Optimización multiobjetivo inteligente del dimensionamiento energético en sistemas ferroviarios señalizados y en plataformas software de tiempo real

La capacidad de transporte es uno de los baremos fundamentales para evaluar la progresión que puede llegar a tener un área económica y social. Es un sector de elevada importancia para la sociedad actual. Englobado en los distintos tipos de transporte, uno de los medios de transporte que se encuentra más en alza en la actualidad, es el ferroviario. Tanto para movilidad de pasajeros como para mercancías, el tren se ha convertido en un medio de transporte muy útil. Se encuentra dentro de las ciudades, entre ciudades con un radio pequeño entre ellas e incluso cada vez más, gracias a la alta velocidad, entre ciudades con gran distancia entre ellas. Esta Tesis pretende ayudar en el diseño de una de las etapas más importantes de los Proyectos de instalación de un sistema ferroviario: el sistema eléctrico de tracción. La fase de diseño de un sistema eléctrico de tracción ferroviaria se enfrenta a muchas dudas que deben ser resueltas con precisión. Del éxito de esta fase dependerá la capacidad de afrontar las demandas de energía de la explotación ferroviaria. También se debe atender a los costes de instalación y de operación, tanto costes directos como indirectos. Con la Metodología que se presenta en esta Tesis se ofrecerá al diseñador la opción de manejar un sistema experto que como soluciones le plantee un conjunto de escenarios de sistemas eléctricos correctos, comprobados por resolución de modelos de ecuaciones. Correctos desde el punto de vista de validez de distintos parámetros eléctrico, como de costes presupuestarios e impacto de costes indirectos. Por tanto, el diseñador al haber hecho uso de esta Metodología, tendría en un espacio de tiempo relativamente corto, un conjunto de soluciones factibles con las que poder elegir cuál convendría más según sus intereses finales. Esta Tesis se ha desarrollado en una vía de investigación integrada dentro del Centro de Investigaciones Ferroviarias CITEF-UPM. Entre otros proyectos y vías de investigación, en CITEF se ha venido trabajando en estudios de validación y dimensionamiento de sistemas eléctricos ferroviarios con diversos y variados clientes y sistemas ferroviarios. A lo largo de los proyectos realizados, el interés siempre ha girado mayoritariamente sobre los siguientes parámetros del sistema eléctrico: - Calcular número y posición de subestaciones de tracción. Potencia de cada subestación. - Tipo de catenaria a lo largo del recorrido. Conductores que componen la catenaria. Características. - Calcular número y posición de autotransformadores para sistemas funcionando en alterna bitensión o 2x25kV. - Posición Zonas Neutras. - Validación según normativa de: o Caídas de tensión en la línea o Tensiones máximas en el retorno de la línea o Sobrecalentamiento de conductores o Sobrecalentamiento de los transformadores de las subestaciones de tracción La idea es que las soluciones aportadas por la Metodología sugieran escenarios donde de estos parámetros estén dentro de los límites que marca la normativa. Tener la posibilidad de tener un repositorio de posibles escenarios donde los parámetros y elementos eléctricos estén calculados como correctos, aporta un avance en tiempos y en pruebas, que mejoraría ostensiblemente el proceso habitual de diseño para los sistemas eléctricos ferroviarios. Los costes directos referidos a elementos como subestaciones de tracción, autotransformadores, zonas neutras, ocupan un gran volumen dentro del presupuesto de un sistema ferroviario. En esta Tesis se ha querido profundizar también en el efecto de los costes indirectos provocados en la instalación y operación de sistemas eléctricos. Aquellos derivados del impacto medioambiental, los costes que se generan al mantener los equipos eléctricos y la instalación de la catenaria, los costes que implican la conexión entre las subestaciones de tracción con la red general o de distribución y por último, los costes de instalación propios de cada elemento compondrían los costes indirectos que, según experiencia, se han pensado relevantes para ejercer un cierto control sobre ellos. La Metodología cubrirá la posibilidad de que los diseños eléctricos propuestos tengan en cuenta variaciones de coste inasumibles o directamente, proponer en igualdad de condiciones de parámetros eléctricos, los más baratos en función de los costes comentados. Analizando los costes directos e indirectos, se ha pensado dividir su impacto entre los que se computan en la instalación y los que suceden posteriormente, durante la operación de la línea ferroviaria. Estos costes normalmente suelen ser contrapuestos, cuánto mejor es uno peor suele ser el otro y viceversa, por