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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
341

Étude des mécanismes de migration du césium dans le dioxyde d'uranium stoechiométrique et sur-stoechiométrique : influence du molybdène / Study of Cesium migration mechanisms in stoichiometric and hyper-stoichiometric uranium dioxide : influence of Molybdenum

Panetier, Clémentine 20 November 2019 (has links)
Dans le combustible nucléaire UO2, utilisé dans les réacteurs à eau pressurisée (REP), le Cs, élément volatil compte parmi les produits de fission (PF) les plus abondamment produits. De plus, l’isotope 137Cs est connu pour être particulièrement radiotoxique. En cas d’accident, le relâchement de cet isotope est donc problématique et son étude est cruciale pour la sûreté nucléaire. En France, l’IRSN (Institut de Radioprotection et de sureté nucléaire) développe des codes de prédictions du relâchement des PF depuis le combustible, tels que MFPR (Module for Fission Product Release). Ces codes nécessitent d’être alimentés par des données fondamentales sur le comportement des PF. Ainsi, la connaissance des coefficients de diffusion de ces éléments dans la matrice combustible en fonction de la température et de l’atmosphère (pouvant oxyder le combustible en UO2+x) est primordiale. Dans ce contexte, l’objectif de cette thèse, menée en collaboration avec l’IRSN, est d’étudier la migration du Cs dans le dioxyde d’uranium stœchiométrique et sur-stœchiométrique, en conditions représentatives d’un fonctionnement normal et accidentel d’un REP, avec et sans la présence de Mo. Ce dernier est un PF abondamment produit qui agit comme tampon d’oxydation du combustible et est capable d’avoir des interactions chimiques avec le césium. De telles interactions pourraient affecter le comportement du Cs, et donc son relâchement depuis le combustible. Il a donc été nécessaire d’envisager les éventuelles interactions entre le Cs et le Mo dans le cadre de notre étude. La démarche expérimentale a consisté à simuler la présence de Cs et/ou Mo dans des pastilles d’UO2 ou d’UO2+x. par implantations ioniques des isotopes stables 133Cs et/ou 95Mo. Des recuits à haute température (950-1600°C) sous atmosphère contrôlée ou des irradiations en régime électronique couplées en température ont ensuite été réalisés, permettant d’induire la migration du Cs et du Mo. La spectrométrie de masse à ionisation secondaire (SIMS) a été utilisée pour suivre l’évolution des profils de concentration des éléments implantés, permettant d’extraire les coefficients de diffusion apparents du Cs dans UO2 et UO2+x en fonction des différents traitements. Une étude complémentaire de la microstructure a été réalisée par spectroscopie Raman et microscopie électronique en transmission (MET). Le Cs est très mobile dans UO2 sous atmosphère réductrice même si une partie et piégée sous forme de bulles à faible profondeur. Nous avons mis en évidence que la présence de Mo diminuait fortement cette mobilité. La même tendance est observée dans UO2+x sous atmosphère oxydante. Néanmoins les mécanismes d’immobilisation du Cs par le Mo diffèrent selon les conditions redox de recuit. En atmosphère réductrice, les expériences MET ont montré la formation de paires bulles de Cs-précipités métalliques de Mo dans les échantillons co-implantés. En