O câncer de mama é uma das principais causas de morte por câncer em mulheres em todo o mundo, apresentando-se como uma doença heterogênea composta por distintos subtipos associados a diferentes prognósticos clínicos, mas as bases moleculares que sustentam sua progressão tumoral ainda não estão completamente elucidadas. Evidências de estudos em larga escala apontam uma potencial participação da proteína EMC1 no desenvolvimento do câncer de mama, mas falham em avaliam seu papel específico na progressão e manutenção deste tipo de tumor. EMC1 faz parte de um complexo definido por dez proteínas presente no retículo endoplasmático denominado Endoplasmic Reticulum Membrane Complex, caracterizado recentemente com potencial papel no enovelamento e maturação de proteínas de membrana e na via secretória. Investimos deste modo na caracterização de EMC1 e no seu envolvimento com o câncer de mama. Utilizando um pequeno painel de linhagens tumorais de mama, mostramos por meio de qPCR que os níveis de RNAm de EMC1 estavam aumentados em linhagens consideradas mais agressivas. Duas linhagens tumorais de mama, MCF-7 e SKBR-3 foram utilizadas para expressão estável de EMC1 mediada pelo vetor plasmidial pcDNA3.1. Os efeitos foram notáveis apenas para a linhagem SKBR-3, que apresenta amplificação no locus HER-2, um receptor do tipo tirosina quinase da família EGFR envolvido em vias de invasão e proliferação celular. Observamos uma nítida alteração morfológica após a superexpressão de EMC1 nesta linhagem, sugerindo uma reprogramação para um fenótipo mesenquimal. As células adquiriram filopódios mais proeminentes e mostraram aumento em sua capacidade proliferativa e crescimento clonogênico, sob condições adesivas ou não, bem como aumento nas capacidades invasiva (transwell) e migratória (wound healing). Análises do ciclo celular por iodeto de propídeo indicaram um ligeiro aumento nas populações celulares nas fases S e G2/M em células superexpressando EMC1, corroborando os ensaios funcionais. Notamos também após a superexpressão de EMC1 um aumento na liberação de MMP-2, justificando o aumento na capacidade invasiva destas células. Os resultados dos ensaios funcionais comprovam as análises in silico realizadas nas quais identificamos uma correlação da expressão de EMC1 com proteínas envolvidas em funções no retículo endoplasmático e no processo de transição epitélio-mesenquimal. Avaliamos ainda o metabolismo celular quanto a funções mitocondriais como consumo de oxigênio utilizando um oxígrafo e quanto a geração de espécies reativas de oxigênio (EROs) através da marcação por DHE. A superexpressão de EMC1 levou à diminuição da respiração, ou seja, no consumo de oxigênio e também da produção de EROs, ao passo que os níveis de lactato foram aumentados, características associadas a maior malignidade de células tumorais de mama. Por fim, mostramos através de ensaio de tumorigênese in vivo utilizando camundongos nude que a superexpressão de EMC1 conduziu a formação de tumores mais agressivos e de maior volume. Em conjunto os dados sugerem um importante papel de EMC1 na progressão tumoral do câncer de mama, sobretudo na transição para estágios mais invasivos, servindo como potencial marcador diagnóstico e alvo para terapias futuras. / Breast cancer is a leading cause of cancer death in women worldwide. It presents as a heterogeneous disease composed of distinct subtypes associated with different clinical prognoses, but the molecular basis underlying their tumor progression are not yet fully comprehended. Evidence from large-scale studies suggests a potential involvement of EMC1 protein in the development of breast cancer, but fail to assess its specific role in the progression and maintenance of this type of tumor. EMC1 is part of a protein complex composed of ten different subunits associated to the endoplasmic reticulum (ER) and recently proposed to play a potential role in the folding and maturation of membrane proteins in the secretory pathway. Thus, our aim here was to do a functional characterization of EMC1 in breast cancer. Using a small panel of breast cancer cell lines, we showed higher EMC1 mRNA expression levels in the most aggressive cell lines, by qPCR. Two breast tumor cell lines, MCF - 7 and SKBR -3 were used for stable expression of EMC1 mediated by the plasmidial vector pcDNA3.1. The effects were remarkable only for the SKBR-3 cell line, which carries an amplification of the HER-2 locus, a tyrosine kinase receptor of the EGFR family, involved in cell proliferation and invasion. We observed a clear morphological change after overexpression of EMC1 in this cell line, suggesting a reprogramming to a mesenchymal phenotype. The cells acquired more prominent filopodia and showed an increase of their proliferative capacity and clonogenic growth upon adhesive and non-adhesive conditions, as well as an increase of invasive (collagen-coated transwell) and migratory (wound healing) properties. Analysis of the cell cycle by propidium iodide showed a slight increase in the cell population in S phase and G2/M for EMC1-overexpressing cells, corroborating other functional assays. Also, EMC1-overexpressing cells showed an increase in the release of MMP-2, which could explain the increase in the invasive capacity of these cells. The results of the functional assays confirm the in silico analysis performed in which we identified a correlation between the EMC1 expression with proteins involved in functions in the endoplasmic reticulum and in the epithelial-mesenchymal transition. We also evaluated the cellular metabolism and mitochondrial functions such as oxygen consumption using an oxygraph and the generation of reactive oxygen species (ROS) with DHE dye. Overexpression of EMC1 led to decreased respiration, i.e. oxygen consumption and also ROS production whereas lactate was increased, characteristics associated with increased malignancy of breast tumor cells. Finally, we show through in vivo tumorigenesis assay using nude mice that overexpression of EMC1 led to formation of more aggressive tumors. Together the data suggest an important role of EMC1 in tumor progression of breast cancer, especially in the transition to more invasive stages, serving as a potential prognostic marker and target for future therapies.

