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Slim, Ferial Amira. "Une isoforme de Allograft Inflammatory Factor-1 (AIF1) impliquée dans le cancer du sein." Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/34495.
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Le cancer du sein (BC) représente l’un des cancers les plus communs et les plus dangereux sur le plan de la mortalité et de l’incidence chez les femmes dans le monde. Celui-ci est d’autant plus récurrent dans les pays développés, notamment le Canada [2]. Il s’agit d’une maladie complexe et multifactorielle dont la sévérité et la réponse au traitement varient selon les cas et dont le diagnostic peut parfois s’avérer délicat dû à l’hétérogénéité de la pathologie. Ce projet a ainsi pour objectif d’étudier un facteur de risque potentiel du BC pouvant servir au diagnostic et au traitement des patientes atteintes. Allograft Inflammatory Factor-1 (AIF1) est une protéine impliquée dans de nombreuses maladies inflammatoires et a été également associée au cancer, cependant, dans la majorité des études, une seule des isoformes a été analysée. Nos analyses de la signature transcriptionnelle d’individus provenant de familles à risque élevé de BC (BRCA1/BRCA2 ou non-BRCA1/2 (BRCAX)) ont permis d’identifier des transcrits significativement et différentiellement exprimés entre ces différents groupes. Parmi ceux-ci, deux variants d’épissage du gène AIF1, appelés AIF1v3 et AIF1v1, étaient significativement surexprimés chez les lignées cellulaires lymphoblastoides (LCLs) des soeurs BRCAX atteintes comparativement à leurs soeurs non-atteintes. Nos études d’expression génique ont par la suite révélé que ces deux isoformes étaient majoritairement exprimées dans les tumeurs mammaires les moins sévères et que cette expression provenait du microenvironnement tumoral, AIF1v1 étant majoritairement exprimé par les lymphocytes et AIF1v3 par les macrophages. Nous avons également démontré l’effet d’un traitement à l’acide gras oméga- 3 docosahexaénoïque (DHA) sur la réduction de l’expression des deux isoformes dans des LCLs d’individus BRCAX. Pour finir, nos données montrent que l’expression des isoformes de AIF1 dans les tumeurs et le tissu adipeux mammaires corrélait avec les paramètres cliniques et métaboliques des patientes. Ainsi, les données et connaissances obtenues à travers cette étude représentent une avancée considérable pour la communauté scientifique et la recherche sur le cancer puisqu’il s’agit de la première étude portant sur AIF1v1 et son implication dans le BC, le microenvironnement tumoral et la réaction inflammatoire.<br>Breast cancer (BC) represents one of the most common and dangerous cancers in terms of mortality and incidence among women worldwide. It is even more recurrent in developed countries including Canada [2]. BC is a complex and multifactorial disorder, its severity and response to treatment differs from case to case and its diagnosis can be tricky due to the heterogeneity of the pathology. Thus, this project aims to study a potential BC risk factor that can be used for diagnosis and treatment of BC patients. Allograft Inflammatory Factor-1 (AIF1) is a protein involved in many inflammatory diseases that has also been associated with cancer, however, in most studies, only one isoform has been analyzed. Our analyses of the transcriptional profile of individuals from French Canadian families with high risk of BC (BRCA1/BRCA2 or not-BRCA1/2 (BRCAX)) identified significantly and differentially expressed transcripts between the different groups. Among them, two AIF1 splice variants were highly overexpressed in the BRCAX lymphoblastoid cell lines (LCLs) of the affected sister comparatively with her non-affected sister. Our gene expression analysis revealed that both isoforms were mostly expressed in the least aggressive BC and this expression resulted from the tumor microenvironment, AIF1v1 being mostly expressed by lymphocytes and AIF1v3 by activated macrophages. We also demonstrated the effect of docosahexaenoic omega-3 fatty acids (DHA) on the downregulation of AIF1 isoforms expression in BRCAX LCLs. Lastly, our data showed that AIF1 isoforms expression in breast tumors and breast adipose tissue correlated with metabolic and clinical parameters of BC patients. Ultimately, all data and information resulting from this study represent a major breakthrough for the scientific community and the cancer research field since it is the first study on AIF1v1 and its involvement in BC, breast tumor microenvironment and inflammatory reaction.
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Azzouz, Doua. "Antigènes leucocytaires humains, microchimérisme et auto-anticorps dans la sclérodermie systémique." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4035.
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La Sclérodermie Systémique (ScS) est une maladie auto-immune rare et complexe, cliniquement divisée en deux sous-groupes : la ScS cutanée diffuse (dc-ScS) et la ScS cutanée limitée (lc-ScS). Les anticorps anti-topoisomérase et anti-centromère (ATA et ACA) sont respectivement les marqueurs de chaque sous-groupe. Beaucoup d'études ont analysé les gènes des Antigènes leucocytaires humains (HLA), fort facteur de risque, dans plusieurs groupes ethniques de patients atteints de ScS. La plupart des allèles de susceptibilité HLA-DRB1 (*11:01, *11:04, *15:01, *08:02…) et DQB1 (*03:01, *03:02, *06:01 and *06:02) ont en commun une séquence d'acides aminés, respectivement 67FLEDR71 et 71TRAELDT77 sur leurs chaînes β. Pour la première fois, nous évaluons le risque relatif conféré par une ou deux doses de 67FLEDR71 et/ou une ou deux doses de 71TRAELDT77 chez des patients Caucasiens Français atteints de SSc. Nous montrons que le motif 67FLEDR71 est fortement associé à la dc-ScS et encore plus à la production d'ATA, alors que l'association de 71TRAELDT77 est plus faible dans les deux sous-groupes. Notre groupe a montré récemment dans la polyarthrite rhumatoïde (PR) que les patients qui n'ont pas les allèles de susceptibilité à la PR peuvent acquérir ces allèles via les cellules fœtales et/ou maternelles, aussi appelé Microchimérisme (Mc). Nous avons testé la même hypothèse dans la ScS. Contrairement à la PR, nos résultats n'ont pas démontré un tel transfert de susceptibilité via le Mc dans la SSc. Finalement, la présence d'auto-anticorps, liée à un génotype HLA, est précieuse au diagnostic et /ou pronostic de la maladie (ex : ACA ou ATA)<br>Systemic sclerosis (SSc) is a rare and complex autoimmune disease clinically divided into two subgroups: diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc). Anti-topoisomerase and anti-centromere antibodies (ATA and ACA) are respectively markers of each subset. Many studies have analyzed Human Leukocyte Antigen (HLA) genes, the strongest genetic risk factor, in several ethnic groups in patients with SSc. Most common HLA-DRB1 (*11:01, *11:04, *15:01, *08:02…) and HLA-DQB1 (*03:01, *03:02, *06:01 and *06:02) susceptibility alleles have in common an amino acid sequence, respectively 67FLEDR71 and 71TRAELDT77 on their β chains. For the first time, we evaluate the relative risk conferred by one or two 67FLEDR71 and/or one or two 71TRAELDT77 motives among Caucasian French patients with SSc. We show that 67FLEDR71 motif is highly associated with dcSSc and even more with ATA production, whereas 71TRAELDT77 association is weaker in both subgroups. Our group has recently shown in Rheumatoid Arthritis (RA) that patients who lack the RA HLA susceptibility that it could be transferred to patients via fetal and/or maternal cells, also called microchimerism (Mc). We test the same hypothesis in SSc. Contrary to RA, our results fail to demonstrate such transfer of HLA susceptibility via Mc in SSc. Finally linked to a particular HLA genotype is the presence of autoantibodies, helpful for disease diagnosis and/or prognosis (i.e. ACA or ATA). Patients who do not have these markers are difficult to diagnose or classify. By ProtoArray® technique, we identify 6 new auto-antigens in the plasmas of SSc patients
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Vahsen, Nicola. "Functional analysis of the apoptosis-inducing factor (AIF)." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=981721702.
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Bassem, Yehia Khaled, and Vahab Abdowod. "Analys av indikatorerna AIT, AIF, SAIDI och SAIFI i lokalnätet." Thesis, Högskolan Väst, Avdelningen för Industriell ekonomi, Elektro- och Maskinteknik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-13584.
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Energimarknadsinspektionen (EI) är en tillsynsmyndighet för el, fjärrvärme och naturgas, där en av myndighetens uppgifter är att kontrollera elnätbolagens distribution av el och om distributionen är av god kvalité. God leveranssäkerhet bestäms utifrån EI:s föreskrifter och allmänna råd i publikationen EIFS 2013:1. Varje år rapporterar elnätsbolag in avbrottsdata till EI som används för att mäta och analysera leveranssäkerheten i det svenska elnätet. Energimarknadsinspektionen använder etablerade indikatorer som beskriver leveranssäkerheten i distributionsnätet i Sverige. Indikatorerna som idag används är SAIDI och SAIFI som är kundviktade index som beskriver medelavbrottstiden och medelavbrottsfrekvensen för ett specifikt nät. Under 2019 överväger EI att införa två indikatorer som skall ersätta de nuvarande indexen SAIDI och SAIFI, indikatorerna benämns AIT och AIF. Enligt EI ska dessa indikatorer ge en mer rättvis bild av leveranssäkerheten än vad SAIDI och SAIFI ger, då de nya indikatorerna tar hänsyn till kundernas effektuttag. Detta arbete syftar till att utreda hur de nya indikatorerna AIT och AIF påverkar mätningen av leveranssäkerheten i GENAB:s nät, där leveranssäkerhetsindikatorerna beräknas på olika typer av nät för att sedan jämföras. Därefter undersöks hur de övervägda leveranssäkerhets-indikatorerna kan förbättras med hjälp av ökad automation i nätet. Utifrån resultatet av undersökningarna kan slutsatsen dras att en övergång till AIT och AIF kommer att medföra att indikatorernas medelavbrottstid och medelavbrottsfrekvens ökar för kunderna per år i GENAB:s nät.<br>Swedish Energy Markets Inspectorate (EI) is a regulatory authority for electricity, district heating and natural gas, where one of their tasks is to control the company's power distribution quality. A good electrical delivery reliability is determined on the basis of EI:s regulations and general advice in the publication EIFS 2013:1. Every year, the power distribution companies reports data to EI of the disturbances they have had in their networks, which is used to measure and analyse the electrical delivery reliability in the Swedish electricity grid. EI uses established indicators that describe the electrical delivery reliability of the distribution networks in Sweden. The indicators used today are named SAIDI and SAIFI, which are customer-weighted indices that describe the average interruption duration and the average interruption frequency for a specific network. In the beginning of 2019, EI will consider introducing two indicators to replace the current SAIDI and SAIFI indices, the indicators are being defined as AIT and AIF. According to EI, these indicators will be better than SAIDI and SAIFI as they take into consideration the customer's expected power consumption during the power outage. The purpose of this report is to investigate how the new indicators AIT and AIF affects the delivery reliability indicators in GENAB:s network, where these indicators are exercised on different types of networks and then compared. How the network can be made more efficient in the future by means of automation in the network is investigated based on the results on the indicators. From the results and investigations, it can be concluded that the transition to AIT and AIF will result in an increase of the indicator´s interruption time and the number of interruptions for customers per year in GENAB:s network.
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Landshamer, Stefan. "Role of Bid and AIF in glutamate induced neuronal cell death." Diss., [S.l.] : [s.n.], 2007. http://edoc.ub.uni-muenchen.de/archive/00006586.
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Mallett, Ross A. History Australian Defence Force Academy UNSW. "The Interplay between Technology, Tactics and Organisation in the First AIF." Awarded by:University of New South Wales - Australian Defence Force Academy. School of History, 1999. http://handle.unsw.edu.au/1959.4/38710.
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The purpose of this thesis is to investigate the interplay between the technology, tactics and organisation of the First AIF. Warfare in the twentieth warfare is characterised by the presence of certain technologies that give it a distinctive nature and which first appeared in the Great War. It was in the Great War that the highly dispersed form of tactics that we know today emerged. Thus, it is a natural starting point not only for the examination of warfare in the era of technology but for considering the nature of technological change itself. My Australian perspective enabled issues to be looked at to a depth that would not be possible in a work of this length with a broader view. I have argued that the Great War was characterised by the problem of trench warfare, and I have traced the progress of tactical, technological and organisational developments that ultimately supplied the solutions. I have also shown how the Great War was not only a war of technology in which new technologies were introduced and developed, but also one which saw the spread of new ways of thinking about military technology. In preparing this thesis, I have inspected the actual battlefields in France, Belgium and Turkey. I have drawn on a broad range of published material, but the thesis is largely based upon the primary documents found in the Australian War Memorial and Australian National Archives.
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Poulin, Éric. "Modélisation pharmacocinétique combinée IRM-TEP." Mémoire, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6351.
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Au cours des dernières années, des modalités d'imagerie comme la tomographie d'émission par positrons (TEP) et l'imagerie par résonance magnétique (IRM) ont été utilisées pour caractériser le microenvironnement tumoral et prédire la réponse au traitement durant la thérapie. La TEP est reconnue pour sa fonctionnalité et elle est utilisée avec une multitude de radiotraceurs. Par contre, sa résolution spatiale est limitée. L'IRM apporte une localisation anatomique précise et une information sur la perfusion des tissus. La modélisation pharmacocinétique augmente le potentiel de ces deux modalités en permettant des études quantitatives. Cependant, ces analyses quantitatives nécessitent l'acquisition de plusieurs images successives afin de suivre la distribution d'un agent de contraste (AC) en IRM et d'un radiotraceur en TEP. Plusieurs types d'analyse pharmacocinétique en IRM et en TEP requièrent la concentration de l'agent en fonction du temps dans le sang, nommée fonction d'entrée artérielle (AIF). Toutefois, cette dernière est difficile à mesurer. En IRM, pour la modélisation, il existe un compromis à faire entre la résolution spatiale et la résolution temporelle. Dans ce mémoire, une approche pour convertir l'AIF d'une modalité à l'autre est proposée pour le petit animal. L'AC gadolinium-acide diéthylène-triamine penta-acétique (Gd-DTPA) en IRM et le radiotraceur [indice supérieur 18] F-fluorodésoxyglucose (FDG) en TEP ont été utilisés. Un modèle mathématique a été développé pour effectuer la conversion et comparer les AIFs. Afin d'évaluer l'efficacité de la méthode, les paramètres pharmacocinétiques ont été calculés pour l'AIF obtenue par prélèvements sanguins et par notre méthode de conversion. Aucune différence statistique n'a été trouvée entre les paramètres des deux méthodes. Ces résultats suggèrent donc qu'une seule AIF serait nécessaire pour faire la modélisation dans les deux modalités. Une méthode qui optimise le temps d'acquisition d'images de même que la résolution spatiale en IRM a été proposée afin d'obtenir une quantification tumorale plus juste. Le temps d'acquisition a été réduit d'un facteur 3,2 avec une perte négligeable (1,5%) de résolution spatiale. Il a également été démontré qu'il est possible d'utiliser la méthode de région de référence combinée avec notre méthode de conversion d'AIF afin de faire la modélisation dans les deux modalités. Il s'agit, à notre connaissance, du premier travail évaluant la synergie entre les acquisitions IRM et TEP combinées. Ce travail pourrait donc avoir un impact significatif sur l'exploitation des deux modalités d'imagerie.
