Experimental models for p53, hepatitis B and aflatoxin hepatocarcinogenesis

The major risk factors for liver cancer in Southeast Asia: HBV infection, aflatoxin exposure and p53 expression/mutation, were examined in experimental models. Four groups were examined for development of hepatocellular carcinoma (HCC) with and without neonatal exposure to aflatoxin (AFB$\sb1)$: (Group I.) Transgenic HBsAg mice with one p53 allele. (Group II) Transgenic HBsAg mice with two p53 alleles. (Group III) Non-transgenic litter mates with one p53 allele. (Group IV) Non-transgenic litter mates with two p53 alleles. HCC developed in Group I animals exposed to aflatoxin at an earlier time and were of a higher grade than those seen later in other groups. These results provide an explanation for as to why p53 is a target for deletion and/or mutation in human HCC especially when found in high risk areas where HBV infection and Aflatoxin B1 food contamination is high, and nicely illustrates a synergistic interaction among these three factors. None of the tumors analyzed had loss or mutation in the p53 gene.^ To determine the significance of the specific p53ser249 mutation found in HBV/aflatoxin associated human hepatomas in an in-vivo experimental model using transgenic mice, a two-nucleotide change in the mouse p53 gene at amino acid position 246, which is equivalent to that of 249 in human p53, was introduced. Transgenic mice with mutant p53 controlled by the albumin promoter were generated and shown to express the p53ser246 mutant RNA and protein specifically in liver. Three groups were examined for development of HCC with and without neonatal exposure to aflatoxin: (Group V) Transgenic p53ser246 mice with two p53 alleles. (Group VI) Transgenic p53ser246 mice with one p53 allele. (Group VII) Double transgenic for p53ser246 and HBsAg with two p53 alleles. One hundred percent of male mice with the three risk factors injected with aflatoxin developed high grade liver tumors, compared to 66.6% from group VI and only 14.2% of group V suggesting synergistic interaction between HBsAg and this particular ser246 p53 mutation.^ In order to examine the growth properties of hepatocytes and correlation with p53 loss and/or mutation, cell proliferation and ploidy analysis of liver from normal heterozyous, homozygous null mice and from transgenic mutant p53ser246, mice were studied. Loss of wild-type p53 increased G1/G0 ratios of cells as well as proliferation and decreased cell ploidy. The mutant p53ser246 did not show a significant effect on cell ploidy or proliferation. However a striking 5-10X increase in G1/G0 ratio suggests that this specific mutation specifically induces G0 to G1 transition, which in turn further predisposes hepatocytes to the damaging effect of Aflatoxin. (Abstract shortened by UMI.) ^

Age models of ODP sites from the Barents Sea-Svalbard region

Based on a revised chronostratigraphy, and compilation of borehole data from the Barents Sea continental margin, a coherent glaciation model is proposed for the Barents Sea ice sheet over the past 3.5 million years (Ma). Three phases of ice growth are suggested: (1) The initial build-up phase, covering mountainous regions and reaching the coastline/shelf edge in the northern Barents Sea during short-term glacial intensification, is concomitant with the onset of the Northern Hemisphere Glaciation (3.6-2.4 Ma). (2) A transitional growth phase (2.4-1.0 Ma), during which the ice sheet expanded towards the southern Barents Sea and reached the northwestern Kara Sea. This is inferred from step-wise decrease of Siberian river-supplied smectite-rich sediments, likely caused by ice sheet blockade and possibly reduced sea ice formation in the Kara Sea as well as glacigenic wedge growth along the northwestern Barents Sea margin hampering entrainment and transport of sea ice sediments to the Arctic-Atlantic gateway. (3) Finally, large-scale glaciation in the Barents Sea occurred after 1 Ma with repeated advances to the shelf edge. The timing is inferred from ice grounding on the Yermak Plateau at about 0.95 Ma, and higher frequencies of gravity-driven mass movements along the western Barents Sea margin associated with expansive glacial growth.

Theoretical Models Based on a Flowchart Approach to Industrial Cluster Policy

This article examined the issue of whether or not the currency exchange rate, country risk, and cooperate tax rate affect decisions of multinational firms to invest in industrial clusters. First, if the exchange rate between a multinational company in an industry of diminishing returns to scale and a developing country is appreciated, then production in the developing country should increase. Second, if the investment period becomes longer, the currency exchange rate of a multinational company's country should be revalued more in order for it to further invest in the developing country. Third, if the investment period becomes longer, the developing country's risk should become less. Fourth, compensation for the developing country's high risk can be made by lowering its corporate tax rate.

Interindustrial Structure in the Asia-Pacific Region: Growth and Integration, by Using 2000 AIO Table

Over the past 20 years Asian countries have achieved a certain degree of economic growth and at the same time deepened spatial interdependence. In January 2006, IDE completed the 2000 Asian International Input-Output Table, which covers eight major East Asian countries/regions as well as Japan and the United States. Given the dynamic changes in the economies of East Asia, this paper attempts to summarize the characteristics and their patterns of change in industrial structures and trade structures of the countries/regions in the Asia-Pacific region from the three viewpoints of time, space, and industry, by using the AIO table for 1985, 1990, 1995, and 2000.

