Benthic foraminiferal accumulation rates of the late Pliocene-Pleistocene in the northern Indian Ocean

During the late Pliocene-middle Pleistocene, 63 species of elongate, bathyal-upper abyssal benthic foraminifera (Extinction Group = Stilostomellidae, Pleurostomellidae, some Nodosariidae) declined in abundance and finally disappeared in the northern Indian Ocean (ODP Sites 722, 758), as part of the global extinction of at least 88 related species at this time. The detailed record of withdrawal of these species differs by depth and geography in the Indian Ocean. In northwest Indian Ocean Site 722 (2045 m), the Extinction Group of 54 species comprised 2-15% of the benthic foraminiferal fauna in the earliest Pleistocene, but declined dramatically during the onset of the mid-Pleistocene Transition (MPT) at 1.2-1.1 Ma, with all but three species disappearing by the end of the MPT (~0.6 Ma). In northeast Indian Ocean Site 758 (2925 m), the Extinction Group of 44 species comprised 1-5% of the benthic foraminiferal fauna at ~3.3-2.6 Ma, but declined in abundance and diversity in three steps, at ~2.5, 1.7, and 1.2 Ma, with all but one species disappearing by the end of the MPT. At both sites there are strong positive correlations between the accumulation rate of the Extinction Group and proxies indicating low-oxygen conditions with a high organic carbon input. In both sites, there was a pulsed decline in Extinction Group abundance and species richness, especially in glacial periods, with some partial recoveries in interglacials. We infer that the glacial declines at the deeper Site 758 were a result of increased production of colder, well-ventilated Antarctic Bottom Water (AABW), particularly in the late Pliocene and during the MPT. The Extinction Group at shallower water depths (Site 722) were not impacted by the deeper water mass changes until the onset of the MPT, when cold, well-ventilated Glacial North Atlantic Intermediate Water (GNAIW) production increased and may have spread into the Indian Ocean. Increased chemical ventilation at various water depths since late Pliocene, particularly in glacial periods, possibly in association with decreased or more fluctuating organic carbon flux, might be responsible for the pulsed global decline and extinction of this rather specialised group of benthic foraminifera.

Thermal diffusion profile by NRA of Deuterium implanted in solid breeder blanket materials

This paper studies the relationship between aging, physical changes and the results of non-destructive testing of plywood. 176 pieces of plywood were tested to analyze their actual and estimated density using non-destructive methods (screw withdrawal force and ultrasound wave velocity) during a laboratory aging test. From the results of statistical analysis it can be concluded that there is a strong relationship between the non-destructive measurements carried out, and the decline in the physical properties of the panels due to aging. The authors propose several models to estimate board density. The best results are obtained with ultrasound. A reliable prediction of the degree of deterioration (aging) of board is presented. Breeder blanket materials have to produce tritium from lithium while fulfilling several strict conditions. In particular, when dealing with materials to be applied in fusion reactors, one of the key questions is the study of light ions retention, which can be produced by transmutation reactions and/or introduced by interaction with the plasma. In ceramic breeders the understanding of the hydrogen isotopes behaviour and specially the diffusion of tritium to the surface is crucial. Moreover the evolution of the microstructure during irradiation with energetic ions, neutrons and electrons is complex because of the interaction of a high number of processes.

Non-destructive methods to estimate physical aging of plywood

This paper studies the relationship between aging, physical changes and the results of non-destructive testing of plywood. 176 pieces of plywood were tested to analyze their actual and estimated density using non-destructive methods (screw withdrawal force and ultrasound wave velocity) during a laboratory aging test. From the results of statistical analysis it can be concluded that there is a strong relationship between the non-destructive measurements carried out, and the decline in the physical properties of the panels due to aging. The authors propose several models to estimate board density. The best results are obtained with ultrasound. A reliable prediction of the degree of deterioration (aging) of board is presented.

Development of an adequate model for verification of design safety-margins of the HTTR nuclear test facility

This work is based on the prototype High Engineering Test Reactor (HTTR) of the Japan Agency of Energy Atomic (JAEA). Its objective is to describe an adequate deterministic model to be used in the assessment of its design safety margins via damage domains. The concept of damage domain is defined and it is shown its relevance in the ongoing effort to apply dynamic risk assessment methods and tools based on the Theory of Stimulated Dynamics (TSD). To illustrate, we present results of an abnormal control rod (CR) withdrawal during subcritical condition and its comparison with results obtained by JAEA. No attempt is made yet to actually assess the detailed scenarios, rather to show how the approach may handle events of its kind

Clasificación de madera estructural de gran escuadría de Pinus sylvestris l. mediante métodos no destructivos