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Courtin, Laurine. "Optimisation de la transformation à froid des tubes de gaine en acier austénitique 15-15TI AIM1." Thesis, Poitiers, 2015. http://www.theses.fr/2015POIT2277/document.
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Afin de faire face aux besoins croissants en énergie, les réacteurs de 4ème génération sont envisagés mondialement. Un premier prototype de réacteur à neutrons rapides à caloporteur sodium (appelé ASTRID) est à l'étude au CEA. Le matériau de référence retenu pour le gainage combustible du premier coeur est l'acier austénitique 15-15Ti - AIM1 (Austenitic Improved Material). L’objectif de la thèse est d’étudier des voies d’optimisation de la gamme de mise en forme à froid du gainage permettant d’améliorer la résistance au gonflement. Les investigations portent principalement sur les conditions de transformation à froid et les traitements thermiques appliqués au cours de la mise en forme (notamment lors du dernier traitement d’hypertrempe). Les effets de ces paramètres sont étudiés en lien avec la microstructure (notamment l’affinement structural, l’état de précipitation, la remise en solution des éléments d’addition et l’arrangement des dislocations).La démarche adoptée se divise en trois étapes principales :- une analyse des gammes de fabrication mises en oeuvre par le passé ainsi qu’une étude des conditions d’étirage à froid et des traitements thermiques appliqués ;- une évaluation de nouveaux procédés de mise en forme tels que le laminage à pas de pèlerin et le martelage visant à valider la fabrication des tubes finis selon les spécifications requises ;- une optimisation des gammes de fabrication à froid et de la microstructure du matériau final. Les résultats de caractérisation de la microstructure et du comportement mécanique permettent d’envisager favorablement l’utilisation d’un procédé alternatif tel que le laminage à pas de pèlerin pour fabriquer les tubes de gaine<br>In order to face the next century energy demand growth, the worldwide development of the 4th generation of nuclear reactors is considered. The construction of a sodium-cooled fast reactor prototype (ASTRID) is currently envisaged at the CEA. The reference material selected for the fuel cladding of its first core is the 15-15Ti-AIM1 austenitic steel (Austenitic Improved Material).The goal of this PhD thesis work is to investigate the different ways of optimization for the coldworking steps undergone by the claddings during their manufacture in order to improve their swelling resistance. The main investigations are focused on the conditions of the cold-working steps and the thermal treatments applied throughout the shaping of the claddings, especially of the last solution annealing treatment. The effects of these parameters on the microstructure are investigated (structural refinement, precipitation and the additive elements dissolution and arrangement of the dislocations).This study is divided into three main steps:- an analysis of the fabrication routes applied in the past along with the study of the “coldwork” and the thermal treatments conditions;- an assessment of new shaping processes, such as the “cold-pilgering” and the hammering, in order to verify the conformity of the manufactured tubes with respect to the required specifications.- an attempt of optimization of the cold-work routes and the microstructure of the final material. The results of microstructure characterization and the mechanical behavior allow envisaging favorably the use of an alternative process such as the cold pilgering to manufacture claddings
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Bakelar, Jeremy W. "Binding Interactions of (R)- and (S)-hydroxypropyl-CoM Dehydrogenases and the Zinc Knuckle Proteins Air1 and Air2." DigitalCommons@USU, 2015. https://digitalcommons.usu.edu/etd/4273.
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This work is focused on understanding protein function by describing how paralogous proteins with overlapping and distinct functions interact with their substrates and with other proteins. Two model systems are the subject of this research: (1) the stereospecific dehydrogenases R- and S-HPCDH, and (2) the zinc knuckle proteins Air1 and Air2.
R- and S-HPCDH are homologous enzymes that are central to the metabolism of propylene and epoxide in the soil bacterium Xanthobacter autotrophicus. The bacterium produces R- and S-HPCDH simultaneously to facilitate transformation of R- and S-enantiomers of epoxypropane to a common achiral product 2-ketopropyl-CoM (2-KPC). Both R- and S-HPCDH are highly stereospecific for their respective substrates as each enzyme displays less than 0.5% activity with the opposite substrate isomer. Presented here are substrate-bound x-ray crystal structures of S-HPCDH. Comparisons to the previously reported product-bound structure of R-HPCDH reveal structural differences that provide each enzyme with a distinct substrate binding pocket. These structures demonstrate how chiral discrimination by R- and S-HPCDH results from alternative binding of the distal end of substrates within each substrate binding pocket, providing a structural basis for stereospecificity displayed by R- and S-HPCDH.
Air1 and Air2 are homologous eukaryotic proteins that individually function within a trimeric protein complex called TRAMP. In the nucleus, TRAMP participates in RNA surveillance, processing, and turnover by stimulating the 3’-5’ exonucleolytic degradation of targeted RNAs by the nuclear exosome. Previous studies have indicated that within TRAMP Air1 and Air2 provide crucial protein-protein interactions that link the individual subunits of the complex. However, the mechanistic details of these protein-protein interactions are poorly understood. The work in this dissertation has characterized a previously unknown binding interface between Air2 and another TRAMP component, the helicase Mtr4. This interaction may explain how helicase activity is modulated in TRAMP. In addition to TRAMP protein interactions, preliminary studies have identified a small region of Air1 that is required for modulating the activity of a protein that is not found in TRAMP, the methyltransferase Hmt1. Collectively, these studies provide important characterization of Air1 and Air2 protein-binding interactions, and establish a foundation for future research efforts aimed at exploring Air protein function.
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Apostolova, Nadezda. "Mitochondrial role of Apoptosis-Inducing Factor (AIF): Oxidative Phosphorylation and Reactive Oxygen Species." Doctoral thesis, Universitat de València, 2008. http://hdl.handle.net/10803/9775.
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The apoptotic function of Apoptosis-inducing factor (AIF) is well documented in theliterature, but its physiological role in the mitochondrion is less certain. Using a smallinterfering RNA (siRNA) strategy, we studied whether modulation of AIF expression incultured cells influenced the production of reactive oxygen species (ROS). We foundthat siAIF-transfected cells had reduced AIF protein levels and this was paralleled by asignificant increase in ROS. We tested the generality of this response by using twodifferent human cell lines, the hepatoma cell line Hep3B and cervix carcinoma lineHeLa, and also by employing a mouse ES AIF-KO cell line. The increased ROS weremitochondrial in origin as a similar silencing strategy in cells devoid of a functioningmitochondrial electron transport chain (ETC) did not result in a ROS-increase. Theaugmented ROS levels were sufficient to activate Hypoxia-inducible factor 1α (HIF-1α),a ROS-sensitive transcription factor, and this effect could be reversed usingantioxidants, both the broad-range general antioxidant (N-acetyl cysteine) and aspecific mitochondrial-targeted antioxidant (MitoQ), proving the implication of ROS inthe HIF-1α stabilization. We also studied another two redox-sensitive transcriptionfactor and thus observed up-regulation in the expression of Nuclear factor (erythroidderived2)-like 2 (Nrf2), however without major changes in Nuclear factor-kappa B(NF-κB) levels. Examination of the cellular oxygen consumption rate revealed that AIFdepletedcells had a major impairment of respiration, at Complex I in the ETC. Westernblot analysis also showed a loss of Complex I 39 and 20 kDa subunits. Studies usingthe antioxidants mentioned above, revealed that the respiratory competence could beregained in AIF-silenced cells. However, neither of the antioxidant treatments we usedcould recover Complex I assembly. Studies of the energetic state of siAIF cells showedthat despite a 30% decrease in the overall intact cell respiration, these cells maintainnormal basal levels of ATP, presumably due to a higher glycolytic capacity and a lowerproliferation rate. Moreover, we analyzed the expression of another redox-activeprotein, thioredoxin, by Western blot and found that the mitochondrial isoform, Trx2,was significantly decreased when AIF was silenced. Preliminary co-immunoprecipitationanalyses and proteomic studies failed to show any direct correlation between AIF andTrx2 at the protein level.Our results lead us to the conclusion that the defect in respiration in siAIF cells isdownstream of Complex I protein loss and is presumably due to ROS-mediateddamage to the ETC. This suggests an integral mitochondrial function of AIF, as a redoxmodifier and chaperone-like molecule, necessary for Complex I assembly. Additionalstudies are required to define the detailed mechanism of the AIF enzymatic activity inthe mitochondrion and to establish its binding partners.<br>La función proapoptótica del Factor Inductor de Apoptosis (AIF) está biendocumentada, sin embargo su papel fisiológico en la mitocondria es menos conocido.Empleando la metodología de interferencia por ARN, estudiamos si la modulación de laexpresión proteica de AIF en cultivo celular modifica la producción celular de especiesreactivas de oxígeno (ROS). Observamos que el silenciamiento de AIF estaba seguidopor un incremento significativo en los niveles de las ROS. Estas ROS fueronmitocondriales de origen, puesto que el silenciamiento de AIF en células que carecende la cadena de transporte electrónico funcional (ETC) en la mitocondria no llevó a unincremento de ROS. Este incremento fue suficiente para activar el Factor inducible porhipoxia (HIF-1α), efecto que se puede revertir usando los antioxidantes, N-AcetilCisteina y MitoQ, demostrando así la implicación de los ROS en la estabilización deHIF1-α. Los análisis del consumo de oxigeno celular mostraron que las células de AIFsilenciado sufren una disminución en la respiración celular, al nivel del Complejo I de laETC, acompañada por una disminución significativa en la expresión de sus subunidades39 y la 20kDa. Tratamientos con los antioxidantes previamente nombrados mostraronque la tasa de respiración se puede recuperar, no siendo así con la expresión delComplejo I de la ETC. Estudios del estado energético de las células siAIF mostraronque a pesar de la disminución de 30% en la tasa de la respiración celular, estas célulasmantienen niveles normales de ATP, como resultado de un incremento en la capacidadglucolítica y una reducción en la tasa de proliferación. Posteriormente, analizamos laexpresión de la proteína tioredoxina y observamos una disminución significativa en laisoforma mitocondrial, la tioredoxina 2 (Trx2), aunque los análisis preliminares de coinmunoprecipitacióny proteómica no mostraron la existencia de una correlacióndirecta entre las proteínas AIF y Trx2.Concluyendo, nuestros resultados sugieren que el defecto de la respiración celular esposterior al defecto en el Complejo I, probablemente como consecuencia al daño de laETC por ROS. Esta observación apunta a un papel integrador de AIF en la mitocondria,como modulador del estatus redox y necesario para el ensamblaje del Complejo I.
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Faraday, Bruce Douglas History Australian Defence Force Academy UNSW. "Half the battle : the administration and higher organisation of the AIF 1914-1918." Awarded by:University of New South Wales - Australian Defence Force Academy. School of History, 1997. http://handle.unsw.edu.au/1959.4/38693.
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Administration of armies has been sadly neglected in historical studies but the ability of the AIF to develop an efficient system of administration and to fit into the equally efficient British system, had much to do with the success of the AIF, especially late in the war. The various Empire governments had made some preparations for an alliance system of fighting in the event of a major war, but in practice these needed a great deal of adjustment. This thesis examines the manner in which the dominions and Britain planned for a possible war and the way in which changes had to be made in practice. It examines the manner in which the AIF developed a system and the many facets of this system, which had developed a remarkable degree of efficiency by the end of the war. Because the AIF and CEF were so alike in size, composition and in the problem they faced, a recurring theme of the thesis is a comparison between the two. It embraces the following: a. Prewar preparation for a combined empire army. b. The organisation of the administrative system of the AIF and the manner this improved through the war. c. The organisation and problems of the CEF administrative system d. The development of a system of capitation to pay for the services supplied to the AIF and CEF. e. Supply of equipment. f. Manner in which both forces worked to maintain their forces. g. The manner in which both forces catered for the needs of the individual soldiers. h. Supply in the field i. Medical administration in the AIF j. The administration in the AIF k. The administration of discipline in the AIF l. The demobilisation of the AIF.
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Silva, Patrícia Lacouth da. "Efeitos das mudanças climáticas na regulação de biomarcadores em Echinaster brasiliensis (Echinodermata: Asteroidea)." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-15032016-101439/.
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Diante do quadro atual de previsões de mudanças climáticas, estudos a respeito das possíveis respostas dos organismos a estas alterações são importantes. Com a finalidade de prever e verificar se estas serão de fato deletérias ou se os organismos são capazes de lidar com elas sem alterações na sua fisiologia, e consequentemente na estrutura do ambiente, E. brasiliensis foi utilizada como modelo para estudar possíveis impactos do aumento da temperatura e acidificação dos oceanos na sua fisiologia. Para isso, espécimes foram expostos a 9 possíveis combinações de temperatura (24ºC, 28ºC e 30ºC) e pH (8.0, 7.7 e 7.3) em diferentes intervalos de tempo (1, 3, 12, 24 e 48 h). Amostras de gônadas e fluido celomático foram coletadas para avaliar a expressão das proteínas de estresse HSP70, AIF-1 e p38-MAPK, e a variação no número e viabilidade dos celomócitos. Nossos resultados mostram que o modelo é sensibilizado pelas mudanças no ambiente, através da hiper-regulação das proteínas de estresse. O cenário considerado mais extremo (30°C + pH7.3) ocasionou a morte de 100% dos organismos após 24horas. E o segundo cenário mais severo (30°C + pH7.7) desencadeou o desenvolvimento de ulceração de pele. Os efeitos são mais pronunciados nos celomócitos e a acidificação da água parece ter efeitos antagônicos com a temperatura nos celomócitos e sinérgicos nas gônadas. Embora a resposta tenha sido sistêmica, o grau e a dinâmica foram distintos em relação às diferentes amostras e estresses. Podendo causar modificações na resposta imune dos organismos e consequentemente na sobrevivência da espécie a longo prazo.<br>Under the current Climate Change context, studies about the potential responses of the organisms to their changing environment are of extreme importance. Recent studies point out the synergy of temperature and ocean acidification altogether. In this study, we used the sea star E. brasiliensis to assess the physiological effects of rising temperature, seawater acidification and the interaction of both factors. Independent individuals (N=225) were exposed to 9 possible combinations of temperature (24ºC, 28ºC and 30ºC) and pH (8.0, 7.7 and 7.3), for 1, 3, 12, 24 and 48 h. We compared the stress produced by these treatments measuring the expression of heat shock proteins (HSP70), the production of the allograft inflammatory factor (AIF−1) and the activation of mitogen kinases (MAPKs) at both gonad and celomic fluid. Furthermore, we assessed the quantity and quality of coelomocytes. Our results demonstrated that E. brasiliensis is vulnerable to the interaction of temperature and acidification. All the stress proteins evaluated were upregulated. The extreme scenario (30°C + pH7.3) caused the death of 100% of organisms after 24 hours, while the second most severe scenario (30°C + pH7.7) triggered skin ulceration. Nevertheless, we found that water acidification produces antagonistic effects to the temperature in coelomocytes and synergistic effects in gonad cells. Furthermore, these effects were more pronounced in the coelomocytes than in the gonads. The systemic response found in this study suggest that the interactive effects of elevated temperatures in conjunction with ocean acidification may endanger the survival of this species, and it could compromise the ecosystem functioning at long term.
