Kinetic assessment of persistent halogenated xenobiotics in cell culture models: comparison of mono- and poly-halogenated compounds

We evaluated the suitability of single and multiple cell type cultures as model systems to characterise cellular kinetics of highly lipophilic compounds with potential ecotoxicological impact. Confluent mono-layers of human skin fibroblasts, rat astrocytoma C6 cells, non-differentiated and differentiated mouse 3T3 cells were kept in culture medium supplemented with 10% foetal calf serum. For competitive uptake experiments up to four different cell types, grown on glass sectors, were exposed for 3h to (14)C-labelled model compounds, dissolved either in organic solvents or incorporated into unilamellar lecithin liposomes. Bromo-, or chloro-benzenes, decabromodiphenylether (DBP), and dichlorodiphenyl ethylene (DDE) were tested in rather high concentration of 20 microM. Cellular toxicity was low. Compound levels were related to protein, DNA, and triglyceride contents. Cellular uptake was fast and dependent on physico-chemical properties of the compounds (lipophilicity, molecular size), formulation, and cell type. Mono-halogenated benzenes showed low and similar uptake levels (=low accumulation compounds). DBP and DDE showed much higher cellular accumulations (=high accumulation compounds) except for DBP in 3T3 cells. Uptake from liposomal formulations was mostly higher than if compounds were dissolved in organic solvents. The extent of uptake correlated with the cellular content of triglycerides, except for DBP. Uptake competition between different cell types was studied in a sectorial multi-cell culture model. For low accumulation compounds negligible differences were found among C6 cells and fibroblasts. Uptake of DDE was slightly and that of DBP highly increased in fibroblasts. Well-defined cell culture systems, especially the sectorial model, are appropriate to screen for bioaccumulation and cytotoxicity of (unknown) chemical entities in vitro.

QUANTIFYING UNCERTAINTY IN GENOTYPE CALLS

Genome-wide association studies (GWAS) are used to discover genes underlying complex, heritable disorders for which less powerful study designs have failed in the past. The number of GWAS has skyrocketed recently with findings reported in top journals and the mainstream media. Mircorarrays are the genotype calling technology of choice in GWAS as they permit exploration of more than a million single nucleotide polymorphisms (SNPs)simultaneously. The starting point for the statistical analyses used by GWAS, to determine association between loci and disease, are genotype calls (AA, AB, or BB). However, the raw data, microarray probe intensities, are heavily processed before arriving at these calls. Various sophisticated statistical procedures have been proposed for transforming raw data into genotype calls. We find that variability in microarray output quality across different SNPs, different arrays, and different sample batches has substantial inuence on the accuracy of genotype calls made by existing algorithms. Failure to account for these sources of variability, GWAS run the risk of adversely affecting the quality of reported findings. In this paper we present solutions based on a multi-level mixed model. Software implementation of the method described in this paper is available as free and open source code in the crlmm R/BioConductor.

Dynamische Standsicherheit von Portalstaplern

Der Artikel beschreibt die Untersuchung der dynamischen Standsicherheit von Portalstaplern. Dazu wurde ein aktueller repräsentativer Portalstapler analysiert und in ein Mehrkörper-Simulationsmodell abgebildet. Die Validierung des Modells erfolgte auf Basis von Messfahrten am realen System. Aus den durchgeführten Simulationsstudien wurden technische Verbesserungsmaßnahmen abgeleitet, welche die dynamische Standsicherheit von Portalstaplern erhöhen.

Erfahrbares Programmieren durch den zielgerichten Einsatz von Flugdrohnen im Informatikunterricht

Informatik- und insbesondere Programmierunterricht sind heute ein wichtiger Bestandteil der schulischen Ausbildung. Vereinfachte Entwicklungsumgebungen, die auf die Abstraktion typischer Programmierkonzepte in Form von grafischen Bausteinen setzen, unterstützen diesen Trend. Zusätzliche Attraktivität wird durch die Verwendung exotischer Laufzeitumgebungen (z. B. Roboter) geschaffen. Die in diesem Paper vorgestellte Plattform “ScratchDrone” führt ergänzend zu diesen Angeboten eine moderne Flugdrohne als innovative Laufzeitumgebung für Scratch-Programme ein. Die Programmierung kann dabei dank modularer Systemarchitektur auf verschiedenen Abstraktionsebenen erfolgen, abhängig vom Lernfortschritt der Schüler. Kombiniert mit einem mehrstufigen didaktischen Modell, der Herausforderung der Bewegung im 3D-Raum sowie der natürlichen menschlichen Faszination für das Fliegen wird so eine hohe Lernmotivation bei jungen Programmieranfängern erreicht.

