Neurite, a finite difference large scale parallel program for the simulation of the electrical signal propagation in neurites under mechanical loading

With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, function of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells has only very recently been proposed (Jerusalem et al., 2013). In this paper, we present the implementation details of Neurite: the finite difference parallel program used in this reference. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite-explicit and implicit-were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between lectrophysiology and mechanics (Jerusalem et al., 2013). This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented dendritic tree, and a damaged axon. The capabilities of the program to deal with large scale scenarios, segmented neuronal structures, and functional deficits under mechanical loading are specifically highlighted.

State of the Art and Future Trends in Grid Codes Applicable to Isolated Electrical Systems

Isolated electrical systems lack electrical interconnection to other networks and are usually placed in geographically isolated areas—mainly islands or locations in developing countries. Until recently, only diesel generators were able to assure a safe and reliable supply in exchange for very high costs for fuel transportation and system operation. Transmission system operators (TSOs) are increasingly seeking to replace traditional energy models based on large groups of conventional generation units with mixed solutions where diesel groups are held as backup generation and important advantages are provided by renewable energy sources. The grid codes determine the technical requirements to be fulfilled by the generators connected in any electrical network, but regulations applied to isolated grids are more demanding. In technical literature it is rather easy to find and compare grid codes for interconnected electrical systems. However, the existing literature is incomplete and sparse regarding isolated grids. This paper aims to review the current state of isolated systems and grid codes applicable to them, specifying points of comparison and defining the guidelines to be followed by the upcoming regulations.

Ypres rally network

Along of this document the reader could find a suitable network design and solution for the Rally Championship of Ypres meeting all the requirements set by the organization of the rally. These requirements have brought many problems in accordance with the network standards, because the area where the boxes are located is pretty large nevertheless technologies to solve those problems are detailed in the project. It has been included different designs in the project, each one of them based on distinct characteristic as they could be efficient, performance… , and the most important, since the organization of the rally is non-profit , the budget. Nevertheless we didn’t dismiss the use of long-lasting devices, as CISCO devices, despite their price. Furthermore a configuration of routing/switching devices has been explained for those who will be commanded to implement this solution. This solution is design to supply internet access as well as video streaming to all boxes for what teams can follow the championship in live time. The maximum connection of internet service provider (ISP) is 160Mbps, this bandwidth has to be distributed for the boxes dynamically. Finally to ensure the network works out it has to be monitored, this is reachable by using network analysis tools which in this project Wireshark has been chosen. RESUMEN. A lo largo de este documento, el lector encontrara un posible diseño y una posible solución para la red local del circuito de Rally celebrado en Ypres, cumpliendo con todos los requisitos y especificaciones establecidos por la organización. Estos requisitos han causado problemas de conformidad con los estándares de la red, debido a que la zona donde se encuentran los Boxes de los equipos es bastante larga, sin embargo las tecnologías para resolver esos problemas se detallan en este proyecto. Se han incluido diferentes diseños, cada uno de ellos centrado en aspectos diferentes así como la eficacia, el rendimiento, el presupuesto, etc... Esta solución está diseñada para suministrar acceso a Internet, así como la transmisión dinámica de video a todos los equipos para que puedan seguir la competición en tiempo real. Finalmente para controlar y asegurar que la red funciona, será monitorizada mediante herramientas de análisis de redes (Wireshark).

La Ordenación del Territorio en las Ciudades Globales Europeas: El caso de Madrid

