Gotowa bibliografia na temat „GITC”

Les DIPG (Diffuse Intrinsic Pontine Glioma) sont des tumeurs cérébrales pédiatriques rares dont la survie médiane après diagnostic est inférieure à un an. Le traitement de référence de ce cancer repose sur la radiothérapie mais cette dernière n’est pas curative. La recherche de nouvelles stratégies thérapeutiques innovantes est donc indispensable pour permettre une prise en charge clinique efficace des enfants atteints d’un DIPG.En 2022, notre équipe a montré in vitro et in vivo que l’inhibition de l’activité méthyltransférase d’EZH2 par le GSK126 sensibilisait les cellules de DIPG aux statines par une augmentation de la synthèse de cholestérol. Cependant, le mécanisme d’action induisant cet effet synergique entre les deux composés restait inconnu. Nos résultats ont montré que l’utilisation du GSK126 entraine une augmentation du métabolisme du cholestérol mais également de celui des acides gras, le tout associé à une accumulation de gouttelettes lipidiques plus importante. Nous avons également montré que le GSK126 tuait de façon sélective les cellules tumorales les plus souches (OPC-like) et que les cellules résistantes mettaient en place un programme pro-survie. Par analyse transcriptomique, nous avons découvert que le GSK126 induit de nombreuses voies moléculaires impliquées dans le stress oxydatif, le stress du réticulum endoplasmique et la mise en place des processus autophagique/mitophagique et l’inflammasome NLRP3. Nos résultats ont également montré que le traitement par le GSK126 empêchait l’activation de la phosphorylation de STAT3-Y705 et induisait la mort cellulaire par pyroptose des cellules les plus sensibles. Enfin, ces travaux ont permis de mettre en évidence l’importance du processus de prénylation protéique dans le programme pro-survie des cellules malgré le stress cellulaire. Le ciblage combiné de certains de ces processus et de l’inhibition de l’activité méthyltransférase d’EZH2 a montré un effet antitumoral synergique dans des modèles in vitro.En parallèle, nous avons réalisé un criblage pharmacologique sur un modèle 3D de cellules différenciées de DIPG afin d’identifier de nouvelles cibles thérapeutiques. Nos résultats ont montré une forte sensibilité de ces cellules à des inhibiteurs de la dynamique des microtubules. Une analyse kinomique sur des cellules traitées par un inhibiteur de microtubules a montré l’activation d’une kinase impliquée dans le contrôle de la division cellulaire et des dommages à l’ADN. Cette seconde étude a, elle aussi, conduit à la découverte d’un effet antitumoral synergique in vitro entre des inhibiteurs de ces deux cibles<br>DIPG (Diffuse Intrinsic Pontine Glioma) is a rare paediatric brain tumour with a median survival after diagnosis of less than one year. The standard treatment for this cancer is radiotherapy, but this is not curative. Research into new and innovative therapeutic strategies is therefore essential to enable effective clinical management of children with DIPG.In 2022, our team showed in vitro and in vivo that inhibition of EZH2 methyltransferase activity by GSK126 sensitised DIPG cells to statins by increasing cholesterol synthesis. However, the mechanism of action inducing this synergistic effect between the two compounds remained unknown. Our results showed that the use of GSK126 increased both cholesterol and fatty acid metabolism, associated with a greater accumulation of lipid droplets. We also showed that GSK126 selectively killed the most proliferating tumour cells (OPC-like) and that resistant cells set up a pro-survival programme. By transcriptomic analysis, we discovered that GSK126 induced numerous molecular pathways involved in oxidative stress, endoplasmic reticulum stress and the setting up of autophagic/mitophagic processes and NLRP3 inflammasome. Our results also showed that treatment with GSK126 prevented the activation of STAT3-Y705 phosphorylation and induced cell death by pyroptosis in the most sensitive cells. Finally, this work highlighted the importance of the protein prenylation process in the pro-survival programme of cells despite cellular stress. Combined targeting of some of these processes and inhibition of EZH2 methyltransferase activity has shown a synergistic anti-tumour effect in in vitro models.In parallel, we carried out a pharmacological screening on a 3D model of differentiated DIPG cells to identify new therapeutic targets. Our results showed that these cells are highly sensitive to inhibitors of microtubule dynamics. A kinomic analysis of cells treated with a microtubule inhibitor showed the activation of a kinase involved in the control of cell division and DNA damage. This second study also led to the discovery of a synergistic anti-tumour effect in vitro between inhibitors of these two targets