Esta Tesis Doctoral aborda el estudio de algunas técnicas no destructivas para la clasificación de madera de pino silvestre (Pinus sylvestris L.) de procedencia española y de gruesa escuadría para uso estructural. Para la estimación del módulo de elasticidad y de la resistencia se han aplicado técnicas basadas en la propagación de una onda a través de la madera: onda de ultrasonidos (Sylvatest) o de impacto (Microsecond Timer) en dirección longitudinal, o vibración en dirección longitudinal y transversal (PLG). Para la estimación de la densidad se han utilizado métodos puntuales basados en el penetrómetro (Pilodyn) y en la resistencia al arranque de un tornillo. Las variables obtenidas han sido relacionadas con los resultados de la clasificación visual y con las propiedades de la madera determinadas mediante ensayo mecánico. Además, se ha estudiado la influencia de la humedad de la madera en la velocidad de propagación de la onda para definir factores de corrección a los equipos comerciales utilizados en esta Tesis Doctoral. La muestra de estudio está formada por 244 piezas procedentes de El Espinar, Segovia, con dimensiones nominales 150 x 200 x 4000 mm (218 piezas) y 100 x 150 x 3000 mm (26 piezas). De todas las piezas se tomaron datos de dimensiones, contenido de humedad y clasificación visual según la norma UNE 56544. En las primeras 218 vigas se aplicaron las técnicas de ultrasonidos, onda de impacto y vibraciones, se determinó la densidad de cada pieza completa y se ensayaron según la norma UNE-EN 408 para obtener el módulo de elasticidad global (en todos los casos) y local (en un porcentaje), así como de la tensión de rotura. Se extrajeron tres rebanadas para los ensayos puntuales y para el cálculo de la densidad. En las otras 26 piezas se repitieron los ensayos (transmisión de onda, vibración y clasificación visual) durante el proceso de secado natural, desde que la madera se encontraba húmeda (en torno al 40 %) hasta la humedad de equilibrio higroscópico (en torno al 9%). Respecto a la clasificación visual no se han observado diferencias significativas entre la calidad MEG o las rechazadas. Se han estudiado las consecuencias del secado (principalmente las deformaciones) y no se ha encontrado justificación para que estos defectos penalicen la clasificación. Para la densidad, el mayor R2 obtenido ha sido de un 47% a partir del uso combinado de los dos equipos puntuales (penetrómetro y arranque de tornillo). Para el módulo de elasticidad y la tensión de rotura, la mejor relación se ha obtenido a partir de la técnica de vibración longitudinal, con unos coeficientes de 79% y un 52% respectivamente. Se ha estimado que el aumento de un punto porcentual en el contenido de humedad de la madera produce una pérdida de velocidad de onda del 0,58% para Sylvatest y Microsecond Timer, y del 0,71% para PLG. Estos valores son generalizables para un rango de humedades entre 9 y 25 %. Abstract This Doctoral Thesis approach the study of some non-destructive techniques as a classification method for structural use of Scots pine wood of Spanish origin with large cross section. To estimate the modulus of elasticity and strength have been used techniques based on the propagation of a wave through the timber: ultrasonic wave (Sylvatest) or stress wave (Microsecond Timer) in longitudinal direction, or vibration in longitudinal and transversal direction (PLG). Local probing methods have been applied to estimate the density, based on penetrometer (Pilodyn) and the screw withdrawal resistance meter. The different variables obtained were compared with the results of the visual grading and the values of the properties of the wood determined by the standardized test of the pieces. Furthermore, the influence of the moisture content of the wood on the velocity of propagation of the waves through the timber has been analyzed in order to establish a correction factor for the commercial devices used in this Doctoral Thesis. The sample tested consists of 244 pieces from El Espinar, Segovia, with nominal dimensions 150 x 200 x 4000 mm (218 pieces) and 100 x 150 x 3000 mm (26 pieces). Data collection about dimensions, moisture content and visual grading according to the UNE 56544 standard were carried out on all the pieces. The first 218 pieces were tested by non destructive techniques based on ultrasonic wave, stress wave and vibration, the density was measured on each piece and bending test according to the UNE-EN 408 standard was carried out for calculating the global modulus of elasticity (all the pieces) and the local one (only a representative group), as well as the bending strength. Three slices were removed for implementing the local probing and to calculate the density. In the other 26 pieces the tests (wave transmission, vibration and visual grading) were repeated during the natural drying process, from wet timber (around 40 % moisture content) up to the equilibrium moisture content (around 9%). Regarding the visual grading no significant differences were observed between MEG or rejected pieces. The effects of drying (deformations) have been studied, and justification for the specification hasn't been found. To estimate the density, the greater R2 obtained was 47% by using both penetrometer and screw withdrawal. For the modulus of elasticity and bending strength, the best relationship has been found with the longitudinal vibration, with coefficients of 79% and 52% respectively. It has been estimated that an increase of a point of the moisture content of the wood produces a decrease on the velocity obtained from ultrasonic or stress wave of 0,58%, and 0,71 % for the one obtained from vibration. Those values can be generalized for a range of moisture content from 9 to 25 %.

Resistance to malathion and lambda-cyhalothrin in Ceratitis capitata (Wiedemann) (Diptera: Tephritidae)