En la Comunidad de Madrid el modelo de ocupación del territorio en las dos últimas décadas ha obedecido a factores de oferta del mercado y no a las necesidades de la población, ello provoca un consumo de suelo y de recursos que conducen a una sobrexplotación insostenible. Las metrópolis globales están experimentando rápidas e intensas transformaciones, basadas en los paradigmas emergentes de la globalización, la gobernanza, la metropolizacion y la dispersión de las actividades en el territorio y a través de ellos se abordan los planes de Londres, París y las tentativas de Madrid. La globalización provoca la pérdida de soberanía de las administraciones publicas y la competitividad entre las ciudades globales en Europa, Londres, Paris y Madrid, son centros de poder, de concentración y crecimiento donde se produce la dualización del espacio y donde la desigualdad participa de la restructuración urbana, concentración de pobreza frente a espacios de la nueva clase emergente en donde dominan los sectores de servicios y las tecnologías de la información. Frente al desarrollo urbano neoliberal de regulación a través del mercado y basada en criterios de eficiencia de la Nueva Gestión Pública, se vislumbra la posibilidad de que la sociedad se administre a si misma por medio de acciones voluntarias y responsables que promuevan los intereses colectivos mediante el reconocimiento de su propia identidad, introduciendo el concepto de gobernanza. Frente, a la explotación del territorio por parte de la sociedad extractiva que genera corrupcion, se propone un modelo de cooperación público-privada basado en la confianza mutua, un marco regulador estable, la transparencia y la información a cuyo flujo más homogéneo contribuirán sin duda las TICs. En todo este proceso, las regiones metropolitanas en Europa se erigen como motores del crecimiento, donde los límites administrativos son superados, en un territorio cada vez más extendido y donde los gobiernos locales tienen que organizarse mediante un proceso de cooperación en la provisión de servicios que ayuden a evitar los desequilibrios territoriales. El fenómeno de la dispersión urbana en desarrollos de baja densidad, los centros comerciales periféricos, la expulsión hacia la periferia de las actividades de menor valor añadido y la concentración de funciones directivas en el centro, conducen a una fragmentación del territorio en islas dependientes del automóvil y a procesos de exclusión social por la huida de las rentas altas y la expulsión de las rentas bajas de los centros urbanos. Se crean fragmentos monofuncionales y discontinuos, apoyados en las autovías, lugares carentes de identidad y generadores de despilfarro de recursos y una falta de sostenibilidad ambiental, económica y social. El estudio de la cultura de la planificación en Europa ayuda a comprender los diferentes enfoques en la ordenación del territorio y el proceso de convergencia entre las diferentes regiones. Los documentos de la UE se basan en la necesidad de la competitividad para el crecimiento europeo y la cohesión social y en relación al territorio en los desarrollos policéntricos, la resolución del dualismo campo-ciudad, el acceso equilibrado a las infraestructuras, la gestión prudente de la naturaleza, el patrimonio y el fomento de la identidad. Se proponen dos niveles de estudio uno actual, los últimos planes de Londres y Paris y el otro la evolución de las tentativas de planes en la Región madrileña siempre en relación a los paradigmas emergentes señalados y su reflejo en los documentos. El Plan de Londres es estratégico, con una visión a largo plazo, donde se confiere un gran interés al proceso, al papel del alcalde como líder y su adaptación a las circunstancias cambiantes, sujeto a las incertidumbres de una ciudad global. El desarrollo del mismo se concibe a través de la colaboración y cooperación entre las administraciones y actores. La estructura del documento es flexible, establece orientaciones y guías indicativas, para la redacción de los planes locales, no siendo las mismas vinculantes y con escasa representación grafica. El Plan de París es más un plan físico, similar al de otros centros europeos, trabaja sobre los sectores y sobre los territorios, con información extensa, con características de “Plan Latino” por la fuerza de la expresión gráfica, pero al mismo tiempo contiene una visión estratégica. Es vinculante en sus determinaciones y normativas, se plantea fomentar, pero también prohibir. Ambos planes tratan la competitividad internacional de sus centros urbanos, la igualdad social, la inclusión de todos los grupos sociales y la vivienda como una cuestión de dignidad humana. Londres plantea la gobernanza como cooperación entre sector público-privado y la necesaria cooperación con las regiones limítrofes, en París las relaciones están más institucionalizadas resaltando la colaboración vertical entre administraciones. Ambos plantean la densificación de nodos servidos por transporte público, modos blandos y el uso los TODs y la preservación de la infraestructura verde jerarquizada, la potenciación de la red azul y la mejora del paisaje de las periferias. En las “tentativas” de planes territoriales de Madrid se constata que estuvieron sujetas a los ciclos económicos. El primer Documento las DOT del año 1984, no planteaba crecimiento, ni económico ni demográfico, a medio plazo y por ello no proponía una modificación del modelo radio concéntrico. Se trataba de un Plan rígido volcado en la recuperación del medio rural, de la ciudad, el dimensionamiento de los crecimientos en función de las dotaciones e infraestructuras existentes. Aboga por la intervención de la administración pública y la promoción del pequeño comercio. Destaca el desequilibrio social en función de la renta, la marginación de determinados grupos sociales, el desequilibrio residencia/empleo y la excesiva densidad. Incide en la necesidad de viviendas para los más desfavorecidos mediante el alquiler, la promoción suelo público y la promoción del ferrocarril para dar accesibilidad al espacio central. Aboga por el equipamiento de proximidad y de pequeño tamaño, el tratamiento paisajístico de los límites urbanos de los núcleos y el control de las actividades ilegales señalando orientaciones para el planeamiento urbano. Las Estrategias (1989) contienen una visión: la modificación del modelo territorial, mediante la intervención pública a través de proyectos. Plantea la reestructuración económica del territorio, la reconversión del aparato