A unified framework of trade in value added : physical, monetary, exchange rates, and GHG emissions

Koopman et al. (2014) developed a method to consistently decompose gross exports in value-added terms that accommodate infinite repercussions of international and inter-sector transactions. This provides a better understanding of trade in value added in global value chains than does the conventional gross exports method, which is affected by double-counting problems. However, the new framework is based on monetary input--output (IO) tables and cannot distinguish prices from quantities; thus, it is unable to consider financial adjustments through the exchange market. In this paper, we propose a framework based on a physical IO system, characterized by its linear programming equivalent that can clarify the various complexities relevant to the existing indicators and is proved to be consistent with Koopman's results when the physical decompositions are evaluated in monetary terms. While international monetary tables are typically described in current U.S. dollars, the physical framework can elucidate the impact of price adjustments through the exchange market. An iterative procedure to calculate the exchange rates is proposed, and we also show that the physical framework is also convenient for considering indicators associated with greenhouse gas (GHG) emissions.

Spatial spillover effects in determining China's regional CO2 emission growth : 2007-2010

This paper proposes an alternative input-output based spatial-structural decomposition analysis to elucidate the role of domestic-regional heterogeneity and interregional spillover effects in determining China's regional CO2 emission growth. Our empirical results based on the 2007 and 2010 Chinese interregional input-output tables show that the changes in most regions' final demand scale, final expenditure structure and export scale give positive spatial spillover effects on other regions' CO2 emission growth, the changes in most regions' consumption and export preference help the reduction of other regions' CO2 emissions, the changes in production technology, and investment preference may give positive or negative impacts on other region's CO2 emission growth through domestic supply chains. For some regions, the aggregate spillover effect from other regions may be larger than the intra-regional effect in determining regional emission growth. All these facts can significantly help better and deeper understanding on the driving forces of China's regional CO2 emission growth, thus can enrich the policy implication concerning a narrow definition of "carbon leakage" through domestic-interregional trade, and relevant political consensus about the responsibility sharing between developed and developing regions inside China.

Sustainable Planning And Land Valuation, New Forms Of Suburban Growth In Areas Of The Spanish Mediterranean Coast

The present study analyzes residential models in coastal areas with large influxes of tourism, the sustainability of their planning and its repercussion on urban values. The project seeks to establish a methodology for territorial valuation through the analysis of externalities that have influenced urban growth and its impact on the formation of residential real estate values. This will make it possible to create a map for qualitative land valuation, resulting from a combination of environmental, landscape, social and productive valuations. This in turn will establish a reference value for each of the areas in question, as well as their spatial interrelations. These values become guidelines for the study of different territorial scenarios, which help improve the sustainable territorial planning process. This is a rating scale for urban planning. The results allow us to establish how the specific characteristics of the coast are valued and how they can be incorporated into sustainable development policies.

Impact attribution models to evaluate drought effects: economic impacts, risk analyses and management strategies in Spain and Chile