BAYESIAN PHASE I DOSE FINDING IN CANCER TRIALS

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model. We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose. The design based on a time-to-DLT model uses patients' DLT information over multiple treatment cycles in estimating the probability of DLT at the end of treatment cycle 1. Dose-escalation decisions are made whenever a cycle-1 DLT occurs, or two months after the previous check point. Compared to the design based on a logistic regression model, the new design shows more safety benefits for trials in which more late-onset toxicities are expected. As a trade-off, the new design requires more patients on average. The design based on a discrete-time multi-state (DTMS) model has three important attributes: (1) Toxicities are categorized over a distribution of severity levels, (2) Early toxicity may inform dose escalation, and (3) No suspension is required between accrual cohorts. The proposed model accounts for the difference in the importance of the toxicity severity levels and for transitions between toxicity levels. We compare the operating characteristics of the proposed design with those from a similar design based on a fully-evaluated model that directly models the maximum observed toxicity level within the patients' entire assessment window. We describe settings in which, under comparable power, the proposed design shortens the trial. The proposed design offers more benefit compared to the alternative design as patient accrual becomes slower.

Macrobenthic abundance, biomass, productivity and production in the deep Arctic ocean

The few existing studies on macrobenthic communities of the deep Arctic Ocean report low standing stocks, and confirm a gradient with declining biomass from the slopes down to the basins as commonly reported for deep-sea benthos. In this study we have further investigated the relationship of faunal abundance (N), biomass (B) as well as community production (P) with water depth, geographical latitude and sea ice concentration. The underlying dataset combines legacy data from the past 20 years, as well as recent field studies selected according to standardized quality control procedures. Community P/B and production were estimated using the multi-parameter ANN model developed by Brey (2012). We could confirm the previously described negative relationship of water depth and macrofauna standing stock in the Arctic deep-sea. Furthermore, the sea-ice cover increasing with high latitudes, correlated with decreasing abundances of down to < 200 individuals/m**2, biomasses of < 65 mg C/m**2 and P of < 75 mg C/m**2/y. Stations under influence of the seasonal ice zone (SIZ) showed much higher standing stock and P means between 400 - 1400 mg C/m**2/y; even at depths up to 3700 m. We conclude that particle flux is the key factor structuring benthic communities in the deep Arctic ocean, explaining both the low values in the ice-covered Arctic basins and the high values along the SIZ.

European mink (Mustela lutreola) and American mink (Neovison vison) detection histories in Northern Spain between 2000 and 2011

Understanding changes over time in the distribution of interacting native and invasive species that may be symptomatic of competitive exclusion is critical to identify the need for and effectiveness of management interventions. Occupancy models greatly increase the robustness of inference that can be made from presence/absence data when species are imperfectly detected, and recent novel developments allow for the quantification of the strength of interaction between pairs of species. We used a two-species multi-season occupancy model to quantify the impact of the invasive American mink on the native European mink in Spain through the analysis of their co-occurrence pattern over twelve years (2000 - 2011) in the entire Spanish range of European mink distribution, where both species were detected by live trapping but American mink were culled. We detected a negative temporal trend in the rate of occupancy of European mink and a simultaneous positive trend in the occupancy of American mink. The species co-occurred less often than expected and the native mink was more likely to become extinct from sites occupied by the invasive species. Removal of American mink resulted in a high probability of local extinction where it co-occurred with the endemic mink, but the overall increase in the probability of occupancy over the last decade indicates that the ongoing management is failing to halt its spread. More intensive culling effort where both species co-exist as well as in adjacent areas where the invasive American mink is found at high densities is required in order to stop thedecline of European mink.

