Dissertations / Theses on the topic 'Lung conditions'

Tumor microenvironmental conditions play a vital role in promoting metastasis and tumor recurrence. Due to inefficient vasculature, cancer cells experience hypoxia, glucose deprivation and low pH even during the early stages of tumor growth. Tumor cells are proposed to adapt to these microenvironmental conditions by acquiring increased migratory and invasion potential and tumor initiating ability. Our research addresses the effect of these biochemical factors of the tumor microenvironment (TME) on motility, epithelial to mesenchymal transition (EMT) and stemness of non-small cell lung cancer (NSCLC). NCI-H292 and NCI-H1650 NSCLC cell lines were used to measure the effect of the above mentioned TME conditions. Apart from acidic pH, low glucose and hypoxia, the effect of high glucose conditions was also measured on H292 and H1650 cell lines. Acidic pH, high and low glucose conditions were observed to have no effect on the motility, EMT and stemness of H1650 cell line. Hence, use of this cell line was discontinued and no further treatment conditions were tested on this cell line. In H292 cell line, acidic pH, low glucose and tumor like conditions combined together (acidic pH + low glucose + hypoxia) [AP+LG+HYP] significantly decreased motility whereas hypoxia significantly increased the motility of H292 cells. High glucose did not affect the motility of H292 cells. Although N-cadherin, a mesenchymal marker, expression was significantly upregulated by acidic pH, high and low glucose conditions, no direct correlation was observed between N-cadherin expression and motility. E-cadherin expression was not affected by acidic pH, high and low glucose conditions. An increase in N-cadherin expression and no change in E-cadherin expression under these conditions might be an indication of partial EMT. Hypoxia and AP+LG+HYP did not alter the expression of E-cadherin and N-cadherin. Although expression of vimentin, another mesenchymal marker, and Sox2, a cancer stem cell marker (CSC), was observed at the mRNA level, no expression of vimentin and Sox2 proteins was observed in H292 cells under any of these treatment conditions. The expression of OCT4, another CSC marker, was also not observed at the protein level in H292 cells. HIF-1α expression was observed in H292 cells under normoxic conditions and was unaffected by hypoxia and AP+LG+HYP. Therefore our research indicates that the effect of these TME conditions might be different on different cancer cell lines or cancer types. Not all cancers may depend on EMT for metastasis. An increase in metastasis under hypoxia may be independent of HIF-1α.

Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury. Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV. In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.

Chronic respiratory diseases, especially chronic obstructive pulmonary disease (COPD), and several molecular mechanisms may predispose to lung cancer (LC) development. Hypothesis: We hypothesized that different biological mechanisms such as oxidative stress, inflammatory events and epigenetic alterations may alter key cellular processes that are strongly involved in tumor initiation and progression in COPD patients. Objectives: In tumor and non-tumor lungs and in blood, to explore potential differences between LC patients with and without COPD, in several biological mechanisms that underlie lung tumor development. To evaluate the different profile of these molecular mechanisms between tumor and non-tumor lungs in either LC or LC-COPD patients. Methods: In lung specimens (tumor and non-tumor), oxidative and nitrosative stress markers, antioxidant systems, Th1 and Th2 cytokines, M1 and M2 macrophages, epigenetic events and downstream biomarkers were determined in LC patients with and without COPD. Redox balance markers and Th1 and Th2 cytokines were also evaluated in the blood compartment of LC patients with and without COPD. Results: In tumor lungs and in the blood of LC patients with COPD, an increased oxidative and nitrosative stress was observed, and an upregulation of the Th1 inflammatory response. Expression of specific microRNAs, DNA methylation levels and downstream biomarkers were altered in the lung tumors of LC patients with COPD, which in turn, promoted an increase in cell proliferation, invasion and angiogenesis. In the tumor lungs of LC patients with and without COPD, redox and nitrosative imbalance was higher, Th1 and Th2 cytokines were greater and epigenetic events and downstream biomarkers were altered. Conclusions: A different expression profile of several molecular mechanisms, involved in tumor development, exist in lung tumors and in blood of LC patients with COPD, which may predispose COPD patients to a higher risk of developing LC.
Las enfermedades crónicas respiratorias, y en especial la enfermedad pulmonar obstructiva crónica (EPOC), así como diversos mecanismos moleculares, podrían ser factores de predisposición al desarrollo de cáncer de pulmón (CP). Hipótesis: La hipótesis de trabajo fue que diferentes mecanismos biológicos como el estrés oxidativo, los procesos inflamatorios y las modificaciones epigenéticas, podrían alterar diversos procesos celulares involucrados en el inicio y en la progresión tumoral en pacientes con EPOC. Objetivos: En tejido pulmonar (tumoral y no tumoral) y en sangre, explorar las diferencias potenciales entre pacientes con CP con y sin EPOC, en diversos mecanismos biológicos que subyacen el desarrollo del tumor pulmonar. Evaluar el perfil diferente de estos mecanismos moleculares entre el pulmón tumoral y no tumoral, tanto en pacientes con CP como en pacientes con CP y EPOC. Métodos: Se determinaron marcadores de estrés oxidativo y nitrosativo, sistemas antioxidantes, citosinas Th1 y Th2, eventos epigenéticos y sus biomarcadores efectores, en el pulmón tumoral y no tumoral de pacientes con CP, con y sin EPOC. También se evaluó el estrés oxidativo y nitrosativo, así como las citosinas Th1 y Th2, en la sangre de pacientes con CP, con y sin EPOC. Resultados: En el tumor pulmonar y en la sangre de los pacientes con CP y EPOC, se observó un aumento del estrés oxidativo y nitrosativo, así como un incremento de la respuesta inflamatoria Th1. La expresión de microRNAs específicos, los niveles de metilación del ADN, y los biomarcadores efectores se vieron alterados en el tumor pulmonar de pacientes con CP y EPOC, lo que a su vez promovió en estos pacientes un aumento de la proliferación celular, la invasión y la angiogénesis. En el tumor pulmonar de los pacientes con CP, con y sin EPOC, se observó un aumento del estrés oxidativo y nitrosativo, un incremento de las citosinas Th1 y Th2, así como alteraciones en los eventos epigenéticos y en los niveles de los biomarcadores efectores. Conclusiones: En los tumores pulmonares y en la sangre de los pacientes con CP y EPOC, existe un perfil de expresión diferente de diversos mecanismos moleculares implicados en el desarrollo tumoral, lo que podría predisponer a los pacientes con EPOC a un mayor riesgo de desarrollar CP.