La mosca mediterránea de la fruta, Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae), es una de las plagas de mayor incidencia económica en cítricos y otros frutales a nivel mundial. En España las medidas de control de esta plaga en cítricos, desde mediados de los 90 hasta 2009, se basaron principalmente en el monitoreo de las poblaciones y en la aplicación de tratamientos aéreos y terrestres con malatión cebo. Sin embargo, desde la retirada en la Unión Europea en 2009 de los productos fitosanitarios que contienen malatión, los insecticidas más utilizados para el control de esta plaga han sido lambda-cihalotrina y spinosad. En 2004-2005 se detectaron poblaciones españolas de C. capitata resistentes a malatión. Esta resistencia se ha asociado a una mutación (G328A) en la acetilcolinesterasa (AChE), a una duplicación del gen de la AChE (Ccace2) (una de las copias lleva la mutación G328A) y a resistencia metabólica mediada por esterasas (posiblemente aliesterasas). Sin embargo, cuando se secuenció la aliesterasa CcE7 en individuos de una línea resistente a malatión, no se encontró ninguna de las mutaciones (G137D y/o W251L/S/G) asociadas a resistencia en otras especies, si bien se encontraron otras mutaciones al compararlos con individuos de una línea susceptible. Asimismo, mediante la selección en laboratorio de una línea resistente a malatión (W-4Km) con lambda-cihalotrina, se ha podido obtener una línea resistente a lambda-cihalotrina (W-1K). Finalmente, se ha demostrado la capacidad de esta especie para desarrollar resistencia a spinosad mediante selección en laboratorio. Los múltiples mecanismos de resistencia identificados evidencian el potencial de esta especie para desarrollar resistencia a insecticidas con diferentes modos de acción. Los objetivos de esta tesis doctoral son: 1) evaluar la susceptibilidad de poblaciones españolas de campo de C. capitata a lambda-cihalotrina y dilucidar los mecanismos de resistencia en la línea W-1Kλ; 2) comparar la herencia, el coste biológico y la estabilidad de la resistencia a malatión mediada por la mutación G328A y la duplicación del gen Ccace2 (una de las copias lleva la mutación G328A); y 3) investigar el papel de las mutaciones identificadas en la aliesterasa CcαE7 en la resistencia a malatión. Estos estudios son de utilidad para el desarrollo de estrategias de manejo de la resistencia que puedan prevenir o retrasar la aparición de resistencia y aumentar la sostenibilidad de los insecticidas disponibles para el control de esta plaga. Nuestros resultados indican que las poblaciones españolas de C. capitata analizadas han desarrollado resistencia a lambda-cihalotrina. Los valores de CL50 estimados para las poblaciones recogidas en la Comunidad Valenciana, Cataluña y Andalucía oscilaron entre 129 ppm y 287 ppm, igualando o sobrepasando la concentración recomendada para los tratamientos de campo (125 ppm). Estos resultados contrastan con los obtenidos con tres poblaciones de campo recogidas en Túnez, cuya susceptibilidad fue similar a la de la línea control (C). La línea resistente a lambda-cihalotrina W-1K se continuó seleccionando en el laboratorio alcanzándose unos niveles de resistencia de 205 veces con respecto a la línea C, siendo su CL50 (4224 ppm) más de 30 veces superior a la concentración recomendada para los tratamientos de campo. Esta línea resistente mostró altos niveles de resistencia cruzada a deltametrina (150 veces) y a etofenprox (240 veces), lo que sugiere que el desarrollo de resistencia a lambda-cihalotrina podría comprometer la eficacia de otros piretroides para el control de esta plaga. Hemos demostrado que la resistencia de la línea W-1K a lambda-cihalotrina fue casi completamente suprimida por el sinergista PBO, lo que indica que las enzimas P450 desempeñan un papel muy importante en la resistencia a este insecticida. Sin embargo, tanto las moscas de la línea susceptible C como las de la línea resistente W-1K perdieron inmediatamente la capacidad de caminar (efecto “knock-down”) al ser tratadas tópicamente con lambda-cihalotrina, lo que sugiere que la resistencia no está mediada por alteraciones en la molécula diana (resistencia tipo “kdr”). La resistencia metabólica mediada por P450 fue analizada comparando la expresión de 53 genes CYP (codifican enzimas P450) de las familias CYP4, CYP6, CYP9 y CYP12 en adultos de la línea resistente W-1K y de la línea susceptible C. Nuestros resultados muestran que el gen CYP6A51 (número de acceso GenBank XM_004534804) fue sobreexpresado (13-18 veces) en la línea W-1K. Por otra parte, la expresión del gen CYP6A51 fue inducida tanto en adultos de la línea W-1K como de la línea C al ser tratados con lambda-cihalotrina. Sin embargo, no se obtuvieron diferencias significativas entre la línea susceptible C y la línea resistente W-1K al comparar la cantidad de P450 y la actividad NADPH-citocromo c reductasa presente en fracciones microsomales obtenidas a partir de abdómenes. Asimismo, no hemos podido correlacionar el metabolismo de deltametrina, estimado in vitro mediante la incubación de este insecticida con fracciones microsomales, con el nivel de resistencia a este piretroide observado en los bioensayos con la línea W-1K. Por otro lado, no se encontró ninguna alteración en la región promotora 5'UTR del gen CYP6A51 (-500 pb desde el inicio de la traducción) que pudiera explicar su sobreexpresión en la línea W-1K. Los datos obtenidos sugieren que la resistencia a lambda-cihalotrina en la línea W-1K está mediada por P450 y que la sobreexpresión de CYP6A51 puede desempeñar un papel importante, aunque se necesitan más evidencias para establecer una asociación directa de la resistencia con este gen. Hemos estudiado la herencia, el coste biológico y la estabilidad de la resistencia a malatión mediada por la mutación G328A y la duplicación del gen Ccace2 (una de las copias lleva la mutación G328A). La línea susceptible C, donde no se encuentra la mutación G328A (genotipo S/S), se cruzó con dos isolíneas establecidas para representar genotipos únicos correspondientes a los dos mecanismos de resistencia asociados a la molécula diana: 1) la isolínea 267Y (genotipo R/R) establecida a partir de una pareja que portaba la mutación G328A en homocigosis; 2) la isolínea 306TY (genotipo RS/RS) establecida a partir de una pareja que portaba en homocigosis la duplicación del gen Ccace2. No se realizaron cruces recíprocos, ya que mediante experimentos de hibridación in situ en cromosomas politénicos se pudo comprobar que el locus de la AChE y la duplicación (probablemente en tándem) se localizan en el cromosoma autosómico 2L. La susceptibilidad al malatión de los parentales resistentes (R/R o RS/RS) y susceptibles (S/S), los cruces F1 (S/R, S/RS y R/RS) y los retrocruzamientos indican que la resistencia a malatión es semi-dominante en ambos casos. Sin embargo, nuestros resultados no fueron concluyentes con respecto a la naturaleza monogénica de la resistencia a malatión en estas isolíneas. Por lo tanto, no podemos descartar que otros genes que contribuyan a la resistencia, además de la mutación G328A (isolínea 267Y) y de la duplicación del gen Ccace2 (isolínea 306TY), puedan haber sido seleccionados durante el proceso de selección de 267Y y 306TY. Varios parámetros biológicos fueron evaluados para determinar si estos dos mecanismos de resistencia a malatión suponen un coste biológico para los genotipos resistentes. Individuos con genotipo R/R mostraron un retraso en el tiempo de desarrollo de huevo a pupa, un peso de pupa reducido y una menor longevidad de los adultos, en comparación con los individuos con genotipo S/S. Sin embargo, el peso de pupa de los individuos con genotipo RS/RS fue similar al de los individuos S/S, y su desarrollo de huevo a pupa intermedio entre S/S y R/R. Estas diferencias en el coste biológico pueden estar relacionadas con la reducción de la eficiencia catalítica de la AChE mutada en los individuos R/R, y al efecto compensatorio que la copia no mutada del gen tiene en los individuos RS/RS que portan la duplicación. La estabilidad de la resistencia a malatión mediada por la mutación G328A y la duplicación se analizó mediante el seguimiento de los caracteres de resistencia en la progenie de retrocruzamientos S/R x R/R y S/RS x RS/RS a lo largo de varias generaciones en ausencia de presión de selección con insecticidas. Nuestros resultados muestran que la frecuencia del alelo que porta la mutación G328A disminuyó desde 67,5% en la primera generación del retrocruzamiento S/R x R/R (75% esperado, asumiendo segregación mendeliana y que sólo hay dos alelos: uno mutado y otro no mutado) a 12% después de 10 generaciones. Por el contrario, la frecuencia de la duplicación sólo disminuyó desde 75% en en la primera generación del retrocruzamiento S/RS x RS/RS (75% esperado, asumiendo