La sequía es un fenómeno natural que se origina por el descenso de las precipitaciones con respecto a una media, y que resulta en la disponibilidad insuficiente de agua para alguna actividad. La creciente presión que se ha venido ejerciendo sobre los recursos hídricos ha hecho que los impactos de la sequía se hayan visto agravados a la vez que ha desencadenado situaciones de escasez de agua en muchas partes del planeta. Los países con clima mediterráneo son especialmente vulnerables a las sequías, y, su crecimiento económico dependiente del agua da lugar a impactos importantes. Para reducir los impactos de la sequía es necesaria una reducción de la vulnerabilidad a las sequías que viene dada por una gestión más eficiente y por una mejor preparación. Para ello es muy importante disponer de información acerca de los impactos y el alcance de este fenómeno natural. Esta investigación trata de abarcar el tema de los impactos de las sequías, de manera que plantea todos los tipos de impactos que pueden darse y además compara sus efectos en dos países (España y Chile). Para ello se proponen modelos de atribución de impactos que sean capaces de medir las pérdidas económicas causadas por la falta de agua. Los modelos propuestos tienen una base econométrica en la que se incluyen variables clave a la hora de evaluar los impactos como es una variable relacionada con la disponibilidad de agua, y otras de otra naturaleza para distinguir los efectos causados por otras fuentes de variación. Estos modelos se adaptan según la fase del estudio en la que nos encontremos. En primer lugar se miden los impactos directos sobre el regadío y se introduce en el modelo un factor de aleatoriedad para evaluar el riesgo económico de sequía. Esto se hace a dos niveles geográficos (provincial y de Unidad de Demanda Agraria) y además en el último se introduce no solo el riesgo de oferta sino también el riesgo de demanda de agua. La introducción de la perspectiva de riesgo en el modelo da lugar a una herramienta de gestión del riesgo económico que puede ser utilizada para estrategias de planificación. Más adelante una extensión del modelo econométrico se desarrolla para medir los impactos en el sector agrario (impactos directos sobre el regadío y el secano e impactos indirectos sobre la Agro Industria) para ello se adapta el modelo y se calculan elasticidades concatenadas entre la falta de agua y los impactos secundarios. Por último se plantea un modelo econométrico para el caso de estudio en Chile y se evalúa el impacto de las sequías debidas al fenómeno de La Niña. iv Los resultados en general muestran el valor que brinda el conocimiento más preciso acerca de los impactos, ya que en muchas ocasiones se tiende a sobreestimar los daños realmente producidos por la falta de agua. Los impactos indirectos de la sequía confirman su alcance a la vez que son amortiguados a medida que nos acercamos al ámbito macroeconómico. En el caso de Chile, su diferente gestión muestra el papel que juegan el fenómeno de El Niño y La Niña sobre los precios de los principales cultivos del país y sobre el crecimiento del sector. Para reducir las pérdidas y su alcance se deben plantear más medidas de mitigación que centren su esfuerzo en una gestión eficiente del recurso. Además la prevención debe jugar un papel muy importante para reducir los riesgos que pueden sufrirse ante situaciones de escasez. ABSTRACT Drought is a natural phenomenon that originates by the decrease in rainfall in comparison to the average, and that results in water shortages for some activities. The increasing pressure on water resources has augmented the impact of droughts just as water scarcity has become an additional problem in many parts of the planet. Countries with Mediterranean climate are especially vulnerable to drought, and its waterdependent economic growth leads to significant impacts. To reduce the negative impacts it is necessary to deal with drought vulnerability, and to achieve this objective a more efficient management is needed. The availability of information about the impacts and the scope of droughts become highly important. This research attempts to encompass the issue of drought impacts, and therefore it characterizes all impact types that may occur and also compares its effects in two different countries (Spain and Chile). Impact attribution models are proposed in order to measure the economic losses caused by the lack of water. The proposed models are based on econometric approaches and they include key variables for measuring the impacts. Variables related to water availability, crop prices or time trends are included to be able to distinguish the effects caused by any of the possible sources. These models are adapted for each of the parts of the study. First, the direct impacts on irrigation are measured and a source of variability is introduced into the model to assess the economic risk of drought. This is performed at two geographic levels provincial and Agricultural Demand Unit. In the latter, not only the supply risk is considered but also the water demand risk side. The introduction of the risk perspective into the model results in a risk management tool that can be used for planning strategies. Then an extension of the econometric model is developed to measure the impacts on the agricultural sector (direct impacts on irrigated and rainfed productions and indirect impacts on the Agri-food Industry). For this aim the model is adapted and concatenated elasticities between the lack of water and the impacts are estimated. Finally an econometric model is proposed for the Chilean case study to evaluate the impact of droughts, especially caused by El Niño Southern Oscillation. The overall results show the value of knowing better about the precise impacts that often tend to be overestimated. The models allow for measuring accurate impacts due to the lack of water. Indirect impacts of drought confirm their scope while they confirm also its dilution as we approach the macroeconomic variables. In the case of Chile, different management strategies of the country show the role of ENSO phenomena on main crop prices and on economic trends. More mitigation measures focused on efficient resource management are necessary to reduce drought losses. Besides prevention must play an important role to reduce the risks that may be suffered due to shortages.

A new method for the identification of old-growth trees in National Forest Inventories: Application to Pinus halepensis Mill. stands in Spain

Old-growth trees play a very important role in the maintenance of biodiversity in forests. However, no clear definition is yet available to help identify them since tree age is usually not recorded in National Forest Inventories. To develop and test a new method to identify old-growth trees using a species-specific threshold for tree diameter in National Forest Inventories. Different nonlinear mixed models for diameter ? age were generated using data from the Spanish Forest Inventory in order to identify the most appropriate one for Aleppo pine in its South-western distribution area. The asymptote of the optimal model indicates the threshold diameter for defining an old-growth tree. Additionally, five site index curves were examined to analyze the influence of site quality on these models.

Mixing effect on volume growth of Fagus sylvatica and Pinus sylvestris is modulated by stand density

Despite the increasing relevance of mixed stands due to their potential benefits; little information is available with regard to the effect of mixtures on yield in forest systems. Hence, it is necessary to study inter-specific relationships, and the resulting yield in mixed stands, which may vary with stand development, site or stand density, etc. In Spain, the province of Navarra is considered one of the biodiversity reservoirs; however, mixed forests occupy only a small area, probably as a consequence of management plans, in which there is an excessive focus on the productivity aspect, favoring the presence of pure stands of the most marketable species. The aim of this paper is to study how growth efficiencies of beech (Fagus sylvatica) and pine (Pinus sylvestris) are modified by the admixture of the other species and to determine whether stand density modifies interspecific relationships and to what extent. Two models were fitted from Spanish National Forest Inventory data, for P. sylvestris and F. sylvatica respectively, which relate the growth efficiency of the species, i.e. the volume increment of the species divided by the species proportion by area, with dominant height, quadratic mean diameter, stocking degree, and the species proportions by area of each species. Growth efficiency of pine increased with the admixture of beech, decreasing this positive effect when stocking degree increased. However, the positive effect of pine admixture on beech growth was greater at higher stocking degrees. Growth efficiency of beech was also dependent on stand dominant height, resulting in a net negative mixing effect when stand dominant heights and stocking degrees were simultaneously low. There is a relatively large range of species proportions and stocking degrees which results in transgressive overyielding: higher volume increments in mixed stands than that of the most productive pure pine stands. We concluded that stocking degree is a key factor in between-species interactions, being the effects of mixing not always greater at higher stand densities, but it depends on species composition.