The purpose of this thesis is to explore the theory, practice and application of costing with specific reference to cancer. In part it reviews the theory and guidelines related to costing methods including the recent focus on the analytical techniques used with cost data. In addition it examines how these theories and guidelines are applied in practice, by reviewing the literature on costs and cancer. The empirical research in this thesis applies costing methods to three specific cancer sites; breast, cervix and lung. This analysis provides information on the total burden of these specified cancers in terms of cost to a typical health authority (Trent). It also explores the hypothesis highlighted in previous studies that the cost of cancer increases with the stage of the disease. The final area of contribution for the thesis is in the application of recently suggested analytical techniques for cost data to the breast, cervical and lung cancer data sets; it investigates a number of proposed techniques for the analysis of skewed cost data and methods for data with incomplete patient follow up.

La radiothérapie constitue l’une des principales modalités de traitement des cancers, mais elle est associée à des atteintes radio-induites aux tissus sains. Les cellules endothéliales (CE) du système vasculaire sont connues pour participer à l’évolution de ces lésions. La sénescence cellulaire est un puissant mécanisme suppresseur de tumeurs mais sa persistance est délétère pour l’homéostasie tissulaire. La présence de cellules sénescentes dans les lésions radio-induites est déjà démontrée mais leur rôle reste encore à élucider. Nous avons cherché à identifier et à comprendre les mécanismes moléculaires impliqués dans la sénescence radio-induite (SRI) ainsi que son rôle dans le développement des lésions après irradiation pulmonaire en conditions stéréotaxiques. In vivo, à l’aide de souris exprimant le gène de la luciférase, placé sous le contrôle de p16, acteur majeur de la sénescence, nous avons détecté des cellules sénescentes au sein de la lésion radio-induite. Nous avons observé par imagerie bioluminescente l’activation de p16 dans le champ d’irradiation et sa persistance jusqu’à 21 mois après irradiation. L’analyse des poumons a révélé une forte hétérogénéité des populations de cellules sénescentes, notamment des pneumocytes, des macrophages et des CE. L’analyse transcriptionnelle de 44 gènes liés à la sénescence, sur 6 types de CE, a montré que les CE de veine ombilicale (HUVEC) sont les plus pertinentes pour étudier la SRI. Le profil moléculaire dynamique des HUVEC a été analysé après 9 doses d’irradiation à différents pas de temps. Une analyse mathématique et bio-informatique approfondie a identifié la voie de l’IL-1 comme acteur clef impactant la sénescence
Radiotherapy is the main modality in cancer treatment but is associated with radiation damages on healthy tissues. Endothelial cells (ECs) play a key role in the evolution of radiation-induced normal tissue injuries. Cellular senescence is a powerful tumor suppressor mechanism but, long-term senescence is deleterious for tissue homeostasis. The presence of senescent cells within the radiation-induced lesions has been shown but their role is not well understood. We aimed to identify and understand the molecular mechanisms involved in radiation-induced senescence (RIS) and its role in radiation-induced lung injuries after stereotactic irradiation. In vivo, using luciferase knock-in mice (p16Ink4-LUC) to detect activation of a senescence player, we explored the presence of senescent cells in radiation-induced pulmonary injury. After high-dose lung irradiation of p16Ink4-LUC mice and using bioluminescence imaging we showed the overexpression of p16 in the irradiation field and its persistence up to 21 months after radiation exposure. Immunostainings revealed a panel of heterogeneous senescent cells including pneumocytes, macrophages and ECs. mRNA expression of 44 genes involved in senescence in 6 human primary irradiated ECs revealed that Human Umbilical Vein Endothelial Cells (HUVECs) are the most relevant in term of gene expression. The dynamic molecular profile associated to RIS in HUVECs was analyzed after 9 doses and 7 time points. Using a deep mathematical/bioinformatics analysis, we deciphered the dynamical transcriptional program involved in RIS and we identified IL1-signaling pathway as a key molecular hub which could modulate the senescence phenotype