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bm, jgarstang@bermudasun, and Edward John Garstang. "Crime and punishment on the Western Front: the Australian Imperial Force and British Army discipline." Murdoch University, 2009. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20090831.143148.
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The Australian Imperial Force in the First World War had a deserved reputation as an effective fighting force, and at the same had the worst disciplinary record away from the frontline when compared with other Dominion forces and the rest of the British Army. Australian indiscipline is a subject that has been largely ignored, or when dealt with as in the Official History by C. E. W. Bean, has had to pass through the filter of the Australian Legend. This study examines the link between Australian indiscipline and the privileged position they held of being the only force immune from the death penalty, except for mutiny, desertion to the enemy and traitorous activity. This simple fact would have a major influence on the relatively high numbers of absentees and desertions within Australian ranks. General Headquarters in France (GHQ) saw these high levels of indiscipline as a direct result of Australian authorities not allowing their soldiers to be placed under the Army Act in full. Further differences surfaced between the British and Australians when it came to punishment, with Australian courts criticised by British Army authorities for not using the powers they possessed to impose penalties that would act as a deterrent, as well as their reluctance to impose Field Punishment No. 1. This study examines these general differences as well as dealing with a specific case of an Australian soldier charged with the murder of a French civilian, a case that attracted the attention of senior political and military figures when it transpired Australians were immune from the death penalty for murder. Maintaining discipline was a constant struggle for the authorities when faced with those determined to avoid frontline duty either by committing military crime or through self-maiming. In this context the high venereal disease rate is discussed and evidence presented that this could be considered as a self-inflicted wound. The mutiny in the 1st Battalion of September 1918 is examined as well as a mutiny in a military prison in France in 1919. It is not the purpose of this study to tarnish the reputation of the many thousands of brave men who fought in the AIF, rather it is an attempt to understand the high levels of indiscipline within the context of the war on the Western Front and the disciplinary code under which they operated.
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Smolová, Kateřina. "Analýza vývoje regulace hedgeových fondů." Master's thesis, Vysoká škola ekonomická v Praze, 2012. http://www.nusl.cz/ntk/nusl-136221.
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The aim of the thesis is to analyze the evolution of hedge funds and their regulation, especially in the context of the global financial crisis. The first part focuses on defining the term "hedge fund", then it is compared with another institutional investor, mutual fund. The history and description of basic investment strategies of hedge funds are also analyzed. The second part overhauls the market of hedge funds, including its quantity, assets under management and performance. The last part is mainly devoted to the theoretical aspects of regulation and supervision of hedge funds, it analyzes the legal status of regulation and supervision of these funds in selected countries before the global financial crisis, the AIFM Directive requirements are discussed and their possible implications are analyzed; the AIFM Directive is compared with the Dodd Frank Act's requirements at the end.
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Yatime, Laure. "Rôle du facteur d'initiation e/aIF2 dans le démarrage de la traduction chez les Eucaryotes et chez les archées." Phd thesis, Ecole Polytechnique X, 2005. http://pastel.archives-ouvertes.fr/pastel-00001539.
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Le facteur hétérotrimérique e/aIF2 joue un rôle central dans le démarrage de la traduction chez les Eucaryotes et chez les Archées. Il conduit l'ARNt initiateur méthionylé jusqu'au ribosome et assure la spécificité de sélection du codon de démarrage sur l'ARNm. La structure cristallographique d'aIF2de l'archée Pyrococcus abyssi, précédemment résolue au laboratoire, a révélé une très forte homologie entre aIF2γ, qui constitue le coeur de l'hétérotrimère, et le facteur d'élongation bactérien EF1A. Cependant, possède des caractéristiques structurales propres qui pourraient être responsables de sa spécificité d'action dans le démarrage de la traduction. Une étape cruciale de ce travail a consisté à développer un test de suivi in vitro de l'association d'aIF2 au Met-ARNti Met. Ce test a permis d'évaluer l'importance des caractéristiques du Met-ARNti Met et la contribution de chacune des sous-unités de l'hétérotrimère dans la formation du complexe aIF2:Met-ARNti Met. Ainsi, il a été montré que le résidu méthionine constitue un déterminant majeur dans la reconnaissance du Met-ARNti Met par aIF2. D'autre part, il apparaît que la sous-unité seule est effectivement capable de lier l'ARNt selon un mode similaire à celui observé pour EF1A mais avec une affinité considérablement réduite par rapport à celle de l'hétérotrimère. Nous avons montré que la présence de la sous-unité αétait nécessaire pour retrouver une affinité optimale vis-à-vis de l'ARNt tandis que la sous-unité βne semble pas jouer de rôle dans cette liaison. L'utilisation d'une stratégie de découpage d'en domaines séparés a montré que c'est le domaine 3 d'aIF2qui lie la sous-unité par l'intermédiaire d'une boucle du domaine 2 de . De plus, le dimère D3semble nécessaire et suffisant pour retrouver une affinité pour l'ARNt comparable à celle du facteur natif. Dans un second temps, des cristaux de la sous-unité entière et d'une forme tronquée correspondant aux domaines 2 et 3 ont été obtenus. Les structures d'D2-3 et d'complet ont été résolues à respectivement 2.26 et 3.37 Å de résolution. L'analyse du modèle structural a révélé une mobilité du domaine 3 d'αpar rapport au bloc rigide formé par les domaines 1 et 2. La comparaison de séquences d'e/aIF2a montré que les zones de conservation d'se situaient principalement dans le domaine 1 et dans le domaine 3 de la protéine, qui possèdent tous les deux des propriétés générales de liaison des ARNs. Le domaine 1 d'αpourrait ainsi interagir avec un autre partenaire de type ARN du démarrage de la traduction, tel que l'ARNm ou l'ARN ribosomal. Finalement, des cristaux d'aIF2de Sulfolobus solfataricus ont été obtenus et la structure de l'hétérodimère a été résolue à 3.0 Å. Cette structure a confirmé les données biochimiques précédemment obtenues : le domaine 3 de la sous-unité interagit avec le domaine 2 de , au niveau de la boucle L1 précédemment caractérisée. L'analyse de cette structure a révélé pour la première fois une conformation des régions Switch de similaire à celle observée au sein du complexe EF1A:GDPNP:ARNt, ce qui permet d'expliquer la GTPdépendance de la fixation du Met-ARNti Met par aIF2. La comparaison de cette structure à celle d'EF1A suggère que seule γpourrait être en contact avec l'ARNt au sein de l'hétérodimère αγ. Le renforcement de l'affinité pour l'ARNt observé en présence d'αnous a conduit à envisager un rôle possible d'αdans l'établissement des conformations observées pour les régions Switch dans la structure d'aIF2γ.
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Whatcott, Clifford Jason. "The Role of ADP-Ribosylation in Mitochondria-Mediated Cell Death." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/195141.
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Poly(ADP)ribose (PAR) metabolism is essential to many cellular functions, including the maintenance of genomic integrity, the regulation of cell death mechanisms, as well as the regulation of gene expression. Recent work has uncovered many new players in the expanding effort to understand PAR metabolism and its cellular impact. PARP-1, the prototypical poly(ADP)ribose polymerase, was the first to be discovered, and has since been shown to be vital in the cellular response to DNA damage. Indeed, one report demonstrating that PARP-1 activation is required for apoptosis-inducing factor (AIF) release from mitochondria uncovered a novel link between DNA damage and signaling for cell death. The events following PARP activation, leading to signaling for AIF release, however, are still poorly understood. Based on our observations, we have developed a model to explain the nuclear/mitochondrial crosstalk that occurs following PARP activation. The work presented here answers several important questions regarding the relationship between ADP-ribose metabolism and mitochondria, including the role of PAR in signaling for the release of AIF, the presence of ADP-ribose metabolism protein members in mitochondria, and mitochondrial transcriptional effects following PARP activation. This work presents several novel findings, including the first report of a mitochondrial matrix isoform of poly(ADP-ribose) glycohydrolase (PARG) as well as direct evidence of mitochondria-associated PARP activity. Furthermore, it provides evidence for a novel effect of PARP-1 activation, in the specific transcriptional upregulation of the mitochondrial gene, NADH dehydrogenase, subunit 1 (ND1). Our data is consistent with the hypothesis that uncontrolled PARP activity results in energy metabolism dysfunction and cell death. Furthermore, it supports a model in which PARP activity is required for normal transcriptional responses in mitochondria following DNA damage. In total, this report adds to the body of work outlining the roles of PARP following DNA damage recognition and activation, demonstrating that ADP-ribose metabolism plays an important role in cell death regulation by both direct and indirect means.
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Pettersson, Niklas. "Vad vill vi med idrotten? : En studie om arbetarpressens syn på den nationella och internationella arbetaridrottsrörelsen under mellankrigstiden." Thesis, Uppsala universitet, Historiska institutionen, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-374605.
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Under mellankrigstiden växte arbetaridrotten i flertalet länder runt om i världen och den nya socialistiska idrotten firades med arbetarolympiader. I Sverige lyckades aldrig arbetaridrotten få sitt stora genombrott och Sverige deltog varken i arbetarolympiader eller hade särskilt stort samarbete med den internationella arbetaridrottsrörelsen. Denna studie har undersökt varför Sveriges samarbete med den internationella arbetaridrottsrörelsen nästintill uteblev och följaktligen varför Sverige aldrig deltog i arbetarolympiaderna. Genom en kvalitativ innehållsanalys av arbetarpressen under mellankrigstiden har denna studie kartlagt huvudanledningarna till varför Sveriges samarbete med den internationella arbetaridrottsrörelsen var förhållandevis liten. Det svenska socialdemokratiska arbetarpartiet ansåg till skillnad från andra socialdemokratiska partier att den vanliga idrotten var bra för arbetare då detta utgjorde ett neutralt forum som tillät umgänge över klassgränserna. Arbetaridrotten hade inte en naturlig plats i det svenska samhället och man ansåg att den bröt mot idrottens allra heligaste, dess politiska neutralitet. Svenska kommunister var därmot av en annan åsikt och ansåg att idrotten inte alls var politiskt neutral utan ett medel som borgerligheten använde för att förblinda och fördumma arbetarklassen. Arbetaridrotten ansågs därför av kommunister som nödvändig för att arbetare ska kunna bedriva idrott. Det var även kommunister som grundade Arbetarnas Idrottsförbund (AIF). Den internationella arbetaridrotten leddes nästan uteslutande av socialdemokrater. Följaktligen ville det kommunistiska AIF inte beblanda sig med dem och man talade i termer som att ledarna för den internanationella arbetaridrotten var "socialfascister". Socialdemokrater hade heller ingen större vilja att engagera sig för den internationella arbetaridrotten då man ansåg att den vanliga idrotten var en tillräckligt god representant för arbetarnas intressen. På Sovjetunionens initiativ inleddes i mitten av 1930-talet det som kom att kallas för folkfrontspolitiken. Detta innebar ett närmande från kommunister till socialdemokrater för att visa en enad socialistisk front mot den växande fascismen. Detta skedde även i Sverige och från den undersökta kommunistiska pressens reportage från arbetarolympiaden i Antwerpen 1937 finner enbart lovord. Delar av den socialdemokratiska pressen som undersökts tycks också ha ändrat inställning till ett eventuellt svenskt deltagande i arbetarolympiaden i samband med 1937-års arbetarolympiad. Detta verkar dock bero på det svenska deltagandet i de olympiska spelen i Berlin år 1936. Dessa olympiska spel hade varit uppenbart politiskt och Nazityskland tilläts demonstrera sin oerhörda propagandamaskin. Därmed var idéen om idrottens politiska neutraliet bruten och det endast genom svenskt deltagade i dess motpart, arbetarolympiaderna, kunde den återupprättas.
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Seidenschwann, Sabine [Verfasser]. "Die Master-Kapitalverwaltungsgesellschaft : Eine rechtliche und wirtschaftliche Untersuchung zu den Grenzen der Auslagerung im Rahmen der AIFM-Regulierung / Sabine Seidenschwann." Baden-Baden : Nomos Verlagsgesellschaft mbH & Co. KG, 2016. http://d-nb.info/1122042922/34.
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Cikala, Mihai. "Molekulare Analyse von Caspasen, AIF und PSR in Hydra zur Untersuchung der Evolution des programmierten Zelltods." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-42798.
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Pietra, Stefano. "Characterization of New Players in Planar Polarity Establishment in Arabidopsis." Doctoral thesis, Umeå universitet, Institutionen för fysiologisk botanik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-87838.