Damping models in the truncated derivative nonlinear Schrödinger equation

Four-dimensional flow in the phase space of three amplitudes of circularly polarized Alfven waves and one relative phase, resulting from a resonant three-wave truncation of the derivative nonlinear Schrödinger equation, has been analyzed; wave 1 is linearly unstable with growth rate , and waves 2 and 3 are stable with damping 2 and 3, respectively. The dependence of gross dynamical features on the damping model as characterized by the relation between damping and wave-vector ratios, 2 /3, k2 /k3, and the polarization of the waves, is discussed; two damping models, Landau k and resistive k2, are studied in depth. Very complex dynamics, such as multiple blue sky catastrophes and chaotic attractors arising from Feigenbaum sequences, and explosive bifurcations involving Intermittency-I chaos, are shown to be associated with the existence and loss of stability of certain fixed point P of the flow. Independently of the damping model, P may only exist as against flow contraction just requiring.In the case of right-hand RH polarization, point P may exist for all models other than Landau damping; for the resistive model, P may exist for RH polarization only if 2+3/2.

Modelos de métrica para sistemas electrónicos de adquisición de datos y de procesamiento para investigación clínica con dispositivos cardiacos implantables

RESUMEN Las enfermedades cardiovasculares constituyen en la actualidad la principal causa de mortalidad en el mundo y se prevé que sigan siéndolo en un futuro, generando además elevados costes para los sistemas de salud. Los dispositivos cardiacos implantables constituyen una de las opciones para el diagnóstico y el tratamiento de las alteraciones del ritmo cardiaco. La investigación clínica con estos dispositivos alcanza gran relevancia para combatir estas enfermedades que tanto afectan a nuestra sociedad. Tanto la industria farmacéutica y de tecnología médica, como los propios investigadores, cada día se ven involucrados en un mayor número de proyectos de investigación clínica. No sólo el incremento en su volumen, sino el aumento de la complejidad, están generando mayores gastos en las actividades asociadas a la investigación médica. Esto está conduciendo a las compañías del sector sanitario a estudiar nuevas soluciones que les permitan reducir los costes de los estudios clínicos. Las Tecnologías de la Información y las Comunicaciones han facilitado la investigación clínica, especialmente en la última década. Los sistemas y aplicaciones electrónicos han proporcionado nuevas posibilidades en la adquisición, procesamiento y análisis de los datos. Por otro lado, la tecnología web propició la aparición de los primeros sistemas electrónicos de adquisición de datos, que han ido evolucionando a lo largo de los últimos años. Sin embargo, la mejora y perfeccionamiento de estos sistemas sigue siendo crucial para el progreso de la investigación clínica. En otro orden de cosas, la forma tradicional de realizar los estudios clínicos con dispositivos cardiacos implantables precisaba mejorar el tratamiento de los datos almacenados por estos dispositivos, así como para su fusión con los datos clínicos recopilados por investigadores y pacientes. La justificación de este trabajo de investigación se basa en la necesidad de mejorar la eficiencia en la investigación clínica con dispositivos cardiacos implantables, mediante la reducción de costes y tiempos de desarrollo de los proyectos, y el incremento de la calidad de los datos recopilados y el diseño de soluciones que permitan obtener un mayor rendimiento de los datos mediante la fusión de datos de distintas fuentes o estudios. Con este fin se proponen como objetivos específicos de este proyecto de investigación dos nuevos modelos: - Un modelo de recuperación y procesamiento de datos para los estudios clínicos con dispositivos cardiacos implantables, que permita estructurar y estandarizar estos procedimientos, con el fin de reducir tiempos de desarrollo Modelos de Métrica para Sistemas Electrónicos de Adquisición de Datos y de Procesamiento para Investigación Clínica con Dispositivos Cardiacos Implantables de estas tareas, mejorar la calidad del resultado obtenido, disminuyendo en consecuencia los costes. - Un modelo de métrica integrado en un Sistema Electrónico de Adquisición de Datos (EDC) que permita analizar los resultados del proyecto de investigación y, particularmente del rendimiento obtenido del EDC, con el fin de perfeccionar estos sistemas y reducir tiempos y costes de desarrollo del proyecto y mejorar la calidad de los datos clínicos recopilados. Como resultado de esta investigación, el modelo de procesamiento propuesto ha permitido reducir el tiempo medio de procesamiento de los datos en más de un 90%, los costes derivados del mismo en más de un 85% y todo ello, gracias a la automatización de la extracción y almacenamiento de los datos, consiguiendo una mejora de la calidad de los mismos. Por otro lado, el modelo de métrica posibilita el análisis descriptivo detallado de distintos indicadores