Ce travail de thèse s'intéresse principalement à la régulation de la respiration mitochondriale in situ dans les cellules de muscle cardiaque et squelettiques. L'oxygraphie, la spectrophotométrie et la microscopie confocale sur cellules isolées ou fibres musculaires perméabilisées à la saponine ont été utilisées ainsi que la modélisation mathématique. Dans les cellules musculaires, les mitochondries sont organisées de manière très précise tel un ‘cristal'. Cet arrangement intracellulaire serait la base d'une organisation à la fois structurale et fonctionnelle au sein desquelles les mitochondries sont couplées fonctionnellement par le cytosquelette aux autres organelles : réticulum sarcoplasmique et myofibrilles : les ICEUs (ou unités énergétiques intracellulaires). Au sein des cellules cardiaques, il existe 2 niveaux de régulation de la respiration mitochondriale par l'ADP exogène : la perméabilité de la membrane mitochondriale externe (VDAC) et des restrictions localisées de diffusion de l'ADP au voisinage des mitochondries. La β-tubuline participe indirectement à ces mécanismes de régulation de même que la protéine STOP, une protéine associée aux microtubules. Ces données expérimentales sont utiles pour expliquer les aspects métaboliques de la loi de Frank-Starling dans le cœur. Cette notion d'ICEU peut servir de diagnostic lors de l'étude clinique du métabolisme énergétique chez des transplantés pulmonaires avant et après un programme d'entraînement à domicile
The aim of this work was to study the regulation of mitochondrial respiration in situ in cardiac and skeletal muscle cells. Oxygraphy, spectrophotometry and confocal microscopy on saponin-permeabilized muscle cells or fibers were used as well as mathematic modelisation. In muscle cells, mitochondria are ordered very precisely in ‘a crystal like pattern'. This intracellular arrangement could be the basis of a structural and functional organisation within which mitochondria are functionally coupled by cytoskeleton to the other organelles: sarcoplasmic reticulum and myofibrils: ICEUs (intracellular energetic units). In cardiac cells, there are two levels of regulation of mitochondrial respiration by exogenous ADP: permeability of the outer mitochondrial membrane (VDAC) and localized restrictions of ADP diffusion in the neighbourhood of mitochondria. β-tubulin and STOP protein, a microtubule-associated protein, participate indirectly to these mechanisms of regulation. These experimental data are useful for explaining the metabolic aspects of the Frank-Starling law of the heart. The notion of ICEU can be diagnostically used in clinical study of energetic metabolism of lung recipients transplants before and after a home-interval training program

A Differentiation Factor (DF) was purified from rat lung conditioned medium by a four-steps procedure. The DF has a molecular weight of 27000, and an isoelectric point of 4.70. Although DF is stable up to 60°C, it is sensitive to digestion by trypsin, chymotrypsin and subtilisin. DF forms granulocyte colonies in soft agar. Studies using anti-NRK CSF antibody demonstrated that DF is distinct from GM-CSF.