atmosphère oxydante, l’absence de mobilité du Cs pourrait être liée à l’oxydation du Mo rendant possible des interactions chimiques Cs-Mo. Pour la première fois, des potentiels semi-empiriques ont été utilisés pour réaliser des calculs de dynamique moléculaire sur la diffusion du Cs et du Mo dans UO2 et UO2+x. Ces calculs nous ont aussi permis de caractériser les mécanismes de diffusion de l’oxygène dans ces matériaux en présence de ces deux PF / In the nuclear fuel UO2, which is widely used in Pressurized Water Reactor (PWR), Cs is a volatile element and is one of the most abundant fission product (FP). Furthermore, 137Cs is known to be highly radiotoxic. During a hypothetical accident, release of Cs would be particularly problematic for the environment. Hence, study of this element is of major concern for nuclear safety. To assess this issue, the French nuclear safety institute (IRSN) develops codes to predict FP release from nuclear fuel in normal and accidental conditions. This code requires fundamental data on FP behavior such as diffusion coefficient of these elements in UO2 as a function of temperature and atmosphere conditions (leading to UO2+x formation in oxidative conditions). The aim of this PhD, supported by the IRSN, is to study Cs migration in stoichiometric and hyper-stoichiometric uranium dioxide with and without the presence of Mo, in normal and accidental conditions of a PWR. This latter element is also an abundant FP, which is important to consider because it acts as an oxygen buffer in the fuel and may interact chemically with Cs. Such interactions may affect Cs behavior, hence its release from the fuel. Therefore, Cs-Mo interactions are considered in our study. The experimental procedure consists in simulating the Cs and/or Mo presence in UO2 and UO2+x pellets by ion implantation of stable isotopes 133Cs and/or 95Mo. Then, high temperature annealing (950 °C - 1600 °C) under controlled atmosphere or electronic excitations induced by irradiation coupled with temperature are performed to induce Cs and Mo migration. Secondary Ion Mass Spectrometry (SIMS) is used to follow the concentration profile evolution of these elements, allowing extracting effective diffusion coefficients of Cs in UO2 and UO2+x as a function of irradiation or thermal treatment. Microstructure characterizations were made by Raman spectroscopy and transmission electron microscopy (TEM). We show that Cs is mobile in UO2 under reducing atmosphere, even though some of the Cs is trapped in Cs-bubbles located near the surface. We evidence that Mo presence prevents Cs to be mobile. The same tendency is observed in UO2+x under oxidizing atmosphere. Nevertheless, Cs immobilization mechanisms in presence of Mo vary upon redox conditions used during annealing. In reducing conditions, TEM experiments showed formation of Cs bubbles associated with Mo metallic precipitates in co-implanted samples. In oxidative conditions, absence of Cs mobility could be explained by Mo oxidation leading to possible Cs-Mo chemical interactions. For the first time, semi-empirical potentials were used to perform molecular dynamic (MD) calculations on Cs and Mo diffusion in UO2 and UO2+x. These simulations also allowed characterizing oxygen diffusion mechanisms in these matrixes in presence of Cs and Mo
342

