Cell mixing induced by myc is required for competitive tissue invasion and destruction

Cell-cell intercalation is used in several developmental processes to shape the normal body plan. There is no clear evidence that intercalation is involved in pathologies. Here we use the proto-oncogene myc to study a process analogous to early phase of tumour expansion: myc-induced cell competition. Cell competition is a conserved mechanism driving the elimination of slow-proliferating cells (so-called 'losers') by faster-proliferating neighbours (so-called 'winners') through apoptosis and is important in preventing developmental malformations and maintain tissue fitness. Here we show, using long-term live imaging of myc-driven competition in the Drosophila pupal notum and in the wing imaginal disc, that the probability of elimination of loser cells correlates with the surface of contact shared with winners. As such, modifying loser-winner interface morphology can modulate the strength of competition. We further show that elimination of loser clones requires winner-loser cell mixing through cell-cell intercalation. Cell mixing is driven by differential growth and the high tension at winner-winner interfaces relative to winner-loser and loser-loser interfaces, which leads to a preferential stabilization of winner-loser contacts and reduction of clone compactness over time. Differences in tension are generated by a relative difference in F-actin levels between loser and winner junctions, induced by differential levels of the membrane lipid phosphatidylinositol (3,4,5)-trisphosphate. Our results establish the first link between cell-cell intercalation induced by a proto-oncogene and how it promotes invasiveness and destruction of healthy tissues.

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Physiological advantages of dwarfing in surviving extinctions in high-CO2 oceans

Excessive CO2 in the present-day ocean-atmosphere system is causing ocean acidification, and is likely to cause a severe biodiversity decline in the future, mirroring effects in many past mass extinctions. Fossil records demonstrate that organisms surviving such events were often smaller than those before, a phenomenon called the Lilliput effect. Here, we show that two gastropod species adapted to acidified seawater at shallow-water CO2 seeps were smaller than those found in normal pH conditions and had higher mass-specific energy consumption but significantly lower whole-animal metabolic energy demand. These physiological changes allowed the animals to maintain calcification and to partially repair shell dissolution. These observations of the long-term chronic effects of increased CO2 levels forewarn of changes we can expect in marine ecosystems as CO2 emissions continue to rise unchecked, and support the hypothesis that ocean acidification contributed to past extinction events. The ability to adapt through dwarfing can confer physiological advantages as the rate of CO2 emissions continues to increase.

Re-thinking Argentina's labour and social security reform in the 1990s : agreement on competitive corporatism

This paper will analyze the Menem administration's social policy reforms during the 1990s. Neo-liberal reforms in Argentina are well-known both in the economy and in the social arena, but in the latter we can discern the presence of tripartite negotiations. The form of such negotiations, the type of agreements reached as a result, and the background to those agreements will be discussed. We also pay attention to the concept of competitive corporatism, which was established under the increase in market competition brought about by globalization.

The rise and fall in the price of food, fuel and manufactured goods : interdependency between prices and technology determining comparative advantages and development paths

Green innovation, which enables us to extract energy from food crops, caused a food shortage in 2008. Countries suffering severe damage started to reconsider their agricultural policy with the aim of becoming more autonomous. The food price hike of the time looks like a reversal of the celebrated Singer-Prebisch thesis proposed in the 1950s. This paper examines the consequences of this trend on the comparative advantages and development strategies of developing countries. For that purpose, first, trends and short-run fluctuations in the prices of fuel and bio-energy crops are investigated. It is shown that the price series of fuels and the crops are synchronized only after the fuel extracting technology came into effect. Second, the reversal of the Singer-Prebisch thesis is underpinned by the generic form of an endogenous growth model developed by Rebelo (1991). It is shown that as an economy grows, appreciation of the non-reproducible, such as mineral resources and raw labor, over the reproducible, such as capital goods, is the norm rather than an anomaly. Third, the consequences of the food price hike and underlying capital accumulation on the development strategies of labor-abundant and low-income countries are explored. It is concluded that the impact of the food price hikes on the alteration of a development strategy is only incremental, without reinforcement from raw-labor-saving innovation. A case study of inventions by JUKI Corporation, a world-leader in the sewing machine market exemplifies the fact that, of all the major inventions the company have made, raw-labor-saving inventions have not dominated, although JUKI's machines are sold to one of the most raw-labor-intensive industries.