Nous nous sommes essentiellement appuye, pami les grands traites, sur la selenographia (1647) de johannes hevelius (1611-l689), sur l'almagestum novum (1651) et l'astronomia reformata (1665) de giovanni battista riccioli, ainsi que sur vastronomia philolaica (1645) d'ismael boulliau ii (1605-1694), qui representent la <> de l'epoque qui nous a retenu. Ces traites definissent un champ problematique au sein duquel les observations des librations lunaires par hevelius et par boulliau (1644-1650) ont pour effet d'instaurer une antinomie, qui atteint sa forme paroxystique dans le texte de hevelius intitule epistola de motu lunae libratorio (1654) et qui fera l'objet d'une rationalisation secondaire dans la theorie de la libration de giovanni domenico cassini (1668), a partir desconcepts mis en uvre par cristophore scheiner, dans la rosa ursina (1630), pour expliquer le mouvement des taches du soleil. L'exploitation, a la bibliotheque nationale de paris, d'une redaction manuscrite de la theorie de la libration de cassini anterieure aux documents similaires conserves a la bibliotheque de l'observatoire permet de preciser les rapports qu'elle presente avec le texte de hevelius, sans, toutefois, negliger l'apport d'une correspondance inedite entre cassini et boulliau.

La thèse se compose de deux grandes parties, consacrées respectivement aux thèmes "géographie et réseaux économiques" et "réseaux et histoire". La première partie a trait à la géographie physique et humaine, aux réseaux fluviaux et terrestres et aux marches. Elle met en relief les particularités du milieu naturel, notamment la présence d'un surplus immédiatement exploitable par l'homme, le rapport des ethnies en présence avantageant les lao qui firent la conquête des vallées, les bases économiques de l'état, l'ensemble des réseaux économiques et l'orientation générale des circuits d'échange. Ces points constituent, dans la méthodologie de l'auteur, non pas un déterminisme conditionnant étroitement les faits historiques exposes dans la deuxième partie, mais un cadre de réflexion constant sur ces derniers. La deuxième partie tente de reconstituer la genèse de la culture Louang-Phrabang, des origines au 16e siècle, époque a laquelle cette dernière semble trouver sa forme achevée. Elle aborde le problème de la genèse de la culture lao plusieurs siècles avant notre ère et traite notamment des grandes familles ethnolinguistiques qui furent a l'origine de la formation du peuple lao, des apports dans les domaines de l'administration et de l'organisation socio-politique, tantôt septentrionaux, tantôt méridionaux, qui pénétrèrent dans la vallée moyenne du mekhong et dont Louang-Phrabang a gardé le témoignage et des différents courants religieux, lies a ces apports, et qui furent finalement supplantes par une vague rénovatrice de bouddhisme ceylanais, dans la première moitié du 16e siècle. Cette dernière légua à Louang-Phrabang une configuration culturelle qui s'est transmise jusqu'aux temps contemporains
The thesis consists in two parts respectively devoted to "geography and economical networks" and to "networks and history". The first part deals with physical and human geography, waterways, thoroughfares and markets. It focusses on the peculiarities of natural environment, especially on provisions in excess which man can immediately make workable, the connections between ethnics facing one another and which have favored lao who conquered valleys, then the economical foundations of state, the whole of economical intercourse and the general outline of trade networks. According to the author's method these matters are not framing determinism which strictly rules historical events as displayed in part 2 but they build a constant reference to think over them. The second part endeavours to frame out the genesis of louang-phrabane se culture from the beginnings to 16th century when it developed its most achieved form. It deals with the question of genesis of lao culture several centuries before our era, especially with the main ethno-linguistic families who originated the lao people. Then, the contribution in administration and socio-political organisation at one time coming from north, at another time from south and which made its way in mid mekhong valley of which louang-phrabang still gives evidences. And then the different religions traditions connected to those northern and southern contributions which were finally superseded by a renewing wave of ceylonese buddhism during the first part of 16th century. This wave has given louang-phrabang a new cultural outline handed down to nowadays

Thesis (Ph. D.)--West Virginia University, 2004.
Title from document title page. Document formatted into pages; contains x, 130 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 120-130).

