NOVEL THERAPEUTIC TARGETS IDENTIFIED BY HIGH-THROUGHPUT TECHNOLOGIES FOR TRIPLE-NEGATIVE BREAST CANCER

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

International Regulation of Emerging Technologies: Global Ideologies and Local Headaches

This paper begins to address the international regulation of emerging technologies taking an approach that includes the co-production of technologies and the nature of wicked problems. Both the development of technologies over time, the role of science in regulation, and results from case studies in the regulation of biotechnologies are discusses. Biotechnology, nanotechnology and synthetic biology receive the most attention.

Learning&Information Technologies Cartography

Nowadays, many researches focus their efforts in studies and applications on the Learning area. However, there is a lack of a reference system that permits to know the positioning and the existing links between Learning and Information Technologies. This paper proposes a Cartography where explains the relationships between the elements that compose the Learning Theories and Information Technologies, considering the own features of the learner and the Information Technologies Properties. This intersection will allow us to know what Information Technologies Properties promote Learning Futures.

Heart Failure Monitoring System Based on Wearable and Information Technologies

In Europe, Cardiovascular Diseases (CVD) are the leading source of death, causing 45% of all deceases. Besides, Heart Failure, the paradigm of CVD, mainly affects people older than 65. In the current aging society, the European MyHeart Project was created, whose mission is to empower citizens to fight CVD by leading a preventive lifestyle and being able to be diagnosed at an early stage. This paper presents the development of a Heart Failure Management System, based on daily monitoring of Vital Body Signals, with wearable and mobile technologies, for the continuous assessment of this chronic disease. The System makes use of the latest technologies for monitoring heart condition, both with wearable garments (e.g. for measuring ECG and Respiration); and portable devices (such as Weight Scale and Blood Pressure Cuff) both with Bluetooth capabilities

An Analysis of the Impact of 2.0 Tools and Technologies on Organizational Processes

In this paper, the authors present results from a study on the usage rate of 2.0 tools and technologies among Spanish enterprises. The main objective of the study is to analyze, from the perceptions of executives, the influence of social software tools on a set of business processes. This analysis has been made using two graphic tools: the “2.0 Success Matrix” and the “Tool’s Footprint”. Both the review of literature and the empirical work have lead to important findings and conclusions.

Comparison of CO2 From Coal Capture Processes and Valorisation Technologies

Coal is the most plentiful and evenly distributed fossil fuel worldwide. Based on current production, it is estimated that the reserves will last approximately 130 years. Its use worldwide has been increasing, mainly due to consumption by emerging countries. CO2 emissions generated by combustion and the repercussions of such on climate change support the view that it could no longer be used. CO2 capture may be the solution to continue using it, which would cater for the growing energy demand worldwide. The aim of this study is to compare different processes concerning CO2 capture that may be economically viable, ultimately showing that coal, a fossil energy source widely distributed around the world, can, as a result of using different CO2 capture processes, be used as a clean source of electricity. Hence, in places where geological hurdles may render the costs of CO2 storage considerably higher, since it might have to travel far, coal may be used for other purposes, thus valorising CO2 within the industrial sector. This research is focused on the technical and economic comparison of the most relevant CO2 capture projects designed in Spain using different existing technologies. The oxyfuel project in Ciuden (Leon, Spain), the IGCC Elcogas, precombustion CO2-capture project (Puertollano, Spain) and the postcombustion project in Carboneras (Almeria, Spain) will be analyzed in order to assess the options available to valorise captured CO2. Valorising captured CO2 may be an adequate solution in areas where, although CO2 capture is still possible, storage is not equally so, thus generating a further benefit. The possible uses of CO2 will be assessed in vegetable growing greenhouses, harnessing CO2 in vegetable life cycles. This will also be used in growing algae for subsequent biodiesel production. Both CO2 capture and valorising will eventually lead to the clean use of coal, which will thus enhance the level of self-supply, aiding the development of electric vehicles, which require large amounts of electricity, as well as improve the level of energy autonomy in countries around the world. Another type of fuel, biodiesel, will also be obtained, without this affecting international food prices.

