Steady-state function of the ubiquitous mammalian Na/H exchanger (NHE1) in relation to dimer coupling models with 2Na/2H stoichiometry

We describe the steady-state function of the ubiquitous mammalian Na/H exchanger (NHE)1 isoform in voltage-clamped Chinese hamster ovary cells, as well as other cells, using oscillating pH-sensitive microelectrodes to quantify proton fluxes via extracellular pH gradients. Giant excised patches could not be used as gigaseal formation disrupts NHE activity within the patch. We first analyzed forward transport at an extracellular pH of 8.2 with no cytoplasmic Na (i.e., nearly zero-trans). The extracellular Na concentration dependence is sigmoidal at a cytoplasmic pH of 6.8 with a Hill coefficient of 1.8. In contrast, at a cytoplasmic pH of 6.0, the Hill coefficient is <1, and Na dependence often appears biphasic. Results are similar for mouse skin fibroblasts and for an opossum kidney cell line that expresses the NHE3 isoform, whereas NHE1(-/-) skin fibroblasts generate no proton fluxes in equivalent experiments. As proton flux is decreased by increasing cytoplasmic pH, the half-maximal concentration (K(1/2)) of extracellular Na decreases less than expected for simple consecutive ion exchange models. The K(1/2) for cytoplasmic protons decreases with increasing extracellular Na, opposite to predictions of consecutive exchange models. For reverse transport, which is robust at a cytoplasmic pH of 7.6, the K(1/2) for extracellular protons decreases only a factor of 0.4 when maximal activity is decreased fivefold by reducing cytoplasmic Na. With 140 mM of extracellular Na and no cytoplasmic Na, the K(1/2) for cytoplasmic protons is 50 nM (pH 7.3; Hill coefficient, 1.5), and activity decreases only 25% with extracellular acidification from 8.5 to 7.2. Most data can be reconstructed with two very different coupled dimer models. In one model, monomers operate independently at low cytoplasmic pH but couple to translocate two ions in "parallel" at alkaline pH. In the second "serial" model, each monomer transports two ions, and translocation by one monomer allosterically promotes translocation by the paired monomer in opposite direction. We conclude that a large fraction of mammalian Na/H activity may occur with a 2Na/2H stoichiometry.

The Future of Ubiquitous Learning

This book explores emerging pedagogical perspectives based on the design of new learning spaces supported by digital technologies and brings together some of the best research in this field. The book is divided into three themes: foundations of emerging pedagogies, learning designs for emerging pedagogies and, adaptive and personalized learning. The chapters provide up-to-date information about new pedagogical proposals, and examples for acquiring the requisite skills to both design and support learning opportunities that improve the potential of available technologies.

Global Cultural Law and Policy in the Age of Ubiquitous Internet

Digital technologies and the Internet in particular have transformed the ways we create, distribute, use, reuse and consume cultural content; have impacted on the workings of the cultural industries, and more generally on the processes of making, experiencing and remembering culture in local and global spaces. Yet, few of these, often profound, transformations have found reflection in law and institutional design. Cultural policy toolkits, in particular at the international level, are still very much offline/analogue and conceive of culture as static property linked to national sovereignty and state boundaries. The article describes this state of affairs and asks the key question of whether there is a need to reform global cultural law and policy and if yes, what the essential elements of such a reform should be.

Effects, but no interactions, of ubiquitous pesticide and parasite stressors on honey bee (Apis mellifera) lifespan and behaviour in a colony environment

Interactions between pesticides and parasites are believed to be responsible for increased mortality of honey bee (Apis mellifera) colonies in the northern hemisphere. Previous efforts have employed experimental approaches using small groups under laboratory conditions to investigate influence of these stressors on honey bee physiology and behaviour, although both the colony level and field conditions play a key role for eusocial honey bees. Here, we challenged honey bee workers under in vivo colony conditions with sublethal doses of the neonicotinoid thiacloprid, the miticide tau-fluvalinate and the endoparasite Nosema ceranae, to investigate potential effects on longevity and behaviour using observation hives. In contrast to previous laboratory studies, our results do not suggest interactions among stressors, but rather lone effects of pesticides and the parasite on mortality and behaviour, respectively. These effects appear to be weak due to different outcomes at the two study sites, thereby suggesting that the role of thiacloprid, tau-fluvalinate and N. ceranae and interactions among them may have been overemphasized. In the future, investigations into the effects of honey bee stressors should prioritize the use of colonies maintained under a variety of environmental conditions in order to obtain more biologically relevant data.