Le diagnostic du gliome infiltrant du tronc cérébral (GITC) chez les enfants est l'un des plus éprouvants en oncologie pédiatrique. Malgré de nombreux essais cliniques explorant divers traitements, le pronostic reste sombre, la plupart des patients succombant entre 9 et 11 mois après le diagnostic. Les mutations génétiques clé associées au GITC incluent H3K27M, ACVR1 et TP53. Chaque mutation a des caractéristiques distinctes, poussant les médecins à suggérer des thérapies personnalisées, soulignant l'importance d'une détection précise des mutations pour guider le traitement. Situées dans la région cruciale du tronc cérébral, les tumeurs GITC présentent des risques significatifs liés à la biopsie en raison de potentiels dommages neurologiques. L'IRM est une méthode indispensable pour le diagnostic de ces tumeurs, évaluant leur extension et permettant de mesurer l'évolution de la maladie au cours de la thérapie. Une prédiction des mutations, combinée à l'identification des patients survivant plus de deux ans, pourrait améliorer la thérapie proposée à ces patients. Dans ce contexte, la radiomique transforme les images en vastes sources de données, extrayant des caractéristiques comme la forme et la texture pour aider à la prise de décision. L'objectif de cette thèse est de prédire les principales mutations génétiques et d'identifier les survivants à long terme, en mettant l'accent sur la normalisation des images et l'applicabilité des modèles radiomiques. Notre étude a utilisé une base de données rétrospective de l'Institut Gustave Roussy, comprenant les données IRM de 80 patients et leurs données cliniques respectives. Les données d'IRM ont mis en évidence des problèmes pour les études radiomiques, tels que l'inhomogénéité du champ de biais et l'effet "scanner". Pour répondre à ces défis, un pipeline de normalisation d'images IRM a été mis en place, et les caractéristiques radiomiques ont été harmonisées par la méthode ComBat. Pour faire face au problème de modalités manquantes dans l'ensemble de données, une stratégie multi-modèles a été employée, conduisant à 16 modèles distincts reposant sur diverses combinaisons de caractéristiques radiomiques et cliniques. Cette approche a ensuite été rationalisée en une méthode multimodale, réduisant le nombre de modèles à cinq, après une phase de sélection de caractéristiques indépendantes. Les résultats de l'approche multimodale se sont avérés être prometteurs. Cette stratégie multimodale a été essentielle pour identifier les patients survivant plus de deux ans et a été complétée par l'approche ICARE pour une analyse de survie détaillée<br>The diagnosis of diffuse intrinsic pontine glioma (DIPG) in children stands as one of the most harrowing within pediatric oncology. Despite numerous clinical trials exploring various treatments, the prognosis remains bleak, with most patients succumbing between 9 to 11 months post-diagnosis. Key gene mutations linked to DIPG include H3K27M, ACVR1, and TP53. Each mutation has distinct characteristics, leading physicians to suggest tailored therapies, underscoring the importance of accurate mutation detection in guiding treatment. Located in the crucial region of the brainstem, the pons, DIPG tumors pose significant biopsy risks due to potential neurological damage. Hence, MRI could become a primordial diagnostic tool for these tumors, assessing their spread and gauging therapy responses. Its use to predict accurate gene mutation, and identify long-term survivors, could enhance patient care significantly. Within this framework, radiomics transforms images into vast data sources, extracting features like shape and texture to aid decision-making. The objective of this thesis is to refine mutation prediction and pinpoint long-term survivors, emphasizing image normalization and the applicability of radiomic models. Our study utilized a retrospective database from Gustave Roussy Institute, encompassing 80 patients MRI data and their respective clinical data. These MRI images highlighted issues in radiomic studies, such as bias field inhomogeneity and the "scanner effect". To address these challenges, a dedicated MR image normalization pipeline was implemented, and radiomic features underwent ComBat harmonization. Given the dataset's missing modalities, a multi-model strategy was employed, leading to 16 distinct models based on various radiomic and clinical feature combinations. This approach was then streamlined into a multi-modal method, reducing the number of models to five. The results from the ensemble of these models proved to be the most promising. This multi-modal strategy incorporated a feature selection phase, pinpointing the most pertinent features. Additionally, this method was applied to identify long-term survivors and was complemented by the ICARE framework for a nuanced survival analysis output