Strain relaxation in InGaN/GaN herostructures / Relaxation des contraintes dans les hétérostuctures InGaN/GaN

Li, Quantong 20 March 2018 (has links)
Dans ce travail, nous avons étudié la relaxation de couches d’hétérostructures InGaN/GaN obtenue par épitaxie en phase vapeur aux organométalliques (EPVOM) et épitaxie aux jets moléculaires (EJM) principalement par microscopie électronique en transmission (MET). Pour ce faire, nous avons fait varier la composition de l'indium de 4.1% au nitrure d'indium pur, ce qui correspond lors de la croissance sur GaN à un décalage paramétrique allant de 1% à 11.3%. Le travail a porté sur des couches dont l’épaisseur allait de 7 nm à 500 nm. A partir d’une composition en indium voisine de 10%, nous mettons en évidence la formation d’un réseau de dislocations vis dont la ligne se promène dans l’interface, avec de très longues sections droites le long des directions <11-20>. Ces dislocations coexistent avec un réseau de dislocations coins qui commence à se former vers 13%, il disparait complétement autour d’une composition en indium de 18%. Le réseau de dislocation vis se densifie de plus en plus au-delà. Outre ces dislocations de décalage paramétrique, d'autres mécanismes qui contribuent à la relaxation de la contrainte dans ces hétérostructures InGaN/GaN ont été mis en évidence. Ainsi, au-dessus d'une composition d'indium supérieure à 25%, de nombreux phénomènes se produisent simultanément. (1) Formation des dislocations de décalage paramétrique à l'hétérointerface; (2) une composition de la couche qui s’enrichit en indium vers la surface; (3) des fortes perturbations de la séquence hexagonale conduisant à un empilement aléatoire; (4) croissance à trois dimensions (3D) pouvant même conduire à des couches poreuses lorsque la composition en indium est comprise entre 40% et 85%. Cependant, on met en évidence qu’il est possible de faire croître de l’InN pur de bonne qualité cristalline s'améliore grâce à la formation systématique d'une couche 3D. / In this work, we have investigated the strain relaxation of InGaN layers grown on GaN templates by MOVPE and PAMBE using TEM. To this end we varied the indium composition from 4.1% to pure indium nitride and the corresponding mismatch was changing from less than 1% to 11.3%, the thickness of the InGaN layers was from 7 nm to 500 nm. When the indium composition is around 10%, one would expect mostly elastically strained layers with no misfit dislocations. However, we found that screw dislocations form systematically at the InGaN/GaN interface. Moreover, below 18% indium composition, screw and edge dislocations coexist, whereas starting at 18%, only edge dislocations were observed in these interfaces. Apart from the edge dislocations (misfit dislocations), other mechanisms have been pointed out for the strain relaxation. It is found that above an indium composition beyond 25%, many phenomena take place simultaneously. (1) Formation of the misfit dislocations at the heterointerface; (2) composition pulling with the surface layer being richer in indium in comparison to the interfacial layer; (3) disruption of the growth sequence through the formation of a random stacking sequence; (4) three dimentional (3D) growth which can even lead to porous layers when the indium composition is between 40% and 85%. However, pure InN is grown, the crystalline quality improves through a systematic formation of a 3D layer.
343

Etude du profil en profondeur des modifications induites par irradiation aux ions sur substrat de saphir et du film mince GaN / Damage depth profile of modifications induced in alpha-Al2O3 substrate and GaN thin film under swift heavy ions

Ribet, Alexis 04 October 2019 (has links)
La famille des matériaux semiconducteurs III-N présente des propriétés adéquates pour diversesapplications que ce soit dans le domaine de l’optique ou de l’électronique. Certaines de ces applicationsconsistent à intégrer ces matériaux dans des environnements hostiles et notamment soumis à l’actiond’ions lourds à différentes énergies. Lors de cette thèse, le travail consistait tout d’abord à comprendrel’évolution microstructurale sous irradiation du substrat alpha-Al2O3, puis du film mince GaN, afin d’établirun profil de l’évolution de l’endommagement en fonction de la profondeur. Un comportement assezsimilaire concernant l’évolution des paramètres de maille a été observé pour les deux matériaux. Dansla direction parallèle à la trajectoire du faisceau d’ions, une importante augmentation du paramètre demaille a été mise en évidence tandis que peu de variations ont été relevées perpendiculairement à latrajectoire du faisceau d’ions. Les formations de couche amorphe pour l’alpha-Al2O3 et de couche fortementendommagée pour le GaN ont été observées en surface. Les épaisseurs de ces couches augmentent enfonction de la fluence, associé à l’augmentation des contraintes résiduelles au sein du matériau. Al’aide d’hypothèses et des différents résultats obtenus, deux profils d’endommagement en profondeuront été proposés. D’autre part, la nanoindentation a montré que les paramètres de dureté et de moduled’élasticité évoluent fortement sous irradiation en fonction de la fluence. / Nitride semiconductors are attractive materials for the development of optical and electronic devices.Some of these applications can expose materials to extreme environments and especially radiation ofheavy ions at different energies. In this thesis, the study focused first on behaviour evolution underirradiation of alpha-Al2O3 and then of GaN thin film, in order to establish a profile of damage evolution asfunction of the depth. Concerning lattice parameter, a similar behaviour was observed for both materials.An important increase of lattice parameter parallel to ion beam was highlighted while few variations wasnoted for the lattice parameter perpendicular to ion beam. Formation of amorphous layer for alpha-Al2O3and highly disordered layer for GaN were observed in surface. Layers thicknesses increase as functionof the fluence with an increase of residual stresses in material. Using different results and assumptions,two damage profiles as function of the depth have been proposed. In addition, nanoindentation hasshown hardness and modulus of elasticity parameter evolve highly under irradiation as function of thefluence.
344