Modeling of the Division Point of Different Propagation Mechanisms in the Near-Region Within Arched Tunnels

An accurate characterization of the near-region propagation of radio waves inside tunnels is of practical importance for the design and planning of advanced communication systems. However, there has been no consensus yet on the propagation mechanism in this region. Some authors claim that the propagation mechanism follows the free space model, others intend to interpret it by the multi-mode waveguide model. This paper clarifies the situation in the near-region of arched tunnels by analytical modeling of the division point between the two propagation mechanisms. The procedure is based on the combination of the propagation theory and the three-dimensional solid geometry. Three groups of measurements are employed to verify the model in different tunnels at different frequencies. Furthermore, simplified models for the division point in five specific application situations are derived to facilitate the use of the model. The results in this paper could help to deepen the insight into the propagation mechanism within tunnel environments.

Improved design of an overhead rail current conductor for application in underground lines

Overhead rail current collector systems for railway traction offer certain features, such as low installation height and reduced maintenance, which make them predominantly suitable for use in underground train infrastructures. Due to the increased demands of modern catenary systems and higher running speeds of new vehicles, a more capable design of the conductor rail is needed. A new overhead conductor rail has been developed and its design has been patented [13]. Modern simulation and modelling techniques were used in the development approach. The new conductor rail profile has a dynamic behaviour superior to that of the system currently in use. Its innovative design permits either an increase of catenary support spacing or a higher vehicle running speed. Both options ensure savings in installation or operating costs. The simulation model used to optimise the existing conductor rail profile included both a finite element model of the catenary and a three-dimensional multi-body system model of the pantograph. The contact force that appears between pantograph and catenary was obtained in simulation. A sensitivity analysis of the key parameters that influence in catenary dynamics was carried out, finally leading to the improved design.

Survey and brain storming studies about machines, constructions, human and environmental risk consideration in the careers of the Universidad Politécnica of Madrid

The Universidad Politécnica of Madrid (UPM) includes schools and faculties that were for engineering degrees, architecture and computer science, that are now in a quick EEES Bolonia Plan metamorphosis getting into degrees, masters and doctorate structures. They are focused towards action in machines, constructions, enterprises, that are subjected to machines, human and environment created risks. These are present in actions such as use loads, wind, snow, waves, flows, earthquakes, forces and effects in machines, vehicles behavior, chemical effects, and other environmental factors including effects of crops, cattle and beasts, forests, and varied essential economic and social disturbances. Emphasis is for authors in this session more about risks of natural origin, such as for hail, winds, snow or waves that are not exactly known a priori, but that are often considered with statistical expected distributions giving extreme values for convenient return periods. These distributions are known from measures in time, statistic of extremes and models about hazard scenarios and about responses of man made constructions or devices. In each engineering field theories were built about hazards scenarios and how to cover for important risks. Engineers must get that the systems they handle, such as vehicles, machines, firms or agro lands or forests, obtain production with enough safety for persons and with decent economic results in spite of risks. For that risks must be considered in planning, in realization and in operation, and safety margins must be taken but at a reasonable cost. That is a small level of risks will often remain, due to limitations in costs or because of due to strange hazards, and maybe they will be covered by insurance in cases such as in transport with cars, ships or aircrafts, in agro for hail, or for fire in houses or in forests. These and other decisions about quality, security for men or about business financial risks are sometimes considered with Decision Theories models, using often tools from Statistics or operational Research. The authors have done and are following field surveys about risk consideration in the careers in UPM, making deep analysis of curricula taking into account the new structures of degrees in the EEES Bolonia Plan, and they have considered the risk structures offered by diverse schools of Decision theories. That gives an aspect of the needs and uses, and recommendations about improving in the teaching about risk, that may include special subjects especially oriented for each career, school or faculty, so as to be recommended to be included into the curricula, including an elaboration and presentation format using a multi-criteria decision model.