Infrastructure and Workflow for the Formal Evaluation of Semantic Search Technologies

This paper describes an infrastructure for the automated evaluation of semantic technologies and, in particular, semantic search technologies. For this purpose, we present an evaluation framework which follows a service-oriented approach for evaluating semantic technologies and uses the Business Process Execution Language (BPEL) to define evaluation workflows that can be executed by process engines. This framework supports a variety of evaluations, from different semantic areas, including search, and is extendible to new evaluations. We show how BPEL addresses this diversity as well as how it is used to solve specific challenges such as heterogeneity, error handling and reuse

Radiofrequency architectures and technologies for software defined radio

Six-port network is an interesting radiofrequency architecture with multiple possibilities. Since it was firstly introduced in the seventies as an alternative network analyzer, the six-port network has been used for many applications, such as homodyne receivers, radar systems, direction of arrival estimation, UWB (Ultra-Wide-Band), or MIMO (Multiple Input Multiple Output) systems. Currently, it is considered as a one of the best candidates to implement a Software Defined Radio (SDR). This thesis comprises an exhaustive study of this promising architecture, where its fundamentals and the state-of-the-art are also included. In addition, the design and development of a SDR 0.3-6 GHz six-port receiver prototype is presented in this thesis, which is implemented in conventional technology. The system is experimentally characterized and validated for RF signal demodulation with good performance. The analysis of the six-port architecture is complemented by a theoretical and experimental comparison with other radiofrequency architectures suitable for SDR. Some novel contributions are introduced in the present thesis. Such novelties are in the direction of the highly topical issues on six-port technique: development and optimization of real-time I-Q regeneration techniques for multiport networks; and search of new techniques and technologies to contribute to the miniaturization of the six-port architecture. In particular, the novel contributions of this thesis can be summarized as: - Introduction of a new real-time auto-calibration method for multiport receivers, particularly suitable for broadband designs and high data rate applications. - Introduction of a new direct baseband I-Q regeneration technique for five-port receivers. - Contribution to the miniaturization of six-port receivers by the use of the multilayer LTCC (Low Temperature Cofired Ceramic) technology. Implementation of a compact (30x30x1.25 mm) broadband (0.3-6 GHz) six-port receiver in LTTC technology. The results and conclusions derived from this thesis have been satisfactory, and quite fruitful in terms of publications. A total of fourteen works have been published, considering international journals and conferences, and national conferences. Aditionally, a paper has been submitted to an internationally recognized journal, which is currently under review.

Clean Coal Technologies Scenario and Evaluation of Present CO2 Dwindling Initiatives to Approach Zero Emission Power Stations By Coal Combustion. Deployment Situation and Evaluation Study

In the present uncertain global context of reaching an equal social stability and steady thriving economy, power demand expected to grow and global electricity generation could nearly double from 2005 to 2030. Fossil fuels will remain a significant contribution on this energy mix up to 2050, with an expected part of around 70% of global and ca. 60% of European electricity generation. Coal will remain a key player. Hence, a direct effect on the considered CO2 emissions business-as-usual scenario is expected, forecasting three times the present CO2 concentration values up to 1,200ppm by the end of this century. Kyoto protocol was the first approach to take global responsibility onto CO2 emissions monitoring and cap targets by 2012 with reference to 1990. Some of principal CO2emitters did not ratify the reduction targets. Although USA and China spur are taking its own actions and parallel reduction measures. More efficient combustion processes comprising less fuel consuming, a significant contribution from the electricity generation sector to a CO2 dwindling concentration levels, might not be sufficient. Carbon Capture and Storage (CCS) technologies have started to gain more importance from the beginning of the decade, with research and funds coming out to drive its come in useful. After first researching projects and initial scale testing, three principal capture processes came out available today with first figures showing up to 90% CO2 removal by its standard applications in coal fired power stations. Regarding last part of CO2 reduction chain, two options could be considered worthy, reusing (EOR & EGR) and storage. The study evaluates the state of the CO2 capture technology development, availability and investment cost of the different technologies, with few operation cost analysis possible at the time. Main findings and the abatement potential for coal applications are presented. DOE, NETL, MIT, European universities and research institutions, key technology enterprises and utilities, and key technology suppliers are the main sources of this study. A vision of the technology deployment is presented.