Adapting autonomously classification data mining algorithms for ubiquitous devices

Abstract Due to recent scientific and technological advances in information sys¬tems, it is now possible to perform almost every application on a mobile device. The need to make sense of such devices more intelligent opens an opportunity to design data mining algorithm that are able to autonomous execute in local devices to provide the device with knowledge. The problem behind autonomous mining deals with the proper configuration of the algorithm to produce the most appropriate results. Contextual information together with resource information of the device have a strong impact on both the feasibility of a particu¬lar execution and on the production of the proper patterns. On the other hand, performance of the algorithm expressed in terms of efficacy and efficiency highly depends on the features of the dataset to be analyzed together with values of the parameters of a particular implementation of an algorithm. However, few existing approaches deal with autonomous configuration of data mining algorithms and in any case they do not deal with contextual or resources information. Both issues are of particular significance, in particular for social net¬works application. In fact, the widespread use of social networks and consequently the amount of information shared have made the need of modeling context in social application a priority. Also the resource consumption has a crucial role in such platforms as the users are using social networks mainly on their mobile devices. This PhD thesis addresses the aforementioned open issues, focusing on i) Analyzing the behavior of algorithms, ii) mapping contextual and resources information to find the most appropriate configuration iii) applying the model for the case of a social recommender. Four main contributions are presented: - The EE-Model: is able to predict the behavior of a data mining algorithm in terms of resource consumed and accuracy of the mining model it will obtain. - The SC-Mapper: maps a situation defined by the context and resource state to a data mining configuration. - SOMAR: is a social activity (event and informal ongoings) recommender for mobile devices. - D-SOMAR: is an evolution of SOMAR which incorporates the configurator in order to provide updated recommendations. Finally, the experimental validation of the proposed contributions using synthetic and real datasets allows us to achieve the objectives and answer the research questions proposed for this dissertation.

Ubiquitous green computing techniques for high demand applications in smart environments

Ubiquitous sensor network deployments, such as the ones found in Smart cities and Ambient intelligence applications, require constantly increasing high computational demands in order to process data and offer services to users. The nature of these applications imply the usage of data centers. Research has paid much attention to the energy consumption of the sensor nodes in WSNs infrastructures. However, supercomputing facilities are the ones presenting a higher economic and environmental impact due to their very high power consumption. The latter problem, however, has been disregarded in the field of smart environment services. This paper proposes an energy-minimization workload assignment technique, based on heterogeneity and application-awareness, that redistributes low-demand computational tasks from high-performance facilities to idle nodes with low and medium resources in the WSN infrastructure. These non-optimal allocation policies reduce the energy consumed by the whole infrastructure and the total execution time.

Self-configuring data mining for ubiquitous computing

Ubiquitous computing software needs to be autonomous so that essential decisions such as how to configure its particular execution are self-determined. Moreover, data mining serves an important role for ubiquitous computing by providing intelligence to several types of ubiquitous computing applications. Thus, automating ubiquitous data mining is also crucial. We focus on the problem of automatically configuring the execution of a ubiquitous data mining algorithm. In our solution, we generate configuration decisions in a resource aware and context aware manner since the algorithm executes in an environment in which the context often changes and computing resources are often severely limited. We propose to analyze the execution behavior of the data mining algorithm by mining its past executions. By doing so, we discover the effects of resource and context states as well as parameter settings on the data mining quality. We argue that a classification model is appropriate for predicting the behavior of an algorithm?s execution and we concentrate on decision tree classifier. We also define taxonomy on data mining quality so that tradeoff between prediction accuracy and classification specificity of each behavior model that classifies by a different abstraction of quality, is scored for model selection. Behavior model constituents and class label transformations are formally defined and experimental validation of the proposed approach is also performed.