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Coordinated polarity and differentiation of cells in the plane of a tissue layer are essential to the development of multicellular organisms. Arabidopsis thaliana root hairs and trichomes provide model systems to study the pathways that control planar polarity and cell fate specification in plants. A concentration gradient of the plant hormone auxin provides an instructive cue that coordinates polar assembly of signalling complexes at plasma membranes of root epidermal cells; however, knowledge about additional players and cytoskeletal effectors driving cell polarization prior to hair emergence remains limited. On the other hand, epidermal cell fate specification is controlled by a well-characterized gene network of transcription factors that translate positional signals and cell-to-cell communication into tissue-wide patterning. Yet, new components are continuously found to interact with the patterning pathway, shedding light on its connections with diverse developmental processes. This thesis presents the SABRE (SAB) gene as a novel player in planar polarity establishment and root epidermal patterning. SAB is a large protein with sequence similarity to proteins present in all eukaryotes and affects planar polarity as well as orientation of cell divisions and cortical microtubules. Genetic interaction with the microtubule-associated protein gene CLASP further supports involvement of SAB in microtubule arrangement, suggesting a role for this gene in cytoskeletal organisation. Strikingly, SAB also interacts genetically with ACTIN7 (ACT7), and both ACT7 and its modulator ACTIN INTERACTING PROTEIN 1-2 (AIP1-2) contribute to planar polarity of root hair positioning. Cell-file specific expression of AIP1-2 depends on the epidermal-patterning regulator WEREWOLF (WER), revealing a connection between actin organization, planar polarity and cell fate specification. Consistent with this finding, SAB also functions in patterning of the root epidermis by stabilizing cell fate acquisition upstream of the core patterning pathway. These results unveil new roles for SAB in planar polarity and epidermal patterning and suggest that organization of the microtubule and the actin cytoskeleton are important to both planar polarity establishment and cell fate specification.<br>Samordning av polaritet och differentiering av celler inom ett vävnadslager är avgörande för utvecklingen av multicellulära organismer. Rothår och bladhår hos Arabidopsis thaliana utgör modellsystem för att studera signalvägar som kontrollerar planpolaritet och specifikation av cellers öde hos växter. En koncentrationsgradient av växthormonet auxin ger en instruktiv signal som koordinerar polär hopsättning av signalkomplex vid plasmamembranet i rotepidermisceller; dock är kunskapen om ytterligare aktörer och hur cytoskelettets aktörer påverkar cellpolaritet innan rothår bildas begränsad. Vad gäller differentieringen av epidermala cellers öde kontrolleras dessa genom ett väl karakteriserat nätverk av transkriptionsfaktorer som överför positionssignaler och cell-till-cell kommunikation till vävnadsomfattande mönsterbildning. Fortfarande hittas dock nya komponenter som interagerar med signalvägarna för mönsterbildning, vilket ger nya insikter om dess förbindelser med diverse utvecklingsprocesser. Denna avhandling presenterar genen SABRE (SAB) som en ny aktör i etableringen av planpolaritet och mönsterbildning av rotepidermis. SAB är ett stort protein som har sekvenslikhet med proteiner som finns i alla eukaryoter och det påverkar planpolaritet, orientering av celldelning och kortikala mikrotubler. Genetisk interaktion med genen för det mikrotubuli-associerade proteinet CLASP stärker ytterligare inblandningen av SAB i organiserandet av mikrotubler och antyder att denna gen har en roll i organiserandet av cytoskelettet. Slående är att SAB även interagerar genetiskt med ACTIN7 (ACT7) och att både ACT7 och dess modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2) bidrar till planpolaritet vid positionering av rothår. Cellfils-specifikt uttryck av AIP1-2 beror på den epidermala mönsterbildande genen WEREWOLF (WER), vilket påvisar ett samband mellan organisationen av aktin, planpolaritet och specifikationen av cellers öde. SAB fungerar även i mönsterbildning av rotens epidermis och stabiliserar förvärvet av cellöde uppströms av den centrala signalvägen för mönsterbildning. Dessa resultat visar på nya roller för SAB i planpolaritet och mönsterbildning av epidermis och indikerar att organiseringen av mikrotubler och aktin-cytoskelettet är viktiga både för etablerandet av planpolaritet och för specificeringen av cellers öde.
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Bouharrour, Aïda. "Etude des mécanismes régulant la mort cellulaire indépendante des caspases médiée par AIF : rôle des « BH3-only »." Paris 6, 2010. http://www.theses.fr/2010PA066714.
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L’homéostasie d’un organisme repose sur une balance entre la mort et le renouveau cellulaire. Ainsi au cours des nombreuses mitoses et différentiations cellulaires qui permettront de créer un organisme à partir d’une cellule œuf, il est en permanence nécessaire d’éliminer les cellules superflues ou potentiellement dangereuses. Ce phénomène d’élimination sélective des cellules est médié par un processus appelé mort cellulaire programmée, MCP. Une dérégulation de la MCP peut être à l’origine de nombreuses pathologies. Certaines sont liées à une inhibition de la mort cellulaire et sont à l’origine du développement de cancers. Pour autant, la MCP est un phénomène de grand intérêt pour la médecine, notamment pour la cancérologie. L’apoptose représente une forme de MCP qui est de nos jours très bien définie. Chez les mammifères, l’apoptose est étroitement liée à l’activation d’une famille de protéases, dites caspases. Cependant, des travaux plus récents indiquent que l’apoptose peut aussi avoir lieu sans l’intervention de cette famille de protéases. Dans ce cas, on parle de mort cellulaire caspase-indépendante. A date d’aujourd’hui, l’un des principaux médiateurs connus de la mort caspase-indépendante est la protéine AIF (ou Apoptosis Inducing Factor). L’objectif de cette thèse a été ainsi de décrire dans un premier temps les caractéristiques morphologiques et biochimiques de la mort cellulaire par caspase-indépendante induite par des agents alkylants de l’ADN. Les différents acteurs de cette voie AIF-dépendante ont été identifiés avec notamment l’intervention de PARP-1, les calpaines, Bax. Malgré ces résultats, des questions clés restent posées : Comment les calpaines peuvent activer la protéine pro-apoptotique Bax ? Est-ce qu’il existe d’autres protéines de la famille des Bcl-2 qui seraient impliquées dans la sortie d’AIF de la mitochondrie lors de ce processus indépendant des caspases ? À travers l’analyse de tous ces mécanismes en amont qui contrôlent la sortie d’AIF de la mitochondrie dans la nécrose induite par le dommage à l’ADN, on a pu démontré le rôle déterminant de Bid dans l’activation de Bax et par conséquent dans notre type de MCP. Un dernier travail a permis d’élucider le mécanisme par lequel AIF induit la chromatinolyse associé à la mort induite par les agents alkylants de l’ADN. Ainsi, on a pu mettre en évidence une nouvelle interaction impliquant AIF et l’histone, H2AX plus précisément -H2AX (forme phosphorylée de H2AX) qui s’est avérée essentielle au processus de MCP indépendante des caspases induit par le MNNG. Mots clés Mort cellulaire caspase-indépendante, AIF, protéine BH3-only. Un dernier travail a permis d’élucider le mécanisme par lequel AIF induit la chromatinolyse associé à la mort induite par les agents alkylants de l’ADN. Ainsi, on a pu mettre en évidence une nouvelle interaction impliquant AIF et l’histone, H2AX plus précisément -H2AX (forme phosphorylée de H2AX) qui s’est avérée essentielle au processus de MCP indépendante des caspases induit par le MNNG. Mots clés Mort cellulaire caspase-indépendante, AIF, protéine BH3-only
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Yang, Jian. "Biochemical studies of the mobility mechanism of group II introns aI1 and aI2 of yeast mitochondrial DNA /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487949508372739.
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Watanabe, Motonobu. "Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation." Kyoto University, 2009. http://hdl.handle.net/2433/124304.
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Majlund, Åsa. "Konsekvensanalys av olika förändringar i intäktsrams-regleringen avseende hänsyn till leveranssäkerhet." Thesis, KTH, Elektroteknisk teori och konstruktion, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-228390.
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The distribution of electricity is a natural monopoly. The infrastructure of the electricity grid is divided into areas and the distribution system operator (DSO) has concession for the distribution of the defined area. The concession is governed by laws and regulation.The Swedish Energy Markets Inspectorate (Ei) is the national regulatory authority. The continuity of supply of electricity is a part of the regulation. The incentive is given by a revenue cap regulation which may result in a reward or penalty.The performance indicators are a measure of the continuity of supply and used in the calculation of the revenue cap regulation.The Master thesis aims to specify the possible consequences for the electricity distribution system operators and their customers utilizing the electricity grid in case of a change of the current methods used to measure the continuity of supply in Sweden.With the current methods, the Ei regulation for year 2016-2019, is the continuity of supply in the local electrical grid estimated from a view where each disruption is treated equal and therefore is SAIFI and SAIDI used. In the regional electrical grid is another method used to measure the continuity of supply, estimated from a view where the loss of supplied energy is considered, therefore uses PNS and ENS. In the documentation is the term ILE used for ENS and ILEffekt for PNS.The Master thesis is constructed to analyze new performance indicators for the local and regional distribution grid. The new performance indicator is the mathematically instrument to measure the continuity of supply and is supported by analytically advantages and disadvantages.The result shows the choice of performance indicators cause a great impact in the revenue cap regulation. AIT, AIF corresponds to ENS and PNS, respectively, divided by power. The three most important results are given by:1. Mathematical and theoretical results show that ENS, PNS are not good indicators individually or in combination with SAIDI, SAIFI and CEMI4 as power consumption within each customer group varies in the local electrical grid.In the regional electrical grid, power consumption may also vary between the norm period and the supervisory period, which means that ENS, PNS can sometimes be misleading.2. The inclusion of power disruption over 12 hours generate stronger incentives in the regulation. Because it requires long term planning to avoid interruptions exceeding 12 hours. The difference is shown mainly in local electrical grid with the indicators SAIDI, SAIFI and CEMI4 and gives a slight increase in rewards in the regulation. This affects the DSO’s and their customers with a marginal difference.3. In the short term, the introduction of AIT, AIF as quality indicators means that customers who consume more power within their customer group get higher-value interruptions. An interruption of a high-consumption customer would then be prioritized compared to a customer with a lower consumption. One way to counteract this is to use CEMI4, in order to capture these customers' interruptions in the regulation.In the long term, the regulation does not become cyclically sensitive, meaning that reasonable rewards or penalties are made. This should benefit a long-term planning of the electrical grid, as the DSO’s do not have to compensate for this.<br>Det elektriska distributionsnätet är ett naturligt monopol. Infrastrukturen av nätet är uppdelat i områden och där nätägaren har nätkoncession för området som omfattas. Koncessionen är styrd av lagar och reglering.Energimarknadsinspektionen (Ei) är en tillsynsmyndighet som arbetar med uppdrag från regeringen. En del av tillsyn för energimarknaden, är reglering av leveranssäkerhet i det elektriska distributionsnätet. Incitamentet i regleringen ges av intäktsramens begränsning vilket kan resultera i en ökning eller minskning av intäktsramen.Kvalitetsindikatorer är ett matematiskt verktyg för att mäta leveranssäkerhet och används i regleringen av intäktsramen.Examensarbetet syftar till att synliggöra de möjliga konsekvenserna för nätföretagen respektive deras kunder av olika förändringar av de mätmetoder som används för att uppskatta leveranssäkerhet.De mätmetoder som används styrs av indikatorer. Indikatorer som mäter antal avbrott per totalt antal kunder kallas SAIFI. Indikatorer som mäter tid för dessa avbrott per totalt antal kunder kallas SAIDI. En annan metod är att de ingående indikatorerna ska mäta icke levererad energi eller effekt och då kallas de ILE respektive ILEffekt.Energimarknadsinspektionen har inför reglerperioden år 2016-2019 tillämpat SAIDI och SAIFI för kunder kopplade till lokalnät och ILE och ILEffekt för kunder och gränspunkter inom regionnätetExamensarbetet är utformat för att analysera nya typer av kvalitetsindikatorer i lokalnät och regionnät. De nya kvalitetsindikatorerna är olika matematiska verktyg för att mäta leveranssäkerheten och motiveras med analytiska för- och nackdelar.Resultatet visar att valet av indikator har stor betydelse i intäktsramens reglering. AIT, AIF motsvarar ILE respektive ILEffekt dividerat med effekt. De tre viktigaste resultaten ges av:1. Matematiska och teoretiska resultat visar att ILE, ILEffekt är inte bra indikatorer enskilt eller i kombination med SAIDI, SAIFI och CEMI4 då effektförbrukningen inom varje kundgrupp varierar för lokalnät.I regionnät så kan effektförbrukningen också variera mellan normperiod och tillsynsperiod vilket ger att ILE, ILEffekt ibland kan bli missvisande.2. Avbrott över 12 timmar genererar ett starkare incitament i regleringen. Eftersom det kräver långsiktig planering för att undvika avbrott som överstiger 12 timmar. Skillnaden visas främst i lokalnät med indikatorerna SAIDI, SAIFI och CEMI4 och ger en svag höjning av tillägg i regleringen sett på en systemnivå. Det påverkar nätföretagen och deras kunder med en marginell skillnad.3. På kort sikt innebär införandet av AIT, AIF som kvalitetsindikatorer att de kunder som förbrukar mer inom sin kundgrupp får högre värderade avbrott. Ett avbrott hos en kund med hög förbrukning skulle då prioriteras före en kund med lägre förbrukning. Ett sätt att motverka detta är att använda CEMI4 för att fånga upp dessa kunders avbrott i regleringen.På lång sikt innebär det att regleringen inte blir konjunkturkänslig, vilket innebär att rimliga tillägg eller avdrag görs. Det borde gynna en långsiktig planering av elnätet då elnätsföretagen inte behöver kompensera för detta inom regionnäten och lokalnäten.
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Abrahão, Dayana Pousa Siqueira. "Expressão de AIF, PARP-1 e do microRNA-9 em modelo de isquemia cerebral experimental associada ao alcoolismo." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-27012017-115339/.