lo que hace falta un sistema que trate ambos objetivos por separado. Para conseguir los objetivos comentados, se ha construido la Metodología sobre tres pilares básicos: - Simulador ferroviario Hamlet: Este simulador integra módulos para construir esquemas de vías ferroviarios completos; módulo de simulación mecánica y de la tracción de material rodante; módulo de señalización ferroviaria; módulo de sistema eléctrico. Software realizado en C++ y Matlab. - Análisis y estudio de cómo focalizar los distintos posibles escenarios eléctricos, para que puedan ser examinados rápidamente. Pico de demanda máxima de potencia por el tráfico ferroviario. - Algoritmos de optimización: A partir de un estudio de los posibles algoritmos adaptables a un sistema tan complejo como el que se plantea, se decidió que los algoritmos genéticos serían los elegidos. Se han escogido 3 algoritmos genéticos, permitiendo recabar información acerca del comportamiento y resultados de cada uno de ellos. Los elegidos por motivos de tiempos de respuesta, multiobjetividad, facilidad de adaptación y buena y amplia aplicación en proyectos de ingeniería fueron: NSGA-II, AMGA-II y ɛ-MOEA. - Diseño de funciones y modelo preparado para trabajar con los costes directos e indirectos y las restricciones básicas que los escenarios eléctricos no deberían violar. Estas restricciones vigilan el comportamiento eléctrico y la estabilidad presupuestaria. Las pruebas realizadas utilizando el sistema han tratado o bien de copiar situaciones que se puedan dar en la realidad o directamente sistemas y problemas reales. Esto ha proporcionado además de la posibilidad de validar la Metodología, también se ha posibilitado la comparación entre los algoritmos genéticos, comparar sistemas eléctricos escogidos con los reales y llegar a conclusiones muy satisfactorias. La Metodología sugiere una vía de trabajo muy interesante, tanto por los resultados ya obtenidos como por las oportunidades que puede llegar a crear con la evolución de la misma. Esta Tesis se ha desarrollado con esta idea, por lo que se espera pueda servir como otro factor para trabajar con la validación y diseño de sistemas eléctricos ferroviarios. ABSTRACT Transport capacity is one of the critical points to evaluate the progress than a specific social and economical area is able to reach. This is a sector of high significance for the actual society. Included inside the most common types of transport, one of the means of transport which is elevating its use nowadays is the railway. Such as for passenger transport of weight movements, the train is being consolidated like a very useful mean of transport. Railways are installed in many geography areas. Everyone know train in cities, or connecting cities inside a surrounding area or even more often, taking into account the high-speed, there are railways infrastructure between cities separated with a long distance. This Ph.D work aims to help in the process to design one of the most essential steps in Installation Projects belonging to a railway system: Power Supply System. Design step of the railway power supply, usually confronts to several doubts and uncertainties, which must be solved with high accuracy. Capacity to supply power to the railway traffic depends on the success of this step. On the other hand is very important to manage the direct and indirect costs derived from Installation and Operation. With the Methodology is presented in this Thesis, it will be offered to the designer the possibility to handle an expert system that finally will fill a set of possible solutions. These solutions must be ready to work properly in the railway system, and they were tested using complex equation models. This Thesis has been developed through a research way, integrated inside Citef (Railway Research Centre of Technical University of Madrid). Among other projects and research ways, in Citef has been working in several validation studies and dimensioning of railway power supplies. It is been working by a large range of clients and railways systems. Along the accomplished Projects, the main goal has been rounded mostly about the next list of parameters of the electrical system: - Calculating number and location of traction substations. Power of each substation. - Type of Overhead contact line or catenary through the railway line. The wires which set up the catenary. Main Characteristics. - Calculating number and position of autotransformers for systems working in alternating current bi-voltage of called 2x25 kV. - Location of Neutral Zones. - Validating upon regulation of: o Drop voltages along the line o Maximum return voltages in the line o Overheating/overcurrent of the wires of the catenary o Avoiding overheating in the transformers of the traction