segregación Mendeliana y que la duplicación segrega como un único alelo) a 50% en el mismo período, lo que indica que la duplicación es más estable que la mutación. Asimismo, se analizó la presencia de la mutación y de la duplicación en poblaciones de campo recogidas en seis localidades en 2004-2007, cuando todavía se usaba el malatión, y se comparó con poblaciones recogidas en los mismos campos en 2010, un año después de la prohibición del malatión en la Unión Europea. La frecuencia media del genotipo susceptible (S/S) aumentó del 55,9% en el período 2004-2007 a 70,8% en 2010, mientras que la frecuencia de los genotipos portadores de la mutación en homocigosis o heterocigosis (R/R y S/R) disminuyó del 30,4 al 9,2%, los que llevan la duplicación en homocigosis o heterocigosis (RS/RS y S/RS) aumentaron levemente desde 12,8 hasta 13,3%, y los que llevan a la vez la mutación y la duplicación (R/RS) también aumentaron del 1 al 6,7%. Estos resultados son consistentes con que la duplicación del gen Ccace2 (con una copia con la mutación G328A y la otra copia no mutada) es más ventajosa que la mutación G328A por si sola, ya que la duplicación mantiene los niveles de resistencia a la vez que limita el coste biológico. Para investigar la asociación entre la resistencia a malatión y las mutaciones encontradas previamente en CcE7, hemos generado isolíneas con mutaciones específicas seleccionadas por su ubicación próxima a la entrada al centro activo de la enzima. La isolínea Sm2 (procedente de una hembra heterocigota para la mutación V96L y un macho homocigoto para el alelo no mutado) mantuvo altos niveles de resistencia a malatión, incluso después de 30 generaciones sin presión de selección. Por el contrario, la isolínea 267Y (compuesta por individuos homocigotos para la mutación L267Y) y la línea 306TY (compuesta por individuos homocigotos para la doble mutación R306T-N307Y) mostraron una reducción significativa en los niveles de resistencia. También hemos encontrado que la resistencia a malatión de la línea Sm2 fue parcialmente revertida por DEF y TPP, y que Sm2 mostró una reducción significativa en la actividad MTB, como se ha descrito en otras especies que muestran resistencia específica a malatión mediada por aliesterases. Además, fue posible asociar la presencia de la mutación V96L en individuos de la línea Sm2 con supervivencia a una concentración discriminante de malatión (5,000 ppm) y con una baja actividad MTB. Estos resultados sugieren una posible relación entre la mutación V96L en la aliesterasa CcE7 y la resistencia a malatión, aunque todavía no se puede concluir que la resistencia es causada por esta mutación, siendo necesarios más estudios para comprobar su contribución a la resistencia. En conclusión, se ha encontrado por primera vez resistencia a lambda-cihalotrina en poblaciones de campo de C. capitata, y nuestros resultados indican que las P450 son el principal mecanismo de resistencia en la línea W-1K. Esta situación se suma al caso previamente descrito de resistencia en campo a malatión asociada a la mutación G328A, a la duplicación del gen Ccace2 (una de las copias lleva la mutación G328A) y a resistencia metabólica mediada por esterasas. Nuestros resultados también indican que la alteración de la molécula diana AChE parece ser responsable de un cierto nivel de resistencia a malatión en C. capitata, que puede ser estimada como aproximadamente 25-40 veces para la mutación G328A y 40-60 veces para la duplicación; mientras que la resistencia mediada por esterasas y que ha sido asociada en este estudio con la mutación V96L en CcE7 puede conferir un efecto multiplicativo (por un factor de 5 a 10) aumentando la resistencia a malatión a 200-400 veces. Por otra parte, hemos demostrado que los insectos resistentes que llevan la duplicación tienen un coste biológico menor y muestran una estabilidad mayor que aquellos con la mutación G328A en ausencia de presión de selección con insecticidas. Esto representa un escenario en el que los genotipos con la duplicación permanecerán en el campo en frecuencias bajas a moderadas, pero podrían ser seleccionados rápidamente si se utilizan malatión u otros insecticidas que muestren resistencia cruzada. Estos resultados tienen importantes implicaciones para los programas de manejo de la resistencia, ya que el repertorio de insecticidas eficaces para el control de C. capitata es cada vez más limitado. Además, la coexistencia de múltiples mecanismos de resistencia en poblaciones de campo ofrece el potencial para desarrollar resistencia frente a otros insecticidas disponibles para el control de esta plaga. Estrategias para de manejo de la resistencia basadas en la alternancia de insecticidas con diferentes modos de acción, y su combinación con otros métodos de control, deben ser implementadas para evitar el desarrollo de resistencia en campo. ABSTRACT The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae), is one of the most economically damaging pests of citrus and other fruit crops worldwide. Control measures in citrus crops in Spain from the mid 90's to 2009 were mainly based on field monitoring of population levels and aerial and ground treatments with malathion bait sprays. However, since the withdrawal of phytosanitary products containing malathion in the European Union in 2009, lambda-cyhalothrin and spinosad have become the most widely used insecticides for the control of this pest. Resistance to malathion was found in Spanish field populations of C. capitata in 2004-2005. This resistance has been associated with a mutation G328A in the acetylcholinesterase (AChE), a duplication of the AChE gene (Ccace2) (one of the copies bearing the mutation G328A), and metabolic resistance mediated by esterases (probably aliesterases). However, when the gene of the aliesterase CcE7 was sequenced in individuals from a malathion resistant strain of C. capitata, none of the known G137D and/or W251L/S/G mutations associated to resistance in other species were found, though other mutations were detected when compared with individuals from a susceptible strain. Noteworthy, a lambda-cyhalothrin resistant strain (W-1K) was obtained by selecting a field-derived malathion resistant strain (W-4Km) with lambda-cyhalothrin. Moreover, it has also been demonstrated the capacity of this species to develop resistance to spinosad by laboratory selection. The multiple resistance mechanisms identified highlight the potential of this species to develop resistance to insecticides with different modes of action. The objectives of this PhD Thesis are: 1) to assess the susceptibility of Spanish field populations of C. capitata to lambda-cyhalothrin and to elucidate the resistance mechanisms in the W-1Kλ strain; 2) to compare the inheritance, fitness cost and stability of the malathion resistance mediated by the G328A mutation and the duplication of the Ccace2 gene (with one of the copies bearing the mutation G328A); and 3) to investigate the role of the aliesterase CcαE7 mutations in malathion resistance. All these studies will be of use for devising proactive resistance management strategies that could prevent or delay resistance development and would increase the sustainability of the insecticides available for Medfly control. Our results indicate that Spanish field populations of C. capitata have developed resistance to lambda-cyhalothrin. The LC50 values estimated for populations collected at Comunidad Valenciana, Cataluña and Andalucía ranged from 129 ppm to 287 ppm, equaling or overpassing the recommended concentration for field treatments (125 ppm). These results contrast with those obtained with three different Tunisian field populations, whose susceptibility was similar to that of the control (C) strain. The lambda-cyhalothrin resistant W-1K strain has been further selected to achieve a 205-fold resistance compared to the C strain, being its LC50 (4,224 ppm) more than 30 times higher than the recommended concentration for field applications. This resistant strain showed high levels of cross-resistance to deltamethrin (150-fold) and etofenprox (240-fold), suggesting that the development of resistance to lambda-cyhalothrin may compromise the effectiveness of other pyrethroids for the control of this species. We have shown that the resistance of the W-1K strain to lambda-cyhalothrin was almost completely suppressed by the synergist PBO, indicating that P450 enzymes play a very important role in resistance to this insecticide. However, both susceptible C and resistant W-1K flies were knocked down after topical treatment with lambda-cyhalothrin, suggesting that kdr resistance mediated by alterations of the target site is not playing a major role. Metabolic resistance mediated by P450 was further analyzed by comparing the expression of 53 genes of the