productivo, la deslocalización de actividades de escaso valor añadido y una mayor ubicuidad de la actividad económica. Incide en la difusión de la centralidad hacia el territorio del sur, equilibrándolo con el norte, tratando de recomponer empleo y residencia, integrando al desarrollo económico las periferias entre sí y con el centro. Las actuaciones de transporte consolidarían las actuaciones, modificando el modelo radio concéntrico facilitando la movilidad mediante la red de cercanías y la intermodalidad. El plan se basaba en el liderazgo del Consejero, no integrando sectores como el medio ambiente, ni estableciendo un documento de seguimiento de las actuaciones que evaluara los efectos de las políticas y su aportación al equilibrio territorial, a través de los proyectos realizados. El Documento Preparatorio de las Bases (1995), es más de un compendio o plan de planes, recoge análisis y propuestas de los documentos anteriores y de planes sectoriales de otros departamentos. Presenta una doble estructura: un plan físico integrador clásico, que abarca los sectores y territorios, y recoge las Estrategias previas añadiendo puntos fuertes, como el malestar urbano y la rehabilitación el centro. Plantea la consecución del equilibrio ambiental mediante el crecimiento de las ciudades existentes, la vertebración territorial basada en la movilidad y en la potenciación de nuevas centralidades, la mejora de la habitabilidad y rehabilitación integral del Centro Urbano de Madrid, y la modernización del tejido productivo existente. No existe una idea-fuerza que aglutine todo el documento, parte del reconocimiento de un modelo existente concentrado y congestivo, un centro urbano dual y dos periferias al este y sur con un declive urbano y obsolescencia productiva y al oeste y norte con una dispersión que amenaza al equilibrio medioambiental. Señala como aspectos relevantes, la creciente polarización y segregación social, la deslocalización industrial, la aparición de las actividades de servicios a las empresas instaladas en las áreas metropolitanas, y la dispersión de las actividades económicas en el territorio por la banalización del uso del automóvil. Se plantea el reto de hacer ciudad de la extensión suburbana y su conexión con el sistema metropolitano, mediante una red de ciudades integrada y complementaria, en búsqueda de un mayor equilibrio y solidaridad territorial. Las Bases del PRET (1997) tenían como propósito iniciar el proceso de concertación en que debe basarse la elaboración del Plan. Parte de la ciudad mediterránea compacta, y diversa, y de la necesidad de que las actividades económicas, los servicios y la residencia estén en proximidad, resolviéndolo mediante una potente red de transporte público que permitiese una accesibilidad integrada al territorio. El flujo de residencia hacia la periferia, con un modelo ajeno de vivienda unifamiliar y la concentración del empleo en el centro producen desequilibrio territorial. Madrid manifiesta siempre apostó por la densificación del espacio central urbanizado, produciendo su congestión, frente al desarrollo de nuevos suelos que permitieran su expansión territorial. Precisa que es necesario preservar los valores de centralidad de Madrid, como generador de riqueza, canalizando toda aquella demanda de centralidad, hacia espacios más periféricos. El problema de la vivienda no lo ve solo como social, sino como económico, debido a la pérdida de empleos que supone su paralización. Observa ya los crecimientos residenciales en el borde de la region por el menor valor del suelo. Plantea como la política de oferta ha dado lugar a un modelo de crecimiento fragmentado, desequilibrado, desestructurado, con fuertes déficits dotacionales y de equipamiento, que inciden en la segregación espacial de las rentas, agravando el proceso de falta de identidad morfológica y de desarraigo de los valores urbanos. El plan señalaba que la presión sobre el territorio creaba su densificación por las limitaciones de espacio, Incidía en limitar el peso de la intervención pública, no planteando propuestas de cooperación público-privado. La mayor incoherencia estriba en que los objetivos eran innovadores y coinciden en su mayoría con las propuestas estudiadas de Londres o Paris, pero se intentan implementar a través de un cambio hacia un modelo reticulado homogéneo, expansivo sobre el territorio, que supone un consumo de suelo y de infraestructuras para solucionar un problema inexistente, la gestión de la densidad. Durante las dos últimas décadas en ausencia de un plan regional, la postura neoliberal fue la de un exclusivo control de legalidad del planeamiento, los municipios entraron en un proceso de competencia para aprovechar las iniciales ventajas económicas de los crecimientos detectados, que proporcionaban una base económica “sólida” a unos municipios con escasos recursos en sus presupuestos municipales. La legislación se modifica a requerimiento de grupos interesados, no existiendo un marco estable. Se pierde la figura del plan no solo a nivel regional, si no en los sectores y el planeamiento municipal donde los municipios tiende a basarse en modificaciones puntuales con la subsiguiente pérdida del modelo urbanístico. La protección ambiental se estructura mediante un extenso nivel de figuras, con diversidad de competencias que impide su efectiva protección y control. Este proceso produce un despilfarro en la ocupación del suelo, apoyada en las infraestructuras viarias, y un crecimiento disperso y de baja densidad, cada vez más periférico, produciéndose una segmentación social por dualización del espacio en función de niveles de renta. Al amparo del boom inmobiliario, se produce una falta de política social de vivienda pública, más basada en la dinamización del mercado con producción de viviendas para rentas medias que en políticas de alquiler para determinados grupos concentrándose estas en los barrios desfavorecidos y en la periferia sur. Se produce un incremento de la vivienda unifamiliar, muchas veces amparada en políticas públicas, la misma se localiza en el oeste principalmente, en espacios de valor como el entorno del Guadarrama o con viviendas más baratas por la popularización de la tipología en la frontera de la Región. El territorio se especializa a modo de islas monofuncionales, las actividades financieras y de servicios avanzados a las empresas se localizan en el norte y oeste próximo, se pierde actividad industrial que se dispersa más al sur, muchas veces fuera de la región. Se incrementan los