substations. Main objective is that the solutions given by the Methodology, could be suggest scenarios where all of these parameters from above, would be between the limits established in the regulation. Having the choice to achieve a repository of possible good scenarios, where the parameters and electrical elements will be assigned like ready to work, that gives a great advance in terms of times and avoiding several tests. All of this would improve evidently the regular railway electrical systems process design. Direct costs referred to elements like traction substations, autotransformers, neutral zones, usually take up a great volume inside the general budget in railway systems. In this Thesis has been thought to bear in mind another kind of costs related to railway systems, also called indirect costs. These could be enveloped by those enmarked during installation and operation of electrical systems. Those derived from environmental impact; costs generated during the maintenance of the electrical elements and catenary; costs involved in the connection between traction substations and general electric grid; finally costs linked with the own installation of the whole electrical elements needed for the correct performance of the railway system. These are integrated inside the set has been collected taking into account own experience and research works. They are relevant to be controlled for our Methodology, just in case for the designers of this type of systems. The Methodology will cover the possibility that the final proposed power supply systems will be hold non-acceptable variations of costs, comparing with initial expected budgets, or directly assuming a threshold of budget for electrical elements in actual scenario, and achieving the cheapest in terms of commented costs from above. Analyzing direct and indirect costs, has been thought to divide their impact between two main categories. First one will be inside the Installation and the other category will comply with the costs often happens during Railway Operation time. These costs normally are opposed, that means when one is better the other turn into worse, in costs meaning. For this reason is necessary treating both objectives separately, in order to evaluate correctly the impact of each one into the final system. The objectives detailed before build the Methodology under three basic pillars: - Railway simulator Hamlet: This software has modules to configure many railway type of lines; mechanical and traction module to simulate the movement of rolling stock; signaling module; power supply module. This software has been developed using C++ and Matlab R13a - Previously has been mandatory to study how would be possible to work properly with a great number of feasible electrical systems. The target comprised the quick examination of these set of scenarios in terms of time. This point is talking about Maximum power demand peaks by railway operation plans. - Optimization algorithms. A railway infrastructure is a very complex system. At the beginning it was necessary to search about techniques and optimization algorithms, which could be adaptable to this complex system. Finally three genetic multiobjective algorithms were the chosen. Final decision was taken attending to reasons such as time complexity, able to multiobjective, easy to integrate in our problem and with a large application in engineering tasks. They are: NSGA-II, AMGA-II and ɛ-MOEA. - Designing objectives functions and equation model ready to work with the direct and indirect costs. The basic restrictions are not able to avoid, like budgetary or electrical, connected hardly with the recommended performance of elements, catenary and safety in a electrical railway systems. The battery of tests launched to the Methodology has been designed to be as real as possible. In fact, due to our work in Citef and with real Projects, has been integrated and configured three real railway lines, in order to evaluate correctly the final results collected by the Methodology. Another topic of our tests has been the comparison between the performances of the three algorithms chosen. Final step has been the comparison again with different possible good solutions, it means power supply system designs, provided by the Methodology, testing the validity of them. Once this work has been finished, the conclusions have been very satisfactory. Therefore this Thesis suggest a very interesting way of research and work, in terms of the results obtained and for the future opportunities can be created with the evolution of this. This Thesis has been developed with this idea in mind, so is expected this work could adhere another factor to work in the difficult task of validation and design of railway power supply systems.