Gene expression profiling of Met receptor tyrosine kinase-induced mouse mammary tumors

Ponzo, Marisa Grace, 1980- January 2009 (has links)
No description available.
345

Transcriptional regulation and subtype specification in breast cancer

Haidar, Salwa 12 1900 (has links)
Le cancer du sein est une maladie hétérogène définie actuellement par plusieurs sous-types classés en fonction de leurs profils d'expression génique et reliés à différentes altérations moléculaires et options thérapeutiques. Les tumeurs luminales, exprimant le récepteur des oestrogènes alpha (ERa), sont traitées par des thérapies endocriniennes. Les tumeurs HER2+ bénéficient également de traitement par des médicaments ciblant ce récepteur. Cependant, les tumeurs de types basal-like, molecular apocrine et claudin-low, sont principalement traitées par chimiothérapie à défaut de cibles thérapeutiques. Les différents sous-types moléculaires du cancer du sein sont supposés provenir d'un blocage de la différenciation épithéliales mammaires à différents stades. Les tumeurs luminales, HER2+ et basal-like sont caractérisées par un phénotype épithélial, alors que les tumeurs claudin-low se distinguent par un phénotype mésenchymateux moins différencié. Jusqu'à présent, les facteurs de transcription qui dictent l'identité épithéliale des tumeurs mammaires et les mécanismes sous-jacents de la spécification des sous-types de cancer du sein restent imparfaitement compris. Dans cette étude, nous montrons que le facteur de transcription (FT) Grainyhead-like 2 (GRHL2) agit en tant que gardien et régulateur principale de phénotype épithélial des lignées cellulaires du cancer du sein. La surexpression de GRHL2 dans des cellules cancéreuses du sein claudin-low induit une transition mésenchymateuse à épithéliale en induisant directement l'expression de plusieurs FT épithéliaux, cofacteurs et microARNs et par interférence avec d'autres voies de signalisation. La surexpression de GRHL2 dans les cellules MDA-MB-231 a entraîné l'ouverture de la chromatine et l'activation transcriptionnelle des gènes cibles tels que les inhibiteurs de l’EMT OVOL1 et OVOL2, réprimés dans les cellules mésenchymateuses. De plus, nous avons identifié le marqueur de type basal-like VGLL1, un cofacteur des TEADs, en tant que nouveau cofacteur de GRHL2, qui médie une partie des effets de GRHL2 dans les cellules MDA-MB-468. L'axe GRHL2/VGLL1 oppose les effecteurs de la voie de signalisation Hippo YAP / TEADs, qui sont dérégulés dans de nombreux cancers, et inhibe l'activation de certains de leurs gènes cibles impliqués dans la progression tumorale et les métastases. Dans la deuxième partie de notre étude, nous avons identifié, par une analyse de corrélation génique dans plusieurs jeux de données transcriptomiques de tumeurs du sein, un cluster de gènes hautement corrélés et spécifiquement exprimés dans les tumeurs basal-like, incluant FOXC1, VGLL1, BCL11A, GABRP, SOX6/8/10 et ELF5. Nous avons montré que la surexpression de FOXC1 dans des cellules épithéliales et mésenchymateuses active des voies de signalisation et induit l’expression de gènes enrichis dans les tumeurs basal-like, y compris le marqueur de type basal-like C1orf106, quoique ces effets soient largement spécifiques du contexte cellulaire. D’un autre côté, nous avons montré que les FT luminaux ERa, FOXA1 et GATA3 répriment directement l'expression des marqueurs de type basal-like VGLL1 et GABRP dans les cellules luminales MCF7. Ces études permettent de mieux comprendre le rôle et les mécanismes de la régulation transcriptionnelle par GRHL2 et ont identifié de nouveaux gènes cibles de VGLL1 et de FOXC1 dans les cellules cancéreuses du sein. Étant donné que les sous-types de cancer du sein sont liés à