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Objetivo: Analisar e descrever o perfil de expressão das proteínas relacionadas ao mecanismo de apoptose (PARP e AIF), e o perfil de expressão gênica sérica do microRNA-9 relacionado ao mecanismo de apoptose, em ratos submetidos à isquemia cerebral focal por oclusão da ACM por 90 minutos, seguida de reperfusão de 48horas, associado ou não com modelo de alcoolismo crônico. Métodos: Foram utilizados 20 ratos Wistar adultos, subdivididos em 4 grupos experimentais: grupo controle (C): animais submetidos apenas à anestesia; grupo isquêmico (I): animais submetidos à isquemia cerebral focal por 90 minutos seguido por reperfusão de 48 horas; grupo alcoolizado (A): animais que receberam diariamente álcool etílico absoluto diluído a 20% em água durante quatro semanas; e, grupo isquêmico e alcoolizado (IA): animais submetidos ao mesmo tratamento do grupo A e que, após quatro semanas foram submetidos à isquemia cerebral focal durante 90 minutos, seguido por reperfusão de 48 horas. As amostras do encéfalo coletadas foram processadas para a análise imunohistoquímica (para a expressão protéica de PARP-1 e AIF); e o sangue da artéria ventral da cauda foi coletado para a análise da expressão gênica do miRNA-9, relacionada ao mecanismo de apoptose, pela técnica de PCR em tempo real. Resultados: A comparação entre os grupos identificou uma redução da expressão proteica de PARP-1 nos animais do grupo AI quando comparado com os demais. Foi observada marcação positiva nuclear para a proteína AIF somente no grupo IA. Não houve diferença estatisticamente significante da expressão sérica do miRNA-9 entre os grupos. Conclusão: O modelo proposto, pode não ter sido suficiente para promover a ativação de AIF nos grupos C, A e I e desta forma, a apoptose celular por essa via analisada. A expressão proteica de PARP-1 no grupo A, associado com a expressão nula de AIF, indica um efeito neuroprotetor do etanol neste grupo. A redução da expressão proteica de PARP-1 não afetou sua atividade enzimática, proporcionando, mesmo em baixas concentrações, ativação de AIF no grupo IA. A expressão de PARP- 1 no grupo I, associada a expressão nula de AIF indica que o modelo de isquemia possivelmente gerou leves danos no DNA o que estimulou a ativação de PARP-1 somente em níveis suficientes para promover a reparação do DNA e não a ativação do processo de apoptose pela translocação de AIF. A expressão gênica sérica do miRNA- 9 observada indicou que a mesma foi suprimida quando exposta a mecanismos de estresse (alcoolismo, isquemia e a associação dos mesmos). A correlação do miRNA-9 com a expressão proteica de PARP-1 e AIF, indicou um aspecto protetor da baixa regulação do miRNA-9 tanto em animais alcoolizados como em animais isquêmicos. O grupo IA apresentou uma tendência a baixa expressão do miRNA-9, baixa expressão de PARP-1 e alta expressão de AIF, indicando que a associação álcool e isquemia tenha interferido no efeito protetor do miRNA-9 visto nos demais grupos<br>Aim: To analyze and describe the expression profile of proteins related to apoptosis mechanism (PARP and AIF), and profile of gene expression of miRNA-9 related to apoptosis mechanism in rats submitted to focal cerebral ischemia by occlusion of the CMA for 90 minutes, followed by 48 hours of reperfusion, associated or without associated to chronic alcoholism model. Methods: 20 adult Wistar rats were used, divided into 4 groups: control group (C): animals submitted only to anesthesia; Ischemic group (I): animals subjected to focal cerebral ischemia for 90 minutes followed by 48 hours of reperfusion; alcoholic group (A): animals that received daily solution of 20% of absolute ethyl alcohol diluted in water during four weeks; and ischemic group and alcoholized (IA): Animals subjected to the same treatment group A and after four weeks were subjected to focal cerebral ischemia for 90 minutes followed by 48 hours of reperfusion. The brain samples were collected and processed for immunohistochemical analysis (for protein expression - PARP-1 and AIF); and the blood from ventral artery of tail was collected for the analysis, by PCR in real time, of gene expression of miRNA-9 related to the mechanism of apoptosis. Results: The comparison between the groups identified a decrease in protein expression (PARP-1) in animals from IA group compared to others groups. Nuclear positive staining was observed for the AIF protein only in the IA group. There was no significant difference in serum expression of miRNA-9 between the groups. Conclusion: The proposed model may not have been sufficient to promote the activation of AIF in groups C, A and I, and thus the apoptosis analyzed in this way. Protein expression of PARP-1 in group A associated with a null expression of AIF, indicate a neuroprotective effect of ethanol in this group. The reduction of protein expression PARP-1 did not affect its enzymatic activity, providing even at low concentrations, activation AIF in IA group. The expression of PARP-1 in group I associated with null expression of AIF showed that model of ischemia, possibly, promoted light damage in DNA which stimulated PARP-1 activation just in sufficient levels to promote DNA repair, and without activation of apoptosis by translocation of AIF. The gene expression of miRNA-9 indicated that it was suppressed when exposed to mechanical stress (alcoholism, ischemia and combination thereof). The correlation of miRNA-9 with the protein expression (PARP-1 and AIF), indicated a protective aspect of downregulation of the miRNA-9 in both animals drunk as ischemic animals. IA group showed a trend to low expression of miRNA-9 and PARP- 1, in other hand an overexpression of AIF, indicating that the association between alcohol and ischemia interfered in protective effect of miRNA-9 seen in the other groups
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Bouaita, Aïcha. "Essais de thérapie génique contre la dégénérescence rétinienne chez la souris Harlequin déficiente pour la protéine mitochondriale AIF." Paris 6, 2012. http://www.theses.fr/2012PA066566.
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La rétine est souvent affectée par des pathologies liées à la dysfonction mitochondriale. Ces pathologies peuvent être liées à une anomalie génétique dans l’ADN mitochondrial, par exemple la NOHL et la NARP. Elles peuvent être liées à une anomalie dans l’ADN nucléaire, par exemple l’AOD. La dysfonction mitochondriale serait également impliquée dans d’autres pathologies comme le glaucome et la DMLA. Le déséquilibre entre la production et l’élimination des ROS serait un des mécanismes moléculaires dans ces dégénérescences rétiniennes. L’œil, par sa petite taille et son confinement représente un organe de choix pour tester une thérapie, et suivre son effet in vivo par des méthodes non invasives. Les travaux du Dr. M. Corral-Debrinski ont permis de mettre en place une thérapie génique pour prévenir des effets délétères d’une mutation de l’ADN mitochondrial chez le rat. Cette approche fondée sur la localisation des ARN messagers sur la surface de l’organite a ouvert la voie pour tester la même stratégie chez la souris Harlequin afin d’entraver la dégénérescence rétinienne et l’atrophie optique dues à la mutation du gène AIF. Après avoir caractérisé la dystrophie rétinienne chez la souris Harlequin, une thérapie par le vecteur AAV2/2-AIFm1 a été réalisée. En fonction des cellules rétiniennes ciblées, la voie d’injection des particules virales était intravitréenne ou sous rétinienne. Le bénéfice de ce traitement sur la préservation de la viabilité des cellules ganglionnaires de la rétine et leurs axones a été vérifié. En conclusion, la stratégie thérapeutique dans le cadre de l’atrophie optique chez la souris Harlequin utilisant un vecteur de type AAV2/2 fut un succès.
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Pilon-Larose, Karine. "Apoptosis-Inducing Factor (AIF) forms a complex with Optic Atrophy 1 (Opa1) to maintain mitochondrial structure and function." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28602.
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The mitochondrial protein Apoptosis-inducing factor (AIF) is a redox active flavoprotein that has a dual role in the regulation of cell death and survival. We have previously identified a novel role for AIF in mitochondrial structure. Here, we examine the mechanism by which AIF controls mitochondrial structure and metabolism and found that AIF deficiency results in mitochondrial fragmentation, cristae malformation and a defect in oxidative phosphorylation. Mitochondrial AIF is essential for organelle fusion as the fission/fusion proteins Mnf1 and dnDrp1 fail to rescue the structural defect seen in AIF deficiency. In contrast, upregulation of Opa1 in AIF deficient neurons restores mitochondrial structure, metabolism and cellular survival. We show that AIF functions upstream of Opa1 because increased mitochondrial AIF cannot rescue neuronal cell death induced by Opa1 deficiency. AIF-deficient neurons display reduced Opa1 oligomerization resulting in impaired cristae formation. Furthermore, we show that AIF interacts with Opa1 to maintain Opa1 oligomerization. This interaction is critical during apoptosis signaling, as Opa1 oligomerization can be preserved by expression of mitochondrial AIF. Apart from AIF, we also identified novel factors that affect the degree of Opa1 oligomerization. Indeed, Opa1 oligomers seem to be modulated by cell metabolism according to levels of NADH and NAD+. These results identify a novel functional interaction between AIF, Opa1 and cell metabolism and links the control of mitochondrial structure with apoptosis signaling and the metabolic state of the cell.
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Wohlfarth, Tobias Joachim [Verfasser], and Jens-Hinrich [Akademischer Betreuer] Binder. "Vergütung und Interessengleichlauf in alternativen Investmentfonds - Eine rechtsökonomische Untersuchung der Regulierung durch AIFM-Richtlinie und Kapitalanlagegesetzbuch / Tobias Joachim Wohlfarth ; Betreuer: Jens-Hinrich Binder." Tübingen : Universitätsbibliothek Tübingen, 2018. http://d-nb.info/119897320X/34.
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Ribeyron, Juliana. "Etude de la physiopathologie du récepteur FcγRIIB dans les lymphomes B malins non-Hodgkiniens". Grenoble 1, 2006. http://www.theses.fr/2006GRE10231.
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Le récepteur de basse affinité pour les fragments Fc des immunoglobulines G, FcgammaRIIB, joue un rôle clé dans la régulation négative des réponses immunes. Il est capable d'inhiber les fonctions cellulaires B induites par le BCR, ainsi que à induire un processus de mort cellulaire, encore très peu caractérisée dans la littérature. Récemment, un rôle potentiel de FcgammaRIIB dans la tumorigenèse a été identifié. En particulier, la dérégulation de l'expression de FcgammaRIIB suite à des translocations chromosomiques a été rapportée dans des cas de lymphomes folliculaires. Nous avons, ainsi étudié les conséquences du recrutement des récepteurs FcgammaRIIB dans des lignées de lymphome B. Nous montrons que le co-recrutement de récepteurs FcgammaRII à l'aide d'anticorps anti-FcgammaRII (FLI 8. 26) induit la mort cellulaire de cellules de lymphome B, mais n'induit pas la mort des lymphocytes B normaux. Ce processus apoptotique dans les cellules tumorales B est caspase dépendant (libération du cytochrome c, clivage de la caspase-9, activation de la caspase-3) et indépendant (libération d'AIF). Nous montrons que la phosphorylation des récepteurs FcgammaRIIB est un événement précoce dans la voie de signalisation apoptotique. De plus, le traitement par FLI 8. 26 a induit l'expression de la protéine HSP27. Nos résultats ont montré pour la première fois les mécanismes de mort cellulaire FcgammaRIIB dépendante dans les lymphomes B humains. Nous suggérons que la mort cellulaire FcgammaRIIB dépendante pourrait ainsi, être mise à profit en thérapeutique<br>FcgammaRIIB the low affinity inhibitory receptor for IgG plas a key role in the negative regulation of immune responses. FcgammaRIIB inhibits BCR-dependent B cell functions, as well as it induces a cellular death process which is poorly characterized. Lately, a potential role of FcgammaRIIB in the tumorigenesis has been identified. In particular, the deregulated expression of FcgammaRIIB as a consequence of the chromosomal translocations in follicular lymphomas has been described. Thus, we have studied the consequences of the homoaggregation of FcgammaRIIB in human B lymphoma cell lines. We show that FcgammaRIIB homoaggregation with anti FcgammaRIIB antibody (FLI 8. 26) induced the cellular death of B lymphoma cells, but did not induce the death of normal human B lymphocytes. This cell death pathway in B tumoral cells is caspase dependent (cytochrome c release, caspase-9 cleavage, caspase-3 activation) and independent (AIF release). FcgammaRIIB receptor phosphorylation was found to be an early signalling event in this cell death pathway. Interestingly, FLI 8. 26 antibody treatment also induced the expression of HSP27. This report constitutes the first investigation of this cell death pathway in human B cells. We propose that this novel cell death pathway offers potential for therapeutic exploitation in lymphoma treatment
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Šeliga, Michal. "Modelování pokročilých funkcí technologie 802.11e v prostředí OPENT Modeler." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2009. http://www.nusl.cz/ntk/nusl-218164.
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This master thesis includes a short review of the structure of WLAN (Wireless Local Area Network) technologies 802.11a/b/g, the description of their physical interface and the description of the basic medium access control mechanisms implementing the PCF (Point Coordination Function) and DCF (Distributed Coordination Function) methods. I mainly focused on the detailed evaluation the new 802.11e standard which was designed to efficiently support real-time services in wireless environment. To provide QoS (Quality of Service) support, this standard specifies the EDCA (Ehanced Distributed Channel Access) and HCF (Hybrid Coordination Function) medium access control methods for the shared wireless environment. The next chapter of my work is devoted to the verification of the theoretical results in OPNET Modeler simulation environment. I studied in details the WLAN model available in OPNET Modeler, the effect of data-flow classification into separate categories and the configuration of several access method parameters. Next, I created my own WLAN model according to the 802.11e standard. This model contains four applications two of them with real-time requirements. The model is divided into several scenarios, each focusing on different aspects of wireless network technologies like QoS support and it´s dependency on the number of clients, mobility of wireless terminals and comparison of the 802.11a/b/g and the 802.11e technology.
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Boujrad, Hanan. "Mort cellulaire programmée indépendante des caspases médiée par AIF : rôle de l'histone H2AX et de sa forme phosphorylée γ-H2AX". Paris 6, 2011. http://www.theses.fr/2011PA066457.
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La mort cellulaire programmée (MCP) est un processus fondamental au sein des organismes. Des dérégulations de la MCP sont impliquées dans diverses pathologies dont les cancers. L'apoptose, caractérisée par l'activation de protéases spécifiques, les caspases, était considérée au départ comme l'unique mode de MCP. Néanmoins, depuis une quinzaine d'années, de nouveaux types de MCP indépendants des caspases ont été décrits. Ces voies alternatives de MCP constituent un intérêt clinique potentiel afin de contourner la résistance tumorale aux traitements ciblant la voie caspase-dépendante. Au sein du laboratoire, nous étudions une voie de mort cellulaire indépendante des caspases et de la protéine p53 (mutée dans de nombreux cancers) et associée au dommage à l'ADN induit par le N-methyl-N'-nitro-N-nitrosoguanidine, un agent alkylant de l'ADN. La protéine AIF (Apoptosis-Inducing Factor) est un des acteurs essentiels de cette voie. Lors du processus de mort cellulaire, AIF, ancrée dans la mitochondrie, est transloquée au niveau du cytosol puis redistribuée au noyau où elle induit la fragmentation de l'ADN. Mon travail de thèse a consisté en l'élucidation des mécanismes moléculaires impliquant AIF, qui est dépourvue d'activité nucléase, dans le processus de chromatinolyse. Ainsi, nous avons pu démontrer la formation d'un complexe entre l'histone H2AX, AIF et l'endonucléase cyclophiline A, capable de dégrader l'ADN des cellules mourantes. La phosphorylation de H2AX au niveau de la sérine 139 (gamma-H2AX) est rapide et essentielle au processus de mort. En conséquence, la dernière partie de ma thèse a été consacrée à l'identification des kinases responsables de cette phosphorylation.
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Stanler, Johan. "Beskattning av carried interest : Riskkapitalbranschens ersättningsform och dess plats i gällande svensk skatterätt." Thesis, Uppsala universitet, Juridiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181022.
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Cabon, Lauriane. "Implication d'AIF dans la mort cellulaire et la physiologie mitochondriale : exemples dans la nécroptose intrinsèque et l'hématopoïèse." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066314/document.
