Rôles de la protéine tyrosine phosphatase DEP-1 dans l'angiogenèse, la perméabilité vasculaire et la progression tumorale

L’angiogenèse et l’augmentation de la perméabilité vasculaire sont des éléments clés pour la croissance et la progression tumorale. Par conséquent, de nombreux efforts sont déployés à comprendre les mécanismes moléculaires impliqués dans la formation et le remodelage des vaisseaux sanguins de manière à identifier de nouvelles cibles thérapeutiques potentielles. De cette optique, les travaux de cette thèse se sont concentrés sur la protéine tyrosine phosphatase DEP-1, initialement identifiée comme un régulateur négatif de la prolifération et de la phosphorylation du VEGFR2 lorsque fortement exprimée dans les cellules endothéliales. Toutefois, en utilisant une approche d’ARNi, il a été démontré que via sa capacité à déphosphoryler la tyrosine inhibitrice de Src (Y529), DEP-1 était également un régulateur positif de l’activation de Src dans les cellules endothéliales stimulées au VEGF. Puisque Src joue un rôle central dans la promotion de l’angiogenèse et la perméabilité vasculaire, nous avons en plus démontré que DEP-1 était un promoteur de ces fonctions in vitro et que la tyrosine phosphorylation de sa queue C-terminale, permettant l’interaction et l’activation de Src, était requise. Les travaux de recherche présentés dans cette thèse démontrent dans un premier temps à partir d’une souris Dep1 KO, dont le développement ne présente aucun phénotype apparent, que la perte de l’expression de DEP-1 se traduit en une inhibition de l’activation de Src et de l’un de ses substrats, la VE-Cadherine, en réponse au VEGF chez la souris adulte. Nos résultats démontrent donc, pour la première fois, le rôle primordial de DEP-1 dans l’induction de la perméabilité vasculaire et de la formation de capillaires in vivo. Conséquemment, la croissance tumorale et la formation de métastases aux poumons sont réduites due à une inhibition de leur vascularisation ce qui se traduit par une diminution de la prolifération et une augmentation de l’apoptose des cellules cancéreuses. De façon intéressante, l’expression élevée de DEP-1 dans les vaisseaux sanguins tumoraux de patientes atteintes du cancer du sein corrèle avec une vascularisation accrue de la tumeur. En plus du rôle de DEP-1 dans la réponse angiogénqiue à l’âge adulte, nos travaux ont également démontré le rôle important de DEP-1 lors de la vascularisation de la rétine, un modèle in vivo d’angiogenèse développementale. Dans ce contexte, DEP-1 inhibe la prolifération des cellules endothéliales et limite leur bourgeonnement et la complexification du réseau vasculaire rétinien en permettant l’expression adéquate du Dll4, un régulateur crucial de l’organisation de la vascularisation développementale. Cette expression du Dll4 découlerait de la stabilisation de la β-caténine par l’inactivation de la GSK3β, un régulateur important de la dégradation de la β-caténine, en réponse au VEGF selon la voie de signalisation VEGFR2-Src-PI3K-Akt-GSK3β. Ainsi, ces travaux identifient DEP-1 comme un régulateur important de l’organisation vasculaire rétinienne. Les rôles positifs de DEP-1 dans les cellules endothéliales découlent principalement de sa capacité à lier et activer la kinase Src. En plus de contribuer à la réponse angiogénique, Src est également un oncogène bien caractérisé notamment pour sa contribution au programme invasif des cellules cancéreuses mammaires. Les travaux de cette thèse illustrent que DEP-1 est préférentiellement exprimée dans les cellules cancéreuses mammaires invasives et qu’il régule l’activation de Src, de voies de signalisation invasives et, par le fait même, de l’invasivité de ces cellules in vitro et in vivo. De façon intéressante, ces observations corrèlent avec des données cliniques où l’expression modérée de DEP-1 est associée à un mauvais pronostic de survie et de rechute. Ces résultats démontrent donc, pour la première fois, le rôle positif de DEP-1 dans l’activation de Src au niveau des cellules endothéliales et des cellules cancéreuses mammaires ce qui permet la régulation du bourgeonnement endothélial, de la perméabilité vasculaire, de l’angiogenèse normale et pathologique en plus de l’invasion tumorale.