Myanmar's apparel industry in the new international environment : prospects and challenges

Myanmar’s apparel industry had long been denied access to Western markets due to sanctions against its military government. The birth of a "civilian" government in March 2011 improved Myanmar’s relations with the international community, and Western sanctions were largely lifted. Regained market access is expected to trigger rapid growth of Myanmar’s apparel exports. This paper examines this impact with a comparison to Vietnam’s apparel industry. The industry’s prospects are getting bright, but the business environment has recently changed drastically in Myanmar. A new challenge for Myanmar’s apparel industry is remaining globally competitive. This paper also examines advantages and disadvantages that apparel firms in Myanmar experience. Although its abundance of low-wage workers remains a source of competitiveness, Myanmar needs its government to play a more active role to build the foundation of the industry.

Governance Structure Choices in Supply Chain Management Evidence from Spanish and Chinese Pork Chain Cases

The author participated in the 6 th EU Framework Project ―Q-pork Chains (FP6-036245-2)‖ from 2007 to 2009. With understanding of work reports from China and other countries, it is found that compared with other countries, China has great problems in pork quality and safety. By comparing the pork chain management between China and Spain, It is found that the difference in governance structure is one of the main differences in pork chain management between Spain and China. In China, spot-market relationship still dominates governance structure of pork chain, especially between the numerous house-hold pig holders and the great number of small slaughters. While in Spain, chain agents commonly apply cooperatives or integrations to cooperate. It also has been proven by recent studies, that in quality management at the chain level that supply chain integration has a direct effect on quality management practices (Han, 2010). Therefore, the author started to investigate the governance structure choices in supply chain management. And it has been set as the first research objective, which is to explain the governance structure choices process and the influencing factors in supply chain management, analyzing the pork chains cases in Spain and in China. During the further investigation, the author noticed the international trade of pork between Spain and China is not smooth since the signature of bi-lateral agreement on pork trade in 2007. Thus, another objective of the research is to find and solve the problems exist in the international pork chain between Spain and China. For the first objective, to explain the governance structure choices in supply chain management, the thesis conducts research in three main sections. 10 First of all, the thesis gives a literature overview in chapter two on Supply Chain Management (SCM), agri-food chain management and pork chain management. It concludes that SCM is a systems approach to view the supply chains as a whole, and to manage the total flow of goods inventory from the supplier to the ultimate customer. It includes the bi-directional flow of products (materials and services) and information, and the associated managerial and operational activities. And it also is a customer focus to create unique and individual source of customer value with an appropriate use of resources, leading to customer satisfaction and building competitive chain advantages. Agri-food chain management and pork chain management are applications of SCM in agri-food sector and pork sector respectively. Then, the research gives a comparative study in chapter three in the pork chain and pork chain management between Spain and China. Many differences are found, while the main difference is governance structure in pork chain management. Furthermore, the author gives an empirical study on governance structure choice in chapter five. It is concluded that governance structure of supply chain consists of a collection of rules/institutions/constraints structuring the transactions between the various stakeholders. Based on the overview on literatures closely related with governance structure, such as transaction cost economics, transaction value analysis and resource-based view theories, seven hypotheses are proposed, which are: Hypothesis 1: Transaction cost has positive relationship with governance structure choice Hypothesis 2: Uncertainty has positive relationship with transaction cost; higher uncertainty exerts high transaction cost Hypothesis 3: The relationship between asset specificity and transaction cost is positive Hypothesis 4: Collaboration advantages and governance structure choice have positive relationship11 Hypothesis 5: Willingness to collaborate has positive relationship with collaboration advantages Hypothesis 6: Capability to collaborate has positive relationship with collaboration advantages Hypothesis 7: Uncertainty has negative effect on collaboration advantages It is noted that as transaction cost value is negative, the transaction cost mentioned in the hypotheses is its absolute value. To test the seven hypotheses, Structural Equation Model (SEM) is applied and data collected from 350 pork slaughtering and processing companies in Jiangsu, Shandong and Henan Provinces in China is used. Based on the empirical SEM model and its results, the seven hypotheses are proved. The author generates several conclusions accordingly. It is found that the governance structure choice of the chain not only depends on transaction cost, it also depends on collaboration advantages. Exchange partners establish more stable and more intense relationship to reduce transaction cost and to maximize collaboration advantages. ―Collaboration advantages‖ in this thesis is defined as the joint value achieved through transaction (mutual activities) of agents in supply chains. This value forms as improvements, mainly in mutual logistics systems, cash response, information exchange, technological improvements and innovative improvements and quality management improvements, etc. Governance structure choice is jointly decided by transaction cost and collaboration advantages. Chain agents take different governance structures to coordinate in order to decrease their transaction cost and to increase their collaboration advantages. In China´s pork chain case, spot market relationship dominates the governance structure among the numerous backyard pig farmer and small family slaughterhouse 12 as they are connected by acquaintance relationship and the transaction cost in turn is low. Their relationship is reliable as they know each other in the neighborhood; as a result, spot market relationship is suitable for their exchange. However, the transaction between large-scale slaughtering and processing industries and small-scale pig producers is becoming difficult. The information hold back behavior and hold-up behavior of small-scale pig producers increase transaction cost between them and large-scale slaughtering and processing industries. Thus, through the more intense and stable relationship between processing industries and pig producers, processing industries reduce the transaction cost and improve the collaboration advantages with their chain partners, in which quality and safety collaboration advantages be increased, meaning that processing industries are able to provide consumers products with better quality and higher safety. It is also drawn that transaction cost is influenced mainly by uncertainty and asset specificity, which is in line with new institutional economics theories developed by Williamson O. E. In China´s pork chain case, behavioral uncertainty is created by the hold-up behaviors of great numbers of small pig producers, while big slaughtering and processing industries having strong asset specificity. On the other hand, ―collaboration advantages‖ is influenced by chain agents´ willingness to collaborate and chain agents´ capabilities to cooperate. With the fast growth of big scale slaughtering and processing industries, they are more willing to know and make effort to cooperate with their chain members, and they are more capable to create joint value together with other chain agents. Therefore, they are now the main chain agents who drive more intense and stable governance structure in China‘s pork chain. For the other objective, to find and solve the problems in the international pork chain between Spain and China, the research gives an analysis in chapter four on the 13 international pork chain. This study gives explanations why the international trade of pork between Spain and China is not sufficient from the chain perspective. It is found that the first obstacle is the high quality and safety requirement set by Chinese government. It makes the Spanish companies difficult to get authorities to export. Other aspects, such as Spanish pork is not competitive in price compared with other countries such as Denmark, United States, Canada, etc., Chinese consumers do not have sufficient information on Spanish pork products, are also important reasons that Spain does not export great quantity of pork products to China. It is concluded that China´s government has too much concern on the quality and safety requirements to Spanish pork products, which makes trade difficult to complete. The two countries need to establish a more stable and intense trade relationship. They also should make the information exchange sufficient and efficient and try to break trade barriers. Spanish companies should consider proper price strategies to win the Chinese pork market

