the natural and given conventions of narrative, the experimental novels of the twentieth century have tried to realize original and unique forms that are able to represent different experiences. Our paper deals with primarily with these new conventions of representing reality and how, despite their fragmentation, experimentation, and violent rupture with the traditions of the past, they have nonetheless successfully produced “representations” of reality that faithfully capture our contemporary history characterized by acceleration as well as fragmentation. In order to justify this argument, we have compared narratives of fiction with the other two domains from which we derive the knowledge of our past, namely history and memory. Where is the place of fiction alongside these two often totalizing and totalitarian pillars of knowledge? Finally, what can literature do to those subjects of history who have systematically excluded from the writing of their dominant History? By taking the pen to write their side of the story, these “others” of the dominant historical document have both inscribed their particular stories on the existing palimpsest of dominant history, but have also forced the literary canons in which they belong to expand both their aesthetic and ethical boundaries.

Introdução - Pacientes com enfisema pulmonar avançado submetidos a redução volumétrica pulmonar endoscópica (ELVR) com válvulas unidirecionais (EBV) apresentam melhores resultados quando o lobo tratado não possui ventilação colateral e atelectasia lobar é alcançada. No entanto, a resposta positiva de desinsuflação está associada a maior ocorrência de pneumotórax nessa população. Recomendações recentes enfatizam a importância de condutas no intra- e pós-operatório que busquem minimizar os riscos associados, porém muito pouco é abordado em relação ao manejo da ventilação mecânica durante a intervenção. Elevada fração inspirada de oxigênio (FiO2) é reconhecida na indução de atelectasia por absorção e pode desempenhar um papel relevante na modulação de redução volumétrica após oclusão seletiva. Atualmente não se monitora os efeitos regionais da ELVR com EBV em tempo real. A tomografia de impedância elétrica (TIE) é uma ferramenta de imagem não-invasiva e sem radiação que fornece dados regionais em tempo real de variação de volume pulmonar por meio de uma cinta de eletrodos aplicadas no tórax. Neste contexto, o objetivo deste estudo é usar a TIE para avaliar a influência da FiO2 na ELVR com EBV em um modelo experimental de pulmão normal suíno, animal que não possui ventilação colateral. Métodos - 5 suínos foram submetidos a um estudo cruzado de oclusão do lobo inferior esquerdo por dois métodos, válvulas unidirecionais (válvulas) e cateter-balão intrabronquial (balão), com FiO2 de 50% e 100% por 15 minutos em cada etapa. O balão serviu como um controle, com oclusão assegurada por visão direta via broncoscópio e medida da pressão expiratória distal à oclusão em um animal representativo. A pressão expiratória positiva final usada foi titulada pela TIE para cada animal e recrutamento alveolar foi realizado ao final de cada etapa para reverter o colapso induzido. Foram analisados o mínimo Z (MinZ), como estimativa do volume pulmonar ao final da expiração, e o DeltaZ, variação cíclica proporcional ao volume corrente, ambos expressos em unidades arbitrárias de variação relativa, desde antes da oclusão (Pré) e em cada minuto do momento da oclusão (T0) até 15 minutos (T15). Em um animal adicional foi realizada aquisição simultânea de tomografia computadorizada (TC) e TIE para quantificação do conteúdo de gás. Em todas as análises as regiões de interesse foram direita (Dir) e esquerda (Esq). Resultados - Houve redução rápida e progressiva do MinZ Esq após oclusão com balão, sendo a magnitude quase 3 vezes maior na FiO2 de 100% comparada a 50% (p < 0,001). Com válvulas a 50% o MinZ Esq apresentou redução inicial, mas teve incremento progressivo de forma que em T15 não mostrou diferença em relação ao Pré (p=0,20). Em média, o MinZ Dir não sofreu alteração significativa. Os dados da TC e pressão distal tiveram padrão similar aos achados de MinZ da TIE. O DeltaZ Esq apresentou redução imediata após oclusão e se manteve estável ao longo dos 15 minutos, sem diferença entre as FiO2 em cada método de oclusão. Conclusão- FiO2 a 100% promove maior taxa de redução volumétrica secundária a oclusão lobar seletiva quando comparado a 50% e a TIE apresentou resultados coerentes e concordantes com métodos complementares / Introduction - Patients with advanced pulmonary emphysema undergoing endoscopic lung volume reduction (ELVR) with one-way endobronchial valves (EBV) present better results when the treated lobe has negative collateral ventilation and lobar atelectasis is achieved. However, the positive response of deflation is associated with a higher occurrence of pneumothorax