families CYP4, CYP6, CYP9 and CYP12 in adults flies from the resistant W-1K and the susceptible C strains. We found that the gene CYP6A51 (GenBank accession number XM_004534804) was overexpressed (13-18-fold) in the W-1K strain. Moreover, the expression of the CYP6A51 gene was induced when adults of the W-1K and C strains were treated with lambda-cyhalothrin. However, no significant differences were obtained between susceptible C and resistant W-1K strains for the quantity of P450 and for the activity of NADPH- cytochrome c reductase measured in microsomal fractions obtained from abdomens. Moreover, we failed to correlate the metabolism of deltamethrin, analyzed in vitro by incubating this insecticide with microsomal fractions, with the resistance level against this pyrethroid observed in bioassays with W-1K. The sequencing of the 5´UTR region of the CYP6A51 gene failed in finding an alteration in the promoter region (-500 bp from translation start site) that could explain overexpression in the W-1K strain. All data obtained suggest that resistance to lambda-cyhalothrin in the W- 1K strain is mediated by P450 and that overexpression of CYP6A51 may play a major role, although further evidences are needed to establish a direct association of resistance with this gene. We have studied the inheritance, fitness cost and stability of the malathion resistance mediated by the G328A mutation and the duplication of the Ccace2 gene (with one of the copies bearing the mutation G328A). The malathion-susceptible C strain where the G328A mutation is not found (S/S genotype) was crossed with two isolines established to represent unique genotypes corresponding to the two target-site resistance mechanisms: 1) the 267Y isoline (genotype R/R) was established from a couple bearing the mutation G328A in homozygosis; and 2) the 306TY isoline (genotype RS/RS) was established from a couple being homozygous for the duplication of the Ccace2 gene. Reciprocal crosses have not been performed, since in situ hybridization on polythene chromosomes showed that the AChE locus and the duplication (most probably in tandem) are placed at the autosomal chromosome 2L. Mortality responses to malathion of resistant isolines (R/R or RS/RS) and susceptible (S/S) genotypes, F1 crosses (S/R, S/RS, and R/RS), and the back-crosses indicated that resistance to malathion is inherited as a semi-dominant trait in both cases. However, our results were not conclusive about the monogenic nature of the resistance to malathion in these isolines. Thus, we can not discard that other genes contributing to resistance, in addition to the mutation G328A (isoline 267Y) and the duplication of the Ccace2 gene (isoline 306TY), may have been selected during the selection process of 267Y and 306TY. Several biological parameters were evaluated to determine if these two malathion resistance mechanisms impose a fitness cost for resistant genotypes. Individuals with genotype R/R have a reduced fitness in terms of developmental time from egg to pupa, pupal weight and adult longevity, when compared to susceptible individuals (genotype S/S). Interestingly, the fitness cost was substantially diminished in individuals with genotype RS/RS. These differences in fitness may be related to the reduction of the catalytic efficiency of mutated AChE in individuals R/R, and the compensatory effect that the non-mutated copy of the gene has on individuals RS/RS bearing the duplication. The stability of malathion reistance associated with the mutation G328A or the duplication was analyzed by following these resistant traits in the progeny of the back-crosses S/RS x RS/RS and S/R x R/R over consecutive generations in the absence of insecticide selection pressure. Our results show that the frequency of the allele bearing the mutation G328A decreased from 67.5% at the first generation of the back-cross S/R x R/R (75% expected, assuming Mendelian segregation and that there are only two alleles: one mutated and the other non-mutated) to 12% after 10 generations. By contrast, the frequency of the duplication only declined from 75% at the first generation of the back-cross S/RS x RS/RS (75% expected, assuming Mendelian segregation and that the duplication segregates as an unique allele) to 50% in the same period, indicating that the duplication is more stable than the mutation. The presence of the mutation and the duplication was analyzed in field populations collected in six localities in 2004-2007, when malathion was still used, and compared to populations collected in the same fields in 2010, one year after the prohibition of malathion in the European Union. The average frequency of the susceptible genotype (S/S) increased from 55.9% in the period 2004-2007 to 70.8% in 2010, whereas the frequency of those genotypes carrying the mutation in homozygosis or heterozygosis (R/R and S/R) declined from 30.4 to 9.2%, those carrying the duplication in homozygosis or heterozygosis (RS/RS and S/RS) increased slightly from 12.8 to 13.3%, and those carrying both the mutation and the duplication (R/RS) also increased from 1 to 6.7%. These results are consistent with the duplication of the Ccace2 gene (with one of the copies bearing the mutation G328A and the other copy non-mutated) being more advantageous than the G328A mutation alone by maintaining resistance while restoring part of the fitness. In order to investigate the association of malathion resistance with mutations previously found in the aliesterase CcE7, we have generated isolines bearing specific mutations selected by their putative location near the upper part of the active site gorge of the enzyme. The isoline Sm2 (originating from a female heterozygous for the mutation V96L and a male homozygous for the non-mutated allele) kept high levels of resistance to malathion, even after 30 generations without selection pressure. On the contrary, the isoline 267Y (composed by individuals homozygous for the mutation L267Y) and the strain 306TY (composed by homozygous for the double mutation R306T-N307Y) showed a significant reduction in the levels of resistance. We have found also that resistance to malathion in the Sm2 isoline was partially reverted by DEF and TPP, and that Sm2 showed a significant reduction in MTB activity, as reported for other species showing malathion-specific resistance mediated by aliesterases. Besides, it was possible to associate the presence of the mutation V96L in individuals from the Sm2 isoline with both survival to a discriminating concentration of malathion (5,000 ppm) and low MTB activity. Our results point out to a possible connection betwen the mutation V96L in the aliesterase CcE7 and resistance to malathion, though we can not yet conclude that the resistance is caused by the mutation, being needed further work to understand its contribution to resistance. In conclusion, resistance to lambda-cyhalothrin has been found for the first time in field populations of C. capitata, and metabolic resistance mediated by P450 appears to be the main resistance mechanism in the resistant strain W-1K. These findings add to the previously reported case of field resistance to malathion, associated to the G328A mutation and the duplication of the Ccace2 gene (with one of the copies bearing the mutation G328A) and to metabolic resistance mediated by esterases. Our results also indicate that altered target site AChE appears to be responsible for a certain level of resistance to malathion in C. capitata, that can be estimated as about 25-40-fold for the mutation G328A and 40-60-fold for the duplication; whereas metabolic resistance mediated by esterases and associated in this study with the mutation V96L in CcE7 may confer a multiplicative effect (by a factor of 5 to10) increasing malathion resistance to 200-400-fold. Moreover, we have shown that resistant insects carrying the duplication have better fitness and exhibit a higher stability than those with the mutation G328A in the absence of insecticide pressure. This represents a scenario where genotypes with the duplication will remain in the field at low to moderate frequencies, but could be rapidly selected if malathion or other insecticides showing cross-resistance are used. These findings have important implications for resistance management programs, as the repertoire of effective insecticides for C. capitata control is becoming very limited. Besides, multiple resistance mechanisms coexisting in field populations provide the potential to develop resistance to other available insecticides for the control of this pest. Appropriate resistance management strategies based on the alternation of insecticides with different modes of action, and their combination with other control methods, must then be implemented to avoid the evolution of resistance in the field.