Career Advancement of MBAs: A study on the effect of personal, professional,organisational and environmental variables

School of Management Studies, Cochin University of Science and Technology

Applying Data mining using Statistical Techniques for Career Selection

For years, choosing the right career by monitoring the trends and scope for different career paths have been a requirement for all youngsters all over the world. In this paper we provide a scientific, data mining based method for job absorption rate prediction and predicting the waiting time needed for 100% placement, for different engineering courses in India. This will help the students in India in a great deal in deciding the right discipline for them for a bright future. Information about passed out students are obtained from the NTMIS ( National technical manpower information system ) NODAL center in Kochi, India residing in Cochin University of science and technology

A Study of a Comprehensive Career Services System in Chinese Universities

Since 1999, with the adoption of expansion policy in higher education by the Chinese government, enrollment and graduate numbers have been increasing at an unprecedented speed. Accustomed to a system in which university graduates were placed, many students are not trained in “selling themselves”, which exacerbates the situation leading to a skyrocketing unemployment rate among new graduates. The idea of emphasizing career services comes with increasing employment pressure among university graduates in recent years. The 1998 “Higher Education Act” made it a legislative requirement. Thereafter, the Ministry of Education issued a series of documents in order to promote the development of career services. All higher education institutions are required to set up special career service centers and to set a ratio of 1:500 between career staff and the total number of students. Related career management courses, especially career planning classes, are required to be clearly included as specific modules into the teaching plan with a requirement of no less than 38 sessions in one semester at all universities. Developing career services in higher education has thus become a hot issue. One of the more notable trends in higher education in recent years has been the transformation of university career service centers from merely being the coordinators of on-campus placement into full service centers for international career development. The traditional core of career services in higher education had been built around guidance, information and placements (Watts, 1997). This core was still in place, but the role of higher education career services has changed considerably in recent years and the nature of each part is being transformed (Watts, 1997). Most services are undertaking a range of additional activities, and the career guidance issue is emphasized much more than before. Career management courses, especially career planning classes, are given special focus in developing career services in the Chinese case. This links career services clearly and directly with the course provision function. In China, most career service centers are engaging in the transformation period from a “management-oriented” organization to a “service-oriented” organization. Besides guidance services, information services and placement activities, there is a need to blend them together with the new additional teaching function, which follows the general trend as regulated by the government. The role of career services has been expanding and this has brought more challenges to its development in Chinese higher education. Chinese universities still remain in the period of exploration and establishment in developing their own career services. In the face of the new situation, it is very important and meaningful to explore and establish a comprehensive career services system to address student needs in the universities. A key part in developing this system is the introduction of career courses and delivering related career management skills to the students. So there is the need to restructure the career service sectors within the Chinese universities in general. The career service centers will operate as a hub and function as a spoke in the wheel of this model system, providing support and information to staff located in individual teaching departments who are responsible for the delivery of career education, information, advice and guidance. The career service centers will also provide training and career planning classes. The purpose of establishing a comprehensive career services system is to provide a strong base for student career development. The students can prepare themselves well in psychology, ideology and ability before employment with the assistance of effective career services. To conclude, according to the different characteristics and needs of students, there will be appropriate services and guidance in different stages and different ways. In other words, related career services and career guidance activities would be started for newly enrolled freshmen and continue throughout their whole university process. For the operation of a comprehensive services system, there is a need for strong support by the government in the form of macro-control and policy guarantee, but support by the government in the form of macro-control and policy guarantee, but also a need for close cooperation with the academic administration and faculties to be actively involved in career planning and employment programs. As an integral function within the universities, career services must develop and maintain productive relationships with relevant campus offices and key stakeholders both within the universities and externally.

More women in informatics research and education

Speaker: Lynda Hardman Organiser: Time: 04/02/2015 12:30-13:30 Location: B32/3077 Abstract The challenges of addressing gender inequalities in science, technology, engineering, mathematics and medicine is widely acknowledged. We currently hold a bronze award and ECS is one of many academic units in the University which has gained Athena Swan Charter status. In this seminar, Professor Lynda Hardman, Chair of the Informatics Europe working group "Women in Informatics Research and Education” will be explaining the causes of issued underlying gender inequality and constructive routes to addressing this important agenda. In undertaking to commit to an action plan which is a prerequisite of gaining charter status, the University or academic department agreed to accept and incorporate the Athena Swan six principles listed below: * To address gender inequalities requires commitment and action from everyone, at all levels of the organisation * To tackle the unequal representation of women in science requires changing cultures and attitudes across the organisation * The absence of diversity at management and policy-making levels has broad implications which the organisation will examine * The high loss rate of women in science is an urgent concern which the organisation will address * The system of short-term contracts has particularly negative consequences for the retention and progression of women in science, which the organisation recognises * There are both personal and structural obstacles to women making the transition from PhD into a sustainable academic career in science, which require the active consideration of the organisation. This seminar is designed to provide an opportunity to explore these issues NOTE: Lynda will be basing here talk on some of the work she directed as chair of the "Women in Informatics Research and Education” working group. The purpose of the working group is to actively participate and promote actions that contribute to improve gender balance in Information and Communication Sciences and Technologies. The first concrete result of the working group's activities was the publication of the booklet "More Women in Informatics Research and Education" in 2013. The booklet is a compact source of clear and simple best practices to deans and heads of departments that aim to increase the participation of women as both students and employees in their institutions. Many tips included were also inspired by colleagues already in leading positions who have already implemented actions in their institutions to attract more women and ensure their continued participation in the organization at commensurate ratios with their male colleagues. The booklet is endorsed by the European Commission and features a foreword by Neelie Kroes, Vice-President of the European Commission, responsible for the Digital Agenda.