in this population. Recent recommendations emphasize the importance of intra- and postoperative procedures that seek to minimize the associated risks, but very little is addressed regarding the management of mechanical ventilation during the intervention. High inspired oxygen fraction (FiO2) is known to induce atelectasis by absorption and may play a relevant role in the modulation of volumetric reduction after selective occlusion. Currently, regional effects of ELVR with EBV is not monitored in real-time. Electrical impedance tomography (EIT) is a non-invasive and radiation-free imaging tool that provides regional real-time lung volume variation data by means of an electrode belt applied to the chest. In this context, the objective of this study is to use EIT to evaluate the influence of FiO2 on ELVR with EBV in an experimental normal lung swine model, an animal that lacks collateral ventilation. Methods - Five pigs were used in a crossover study of left lower lobe occlusion by two methods, one-way valves (valves) and intrabronchial balloon catheter (balloon), with FiO2 of 50% and 100% for 15 minutes at each stage. The balloon served as a control, where occlusion was ensured by direct bronchoscopic inspection and allowed a measurement of expiratory pressure distal to the occlusion in a representative animal. The positive end-expiratory pressure used was titrated by EIT for each animal and alveolar recruitment was performed at the end of each step to reverse the induced collapse. Minimum impedance value (MinZ) was recorded as an estimate of end-expiratory lung volume and tidal impedance variation (DeltaZ) as proportional to tidal volume, both expressed in arbitrary units of relative variation, from pre-occlusion (Pre) and every minute since occlusion (T0) up to 15 minutes (T15). In an additional animal, simultaneous acquisition of computed tomography (CT) and EIT was performed to quantify gas content. In all the analysis, regions of interest were right (R) and left (L). Results - There was a rapid and progressive reduction of MinZ-L after occlusion, with almost 3 times greater magnitude in FiO2 100% compared to 50% (p < 0.001). With valves at 50%, the MinZ-L presented initial reduction, but had a progressive increase so that in T15 there was no difference in relation to Pre (p = 0.20). On average, MinZ-R did not change significantly. CT and distal pressure data were consistent with EIT MinZ findings. DeltaZ-L presented immediate reduction after occlusion and remained stable throughout all 15 minutes, with no difference between FiO2 in each method of occlusion. Conclusion- FiO2 of 100% promotes greater rate of volumetric reduction following selective lobar occlusion when compared to 50%, and EIT presented coherent results in agreement with complementary methods

[pt] Este trabalho compõe-se de diferentes modos de estruturação textual, acompanhando uma tendência pós-moderna. Através da fabricação de suas memórias pessoais, o autor apresenta e avalia a atuação do CEP 20.000, de que participa como coordenador, desde a fundação, em 1990. A perspectiva crítica é a do observador da cidade, uma espécie de flâneur do panorama cultural, de onde colhe a matéria para sua escrita, produzida em intercâmbio com uma rede de amigos. A primeira pessoa do discurso quer-se propositalmente frágil, empenhada na experiência de deixar-se atravessar por uma pluralidade de vozes e pontos de vista. Ao longo dos capítulos, misturam-se crônicas, desenhos, e-mails, cartas, entrevistas, notícias de jornal, fotografias, poemas, contos e fragmentos de outros textos, inéditos ou já publicados, cuja seleção e articulação foi planejada de modo a dialogar com o discurso acadêmico. Trata-se de uma proposta alternativa de trabalho escritural adequado a uma compreensão ampla da história do presente. / [en] This work is composed by different modes of text framing, according to a postmodern tendency. While weaving his fictionalized memories, the author presents and evaluates the performance of CEP 20.000 which he has helped founding, in 1990, and coordinates till this day. His perspective is that of the spectator of the town life, a kind of flâneur in the cultural scenery, where he gathers up the subjects for his writing produced in interchange with a net of friends. The first person of speech intends to be fragile since it is meant as an experience of textuality intertwined by a plurality of voices and viewpoints. The chapters are built in blocs alternating with a miscellany of chronicles, drawings, e-mails, letters, intervews, news, photographs, poems, short stories and fragments of other types of texts, published or not. The choice and articulation of this material was planned to establish a dialogue with the accademic discourse. The goal of the essay is to propose a writing strategy adequate to a broad understanding of the history of the present.