des aberrations génétiques affectant de manière distincte les patrons d'expression des gènes, l’identification des réseaux de régulation transcriptionnels spécifiques à chaque sous-type et une meilleure compréhension de l'impact de leur dérégulation sur les phénotypes tumoraux peuvent conduire à la découverte de nouvelles cibles thérapeutiques spécifiques à chaque sous-type. / Breast cancer is a heterogenous disease currently defined by several subtypes that have been identified based on gene expression profiling and are related to different molecular alterations and clinical outcomes. Luminal tumors, expressing estrogen receptor alpha (ERa), are treated with endocrine therapies. HER2-enriched tumors also benefit from treatment with drugs targeting this receptor. However, basal-like, molecular apocrine and claudin-low tumors, lacking the expression of specific molecular targets, are mainly treated by chemotherapy. Breast cancer molecular subtypes are thought to be originated from a block of mammary epithelial cell differentiation at different stages. Luminal, HER2-enriched and basal-like tumors are characterized by an epithelial phenotype, however claudin-low tumors are distinguished by a less differentiated mesenchymal phenotype. Until now, transcription factors that dictate the epithelial identity of breast tumors and that underlie breast cancer subtype specification have not been well characterized. Here, we show that the transcription factor (TF) Grainyhead-like 2 (GRHL2) is a gatekeeper and a master regulator of the epithelial phenotype of breast cancer cell lines. GRHL2 overexpression in claudin-low breast cancer cells induces mesenchymal to epithelial transition by directly upregulating the expression of several epithelial TFs, cofactors and microRNAs and by crosstalk with other signaling pathways. GRHL2 overexpression in MDA-MB-231 cells resulted in chromatin opening and transcriptional activation of direct target genes such as the EMT inhibitors OVOL1 and OVOL2, repressed in mesenchymal cells. In addition, we uncovered the basal-like marker VGLL1, a TEAD cofactor, as a novel cofactor of GRHL2, which mediates part of GRHL2 effects in MDA-MB-468 cells. The GRHL2/VGLL1 axis counteracts the downstream effectors of the Hippo signaling pathway YAP/TEADs, which are deregulated in many cancers, and inhibits the activation of some of their target genes implicated in tumor progression and metastasis. In the second part of our study, we identified by performing gene correlation analysis in large transcriptome datasets of breast tumors a cluster of highly correlated genes specifically expressed in basal-like tumors, comprising FOXC1, VGLL1, BCL11A, GABRP, SOX6/8/10 and ELF5. We showed that FOXC1 overexpression in both mesenchymal and epithelial cells upregulates basallike signaling pathways and markers such as the basal-like marker C1orf106, although with little overlap indicating context-dependent gene regulation. Conversely, we showed that luminal TFs ERa, FOXA1 and GATA3 directly repress the expression of basal-like markers VGLL1 and GABRP in MCF7 luminal cells. These studies help to better understand the role and the mechanisms of transcriptional regulation by the epithelial transcription factor GRHL2 and identified previously unknown targets of basallike transcription factor FOXC1 and cofactor VGLL1 in breast cancer cells. As breast cancer subtypes are linked to genetic defects differentially affecting gene expression patterns, the characterization of relevant subtype-specific transcriptional regulatory networks and better understanding of the impact of their deregulation on the tumor phenotype may lead to the discovery of new therapeutic strategies specific to each subtype.
346