Les ILC2s sont retrouvées au niveau des muqueuses comme les poumons et l’intestin, ainsi que dans divers ganglions et organes liés au métabolisme comme les tissus adipeux (ATs). Elles jouent un rôle important dans l’induction des réponses immunitaires de type Th2 comme équivalents innées dans lymphocytes Th2. Elles sont activées par des alarmines (IL-25 et IL-33) et des activateurs environnementaux (allergènes, métabolites et neuromédiateurs). Les ILC2s sécrètent des cytokines de type Th2 permettant de recruter et d’activer des cellules myéloïdes, d’augmenter la production de mucus et la contraction musculaire, ainsi que d’initier la réparation et le renouvellement des tissus. Cependant, une activation non contrôlée des ILC2s participe au développement de maladies chroniques. Les ILCs sont généralement considérées comme des cellules résidentes. Cependant, plusieurs études ont suggéré que la migration pourrait être un processus important pour la maturation des capacités effectrices. La circulation des ILCs reste peu documentée, et aucun mécanisme n’est pour l’instant capable d’expliquer le renouvellement des ILC2s pour agir dans de nombreux tissus suite à une stimulation. Nous avons montré que des quantités significatives d’ILC2s matures et immatures peuvent être collectées dans la lymphe du canal thoracique de souris canulées durant plusieurs heures. Les ILC2s circulantes forment 3 groupes distincts avec des expressions de molécules d’adhésion et récepteurs de migration spécifiques. Nos expériences de transferts cellulaires montrent que ces groupes spécifiques de molécules exprimées sont liés à des tropismes particuliers pour l’intestin, les poumons ou les ATs. Pour analyser le comportement des ILC2s dans un contexte de réponse de type Th2, nous avons injecter les cytokines IL-25 et IL-33 et étudié la lymphe de ces souris. La stimulation à l’IL-33 augmente le nombre de cellules ILC2s circulants dans la lymphe. Les différents groupes d’ILC2s montrent des réponses différentes à l’IL-33. Ainsi, les ILC2s migrants vers l’intestin sont majoritairement prolifératives tandis que le groupe migrant vers les poumons et les ATs secrètent de l’IL-5, de l’IL-13 et de l’Areg. Cela suggère que les ILC2s migrants de façon spécifique possèdent une empreinte fonctionnelle. Nous confirmons les fonctions des groupes d’ILC2s circulants en utilisant des modèles plus physiologiques mimant des réactions allergiques et des infections parasitaires (stimulation par la papaïne et le succinate). Les migrations vers l’intestin et les poumons jouent un rôle primordial dans l’induction de réponse de type Th2 par sécrétion d’IL-5 et d’IL-13, et à l’initiation de la réparation tissulaire par production d’Areg. De façon intéressante, les ILC2s migrants vers les poumons participent au renouvellement des populations résidentes participant principalement à la production d’Areg. Finalement, nous caractérisons un rôle important du trafic des ILC2s à différents temps suivant l’infection par Nippostrongulus brasiliensis, confirmant la fonction des ILC2s migrantes
ILC2s are found in mucosal tissues as lung and intestine, in lymph nodes, and in metabolic tissues such as the adipose tissues. They play important role in maintaining or inducing type-2 immune responses as innate equivalent of Th2 lymphocytes. They are activated by alarmins (IL-25 and IL-33) and by external activators (allergens, metabolites and neuromediators). ILC2s are secreting type-2 cytokines to facilitate the activation of other cells and to induce an important repair program. Their activation allows large type of events as diverse as myeloid cells recruitment and activation, mucus production, muscle contractility and tissue repair. They have key role in lung and adipose tissue development and maintain their homeostasis by early responding against parasitic pathogens. Abnormal activation of ILC2s is also participating to chronic diseases.ILCs are mostly considered as resident cells. However, different studies suggested that migration could be important for the maturation of their effector capacities and to correctly target the injured tissue. Circulation and trafficking of ILC subsets is still unclear. No mechanism is yet available to explain the turnover of ILC2s and how they can act in many tissues following stimuli.We found that large numbers of mature and immature ILC2s could be collected in the thoracic duct lymph of mice perfused over several hours, showing that ILC2s are in fact actively circulating through the hemo-lymphatic circuit. Furthermore, circulating mature ILC2s could be separated into three distinct subsets depending on their pattern of receptor and adhesion molecule expression. Cell transfer experiments proved that specific patterns are representative of specific tropism for gut, lung and adipose tissues.To analyse ILC2 behaviour in the context of a type-2 response, we injected IL-25 and IL-33 before lymph collection. IL-33 stimulation largely enhanced the number of circulating ILC2s in the lymph. These different ILC2 tissue targeted subsets responded differently to IL-33. Specifically, gut-trafficking ILC2s were mainly stimulated to proliferate whereas lung and adipose tissue subsets were stimulated to produce IL-13, IL-5 and Areg. This suggests that, in ILC2s, specific tissue targeting is associated with already imprinted functions while transiting through the hemo-lymphatic system. We confirmed these functions of circulating ILC2 subsets in more physiological context by mimicking allergy and helminth infection (stimulation by papain and succinate) where specific migration to lungs and intestine play important roles in mounting the type-2 response by IL-5/IL-13 secretion, and also initiating tissue repair by Areg production. Interestingly, we showed that lung migrating ILC2s participated to resident pool renewal that main function is Areg production. Finally, we characterized important trafficking of ILC2 at different stages of Nippostrongulus brasiliensis infection, confirming the functional relevance of ILC2 trafficking

