957 resultados para Coordination of intersections
Resumo:
Alveolar echinococcosis, caused by the tapeworm Echinococcus multilocularis, is one of the most severe parasitic diseases in humans and represents one of the 17 neglected diseases prioritised by the World Health Organisation (WHO) in 2012. Considering the major medical and veterinary importance of this parasite, the phylogeny of the genus Echinococcus is of considerable importance; yet, despite numerous efforts with both mitochondrial and nuclear data, it has remained unresolved. The genus is clearly complex, and this is one of the reasons for the incomplete understanding of its taxonomy. Although taxonomic studies have recognised E. multilocularis as a separate entity from the Echinococcus granulosus complex and other members of the genus, it would be premature to draw firm conclusions about the taxonomy of the genus before the phylogeny of the whole genus is fully resolved. The recent sequencing of E. multilocularis and E. granulosus genomes opens new possibilities for performing in-depth phylogenetic analyses. In addition, whole genome data provide the possibility of inferring phylogenies based on a large number of functional genes, i.e. genes that trace the evolutionary history of adaptation in E. multilocularis and other members of the genus. Moreover, genomic data open new avenues for studying the molecular epidemiology of E. multilocularis: genotyping studies with larger panels of genetic markers allow the genetic diversity and spatial dynamics of parasites to be evaluated with greater precision. There is an urgent need for international coordination of genotyping of E. multilocularis isolates from animals and human patients. This could be fundamental for a better understanding of the transmission of alveolar echinococcosis and for designing efficient healthcare strategies.
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Selection of division sites and coordination of cytokinesis with other cell cycle events are critical for every organism to proliferate. In E. coli, the nucleoid is proposed to exclude division from the site of the chromosome (nucleoid occlusion model). We studied the effect of the nucleoid on timing and placement of cell division. An early cell division protein, FtsZ, was used to follow development of the division septum. FtsZ forms a ring structure (Z ring) at potential division sites. The dynamics of Z ring was visualized in live cells by fusing FtsZ with a green fluorescent protein (GFP). Emanating FtsZ-GFP polymers from the constricted septum or aggregates in daughter cells were also observed, probably representing the FtsZ depolymerization and immature FtsZ nucleation processes. We next examined the nucleoid occlusion model. Mutants carrying abnormally positioned chromosomes were employed. In chromosomal partition mutants, replicated chromosomes cannot segregate. The Z ring was excluded from midcell to the edge of the nucleoid. This negative effect of nucleoids was further confirmed in replication deficient dnaA mutants, in which only a single chromosome is present in the cell center. These results suggest that the nucleoid, replicating or not, inhibits division in the area where the chromosome occupies. In addition, increasing the level of FtsZ does not overcome nucleoid inhibition. Interestingly in anucleate cells produced by both mutants, the Z ring was localized in the central part of the cell, which indicates that the nucleoid is not required for FtsZ assembly. Relaxation of chromosomes by reducing the gyrase activity or disruption of protein translation/translocation did not abolish the division inhibition capacity of the nucleoid. However, preventing transcription did compromise the nucleoid occlusion effect, leading to formation of multiple FtsZ rings above the nucleoid. In summary, we demonstrate that nucleoids negatively regulate the timing and position of division by inhibiting FtsZ assembly at unselected sites. Relief of this inhibition at midcell is coincident with the completion of DNA replication. On the other hand, FtsZ assembly does not require the nucleoid. ^
Resumo:
Cancer is a result of defects in the coordination of cell proliferation and programmed cell death. The extent of cell death is physiologically controlled by the activation of a programmed suicide pathway that results in a morphologically recognizable form of death termed apoptosis. Inducing apoptosis in tumor cells by gene therapy provides a potentially effective means to treat human cancers. The p84N5 is a novel nuclear death domain containing protein that has been shown to bind an amino terminal domain of retinoblastoma tumor suppressor gene product (pRb). Expression of N5 can induce apoptosis that is dependent upon its intact death domain and is inhibited by pRb. In many human cancer cells the functions of pRb are either lost through gene mutation or inactivated by different mechanisms. N5 based gene therapy may induce cell death preferentially in tumor cells relative to normal cells. We have demonstrated that N5 gene therapy is less toxic to normal cells than to tumor cells. To test the possibility that N5 could be used in gene therapy of cancer, we have generated a recombinant adenovirus engineered to express N5 and test the effects of viral infection on growth and tumorigenicity of human cancer cells. Adenovirus N5 infection significantly reduced the proliferation and tumorigenicity of breast, ovarian, and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were mediated by an induction of apoptosis as indicated by DNA fragmentation in infected cells. We also test the potential utility of N5 for gene therapy of pancreatic carcinoma that typically respond poorly to conventional treatment. Adenoviral mediated N5 gene transfer inhibits the growth of pancreatic cancer cell lines in vitro. N5 gene transfer also reduces the growth and metastasis of human pancreatic adenocarcinoma in subcutaneous and orthotopic mouse model. Interestingly, the pancreatic adenocarcinoma cells are more sensitive to N5 than they are to p53, suggesting that N5 gene therapy may be effective in tumors resistant to p53. We also test the possibilities of the use of N5 and p53 together on the inhibition of pancreatic cancer cell growth in vitro and vivo. Simultaneous use of N5 and RbΔCDK has been found to exert a greater extent on the inhibition of pancreatic cancer cell growth in vitro and in vivo. ^