Basketball retirement: process and outcomes

Retirement from a sport career represents a turning point in the life of a sportsman. The aim of this study was to determine how the process of withdrawal of professional basketball players and the factors that influence it. Using a qualitative methodology, semi-structured interviews were conducted with 6 professional players focusing on their experiences during the process. Analysis of the interviews revealed the need to treat this process from a multidimensional perspective, as several factors interact. The results obtained show that the players assign great importance to the economic, academic and adjustment difficulties. Consequently, we discuss the need for specific assistance programs for these athletes, regardless of their previous professional level.

One-dimensional linear analysis of the liquid injection or removal in a liquid bridge

The filling-withdrawal process of a long liquid bridge is analyzed using a one-dimensional linearized model for the dynamics of the liquid column. To carry out this study, a well-known standard operational method (Laplace transform) has been used, and time variation of both liquid velocity field and interface shape are obtained.

Assessment of damage domains of the High-Temperature Engineering Test Reactor (HTTR)

This paper presents an assessment analysis of damage domains of the 30 MWth prototype High-Temperature Engineering Test Reactor (HTTR) operated by the Japan Atomic Energy Agency (JAEA). For this purpose, an in-house deterministic risk assessment computational tool was developed based on the Theory of Stimulated Dynamics (TSD). To illustrate the methodology and applicability of the developed modelling approach, assessment results of a control rod (CR) withdrawal accident during subcritical conditions are presented and compared with those obtained by the JAEA.

Evaluación de un sistema de energía solar térmica basado en colectores de tubos de vacío para suministro de agua a alta temperatura

Esta tesis pretende contribuir al fomento y utilización de la energía solar como alternativa para la producción de agua caliente en el sector agroindustrial. La demanda de agua caliente es un aspecto clave en un gran número de agroindustrias y explotaciones agrarias. Esta demanda presenta una gran variabilidad, tanto en los horarios en que se solicita como en la temperatura del agua del depósito requerida (TADr), difiriendo del perfil de demanda habitual para uso doméstico. Existe una necesidad de profundizar en la influencia que tiene la variación de la TADr en la eficiencia y viabilidad de estos sistemas. El objetivo principal de esta tesis es caracterizar el funcionamiento de un sistema solar térmico (SST) con captador de tubos de vacío (CTV) para producir agua a temperaturas superiores a las habituales en estos sistemas. Se pretende determinar la influencia que la TADr tiene sobre la eficiencia energética del sistema, cuantificar el volumen de agua caliente que es capaz de suministrar en función de la TADr y determinar la rentabilidad del SST como sistema complementario de suministro. Para ello, se ha diseñado, instalado y puesto a punto un sistema experimental de calentamiento de agua, monitorizando su funcionamiento a diferentes TADr bajo condiciones ambientales reales. Los resultados cuantifican cómo el aumento de la TADr provoca una disminución de la energía suministrada al depósito, pudiendo superar diferencias de 1000 Wh m-2 d-1 entre 40 ºC y 80 ºC, para valores de irradiación solar próximos a 8000 Wh m-2 d-1 (la eficiencia del sistema oscila entre 73% y 56%). Esta reducción es consecuencia de la disminución de la eficiencia del captador y del aumento de las pérdidas de calor en las tuberías del circuito. En cuanto al agua suministrada, cuanto mayor es la TADr, mayor es la irradiación solar requerida para que tenga lugar la primera descarga de agua, aumentando el tiempo entre descargas y disminuyendo el número de éstas a lo largo del día. A medida que se incrementa la TADr, se produce una reducción del volumen de agua suministrado a la TADr, por factores como la pérdida de eficiencia del captador, las pérdidas en las tuberías, la energía acumulada en el agua que no alcanza la TADr y la mayor energía extraída del sistema en el agua producida. Para una TADr de 80 ºC, una parte importante de la energía permanece acumulada en el depósito sin alcanzar la TADr al final del día. Para aprovechar esta energía sería necesario disponer de un sistema complementario de suministro, ya que las pérdidas de calor nocturnas en el depósito pueden reducir considerablemente la energía útil disponible al día siguiente. La utilización del sistema solar como sistema único de suministro es inviable en la mayoría de los casos, especialmente a TADr elevadas, al no ajustarse la demanda de agua caliente a la estacionalidad de la producción del sistema solar, y al existir muchos días sin producción de agua caliente por la ausencia de irradiación mínima. Por el contrario, la inversión del sistema solar como sistema complementario para suministrar parte de la demanda térmica de una instalación es altamente recomendable. La energía útil anual del sistema solar estimada oscila entre 1322 kWh m-2 y 1084 kWh m-2. La mayor rentabilidad se obtendría suponiendo la existencia de una caldera eléctrica, donde la inversión se recuperaría en pocos años -entre 5.7 años a 40 ºC y 7.2 años a 80 ºC -. La rentabilidad también es elevada suponiendo la existencia de una caldera de gasóleo, con periodos de recuperación inferiores a 10 años. En una industria ficticia con demanda de 100 kWh d-1 y caldera de gasóleo existente, la inversión en una instalación solar optimizada sería rentable a cualquier TADr, con valores de VAN cercanos a la inversión realizada -12000 € a 80 ºC y 15000€ a 40 ºC- y un plazo de recuperación de la inversión entre 8 y 10 años. Los resultados de este estudio pueden ser de gran utilidad a la hora de determinar la viabilidad de utilización de sistemas similares para suministrar la demanda de agua caliente de agroindustrias y explotaciones agropecuarias, o para otras aplicaciones en las que se demande agua a temperaturas distintas de la habitual en uso doméstico (60 ºC). En cada caso, los rendimientos y la rentabilidad vendrán determinados por la irradiación de la zona, la temperatura del agua requerida y la curva de demanda de los procesos específicos. ABSTRACT The aim of this thesis is to contribute to the development and use of solar energy as an alternative for producing hot water in the agribusiness sector. Hot water supply is a key issue for a great many agribusinesses and agricultural holdings. Both hot water demand times and required tank water temperature (rTWT) are highly variable, where the demand profile tends to differ from domestic use. Further research is needed on how differences in rTWT influence the performance and feasibility of these systems. The main objective of this thesis is to characterize the performance and test the feasibility of an evacuated tube collector (ETC) solar water heating (SWH) system providing water at a higher temperature than is usual for such systems. The aim is to determine what influence the rTWT has on the system’s energy efficiency, quantify the volume of hot water that the system is capable of supplying at the respective rTWT and establish whether SWH is feasible as a booster supply system for the different analysed rTWTs. To do this, a prototype water heating system has been designed, installed and commissioned and its performance monitored at different rTWTs under real operating conditions. The quantitative results show that a higher rTWT results in a lower energy supply to the tank, where the differences may be greater than 1000 Wh m-2 d-1 from 40 ºC to 80 ºC for insolation values of around 8000 Wh m-2 d-1 (system efficiency ranges from 73% to 56%). The drop in supply is due to lower collector efficiency and greater heat losses from the pipe system. As regards water supplied at the rTWT, the insolation required for the first withdrawal of water to take place is greater at higher rTWTs, where the time between withdrawals increases and the number of withdrawals decreases throughout the day. As rTWT increases, the volume of water supplied at the rTWT decreases due to factors such as lower collector efficiency, pipe system heat losses, energy stored in the water at below the rTWT and more energy being extracted from the system by water heating. For a rTWT of 80 ºC, much of the energy is stored in the tank at below the rTWT at the end of the day. A booster supply system would be required to take advantage of this energy, as overnight tank heat losses may significantly reduce the usable energy available on the following day. It is often not feasible to use the solar system as a single supply system, especially at high rTWTs, as, unlike the supply from the solar heating system which does not produce hot water on many days of the year because insolation is below the required minimum, hot water demand is not seasonal. On the other hand, investment in a solar system as a booster system to meet part of a plant’s heat energy demand is highly recommended. The solar system’s estimated annual usable energy ranges from 1322 kWh m-2 to 1084 kWh m-2. Cost efficiency would be greatest if there were an existing electric boiler, where the payback period would be just a few years —from 5.7 years at 40 ºC to 7.2 years at 80 ºC—. Cost efficiency is also high if there is an existing diesel boiler with payback periods of under 10 years. In a fictitious industry with a demand of 100 kWh day-1 and an existing diesel boiler, the investment in the solar plant would be highly recommended at any rTWT, with a net present value similar to investment costs —12000 € at 80 ºC and 15000 € at 40 ºC— and a payback period of 10 years. The results of this study are potentially very useful for determining the feasibility of using similar systems for meeting the hot water demand of agribusinesses and arable and livestock farms or for other applications demanding water at temperatures not typical of domestic demand (60ºC). Performance and cost efficiency will be determined by the regional insolation, the required water temperature and the demand curve of the specific processes in each case.