Algoritmos de decisión para priorizar las acciones de restauración en el mantenimiento de redes

En la actualidad, cualquier compañía de telecomunicaciones que posea su propia red debe afrontar el problema del mantenimiento de la misma. Ofrecer un mínimo de calidad de servicio a sus clientes debe ser uno de sus objetivos principales. Esta calidad debe mantenerse aunque ocurran incidencias en la red. El presente trabajo pretende resolver el problema de priorizar el orden en que se restauran los cables, caminos y circuitos, dañados por una incidencia, dentro de una red troncal de transporte perteneciente a una operadora de telecomunicaciones. Tras un planteamiento detallado del problema y de todos los factores que influirán en la toma de decisión, en primer lugar se acomete una solución basada en Métodos Multicriterio Discretos, concretamente con el uso de ELECTRE I y AHP. A continuación se realiza una propuesta de solución basada en Redes Neuronales (con dos aproximaciones diferentes al problema). Por último se utiliza un método basado en la Optimización por Enjambre de Partículas (PSO), adaptado a un problema de permutación de enteros (ordenación), y con una forma particular de evaluar la mejor posición global del enjambre. Complementariamente se realiza una exposición de lo que es una empresa Operadora de telecomunicaciones, de sus departamentos y procesos internos, de los servicios que ofrece, de las redes sobre las que se soportan, y de los puntos clave a tener en cuenta en la implementación de sus sistemas informáticos de gestión integral. ABSTRACT: Nowadays, any telecommunications company that owns its own network must face the problem of maintaining it (service assurance). Provide a minimum quality of service to its customers must be one of its main objectives. This quality should be maintained although any incidents happen to occur in the network. This thesis aims to solve the problem of prioritizing the order in which the damaged cables, trails, path and circuits, within a backbone transport network, should be restored. This work begins with a detailed explanation about network maintenance issues and all the factors that influence decision-making problem. First of all, one solution based on Discrete Multicriteria methods is tried (ELECTRE I and AHP algorithms are used). Also, a solution based on neural networks (with two different approaches to the problem) is analyzed. Finally, this thesis proposes an algorithm based on Particle Swarm Optimization (PSO), adapted to a problem of integers permutation, and a particular way of evaluating the best overall position of the swarm method. In addition, there is included an exhibition about telecommunications companies, its departments, internal processes, services offered to clients, physical networks, and key points to consider when implementing its integrated management systems.

Analysing the complexity of the model-based decision making processes within the industrial management context

PURPOSE The decision-making process plays a key role in organizations. Every decision-making process produces a final choice that may or may not prompt action. Recurrently, decision makers find themselves in the dichotomous question of following a traditional sequence decision-making process where the output of a decision is used as the input of the next stage of the decision, or following a joint decision-making approach where several decisions are taken simultaneously. The implication of the decision-making process will impact different players of the organization. The choice of the decision- making approach becomes difficult to find, even with the current literature and practitioners’ knowledge. The pursuit of better ways for making decisions has been a common goal for academics and practitioners. Management scientists use different techniques and approaches to improve different types of decisions. The purpose of this decision is to use the available resources as well as possible (data and techniques) to achieve the objectives of the organization. The developing and applying of models and concepts may be helpful to solve managerial problems faced every day in different companies. As a result of this research different decision models are presented to contribute to the body of knowledge of management science. The first models are focused on the manufacturing industry and the second part of the models on the health care industry. Despite these models being case specific, they serve the purpose of exemplifying that different approaches to the problems and could provide interesting results. Unfortunately, there is no universal recipe that could be applied to all the problems. Furthermore, the same model could deliver good results with certain data and bad results for other data. A framework to analyse the data before selecting the model to be used is presented and tested in the models developed to exemplify the ideas. METHODOLOGY As the first step of the research a systematic literature review on the joint decision is presented, as are the different opinions and suggestions of different scholars. For the next stage of the thesis, the decision-making process of more than 50 companies was analysed in companies from different sectors in the production planning area at the Job Shop level. The data was obtained using surveys and face-to-face interviews. The following part of the research into the decision-making process was held in two application fields that are highly relevant for our society; manufacturing and health care. The first step was to study the interactions and develop a mathematical model for the replenishment of the car assembly where the problem of “Vehicle routing problem and Inventory” were combined. The next step was to add the scheduling or car production (car sequencing) decision and use some metaheuristics such as ant colony and genetic algorithms to measure if the behaviour is kept up with different case size problems. A similar approach is presented in a production of semiconductors and aviation parts, where a hoist has to change from one station to another to deal with the work, and a jobs schedule has to be done. However, for this problem simulation was used for experimentation. In parallel, the scheduling of operating rooms was studied. Surgeries were allocated to surgeons and the scheduling of operating rooms was analysed. The first part of the research was done in a Teaching hospital, and for the second part the interaction of uncertainty was added. Once the previous problem had been analysed a general framework to characterize the instance was built. In the final chapter a general conclusion is presented. FINDINGS AND PRACTICAL IMPLICATIONS The first part of the contributions is an update of the decision-making literature review. Also an analysis of the possible savings resulting from a change in the decision process is made. Then, the results of the survey, which present a lack of consistency between what the managers believe and the reality of the integration of their decisions. In the next stage of the thesis, a contribution to the body of knowledge of the operation research, with the joint solution of the replenishment, sequencing and inventory problem in the assembly line is made, together with a parallel work with the operating rooms scheduling where different solutions approaches are presented. In addition to the contribution of the solving methods, with the use of different techniques, the main contribution is the framework that is proposed to pre-evaluate the problem before thinking of the techniques to solve it. However, there is no straightforward answer as to whether it is better to have joint or sequential solutions. Following the proposed framework with the evaluation of factors such as the flexibility of the answer, the number of actors, and the tightness of the data, give us important hints as to the most suitable direction to take to tackle the problem. RESEARCH LIMITATIONS AND AVENUES FOR FUTURE RESEARCH In the first part of the work it was really complicated to calculate the possible savings of different projects, since in many papers these quantities are not reported or the impact is based on non-quantifiable benefits. The other issue is the confidentiality of many projects where the data cannot be presented. For the car assembly line problem more computational power would allow us to solve bigger instances. For the operation research problem there was a lack of historical data to perform a parallel analysis in the teaching hospital. In order to keep testing the decision framework it is necessary to keep applying more case studies in order to generalize the results and make them more evident and less ambiguous. The health care field offers great opportunities since despite the recent awareness of the need to improve the decision-making process there are many opportunities to improve. Another big difference with the automotive industry is that the last improvements are not spread among all the actors. Therefore, in the future this research will focus more on the collaboration between academia and the health care sector.