grandes centros comerciales colgados de las autovías y sin población en su entorno. Todo este proceso ha provocado una pérdida de utilización del transporte público y un aumento significativo del uso del vehículo privado. En la dos últimas décadas se ha producido en la región de Madrid desequilibrio territorial y segmentación social, falta de implicación de la sociedad en el territorio, dispersión del crecimiento y un incremento de los costes ambientales, sociales y económicos, situación, que solo, a través del uso racional del territorio se puede reconducir, apoyado en una planificación integrada sensible y participativa. ABSTRACT In Madrid the model of land occupation in the past two decades has been driven by market supply factors rather than the needs of the population. This results in a consumption of land and resources that leads to unsustainable overexploitation. Addressing this issue must be done through sensitive and participatory integrated planning. Global cities are experiencing rapid and intense change based on the emerging paradigms of globalization, governance, metropolization and the dispersion of activities in the territory. Through this context, a closer look will be taken at the London and Paris plans as well as the tentative plans of Madrid. Globalization causes the loss of state sovereignty and the competitiveness among global cities in Europe; London, Paris and Madrid. These are centres of power, concentration and growth where the duality of space is produced, and where inequality plays a part in urban restructuration. There are concentrated areas of poverty versus areas with a new emerging class where the services sector and information technologies are dominant. The introduction of ICTs contributes to a more homogeneous flow of information leading, us to the concept of governance. Against neoliberal urban development based on free market regulations and efficiency criteria as established by the “New Public Management”, emerge new ways where society administers itself through voluntary and responsible actions to promote collective interests by recognizing their own identity. A new model of public-private partnerships surfaces that is based on mutual trust, transparency, information and a stable regulatory framework in light of territorial exploitation by the “extractive society” that generates corruption. Throughout this process, European metropolitan regions become motors of growth where administrative boundaries are overcome in an ever expanding territory where government is organized through cooperative processes to provide services that protect against regional imbalances. Urban sprawl or low-density development as seen in peripheral shopping centres, the off-shoring of low added-value activities to the periphery, and the concentration of business and top management functions in the centre, leads to a fragmentation of the territory in automobile dependent islands and a process of social exclusion brought on by the disappearance of high incomes. Another effect is the elimination of low income populations from urban centres. In consequence, discontinuous expansions and mono-functional places that lack identity materialize supported by a highway network and high resource consumption. Studying the culture of urban planning in Europe provides better insight into different approaches to spatial planning and the process of convergence between different regions. EU documents are based on the need of competitiveness for European growth and social cohesion. In relation to polycentric development territory they are based on a necessity to solve the dualism between field and city, balanced access to infrastructures, prudent management of nature and solidifying heritage and identity Two levels of study unfold, the first being the current plans of London and Île-de-France and the second being the evolution of tentative plans for the Madrid region as related to emerging paradigms and how this is reflected in documents. The London Plan is strategic with a long-term vision that focuses on operation, the role of the mayor as a pivotal leader, and the adaptability to changing circumstances brought on by the uncertainties of a global city. Its development is conceived through collaboration and cooperation between governments and stakeholders. The document structure is flexible, providing guidance and indicative guidelines on how to draft local plans so they are not binding, and it contains scarce graphic representation. The Plan of Paris takes on a more physical form and is similar to plans of other European centres. It emphasizes sectors and territories, using extensive information, and is more characteristic of a “Latin Plan” as seen in its detailed graphic expression. However, it also contains a strategic vision. Binding in its determinations and policy, it proposes advancement but also prohibition. Both plans address the international competitiveness of urban centres, social equality, inclusion of all social groups and housing as issues of human dignity. London raises governance and cooperation between public and private sector and the need for cooperation with neighbouring regions. In Paris, the relations are more institutionalized highlighting vertical collaboration between administrations. Both propose nodes of densification served by public transportation, soft modes and the use of TOD, the preservation of a hierarchical green infrastructure, and enhancing the landscape in urban peripheries. The tentative territorial plans for the Madrid region provide evidence that they were subject to economic cycles. The first document of master guidelines (1984) does not address either economic or demographic growth in the mid term and therefore does not propose the modification of the radio-concentric model. It is a rigid plan focused on rural and urban recovery and the dimensioning of growth that depends on endowments and infrastructures. It advocates government intervention and promotes small business. The plan emphasizes social imbalance in terms of income, marginalization of certain social groups, the imbalance of residence/employment and excessive density. It stresses the need for social rent housing for the underprivileged, promotes public land, and the supports rail accessibility to the central area. It backs facilities of proximity and small size, enhancing the landscaping of city borders, controlling illegal activities and draws out guidelines for urban planning. The strategies (1989) contain a vision: Changing the territorial model through public intervention by means of projects. They bring to light economic restructuring of territory, the reconversion of the productive apparatus, relocation of low value-added activities, and greater ubiquity of economic activity. They also propose the diffusion of centrality towards southern territories, balancing it with the north in an attempt to reset employment and residence that integrates peripheral economic development both in the periphery and the centre. Transport would consolidate the project, changing the radius-concentric model and facilitating mobility through a commuter and inter-modality network. The plan derives itself from the leadership of the minister and does not integrate sectors such as environment. It also does not incorporate the existence of a written document that monitors performance to evaluate the effects of policies and their contribution to the territorial balance. The Preparatory Document of the Bases, (1995) is more a compendium, or plan of plans, that compiles analysis and proposals from previous documents and sectorial plans from other departments. It has a dual structure: An integrating physical plan covering the sectors and territories that includes the previous strategies while adding some strengths. One such point is the urban discomfort and the rehabilitation of the centre. It also poses the achievement of environmental balance through the growth of existing cities, the territorial linking based on mobility, strengthening new centres, improving the liveability and comprehensive rehabilitation of downtown Madrid, and the modernization of the existing production network. There is no one powerful idea that binds this document. This is due to the recognition of an existing concentrate and congestive model, a dual urban centre, two eastern and southern suburbs suffering from urban decay, and an obsolescent productive north and west whose dispersion threatens the environmental balance. Relevant aspects the document highlights are increasing polarization and social segregation, industrial relocation, the emergence of service activities to centralized companies in metropolitan areas and the dispersion of economic activities in the territory by the trivialization of car use. It proposes making the city from the suburban sprawl and its connection to the metropolitan system through a network of integrated and complementary cities in search of a better balance and territorial solidarity. The Bases of PRET (1997) aims to start the consultation process that must underpin the development of the plan. It stems from a compact and diverse Mediterranean city along with the need for economic activities, services and residences that are close. To resolve the issue, it presents a powerful network of public transport that allows integrated accessibility to the territory. The flow of residence to the periphery based on a foreign model of detached housing and an employment concentration in the centre produces territorial imbalance. Madrid always opted for the densification of the central space, producing its congestion, against the development of new land that would allow its territorial expansion. The document states that the necessity to preserve the values of the housing problem is not only viewed as social, but also economic due to the loss of jobs resulting from their paralysis. It notes the residential growth in the regional border due to the low price of land and argues that the policy of supply has led to a fragmented model of growth that is unbalanced, unstructured, with strong infrastructure and facility deficits that affect the spatial segregation of income and aggravate the lack of morphological identity, uprooting urban values. The pressure on the territory caused its densification due to space limitation; the proposed grid model causes land consumption and infrastructure to solve a non-problem, density. Focusing on limiting the weight of public intervention, it does not raise proposals for public-private cooperation. The biggest discrepancy is that the targets were innovative and mostly align with the proposals in London and Paris. However, it proposes to be implemented through a shift towards a uniform gridded model that is expansive over territory. During the last two decades, due to the absence of a regional plan, a neoliberal stance held exclusive control of the legality of urban planning. The municipalities entered a competition process to take advantage of initial economic benefits of such growth. This provided a “solid” economic base for some municipalities with limited resources in their municipal budgets. The law was amended without a legal stable framework at the request of stakeholders. The character of the plan is lost not only regionally, but also in the sectors and municipal planning. This tends to be based on specific changes with the loss of an urban model. Environmental protection is organized through an extensive number of protection figures with diverse competencies that prevent its effective protection. This process squanders the use of the land, backed by increasing road infrastructure, dispersed occupations with low-density growth causing a social segmentation due to space duality based on income levels. During the housing boom, there is a reduction in social public housing policy mostly due to a boost in the market of housing production for average incomes than in rental policies for needy social groups that focus on disadvantaged neighbourhoods and southern suburbs. As a result, there is an increase in single-family housing, often protected by public policy. This is located primarily in the west in areas of high environmental value such as Guadarrama. There is also cheaper housing due to the popularization of typology in the border region. There, territory works as a mono-functional islands. Financial activities and advanced services for companies are located to the north and west where industrial activity is lost as it migrates south, often outside the region. The number of large shopping centres hanging off the highway infrastructure with little to no surrounding population increases. This process leads to the loss of dependency on public transport and a significant increase in the use of private vehicles. The absence of regional planning has produced more imbalance, more social segmentation, more dispersed growth and a lot of environmental, social and economic costs that can only be redirected through rational territorial.