Cardiomyopathies and arrhythmias are major causes of death in untreated hereditary haemochromatosis, acute iron poisoning and during secondary iron overload resulting from repeated blood transfusions in β-thalassaemia. Iron overload cardiomyopathies are associated with systolic and diastolic dysfunction, suggesting that Ca2+ homeostasis is impaired. However, the cellular mechanisms of these dysfunctions are unknown. The data presented in this thesis establishes for the first time iron effects on cardiomyocyte Ca2+ handling, as well as the potential cellular substrates responsible for this impairment during iron overload. Exposure of isolated rat ventricular cardiomyocytes to 200μM iron led to biphasic changes in systolic Ca2+ release. Phase 1: an initial reduction of systolic Ca2+ release followed by; Phase 2: increased Ca2+ release with arrhythmogenic spontaneous Ca2+ release, cell contracture and cell death. There is evidence that Fe2+ enters cardiomyocytes via L-type Ca2+ channels (LTCC) and reduces the Ca2+ trigger. The close apposition of LTCCs to cardiac ryanodine receptors (RyR2) suggests RyR2 may be a first target. Indeed RyR2 activity was drastically reduced on exposure to nanomolar [Fe2+] in single channel studies. Together with evidence that Fe2+ may reduce the Ca2+ trigger from LTCC, this is consistent with iron reducing sarcoplasmic reticulum (SR) Ca2+ release during Phase 1. In Phase 2, the presence of spontaneous Ca2+ release events is consistent with SR Ca2+ overload. Indeed, in single rat ventricular cardiomyocytes SR Ca2+ content was found to be increased by 27% during Phase 2. The cellular substrates responsible for this increased SR Ca2+ content were 2-fold: 1) through reduced extrusion via both the Na+ Ca2+ Exchanger (NCX) and Plasmalemmal Ca2+ ATPase (PMCA) and 2) through increased resequestration via the SR Ca2+ ATPase. Iron catalyses the production of reactive oxygen species (ROS) during the Fenton reaction. To investigate whether iron effects might be due to ROS, I used the cell permeant ROS scavenger Tempol. Tempol attenuated Phase 2 effects but Phase 1 effects were not affected. This is consistent with the hypothesis that Phase 1 effects were due to direct effects of Fe2+ affecting LTCC trigger and RyR2 function. The attenuation of Phase 2 effects suggests that ROS damage to key Ca2+ handling mechanisms, such as NCX and PMCA might account for a reduced Ca2+ extrusion and subsequent SR Ca2+ overload.