L'objet de cette thèse est de proposer une étude numérique, fondée sur l'application de résultats de la théorie du contrôle optimal géométrique, des trajectoires spatiales du système Terre-Lune dans un contexte de poussée faible. Le mouvement du satellite est décrit par les équations du problème restreint des trois corps controlé. Nous nous concentrons sur la minimisation de la consommation énergétique et du temps de transfert. Les trajectoires optimales sont recherchées parmi les projections des courbes extrémales solutions du principe du maximum de Pontryagin et peuvent être calculées grâce à une méthode de tir. Ce procédé fait intervenir l'algorithme de Newton dont la convergence nécessite une initialisation précise. Nous surmontons cette difficulté au moyen de techniques homotopiques ou d'études géométriques du système de contrôle linéarisé. L'optimalité locale des trajectoires extrémales est ensuite vérifée en utilisant les conditions du second ordre liées au concept de point conjugué. Dans le cas du problème de minimisation de l'énergie, une technique de "recollement" de trajectoires optimales kepleriennes autour de la Terre et La Lune et d'une solution optimale de l'équation du mouvement linéarisée au voisinage du point d'équilibre L1 est également proposée pour approximer les transferts Terre-Lune à énergie minimale
This PhD thesis provides a numerical study of space trajectories in the Earth-Moon system when low-thrust is applied. Our computations are based on fundamental results from geometric control theory. The spacecraft's motion is modelled by the equations of the controlled restricted three-body problem. We focus on minimizing energy cost and transfer time. Optimal trajectories are found among a set of extremal curves, solutions of the Pontryagin's maximum principle, which can be computed solving a shooting equation thanks to a Newton algorithm. In this framework, initial conditions are found using homotopic methods or studying the linearized control system. We check local optimality of the trajectories using the second order optimality conditions related to the concept of conjugate points. In the case of the energy minimization problem, we also describe the principle of approximating Earth-Moon optimal transfers by concatening optimal keplerian trajectories around The Earth and the Moon and an energy-minimal solution of the linearized system in the neighbourhood of the equilibrium point L1

Cette thèse se propose d'étudier les conditions d'avancée des savoirs dans la classe à partir de situations de classe en cycle 3 de l'école élémentaire française. Ces situations concernent la compréhension des phases de la Lune. Les analyses de pratiques effectives visent à inférer les déterminants de l'action professorale et leur rôle. Trois déterminants ont été retenus, à savoir l'action adressée du professeur, son épistémologie pratique ainsi que les savoirs en jeu. Afin d'identifier ces déterminants dans l'action in situ, leurs caractéristiques ont préalablement été établies à travers une analyse a priori des savoirs en jeu, des instructions officielles et de l'épistémologie pratique des enseignants. Une enquête, diffusée à l'échelle nationale, a permis de mettre en évidence les représentations des enseignants vis-à-vis des sciences et de leur enseignement. L'élaboration des items de cette enquête repose sur une étude épistémologique des démarches scientifiques et du statut des savoirs. Cette étude a également été mobilisée pour l'analyse des instructions officielles. Les analyses de l'action professorale s'appuient sur la théorie de l'action conjointe en didactique (TACD). Les notions de tâches épistémiques et de niveaux de modélisation ont été convoquées pour la description de l'avancée des savoirs dans la classe. Ces notions permettent une analyse fine de l'action didactique en documentant notamment le triplet des genèses et en particulier la chronogénèse. Cette recherche précise le rôle des tâches épistémiques et des niveaux de modélisation sollicités dans l'avancée des savoirs et montre que le poids des déterminants varie d'une part selon la phase de travail du professeur et d'autre part selon l'anticipation de l'action enseignante en réaction
This PhD analyses the conditions to advance knowledge in class during a science lesson in higher level of primary school (5th grade,10-year-old pupils) of the French elementary school. The teaching situations concern the phases of the moon. From the analysis of effective practices, this research deduce the determiners of teacher’s action and their role.The determiners analysed are : the knowledge, official instructions and teachers’ representations towards science and science teaching. In order to identify these determiners through effective pratices, their characteristics have been established: an a priori analysis of knowledge, official instructions and practical epistemology of teachers is proposed. A questionnaire aiming at collecting data on teachers’ views of science and sciences teaching have been disseminated at the national leevl. An epistemological study of science approach and knowledge guided the elaboration of items and underlies the analysis the official instructions.. The analysis the teachers’ activities is based on the Joint Action Theory in Didactics (JATD). Additional theoretical tools have been integrated to describe the way knowledge progresses in the classroom : epistemic tasks and modeling levels. These additional concepts allow a detailed analysis of the didactic action including the triple genesis, especially chronogenesis. Our research precises the role of epistemic tasks and modeling levels requested in order to advance knowledge and shows that some determinants act primarily to other, depending on the teachers’ tasks concerning the lesson and the anticipation of students’ actions