Excitatory–inhibitory network in the visual cortex: Psychophysical evidence

At early stages in visual processing cells respond to local stimuli with specific features such as orientation and spatial frequency. Although the receptive fields of these cells have been thought to be local and independent, recent physiological and psychophysical evidence has accumulated, indicating that the cells participate in a rich network of local connections. Thus, these local processing units can integrate information over much larger parts of the visual field; the pattern of their response to a stimulus apparently depends on the context presented. To explore the pattern of lateral interactions in human visual cortex under different context conditions we used a novel chain lateral masking detection paradigm, in which human observers performed a detection task in the presence of different length chains of high-contrast-flanked Gabor signals. The results indicated a nonmonotonic relation of the detection threshold with the number of flankers. Remote flankers had a stronger effect on target detection when the space between them was filled with other flankers, indicating that the detection threshold is caused by dynamics of large neuronal populations in the neocortex, with a major interplay between excitation and inhibition. We considered a model of the primary visual cortex as a network consisting of excitatory and inhibitory cell populations, with both short- and long-range interactions. The model exhibited a behavior similar to the experimental results throughout a range of parameters. Experimental and modeling results indicated that long-range connections play an important role in visual perception, possibly mediating the effects of context.

Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network

A major activity of molecular chaperones is to prevent aggregation and refold misfolded proteins. However, when allowed to form, protein aggregates are refolded poorly by most chaperones. We show here that the sequential action of two Escherichia coli chaperone systems, ClpB and DnaK-DnaJ-GrpE, can efficiently solubilize excess amounts of protein aggregates and refold them into active proteins. Measurements of aggregate turbidity, Congo red, and 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid binding, and of the disaggregation/refolding kinetics by using a specific ClpB inhibitor, suggest a mechanism where (i) ClpB directly binds protein aggregates, ATP induces structural changes in ClpB, which (ii) increase hydrophobic exposure of the aggregates and (iii) allow DnaK-DnaJ-GrpE to bind and mediate dissociation and refolding of solubilized polypeptides into native proteins. This efficient mechanism, whereby chaperones can catalytically solubilize and refold a wide variety of large and stable protein aggregates, is a major addition to the molecular arsenal of the cell to cope with protein damage induced by stress or pathological states.

A Late Mitotic Regulatory Network Controlling Cyclin Destruction in Saccharomyces cerevisiae

Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinase–cyclin complexes, primarily by ubiquitin-dependent cyclin proteolysis. Cyclin destruction is regulated by a ubiquitin ligase known as the anaphase-promoting complex (APC). In the budding yeast Saccharomyces cerevisiae, members of a large class of late mitotic mutants, including cdc15, cdc5, cdc14, dbf2, and tem1, arrest in anaphase with a phenotype similar to that of cells expressing nondegradable forms of mitotic cyclins. We addressed the possibility that the products of these genes are components of a regulatory network that governs cyclin proteolysis. We identified a complex array of genetic interactions among these mutants and found that the growth defect in most of the mutants is suppressed by overexpression of SPO12, YAK1, and SIC1 and is exacerbated by overproduction of the mitotic cyclin Clb2. When arrested in late mitosis, the mutants exhibit a defect in cyclin-specific APC activity that is accompanied by high Clb2 levels and low levels of the anaphase inhibitor Pds1. Mutant cells arrested in G1 contain normal APC activity. We conclude that Cdc15, Cdc5, Cdc14, Dbf2, and Tem1 cooperate in the activation of the APC in late mitosis but are not required for maintenance of that activity in G1.