Collaborative data stream mining in ubiquitous environments using dynamic classifier selection

In ubiquitous data stream mining applications, different devices often aim to learn concepts that are similar to some extent. In these applications, such as spam filtering or news recommendation, the data stream underlying concept (e.g., interesting mail/news) is likely to change over time. Therefore, the resultant model must be continuously adapted to such changes. This paper presents a novel Collaborative Data Stream Mining (Coll-Stream) approach that explores the similarities in the knowledge available from other devices to improve local classification accuracy. Coll-Stream integrates the community knowledge using an ensemble method where the classifiers are selected and weighted based on their local accuracy for different partitions of the feature space. We evaluate Coll-Stream classification accuracy in situations with concept drift, noise, partition granularity and concept similarity in relation to the local underlying concept. The experimental results show that Coll-Stream resultant model achieves stability and accuracy in a variety of situations using both synthetic and real world datasets.

Contribution towards intelligent service management in wearable and ubiquitous devices

Hoy en día asistimos a un creciente interés por parte de la sociedad hacia el cuidado de la salud. Esta afirmación viene apoyada por dos realidades. Por una parte, el aumento de las prácticas saludables (actividad deportiva, cuidado de la alimentación, etc.). De igual manera, el auge de los dispositivos inteligentes (relojes, móviles o pulseras) capaces de medir distintos parámetros físicos como el pulso cardíaco, el ritmo respiratorio, la distancia recorrida, las calorías consumidas, etc. Combinando ambos factores (interés por el estado de salud y disponibilidad comercial de dispositivos inteligentes) están surgiendo multitud de aplicaciones capaces no solo de controlar el estado actual de salud, también de recomendar al usuario cambios de hábitos que lleven hacia una mejora en su condición física. En este contexto, los llamados dispositivos llevables (weareables) unidos al paradigma de Internet de las cosas (IoT, del inglés Internet of Things) permiten la aparición de nuevos nichos de mercado para aplicaciones que no solo se centran en la mejora de la condición física, ya que van más allá proponiendo soluciones para el cuidado de pacientes enfermos, la vigilancia de niños o ancianos, la defensa y la seguridad, la monitorización de agentes de riesgo (como bomberos o policías) y un largo etcétera de aplicaciones por llegar. El paradigma de IoT se puede desarrollar basándose en las existentes redes de sensores inalámbricos (WSN, del inglés Wireless Sensor Network). La conexión de los ya mencionados dispositivos llevables a estas redes puede facilitar la transición de nuevos usuarios hacia aplicaciones IoT. Pero uno de los problemas intrínsecos a estas redes es su heterogeneidad. En efecto, existen multitud de sistemas operativos, protocolos de comunicación, plataformas de desarrollo, soluciones propietarias, etc. El principal objetivo de esta tesis es realizar aportaciones significativas para solucionar no solo el problema de la heterogeneidad, sino también de dotar de mecanismos de seguridad suficientes para salvaguardad la integridad de los datos intercambiados en este tipo de aplicaciones. Algo de suma importancia ya que los datos médicos y biométricos de los usuarios están protegidos por leyes nacionales y comunitarias. Para lograr dichos objetivos, se comenzó con la realización de un completo estudio del estado del arte en tecnologías relacionadas con el marco de investigación (plataformas y estándares para WSNs e IoT, plataformas de implementación distribuidas, dispositivos llevables y sistemas operativos y lenguajes de programación). Este estudio sirvió para tomar decisiones de diseño fundamentadas en las tres contribuciones principales de esta tesis: un bus de servicios para dispositivos llevables (WDSB, Wearable Device Service Bus) basado en tecnologías ya existentes tales como ESB, WWBAN, WSN e IoT); un protocolo de comunicaciones inter-dominio para dispositivos llevables (WIDP, Wearable Inter-Domain communication Protocol) que integra en una misma solución protocolos capaces de ser implementados en dispositivos de bajas capacidades (como lo son los dispositivos llevables y los que forman parte de WSNs); y finalmente, la tercera contribución relevante es una propuesta de seguridad para WSN basada