A participação das espécies reativas de oxigênio (ERO) no mecanismo de ação dos antifúngicos azólicos, bem como a relação entre resistência aos antifúngicos e resposta ao estresse oxidativo, têm sido sugeridos. Entretanto, os dados ainda são inconclusivos e diferem entre os micro-organismos. Neste estudo estão apresentados os resultados da geração de ERO pelo fluconazol em isolados de C. glabrata sensíveis e resistentes a esse antifúngico e a resposta antioxidante da levedura. Nesses isolados, tratados e não tratados com fluconazol em concentração subinibitória, de acordo com sua concentração inibitória mínima (CIM), até fase de crescimento estacionário, foi avaliado se o fluconazol geraria ERO. Subsequentemente, foram analisadas as defesas antioxidantes glutationa peroxidase (GPx), superóxido dismutase (SOD), glutationa-S-transferase (GST), consumo de peróxido de hidrogênio e glutationa total, bem como possível dano oxidativo causado pelo fluconazol em lipídeos, proteínas e ácidos nucleicos e os níveis de nitritos e nitratos. Os resultados mostram que nos isolados de C. glabrata sensíveis e resistentes ao fluconazol, na presença do antifúngico, houve um aumento da geração ERO e maior atividade enzimática da GPx e SOD comparada a dos isolados não tratados com fluconazol, não havendo diferença estatística entre isolados sensíveis e resistentes nesses três parâmetros citados. Em relação à enzima GST, os isolados sensíveis mostraram maior atividade enzimática comparada aos resistentes, e quando as células sensíveis foram tratadas com fluconazol, a atividade da GST diminuiu. O fluconazol não induziu dano oxidativo em proteínas e em lipídeos, entretanto foi observado dano oxidativo ao DNA. Diante disso, sugere-se que o fluconazol gera ERO como parte do seu mecanismo antifúngico em C. glabrata em fase de crescimento estacionário, induzindo dano oxidativo no DNA. Como resposta, observa-se aumento na atividade enzimática da SOD e da GPx na levedura. O entendimento da resposta antioxidante de leveduras patogênicas tem importante interesse clínico, uma vez que o desenvolvimento racional de novas drogas antifúngicas requer conhecimento do metabolismo fúngico. / The participation of reactive oxygen species (ROS) in azoles antifungal mechanism of action has been suggested, as well as the relation between antifungal resistance and oxidative stress response. However, data are still inconclusive and differ between microorganisms. This study presents the results of ROS generation by fluconazole in fluconazole-susceptible and resistant C. glabrata strains and their antioxidant response. It was evaluated whether fluconazole generates ROS in those isolates treated and untreated with fluconazole at sub-inhibitory concentration according to their minimal inhibitory concentration (MIC). This treatment was conducted until stationary growth phase was reached. Subsequently, the antioxidant defenses glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione-S-transferase (GST), consumption of hydrogen peroxide and total glutathione, the possible oxidative damage in lipids, proteins and nucleic acids and the levels of nitrites and nitrates were analyzed. Results showed increased ROS generation in fluconazole-susceptible and resistant C. glabrata strains treated with fluconazole, and also higher GPx and SOD enzymatic activity, compared to untreated cells. No statistical difference of those three parameters was observed between susceptible and resistant strains. In relation to GST, susceptible strains demonstrated higher activity compared to the resistant ones, and when susceptible cells were treated with fluconazole the GST activity decreased compared to untreated. Fluconazole did not induce oxidative damage in proteins and in lipids, however oxidative DNA damage was observed. Therefore, it is suggested that fluconazole generates ROS as part of its antifungal mechanism in C. glabrata at stationary growth phase, inducing oxidative DNA damage. In response, there was increase in the enzymatic activity of SOD and GPx in yeast. The understanding of the pathogenic yeast antioxidant response has important clinical interest, since the rational development of new antifungal drugs requires knowledge about the fungal metabolism.