Depuis le début des années 1980, les changements politico-économiques organisés par l’État laotien ont remodelé le visage du pays. Ces changements œuvrent tant pour une plus grande intégration aux marchés économiques internationaux qu’à la construction nationale du pays. Les conséquences de ces transformations sont notamment visibles dans le paysage rural et montagnard, comme dans l’évolution des moyens de subsistance et des modes de vie des populations ethniques minoritaires. Le développement récent des plantations agro-commerciales contribue, entre autres, à réorganiser la géographie socioéconomique des provinces du nord du pays, dont celle de la province de Luang Namtha. Comment les populations locales s’adaptent-elles à ces transformations rapides ? Quels changements cela implique-t-il ? Cette recherche, qui emploie une approche multiscalaire, aide à comprendre les rouages de l’intégration et de l’adaptation locale aux systèmes nationaux et internationaux. MOTS-CLES : Laos, intégration, monde rural, minorités ethniques, moyens de subsistance, adaptation.
Since the beginning of the 1980s, the political and economic changes undertaken by the Laotian State have reshaped the face of the country. These changes work to foster greater integration into international markets and to further develop the country. The results of these transformations are noticeable in rural and mountainous landscape and have influenced the evolution of the ethnic minorities’ livelihoods and lifestyles. The recent development of agro-commercial plantations has contributed to reorganize the socio-economical geography of the northern Laotian provinces, including Luang Namtha. How do local populations adapt to these quick transformations? What changes do these changes involve? This research, which utilizes a multiscalar approach, helps to better understand the inner workings of this integration and the local adaptation process into the national and international systems. KEYWORDS: Laos, integration, rural world, ethnic minorities, livelihoods, adaptation.

Alan George Miller.
Thesis (Ph.D.)--Chinese University of Hong Kong, 1997.
Includes bibliographical references (p. 204-230).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.

博士
國防醫學院
醫學科學研究所
106
While anesthetics are often used on cancer patients during surgical procedures, their consequence on cancer progression remains to be clarified. In this study, we sought to investigate the mechanism of the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 and H1975 human lung adenocarcinoma cancer cells were processed with various local anesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. The cell barrier property was evaluated using an electric cell-substrate impedance sensing (ECIS) system. The epithelial-to-mesenchymal transition (EMT) of treated cells was analyzed by immunofluorescence staining. In vitro and in vivo cancer cell dissemination were investigated. Gene expression microarray and quantitative real-time PCR (qrt-PCR) assays were used to identify the genes responsible for levobupivacaine-mediated cancer cell dissemination. The results illustrated that only levobupivacaine induced EMT in the treated A549 cells and also caused the dissemination of cancer cells in vitro. In addition, after intravenous injection, levobupivacaine encouraged cancer cell dissemination in vivo (7/10 in the levobupivacaine treatment group compared to 1/10 in the control group). Gene expression microarray, qrt-PCR and immunoblotting revealed that after levobupivacaine treatment, the hypoxia-inducible factor (HIF)- 2α gene was upregulated in cancer cells. Our findings suggest that levobupivacaine may induce A549 lung cancer cell dissemination both in vitro and in vivo. More specifically, HIF-2α signaling possibly contributes to levobupivacaine-mediated A549 lung cancer cell spreading.

碩士
國防醫學院
航太及海底醫學研究所
102
Backgrounds: Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. Despite extensive research into the pathogenesis and management of ischemia-reperfusion (IR)-induced lung injury, inhospital mortality still remains high. In several preclinical studies, adult stem cells have been proved to be therapeutic ability through paracrine mechanisms. We hypothesized that neural crest stem cell (NCSC)-derived conditioned medium (CdM) protects against IR-induced lung injury. Materials and Methods: In 24 adult male Sprague-Dawley rats (300-350g), acute lung injury was induced in clinically relevant ex vivo animal model. Animal were divided into four group (n=6 in each group)：the control group, the ischemia-reperfusion(IR) group, the IR+Medium only group, the NCSC-CdM group (IR+CdM), and the heated CdM group (IR+heated CdM). Results: IR activated IKK-NFκB inflammation pathway and caused acute lung injury as evidenced by the increases in BALF concentration, pulmonary arterial pressure, lung weight to body weight ratio, wet to dry ratio of lung weight, and filtration coefficient. Adding CdM to the perfusate significantly suppressed inflammation and attenuated lung injury caused by IR. The protective effects, however, diminished when the CdM was priorly heated. Conclusion: NCSCs may secret heat vulnerable factors that suppresses inflammatory response and attenuate acute lung injury caused by ischemia and reperfusion in isolated rat lungs.