Estudio del radón en viviendas mediante modelos de minería de datos basados en cubos OLAP

En esta tesis doctoral se estudian las variaciones de radón en el interior de dos viviendas similares de construcción nueva en Madrid, una de ellas ocupada y la otra no, que forman parte del mismo edificio residencial. La concentración de radón y los parámetros ambientales (presión, temperatura y humedad) se midieron durante ocho meses. La monitorización del gas radón se realizó mediante detectores de estado sólido. Simultáneamente, se adquirieron algunas variables atmosféricas de un modelo atmosférico. En el análisis de los datos, se utilizó principalmente el método de la Transformada Wavelet. Los resultados muestran que el nivel de radón es ligeramente más alto en la vivienda ocupada que en la otra. A partir del análisis desarrollado en este estudio, se encontró que había un patrón específico estacional en la concentración de radón interior. Además, se analizó también la influencia antropogénica. Se pudieron observar patrones periódicos muy similares en intervalos concretos sin importar si la vivienda está ocupada o no. Por otra parte, los datos se almacenaron en cubos OLAP. El análisis se realizó usando unos algoritmos de agrupamiento (clustering) y de asociación. El objetivo es descubrir las relaciones entre el radón y las condiciones externas como la presión, estabilidad, etc. Además, la metodología aplicada puede ser útil para estudios ambientales en donde se mida radón en espacios interiores. ABSTRACT The present thesis studies the indoor radon variations in two similar new dwellings, one of them occupied and the other unoccupied, from the same residential building in Madrid. Radon concentration and ambient parameters were measured during eight months. Solid state detectors were used for the radon monitoring. Simultaneously, several atmospheric variables were acquired from an atmospheric model. In the data analysis, the Wavelet Transform Method was mainly used. The results show that radon level is slightly higher in the unoccupied dwelling than in the other one. From the analysis developed in this study, it is found that a specific seasonal pattern exists in the indoor radon concentration. Besides, the anthropogenic influence is also analysed. Nearly periodical patterns could be observed in specific periods whether dwelling is occupied or not. Otherwise, data were stored in cubes OLAP. Analysis was carried out using clustering and association algorithms. The aim is to find out the relationships among radon and external conditions like pressure, stability, etc. Besides, the methodology could be useful to assess environmental studies, where indoor radon is measured.