Esta tese está inserida no debate sobre a utilização da experimentação construtiva ao longo da concepção da materialidade e seu papel como recurso pedagógico. Trata mais especificamente, dos espaços e práticas experimentais no contexto acadêmico nacional, objetivando compreender o processo de configuração dos espaços da área técnico-construtiva implantados nas escolas públicas de arquitetura de acordo com as particularidades advindas de diferentes contextos do país, das políticas educacionais e das ações dos atores envolvidos, com a identificação das condições essenciais para que estas práticas sejam implantadas e potencializadas no contexto acadêmico. O trabalho foi desenvolvido a partir de pesquisas documentais e por meio de visitas técnicas realizadas em 21 escolas públicas de arquitetura localizadas em diferentes regiões do país, com entrevistas direcionadas aos principais atores que atualmente estão à frente da área da Tecnologia da Construção. O trabalho trouxe contribuições de ordem teórica a partir da sistematização de uma bibliografia abrangente sobre um tema pouco estudado no contexto nacional. Quanto às contribuições de ordem prática, os dados obtidos nas visitas técnicas possibilitaram contextualizar os desafios enfrentados no ensino da Tecnologia da Construção, que não se resumem ao arranjo físico laboratorial, mas a uma dimensão mais ampla, abrangendo aspectos político-educacionais, estruturais e sócio-econômicos e também, questões de fundo, como as relações interpessoais e burocráticas. Estes resultados permitiram identificar as condições consideradas como essenciais na (re)formulação de estratégias voltadas à área da Tecnologia da Construção e sua infraestrutura, de maneira que as experiências existentes possam ser potencializadas e novas implantações tenham maior respaldo técnico de acordo com as particularidades contextuais. / This thesis is inserted in the debate about the use of experimentation in building along with the conception of materiality and its role as pedagogical resource. It approaches, more specifically, the experimental workspaces and practices in the Brazilian academic context. It aims to understand the process of shaping the workspaces of the technology and construction fields established in public schools of architecture according to the singularities from different contexts of the country, educational policies and activities of the actors involved, identifying the essential conditions for those practices to be implemented and strengthened in the academic context. The work was developed based on documentary research and through technical visits in 21 public schools of architecture located in different regions of the country, with interviews directed to the main actors who are currently in charge of the field of Technology of Construction. In relation to the practical contributions, the data obtained in the technical visits made it possible to contextualize the challenges faced in the education of Technology of Construction. These challenges are not limited to the physical arrangement of the laboratory; they embrace a broader dimension, covering education politics, structural and socioeconomic aspects and, still, background issues such as interpersonal relations and bureaucracy. These results enabled the identification of conditions considered essential in the (re) formulation of strategies directed to the field of Technology of Construction and its infrastructure, so that the existing experiences can be strengthened and new applications can have a greater technical support according to the contextual singularities.

O processo de criação fundamenta esta pesquisa. A vivência entre a paisagem da Praia da Daniela em Florianópolis, Santa Catarina, e o ateliê com a gravura em metal, suas especificidades e possibilidades gráficas, levaram à elaboração deste livro de artista. O que procuro são aproximações entre o estuário vivo e em constante movimento transformador da paisagem da Praia da Daniela com o meu estuário fictício, que segue na busca de um contínuo formar, desafiando o metal, provocando reações e transformações que acontecem em sua materialidade. / This is a practice-based research in which the creative process is at it\'s core. The construction of this artist\'s book is a fruit of the lived experience between two places: the landscape at the Daniela Beach, in Florianopolis, Santa Catarina, Brazil, and the printmaking studio, considering the specificities and graphic possibilities of the Etching technique. What I seek is to interweave the living and transforming estuary in constant movement of the landscape at Daniela Beach, and my own fictitious estuary, which continuously seeks to give form, defying the nature of the metal, provoking reactions and transformations that happen in its materiality.