[en] HYDROGEN INTERACTION WITH THE MICROSTRUCTURE OF THE WELDED JOINT OF DUPLEX AND AUSTENITIC STAINLESS STEEL / [pt] INTERAÇÃO DO HIDROGÊNIO COM A MICROESTRUTURA DOS AÇOS INOXIDÁVEIS AUSTENÍTICO P550 E DUPLEX S31803

VANESSA FELICIANO M DE QUEIROZ 26 August 2021 (has links)
[pt] A exposição de aços a condições de geração de hidrogênio, como em ambientes que contenham H2S ou sob proteção catódica, pode provocar o aumento do teor de hidrogênio na sua superfície, fragilizando o material. Foi desenvolvido um estudo com o objetivo de comparar o comportamento das microestruturas de dois diferentes aços inoxidáveis, um austenítico de classe P550 e um duplex S31803, com relação à permeação e consequente fragilização pelo hidrogênio. Os aços foram testados nas condições com e sem solda autógena utilizando os mesmos parâmetros de soldagem. Foram realizados análise microestrutural por MO, MEV e MET, ensaios de tração, ensaios de BTD com os corpos de prova imersos em solução de água do mar sintética e sob aplicação de potencial catódico de -1200 mV SCE, com o objetivo de simular condições de serviço e fractografia por MEV dos corpos de prova ensaiados por BTD. Observou-se que ambas as classes de aços sofreram alguma fragilização, no entanto, com relação à perda de ductilidade em função da redução de área dos corpos de prova, esta ocorreu de forma mais pronunciada para o aço inoxidável duplex. Foi observado que o aço austenítico no metal de base continha maior densidade de maclas do que o metal de solda, resultando em maior fragilização. Além disto, no metal de base, observou-se mais alta densidade de discordâncias e de precipitados. O aço duplex, por outro lado, apresentou fragilização muito maior do que o austenítico em ambas as condições quando permeado pelo hidrogênio. No entanto, esta fragilização foi mais pronunciada na condição de como soldado. Atribuiu-se este comportamento à ferritização parcial da estrutura e à formação de austenita Widmanstätten. As análises fractográficas sugerem a alteração do mecanismo de fratura dos corpos de prova de dúctil, quando ensaiados ao ar, para frágil, na condição de ensaio com geração de hidrogênio. Esta observação fundamenta-se no fato de que as superfícies de fratura de todos os corpos de prova ensaiados ao ar são formadas predominantemente por dimples (dúctil), enquanto no ensaio com geração de hidrogênio, as superfícies de fratura se apresentam com aspecto frágil de diferentes formas para cada aço. / [en] Steel exposure to hydrogen generation conditions, such as in environments containing H2S or under cathodic protection, can cause an increase in the hydrogen content on the surface which leads to the material embrittlement. A comparative study was carried out on the structure behavior of two different stainless steels, an austenitic class P550 and a duplex S31803, concerning permeation and consequent hydrogen embrittlement. The steels were tested in conditions with and without autogenous welding using the same welding parameters. It was performed microstructural analysis by OM, SEM and TEM, tensile tests, BTD tests with the specimens immersed in a synthetic seawater solution and under application of a cathodic potential of -1200 mV SCE, in order to simulate service conditions, and surface fractography of these specimens by SEM. It was observed that both grades of steel suffered some fragility. However, the loss of ductility due to the reduction of the area of the specimens occurred in a more pronounced way for the duplex stainless steel. It was also observed that the austenitic steel in the base metal contained a higher density of twinnings than the weld metal, resulting in greater embrittlement. In addition, a higher density of dislocations and precipitates was observed in the base metal. On the other hand, duplex steel showed much more significant embrittlement than austenitic in both conditions when permeated by hydrogen. However, this weakness was more pronounced in the as welded condition. This behavior was attributed to the partial ferritization of the structure and the formation of Widmanstätten austenite. Fractographic analyzes suggest that the fracture mechanism morphology changed from ductile to brittle when the specimens were tested in the air and hydrogen condition respectively. This observation is based on the fact that the fracture surfaces of all samples tested in the air consisted predominantly of dimples (ductile). In contrast, in the test with hydrogen generation, the fracture surfaces appear with different brittle morphologies for each steel.
347