que caracterizan el rendimiento del proyecto de investigación clínica, haciendo factible además la comparación entre distintos estudios. La conclusión de esta tesis doctoral es que los resultados obtenidos han demostrado que la utilización en estudios clínicos reales de los dos modelos desarrollados ha conducido a una mejora en la eficiencia de los proyectos, reduciendo los costes globales de los mismos, disminuyendo los tiempos de ejecución, e incrementando la calidad de los datos recopilados. Las principales aportaciones de este trabajo de investigación al conocimiento científico son la implementación de un sistema de procesamiento inteligente de los datos almacenados por los dispositivos cardiacos implantables, la integración en el mismo de una base de datos global y optimizada para todos los modelos de dispositivos, la generación automatizada de un repositorio unificado de datos clínicos y datos de dispositivos cardiacos implantables, y el diseño de una métrica aplicada e integrable en los sistemas electrónicos de adquisición de datos para el análisis de resultados de rendimiento de los proyectos de investigación clínica. ABSTRACT Cardiovascular diseases are the main cause of death worldwide and it is expected to continue in the future, generating high costs for health care systems. Implantable cardiac devices have become one of the options for diagnosis and treatment of cardiac rhythm disorders. Clinical research with these devices has acquired great importance to fight against these diseases that affect so many people in our society. Both pharmaceutical and medical technology companies, and also investigators, are involved in an increasingly number of clinical research projects. The growth in volume and the increase in medical research complexity are contributing to raise the expenditure level associated with clinical investigation. This situation is driving health care sector companies to explore new solutions to reduce clinical trial costs. Information and Communication Technologies have facilitated clinical research, mainly in the last decade. Electronic systems and software applications have provided new possibilities in the acquisition, processing and analysis of clinical studies data. On the other hand, web technology contributed to the appearance of the first electronic data capture systems that have evolved during the last years. Nevertheless, improvement of these systems is still a key aspect for the progress of clinical research. On a different matter, the traditional way to develop clinical studies with implantable cardiac devices needed an improvement in the processing of the data stored by these devices, and also in the merging of these data with the data collected by investigators and patients. The rationale of this research is based on the need to improve the efficiency in clinical investigation with implantable cardiac devices, by means of reduction in costs and time of projects development, as well as improvement in the quality of information obtained from the studies and to obtain better performance of data through the merging of data from different sources or trials. The objective of this research project is to develop the next two models: • A model for the retrieval and processing of data for clinical studies with implantable cardiac devices, enabling structure and standardization of these procedures, in order to reduce the time of development of these tasks, to improve the quality of the results, diminish therefore costs. • A model of metric integrated in an Electronic Data Capture system (EDC) that allow to analyze the results of the research project, and particularly the EDC performance, in order to improve those systems and to reduce time and costs of the project, and to get a better quality of the collected clinical data. As a result of this work, the proposed processing model has led to a reduction of the average time for data processing by more than 90 per cent, of related costs by more than 85 per cent, and all of this, through automatic data retrieval and storage, achieving an improvement of quality of data. On the other hand, the model of metrics makes possible a detailed descriptive analysis of a set of indicators that characterize the performance of each research project, allowing inter‐studies comparison. This doctoral thesis results have demonstrated that the application of the two developed models in real clinical trials has led to an improvement in projects efficiency, reducing global costs, diminishing time in execution, and increasing quality of data collected. The main contributions to scientific knowledge of this research work are the implementation of an intelligent processing system for data stored by implantable cardiac devices, the integration in this system of a global and optimized database for all models of devices, the automatic creation of an unified repository of clinical data and data stored by medical devices, and the design of a metric to be applied and integrated in electronic data capture systems to analyze the performance results of clinical research projects.