Resumo:
The data collection "Deep Drilling of Glaciers: Soviet-Russian projects in Arctic, 1975-1995" was collected by the following basic considerations: - compilation of deep (>100 m) drilling projects on Arctic glaciers, using data of (a) publications; (b) archives of IGRAN; (c) personal communication of project participants; - documentation of parameters, references. Accuracy of data and techniques applied to determine different parameters are not evaluated. The accuracy of some geochemical parameters (up to 1984 and heavy metalls) is uncertain. Most reconstructions of ice core age and of annual layer thickness are discussed; - digitizing of published diagrams (in case, when original numerical data were lost) and subsequent data conversion to equal range series and adjustment to the common units. Therefore, the equal-range series were calculated from original data or converted from digitized chart values as indicated in the metadata. For the methodological purpose, the equal-range series obtained from original and reconstructed data were compared repeatedly; the systematic difference was less then 5-7%. Special attention should be given to the fact, that the data for individual ice core parameters varies, because some parameters were originally measured or registered. Parameters were converted in equal-range series using 2 m steps; - two or more parameter values were determined, then the mean-weighted (i.e. accounting the sample length) value is assigned to the entire interval; - one parameter value was determined, measured or registered independently from the parameter values in depth intervals which over- and underlie it, then the value is assigned to the entire interval; - one parameter value was determined, measured or registered for two adjoining depth intervals, then the specific value is assigned to the depth interval, which represents >75% of sample length ; if each of adjoining depth intervals represents <75% of sample length, then the correspondent parameter value is assigned to both intervals of depth. This collection of ice core data (version 2000) was made available through the EU funded QUEEN project by S.M. Arkhipov, Moscow.
Resumo:
El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área
Resumo:
El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área
Resumo:
El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área
Resumo:
In recent decades, there has been an increasing interest in systems comprised of several autonomous mobile robots, and as a result, there has been a substantial amount of development in the eld of Articial Intelligence, especially in Robotics. There are several studies in the literature by some researchers from the scientic community that focus on the creation of intelligent machines and devices capable to imitate the functions and movements of living beings. Multi-Robot Systems (MRS) can often deal with tasks that are dicult, if not impossible, to be accomplished by a single robot. In the context of MRS, one of the main challenges is the need to control, coordinate and synchronize the operation of multiple robots to perform a specic task. This requires the development of new strategies and methods which allow us to obtain the desired system behavior in a formal and concise way. This PhD thesis aims to study the coordination of multi-robot systems, in particular, addresses the problem of the distribution of heterogeneous multi-tasks. The main interest in these systems is to understand how from simple rules inspired by the division of labor in social insects, a group of robots can perform tasks in an organized and coordinated way. We are mainly interested on truly distributed or decentralized solutions in which the robots themselves, autonomously and in an individual manner, select a particular task so that all tasks are optimally distributed. In general, to perform the multi-tasks distribution among a team of robots, they have to synchronize their actions and exchange information. Under this approach we can speak of multi-tasks selection instead of multi-tasks assignment, which means, that the agents or robots select the tasks instead of being assigned a task by a central controller. The key element in these algorithms is the estimation ix of the stimuli and the adaptive update of the thresholds. This means that each robot performs this estimate locally depending on the load or the number of pending tasks to be performed. In addition, it is very interesting the evaluation of the results in function in each approach, comparing the results obtained by the introducing noise in the number of pending loads, with the purpose of simulate the robot's error in estimating the real number of pending tasks. The main contribution of this thesis can be found in the approach based on self-organization and division of labor in social insects. An experimental scenario for the coordination problem among multiple robots, the robustness of the approaches and the generation of dynamic tasks have been presented and discussed. The particular issues studied are: Threshold models: It presents the experiments conducted to test the response threshold model with the objective to analyze the system performance index, for the problem of the distribution of heterogeneous multitasks in multi-robot systems; also has been introduced additive noise in the number of pending loads and has been generated dynamic tasks over time. Learning automata methods: It describes the experiments to test the learning automata-based probabilistic algorithms. The approach was tested to evaluate the system performance index with additive noise and with dynamic tasks generation for the same problem of the distribution of heterogeneous multi-tasks in multi-robot systems. Ant colony optimization: The goal of the experiments presented is to test the ant colony optimization-based deterministic algorithms, to achieve the distribution of heterogeneous multi-tasks in multi-robot systems. In the experiments performed, the system performance index is evaluated by introducing additive noise and dynamic tasks generation over time.