Explorations into Machine Learning Techniques for Precipitation Nowcasting

Nagarajan, Aditya 24 March 2017 (has links) (PDF)
Recent advances in cloud-based big-data technologies now makes data driven solutions feasible for increasing numbers of scientific computing applications. One such data driven solution approach is machine learning where patterns in large data sets are brought to the surface by finding complex mathematical relationships within the data. Nowcasting or short-term prediction of rainfall in a given region is an important problem in meteorology. In this thesis we explore the nowcasting problem through a data driven approach by formulating it as a machine learning problem. State-of-the-art nowcasting systems today are based on numerical models which describe the physical processes leading to precipitation or on weather radar extrapolation techniques that predict future radar precipitation maps by advecting from a sequence of past maps. These techniques, while they can perform well over very short prediction horizons (minutes) or very long horizons (hours to days), tend not to perform well over medium horizons (1-2 hours) due to lack of input data at the necessary spatial and temporal scales for the numerical prediction methods or due to the inability of radar extrapolation methods to predict storm growth and decay. Given that water must first concentrate in the atmosphere as water vapor before it can fall to the ground as rain, one goal of this thesis is to understand if water vapor information can improve radar extrapolation techniques by giving the information needed to infer growth and decay. To do so, we use the GPS-Meteorology technique to measure the water vapor in the atmosphere and weather radar reflectivity to measure rainfall. By training a machine learning nowcasting algorithm using both variables and comparing its performance against a nowcasting algorithm trained on reflectivity alone, we draw conclusions as to the predictive power of adding water vapor information. Another goal of this thesis is to compare different machine learning techniques, viz., the random forest ensemble learning technique, which has shown success on a number of other weather prediction problems, and the current state-of-the-art machine learning technique for images and image sequences, convolutional neural network (CNN). We compare these in terms of problem representation, training complexity, and nowcasting performance. A final goal is to compare the nowcasting performance of our machine learning techniques against published results for current state-of-the-art model based nowcasting techniques.
348

MET Alterations in Glioblastoma: Characterization of Patient-Derived Xenografts and Therapeutic Strategies

Musket, Anna 01 August 2023 (has links) (PDF)
Glioblastoma is the most commonly diagnosed central nervous system primary malignancy and it is considered a terminal diagnosis with few treatment options available. Glioblastoma tumors frequently develop treatment resistance due in part to their highly heterogenic nature. The heterogeneity of glioblastoma is partially attributed to the presence of glioma stem-like cells (GSC), which are highly invasive and resistant to chemotherapy and irradiation treatments. Signaling of the receptor tyrosine kinase MET is a known regulator of GSC. Glioblastoma patients have an increasingly poor prognosis that corresponds with increasing MET expression. Both GSC and MET are known to contribute to treatment resistance in glioblastoma and several MET alterations have been observed in glioblastoma. In these studies, we investigated MET alterations that are commonly found in glioblastoma. Using patient-derived xenograft (PDX) lines, the MET alterations were characterized and confirmed to be MET positive, MET amplified, or harbor a PTPRZ1-MET fusion. We also included a MET null glioblastoma PDX line. The PDX lines demonstrated markers for GSC potential with all showing neurosphere formation, the ability to initiate tumor growth in immune-compromised mice, and expression of GSC markers GFAP, Sox2, and nestin. The MET alterations were further examined by examining tyrosine kinase inhibitors' effect on viability and MET signaling. Oncogene addiction through MET amplification was found to have the best response to inhibition. The MET fusion bearing line demonstrated less sensitivity to inhibition than has been shown in other studies, indicating a need for further research into co-mutations that increase sensitivity to MET inhibition. We also investigated the efficacy of novel MET-targeting chimeric antigen receptor T cells (MET.CART cells). The MET.CART cells were able to specifically target and successfully kill MET-expressing glioblastoma cells. Together these results imply the need for more personalized treatment of glioblastoma based on the molecular biology of the tumor.
349