Guidance for the development of accessibility evaluation tools following the Unified Software Development Process

Automated and semi-automated accessibility evaluation tools are key to streamline the process of accessibility assessment, and ultimately ensure that software products, contents, and services meet accessibility requirements. Different evaluation tools may better fit different needs and concerns, accounting for a variety of corporate and external policies, content types, invocation methods, deployment contexts, exploitation models, intended audiences and goals; and the specific overall process where they are introduced. This has led to the proliferation of many evaluation tools tailored to specific contexts. However, tool creators, who may be not familiar with the realm of accessibility and may be part of a larger project, lack any systematic guidance when facing the implementation of accessibility evaluation functionalities. Herein we present a systematic approach to the development of accessibility evaluation tools, leveraging the different artifacts and activities of a standardized development process model (the Unified Software Development Process), and providing templates of these artifacts tailored to accessibility evaluation tools. The work presented specially considers the work in progress in this area by the W3C/WAI Evaluation and Report Working Group (ERT WG)

Análisis de los factores de adopción de comercio electrónico en segmentos de consumidores finales. Aplicación al caso español

El comercio electrónico ha experimentado un fuerte crecimiento en los últimos años, favorecido especialmente por el aumento de las tasas de penetración de Internet en todo el mundo. Sin embargo, no todos los países están evolucionando de la misma manera, con un espectro que va desde las naciones pioneras en desarrollo de tecnologías de la información y comunicaciones, que cuentan con una elevado porcentaje de internautas y de compradores online, hasta las rezagadas de rápida adopción en las que, pese a contar con una menor penetración de acceso, presentan una alta tasa de internautas compradores. Entre ambos extremos se encuentran países como España que, aunque alcanzó hace años una tasa considerable de penetración de usuarios de Internet, no ha conseguido una buena tasa de transformación de internautas en compradores. Pese a que el comercio electrónico ha experimentado importantes aumentos en los últimos años, sus tasas de crecimiento siguen estando por debajo de países con características socio-económicas similares. Para intentar conocer las razones que afectan a la adopción del comercio por parte de los compradores, la investigación científica del fenómeno ha empleado diferentes enfoques teóricos. De entre todos ellos ha destacado el uso de los modelos de adopción, proveniente de la literatura de adopción de sistemas de información en entornos organizativos. Estos modelos se basan en las percepciones de los compradores para determinar qué factores pueden predecir mejor la intención de compra y, en consecuencia, la conducta real de compra de los usuarios. Pese a que en los últimos años han proliferado los trabajos de investigación que aplican los modelos de adopción al comercio electrónico, casi todos tratan de validar sus hipótesis mediante el análisis de muestras de consumidores tratadas como un único conjunto, y del que se obtienen conclusiones generales. Sin embargo, desde el origen del marketing, y en especial a partir de la segunda mitad del siglo XIX, se considera que existen diferencias en el comportamiento de los consumidores, que pueden ser debidas a características demográficas, sociológicas o psicológicas. Estas diferencias se traducen en necesidades distintas, que sólo podrán ser satisfechas con una oferta adaptada por parte de los vendedores. Además, por contar el comercio electrónico con unas características particulares que lo diferencian del comercio tradicional –especialmente por la falta de contacto físico entre el comprador y el producto– a las diferencias en la adopción para cada consumidor se le añaden las diferencias derivadas del tipo de producto adquirido, que si bien habían sido consideradas en el canal físico, en el comercio electrónico cobran especial relevancia. A la vista de todo ello, el presente trabajo pretende abordar el estudio de los factores determinantes de la intención de compra y la conducta real de compra en comercio electrónico por parte del consumidor final español, teniendo en cuenta el tipo de segmento al que pertenezca dicho comprador y el tipo de producto considerado. Para ello, el trabajo contiene ocho apartados entre los que se encuentran cuatro bloques teóricos y tres bloques empíricos, además de las conclusiones. Estos bloques dan lugar a los siguientes ocho capítulos por orden de aparición en el trabajo: introducción, situación del comercio electrónico, modelos de adopción de tecnología, segmentación en comercio electrónico, diseño previo del trabajo empírico, diseño de la investigación, análisis de los resultados y conclusiones. El capítulo introductorio justifica la relevancia de la investigación, además de fijar los objetivos, la metodología y las fases seguidas para el desarrollo del trabajo. La justificación se complementa con el segundo capítulo, que cuenta con dos elementos principales: en primer lugar se define el concepto de comercio electrónico y se hace una breve retrospectiva desde sus orígenes hasta la situación actual en un contexto global; en segundo lugar, el análisis estudia la evolución del comercio electrónico en España, mostrando su desarrollo y situación presente a partir de sus principales indicadores. Este apartado no sólo permite conocer el contexto de la investigación, sino que además permite contrastar la relevancia de la muestra utilizada en el presente estudio con el perfil español respecto al comercio electrónico. Los capítulos tercero –modelos de adopción de tecnologías– y cuarto –segmentación en comercio electrónico– sientan las bases teóricas necesarias para abordar el estudio. En el capítulo tres se hace una revisión general de la literatura de modelos de adopción de tecnología y, en particular, de los modelos de adopción empleados en el ámbito del comercio electrónico. El resultado de dicha revisión deriva en la construcción de un modelo adaptado basado en los modelos UTAUT (Unified Theory of Acceptance and Use of Technology, Teoría unificada de la aceptación y el uso de la tecnología) y UTAUT2, combinado con dos factores específicos de adopción del comercio electrónico: el riesgo percibido y la confianza percibida. Por su parte, en el capítulo cuatro se revisan las metodologías de segmentación de clientes y productos empleadas en la literatura. De dicha revisión se obtienen un amplio conjunto de variables de las que finalmente se escogen nueve variables de clasificación que se consideran adecuadas tanto por su adaptación al contexto del comercio electrónico como por su adecuación a las características de la muestra empleada para validar el modelo. Las nueve variables se agrupan en tres conjuntos: variables de tipo socio-demográfico –género, edad, nivel de estudios, nivel de