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AIF fait partie des protéines mitochondriales inductrices de mort mais possède aussi un rôle vital nécessaire à la respiration cellulaire. Les recherches menées lors de cette thèse portent sur ces deux fonctions. D'une part, j'ai approfondi l'étude de la nécrose régulée induite par un agent alkylant de l'ADN. J'ai découvert l'importance de RIP1 dans cette voie de mort cellulaire et ainsi conduit à la définir comme nécroptose. J'ai aussi mis en évidence le rôle de BID, BH3-only de la famille BCL-2, dans la libération d'AIF des mitochondries. J'ai montré que les protéases calpaïnes clivaient BID permettant à sa forme tronquée de relocaliser aux mitochondries et d'y activer le facteur pro-apoptotique BAX. Cette étude contribue à replacer le rôle des BH3-only dans des voies de mort cellulaire au delà de l'apoptose. D'autre part, j'ai étudié le rôle d'AIF dans l'hématopoïèse grâce à un modèle murin invalidé pour AIF dans ce système. J'ai observé un blocage de différenciation thymique et le développement d'une pancytopénie sévère. J'ai démontré que cette dernière est associée à la perte des cellules souches hématopoïétiques dont j'ai testé les capacités ex vivo et in vivo. Pour comprendre les raisons de ce défaut, j'ai caractérisé les conséquences associées à la perte d'AIF : perte du complexe I de la chaine respiratoire, diminution d'activité de phosphorylation oxydative, diminution de la production d'ATP, augmentation des espèces réactives de l'oxygène. Cette deuxième étude démontre l'importance d'une phosphorylation oxydative fonctionnelle et de mitochondries saines pour une hématopoïèse normale et particulièrement pour le maintien des cellules souches hématopoïétiques<br>AIF is one of the cell death effectors released from mitochondria but it also possess a vital role by regulating the cellular respiration. Throughout this thesis work, I have focused my studies on these two functions. On one hand, I have performed a deeper characterization of the DNA alkylating agent induced regulated necrosis. I have identified RIP1 as a crucial determinant of this cell death pathway, hence linking it to necroptosis. I have also highlighted the role of BID, a BH3-only member of the BCL-2 family, in the mitochondrial release of AIF. I have shown that calpains proteases cleave BID into tBID which relocalize to mitochondria where it helps activating the pro-apoptotic factor BAX. This study contributes to reconsider the role of BH3-only proteins in cell death pathways beyond apoptosis. On the other hand, I have studied AIF role in hematopoiesis thanks to a mouse model with hematopoietic lineage-specific deletion of AIF. I have observed a block in T-cell development and the rapid development of severe pancytopenia. I have demonstrated that this pancytopenia is associated with the loss of hematopoietic stem cells whom capacities were tested both ex vivo and in vivo. In order to understand the underlying determinants of these defects, I have characterized the cellular consequences related to AIF deletion : loss of the respiratory chain complex I, decrease of the oxidative phosphorylation capacity, decreased levels of ATP, increased levels of reactive oxygen species. This second study reveals the importance of a proper oxidative phosphorylation system combined with healthy mitochondria for a normal hematopoiesis and hematopoietic stem cells maintenance
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Moubarak, Rana. "Caractérisation de la voie de mort cellulaire programmée induite par le dommage à l'ADN : rôles de PARP-1, calpaine, Bax et AIF." Paris 6, 2007. http://www.theses.fr/2007PA066045.
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Le dommage à l’ADN induit une mort cellulaire programmée de type nécrotique à travers les poly(ADP-ribose) polymerases (PARP) et Apoptosis-Inducing Factor (AIF). Suite à l’activation de PARP, AIF est relargué de la mitochondrie et transloque au noyau où il cause la condensation de la chromatine et la fragmentation de l’ADN. Nous avons identifié deux liens moléculaires entre PARP et AIF: les calpaines et Bax. Le dommage à l’ADN induit une mort indépendante de p53 mais impliquant PARP-1 et pas PARP-2. La nécrose due à la sortie d’AIF de la mitochondrie est dépendante des calpaines, mais pas des cathepsines ni des caspases. L’invalidation génétique de Bax, un membre pro-apoptotique de la famille Bcl-2, mais pas de Bak, inhibe à la fois la sortie d’AIF et la mort induite par le dommage à l’ADN. Finalement, nous avons établi l’ordre moléculaire d’activation de PARP-1, les calpaines, Bax puis AIF, et nous démontrons que la sous-expression d’AIF confère une résistance à la nécrose induite par le dommage à l’ADN. Ces études contribuent à l’élucidation des mécanismes régulant la nécrose dépendante d’AIF et impliquent que la nécrose est, comme l’apoptose, une forme de mort cellulaire programmée.
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Richard, Marie Anne. "Modélisation pharmacocinétique en imagerie par résonance magnétique et en tomographie d’émission par positrons appliquée à un modèle de glioblastome chez le rat." Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9709.
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Résumé : En imagerie médicale, il est courant d’associer plusieurs modalités afin de tirer profit des renseignements complémentaires qu’elles fournissent. Par exemple, la tomographie d’émission par positrons (TEP) peut être combinée à l’imagerie par résonance magnétique (IRM) pour obtenir à la fois des renseignements sur les processus biologiques et sur l’anatomie du sujet. Le but de ce projet est d’explorer les synergies entre l’IRM et la TEP dans le cadre d’analyses pharmacocinétiques. Plus spécifiquement, d’exploiter la haute résolution spatiale et les renseignements sur la perfusion et la perméabilité vasculaire fournis par l’IRM dynamique avec agent de contraste afin de mieux évaluer ces mêmes paramètres pour un radiotraceur TEP injecté peu de temps après. L’évaluation précise des paramètres de perfusion du radiotraceur devrait permettre de mieux quantifier le métabolisme et de distinguer l’accumulation spécifique et non spécifique. Les travaux ont porté sur deux radiotraceurs de TEP (18F-fluorodésoxyglucose [FDG] et 18F-fluoroéthyle-tyrosine [FET]) ainsi que sur un agent de contraste d’IRM (acide gadopentétique [Gd DTPA]) dans un modèle de glioblastome chez le rat. Les images ont été acquises séquentiellement, en IRM, puis en TEP, et des prélèvements sanguins ont été effectués afin d’obtenir une fonction d’entrée artérielle (AIF) pour chaque molécule. Par la suite, les images obtenues avec chaque modalité ont été recalées et l’analyse pharmacocinétique a été effectuée par régions d’intérêt (ROI) et par voxel. Pour le FDG, un modèle irréversible à 3 compartiments (2 tissus) a été utilisé conformément à la littérature. Pour la FET, il a été déterminé qu’un modèle irréversible à 2 tissus pouvait être appliqué au cerveau et à la tumeur, alors qu’un modèle réversible à 2 tissus convenait aux muscles. La possibilité d’effectuer une conversion d’AIF (sanguine ou dérivée de l’image) entre le Gd DTPA et la FET, ou vice versa, a aussi été étudiée et s’est avérée faisable dans le cas des AIF sanguines obtenues à partir de l’artère caudale, comme c’est le cas pour le FDG. Finalement, l’analyse pharmacocinétique combinée IRM et TEP a relevé un lien entre la perfusion du Gd-DTPA et du FDG, ou de la FET, pour les muscles, mais elle a démontré des disparités importantes dans la tumeur. Ces résultats soulignent la complexité du microenvironnement tumoral (p. ex. coexistence de divers modes de transport pour une même molécule) et les nombreux défis rencontrées lors de sa caractérisation chez le petit animal.<br>Abstract : In medical imaging, different modalities are frequently combined in order to obtain complementary information. For example, positron emission tomography (PET) can be associated with magnetic resonance imaging (MRI) to derive both anatomical and biological information. This project explores the synergies between MRI and PET for pharmacokinetic modeling. Specifically, it exploits the high spatial resolution of MRI as well as the information about perfusion and vascular permeability derived from dynamic contrast-enhanced studies to better assess these parameters in a PET radiotracer injected shortly after the MRI examination. This more precise assessment of perfusion is thought to improve metabolism quantification for the radiotracer and to discriminate between its specific and non-specific accumulation. The present work focussed on 2 PET radiotracers, (18F-fluorodeoxyglucose [FDG] and 18F-fluoroethyltyrosine [FET]) as well as a MRI contrast agent (gadopentetic acid [Gd-DTPA]) applied to a rat glioblastoma model. Images were acquired using a sequential MRI-PET protocol and blood was drawn to derive the arterial input function (AIF) for each molecule. PET and MR images were subsequently registered and pharmacokinetic modeling was performed on regions of interest (ROI) or voxel-wise. For FDG, an irreversible 3 compartments (2-tissue) model was used in accordance to the literature. For FET, it was determined that an irreversible 2-tissue model is applicable for the brain and the tumor and a reversible 2-tissue model is preferred for the muscles. AIF (blood or image-derived) conversion between Gd-DTPA and FET, or vice versa, was also considered and proved feasible for the blood AIF derived from the caudal artery, similar to FDG. Finally, combined kinetic modeling for MRI and PET showed a relationship between the perfusion of FDG, or FET, and that of Gd-DTPA in muscle. Important disparities were noted for the tumor. These results illustrate the complexity of the tumor microenvironment (e.g. presence of various transport mechanisms for the same molecule) and the numerous challenges encountered during its characterization in small animals.
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Bertaux, Audrey. "Influence du métabolisme mitochondrial dans l'hématopoïèse : Analyse de la réponse adaptative des cellules de la moelle osseuse et des thymocytes au dysfonctionnement de l’OXPHOS." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS040/document.
Full textAbstract:
Les mitochondries sont des organelles qui jouent un rôle clé dans le métabolisme cellulaire en centralisant la production d'ATP à partir de nombreux substrats via la phosphorylation oxydative (OXPHOS). Les réactions enzymatiques impliquées dans ce processus régulent la prolifération, la différenciation, l'activation et l'auto renouvellement cellulaire. Le but de mon travail a été d'identifier le rôle de l'OXPHOS dans l'hématopoïèse et les mécanismes d'adaptation métabolique des cellules sanguines de la moelle, des lymphocytes B et des thymocytes à la dysfonction mitochondriale. L'atout majeur de cette étude est la génération de deux modèles murins déficients pour les protéines mitochondriales AIF ou NDUFS4 dans le système hématopoïétique. Nous avons observé que l'absence de ces protéines entraine des dysfonctions de l'OXPHOS sévère (AIF KO) ou modérée (NDUFS4 KO), entrainant des anomalies dans le développement hématopoïétique. Dans les deux modèles, en réponse au stress métabolique induit par la dysfonction de l'OXPHOS, les cellules de moelle activent la glycolyse anaérobie et la biogenèse mitochondriale tandis que les thymocytes favorisent l'assimilation et la dégradation des acides gras. Cette étude multiparamétrique, incluant des approches in vivo, ex vivo et in vitro, souligne l'importance de l'OXPHOS et du métabolisme mitochondrial dans le développement hématopoïétique<br>By integrating different biochemical pathways and generating energy in form of ATP, through the electron transfer associated to oxidative phosphorylation (OXPHOS), mitochondria play a key role in cellular metabolism. In the hematopoietic cells, the mitochondrial metabolism appears implicated in proliferation, differentiation, activation and self-renewal regulation. In this context, the aim of my PhD work was to unravel the response of bone marrow (BM) cells, B-cells and thymocytes to OXPHOS dysfunction. To do that, we have developed two original hematopoietic cell-specific murine models deficient in the mitochondrial proteins AIF or NDUFS4. Severe (AIF KO) or moderate (NDUFS4 KO) OXPHOS dysfunction leads to pleiotropic consequences on hematopoietic development, including pancytopenia, BM aplasia, alterations in the development of the B-cell and erythroid lineages and T-cell developmental blockade at the immature stage. Strikingly, in response to OXPHOS dysfunction, BM cells stimulate anaerobic glycolysis and mitochondrial biogenesis, whereas thymocytes favor the assimilation and degradation of fatty acids. Overall my work, which included in vivo, ex vivo and in vitro approaches, underlines the relevance of OXPHOS and mitochondrial metabolism in the development of the hematopoietic cells
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Reinhardt, Camille. "Impact de la voie d’import mitochondrial contrôlée par le complexe AIF/CHCHD4 sur la survie des cellules cancéreuses et la réponse aux traitements anticancéreux." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS542.
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Dans la majorité des cas, les mitochondries sont nécessaires à la tumorigenèse et à la réponse des cellules cancéreuses aux signaux générés par les facteurs micro-environnementaux (exemples : privation de nutriments, hypoxie) ou par les traitements anticancéreux (exemples : chimiothérapie, radiothérapie). Presque toutes les protéines mitochondriales sont codées par le génome nucléaire et importées dans l'organelle. Des machineries d'import ont donc évolué afin de répondre aux besoins d'import protéique. Dans ce contexte, la machinerie régulée par CHCHD4/Mia40 fonctionne dans l’espace intermembranaire et contrôle l’import d’un groupe de protéines (substrats) qui joue des rôles importants dans la survie et la réponse au stress. Les substrats de CHCHD4/Mia40 sont impliqués dans un vaste panel d’activités mitochondriales qui inclut la biogenèse des complexes de la chaîne respiratoire, l’homéostasie lipidique, le stockage du calcium, ainsi que l'ultrastructure et la dynamique mitochondriale. Ce programme de thèse a été dédié à l’étude de la voie d’import CHCHD4/Mia40 dans les cellules cancéreuses et a porté un intérêt tout particulier à l'un des substrats CHCHD4/Mia40 qui façonne l'ultrastructure mitochondriale. En utilisant des techniques d’ARN interférence et de sur-expression de protéines recombinantes, dans un modèle de cancer du côlon, nous avons montré que l’expression du substrat étudié a un effet crucial sur la prolifération et la croissance tumorale. Nos données ont également impliqué cette protéine dans la réponse aux traitements anticancéreux. Dans l'ensemble, ces travaux ouvrent un nouveau champ d'investigations qui non seulement permettra de mieux comprendre la plasticité métabolique des cellules cancéreuses, mais aidera également à identifier de nouveaux biomarqueurs métaboliques<br>In the vast majority of cases, mitochondria are required for tumorigenesis and also for the tumoral response to signals generated by the microenvironmental factors (e.g. nutrient deprivation, hypoxia) or to the effects of anti-cancer treatments (e.g. chemotherapy, radiotherapy). As almost all mitochondrial proteins are nuclear-encoded and imported into the organelle, specialized import machineries have evolved in order to meet the need for protein import. Among these machineries, the one that operates in the intermembrane space and is controlled by CHCHD4/Mia40, regulates the import of a group of proteins (substrates) that play important roles in survival and stress response. Substrates of CHCHD4/Mia40 are involved in a broad panel of mitochondrial activities that includes the biogenesis of respiratory chain complexes, lipid homeostasis, calcium storage, as well as ultrastructure and mitochondrial dynamics. This thesis program was dedicated to the study of the CHCHD4/Mia40 import pathway in cancer cells, with a particular interest for one of the CHCHD4/Mia40 substrates that shapes mitochondrial ultrastructure. Using RNA interference approach and recombinant protein overexpression technique, in a colon cancer model, we showed that the expression of this substrate had a crucial effect on proliferation and tumor growth. Our data also involved this protein in the response to anti-cancer treatments. All together, this work opens a new field of investigations that will not only shed new lights on the metabolic plasticity of cancer cells but also help to identify new metabolic biomarkers
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Rivière, Anne. "La régulation des gestionnaires de hedge funds en droit européen et américain : Enjeux et perspectives. Une étude comparée des régimes juridiques issus de la directive AIFM et du Dodd Franck Act." Thesis, Tours, 2017. http://www.theses.fr/2017TOUR1005.