EvAAL: Evaluating AAL Systems through Competitive Benchmarking

Owing to the complexity of Ambient Assisted Living (AAL) systems and platforms, the evaluation of AAL solutions is a complex task that will challenge researchers for years to come. However, the analysis and comparison of proposed solutions is paramount to enable us to assess research results in this area. We have thus organized an international contest called EvAAL: Evaluating AAL Systems through Competitive Benchmarking. Its aims are to raise interest within the research and developer communities in the multidisciplinary research fields enabling AAL, and to create benchmarks for the evaluation and comparison of AAL systems.

Differences and Relationship Between Standard and Specific Throwing Test in Handball According to the Competitive and Professional Level

The present study analyzed the differences in distance throwing with heavy and light medicine ball and throwing velocity between handball players of different competitive and professional level. Likewise, the relationship between the three throwing test of progressive specificity was analyzed: throwing with heavy medicinal ball (TH), throwing with light medicinal ball (TL) and throwing velocity (TV). For this purpose, sixty-five professional (P), semiprofessional (S) and non-professional (N) players were evaluated. El presente estudio analizó las diferencias en la distancia de lanzamiento realizado con balón medicinal pesado y ligero y en la velocidad de lanzamiento entre jugadores de balonmano de diferente nivel competitivo y profesional. Igualmente, la relación entre los tres test de lanzamiento, de progresiva especificidad, fue analizado: lanzamiento con balón medicinal pesado (TH), lanzamiento con balón medicinal ligero (TL) y velocidad de lanzamiento (TV). Para ello, sesenta y cinco jugadores profesionales (P), semi-profesionales (S) y no-profesionales (N) fueron evaluados.