ingresos, tamaño de la unidad familiar y estado civil–, de comportamiento de compra – experiencia de compra por Internet y frecuencia de compra por Internet– y de tipo psicográfico –motivaciones de compra por Internet. La segunda parte del capítulo cuatro se dedica a la revisión de los criterios empleados en la literatura para la clasificación de los productos en el contexto del comercio electrónico. De dicha revisión se obtienen quince grupos de variables que pueden tomar un total de treinta y cuatro valores, lo que deriva en un elevado número de combinaciones posibles. Sin embargo, pese a haber sido utilizados en el contexto del comercio electrónico, no en todos los casos se ha comprobado la influencia de dichas variables respecto a la intención de compra o la conducta real de compra por Internet; por este motivo, y con el objetivo de definir una clasificación robusta y abordable de tipos de productos, en el capitulo cinco se lleva a cabo una validación de las variables de clasificación de productos mediante un experimento previo con 207 muestras. Seleccionando sólo aquellas variables objetivas que no dependan de la interpretación personal del consumidores y que determinen grupos significativamente distintos respecto a la intención y conducta de compra de los consumidores, se obtiene un modelo de dos variables que combinadas dan lugar a cuatro tipos de productos: bien digital, bien no digital, servicio digital y servicio no digital. Definidos el modelo de adopción y los criterios de segmentación de consumidores y productos, en el sexto capítulo se desarrolla el modelo completo de investigación formado por un conjunto de hipótesis obtenidas de la revisión de la literatura de los capítulos anteriores, en las que se definen las hipótesis de investigación con respecto a las influencias esperadas de las variables de segmentación sobre las relaciones del modelo de adopción. Este modelo confiere a la investigación un carácter social y de tipo fundamentalmente exploratorio, en el que en muchos casos ni siquiera se han encontrado evidencias empíricas previas que permitan el enunciado de hipótesis sobre la influencia de determinadas variables de segmentación. El capítulo seis contiene además la descripción del instrumento de medida empleado en la investigación, conformado por un total de 125 preguntas y sus correspondientes escalas de medida, así como la descripción de la muestra representativa empleada en la validación del modelo, compuesta por un grupo de 817 personas españolas o residentes en España. El capítulo siete constituye el núcleo del análisis empírico del trabajo de investigación, que se compone de dos elementos fundamentales. Primeramente se describen las técnicas estadísticas aplicadas para el estudio de los datos que, dada la complejidad del análisis, se dividen en tres grupos fundamentales: Método de mínimos cuadrados parciales (PLS, Partial Least Squares): herramienta estadística de análisis multivariante con capacidad de análisis predictivo que se emplea en la determinación de las relaciones estructurales de los modelos propuestos. Análisis multigrupo: conjunto de técnicas que permiten comparar los resultados obtenidos con el método PLS entre dos o más grupos derivados del uso de una o más variables de segmentación. En este caso se emplean cinco métodos de comparación, lo que permite asimismo comparar los rendimientos de cada uno de los métodos. Determinación de segmentos no identificados a priori: en el caso de algunas de las variables de segmentación no existe un criterio de clasificación definido a priori, sino que se obtiene a partir de la aplicación de técnicas estadísticas de clasificación. En este caso se emplean dos técnicas fundamentales: análisis de componentes principales –dado el elevado número de variables empleadas para la clasificación– y análisis clúster –del que se combina una técnica jerárquica que calcula el número óptimo de segmentos, con una técnica por etapas que es más eficiente en la clasificación, pero exige conocer el número de clústeres a priori. La aplicación de dichas técnicas estadísticas sobre los modelos resultantes de considerar los distintos criterios de segmentación, tanto de clientes como de productos, da lugar al análisis de un total de 128 modelos de adopción de comercio electrónico y 65 comparaciones multigrupo, cuyos resultados y principales consideraciones son elaboradas a lo largo del capítulo. Para concluir, el capítulo ocho recoge las conclusiones del trabajo divididas en cuatro partes diferenciadas. En primer lugar se examina el grado de alcance de los objetivos planteados al inicio de la investigación; después se desarrollan las principales contribuciones que este trabajo aporta tanto desde el punto de vista metodológico, como desde los punto de vista teórico y práctico; en tercer lugar, se profundiza en las conclusiones derivadas del estudio empírico, que se clasifican según los criterios de segmentación empleados, y que combinan resultados confirmatorios y exploratorios; por último, el trabajo recopila las principales limitaciones de la investigación, tanto de carácter teórico como empírico, así como aquellos aspectos que no habiendo podido plantearse dentro del contexto de este estudio, o como consecuencia de los resultados alcanzados, se presentan como líneas futuras de investigación. ABSTRACT Favoured by an increase of Internet penetration rates across the globe, electronic commerce has experienced a rapid growth over the last few years. Nevertheless, adoption of electronic commerce has differed from one country to another. On one hand, it has been observed that countries leading e-commerce adoption have a large percentage of Internet users as well as of online purchasers; on the other hand, other markets, despite having a low percentage of Internet users, show a high percentage of online buyers. Halfway between those two ends of the spectrum, we find countries such as Spain which, despite having moderately high Internet penetration rates and similar socio-economic characteristics as some of the leading countries, have failed to turn Internet users into active online buyers. Several theoretical approaches have been taken in an attempt to define the factors that influence the use of electronic commerce systems by customers. One of the betterknown frameworks to characterize adoption factors is the acceptance modelling theory, which is derived from the information systems adoption in organizational environments. These models are based on individual perceptions on which factors determine purchase intention, as a mean to explain users’ actual purchasing behaviour. Even though research on electronic commerce adoption models has increased in terms of volume and scope over the last years, the majority of studies validate their hypothesis by using a single sample of consumers from which they obtain general conclusions. Nevertheless, since the birth of marketing, and more specifically from the second half of the 19th century, differences in consumer behaviour owing to demographic, sociologic and psychological characteristics have also been taken into account. And such differences are generally translated into different needs