The Zebrafish Information Network (ZFIN): a resource for genetic, genomic and developmental research

The Zebrafish Information Network, ZFIN, is a WWW community resource of zebrafish genetic, genomic and developmental research information (http://zfin.org). ZFIN provides an anatomical atlas and dictionary, developmental staging criteria, research methods, pathology information and a link to the ZFIN relational database (http://zfin.org/ZFIN/). The database, built on a relational, object-oriented model, provides integrated information about mutants, genes, genetic markers, mapping panels, publications and contact information for the zebrafish research community. The database is populated with curated published data, user submitted data and large dataset uploads. A broad range of data types including text, images, graphical representations and genetic maps supports the data. ZFIN incorporates links to other genomic resources that provide sequence and ortholog data. Zebrafish nomenclature guidelines and an automated registration mechanism for new names are provided. Extensive usability testing has resulted in an easy to learn and use forms interface with complex searching capabilities.

BIND—The Biomolecular Interaction Network Database

The Biomolecular Interaction Network Database (BIND; http://binddb.org) is a database designed to store full descriptions of interactions, molecular complexes and pathways. Development of the BIND 2.0 data model has led to the incorporation of virtually all components of molecular mechanisms including interactions between any two molecules composed of proteins, nucleic acids and small molecules. Chemical reactions, photochemical activation and conformational changes can also be described. Everything from small molecule biochemistry to signal transduction is abstracted in such a way that graph theory methods may be applied for data mining. The database can be used to study networks of interactions, to map pathways across taxonomic branches and to generate information for kinetic simulations. BIND anticipates the coming large influx of interaction information from high-throughput proteomics efforts including detailed information about post-translational modifications from mass spectrometry. Version 2.0 of the BIND data model is discussed as well as implementation, content and the open nature of the BIND project. The BIND data specification is available as ASN.1 and XML DTD.

Vps10p Transport from the trans-Golgi Network to the Endosome Is Mediated by Clathrin-coated Vesicles

A native immunoisolation procedure has been used to investigate the role of clathrin-coated vesicles (CCVs) in the transport of vacuolar proteins between the trans-Golgi network (TGN) and the prevacuolar/endosome compartments in the yeast Saccharomyces cerevisiae. We find that Apl2p, one large subunit of the adaptor protein-1 complex, and Vps10p, the carboxypeptidase Y vacuolar protein receptor, are associated with clathrin molecules. Vps10p packaging in CCVs is reduced in pep12Δ and vps34Δ, two mutants that block Vps10p transport from the TGN to the endosome. However, Vps10p sorting is independent of Apl2p. Interestingly, a Vps10CtΔp mutant lacking its C-terminal cytoplasmic domain, the portion of the receptor responsible for carboxypeptidase Y sorting, is also coimmunoprecipitated with clathrin. Our results suggest that CCVs mediate Vps10p transport from the TGN to the endosome independent of direct interactions between Vps10p and clathrin coats. The Vps10p C-terminal domain appears to play a principal role in retrieval of Vps10p from the prevacuolar compartment rather than in sorting from the TGN.

Folliculostellate cell network: A route for long-distance communication in the anterior pituitary

All higher life forms critically depend on hormones being rhythmically released by the anterior pituitary. The proper functioning of this master gland is dynamically controlled by a complex set of regulatory mechanisms that ultimately determine the fine tuning of the excitable endocrine cells, all of them heterogeneously distributed throughout the gland. Here, we provide evidence for an intrapituitary communication system by which information is transferred via the network of nonendocrine folliculostellate (FS) cells. Local electrical stimulation of FS cells in acute pituitary slices triggered cytosolic calcium waves, which propagated to other FS cells by signaling through gap junctions. Calcium wave initiation was because of the membrane excitability of FS cells, hitherto classified as silent cells. FS cell coupling could relay information between opposite regions of the gland. Because FS cells respond to central and peripheral stimuli and dialogue with endocrine cells, the form of large-scale intrapituitary communication described here may provide an efficient mechanism that orchestrates anterior pituitary functioning in response to physiological needs.

The vesicular monoamine transporter 2 is present in small synaptic vesicles and preferentially localizes to large dense core vesicles in rat solitary tract nuclei.