Les travaux de thèse s’inscrivent dans le cadre d’une relation pérenne que le CRAN entretient depuis 10 ans avec le CNES. Il s’agit d’étudier la pertinence du remplacement des réseaux de type bus actuellement embarqués dans les lanceurs européens, par des architectures Ethernet commutées standard sur étagères. Les précédents travaux ont permis de qualifier Ethernet sur 2 items de qualité de service : temps-réel et disponibilité. Nous nous attachons à poursuivre ce travail en validant ces premiers résultats sur une plateforme, reproduction à l’échelle de l’architecture qui sera embarquée dans les lanceurs. Ensuite, nous travaillons sur un item original de qualité de service, exigence typique du spatial, appelé observabilité. L’objectif est de rejouer tout vol, après coup, au sol, sachant que le lanceur n’y revient pas, et que l’architecture est commutée, conférant au réseau une dimension multi-domaines d’observation non synchronisés. La synthèse de toutes les captures impose donc de garantir que l’ordonnancement et la fraîcheur des informations de contrôle du lanceur véhiculées dans les trames soient en cohérence avec le fonctionnement applicatif spécifié, et que ce qui est observé soit conforme à ce qui s’est réellement passé. Enfin, nous proposons un sur-échantillonnage réglé dynamiquement pour profiter de la bande passante disponible sans remettre en cause les exigences temps-réel, de reconfiguration et d’observabilité / This thesis is part of a long-lasting relationship between the CRAN and the CNES since 10 years. This involves studying the pertinence of replacing the buses currently embedded in European’s launchers, by off-the-shelf switched standard Ethernet architecture. Previous works qualified Ethernet regarding two quality of service items: real time and reliability. We continue this work by validating these first results on a platform, true scale architecture reproduction which will be embedded in launchers. Then, we work on an original quality of service item, typical of the spatial requirements, called observability. The objective is to re-play the whole flight, afterwards, on ground, knowing that the launcher will not come back, and the architecture is segmented, conferring to the network the dimension of non synchronized multi-domains of observation. The synthesis of all the captures implies to guarantee that the order and the freshness of launcher control information are consistent with the specified applicative operation, and that what is observed is compliant to what really happened. Finally, we propose an over-sampling which is dynamically regulated in order to benefit from the available bandwidth without disturbing real time, reconfiguration and observability requirements

Die Besonderheit der drahtlosen Kommunikation gegenüber den drahtgebundenen Netzwerken liegt im drahtlosen Übertragungsmedium. Aufgrund der Broadcast-Eigenschaft des Übertragungsmediums werden Nachrichten potentiell von allen Netzwerkstationen empfangen, welche sich in der Übertragungsreichweite des Senders aufhalten. Als Konsequenz können bei einem unsynchronisierten Medienzugriff mehrere Nachrichten beim Empfänger kollidieren und nicht korrekt empfangen werden. Dieses Phänomen wird auch als Interferenz bezeichnet. Um solche Interferenzen zu vermeiden, wurden spezielle Protokolle für den Medienzugriff in drahtlosen Netzen entwickelt. Ein solcher Ansatz für drahtlose Maschennetze ist die verteilte Kanalzuweisung. Bei der verteilten Kanalzuweisung werden sich nicht-überlappende Kanäle im verfügbaren Frequenzspektrum für Übertragungen verwendet, die auf dem gleichen Kanal Interferenzen erzeugen würden. Dieser Ansatz ist möglich, da die verwendeten Funktechnologien, wie zum Beispiel IEEE 802.11 (WLAN), mehrere nicht-überlappende Kanäle bereitstellen. Aufgrund der großen Verbreitung von IEEE 802.11, ist eine hohe Dichte von privaten wie kommerziellen Netzen im urbanen Raum die Norm. Diese räumlich überlappenden Netze konkurrieren um den Medienzugriff. Daher ist es für die Leistung von Kanalzuweisungsalgorithmen von großer Bedeutung, die Aktivität der externen Netze mit einzubeziehen. Die Leistung der vorgelegten Arbeit umfasst das Design, die Implementierung und Validierung von Modellen und Algorithmen zur Reduzierung von Interferenzen in drahtlosen Maschennetzen. Die Arbeit beinhaltet die Entwicklung eines Messungs-basierten Interferenzmodells, mit dem Interferenzabhängigkeiten der Maschenrouter untereinander effizient bestimmt werden können. Weiterhin wurde ein Algorithmus für die verteilte Kanalzuweisung entwickelt, der die Aktivität von externen Netzen berücksichtigt. Die Gesamtlösung wurde in einem großen drahtlosen Maschennetz experimentell validiert. / Due to the broadcast nature of the shared medium, wireless transmissions are potentially received by all network stations in the communication range of the sender. With an unsynchronized medium access, multiple transmissions may be active at the same time and thus interfere with each other. In consequence, multiple transmissions may collide at the receiver side and cannot be properly decoded. For this reason, protocols have been developed on the MAC layer to synchronize the medium access and thus reduce interference effects. One of these approaches in wireless mesh networks is channel assignment. The idea of channel assignment is to minimize the network-wide interference by utilizing non-overlapping channels for otherwise interfering wireless transmissions. This is feasible, since wireless mesh routers are usually equipped with multiple radios and commonly used wireless network technologies, such as IEEE 802.11, provide multiple non-overlapping channels. Since IEEE 802.11 operates in the unlicensed frequency spectrum, the dense distribution of private and commercial network deployments of WLANs in urban areas poses a new challenge. Co-located networks compete for the wireless medium, thus decreasing the achievable network performance in terms of throughput and latency. Therefore, an important issue for efficient channel assignment is to also address external interference The contributions of this dissertation comprise the design, implementation, and validation of models and algorithms to enable wireless multi-hop networks to become interference-aware. This includes a measurement-based interference model suitable for large-scale network deployments. A distributed channel assignment algorithm has been developed that considers external sources of interference. The overall solution has been experimentally validated in a large-scale wireless multi-hop multi-radio testbed and has significantly increased the network performance with regard to the network capacity.