This M.A. thesis presents a rhetorical analysis of the Indian philosophical and religious text, The Bhagavad Gita. Utilizing Kenneth Burke's Pentad of act, scene, agent, agency and purpose as a primary interpretive lens for uncovering universal human motivations, this rhetorical critique conceptualizes the idea of rhetorical agency as a model for action in the Gita's dialogical progression between Krishna and Arjuna. Rhetorical agency in the Gita differs from a traditional understanding of agency in that the former amalgamates competing yet co-existing pragmatic and consummatory agencies that Arjuna may utilize to act in the here and now but also relinquish the control on the fruits of his act, to ultimately transcend all human action by breaking the cycle of birth and death. In that sense, by virtue of rhetorical agency, the Gita may be considered in Burke's words Equipment for Living, because it provides a template for life across the universe.

Tesis para optar al grado de Magíster en Administración<br>Cataldo Yañez, Cristobál [Parte I], Mella Pineda, Ronald [Parte II]<br>Hoy en día existe un número importante de industrias que tienen establecimientos y/o sucursales de atención presencial a lo largo de todo Chile para sus clientes y usuarios. Muchos de ellos, poseen una alta demanda de servicios que se traduce en un gran volumen de usuarios que requieren ser atendidos. El mercado ante esta demanda, ha implementado sistemas de atención con el fin de dar un orden y secuencia. Muchos de los sistemas implementados son de carácter presencial y consideran un rollo de papel enumerado y un display que muestra el número actual de atención, esto obliga al usuario a encontrarse presencialmente esperando que sea su turno, sin poder utilizar su tiempo para lo que estime mejor. En base a este contexto, se ha detectado una oportunidad de negocio que da origen a e-GIT que nace cómo una solución al problema de optimización en el uso del tiempo que tienen las atareadas personas actualmente en Chile. Con el sistema de gestión inteligente de ticket de atención diseñado por e-GIT, el usuario puede solicitar su número virtualmente, puede mantenerse informado, ver el avance de la fila y en qué número de atención se encuentra, sin tener que estar en forma presencial, con lo cual puede manejar de mejor manera su valioso tiempo, adicionalmente el usuario se puede mantener en distintas filas, las cuales puede seguir desde una misma aplicación. Y la incorporación de alertas simplifica la experiencia del cliente, ya que es avisado del tiempo restante para su atención según la configuración que el usuario haya ingresado. Desde el punto de vista de la empresa se facilita el uso de sus espacios, reduce la cantidad de clientes que no aparecen, se reduce el tiempo de espera percibido por el cliente, lo que se traduce en una mejor percepción del servicio. La aplicación de gestión para la empresa provee gran cantidad de estadísticas fácil de obtener en función de la data generada, por ejemplo, tiempo de espera promedio, número de clientes atendidos, número de clientes que desertan, atenciones por empleado, sucursal con mayor número de atenciones, y mucho más.

The proposed thesis analyzes on the methods of analyzing Git-based software repositories, and focuses on mining GitHub based repositories. The introduction includes a summary of VCS history and usage, with many details that cover the interactions between users, Git and GitHub. The “related works” chapter presents the methods used by other researchers to mine Git data. Four different datasets are used in this thesis: the historical MSR14, and other three ad-hoc collected datasets. The datasets are analyzed and compared, both for a deeper understanding of the data and to validate the three “new” datasets with the already researched MSR14. Interesting findings are presented, and include considerations on the identification of a commit author. The main objective of the thesis is to present a graphic approach to analyze the interactions between different repositories through users. The results are shown to the researcher as an animated network graph through Gephi. Many examples are shown to investigate on the approach performances and capabilities, and are compared to expert knowledge on the repositories.<br>The proposed thesis analyzes on the methods of analyzing Git-based software repositories, and focuses on mining GitHub based repositories. The introduction includes a summary of VCS history and usage, with many details that cover the interactions between users, Git and GitHub. The “related works” chapter presents the methods used by other researchers to mine Git data. Four different datasets are used in this thesis: the historical MSR14, and other three ad-hoc collected datasets. The datasets are analyzed and compared, both for a deeper understanding of the data and to validate the three “new” datasets with the already researched MSR14. Interesting findings are presented, and include considerations on the identification of a commit author. The main objective of the thesis is to present a graphic approach to analyze the interactions between different repositories through users. The results are shown to the researcher as an animated network graph through Gephi. Many examples are shown to investigate on the approach performances and capabilities, and are compared to expert knowledge on the repositories.