Bundeltitel as globale metafoor vir T.T. Cloete se bundel: Met die aarde praat (1992)

Burger, Frederik Christiaan 12 1900 (has links)
This study examines the relationship between the metaphor in the title and the content of T.T. Cloete’s Volume of Poetry titled Met die aarde praat. It will be demonstrated that the volume title as global metaphor is an integral part of the textual element of the text, that it also fulfills a hermeneutical function in respect to the text in that it offers clues and insights into reading and understanding of the poems or volume contents. In light of the aforementioned metaphor theory is investigated on three levels: on a cognitive or conceptual level, on a linguistic/textual level and on a communicative level. The titles and mottos of the eight sections frame the sections as well as refer to themes and provide clues to reading and understanding the individual poems or volume contents. Section titles are framed by the volume title and often interact with the volume title as global metaphor and together. / Afrikaans and Theory of Literature
350

Gesindheid van onderwysers in gewone skole teenoor leerders met spesiale onderwysbehoeftes

Wessels, Daniel 04 1900 (has links)
Summaries in Afrikaans and English / Die wereldwye neiging in die onderwys wat bekend staan as lnsluiting is teweeggebring deur die reg van elke individu op onderrig, soos vasgele in die Universele Verklaring van Menseregte van 1948, tesame met die hernieude onderneming van die wereldgemeenskap' op die Wereldkonferensie oor Opvoeding vir Almal van 1990 om daardie reg, ten spyte van individuele • verskille, te verskans. Aile aanduidings is dat Suid-Afrika ook die beleid van lnsluiting sal aanvaar in die regering se pogings om die onderwys te hervorm. Hierdie beleid van lnsluiting hou groot implikasies in vir die onderwyser in, die gewone skole, aangesien hulle beida die voorwerp en die . agent is van sodanige hervorming. Daar word aanvaar dat die onderwyser se houding teenoor leerders in die algemeen 'n belangrike rol speel met betrekking tot die sukses van die onderrig- en leergebeure in die klaskamer. Hierdie houding word dikwels bepaal deur die · onderwyser se kennis van leerders in die klaskamer en sy vaardighede met betrekking tot hul onderrig. In die lig van die literatuurstudie, wat daarop dui dat onderwysers nie voldoende opleiding ontvang om aan die behoeftes van leerders met spesiale onderwysbehoeftes te voldoen nie, word in hierdie navorsing die houding van die onderwyser in die gewone skool teenoor die leerders met spesiale onderwysbehoeftes soos dit in die praktyk openbaar word bepaal. / The right of every individual to education, as enshrined in the 1948 Universal Declaration of Human Rights, and the renewing of the pledge made by the world community at the 1990 World Conference on Education for All to ensure that right, regardless of individual differences, gave rise to the worldwide trend in education known as Inclusion. All indications are that South Africa will also adopt the policy of Inclusion as part of the government's efforts to reform education. The policy of Inclusion has major implications for the teachers in the ordinary school, as they are both the subjects and the agents of reform. It is generally believed that teachers' attitudes towards learners plays a major role ·in the success of the teaching-learning events in the classroom. These attitudes are often influenced by .. the teachers' knowledge of the learners in their classrooms and their skill in teaching them. In view of literature that suggests that teachers are not adequately trained to meet the needs of learners, with special Educational needs, this study undertakes to investigate the attitude of teachers in the ordinary school towards learners with special educational needs, as it manifests in practice. / Educational Studies / M.Ed. (Ortopedagogiek)

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