that can only be satisfied when sellers adapt their offer to their target market. Electronic commerce has a number of features that makes it different when compared to traditional commerce; the best example of this is the lack of physical contact between customers and products, and between customers and vendors. Other than that, some differences that depend on the type of product may also play an important role in electronic commerce. From all the above, the present research aims to address the study of the main factors influencing purchase intention and actual purchase behaviour in electronic commerce by Spanish end-consumers, taking into consideration both the customer group to which they belong and the type of product being purchased. In order to achieve this goal, this Thesis is structured in eight chapters: four theoretical sections, three empirical blocks and a final section summarizing the conclusions derived from the research. The chapters are arranged in sequence as follows: introduction, current state of electronic commerce, technology adoption models, electronic commerce segmentation, preliminary design of the empirical work, research design, data analysis and results, and conclusions. The introductory chapter offers a detailed justification of the relevance of this study in the context of e-commerce adoption research; it also sets out the objectives, methodology and research stages. The second chapter further expands and complements the introductory chapter, focusing on two elements: the concept of electronic commerce and its evolution from a general point of view, and the evolution of electronic commerce in Spain and main indicators of adoption. This section is intended to allow the reader to understand the research context, and also to serve as a basis to justify the relevance and representativeness of the sample used in this study. Chapters three (technology acceptance models) and four (segmentation in electronic commerce) set the theoretical foundations for the study. Chapter 3 presents a thorough literature review of technology adoption modelling, focusing on previous studies on electronic commerce acceptance. As a result of the literature review, the research framework is built upon a model based on UTAUT (Unified Theory of Acceptance and Use of Technology) and its evolution, UTAUT2, including two specific electronic commerce adoption factors: perceived risk and perceived trust. Chapter 4 deals with client and product segmentation methodologies used by experts. From the literature review, a wide range of classification variables is studied, and a shortlist of nine classification variables has been selected for inclusion in the research. The criteria for variable selection were their adequacy to electronic commerce characteristics, as well as adequacy to the sample characteristics. The nine variables have been classified in three groups: socio-demographic (gender, age, education level, income, family size and relationship status), behavioural (experience in electronic commerce and frequency of purchase) and psychographic (online purchase motivations) variables. The second half of chapter 4 is devoted to a review of the product classification criteria in electronic commerce. The review has led to the identification of a final set of fifteen groups of variables, whose combination offered a total of thirty-four possible outputs. However, due to the lack of empirical evidence in the context of electronic commerce, further investigation on the validity of this set of product classifications was deemed necessary. For this reason, chapter 5 proposes an empirical study to test the different product classification variables with 207 samples. A selection of product classifications including only those variables that are objective, able to identify distinct groups and not dependent on consumers’ point of view, led to a final classification of products which consisted on two groups of variables for the final empirical study. The combination of these two groups gave rise to four types of products: digital and non-digital goods, and digital and non-digital services. Chapter six characterizes the research –social, exploratory research– and presents the final research model and research hypotheses. The exploratory nature of the research becomes patent in instances where no prior empirical evidence on the influence of certain segmentation variables was found. Chapter six also includes the description of the measurement instrument used in the research, consisting of a total of 125 questions –and the measurement scales associated to each of them– as well as the description of the sample used for model validation (consisting of 817 Spanish residents). Chapter 7 is the core of the empirical analysis performed to validate the research model, and it is divided into two separate parts: description of the statistical techniques used for data analysis, and actual data analysis and results. The first part is structured in three different blocks: Partial Least Squares Method (PLS): the multi-variable analysis is a statistical method used to determine structural relationships of models and their predictive validity; Multi-group analysis: a set of techniques that allow comparing the outcomes of PLS analysis between two or more groups, by using one or more segmentation variables. More specifically, five comparison methods were used, which additionally gives the opportunity to assess the efficiency of each method. Determination of a priori undefined segments: in some cases, classification criteria did not necessarily exist for some segmentation variables, such as customer motivations. In these cases, the application of statistical classification techniques is required. For this study, two main classification techniques were used sequentially: principal component factor analysis –in order to reduce the number of variables– and cluster analysis. The application of the statistical methods to the models derived from the inclusion of the various segmentation criteria –for both clients and products–, led to the analysis of 128 different electronic commerce adoption models and 65 multi group comparisons. Finally, chapter 8 summarizes the conclusions from the research, divided into four parts: first, an assessment of the degree of achievement of the different research objectives is offered; then, methodological, theoretical and practical implications of the research are drawn; this is followed by a discussion on the results from the empirical study –based on the segmentation criteria for the research–; fourth, and last, the main limitations of the research –both empirical and theoretical– as well as future avenues of research are detailed.

Discrete (MD) and continuum (DD) simulations of void growth in single crystals.

Void growth in ductile materials is an important problem from the fundamental and technological viewpoint. Most of the models developed to quantify and understand the void growth process did not take into account two important factors: the anisotropic nature of plastic flow in single crystals and the size effects that appear when plastic flow is confined into very small regions.