A Survey on Underwater Acoustic Sensor Network Routing Protocols

Underwater acoustic sensor networks (UASNs) have become more and more important in ocean exploration applications, such as ocean monitoring, pollution detection, ocean resource management, underwater device maintenance, etc. In underwater acoustic sensor networks, since the routing protocol guarantees reliable and effective data transmission from the source node to the destination node, routing protocol design is an attractive topic for researchers. There are many routing algorithms have been proposed in recent years. To present the current state of development of UASN routing protocols, we review herein the UASN routing protocol designs reported in recent years. In this paper, all the routing protocols have been classified into different groups according to their characteristics and routing algorithms, such as the non-cross-layer design routing protocol, the traditional cross-layer design routing protocol, and the intelligent algorithm based routing protocol. This is also the first paper that introduces intelligent algorithm-based UASN routing protocols. In addition, in this paper, we investigate the development trends of UASN routing protocols, which can provide researchers with clear and direct insights for further research.

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray HybridizationD⃞

We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures synchronized by three independent methods: α factor arrest, elutriation, and arrest of a cdc15 temperature-sensitive mutant. Using periodicity and correlation algorithms, we identified 800 genes that meet an objective minimum criterion for cell cycle regulation. In separate experiments, designed to examine the effects of inducing either the G1 cyclin Cln3p or the B-type cyclin Clb2p, we found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins. Furthermore, we analyzed our set of cell cycle–regulated genes for known and new promoter elements and show that several known elements (or variations thereof) contain information predictive of cell cycle regulation. A full description and complete data sets are available at http://cellcycle-www.stanford.edu

Real-time quantitative measurement of autocrine ligand binding indicates that autocrine loops are spatially localized

Autocrine ligands are important regulators of many normal tissues and have been implicated in a number of disease states, including cancer. However, because by definition autocrine ligands are synthesized, secreted, and bound to cell receptors within an intrinsically self-contained “loop,” standard pharmacological approaches cannot be used to investigate relationships between ligand/receptor binding and consequent cellular responses. We demonstrate here a new approach for measurement of autocrine ligand binding to cells, using a microphysiometer assay originally developed for investigating cell responses to exogenous ligands. This technique permits quantitative measurements of autocrine responses on the time scale of receptor binding and internalization, thus allowing investigation of the role of receptor trafficking and dynamics in cellular responses. We used this technique to investigate autocrine signaling through the epidermal growth factor receptor by transforming growth factor alpha (TGFα) and found that anti-receptor antibodies are far more effective than anti-ligand antibodies in inhibiting autocrine signaling. This result indicates that autocrine-based signals can operate in a spatially restricted, local manner and thus provide cells with information on their local microenvironment.

Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma

Transthyretin (TTR) tetramer dissociation and misfolding facilitate assembly into amyloid fibrils that putatively cause senile systemic amyloidosis and familial amyloid polyneuropathy. We have previously discovered more than 50 small molecules that bind to and stabilize tetrameric TTR, inhibiting amyloid fibril formation in vitro. A method is presented here to evaluate the binding selectivity of these inhibitors to TTR in human plasma, a complex biological fluid composed of more than 60 proteins and numerous small molecules. Our immunoprecipitation approach isolates TTR and bound small molecules from a biological fluid such as plasma, and quantifies the amount of small molecules bound to the protein by HPLC analysis. This approach demonstrates that only a small subset of the inhibitors that saturate the TTR binding sites in vitro do so in plasma. These selective inhibitors can now be tested in animal models of TTR amyloid disease to probe the validity of the amyloid hypothesis. This method could be easily extended to evaluate small molecule binding selectivity to any protein in a given biological fluid without the necessity of determining or guessing which other protein components may be competitors. This is a central issue to understanding the distribution, metabolism, activity, and toxicity of potential drugs.