In central neurons, monamine neurotransmitters are taken up and stored within two distinct classes of regulated secretory vesicles: small synaptic vesicles and large dense core vesicles (DCVs). Biochemical and pharmacological evidence has shown that this uptake is mediated by specific vesicular monamine transporters (VMATs). Recent molecular cloning techniques have identified the vesicular monoamine transporter (VMAT2) that is expressed in brain. This transporter determines the sites of intracellular storage of monoamines and has been implicated in both the modulation of normal monoaminergic neurotransmission and the pathogenesis of related neuropsychiatric disease. We used an antiserum against VMAT2 to examine its ultrastructural distribution in rat solitary tract nuclei, a region that contains a dense and heterogeneous population of monoaminergic neurons. We find that both immunoperoxidase and immunogold labeling for VMAT2 localize to DCVs and small synaptic vesicles in axon terminals, the trans-Golgi network of neuronal perikarya, tubulovesicles of smooth endoplasmic reticulum, and potential sites of vesicular membrane recycling. In axon terminals, immunogold labeling for VMAT2 was preferentially associated with DCVs at sites distant from typical synaptic junctions. The results provide direct evidence that a single VMAT is expressed in two morphologically distinct types of regulated secretory vesicles in central monoaminergic neurons.

The Role of Citizen Participation in Wildlife-Sensitive Transportation Projects

An extensive and growing road system in the United States bisects vital wildlife habitat and is causing deleterious ecological effects on many wildlife species. The primary impacts include collisions between wildlife and vehicles, altered movement patterns within habitat, and/or the complete blockage of movements between vital habitats. The increasing size of the road network and number of vehicles will only intensify the problem unless proactive wildlife mitigation measures are developed to minimize these adverse effects. Therefore, this capstone project examines the role of citizen advocacy for promoting wildlife protection in the planning and development of wildlife-sensitive transportation projects in the United States. Based upon a data analysis of 21 questionnaires from qualified participants, it was determined that citizen participation is an important component associated with the development of wildlife-sensitive transportation projects. However, four major barriers to facilitating effective citizen participation processes were identified. 1) A lack of awareness. Citizens are only minimally aware of wildlife and transportation issues, including: a) the ecological impacts of roads, b) the solutions available to mitigate these impacts, and c) the opportunities to advocate for the protection of wildlife during transportation planning processes; 2) Public apathy or a lack of citizen interest in wildlife and transportation issues; 3) Ineffective citizen participation techniques and processes; and 4) Poor communication with citizens. Four recommendations were provided to assist in overcoming these barriers and to help define a better role for citizen advocacy in protecting wildlife from the growing road network.

Breaking down complex saproxylic communities: understanding sub-networks structure and implications to network robustness

Saproxylic insect communities inhabiting tree hollow microhabitats correspond with large food webs which simultaneously are constituted by multiple types of plant-animal and animal-animal interactions, according to the use of trophic resources (wood- and insect-dependent sub-networks), or to trophic habits or interaction types (xylophagous, saprophagous, xylomycetophagous, predators and commensals). We quantitatively assessed which properties of specialised networks were present in a complex networks involving different interacting types such as saproxylic community, and how they can be organised in trophic food webs. The architecture, interacting patterns and food web composition were evaluated along sub-networks, analysing their implications to network robustness from random and directed extinction simulations. A structure of large and cohesive modules with weakly connected nodes was observed throughout saproxylic sub-networks, composing the main food webs constituting this community. Insect-dependent sub-networks were more modular than wood-dependent sub-networks. Wood-dependent sub-networks presented higher species degree, connectance, links, linkage density, interaction strength, and were less specialised and more aggregated than insect-dependent sub-networks. These attributes defined high network robustness in wood-dependent sub-networks. Finally, our results emphasise the relevance of modularity, differences among interacting types and interrelations among them in modelling the structure of saproxylic communities and in determining their stability.

On Modeling an Innovative Monitoring Network for Protecting and Managing Cultural Heritage from Risk Events

In this paper the model of an Innovative Monitoring Network involving properly connected nodes to develop an Information and Communication Technology (ICT) solution for preventive maintenance of historical centres from early warnings is proposed. It is well known that the protection of historical centres generally goes from a large-scale monitoring to a local one and it could be supported by a unique ICT solution. More in detail, the models of a virtually organized monitoring system could enable the implementation of automated analyses by presenting various alert levels. An adequate ICT solution tool would allow to define a monitoring network for a shared processing of data and results. Thus, a possible retrofit solution could be planned for pilot cases shared among the nodes of the network on the basis of a suitable procedure utilizing a retrofit catalogue. The final objective would consist in providing a model of an innovative tool to identify hazards, damages and possible retrofit solutions for historical centres, assuring an easy early warning support for stakeholders. The action could proactively target the needs and requirements of users, such as decision makers responsible for damage mitigation and safeguarding of cultural heritage assets.