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The goal of this paper is to evaluate whether the incentives incorporated in toll highway concession contracts in order to encourage private operators to adopt measures to reduce accidents are actually effective at improving safety. To this end, we implemented negative binomial regression models using information about highway characteristics and accident data from toll highway concessions in Spain from 2007 to 2009. Our results show that even though road safety is highly influenced by variables that are not managed by the contractor, such as the annual average daily traffic (AADT), the percentage of heavy vehicles on the highway, number of lanes, number of intersections and average speed; the implementation of these incentives has a positive influence on the reduction of accidents and injuries. Consequently, this measure seems to be an effective way of improving safety performance in road networks.
Resumo:
Este trabajo de Tesis se desarrolla en el marco de los escenarios de ejecución distribuida de servicios móviles y contribuye a la definición y desarrollo del concepto de usuario prosumer. El usuario prosumer se caracteriza por utilizar su teléfono móvil para crear, proveer y ejecutar servicios. Este nuevo modelo de usuario contribuye al avance de la sociedad de la información, ya que el usuario prosumer se transforma de creador de contenidos a creador de servicios (estos últimos formados por contenidos y la lógica para acceder a ellos, procesarlos y representarlos). El objetivo general de este trabajo de Tesis es la provisión de un modelo de creación, distribución y ejecución de servicios para entorno móvil que permita a los usuarios no programadores (usuarios prosumer), pero expertos en un determinado dominio, crear y ejecutar sus propias aplicaciones y servicios. Para ello se definen, desarrollan e implementan metodologías, procesos, algoritmos y mecanismos adaptables a dominios específicos, para construir entornos de ejecución distribuida de servicios móviles para usuarios prosumer. La provisión de herramientas de creación adaptadas a usuarios no expertos es una tendencia actual que está siendo desarrollada en distintos trabajos de investigación. Sin embargo, no se ha propuesto una metodología de desarrollo de servicios que involucre al usuario prosumer en el proceso de diseño, desarrollo, implementación y validación de servicios. Este trabajo de Tesis realiza un estudio de las metodologías y tecnologías más innovadoras relacionadas con la co‐creación y utiliza este análisis para definir y validar una metodología que habilita al usuario para ser el responsable de la creación de servicios finales. Siendo los entornos móviles prosumer (mobile prosumer environments) una particularización de los entornos de ejecución distribuida de servicios móviles, en este trabajo se tesis se investiga en técnicas de adaptación, distribución, coordinación de servicios y acceso a recursos identificando como requisitos las problemáticas de este tipo de entornos y las características de los usuarios que participan en los mismos. Se contribuye a la adaptación de servicios definiendo un modelo de variabilidad que soporte la interdependencia entre las decisiones de personalización de los usuarios, incorporando mecanismos de guiado y detección de errores. La distribución de servicios se implementa utilizando técnicas de descomposición en árbol SPQR, cuantificando el impacto de separar cualquier servicio en distintos dominios. Considerando el plano de comunicaciones para la coordinación en la ejecución de servicios distribuidos hemos identificado varias problemáticas, como las pérdidas de enlace, conexiones, desconexiones y descubrimiento de participantes, que resolvemos utilizando técnicas de diseminación basadas en publicación subscripción y algoritmos Gossip. Para lograr una ejecución flexible de servicios distribuidos en entorno móvil, soportamos la adaptación a cambios en la disponibilidad de los recursos, proporcionando una infraestructura de comunicaciones para el acceso uniforme y eficiente a recursos. Se han realizado validaciones experimentales para evaluar la viabilidad de las soluciones propuestas, definiendo escenarios de aplicación relevantes (el nuevo universo inteligente, prosumerización de servicios en entornos hospitalarios y emergencias en la web de la cosas). Abstract This Thesis work is developed in the framework of distributed execution of mobile services and contributes to the definition and development of the concept of prosumer user. The prosumer user is characterized by using his mobile phone to create, provide and execute services. This new user model contributes to the advancement of the information society, as the prosumer is transformed from producer of content, to producer of services (consisting of content and logic to access them, process them and represent them). The overall goal of this Thesis work is to provide a model for creation, distribution and execution of services for the mobile environment that enables non‐programmers (prosumer users), but experts in a given domain, to create and execute their own applications and services. For this purpose I define, develop and implement methodologies, processes, algorithms and mechanisms, adapted to specific domains, to build distributed environments for the