Estudio de la madurez vocacional de los estudiantes españoles de Educación Secundaria mediante el Career Development Inventory-School Form.

Resumen tomado de la revista

The National Literacy Strategy. Phonics : progression in phonics : materials for whole-class teaching.

Es un hecho ampliamente aceptado que el éxito de la lectura depende de aprender a utilizar una serie de estrategias, y el Programa Nacional de Estudios (National Currículo) ya las establece. La mayoría de maestros de primaria conocen la importancia de enseñar a los niños a predecir y controlar la lectura, en relación con el contexto, así como,la gramática del texto.Tienen que comprobar si ésta tiene sentido y, si no es así, volver a comprobarlo, identificar los errores y tratar de corregirlos. Estas estrategias son esenciales para la comprensión,al igual que también lo es aprender a decodificar palabras.

Progression in Secondary drama.

Comunicarse a través del lenguaje del teatro implica ser capaz, conscientemente, de manejar e interpretar las combinaciones del volumen y el tono en que se habla, el movimiento, la luz y el espacio. En este texto se estudia la naturaleza del teatro como una asignatura del currículo y esboza los criterios aplicados en la actualidad en el sistema educativo inglés. Ofrece un marco detallado para la planificación de la supervisión y evaluación del progreso de los estudiantes y proporciona recursos e ideas prácticas para asesorar a los profesores cómo ayudar a los alumnos a desarrollar sus conocimientos, habilidades y la comprensión del teatro así como su evaluación. Para alumnos entre once y dieciocho años. Incluye índice y referencias bibliográficas.

Go science! 1. Teacher planning and resource pack : motivation progression success.

Cumple con los requisitos de la etapa 3 de secundaria (key stage 3). Este recurso proporciona al profesor material didáctico que le ayuda a enseñar la forma de trabajar con las ciencias a través de sus principales conceptos y procesos. Incluye guías con orientaciones para actividades y preguntas que se apoyan en las lecciones del libro del alumno y, de tests al final de cada capítulo para los alumnos además de pruebas de evaluación para el profesor. Se acompaña de un CD-ROM, que contiene el texto del libro e incluye actividades interactivas, Powepoints y concursos.

Go science! 1 : motivation progression success.

Cumple con los requisitos de la etapa 3 de secundaria (key stage 3) del curriculo nacional inglés. Ayuda a los alumnos en el aprendizaje de las ciencias y de cómo funcionan éstas a través de sus principales conceptos y procesos. Va acompañado de material de apoyo para el profesor.

Go science! 2 : motivation progression success.

Cumple con los requisitos de la etapa 3 de secundaria (key stage 3) del curriculo nacional inglés. Ayuda a los alumnos en el aprendizaje de las ciencias y de cómo funcionan éstas a través de sus principales conceptos y procesos. Va acompañado de material de apoyo para el profesor.

Go science! 3 : motivation progression success.

Cumple con los requisitos de la etapa 3 de secundaria (key stage 3) del curriculo nacional inglés. Ayuda a los alumnos en el aprendizaje de las ciencias y de cómo funcionan éstas a través de sus principales conceptos y procesos. Va acompañado de material de apoyo para el profesor.

Go science! 2. Teacher planning and resource pack : motivation progression success.

Cumple con los requisitos de la etapa 3 de secundaria (key stage 3). Este recurso proporciona al profesor material didáctico que le ayuda a enseñar la forma de trabajar en las ciencias a través de sus principales conceptos y procesos. Incluye guías con orientaciones para actividades y preguntas que se apoyan en las lecciones del libro del alumno y, tests al final de cada capítulo para los alumnos además de pruebas de evaluación para el profesor. Se acompaña de un CD-ROM, que contiene el texto del libro e incluye actividades interactivas, Powepoints y concursos.