Globular cluster ages

We review two new methods to determine the age of globular clusters (GCs). These two methods are more accurate than the classical isochrone fitting technique. The first method is based on the morphology of the horizontal branch and is independent of the distance modulus of the globular cluster. The second method uses a careful binning of the stellar luminosity function and determines simultaneously the distance and age of the GC. We find that the oldest galactic GCs have an age of 13.5 ± 2 gigayears (Gyr). The absolute minimum age for the oldest GCs is 10.5 Gyr (with 99% confidence) and the maximum 16.0 Gyr (with 99% confidence). Therefore, an Einstein–De Sitter Universe (Ω = 1) is not totally ruled out if the Hubble constant is about 65 ± 10 Km s−1 Mpc−1.

Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).

We have molecularly cloned a cDNA encoding a protein uniquely expressed and hyperphosphorylated at tyrosine residues in a Ki-1 lymphoma cell that contained chromosomal translocation t(2;5). The encoded protein p80 was shown to be generated by fusion of a protein-tyrosine kinase and a nucleolar protein B23/nucleophosmin (NPM). The coding sequence of this cDNA turned out to be virtually identical to that of the fusion cDNA for NPM-anaplastic lymphoma kinase (ALK) previously cloned from the transcript of the gene at the breakpoint of the same translocation. Overexpression of p80 in NIH 3T3 cells induced neoplastic transformation, suggesting that the p80 kinase is aberrantly activated. The normal form of p80 was predicted to be a receptor-type tyrosine kinase on the basis of its sequence similarity to the insulin receptor family of kinases. However, an immunofluorescence study using COS cells revealed that p80 was localized to the cytoplasm. Thus, subcellular translocation and activation of the tyrosine kinase presumably by its structural alteration would cause the malignant transformation. We also showed that a mutant p80 lacking the NPM portion was unable to transform NIH 3T3 cells. Thus, the NPM sequence is essential for the transforming activity, suggesting that the chromosomal translocation is responsible for the oncogenesis. Finally, Shc and insulin receptor substrate 1 (IRS-1) were tyrosine-phosphorylated and bound to p80 in p80-transformed cells. However, mutants of p80 that were defective for binding to and phosphorylation of Shc and insulin receptor substrate 1 could transform NIH 3T3 cells. Association of these mutants with GRB2 was still observed, suggesting that interaction of p80 with GRB2 but not with Shc or IRS-1 was relevant for cell transformation.

Commercial applications of speech interface technology: an industry at the threshold.

Speech interface technology, which includes automatic speech recognition, synthetic speech, and natural language processing, is beginning to have a significant impact on business and personal computer use. Today, powerful and inexpensive microprocessors and improved algorithms are driving commercial applications in computer command, consumer, data entry, speech-to-text, telephone, and voice verification. Robust speaker-independent recognition systems for command and navigation in personal computers are now available; telephone-based transaction and database inquiry systems using both speech synthesis and recognition are coming into use. Large-vocabulary speech interface systems for document creation and read-aloud proofing are expanding beyond niche markets. Today's applications represent a small preview of a rich future for speech interface technology that will eventually replace keyboards with microphones and loud-speakers to give easy accessibility to increasingly intelligent machines.

What does voice-processing technology support today?

This paper describes the state of the art in applications of voice-processing technologies. In the first part, technologies concerning the implementation of speech recognition and synthesis algorithms are described. Hardware technologies such as microprocessors and DSPs (digital signal processors) are discussed. Software development environment, which is a key technology in developing applications software, ranging from DSP software to support software also is described. In the second part, the state of the art of algorithms from the standpoint of applications is discussed. Several issues concerning evaluation of speech recognition/synthesis algorithms are covered, as well as issues concerning the robustness of algorithms in adverse conditions.

Speech technology in 2001: new research directions.

Research in speech recognition and synthesis over the past several decades has brought speech technology to a point where it is being used in "real-world" applications. However, despite the progress, the perception remains that the current technology is not flexible enough to allow easy voice communication with machines. The focus of speech research is now on producing systems that are accurate and robust but that do not impose unnecessary constraints on the user. This chapter takes a critical look at the shortcomings of the current speech recognition and synthesis algorithms, discusses the technical challenges facing research, and examines the new directions that research in speech recognition and synthesis must take in order to form the basis of new solutions suitable for supporting a wide range of applications.