Evolución y crisis de la región metropolitana de Madrid 1985-2007. Análisis de las diversas perspectivas para la transformación del gobierno urbano: una revisión crítica del planeamiento

La Región Metropolitana de Madrid (RMM) ha sufrido una gran transformación urbana en el periodo 1985-2007, en el cual ha crecido la población, ha crecido fuertemente el cuerpo físico, pero sobre todo han crecido su coste y su consumo, lo que supone que se ha vuelto más insostenible. Para tratar de comprender esta evolución asimétrica se ensayan sucesivos modelos que tratan de explicar la transformación de la realidad a través de la articulación de las formas de poder y sus políticas asociadas dentro del contexto local-metropolitano. Si se compara la transformación urbana en el periodo 1985-2007 respecto a la registrada durante el desarrollismo previo al presente periodo democrático, se encuentran similitudes, como el amplio consumo de suelo, pero el modelo desarrollista se inscribe en otras lógicas y tiene otros parámetros de contexto y es congruente ya que las últimas décadas del Régimen Franquista se caracterizan por un importantísimo aumento poblacional que se correspondía con el fuerte crecimiento industrial de la RMM. Esa congruencia relativa se pierde en el periodo estudiado, a pesar de que en 1985, se aprueba el Plan General de Ordenación Urbana de Madrid centrado en la ciudad existente y con un crecimiento contenido, y que puede considerarse un modelo abortado. Tras numerosas transformaciones políticas, económicas, sociales y urbanísticas se llega a una situación opuesta a la prevista en el citado Plan. Más de veinte años después, en 2007, se presentan no solo síntomas de agotamiento del modelo finalmente adoptado, sino su quiebra dramática tanto en su dimensión inmobiliario-financiera como del espacio del bienestar. Es precisamente la supresión de los mecanismos de regulación lo que ha caracterizado la evolución de los modelos urbanos, en correspondencia con la desregulación de las actividades económicas y de los flujos de capital propios del modelo "neoliberal". La actual crisis financiera internacional, en especial en algunos países periféricos europeos como España, ha demostrado cómo las políticas económicas que se han llevado a cabo, fuera de toda regulación, han resultado insostenibles. Pero no se trata solo de una crisis económica. En el caso español, de todas las dimensiones de la crisis, destaca la dimensión urbana, o el auge y caída del ciclo inmobiliario, debido a la urbanización intensiva del territorio en relación con el circuito secundario de la acumulación capitalista, habiendo tenido especial incidencia en algunos territorios como la RMM. En la Región Metropolitana de Madrid la situación actual es de crisis urbana, causada principalmente por el divorcio entre las necesidades y la producción de ciudad, pues no se ha basado el crecimiento en la creación de nuevos hogares, u otras cuestiones demográficas, sino en la acumulación de capital a través del crecimiento de la ciudad. Además, dicho crecimiento está conformado por una expansión urbana descontrolada, con mayores requerimientos energéticos que el modelo compacto y complejo tradicional, lo que unido a la escala de los procesos, supone un sistema urbano progresivamente ineficiente. El caso de la RMM resulta paradigmático, ya que la región ha desempeñado un papel como laboratorio de nuevas formas de gobierno y planificación que han dado un mayor protagonismo al espacio, que ha entrado en las dinámicas centrales principalmente por el apoyo al crecimiento físico, a la vez que han confluido circunstancias específicas, como un nuevo impulso al centralismo, lo que ha potenciado ciertas políticas, como considerar la ciudad como motor de crecimiento económico y de competitividad en el concierto europeo y mundial de ciudades. El estudio del papel de la planificación y sus crisis en la sucesión de los modelos, muestra su función nuclear en la propia constitución de estos —es parte fundamental de su aparato de regulación— y su valor no solo para poder entender el periodo, sino para poder proyectar otro futuro urbano. Este enfoque conduce a establecer la relación del planeamiento con las diferentes crisis económicas en el periodo de estudio lo que permite diferenciar tres momentos de dicha relación: la planificación urbanística austera bajo la influencia de la crisis fordista, la salida de la crisis a través de la imposición de un modelo urbano basado en el sobreproducción de espacio urbano, y la entrada en una crisis inmobiliaria y de financiarización en relación a la adopción de un modelo multidimensionalmente insostenible. El análisis de este periodo es la base para apuntar perspectivas que permitan transformar el gobierno urbano hacia un modelo urbano