en la aplicación de dominios de confianza. Aunque las contribuciones aquí recogidas son de aplicación genérica, para su validación se utilizó un escenario concreto de aplicación: una solución para control de parámetros físicos en entornos deportivos, desarrollada dentro del proyecto europeo de investigación “LifeWear”. En este escenario se desplegaron todos los elementos necesarios para validar las contribuciones principales de esta tesis y, además, se realizó una aplicación para dispositivos móviles por parte de uno de los socios del proyecto (lo que contribuyó con una validación externa de la solución). En este escenario se usaron dispositivos llevables tales como un reloj inteligente, un teléfono móvil con sistema operativo Android y un medidor del ritmo cardíaco inalámbrico capaz de obtener distintos parámetros fisiológicos del deportista. Sobre este escenario se realizaron diversas pruebas de validación mediante las cuales se obtuvieron resultados satisfactorios. ABSTRACT Nowadays, society is shifting towards a growing interest and concern on health care. This phenomenon can be acknowledged by two facts: first, the increasing number of people practising some kind of healthy activity (sports, balanced diet, etc.). Secondly, the growing number of commercial wearable smart devices (smartwatches or bands) able to measure physiological parameters such as heart rate, breathing rate, distance or consumed calories. A large number of applications combining both facts are appearing. These applications are not only able to monitor the health status of the user, but also to provide recommendations about routines in order to improve the mentioned health status. In this context, wearable devices merged with the Internet of Things (IoT) paradigm enable the proliferation of new market segments for these health wearablebased applications. Furthermore, these applications can provide solutions for the elderly or baby care, in-hospital or in-home patient monitoring, security and defence fields or an unforeseen number of future applications. The introduced IoT paradigm can be developed with the usage of existing Wireless Sensor Networks (WSNs) by connecting the novel wearable devices to them. In this way, the migration of new users and actors to the IoT environment will be eased. However, a major issue appears in this environment: heterogeneity. In fact, there is a large number of operating systems, hardware platforms, communication and application protocols or programming languages, each of them with unique features. The main objective of this thesis is defining and implementing a solution for the intelligent service management in wearable and ubiquitous devices so as to solve the heterogeneity issues that are presented when dealing with interoperability and interconnectivity of devices and software of different nature. Additionally, a security schema based on trust domains is proposed as a solution to the privacy problems arising when private data (e.g., biomedical parameters or user identification) is broadcasted in a wireless network. The proposal has been made after a comprehensive state-of-the-art analysis, and includes the design of a Wearable Device Service Bus (WDSB) including the technologies collected in the requirement analysis (ESB, WWBAN, WSN and IoT). Applications are able to access the WSN services regardless of the platform and operating system where they are running. Besides, this proposal also includes the design of a Wearable Inter-Domain communication Protocols set (WIDP) which integrates lightweight protocols suitable to be used in low-capacities devices (REST, JSON, AMQP, CoAP, etc...). Furthermore, a security solution for service management based on a trustworthy domains model to deploy security services in WSNs has been designed. Although the proposal is a generic framework for applications based on services provided by wearable devices, an application scenario for testing purposes has been included. In this validation scenario it has been presented an autonomous physical condition performance system, based on a WSN, bringing the possibility to include several elements in an IoT scenario: a smartwatch, a physiological monitoring device and a smartphone. In summary, the general objective of this thesis is solving the heterogeneity and security challenges arising when developing applications for WSNs and wearable devices. As it has been presented in the thesis, the solution proposed has been successfully validated in a real scenario and the obtained results were satisfactory.