Chimeric tumor necrosis factor receptors with constitutive signaling activity.

Many hormone and cytokine receptors are crosslinked by their specific ligands, and multimerization is an essential step leading to the generation of a signal. In the case of the tumor necrosis factor (TNF) receptors (TNF-Rs), antibody-induced crosslinking is sufficient to trigger a cytolytic effect. However, the quaternary structural requirements for signaling--i.e., the formation of dimers, trimers, or higher-order multimers--have remained obscure. Moreover, it has not been clear whether the 55-kDa or 75-kDa TNF-R is responsible for initiation of cytolysis. We reasoned that an obligate receptor dimer, targeted to the plasma membrane, might continuously signal the presence of TNF despite the actual absence of the ligand. Such a molecule, inserted into an appropriate vector, could be used to project receptor-specific "TNF-like" activity to specific cells and tissues in vivo. Accordingly, we constructed sequences encoding chimeric receptors in which the extracellular domain of the mouse erythropoietin receptor (Epo-R) was fused to the "stem," transmembrane domain, and cytoplasmic domain of the two mouse TNF-Rs. Thus, the Epo-R group was used to drive dimerization of the TNF-R cytoplasmic domain. These chimeric proteins were well expressed in a variety of cell lines and bound erythropoietin at the cell surface. Both the 55-kDa and the 75-kDa Epo/TNF-R chimeras exerted a constitutive cytotoxic effect detected by cotransfection or clonogenic assay. Thus, despite the lack of structural homology between the cytoplasmic domains of the two TNF-Rs, a similar signaling endpoint was observed. Moreover, dimerization (rather than trimerization or higher-order multimerization) was sufficient for elicitation of a biological response.

Adubação do café conilon irrigado por gotejamento: fertirrigação x fertilizantes de eficiência aprimorada

O uso da irrigação em cafeeiro é uma tecnologia que vem se consolidando e mostrando-se economicamente viável ao longo dos tempos, trazendo junto com ela a técnica da fertirrigação. Desta forma, o presente estudo teve como objetivo avaliar a influência de formas de aplicação e fontes de fertilizantes sobre a condutividade elétrica e pH da solução do solo, bem como no desenvolvimento e produção do café conilon irrigado por gotejamento. O trabalho foi desenvolvido em São Gabriel da Palha, Espírito Santo, utilizando o clone 12V da variedade INCAPER 8142. O experimento foi delineado em blocos ao acaso (DBC) com seis tratamentos e quatro blocos. Os tratamentos adotados foram: T1 - Controle - adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio; T2 - Adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio de liberação controlada; T3 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes ureia e cloreto de potássio; T4 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes nitrato de amônio e sulfato de potássio; T5 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes nitrato de amônio e nitrato de potássio; T6 - Adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio de liberação controlada no período de outubro a março (período chuvoso) e adubação nitrogenada e potássica aplicada via fertirrigação, nas fontes nitrato de amônio e sulfato de potássio no período de abril a setembro (período seco). Foi monitorado o pH e condutividade elétrica da solução do solo, avaliações biométricas das plantas tais como altura, comprimento do primeiro ramo plagiotrópico e número de nós no primeiro ramo plagiotrópico, além da produção por planta e estimativa de produtividade. Os tratamentos T1 e T3 que utilizaram ureia e cloreto de potássio e o T4 - nitrato de amônio e sulfato de potássio disponibilizaram maiores quantidade de nitrogênio na forma amoniacal, causando maior acidificação do bulbo. Em contrapartida os tratamentos T2, T5 e T6 apresentaram menor acidificação, com diferença estatística significativa na variação do pH nas duas profundidades analisadas a partir de 18 meses da aplicação dos tratamentos. Nos tratamentos T2 e T6 observou-se menor salinidade inicial na avaliação aos 90 dias após o plantio através da leitura da condutividade elétrica da solução do solo. Para as avaliações biométricas, os tratamentos T2, T4, T5 e T6 diferiram estatisticamente dos tratamentos T1 e T3, influenciando positivamente à altura de plantas, comprimento e número de nós no primeiro ramo plagiotrópico.