Comparison of CO2 from coal captureprocesses and valorisation technologies

Coal is the most plentiful and evenly distributed fossil fuel worldwide. Based on current production, it is estimated that the reserves will last approximately 130 years. Its use worldwide has been increasing, mainly due to consumption by emerging countries. CO2 emissions generated by combustion and the repercussions of such on climate change support the view that it could no longer be used. CO2 capture may be the solution to continue using it, which would cater for the growing energy demand worldwide. The aim of this study is to compare different processes concerning CO2 capture that may be economically viable, ultimately showing that coal, a fossil energy source widely distributed around the world, can, as a result of using different CO2 capture processes, be used as a clean source of electricity. Hence, in places where geological hurdles may render the costs of CO2 storage considerably higher, since it might have to travel far, coal may be used for other purposes, thus valorizing CO2 within the industrial sector. This research is focused on the technical and economic comparison of the most relevant CO2 capture projects designed in Spain using different existing technologies. The oxyfuel project in Ciuden (Leon, Spain), the IGCC Elcogas, precombustion CO2-capture project (Puertollano, Spain) and the postcombustion project in Carboneras (Almeria, Spain) will be analyzed in order to assess the options available to valorizecaptured CO2. Valorizing captured CO2 may be an adequate solution in areas where, although CO2 capture is still possible, storage is not equally so, thus generating a further benefit. The possible uses of CO2 will be assessed in vegetable growing greenhouses, harnessing CO2 in vegetable life cycles. This will also be used in growing algae for subsequent biodiesel production. Both CO2capture and valorizing will eventually lead to the clean use of coal, which will thus enhance the level of self-supply, aiding the development of electric vehicles, which require large amounts of electricity, as well as improve the level of energy autonomy in countries around the world. Another type of fuel, biodiesel, will also be obtained, without this affecting international food prices.

Semantic technologies in idea management systems: a model for interoperability, linking and filtering

Abstract Idea Management Systems are web applications that implement the notion of open innovation though crowdsourcing. Typically, organizations use those kind of systems to connect to large communities in order to gather ideas for improvement of products or services. Originating from simple suggestion boxes, Idea Management Systems advanced beyond collecting ideas and aspire to be a knowledge management solution capable to select best ideas via collaborative as well as expert assessment methods. In practice, however, the contemporary systems still face a number of problems usually related to information overflow and recognizing questionable quality of submissions with reasonable time and effort allocation. This thesis focuses on idea assessment problem area and contributes a number of solutions that allow to filter, compare and evaluate ideas submitted into an Idea Management System. With respect to Idea Management System interoperability the thesis proposes theoretical model of Idea Life Cycle and formalizes it as the Gi2MO ontology which enables to go beyond the boundaries of a single system to compare and assess innovation in an organization wide or market wide context. Furthermore, based on the ontology, the thesis builds a number of solutions for improving idea assessment via: community opinion analysis (MARL), annotation of idea characteristics (Gi2MO Types) and study of idea relationships (Gi2MO Links). The main achievements of the thesis are: application of theoretical innovation models for practice of Idea Management to successfully recognize the differentiation between communities, opinion metrics and their recognition as a new tool for idea assessment, discovery of new relationship types between ideas and their impact on idea clustering. Finally, the thesis outcome is establishment of Gi2MO Project that serves as an incubator for Idea Management solutions and mature open-source software alternatives for the widely available commercial suites. From the academic point of view the project delivers resources to undertake experiments in the Idea Management Systems area and managed to become a forum that gathered a number of academic and industrial partners. Resumen Los Sistemas de Gestión de Ideas son aplicaciones Web que implementan el concepto de innovación abierta con técnicas de crowdsourcing. Típicamente, las organizaciones utilizan ese tipo de sistemas para conectar con comunidades grandes y así recoger ideas sobre cómo mejorar productos o servicios. Los Sistemas de Gestión de Ideas lian avanzado más allá de recoger simplemente ideas de buzones de sugerencias y ahora aspiran ser una solución de gestión de conocimiento capaz de seleccionar las mejores ideas por medio de técnicas colaborativas, así como métodos de evaluación llevados a cabo por expertos. Sin embargo, en la práctica, los sistemas contemporáneos todavía se enfrentan a una serie de problemas, que, por lo general, están relacionados con la sobrecarga de información y el reconocimiento de las ideas de dudosa calidad con la asignación de un tiempo y un esfuerzo razonables. Esta tesis se centra en el área de la evaluación de ideas y aporta una serie de soluciones que permiten filtrar, comparar y evaluar las ideas publicadas en un Sistema de Gestión de Ideas. Con respecto a la interoperabilidad de los Sistemas de Gestión de Ideas, la tesis propone un modelo teórico del Ciclo de Vida de la Idea y lo formaliza como la ontología Gi2MO que permite ir más allá de los límites de un sistema único para comparar y evaluar la innovación en un contexto amplio dentro de cualquier organización o mercado. Por otra parte, basado en la ontología, la tesis desarrolla una serie de soluciones para mejorar la evaluación de las ideas a través de: análisis de las opiniones de la comunidad (MARL), la anotación de las características de las ideas (Gi2MO Types) y el estudio de las relaciones de las ideas (Gi2MO Links). Los logros principales de la tesis son: la aplicación de los modelos teóricos de innovación para la práctica de Sistemas de Gestión de Ideas para reconocer las diferenciasentre comu¬nidades, métricas de opiniones de comunidad y su reconocimiento como una nueva herramienta para la evaluación de ideas, el descubrimiento de nuevos tipos de relaciones entre ideas y su impacto en la agrupación de estas. Por último, el resultado de tesis es el establecimiento de proyecto Gi2MO que sirve como incubadora de soluciones para Gestión de Ideas y herramientas de código abierto ya maduras como alternativas a otros sistemas comerciales. Desde el punto de vista académico, el proyecto ha provisto de recursos a ciertos experimentos en el área de Sistemas de Gestión de Ideas y logró convertirse en un foro que reunión para un número de socios tanto académicos como industriales.