Autonomous classification models in ubiquitous environments

Stream-mining approach is defined as a set of cutting-edge techniques designed to process streams of data in real time, in order to extract knowledge. In the particular case of classification, stream-mining has to adapt its behaviour to the volatile underlying data distributions, what has been called concept drift. Moreover, it is important to note that concept drift may lead to situations where predictive models become invalid and have therefore to be updated to represent the actual concepts that data poses. In this context, there is a specific type of concept drift, known as recurrent concept drift, where the concepts represented by data have already appeared in the past. In those cases the learning process could be saved or at least minimized by applying a previously trained model. This could be extremely useful in ubiquitous environments that are characterized by the existence of resource constrained devices. To deal with the aforementioned scenario, meta-models can be used in the process of enhancing the drift detection mechanisms used by data stream algorithms, by representing and predicting when the change will occur. There are some real-world situations where a concept reappears, as in the case of intrusion detection systems (IDS), where the same incidents or an adaptation of them usually reappear over time. In these environments the early prediction of drift by means of a better knowledge of past models can help to anticipate to the change, thus improving efficiency of the model regarding the training instances needed. By means of using meta-models as a recurrent drift detection mechanism, the ability to share concepts representations among different data mining processes is open. That kind of exchanges could improve the accuracy of the resultant local model as such model may benefit from patterns similar to the local concept that were observed in other scenarios, but not yet locally. This would also improve the efficiency of training instances used during the classification process, as long as the exchange of models would aid in the application of already trained recurrent models, that have been previously seen by any of the collaborative devices. Which it is to say that the scope of recurrence detection and representation is broaden. In fact the detection, representation and exchange of concept drift patterns would be extremely useful for the law enforcement activities fighting against cyber crime. Being the information exchange one of the main pillars of cooperation, national units would benefit from the experience and knowledge gained by third parties. Moreover, in the specific scope of critical infrastructures protection it is crucial to count with information exchange mechanisms, both from a strategical and technical scope. The exchange of concept drift detection schemes in cyber security environments would aid in the process of preventing, detecting and effectively responding to threads in cyber space. Furthermore, as a complement of meta-models, a mechanism to assess the similarity between classification models is also needed when dealing with recurrent concepts. In this context, when reusing a previously trained model a rough comparison between concepts is usually made, applying boolean logic. The introduction of fuzzy logic comparisons between models could lead to a better efficient reuse of previously seen concepts, by applying not just equal models, but also similar ones. This work faces the aforementioned open issues by means of: the MMPRec system, that integrates a meta-model mechanism and a fuzzy similarity function; a collaborative environment to share meta-models between different devices; a recurrent drift generator that allows to test the usefulness of recurrent drift systems, as it is the case of MMPRec. Moreover, this thesis presents an experimental validation of the proposed contributions using synthetic and real datasets.

Ubiquitous, heritable damage in cell populations that survive treatment with methotrexate

A permanent line of mouse embryo fibroblasts was treated with concentrations of the anticancer drug methotrexate (MTX) that left 20–50% surviving colonies. The surviving population initially multiplied at a much slower rate than controls after subculture in the absence of the drug, and required 9–12 days of serial subculture, with selective growth of the faster growing cells, to approximate the control rate. To determine the distribution of growth rates of cells in the original posttreatment populations, many single cells were isolated in multiwell plates immediately after the treatment period, and the resulting clones were serially subcultured. Most of the control clones underwent about 2 population doublings per day (PD/D). Almost all the survivors of MTX treatment multiplied at heterogeneously reduced rates, ranging from 0.6 PD/D to as high as control rates for a very few clones. They maintained the reduced rates through many subcultivations. The heritability of the reduced growth rates indicates that most cells that retain proliferative capacity after treatment with MTX carry random genetic damage that is perpetuated through many divisions of their progeny. Similar results have been described for cells that survive x-irradiation, and suggest random genetic damage is a common occurrence among cells in rapidly growing tissues that survive cytotoxic treatment. It also occurs in serial subcultures of cells that had been held under the constraint of confluence for extended periods, which suggests that the accumulation of random genetic damage to somatic cells during aging of mammals underlies the reduction of growth rate and function of the cells that characterizes the aging process.

Phosducin is a ubiquitous G-protein regulator.

Phosducin is a 33-kDa cytosolic regulator of G-protein-mediated signaling that has previously been thought to be specific for retina and pineal gland. In this study, we show widespread tissue distribution of phosducin by the amplification of its cDNA and the detection of two different transcripts in Northern analyses in liver, lung, heart, brain, and retina. On the protein level, phosducin could be detected in 12 bovine tissues by immune precipitation and subsequent Western analysis using anti-phosducin antibodies generated in two different species. Masking of phosducin in direct Western blots appears to explain the failure to detect phosducin in earlier studies. The concentration of phosducin in bovine brain was calculated in the range of 10 pmol/mg total cytosolic protein (approximately 1 microM), whereas in the other tissues, it was slightly less. In these concentrations, phosducin inhibited receptor-stimulated adenylyl cyclase activity in cell membranes by about 50%. Taken together, our results indicate that phosducin is a ubiquitous regulator of G-protein function.