execution of mobile services for prosumer users. The provision of creation tools adapted to non‐expert users is a current trend that is being developed in different research works. However, it has not been proposed a service development methodology involving the prosumer user in the process of design, development, implementation and validation of services. This thesis work studies innovative methodologies and technologies related to the co‐creation and relies on this analysis to define and validate a methodological approach that enables the user to be responsible for creating final services. Being mobile prosumer environments a specific case of environments for distributed execution of mobile services, this Thesis work researches in service adaptation, distribution, coordination and resource access techniques, and identifies as requirements the challenges of such environments and characteristics of the participating users. I contribute to service adaptation by defining a variability model that supports the dependency of user personalization decisions, incorporating guiding and error detection mechanisms. Service distribution is implemented by using decomposition techniques based on SPQR trees, quantifying the impact of separating any service in different domains. Considering the communication level for the coordination of distributed service executions I have identified several problems, such as link losses, connections, disconnections and discovery of participants, which I solve using dissemination techniques based on publish‐subscribe communication models and Gossip algorithms. To achieve a flexible distributed service execution in mobile environments, I support adaptation to changes in the availability of resources, while providing a communication infrastructure for the uniform and efficient access to resources. Experimental validations have been conducted to assess the feasibility of the proposed solutions, defining relevant application scenarios (the new intelligent universe, service prosumerization in hospitals and emergency situations in the web of things).
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In weak grids, an important problem with voltage stability and protections coordination of power plants exists. This problem appears because all the generation groups are connected to the same bus bar. As a result, if a fault occurs in any of the generation groups, or in the bus bar that connect them, the system voltage will have large oscillations. Hence, in weak grids the correct adjustment of AVR (Automatic Voltage Regulator) is critical. In this work an experimental study of differents AVR adjustments against fault in weak grids is described.
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One of the main concerns when conducting a dam test is the acute determination of the hydrograph for a specific flood event. The use of 2D direct rainfall hydraulic mathematical models on a finite elements mesh, combined with the efficiency of vector calculus that provides CUDA (Compute Unified Device Architecture) technology, enables nowadays the simulation of complex hydrological models without the need for terrain subbasin and transit splitting (as in HEC-HMS). Both the Spanish PNOA (National Plan of Aereal Orthophotography) Digital Terrain Model GRID with a 5 x 5 m accuracy and the CORINE GIS Land Cover (Coordination of INformation of the Environment) that allows assessment of the ground roughness, provide enough data to easily build these kind of models
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Fatty acid synthesis in chloroplasts is regulated by light. The synthesis of malonyl-CoA, which is catalyzed by acetyl-CoA carboxylase (ACCase) and is the first committed step, is modulated by light/dark. Plants have ACCase in plastids and the cytosol. To determine the possible involvement of a redox cascade in light/dark modulation of ACCase, the effect of DTT, a known reductant of S-S bonds, was examined in vitro for the partially purified ACCase from pea plant. Only the plastidic ACCase was activated by DTT. This enzyme was activated in vitro more efficiently by reduced thioredoxin, which is a transducer of redox potential during illumination, than by DTT alone. Chloroplast thioredoxin-f activated the enzyme more efficiently than thioredoxin-m. The ACCase also was activated by thioredoxin reduced enzymatically with NADPH and NADP-thioredoxin reductase. These findings suggest that the reduction of ACCase is needed for activation of the enzyme, and a redox potential generated by photosynthesis is involved in its activation through thioredoxin as for enzymes of the reductive pentose phosphate cycle. The catalytic activity of ACCase was maximum at pH 8 and 2–5 mM Mg2+, indicating that light-produced changes in stromal pH and Mg2+ concentration modulate ACCase activity. These results suggest that light directly modulates a regulatory site of plastidic prokaryotic form of ACCase via a signal transduction pathway of a redox cascade and indirectly modulates its catalytic activity via stromal pH and Mg2+ concentration. A redox cascade is likely to link between light and fatty acid synthesis, resulting in coordination of fatty acid synthesis with photosynthesis.
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Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.