Full textAbstract:
Plusieurs trillions de dollars d’actifs sous gestion : tel est le poids de l’industrie des hedge funds dans le système financier. Acteurs indispensables des marchés, les hedge funds sont pourtant des créatures méconnues. Réservés aux investisseurs professionnels ou qualifiés, ils ont longtemps tiré partie d’exemptions et échappé à une trop forte contrainte réglementaire. La crise financière de 2008 a bouleversé ce schéma et fait apparaître, en Europe et aux États-Unis, une même volonté d’encadrer davantage ces structures, par le biais de leurs gestionnaires. Aussi cette étude propose-t-elle une analyse comparée des dispositions introduites en la matière par la directive AIFM et par le Dodd Frank Act. Après un nécessaire éclairage sur cette industrie de l’ombre, elle examine les apports des deux textes, les confronte avant d’en dégager forces et faiblesses. Le traumatisme de la crise a fait émerger un double impératif : mieux protéger les investisseurs et prévenir le risque systémique. C’est à la lumière de ces deux objectifs que la seconde partie s’attarde sur le bien-fondé des réformes, leur portée réelle ainsi que leurs limites. Cette vue d’ensemble de la régulation applicable aux gestionnaires de hedge funds est également prétexte à une réflexion plus large sur la régulation financière, ses finalités, ses contours et ses défis. Nous concluons sur une feuille de route pour un acte II de la directive AIFM et formulons plusieurs propositions, en particulier l’interdiction totale de commercialisation auprès d’investisseurs de détail et la création d’une base de données mondiale du risque systémique<br>The hedge fund industry manages several trillion dollars in assets. Though they are key players of the financial system, hedge funds remain mysterious creatures. Available only to professional or qualified investors, they managed, for a long time, to take advantage of exemptions and to avoid a heavy regulatory burden. The 2008 financial crisis profoundly changed perspectives and led the European Union and the United States to introduce new regulations targeting hedge funds, through their managers and advisers. This study is a comparative analysis of such regulations, brought about by the AIFM Directive and the Dodd Frank Act. After a brief overview of the industry, both texts are examined and compared so as to identify their respective strengths and weaknesses. Two imperatives emerged out of the crisis: increasing investor protection and preventing systemic risk. In light of these two objectives, part II discusses the validity of the reforms, their scope and their limits. This extensive analysis of hedge fund regulation also leads to broader remarks on financial regulation, its aims, contours and challenges. Finally, a roadmap for a revised version of the AIFM Directive is proposed and concrete measures are suggested, such as the total prohibition of marketing to retail investors and the creation of a global database of systemic risk
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Santin, Thiago. "Emprego de dispositivos vaginais de único uso (monodose) ou de três usos para liberação sustentada de progesterona em vacas de corte: testes in vitro, in vivo e de dinâmica folicular." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-14022014-155022/.
Full textAbstract:
Este trabalho teve como objetivo comparar a eficiência de dois dispositivos intravaginais de progesterona (P4) comerciais constituídos de matriz de silicone, um contendo um grama (g) de progesterona (Cronipres® de 3usos, Biogénesis Bagó, Argentina) e outro contendo 0,558 g de P4 (Cronipres® Mono Dose M-24, Biogénesis Bagó, Argentina). O presente estudo foi dividido em três experimentos: O primeiro comparou a cinética de liberação de P4 (Teste in vitro). O segundo, avaliou as concentrações plasmáticas de P4 em vacas ovariectomizadas (Teste in vivo). No terceiro, vacas multíparas ciclícas passaram por um protocolo de sincronização da ovulação para IATF, onde foi avaliada a dinâmica folicular, desde a colocação do implante no D0, até o momento da inseminação (Dinâmica folicular). Nesse experimento as concentrações séricas de P4 foram dosadas nos dias 6, 7 e 8 do protocolo de IATF. No experimento In vitro supracitado, os dois dispositivos, foram alocados em duplicata, no dissolutor de comprimidos, o qual continha álcool e água na proporção de 60:40. Amostras foram colhidas nos seguintes momentos: 2min, 24, 48, 72, e 96 horas. As quantidades de P4 foram dosadas por Cromatografia Líquida de Alto Desempenho (HPLC). Para quantidade acumulada de P4, segundo dispositivo, em função do tempo, houve interação tempo*tratamento (P=0,0002). A quantidade de P4 diferiu entre os dois dispositivos testados e também em relação ao tempo (P<0.0001). Houve diferença estatísitica, nos tempos 2min, 72 e 96 horas. As equações que descrevem as quantidades liberadas são: dispositivos Cronipres® 3 usos Y= 62,396x + 175,70 (R2 = 0,99) Cronipres® Mono Dose Y= 53,314x + 127,7(R2=0,98). No experimento in vivo, 8 vacas ovariectomizadas foram divididas em dois grupos, metade recebeu o Cronipres® de 3 usos e a outra metade recebeu o Cronipres® Mono Dose durante 11 os dias de tratamento. Foram colhidas amostras nos tempos 0 (colocação do dispositivo ), 2, 4, 8, 12, 24, 48, 96, 144, 192, 216, 240 e 264 horas. Foram comparados os teores plasmáticos de P4, por espectrometria de massas no laboratório Thomson da Universidade de Campinas (UNICAMP). Houve efeito de tratamento e de tempo (p < 0,05), entretanto, não houve efeito de tempo (p > 0,05). No terceiro experimento, 20 vacas multíparas cíclicas foram submetidas a um protocolo de sincronização da ovulação. Os animais receberam 2 mg intramuscular (IM) de Benzoato de Estradiol . Metade do grupo (n=10) recebeu um dispositivo intravaginal de P4, Cronipres® 3 usos, e a outra metade (n=10) recebeu o Cronipres® Mono Dose M-24. No D8 procedeu-se a retirada do implante e aplicação IM de 150 g de D-cloprostenol . No D9, todos os animais receberam 1mg IM de Benzoato de estradiol . Foi realizado o escaneamento dos ovários por ultrassonografia a cada 24 horas, do momento da inserção do dispositivo até à retirada no D8. A partir da indução, todas as vacas tiveram seus ovários escaneados e mapeados a cada 12 horas, durante 4 dias. Coletas de sangue foram efetuadas nos dias seis, sete e oito do protocolo para comparar as concentrações plasmáticas de P4 antes da retirada do dispositivo. Foram avaliadas as variáveis, início da nova onda de crescimento folicular, diâmetro do folículo préovulatório (de forma retrospectiva) e momento da ovulação pelo teste qui quadrado. Os dados de ovulação, foram submetidos à análise de regressão logística, pelo PROC MIXED e os dados de desenvolvimento folicular, pelo PROC LOGISTIC (SAS, versão 9.3). Não houve diferença no início da nova onda de crescimento folicular, diâmetro do folículo pré-ovulatório e taxa de ovulação (P>0,05). Houve uma tendência de antecipação da ovulação (P=0.06), das vacas do grupo cronipres Mono Dose, uma vaca desse grupo antecipou a ovulação em cerca de 36 h.Mesmo apressentando diferenças estatísticas nos testes in vítro e in vivo, os animais tratados com dispositivo de 0,558 gramas apresentaram padrão de desenvolvimento folicular semelhante ao grupo tratado com o dispositivo de 1g.<br>This study aimed to compare the efficiency of two commercial intravaginal progesterone (P4) devices consisting of silicone matrix, containing 1 gram (g) of progesterone (Cronipres of 3uses ®, Biogenesis Bagó, Argentina) and another containing 0.558 g P4 (Cronipres ® Mono Dose M-24, Biogenesis Bagó, Argentina). This study was divided into three experiments: The first compared the kinetics of release of P4 (in vitro test). The second evaluated the plasma concentrations of P4 in ovariectomized cows (in vivo test). In the third, multiparous cyclical cows passed a complete protocol where TAI was evaluated follicular dynamics, since the placement of the implant in D0, until the time of insemination (follicular dynamics) and serum concentrations of P4 before removing devices (follicular dynamics). In vitro experiment above, the two devices were placed in triplicate in dissolver of tablets, which contained alcohol and water in the ratio of 60:40. Samples were collected at the following times: 2min, 24, 48, 72, and 96 hours. The amounts of P4 were measured by High Performance Liquid Chromatography (HPLC). To cumulative amount of P4, the second device as a function of time, treatment time * significant interaction (P = 0.0002). The amount of P4 differed between the two implants Cronipres ® and also in relation to time (P <0.0001). There were differences in the times 1, 4, 5. The equations that describe the quantities released are Cronipres device 3 uses ® Y - = 175.70 + 62.396 x (R2 = 0.99) Cronipres Dose ® Mono Y = 53.314 x + 127.7 (R2 = 0.98). In the in vivo experiment, 8 ovariectomized cows were divided into two groups, half received Cronipres ® 3 uses the other half received the Cronipres ® Mono Dose for 11 treatment days. Samples were collected at 0 (implant placement), 2, 4, 8, 12, 24, 48, 96, 144, 192, 216, 240, 264 hours. We compared the plasma levels of P4, mass spectrometry laboratory Thomson of the University of Campinas (UNICAMP). No effect was observed treatment and animal (p> 0.05) however there was only time effect (p <0.05). In the third experiment, 20 multiparous cows and cyclic undergone a complete protocol for fixed-time artificial insemination (TAI). In D0 treatment, all animals received 2 mg intramuscular (IM) of estradiol benzoate (Cronibest ® - Biogenesis-Tobago, Argentina). Half of the group (n = 10) received an intravaginal P4 device, Cronipres ® 3 uses, and the other half (n = 10) received the Cronipres ® Mono Dose M-24. In D8 proceeded to implant removal and application of IM 150 mg of D-cloprostenol (Croniben ®, Biogenesis-Bagó, Argentina). On Day 9, all animals received 1 mg IM. of estradiol benzoate (Cronibest ® Biogenesis-Bagó, Argentina). Was performed by ultrasound scanning of the ovaries every 24 hours from time of insertion of the implant to the withdrawal D8. From induction, all cows had their ovaries scanned and mapped every 12 hours for 4 days. Blood samples were taken on days six, seven and eight protocol to compare the plasma concentrations of P4 before removing the device. The variables, early new wave of follicular growth, diameter of the preovulatory follicle (retrospectively), ovulation rate and time of ovulation. Ovulation data were analyzed by logistic regression using PROC LOGISTIC and follicular development data, using PROC MIXED (SAS, version 9.3). The ovulation rate was 80% for both groups (P> 0.05). There was a tendency to anticipate ovulation (P = 0:07), cows in group B. A cow\'s ovulation group B anticipated for about 36 h. There was no difference in estatístisca dominant follicle diameter at the time of TAI, on the emergence of a new wave and pre ovulatory follicle size (p> 0.05).
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Claase, Etienne H. "Robust multi-H2 output-feedback approach to aerial refuelling automation of large aircraft via linear matrix inequalities." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80195.
Full textAbstract:
Thesis (MScEng)--Stellenbosch University, 2013.<br>ENGLISH ABSTRACT: In recent years the aviation industry has shown an interest in the airborne refuelling
of large transport aircraft to enable increased payload mass at take-off and
to extend aircraft range. Due to the large volume of fuel to be transferred, a boom
and receptacle refuelling system with a larger fuel transfer rate is employed. The
refuelling operation is particularly difficult and strenuous for the pilot of the receiver
aircraft, because the position of the receptacle relative to the tanker aircraft must
be maintained within a narrow window for a relatively long period of time. The
airborne refuelling of a large aircraft is typically much more difficult than that of a
fighter aircraft, since the large aircraft is more sluggish, takes much longer to refuel,
and has a relatively large distance between its refuelling receptacle and its centre of
mass. These difficulties provide the motivation for developing flight control laws for
Autonomous In-Flight Refuelling (AIFR) to alleviate the workload on the pilot.
The objective of the research is to design a flight control system that can regulate
the receptacle of a receiver aircraft to remain within the boom envelope of a tanker
aircraft in light and medium turbulence. The flight control system must be robust
to uncertainties in the aircraft dynamic model, and must obey actuator deflection
and slew rate limits.
Literature on AIFR shows a wide range of approaches, including Linear Quadratic
Regulator (LQR), μ-synthesis and neural-network based adaptive control, none of
which explicitly includes constraints on actuator amplitudes, actuator rates and
regulation errors in the design/synthesis. A new approach to designing AIFR flight
control laws is proposed, based on Linear Matrix Inequality (LMI) optimisation.
The relatively new LMI technique enables optimised regulation of stochastic systems
subject to time-varying uncertainties and coloured noise disturbance, while simultaneously
constraining transient behaviour and multiple outputs and actuators to
operate within their amplitude, saturation and slew rate limits. These constraints
are achieved by directly formulating them as inequalities.<br>AFRIKAANSE OPSOMMING: Die lugvaart industrie toon huidiglik ’n belangstelling in die brandstof oordrag
tussen twee groot vervoervliegtuie gedurende vlug, met die doel om die maksimum
opstyggewig kapasiteit sowel as die maksimum ononderbroke vlugafstand vermoë
van die hervulde vliegtuig te vermeerder. ’n Boom hervulling-stelsel word geïmplementeer
om die hoë spoed van brandstof oordrag te voorsien. Die verrigting van
vluggebonde hervulling van ’n groot, trae vliegtuig is moeiliker en meer veeleisend
as bv. van ’n vegvliegtuig, veral vir die vlieënier van die hervulde vliegtuig, wat
sy boom-skakel moet reguleer binne ’n relatiewe klein boom bewegingsruimte vir ’n
relatiewe lang tydperk. Die kinematika betrokke speel ook ’n groter rol in ’n groot
hervulde vliegtuig a.g.v. die langer afstand tussen die boom-skakel en die massa middelpunt/
draaipunt. Hierdie bied die motivering om ’n beheerstelsel te ontwikkel wat
die taak outomaties uitvoer.
Die doel van die navorsing is om ’n beheerstelsel te ontwerp wat die boom-skakel
van die hervulde vliegtuig outomaties reguleer binne die bewegingsruimte van die
boom, gedurende ligte en matige turbulensie. Daar word van die beheerder vereis
om robuust te wees teen onsekerhede in die vliegtuig se meganika, sowel as om die
beheer oppervlaktes en turbines van die vliegtuig binne hul defleksie-, wringkrag- en
sleurtempo-perke te hou.
Daar bestaan reeds ’n groot verskeidenheid van benaderings tot die outomatisering
van luggebonde hervulling, onder andere LQR, μ-sintese en neurale-netwerk
gebaseerde aanpasbare beheer, waarvan geeneen perke op aktueerders en regulasie
foute direk in die ontwerp insluit nie. ’n Nuwe benadering word voorgestel wat
gebaseer is op Linear Matrix Inequality (LMI) optimering. Die LMI tegniek is relatief
nuut in die gebruik van beheerstelsel ontwerp. Dit stel die ontwerper in staat
om ’n stogastiese stelsel, onderworpe aan tydvariante-stelsel-variasie en gekleurde
ruis versteurings, optimaal te reguleer, terwyl aktueerders en stelsel gedrag direk
beperk word.
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Laziz, Iman. "Etude de l'implication de deux molécules dans la régénération du muscle squelettique chez la souris : un facteur de croissance, le FGF6 et une protéine du métabolisme anti-oxydant, AIF." Paris 6, 2007. http://www.theses.fr/2007PA066458.