más deseable, o mejor aún, otros futuros posibles, que se enmarcan dentro de la alternativa principal que supone la sostenibilidad. Madrid's Metropolitan Region (MMR) has undergone a major urban transformation in the period 1985-2007, where the population has grown up, the built environment has grown strongly, but mostly its cost and consumption have grown, which means that it has become unsustainable. To try to understand this evolution successive asymmetric models are tested in order to explain the transformation of reality through the articulation of forms of power and its associated policies in that localmetropolitan context. Comparing the urban transformation in the period 1985-2007 to the existing during developmentalism in the current predemocratic period, both have similarities in terms of land consumption, but the previous developmentalism model is part of another logics and has got other context parameters. It is consistent since the last decades of the Franco Regime was characterized by an important population increase that corresponded to strong industrial growth of the MMR. This relative consistency is lost during the study period, although in 1985, with the approval of the Master Plan of Madrid that was focused on the existing city, with a limited growth, and it may be considered an interrupted model. After numerous political, economic, social and urban changes, there is the opposite situation to that foresight under that Plan. Over twenty years later, in 2007, there are not only signs of exhaustion of the model which was finally adopted, but also its dramatic collapse in both real estate and financial dimension of space as well. The urban transformation under analysis has relaunched the hegemony of the sectors that rule the growth of the Madrid's Metropolitan Region and it is supported by decision making and financing of the different administrations with the passivity of the social stakeholders and citizens. This has meant the removal of regulatory mechanisms that have characterized the evolution of urban models, corresponding to the deregulation of economic activities and capital flows according to "neoliberal" model. The current international financial crisis, especially in some European peripheral countries like Spain, has shown how economic policies that have been carried out, without any regulation, have proven unsustainable. But it is not only an economic crisis. In the Spanish case, of all the dimensions of the crisis, it is the urban dimension that is highlighted, or the rise and fall of real estate cycle, due to intensive urbanization of the territory in relation to the secondary circuit of capital accumulation, having had a particular impact in some territories such as the Madrid's Metropolitan Region. In Madrid's Metropolitan Region there is the current situation of urban crisis, mainly caused by the divorce between needs and the city (space) production, because no growth has been based on creating new homes, or other demographic issues, but in the capital accumulation through growth of the city. Furthermore, this growth is made up of urban sprawl, with higher energy requirements than the traditional compact and complex one, which together with the scale of processes, is increasingly an inefficient urban system. The case of Madrid's Metropolitan Region is paradigmatic, since the region has played a role as a laboratory for new forms of governance and planning have given a greater role to space, which has entered the core dynamics supported mainly by physical growth, while specific circumstances have come together as a new impulse to centralization. This has promoted policies such as considering the city as an engine of economic growth and competitiveness in the international and the European hierarchy of cities. The study of the role of planning and crisis in the succession of models, shows its nuclear role in the constitution of these models is a fundamental part of its regulatory apparatus- and also its value not only to understand the period, but to anticipate to other urban future. This approach leads to establish the relationship of planning with the various crises in the study period, allowing three different moments of that relationship: the austere urban planning under the influence of Fordist crisis, the output of the crisis through imposition of an urban model based on the overproduction of urban space, and entry into a housing crisis and financialisation in relation to the adoption of a multi-dimensionally unsustainable model. The analysis of this period is the basis for targeting prospects that translate urban governance towards a more desirable urban model, or better yet, other possible futures, which are part of the main alternative that is sustainability.