O câncer de mama é uma das principais causas de morte por câncer em mulheres em todo o mundo, apresentando-se como uma doença heterogênea composta por distintos subtipos associados a diferentes prognósticos clínicos, mas as bases moleculares que sustentam sua progressão tumoral ainda não estão completamente elucidadas. Evidências de estudos em larga escala apontam uma potencial participação da proteína EMC1 no desenvolvimento do câncer de mama, mas falham em avaliam seu papel específico na progressão e manutenção deste tipo de tumor. EMC1 faz parte de um complexo definido por dez proteínas presente no retículo endoplasmático denominado Endoplasmic Reticulum Membrane Complex, caracterizado recentemente com potencial papel no enovelamento e maturação de proteínas de membrana e na via secretória. Investimos deste modo na caracterização de EMC1 e no seu envolvimento com o câncer de mama. Utilizando um pequeno painel de linhagens tumorais de mama, mostramos por meio de qPCR que os níveis de RNAm de EMC1 estavam aumentados em linhagens consideradas mais agressivas. Duas linhagens tumorais de mama, MCF-7 e SKBR-3 foram utilizadas para expressão estável de EMC1 mediada pelo vetor plasmidial pcDNA3.1. Os efeitos foram notáveis apenas para a linhagem SKBR-3, que apresenta amplificação no locus HER-2, um receptor do tipo tirosina quinase da família EGFR envolvido em vias de invasão e proliferação celular. Observamos uma nítida alteração morfológica após a superexpressão de EMC1 nesta linhagem, sugerindo uma reprogramação para um fenótipo mesenquimal. As células adquiriram filopódios mais proeminentes e mostraram aumento em sua capacidade proliferativa e crescimento clonogênico, sob condições adesivas ou não, bem como aumento nas capacidades invasiva (transwell) e migratória (wound healing). Análises do ciclo celular por iodeto de propídeo indicaram um ligeiro aumento nas populações celulares nas fases S e G2/M em células superexpressando EMC1, corroborando os ensaios funcionais. Notamos também após a superexpressão de EMC1 um aumento na liberação de MMP-2, justificando o aumento na capacidade invasiva destas células. Os resultados dos ensaios funcionais comprovam as análises in silico realizadas nas quais identificamos uma correlação da expressão de EMC1 com proteínas envolvidas em funções no retículo endoplasmático e no processo de transição epitélio-mesenquimal. Avaliamos ainda o metabolismo celular quanto a funções mitocondriais como consumo de oxigênio utilizando um oxígrafo e quanto a geração de espécies reativas de oxigênio (EROs) através da marcação por DHE. A superexpressão de EMC1 levou à diminuição da respiração, ou seja, no consumo de oxigênio e também da produção de EROs, ao passo que os níveis de lactato foram aumentados, características associadas a maior malignidade de células tumorais de mama. Por fim, mostramos através de ensaio de tumorigênese in vivo utilizando camundongos nude que a superexpressão de EMC1 conduziu a formação de tumores mais agressivos e de maior volume. Em conjunto os dados sugerem um importante papel de EMC1 na progressão tumoral do câncer de mama, sobretudo na transição para estágios mais invasivos, servindo como potencial marcador diagnóstico e alvo para terapias futuras. / Breast cancer is a leading cause of cancer death in women worldwide. It presents as a heterogeneous disease composed of distinct subtypes associated with different clinical prognoses, but the molecular basis underlying their tumor progression are not yet fully comprehended. Evidence from large-scale studies suggests a potential involvement of EMC1 protein in the development of breast cancer, but fail to assess its specific role in the progression and maintenance of this type of tumor. EMC1 is part of a protein complex composed of ten different subunits associated to the endoplasmic reticulum (ER) and recently proposed to play a potential role in the folding and maturation of membrane proteins in the secretory pathway. Thus, our aim here was to do a functional characterization of EMC1 in breast cancer. Using a small panel of breast cancer cell lines, we showed higher EMC1 mRNA expression levels in the most aggressive cell lines, by qPCR. Two breast tumor cell lines, MCF - 7 and SKBR -3 were used for stable expression of EMC1 mediated by the plasmidial vector pcDNA3.1. The effects were remarkable only for the SKBR-3 cell line, which carries an amplification of the HER-2 locus, a tyrosine kinase receptor of the EGFR family, involved in cell proliferation and invasion. We observed a clear morphological change after overexpression of EMC1 in this cell line, suggesting a reprogramming to a mesenchymal phenotype. The cells acquired more prominent filopodia and showed an increase of their proliferative capacity and clonogenic growth upon adhesive and non-adhesive conditions, as well as an increase of invasive (collagen-coated transwell) and migratory (wound healing) properties. Analysis of the cell cycle by propidium iodide showed a slight increase in the cell population in S phase and G2/M for EMC1-overexpressing cells, corroborating other functional assays. Also, EMC1-overexpressing cells showed an increase in the release of MMP-2, which could explain the increase in the invasive capacity of these cells. The results of the functional assays confirm the in silico analysis performed in which we identified a correlation between the EMC1 expression with proteins involved in functions in the endoplasmic reticulum and in the epithelial-mesenchymal transition. We also evaluated the cellular metabolism and mitochondrial functions such as oxygen consumption using an oxygraph and the generation of reactive oxygen species (ROS) with DHE dye. Overexpression of EMC1 led to decreased respiration, i.e. oxygen consumption and also ROS production whereas lactate was increased, characteristics associated with increased malignancy of breast tumor cells. Finally, we show through in vivo tumorigenesis assay using nude mice that overexpression of EMC1 led to formation of more aggressive tumors. Together the data suggest an important role of EMC1 in tumor progression of breast cancer, especially in the transition to more invasive stages, serving as a potential prognostic marker and target for future therapies.