碩士
國立臺灣科技大學
工業管理系
106
In Taiwan, the statistics of the Ministry of Health and Welfare indicated lung cancer is the leading cause of cancer. About 10,000 new cases of lung cancer each year, which caused more than 7,000 people dead in 2016. In addition, lung cancer usually accompanied with comorbidity which was negatively associated with survival and leaded to medical financial burden. This study used National Health Insurance Research Database from 1996 to 2010 who diagnosed lung cancer, and 85,745 cases were selected as experiment data. By using Kaplan-Meier estimation to get residual life of patient and used risk factors to construct Conditional Gaussian Bayesian network model of survivability and medical expenditure. The prediction R-square of survivability in stage I is 69.50%, stage II is 73.75%. The prediction R-square of medical expenditure in stage I is 93.95%, stage II is 74.77%. And proposed model not only can predict survivability and medical expenditure, but also can calculate the posterior probability of variety of medical related query.

碩士
國防醫學院
生理學研究所
99
In Taiwan, lung cancer is the first place in top ten causes of cancer death, and there is increasing trends recent years. The survival rate of lung cancer is only about 10% of in 5 years. Its biological characteristic and clinical manifestation of lung cancer are divided into small cell lung cancer (SCLC) and non-small cell lung cancer(NSCLC). Tumour hypoxia is a microenvironmental feature of chronically inflamed tissues. ROS levels are increased in hypoxia. Two central transcription factors involved in the regulation of this response are hypoxia inducible factor (HIF) and nuclear factor-κb (p65 NF-κB) which demonstrate an intimate interdependence at several mechanistic levels. Previous studies have shown that activation of hypoxia-inducible factor 1alpha (HIF-1α) during hypoxia, triggering various target genes expression including vascular endothelial growth factor (VEGF), plays an important role in tumor angiogenesis and progression. Dextromethorphan (DXM) is the most commonly used as an antitussive drug. DXM is also used to suppress cough on late stage lung cancer patients. Recently, several studies have shown that DXM exerts an antioxidative activity, attenuates vascular oxidative stress formation and inflammatory markers functions. However, in hypoxia condition, effects of Dextromethorphan on HIF-1α-mediated angiogenesis in human lung adenocarcinoma epithelial cell are still unreported.

碩士
國立清華大學
生醫工程與環境科學系
103
Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer are deadly disease related to smoking. COPD and lung cancer were among the 10 leading causes of death in the world in 2012. Previous studies suggest that epithelial-mesenchymal transition (EMT) may play a role in COPD, IPF and lung cancer; however, the mechanism linking EMT to these dieases remains incompletely understood. EMT describes a biological process by which epithelial cells lose their epithelial characteristics and gradually acquire mesenchymal traits, and this process mainly occurs in embryogenesis, tissue regeneration, organ fibrosis, cancer progression and metastasis. The causes of lung diseases mentioned above are highly associated with fibrosis, cancer progression and metastasis. Therefore, study on cigarette smoke-induced EMT in lung epithelial cells contributes to understanding and better treatment for these diseases. We investigated the effect of cigarette smoke extract (CSE) on human lung epithelial A549 cell line in vitro. Our results demonstrated that CSE induced A549 cell death in a concentration- and time-dependent manner. In addition, the cells escaped from CSE-induced cell death exhibited some EMT properties: elongated shape, lack of apical microvilli, increased motility, decreased E-cadherin expression, and increased Vimentin and -smooth muscle actin expression. Recent studies suggest the therapeutic potential of mesenchymal stem cells for lung diseases, which is probably mediated by paracrine actions of mesenchymal stem cells. Accordingly, A549 cells were cultured with adipose-derived stem cell condition medium (ADSC-CM), and we found that ADSC-CM had a protective effect on CSE-induced cell death; moreover, ADSC-CM repressed CSE-indued EMT properties in A549 cells. These results imply that microenvironment plays an important role in EMT induction. A549 cells tended to undergo EMT in adverse condition, but CSE induced EMT properties in A549 cells became less evident in a less adverse condition such as with the inclusion of ADSC-CM. Finally, we investigated EMT related genes by microarray analysis. After CSE exposure, we found that genes as epithelial markers were downregulated in A549 cells, but only few genes as mesenchymal markers were upregualted. As a result, A549 cells underwent “partial EMT” by CSE induction, and we show that such EMT-like phenomena can be further confirmed by microarray analysis. In summary, we demonstrated the effect of CSE on A549 cells, including cell death and EMT. Furthermore, we discussed EMT-like features in A549 cells via different methods for image analysis. Finally, we used ADSC-CM to repress CSE-indued cell death and EMT in A549 cells, which suggest that ADSCs have therapeutic potential for smoking related lung diseases by paracrine actions.