A MAUT approach for reusing ontologies

Knowledge resource reuse has become a popular approach within the ontology engineering field, mainly because it can speed up the ontology development process, saving time and money and promoting the application of good practices. The NeOn Methodology provides guidelines for reuse. These guidelines include the selection of the most appropriate knowledge resources for reuse in ontology development. This is a complex decision-making problem where different conflicting objectives, like the reuse cost, understandability, integration workload and reliability, have to be taken into account simultaneously. GMAA is a PC-based decision support system based on an additive multi-attribute utility model that is intended to allay the operational difficulties involved in the Decision Analysis methodology. The paper illustrates how it can be applied to select multimedia ontologies for reuse to develop a new ontology in the multimedia domain. It also demonstrates that the sensitivity analyses provided by GMAA are useful tools for making a final recommendation.

Dominance intensity measure within fuzzy weight oriented MAUT: an application

We introduce a dominance intensity measuring method to derive a ranking of alternatives to deal with incomplete information in multi-criteria decision-making problems on the basis of multi-attribute utility theory (MAUT) and fuzzy sets theory. We consider the situation where there is imprecision concerning decision-makers’ preferences, and imprecise weights are represented by trapezoidal fuzzy weights.The proposed method is based on the dominance values between pairs of alternatives. These values can be computed by linear programming, as an additive multi-attribute utility model is used to rate the alternatives. Dominance values are then transformed into dominance intensity measures, used to rank the alternatives under consideration. Distances between fuzzy numbers based on the generalization of the left and right fuzzy numbers are utilized to account for fuzzy weights. An example concerning the selection of intervention strategies to restore an aquatic ecosystem contaminated by radionuclides illustrates the approach. Monte Carlo simulation techniques have been used to show that the proposed method performs well for different imprecision levels in terms of a hit ratio and a rank-order correlation measure.

A Maut aprroach for reusing domain ontologies on the basis of the NeOn Methodlogy

Knowledge resource reuse has become a popular approach within the ontology engineering field, mainly because it can speed up the ontology development process, saving time and money and promoting the application of good practices. The NeOn Methodology provides guidelines for reuse. These guidelines include the selection of the most appropriate knowledge resources for reuse in ontology development. This is a complex decision-making problem where different conflicting objectives, like the reuse cost, understandability, integration workload and reliability, have to be taken into account simultaneously. GMAA is a PC-based decision support system based on an additive multi-attribute utility model that is intended to allay the operational difficulties involved in the Decision Analysis methodology. The paper illustrates how it can be applied to select multimedia ontologies for reuse to develop a new ontology in the multimedia domain. It also demonstrates that the sensitivity analyses provided by GMAA are useful tools for making a final recommendation.

Introducción de criterios de sostenibilidad en la elección de emplazamientos industriales mediante modelos multicriterio

(SPA) La elección de localizaciones para la implantación de actividades industriales es un problema complejo, donde a los criterios de coste y eficiencia se han ido añadiendo otros nuevos relativos tanto al impacto en el medio ambiente como a la imagen de la empresa reflejada en la Responsabilidad Social Empresarial. Los criterios medioambientales han ido adquiriendo gran relevancia en la decisión final, hasta convertirse, gracias a la obligación de someter los proyectos a evaluación ambiental, en elementos clave en la decisión final. Por ello, resulta relativamente frecuente que los promotores consulten previamente con la Administración sobre la viabilidad de sus proyectos antes de iniciar un dilatado procedimiento administrativo. En este trabajo se plantea la utilización de indicadores de sostenibilidad y su aplicación, a través de un modelo de decisiones multicriterio, para la ordenación de las distintas opciones de ubicación inicialmente consideradas, de tal forma que se conviertan en instrumento de tanteo y ayuda en la toma de estas decisiones. Para mostrar su utilidad se propone la utilización de la herramienta de apoyo basada en la metodología PROMETHEE y su aplicación en la ordenación de cinco emplazamientos alternativos para la instalación de una cementera en la Comunidad de Madrid según criterios de sostenibilidad. (ENG) The choice of locations for the implementation of industrial activities is a complex problem where the cost and efficiency criteria have been adding new ones relating to the environment impact and the company’s corporate image reflected in Corporate Social Responsability. The environmental criteria have been getting big importance in the final decision, to become key elements in the final decision, due to the duty of submit of environmental assessment projects. Therefore, promoters, quite often, ask previously to the Administration about the viability of their projects before starting a lengthy administrative procedure. This paper proposes the use of sustainability indicators and their application through a multi-criteria decision model for managing the establishment options initially considered, so that they become an help instrument of estimation in order to making these decisions. To show its usefulness we propose the use of the support tool for decision making based on the PROMETHEE methodology and its application in the management of 5 alternative sites for the installation of a cement factory in the Community of Madrid under sustainability criteria.