abstract: For a conventional quadcopter system with 4 planar rotors, flight times vary between 10 to 20 minutes depending on the weight of the quadcopter and the size of the battery used. In order to increase the flight time, either the weight of the quadcopter should be reduced or the battery size should be increased. Another way is to increase the efficiency of the propellers. Previous research shows that ducting a propeller can cause an increase of up to 94 % in the thrust produced by the rotor-duct system. This research focused on developing and testing a quadcopter having a centrally ducted rotor which produces 60 % of the total system thrust and 3 other peripheral rotors. This quadcopter will provide longer flight times while having the same maneuvering flexibility in planar movements. / Dissertation/Thesis / Experimental flight test for ductless quadcopter configuration / Masters Thesis Mechanical Engineering 2019

Compared to normal cells, cancer cells tend to have higher concentrations of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) due to an accelerated cellular metabolism. The high ROS content leaves cancer cells increasingly susceptible to oxidative stress-induced cell death. This susceptibility can be manipulated in selective cancer therapy by further increasing production of ROS or inhibiting peroxide removal systems or a combination of the two. Pharmacological ascorbate (high-dose intravenous ascorbate) has been shown to sensitize pancreatic cancer to ionizing radiation (IR) by increasing production of ROS such as H2O2. Glutathione reductase (GR) and thioredoxin reductase (TrxR) are both important enzymes in peroxide removal systems. GR and TrxR function to recycle key electron donors in the cellular removal of H2O2. We hypothesized that inhibiting the peroxide removal systems via inhibition of GR and TrxR would enhance ascorbate-induced cytotoxicity in pancreatic cancer cells. Inhibition of TrxR activity enhanced ascorbate-induced cytotoxicity in MIA PaCa-2 pancreatic cancer cells. Additionally, knockdown of GR protein expression in combination with pharmacological ascorbate treatment increased MIA PaCa-2 pancreatic cancer cell sensitivity to IR. In MIA PaCa-2 and 403 F1 patient-derived pancreatic cancer cells, inhibition of both TrxR and GR activity combined with pharmacological ascorbate enhanced radiosensitivity. However, this effect was not seen in 339 patient-derived pancreatic cancer cells treated with the same dose of ascorbate. In conclusion, inhibition of TrxR activity, GR activity, or both enhances radiosensitivity and ascorbate-induced cytotoxicity in some, but not all, pancreatic cancer cell lines. Treatments combining ascorbate with inhibition of H2O2 removal may be an effective strategy for treatment of pancreatic adenocarcinoma.

<p>ROS är ett produktnära system som stödjer planering och återrapportering i stålverket. Sandvik vill undersöka möjligheterna att modernisera användargränssnittet på detta system som idag är terminalbaserat till ett modernt grafiskt interface. Två metoder analyseras, den ena innebär att använda en kommersiell produkt för screen scraping och den andra metoden är Web Services Integration Toolkit som är freeware. Resultatet från analysen visar att Web Services Integration Toolkit klarar av att uppfylla de mål som är satta. En testkörning av Web Services Integration Toolkit görs också på ROS och resultat visar att metoden fungerar även fungerar i praktiken.</p>

<p>The Antiepilptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), tri- and dimethadione (TMD and DMD) are known teratogens having a common malformation pattern in human and animal studies. This thesis was designed chiefly to test a hypothesis correlating the teratogenicity of these AEDs to episodes of pharmacologically induced embryonic arrhythmia and hypoxia-reoxygenation damage.</p><p>Effects on the embryonic heart were studied both after maternal administration in mice and in</p><p>mouse embryos cultured in vitro. Only AEDs, correlated with the same type of malformation as could be induced by episodes of interrupted oxygen supply to the embryo (e.g. cleft palate) caused concentration dependent bradycardia and arrhythmia. PHT and DMD had the highest potential and affected embryonic heart at clinically relevant concentration, followed by CBZ, TMD and PB. Valproate and vigabatrin not associated with hypoxia-related malformations caused neither arrhythmia nor severe bradycardia.