The effect of moisture content on nondestructive probing measurements

When assessing existing timber structures it is not possible to obtain density as the ratio mass/volume, so nondestructive probing methods are used to predict density. As in other nondestructive techniques, moisture content influences measurements. The goal of this paper is to study the influence of timber moisture content on two nondestructive probing techniques (penetration resistance and pullout resistance). 25 large cross section specimens of laricio pine from Spain were measured. The moisture content ranged from 65.1% to 8.3%. Penetration depth decreases and screw withdrawal strength increases when moisture content decreases below the fiber saturation point. There are lineal tendencies in both techniques. No moisture content influence was found in measures above fiber saturation point.

Fernando García Mercadal y el Movimiento Moderno

La tesis plantea el estudio de la figura de Fernando García Mercadal (1896- 1985) y su obra, en el contexto del proyecto moderno perteneciente a la racionalidad teórica colectiva de la segunda generación del Movimiento Moderno en Europa, y explora la vida y circunstancias de un arquitecto que aunque nacido en el XIX, trajo la modernidad a España. El Movimiento Moderno en España, se articula en las décadas de los años 20 y 30 a través del GATEPAC y un grupo de arquitectos racionalistas en Madrid que Carlos Flores denomina Generación del 1925. Fernando García Mercadal, primero de su promoción en 1921 y pensionado en Roma, pertenece a ambos y pronto se convierte junto con Josep Lluis Sert, en una de las figuras más relevantes del panorama moderno español. Único miembro fundador del GATEPAC que había nacido en el siglo XIX, publica habitualmente en la revista AC (1931-1937), y en la revista Arquitectura desde 1920. Organiza en la Residencia de Estudiantes, entre 1928 y 1932, un famoso ciclo de Conferencias que imparten Le Corbusier, Mendelsohn, Van Doesburg, Gropius y Giedion. También asiste a la reunión constituyente de los CIAM en La Sarraz en 1928, al CIAM II en Frankfurt en 1929 y al CIAM III en Bruselas en 1930. Fue profesor en la Escuela de Arquitectura de Madrid y Arquitecto Jefe de la Oficina de Urbanismo y de Parques y Jardines del Ayuntamiento de Madrid, cargo al que accede por oposición en 1932. Tras la guerra fue depurado e inhabilitado profesionalmente, hasta que en 1946 comienza a trabajar en el Departamento de Arquitectura del I.N.P. donde continúa hasta los años 70. En 1979 es nombrado Académico de número de la Real Academia de Bellas Artes de San Fernando y muere en Madrid en 1985. Estos son los datos conocidos y aunque en la tesis se aportan nuevos datos inéditos, es en las premisas para su interpretación donde este trabajo de investigación pone el acento. En la historiografía de nuestra arquitectura moderna, pervive una tendencia a suponer una desconexión entre la vanguardia arquitectónica en los años 20 y 30 y el movimiento moderno internacional. El manto de silencio que cayó sobre la generación anterior a la guerra, una vez terminada esta, contribuye a reforzar la idea, cuyo origen y causas exceden el ámbito de trabajo, aunque se tratarán tangencialmente por ser ineludible hacerlo. La tesis pone en cuestión ese planteamiento desde el convencimiento fundamentado en los datos y en la consulta de fuentes originales, que la arquitectura española anterior a la guerra, aun con las circunstancias particulares del país, estuvo en sintonía con la europea, siendo esta la hipótesis de partida de la investigación. Las aportaciones más significativas que, a mi entender, presenta la tesis doctoral, y tienen mayor originalidad, son las siguientes; 1.Puesta en valor de la arquitectura de FGM, antes y después de la guerra, abandonando la idea de su supuesta renuncia a las ideas modernas a partir de los 30; 2. Puesta en valor, con aportación de datos concretos, de la Intensa relación mantenida por FGM y otros arquitectos españoles del Movimiento Moderno con los arquitectos de igual tendencia en el resto de Europa, a través de contactos recíprocos y continuos; 3. Estudio de la obra de FGM en el marco del Movimiento Moderno como una nueva arquitectura basada no tanto en la epidermis, como en una forma de hacer y encarar los problemas donde el proceso es tan importante como el resultado; con el Urbanismo como una nueva ciencia, y con el desarrollo de nuevos programas funcionales acordes a las necesidades de la sociedad contemporánea como el Rincón de Goya y el Hospital de Zaragoza. Se manejan tres métodos de trabajo. Los dos primeros aportan un nuevo enfoque al análisis crítico de FGM y su obra, situándole en el contexto internacional, además del español. El tercero, de carácter instrumental, permite el manejo y sistematización de la documentación. El primer método, consiste en aplicar el criterio generacional de Pevsner o Giedion entre otros, al Movimiento Moderno en España, situando a Fernando García Mercadal como arquitecto de la segunda generación, para hacer un análisis crítico comparativo de su trayectoria con otros arquitectos europeos de la misma, que permita establecer semejanzas y diferencias. El segundo método, complementario al anterior, consiste en estudiar las relaciones internacionales de FGM con las figuras más próximas a él y sus posibles influencias. Por último, y en relación con la documentación de obras y proyectos, se manejan a su vez dos criterios. Para la obra completa, y debido a la inexistencia de originales del Legado García Mercadal, se utiliza con carácter general el material ya publicado, disperso en libros y revistas. En el caso de las cinco obras seleccionadas, se completa con búsqueda en archivos, toma de datos in situ actualizados cuando es posible, y una recopilación de su repercusión en prensa escrita de su momento. ABSTRACT This research study focuses on Fernando Garcia Mercadal (1896-1985) and his work in the context of the Modern project as part of the collective theoretical rationality of the second generation of European Modern architecture. It explores the life and circumstances of the architect, who even though born in 19th century introduced Modern architecture in Spain. Modern architecture (Modern Movement) in Spain covered two decades between 20's and 30's through GATEPAC and a group of rationalists in Madrid that Carlos Flores named “generation of '25”. Fernando Garcia Mercadal, top of his class in 1921 and granted with the scholarship in Rome, belonged to both groups and early in his career he became, along with Josep Lluis Sert, one of the most relevant figures of Modern Architecture in Spain. He was the only member of GATEPAC who was born in 19th century. He frequently published on the magazine “AC” (1931-1937) and on “Arquitecture” magazine since 1920. He organized a series of famous lectures at “Residencia de Estudiantes” (Madrid) between 1928 and 1932 in which Le Corbusier, Mendelsohn, Van Doesburg, Gropius or Giedion took part. He was a member of the constituent meeting of CIAM in La Sarraz in 1928, CIAM II in Frankfurt in 1929 and CIAM III in Brussels in 1930. Mercadal was a teacher at Escuela de Arquitectura de Madrid and the Chief of the Urban Planning, Parks and Gardens Office of the Council of Madrid. He earned his position by public examination in 1932. After the civil war he was disqualified professionally until 1946, when he started working at the Architecture Department at INP until 70's. In 1979 he was elected as an academic member of “Real Academia de Bellas Artes de San Fernando” and later died in 1985. These are the well-known facts and even though this research study provides unpublished facts, it focuses on the premises to interpret them. Throughout the historiographical discourse of Spanish Modern architecture there is a tendency to assume a disconnection between the Avant-garde architecture movements in 20's and 30's and International Modern architecture (Modern Movement). The generation preceding the war remained silent in regard to this issue and once the war was over, they contributed to support the disconnection. The origin and cause exceed the frame of this work, even though they are incidentally commented due to its importance. This research study questions the approach explained above, based on the facts and the original sources. Its first hypothesis states that Spanish architecture before the civil war was, under its own circumstances, in tune with European architecture. The most important and original contributions of this research study are the following under my point of view: 1. To highlight the architecture of FGM, before and after the war, leaving behind his reputed withdrawal of Modernity after 30's; 2. To highlight the intense relationship between FGM and other Modern Spanish architects and other European architects sharing the same ideas, providing detailed facts; 3. Study of FGM's work in the context of Modern architecture as a new architecture based on its know-how and the way problems are faced. The process is as important as the result, not so much based on the dermis; with urban planning as the new science and with the development of the new functional programs based on the needs of contemporary society as in Rincón de Goya or Hospital de Zaragoza. Three work methods are used. The first two add a new vision of the critical analysis related to FGM and his work, positioning him in the international context in addition to Spain. The third is used as an instrument to manage and systematize the documentation. The first method applies the generational criteria of Pevsner or Giedion (among others) to Modern architecture in Spain, positioning Fernando Garcia Mercadal as a second generation architect. A critical-comparative analysis of his career and contemporary European architects is made to establish similarities and differences. The second method is complementary to the previous one and studies the international relationships of FGM with other recognised architects that were close to him and their possible influences. At last, in relation to his works and projects, two methods are used. For the complete works, due to the lack of originals, published material found on magazines and books is used as the source. In the case of the five selected buildings, it is complemented with archive search, onsite data collection when possible and the impact on the press at that moment.