Strategic Airline Alliances: Advantages for Major Airlines Being Aligned

SSome factors including the deregulation in the U.S and the liberalization in Europe of the airline industry are essential to understanding why the number of partnership agreements between airlines has increased during the last 25 years. These events, coupled with the continuous economic downturn and the 9/11 catastrophe seem to be the perfect framework for the tendency to develop airline strategic alliances. However, it has been observed that this trend was not followed during the period 2005-2008. The purpose of this paper is to analyze if a benefit was experienced by the major airlines who became a member of the current 3 big alliances compared to the major airlines that decided not to become a member or were not admitted into the alliances during 2005-2008. The methodology of this report includes an analysis of several airlines’ performance figures. These performance figures include the revenue passenger kilometers (RPKs), the passenger load factor (PLF) and also the market share (MS). The figures will be compared between the aligned airlines and others which have similar business models. The value of this paper is to reveal whether being aligned provides advantages to major airlines under a bearish airline market in a globalized environment.

Agile Construction and Evolution of Product-Line Architectures

Software Product Line Engineering (SPLE) has proved to have significant advantages in family-based software development, but also implies the up¬front design of a product-line architecture (PLA) from which individual product applications can be engineered. The big upfront design associated with PLAs is in conflict with the current need of "being open to change". However, the turbulence of the current business climate makes change inevitable in order to stay competitive, and requires PLAs to be open to change even late in the development. The trend of "being open to change" is manifested in the Agile Software Development (ASD) paradigm, but it is spreading to the domain of SPLE. To reduce the big upfront design of PLAs as currently practiced in SPLE, new paradigms are being created, one being Agile Product Line Engineering (APLE). APLE aims to make the development of product-lines more flexible and adaptable to changes as promoted in ASD. To put APLE into practice it is necessary to make mechanisms available to assist and guide the agile construction and evolution of PLAs while complying with the "be open to change" agile principle. This thesis defines a process for "the agile construction and evolution of product-line architectures", which we refer to as Agile Product-Line Archi-tecting (APLA). The APLA process provides agile architects with a set of models for describing, documenting and tracing PLAs, as well as an algorithm to analyze change impact. Both the models and the change impact analysis offer the following capabilities: Flexibility & adaptability at the time of defining software architectures, enabling change during the incremental and iterative design of PLAs (anticipated or planned changes) and their evolution (unanticipated or unforeseen changes). Assistance in checking architectural integrity through change impact analysis in terms of architectural concerns, such as dependencies on earlier design decisions, rationale, constraints, and risks, etc.Guidance in the change decision-making process through change im¬pact analysis in terms of architectural components and connections. Therefore, APLA provides the mechanisms required to construct and evolve PLAs that can easily be refined iteration after iteration during the APLE development process. These mechanisms are provided in a modeling frame¬work called FPLA. The contributions of this thesis have been validated through the conduction of a project regarding a metering management system in electrical power networks. This case study took place in an i-smart software factory and was in collaboration with the Technical University of Madrid and Indra Software Labs. La Ingeniería de Líneas de Producto Software (Software Product Line Engi¬neering, SPLE) ha demostrado tener ventajas significativas en el desarrollo de software basado en familias de productos. SPLE es un paradigma que se basa en la reutilización sistemática de un conjunto de características comunes que comparten los productos de un mismo dominio o familia, y la personalización masiva a través de una variabilidad bien definida que diferencia unos productos de otros. Este tipo de desarrollo requiere el diseño inicial de una arquitectura de línea de productos (Product-Line Architecture, PLA) a partir de la cual los productos individuales de la familia son diseñados e implementados. La inversión inicial que hay que realizar en el diseño de PLAs entra en conflicto con la necesidad actual de estar continuamente "abierto al cam¬bio", siendo este cambio cada vez más frecuente y radical en la industria software. Para ser competitivos es inevitable adaptarse al cambio, incluso en las últimas etapas del desarrollo de productos software. Esta tendencia se manifiesta de forma especial en el paradigma de Desarrollo Ágil de Software (Agile Software Development, ASD) y se está extendiendo también al ámbito de SPLE. Con el objetivo de reducir la inversión inicial en el diseño de PLAs en la manera en que se plantea en SPLE, en los último años han surgido nuevos enfoques como la Ingeniera de Líneas de Producto Software Ágiles (Agile Product Line Engineering, APLE). APLE propone el desarrollo de líneas de producto de forma más flexible y adaptable a los cambios, iterativa e incremental. Para ello, es necesario disponer de mecanismos que ayuden y guíen a los arquitectos de líneas de producto en el diseño y evolución ágil de PLAs, mientras se cumple con el principio ágil de estar abierto al cambio. Esta tesis define un proceso para la "construcción y evolución ágil de las arquitecturas de lineas de producto software". A este proceso se le ha denominado Agile Product-Line Architecting (APLA). El proceso APLA proporciona a los arquitectos software un conjunto de modelos para de¬scribir, documentar y trazar PLAs, así como un algoritmo para analizar vel impacto del cambio. Los modelos y el análisis del impacto del cambio ofrecen: Flexibilidad y adaptabilidad a la hora de definir las arquitecturas software, facilitando el cambio durante el diseño incremental e iterativo de PLAs (cambios esperados o previstos) y su evolución (cambios no previstos). Asistencia en la verificación de la integridad arquitectónica mediante el análisis de impacto de los cambios en términos de dependencias entre decisiones de diseño, justificación de las decisiones de diseño, limitaciones, riesgos, etc. Orientación en la toma de decisiones derivadas del cambio mediante el análisis de impacto de los cambios en términos de componentes y conexiones. De esta manera, APLA se presenta como una solución para la construcción y evolución de PLAs de forma que puedan ser fácilmente refinadas iteración tras iteración de un ciclo de vida de líneas de producto ágiles. Dicha solución se ha implementado en una herramienta llamada FPLA (Flexible Product-Line Architecture) y ha sido validada mediante su aplicación en un proyecto de desarrollo de un sistema de gestión de medición en redes de energía eléctrica. Dicho proyecto ha sido desarrollado en una fábrica de software global en colaboración con la Universidad Politécnica de Madrid e Indra Software Labs.