</p><p>The results showed that the embryonic heart is extremely susceptible to PHT and DMD only</p><p>during a restricted period of development, between gestational days 9-13 (weeks 5-9 of human pregnancy).An observed genetic susceptibility to react with arrhythmia at low concentrations when exposed to PHT or to external stress, could explain why A/J strain of mice is more susceptible to develop cleft palate compared to other strains. High activities of reactive oxygen species (ROS) capturing antioxidant enzymes observed in untreated A/J embryos supported this assumption. The potential to cause embryonic arrythmia by an AED was related to the potential to inhibit the rapid component of the delayed rectifier potassium channel (I _kr ).A marked I _kr blocking activity (70%)of DMD in voltage clamping studies was observed. The I _kr inhibition occurred at similar concentrations, which causes severe arrhythmia.</p><p>The idea of a relation between teratogenicity and arrhythmia, resulting in ischemia followed by reperfusion and generation of ROS was supported by mechanistic studies. Pre-treatment with the spin-trapping agent PBN, which has the capacity to capture ROS, markedly reduced the incidence of PHT and DMD-induced cleft palate. In utero exposure to teratogenic doses of DMD and PHT resulted in hemorrhages in the embryonic palatal region. The same type of haemorrhage in the palatal region precedes orofacial clefts induced by episodic hypoxia.</p>

Cette th��se ��tudie le parall��le ��tabli par les chercheurs et les sp��cialistes de la litt��rature compar��e entre Esfandiy��r et Achille. L'objectif majeur de cette ��tude est de savoir si le po��te iranien Ferdowsi ��tait sous l'influence de son homologue grec, l'a��de de l'Iliade et l'Odyss��e, lors de la cr��ation de son ��uvre le Chahnameh, ��pop��e nationale persane, et plus pr��cis��ment du h��ros de celle-ci, Esfandiy��r. L'��tude de la figure d'Esfandiy��r suivie de celle de l'oiseau l��gendaire S��morgh, de celle de Rostam, le meurtrier du prince kayanide, et enfin, l'��tude de l'espace mythique du Sist��n font l'objet de la premi��re partie de la th��se. Dans la deuxi��me partie, nous ��tudions de fa��on d��taill��e le parall��le existant entre Achille et Esfandiy��r tel qu'il a ��t�� propos�� par les chercheurs ��trangers et iraniens en tentant une approche plus minutieuse et approfondie de cette ��tude �� propos du h��ros grec Achille. La troisi��me partie propose une nouvelle approche comparative des h��ros dans laquelle sera ��tudi��e, �� c��t�� de la figure d'Achille et de celle d'Esfandiy��r, celle d'un troisi��me h��ros, Gilgamesh appartenant �� la tradition m��sopotamienne. Cet ��largissement a pour but de se demander si les traits que les chercheurs pr��c��dents ont d��gag��s comme preuves ou indices du parall��le entre Achille et Esfandiy��r, puisqu'ils se retrouvent au moins en partie chez Gilgamesh, ne sont pas tout simplement caract��ristiques du h��ros ��pique et repr��sentatifs du genre de l'��pop��e.

Cette th��se ��tudie le parall��le ��tabli par les chercheurs et les sp��cialistes de la litt��rature compar��e entre Esfandiy��r et Achille. L'objectif majeur de cette ��tude est de savoir si le po��te iranien Ferdowsi ��tait sous l'influence de son homologue grec, l'a��de de l'Iliade et l'Odyss��e, lors de la cr��ation de son ��uvre le Chahnameh, ��pop��e nationale persane, et plus pr��cis��ment du h��ros de celle-ci, Esfandiy��r. L'��tude de la figure d'Esfandiy��r suivie de celle de l'oiseau l��gendaire S��morgh, de celle de Rostam, le meurtrier du prince kayanide, et enfin, l'��tude de l'espace mythique du Sist��n font l'objet de la premi��re partie de la th��se. Dans la deuxi��me partie, nous ��tudions de fa��on d��taill��e le parall��le existant entre Achille et Esfandiy��r tel qu'il a ��t�� propos�� par les chercheurs ��trangers et iraniens en tentant une approche plus minutieuse et approfondie de cette ��tude �� propos du h��ros grec Achille. La troisi��me partie propose une nouvelle approche comparative des h��ros dans laquelle sera ��tudi��e, �� c��t�� de la figure d'Achille et de celle d'Esfandiy��r, celle d'un troisi��me h��ros, Gilgamesh appartenant �� la tradition m��sopotamienne. Cet ��largissement a pour but de se demander si les traits que les chercheurs pr��c��dents ont d��gag��s comme preuves ou indices du parall��le entre Achille et Esfandiy��r, puisqu'ils se retrouvent au moins en partie chez Gilgamesh, ne sont pas tout simplement caract��ristiques du h��ros ��pique et repr��sentatifs du genre de l'��pop��e.