DE UMA CRISE A OUTRA, DE UM DARWINISMO A OUTRO: A IMPLANTAÇÃO DA PROGRESSÃO CONTINUADA NO ESTADO DE SÃO PAULO

O presente trabalho investiga a implantação do regime de progressão continuada nas escolas públicas do estado de São Paulo em 1998, de modo que tem como eixo de pesquisa e reflexões a política pública progressão continuada e seu processo de implantação e implementação. Houve o uso de duas linhas de pesquisa: pesquisa bibliográfica e pesquisa e análise do discurso oficial, não somente aquele que implanta o regime citado, mas também a gradação das leis e suas características. O suporte central de pesquisa apoia-se em duas consagradas obras: “A estrutura das revoluções científicas” e “A origem das espécies”, de Thomas Kuhn e Charles Darwin, respectivamente. As obras citadas farão jus ao título desse trabalho, a qual utiliza das discussões propostas por Kuhn sobre ‘crise’, tendo esta como uma das linhas mestras para analisar os períodos pré e pós implantação do regime combinado ao darwinismo, que aqui se denomina darwinismo pedagógico. Para estabelecer uma conexão entre o objeto central de pesquisa e as obras acima citadas, houve a necessidade de pesquisar e discutir temáticas diretamente relacionadas, como ‘um rio e seus afluentes’. Os ‘afluentes’ pesquisados e discutidos foram: pedagogia e ciência, regime de seriação, darwinismo, metáfora, políticas públicas, gradação das leis, identidade, resistência e desistência. Os ‘afluentes’ não ficaram restritos a pesquisa bibliográfica, houve a necessidade de também no discurso oficial realizar esta linha metodológica. A pesquisa revelou que a partir das contribuições de Kuhn, a implantação do regime de progressão continuada nas escolas públicas do estado de São Paulo apenas fez com que a educação no estado saísse de uma crise e entrasse em outra. Além disso, revelou também que o darwinismo pedagógico que imperava no regime de seriação, muda de face no regime de progressão continuada, porém continua ativo, agora afetando diretamente os docentes, que resistem ativamente ou em oposição, ou desistem, seja de forma anunciada ou velada.

Different mechanisms for suppression of apoptosis by cytokines and calcium mobilizing compounds

Overexpression of wild-type p53 in M1 myeloid leukemia cells induces apoptotic cell death that was suppressed by the calcium ionophore A23187 and the calcium ATPase inhibitor thapsigargin (TG). This suppression of apoptosis by A23187 or TG was associated with suppression of caspase activation but not with suppression of wild-type-p53-induced expression of WAF-1, mdm-2, or FAS. In contrast to suppression of apoptosis by the cytokines interleukin 6 (IL-6) and interferon γ, a protease inhibitor, or an antioxidant, suppression of apoptosis by A23187 or TG required extracellular Ca2+ and was specifically abolished by the calcineurin inhibitor cyclosporin A. IL-6 induced immediate early activation of junB and zif/268 (Egr-1) but A23187 and TG did not. A23187 and TG also suppressed induction of apoptosis by doxorubicin or vincristine in M1 cells that did not express p53 by a cyclosporin A-sensitive mechanism. Suppression of apoptosis by A23187 or TG was not associated with autocrine production of IL-6. Apoptosis induced in IL-6-primed M1 cells after IL-6 withdrawal was not suppressed by A23187 or TG but was suppressed by the cytokines IL-6, IL-3, or interferon γ. The results indicate that these Ca2+-mobilizing compounds can suppress some pathways of apoptosis suppressed by cytokines but do so by a different mechanism.

Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment

Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100–300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: (i) spatially, by growing tumors in subcutaneous or cranial locations and (ii) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 μm. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: (i) delivery may be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery may be reduced during tumor regression induced by hormonal ablation, and (iii) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.