A program transformation for continuation call-based tabled execution

The advantages of tabled evaluation regarding program termination and reduction of complexity are well known —as are the significant implementation, portability, and maintenance efforts that some proposals (especially those based on suspensión) require. This implementation effort is reduced by program transformation-based continuation cali techniques, at some eñrciency cost. However, the traditional formulation of this proposal by Ramesh and Cheng limits the interleaving of tabled and non-tabled predicates and thus cannot be used as-is for arbitrary programs. In this paper we present a complete translation for the continuation cali technique which, using the runtime support needed for the traditional proposal, solves these problems and makes it possible to execute arbitrary tabled programs. We present performance results which show that CCall offers a useful tradeoff that can be competitive with state-of-the-art implementations.

Biosensors based on vertically interrogated optofluidic sensing cells

El objetivo de la presente tesis doctoral es el desarrollo de un nuevo concepto de biosensor óptico sin marcado, basado en una combinación de técnicas de caracterización óptica de interrogación vertical y estructuras sub-micrométricas fabricadas sobre chips de silicio. Las características más importantes de dicho dispositivo son su simplicidad, tanto desde el punto de vista de medida óptica como de introducción de las muestras a medir en el área sensible, aspectos que suelen ser críticos en la mayoría de sensores encontrados en la literatura. Cada uno de los aspectos relacionados con el diseño de un biosensor, que son fundamentalmente cuatro (diseño fotónico, caracterización óptica, fabricación y fluídica/inmovilización química) son desarrollados en detalle en los capítulos correspondientes. En la primera parte de la tesis se hace una introducción al concepto de biosensor, en qué consiste, qué tipos hay y cuáles son los parámetros más comunes usados para cuantificar su comportamiento. Posteriormente se realiza un análisis del estado del arte en la materia, enfocado en particular en el área de biosensores ópticos sin marcado. Se introducen también cuáles son las reacciones bioquímicas a estudiar (inmunoensayos). En la segunda parte se describe en primer lugar cuáles son las técnicas ópticas empleadas en la caracterización: Reflectometría, Elipsometría y Espectrometría; además de los motivos que han llevado a su empleo. Posteriormente se introducen diversos diseños de las denominadas "celdas optofluídicas", que son los dispositivos en los que se va a producir la interacción bioquímica. Se presentan cuatro dispositivos diferentes, y junto con ellos, se proponen diversos métodos de cálculo teórico de la respuesta óptica esperada. Posteriormente se procede al cálculo de la sensibilidad esperada para cada una de las celdas, así como al análisis de los procesos de fabricación de cada una de ellas y su comportamiento fluídico. Una vez analizados todos los aspectos críticos del comportamiento del biosensor, se puede realizar un proceso de optimización de su diseño. Esto se realiza usando un modelo de cálculo simplificado (modelo 1.5-D) que permite la obtención de parámetros como la sensibilidad y el límite de detección de un gran número de dispositivos en un tiempo relativamente reducido. Para este proceso se escogen dos de las celdas optofluídicas propuestas. En la parte final de la tesis se muestran los resultados experimentales obtenidos. En primer lugar, se caracteriza una celda basada en agujeros sub-micrométricos como sensor de índice de refracción, usando para ello diferentes líquidos orgánicos; dichos resultados experimentales presentan una buena correlación con los cálculos teóricos previos, lo que permite validar el modelo conceptual presentado. Finalmente, se realiza un inmunoensayo químico sobre otra de las celdas propuestas (pilares nanométricos de polímero SU-8). Para ello se utiliza el inmunoensayo de albumina de suero bovino (BSA) y su anticuerpo (antiBSA). Se detalla el proceso de obtención de la celda, la funcionalización de la superficie con los bioreceptores (en este caso, BSA) y el proceso de biorreconocimiento. Este proceso permite dar una primera estimación de cuál es el límite de detección esperable para este tipo de sensores en un inmunoensayo estándar. En este caso, se alcanza un valor de 2.3 ng/mL, que es competitivo