Role of stromal Caveolin-1 (CAV1) levels in breast cancer angiogenesis

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 19-10-2018Tumors have been described as “wounds that never heal”; and non-tumoral surrounding cell populations involved in angiogenesis and response to injury, such as endothelial cells, immune cells and fibroblasts are actively engaged to support the aberrant growth and remodeling of the tumor mass, which conversely determine tumor architecture and behavior. These cells, along with extracellular matrix (ECM) components, define the tumor microenvironment or tumor stroma. While breast cancer progression was conceived for a long time to be largely dependent on aberrant mutations in tumor cells, stromal Cancer-Associated Fibroblasts (CAFs) have been demonstrated to modulate breast cancer growth, invasion, metastasis and therapeutic resistance. Caveolin-1 (CAV1), a prominent organizer of plasma membrane properties and function, exhibits extensive ties with many events defining tumor onset and progression. Although previous studies have shown CAV1 expression levels in CAFs to influence breast cancer growth and metastasis, the underlying driving mechanisms remain incompletely characterized. In this regard, ECM modification and metabolic reprogramming have been proposed as key aspects of a stromal CAV1-dependent role in tumor biology. This thesis research report aims to contribute to our understanding as to how CAV1 expression in stromal CAFs impact tumor angiogenesis, and thus tumor hypoxia, cancer aggressiveness and metastasis. The present work showcases evidence supporting a positive reciprocal feedback relationship between stromal CAV1 downregulation and endoplasmic reticulum (ER) stress, which can drive exacerbated proangiogenic signaling, causative of the generation of an aberrant and dysfunctional tumor vasculature. This report proposes defective angiogenesis and consequent hypoxia as major driving causes for increased aggressiveness of breast cancer in low stromal CAV1 tumors

Modelling and Design of Resilient Networks under Challenges

Communication networks, in particular the Internet, face a variety of challenges that can disrupt our daily lives resulting in the loss of human lives and significant financial costs in the worst cases. We define challenges as external events that trigger faults that eventually result in service failures. Understanding these challenges accordingly is essential for improvement of the current networks and for designing Future Internet architectures. This dissertation presents a taxonomy of challenges that can help evaluate design choices for the current and Future Internet. Graph models to analyse critical infrastructures are examined and a multilevel graph model is developed to study interdependencies between different networks. Furthermore, graph-theoretic heuristic optimisation algorithms are developed. These heuristic algorithms add links to increase the resilience of networks in the least costly manner and they are computationally less expensive than an exhaustive search algorithm. The performance of networks under random failures, targeted attacks, and correlated area-based challenges are evaluated by the challenge simulation module that we developed. The GpENI Future Internet testbed is used to conduct experiments to evaluate the performance of the heuristic algorithms developed

The Christianisation of Iceland: priests, power and social change 1000-1300

The dissertation deals with the institutional development of the church in Iceland from the 11th century to the end of the 13th and the influence of the church on the development of secular power structures in the same period. It is concerned mainly with identifying and describing factors which explain how the Icelandic church was originally fostered by the aristocracy; how the chieftains' involvement with the church helped them consolidate their authority and accumulate more power; how the church only very slowly began to create its own identity and how class-consciousness among clerics developed. The question of cult-continuity is considered and the sources for the history of the church in the 11th century are subjected to scrutiny. The importance earlier scholarship has attached to the early 12th century as a formative period of the Icelandic church is reconsidered. The introduction of the tithe in 1097 is discussed in detail and its significance subjected to revaluation. Evidence for early church building is assembled and the development of ministerial organisation is described. Particular emphasis is attached to the definition of church-ownership in the 12th century and a new interpretation of the church's bid for increased control over ecclesiastical property in the late 12th century is presented. The social origins of the bishops are considered and their administration and political involvement is described. Emphasis is put on studying the changing social status of priests, from being mainly chieftains or influential farmers, to whom ordination was a means to augment their temporal authority, to becoming younger and illegitimate sons who by the mid 13th century had adopted an ecclesiastical identity and who differentiated between secular and ecclesiastical interests

Factors Influencing Customer Satisfaction towards E-shopping in Malaysia

Online shopping or e-shopping has changed the world of business and quite a few people have decided to work with these features. What their primary concerns precisely and the responses from the globalisation are the competency of incorporation while doing their businesses. E-shopping has also increased substantially in Malaysia in recent years. The rapid increase in the e-commerce industry in Malaysia has created the demand to emphasize on how to increase customer satisfaction while operating in the e-retailing environment. It is very important that customers are satisfied with the website, or else, they would not return. Therefore, a crucial fact to look into is that companies must ensure that their customers are satisfied with their purchases that are really essential from the ecommerce’s point of view. With is in mind, this study aimed at investigating customer satisfaction towards e-shopping in Malaysia. A total of 400 questionnaires were distributed among students randomly selected from various public and private universities located within Klang valley area. Total 369 questionnaires were returned, out of which 341 questionnaires were found usable for further analysis. Finally, SEM was employed to test the hypotheses. This study found that customer satisfaction towards e-shopping in Malaysia is to a great extent influenced by ease of use, trust, design of the website, online security and e-service quality. Finally, recommendations and future study direction is provided. Keywords: E-shopping, Customer satisfaction, Trust, Online security, E-service quality, Malaysia