Developing front-end Web 2.0 technologies to access services, content and things in the future Internet

The future Internet is expected to be composed of a mesh of interoperable web services accessible from all over the web. This approach has not yet caught on since global user?service interaction is still an open issue. This paper states one vision with regard to next-generation front-end Web 2.0 technology that will enable integrated access to services, contents and things in the future Internet. In this paper, we illustrate how front-ends that wrap traditional services and resources can be tailored to the needs of end users, converting end users into prosumers (creators and consumers of service-based applications). To do this, we propose an architecture that end users without programming skills can use to create front-ends, consult catalogues of resources tailored to their needs, easily integrate and coordinate front-ends and create composite applications to orchestrate services in their back-end. The paper includes a case study illustrating that current user-centred web development tools are at a very early stage of evolution. We provide statistical data on how the proposed architecture improves these tools. This paper is based on research conducted by the Service Front End (SFE) Open Alliance initiative.

Enabling query technologies for the semantic sensor web

Sensor networks are increasingly being deployed in the environment for many different purposes. The observations that they produce are made available with heterogeneous schemas, vocabularies and data formats, making it difficult to share and reuse this data, for other purposes than those for which they were originally set up. The authors propose an ontology-based approach for providing data access and query capabilities to streaming data sources, allowing users to express their needs at a conceptual level, independent of implementation and language-specific details. In this article, the authors describe the theoretical foundations and technologies that enable exposing semantically enriched sensor metadata, and querying sensor observations through SPARQL extensions, using query rewriting and data translation techniques according to mapping languages, and managing both pull and push delivery modes.

Calibration proposal for new antenna array architectures and technologies for space communications

In large antenna arrays with a large number of antenna elements, the required number of measurements for the characterization of the antenna array is very demanding in cost and time. This letter presents a new offline calibration process for active antenna arrays that reduces the number of measurements by subarray-level characterization. This letter embraces measurements, characterization, and calibration as a global procedure assessing about the most adequate calibration technique and computing of compensation matrices. The procedure has been fully validated with measurements of a 45-element triangular panel array designed for Low Earth Orbit (LEO) satellite tracking that compensates the degradation due to gain and phase imbalances and mutual coupling.