comparado con otros ensayos similares encontrados en la literatura. La principal conclusión de la tesis es que esta tipología de dispositivos puede ser usada como inmunosensor, y presenta ciertas ventajas respecto a los actualmente existentes. Estas ventajas vienen asociadas, de nuevo, a su simplicidad, tanto a la hora de medir ópticamente, como dentro del proceso de introducción de los bioanalitos en el área sensora (depositando simplemente una gota sobre la micro-nano-estructura). Los cálculos teorícos realizados en los procesos de optimización sugieren a su vez que el comportamiento del sensor, medido en magnitudes como límite de detección biológico puede ser ampliamente mejorado con una mayor compactación de pilares, alcanzandose un valor mínimo de 0.59 ng/mL). The objective of this thesis is to develop a new concept of optical label-free biosensor, based on a combination of vertical interrogation optical techniques and submicron structures fabricated over silicon chips. The most important features of this device are its simplicity, both from the point of view of optical measurement and regarding to the introduction of samples to be measured in the sensing area, which are often critical aspects in the majority of sensors found in the literature. Each of the aspects related to the design of biosensors, which are basically four (photonic design, optical characterization, fabrication and fluid / chemical immobilization) are developed in detail in the relevant chapters. The first part of the thesis consists of an introduction to the concept of biosensor: which elements consists of, existing types and the most common parameters used to quantify its behavior. Subsequently, an analysis of the state of the art in this area is presented, focusing in particular in the area of label free optical biosensors. What are also introduced to study biochemical reactions (immunoassays). The second part describes firstly the optical techniques used in the characterization: reflectometry, ellipsometry and spectrometry; in addition to the reasons that have led to their use. Subsequently several examples of the so-called "optofluidic cells" are introduced, which are the devices where the biochemical interactions take place. Four different devices are presented, and their optical response is calculated by using various methods. Then is exposed the calculation of the expected sensitivity for each of the cells, and the analysis of their fabrication processes and fluidic behavior at the sub-micrometric range. After analyzing all the critical aspects of the biosensor, it can be performed a process of optimization of a particular design. This is done using a simplified calculation model (1.5-D model calculation) that allows obtaining parameters such as sensitivity and the detection limit of a large number of devices in a relatively reduced time. For this process are chosen two different optofluidic cells, from the four previously proposed. The final part of the thesis is the exposition of the obtained experimental results. Firstly, a cell based sub-micrometric holes is characterized as refractive index sensor using different organic fluids, and such experimental results show a good correlation with previous theoretical calculations, allowing to validate the conceptual model presented. Finally, an immunoassay is performed on another typology of cell (SU-8 polymer pillars). This immunoassay uses bovine serum albumin (BSA) and its antibody (antiBSA). The processes for obtaining the cell surface functionalization with the bioreceptors (in this case, BSA) and the biorecognition (antiBSA) are detailed. This immunoassay can give a first estimation of which are the expected limit of detection values for this typology of sensors in a standard immunoassay. In this case, it reaches a value of 2.3 ng/mL, which is competitive with other similar assays found in the literature. The main conclusion of the thesis is that this type of device can be used as immunosensor, and has certain advantages over the existing ones. These advantages are associated again with its simplicity, by the simpler coupling of light and in the process of introduction of bioanalytes into the sensing areas (by depositing a droplet over the micro-nano-structure). Theoretical calculations made in optimizing processes suggest that the sensor Limit of detection can be greatly improved with higher compacting of the lattice of pillars, reaching a minimum value of 0.59 ng/mL).