Full textAbstract:
Nous avons étudié du rôle du FGF6 dans la régénération musculaire en caractérisant le phénotype du Tibialis Antérieur (non lésé et après régénération) de souris Fgf6-/- selon une approche histologique, immunohistochimique et fonctionnelle. Puis nous avons étudié le profil d’expression spatio-temporel des gènes Spry (régulateurs négatifs de la voie de signalisation des FGFs) par des expériences de RT-PCR semi-quantitatives, en temps réel et par hybridations in situ. Ces analyses ont été menées sur des soleus de souris sauvages et Fgf6-/- en cours de régénération. Enfin, nous nous sommes intéressés à l’effet du stress oxydant sur ce processus. Le modèle utilisé est la souris Harlequin, présentant une déficience en la protéine AIF impliquée dans la réduction du stress oxydant. Ainsi, les souris Harlequin sujettes à un important stress oxydant présentent un retard de régénération, une atrophie musculaire, une typologie musculaire plus lente et une altération du pool de cellules satellites.
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au, petcell@arach net, and Pamela M. Etcell. "Our Daily Bread: The Field Bakery & the Anzac Legend." Murdoch University, 2004. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20041107.152144.
Full textAbstract:
The First World War and the Australian Imperial Force have generated thousands of books and articles. Many studies adhere to the emphasis of C.E.W. Bean, and recount the history of the infantry or a particular infantry battalion. Others examine both the short term and long-lasting effects of the war on the Australian psyche. Some historians have acknowledged that a particular group of non-fighting combatants has been neglected, but generally, this group has been employed in dangerous and difficult pursuits. Very few historians have studied the roles of non-fighting combatants whose contribution is considered as lacklustre, such as the Australian Field Bakeries.
When I began my research, I could not understand why the Australian Field Bakeries did not play any part in the historiography of World War One. An examination of the Anzac legend revealed an emphasis on the characteristics of the Anzac, especially masculinity and heroism. I argue that the bakers employment might be considered as being situated within the womans sphere and therefore unmasculine, whilst that same employment did not offer the chance for acts of heroism. Because of an emphasis on the exciting exploits of the infantry within Anzac historiography, the Australian Field Bakeries and their role as support troops have been ignored and omitted.
Comparing demographic statistics and the war experiences, values and attitudes of the Australian Imperial Force and the bakers, I conclude that the bakers of the Australian Field Bakeries were extraordinarily similar to the men of the Australian Imperial Force. Only those experiences and statistics directly related to the two groups specific fields of employment are significantly different. I argue that specialised skills and a perceived lack of masculinity and heroism have seen the men of the Australian Field Bakeries excluded from all existing Anzac historiography.
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Jouanneaux, Alain. "Etude par resonance paramagnetique electronique de cristaux mixtes rb::(x)(nh::(4))::(1-x)aif::(4) : desordre chimique, ordre local, ordre a longue distance (modele d'annni), transition de phase." Caen, 1986. http://www.theses.fr/1986CAEN2029.
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Etude pour x variant de 0 a 0,35. Mise en evidence du caractere aleatoire de la substitution des ions rb**(+) qui permet de mesurer simplement et rapidement x avec une tres bonne precision. L'importance de la configuration et de l'organisation de la couche de cations seconds voisins de la sonde paramagnetique fe**(+). Analyse de l'ordre a basse temperature des ions nh::(4)**(+) pour x variant de 0 a 0,25. Mise en evidence de l'efficacite des mesures rpe pour determiner l'ordre local,l'ordre parallele a longue distance dans les couches 2d et la distance moyenne des discommensurations. Interpretation des resultats dans le cadre de modeles theoriques recents (modele d'annni)
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Marklund, Sandra. "Feasibility Study of Phase Measurements of the Arterial Input Function in Dynamic Contrast Enhanced MRI." Thesis, Umeå University, Radiation Physics, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-23226.
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<p> </p><p>Acquired data from dynamic contrast enhanced MRI measurements can be used to non-invasively assess tumour vascular characteristics through pharmacokinetic modelling. The modelling requires an arterial input function which is the concentration of contrast agent in the blood reaching the volume of interest as a function of time. The aim of this work is testing and optimizing a turboFLASH sequence to appraise its suitability for measuring the arterial input function by measuring phase.</p><p>Contrast concentration measurements in a phantom were done with both phase and relaxivity techniques. The results were compared to simulations of the experiment conditions to compare the conformance. The results using the phase technique were promising, and the method was carried on to in-vivo testing. The in-vivo data displayed a large signal loss which motivated a new phantom experiment to examine the cause of this signal reduction. Dynamic measurements were made in a phantom with pulsatile flow to mimic a blood vessel with a somewhat modified turboFLASH sequence. The conclusions drawn from analyzing the data were used to further improve the sequence and this modified turboFLASH sequence was tested in an in-vivo experiment. The obtained concentration curve showed significant improvement and was deemed to be a good representation of the true blood concentration.</p><p>The conclusion is that phase measurements can be recommended over relaxivity based measurements. This recommendation holds for using a slice selective saturation recovery turboFLASH sequence and measuring the arterial input function in the neck. Other areas of application need more thorough testing.</p><p> </p>
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Liljenberg, Helena. "Marknadsföring av alternativa investeringsfonder till icke-professionella investerare : En analys av regleringens ändamålsenlighet." Thesis, Linköpings universitet, Filosofiska fakulteten, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-159042.
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I kölvattnet av finanskrisen 2008 har regleringen på det finansiella området ökat markant. En del av den finansiella marknaden som varit nästintill oreglerad innan 2008 års finanskris är verksamheten för förvaltare av alternativa investeringsfonder (AIF-förvaltare). Sedan 2011 omfattas dock denna verksamhet av reglering på såväl unionsrättslig nivå, i och med Europaparlamentets och rådets direktiv 2011/61/EU, som på nationell nivå, i och med direktivets implementering i svensk rätt genom lagen (2013:561) om förvaltare av alternativa investeringsfonder (LAIF). Motiven för reglering på det finansiella området i allmänhet och för AIF-förvaltare i synnerhet har varit flera, emellertid är säkerställande av stabilitet i det finansiella systemet det mest framträdande. I uppsatsen undersöks huruvida regleringen avseende marknadsföring av AIF-fonder till icke-professionella investerare är ändamålsenlig. För att besvara frågeställningen om regleringens ändamålsenlighet identifieras LAIF:s övergripande såväl som underliggande ändamål och används som utvärderingsvariabel. Med hjälp av utvärderingsvariabeln undersöks i vilken utsträckning de övergripande ändamålen tillgodoses med regleringens utformning. Regleringen av marknadsföring av AIF-fonder till icke-professionella investerare skiljer sig åt. Dessa skillnader föranleds av motivet att skydda investerare, ty olika AIF-fonder har olika starkt investerarskydd. Investerarskyddet vid marknadsföring av AIF-fonder tar sig uttryck genom bestämmelser om informationsgivning och produktingripande åtgärder. Kraven på informationsgivning ämnar hjälpa investerare att fatta väl övervägda och kvalitativt bättre investeringsbeslut. I uppsatsen påvisas dock att omfattande informationsgivning, något som kraven på informationsgivning i LAIF föranleder, till stora delar är ett ineffektivt skydd emedan informationsgivningen inte sällan leder till informationsöverflöd. Anledningen härför är investerares, främst konsumenters, tillkortakommanden i form av bristande kognitiv förmåga. Vidare försvårar den befintliga investerarklassificeringen för investerare att erhålla ett adekvat skydd genom informationsgivning. Klassificeringen av investerare medför att även institutionella investerare faller in under kategorin ”icke-professionella investerare” trots att skyddsnivån i regleringen är anpassad efter konsumenters skyddsbehov. De produktingripande åtgärderna, å andra sidan, förhindrar marknadsföring av AIF-fonder, i form av riskkapitalfonder, till konsumenter med anledning av att dessa AIF-fonder bedöms för riskfyllda för konsumenter att investera i. Utformningen av de produktingripande åtgärderna i LAIF får dock följden att erhållet skydd beror på personlig status, eftersom det skydd konsumenterna erhåller utgörs av en miniminivå för investering. I uppsatsen ifrågasätts således investerarskyddets utformning vid marknadsföring av AIF-fonder i LAIF och hur långt detta skydd kan sträcka sig i förhållande till andra i lagen beaktansvärda intressen. Till diskussionen är även gränsdragningen mellan investerares legitima skyddsbehov och överbeskydd, av vikt. Frågan om huruvida regleringen avseende marknadsföring av AIF-fonder till icke-professionella investerare är adekvat utformad, besvaras i uppsatsen nekande. Därtill presenteras förslag på förändring av regleringens utformning de lege ferenda, i syfte att uppnå en mer ändamålsenlig reglering.
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Krátká, Lucie. "Akvizice MRI obrazových sekvencí pro preklinické perfusní zobrazování." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219733.
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The task of this thesis is to study methods for the acquisition perfusní imaging based on dynamic MR imaging with T1 contrast. It describes methods of measurement of T1 relaxation time and the possibility of evaluating the results. It further describes the phantoms and their use. And it is here mentioned for the dynamic acquisition protocol perfusní imaging. There is also described in detail created a program for automatic control of the NMR system. In the experimental measurements are performed on static and dynamic phantom, are also evaluated perfusion parameters from the Flash sequence.
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Ravagnan, Luigi. "Mitochondries et apoptose : effets de l'agent antitumoral Lonidamine sur les mitochondries et étude fonctionnelle de l'Apoptosis Inducing Factor." Paris 6, 2002. http://www.theses.fr/2002PA066310.
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Graf, Justin T. "Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation." Queensland University of Technology, 2008. http://eprints.qut.edu.au/25913/.
Full textAbstract:
This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation.
In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation.
The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity.
Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes.
This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.
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Louis, Jean-Sébastien. "Développements en IRM quantitative de perfusion pour le diagnostic de fibrose myocardique." Thesis, Université de Lorraine, 2020. http://www.theses.fr/2020LORR0061.
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L’insuffisance cardiaque est un enjeu de santé publique majeur dans les pays occidentaux. Ce syndrome complexe peut être la résultante de pathologies sous-jacentes du myocarde comme le dépôt de fibrose, diffusant sur l’ensemble du tissu myocardique. L’Imagerie par Résonance Magnétique (IRM) est la modalité de référence dans l’exploration clinique des tissus mous du tissu myocardique. Plusieurs biomarqueurs d’IRM comme le temps de relaxation T1 ou encore la quantification du volume extracellulaire (ECV) ont révélé leur utilité clinique dans le diagnostic de fibroses localisées. L’IRM avec injection de produit de contraste a également montré son fort pouvoir diagnostic dans la détection de lésions post-infarctus. Le suivi dynamique de rehaussement de contraste (DCE) semble être une technique prometteuse dans la différenciation de zones dont la perfusion/perméabilité tissulaire est altérée par un dépôt fibrotique. Dans ces travaux de thèse, nous sommes partis de l’hypothèse que la quantification de la perméabilité cardiaque et l’extraction du volume extracellulaire extravasculaire Ve, permettraient la détection de lésions diffuses avec comme corolaire un raccourcissement de la durée totale d’examen pour l’estimation de l’ECV. Ce mémoire présente dans un premier temps, les travaux méthodologiques mis en œuvre pour permettre l’analyse quantitative DCE myocardique. Pour cela, une méthode de reconstruction de fonction d’entrée artérielle est présentée afin de permettre la quantification DCE sans séquence ou protocole spécifique. Un algorithme de recalage des images dynamiques est décrit, afin de rendre possible l’analyse sous forme de cartes paramétriques. Les conditions d’acquisition des données ont également été étudiées par simulations de Monte-Carlo et cela a permis de proposer un protocole le plus court possible pour l’estimation de Ve. Dans un second temps, les résultats obtenus par analyse DCE ont été comparés aux résultats obtenus par analyse ECV dans le diagnostic de fibrose diffuse. Une corrélation entre ces deux paramètres a été démontrée sur un groupe de 12 patients présentant un prolapsus de la valve mitrale. Un test de permutation a permis de séparer l’échantillon en deux sous-groupes de manière équivalente à l’ECV. Ces travaux de thèse proposent un flux de post traitement complet d’analyse quantitative DCE myocardique et ouvrent la voie à une estimation plus rapide du volume extracellulaire pour la quantification de la fibrose diffuse myocardique<br>Heart failure represents a major public health issue in western world. It is a complex syndrome that could be the cause and/or the consequence of underlying pathologies such interstitial diffuse fibrosis. Magnetic Resonance Imaging (MRI) is the reference imaging modality for soft tissue assessment and especially the myocardium. Several imaging biomarkers such relaxation time T1 or extracellular volume fraction (ECV) have proven their diagnostic power in term of sensitivity and specificity. MRI with contrast agent injection has also demonstrated its usefulness in diagnostic of post-infarct local fibrosis for instance. Dynamic contrast enhancement (DCE) is widely investigated for its supposed ability to discriminate areas from which perfusion/permeability properties have been altered by the presence of fibrosis deposition. We hypothesized that the quantification of myocardial permeability and the estimation of the extracellular extravascular volume fraction Ve could led to a better detection of diffuse fibrosis. Consequently, we investigated the possibility of a shorter protocol for the evaluation of ECV. In this manuscript, we first present the methodological developments that allow the quantitative analysis of DCE cardiac MRI. This implied the development of a post-processing method for Arterial Input Function reconstruction, allowing DCE quantification without the need of specific sequences or protocols. A post-processing algorithm for perfusion images registration have been developed for pixel-wise parametric maps reconstruction. Data acquisition have been simulated in a Monte-Carlo fashion in order to assess the impact of acquisition strategies on parameters accuracy. This eventually led to the design of the shortest possible imaging strategy for Ve quantification. Secondly, clinical results obtained with our quantitative DCE analysis framework have been confronted to those obtained with classical ECV method for diffuse fibrosis detection. Correlation between those two parameters have been found a group of 12 patients presenting mitral valve prolapses. Permutation test on Ve distribution allowed us to show a significant difference between two groups the same way the ECV values did. The presented work describes a full quantitative DCE analysis framework that could allow to a shorter imaging protocol for extracellular extravascular estimation for diffuse myocardial fibrosis diagnosis
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Holeček, Tomáš. "Škálování arteriální vstupní funkce v DCE-MRI." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2015. http://www.nusl.cz/ntk/nusl-221306.
Full textAbstract:
Perfusion magnetic resonance imaging is modern diagnostic method used mainly in oncology. In this method, contrast agent is injected to the subject and then is continuously monitored the progress of its concentration in the affected area in time. Correct determination of the arterial input function (AIF) is very important for perfusion analysis. One possibility is to model AIF by multichannel blind deconvolution but the estimated AIF is necessary to be scaled. This master´s thesis is focused on description of scaling methods and their influence on perfussion parameters in dependence on used model of AIF in different tissues.