Mestrado em Engenharia do Ambiente<br>Portugal possui uma enorme e vulnerável faixa costeira. Estas zonas têm vindo a ser afectadas por actividade humanas exercendo uma forte pressão sobre o meio marinho. As zonas costeiras estão também associadas a actividades socioeconómicas significativas, tornando-se desta forma zonas bastante sensíveis. Surge assim, como pressão adicional a estas zonas, as alterações climáticas. Estas estão ligadas à subida do nível do mar, a alterações da frequência e/ou da intensidade das tempestades e furacões associados às consequentes cheias. Os impactes das alterações climáticas nas zonas costeiras serão assim provavelmente agravados pelo facto de nestas se localizarem as principais áreas metropolitanas do país. Assim o potencial para afectar um número elevado de pessoas é, nesta faixa, particularmente alto, tornando-se também um risco acrescido para os ecossistemas, e para a saúde humana. Com a realização deste trabalho, pretende-se, verificar as medidas de adaptação existentes na estratégia de gestão integrada portuguesa, no âmbito das alterações climáticas, efectuando uma comparação entre as medidas existentes em algumas das estratégias existentes no espaço Europeu e propondo algumas medidas a aplicar na estratégia existente em Portugal. ABSTRACT: Portugal posses a huge and vulnerable coastline that has been affected by human activities, putting its sea life to a high stress. The coastal areas are also associated with significant socio-economic activities, thus making them very sensitive areas. Therefore and as an additional problem comes the climate changes.These are combined with the rising sea levels, changes in frequency and/or intensity of storms and hurricanes associated with the resulting flood. Thus, the impacts of climate change on coastal areas will be, probably, aggravated by the fact that these areas are located in the major metropolitan areas of the country. As a result, the probability to affect a large number of people is particularly high, making it also increase the risk for ecosystems as for human health. The purpose of this thesis is to verify the adaptation measures, relative to the climate changes, within IZCM’s strategy. This is achieved by making a comparison between the existing measures in Portugal and in other European zones, and also, proposing some measures to implement to the current national strategy.

Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2015.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 75-77).<br>It is commonly asserted that the success of a software development project, and the usability of the final product, depend on the quality of the concepts that underlie its design. Yet this hypothesis has not been systematically explored by researchers, and conceptual design has not played the central role in the research and teaching of software engineering that one might expect. As part of a new research project to explore conceptual design, we are engaging in a series of case studies. This thesis reports on our case study on Git, a popular-yet sometimes puzzling-version control system. In an attempt to understand the root causes of its complexity, we analyze its conceptual model and identify some undesirable properties; we then present a reworking of the conceptual model that forms the basis of Gitless, our redesign of Git.<br>by Santiago Perez De Rosso.<br>S.M.

Git is a distributed version control system that tracks changes to a project overtime and is used to save these changes. Today it is being used by millions of people and is becoming a demand on the job market. For this reason it has become important to learn the version control system. Learning Git however may be difficult for beginners and learning it through tutorials may not always be effective. Learning it through a serious educational game (SEG) may be more effective as a SEG can provide motivation and feedback which are two factors for successful learning. This study seeks to assess how effective a SEG is in teaching Git by looking at the amount of knowledge gained from playing a SEG. This study also seeks to assess how much participants learned Git using a tutorial compared to participants who used a serious educational game. From the results, the study found that the SEG expanded the understanding of Git. The study also found that there was no significant difference in the amount of understanding gained from the SEG and the tutorial.