962 resultados para Two variable oregonator model
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A finite element model was used to simulate timberbeams with defects and predict their maximum load in bending. Taking into account the elastoplastic constitutive law of timber, the prediction of fracture load gives information about the mechanisms of timber failure, particularly with regard to the influence of knots, and their local graindeviation, on the fracture. A finite element model was constructed using the ANSYS element Plane42 in a plane stress 2D-analysis, which equates thickness to the width of the section to create a mesh which is as uniform as possible. Three sub-models reproduced the bending test according to UNE EN 408: i) timber with holes caused by knots; ii) timber with adherent knots which have structural continuity with the rest of the beam material; iii) timber with knots but with only partial contact between knot and beam which was artificially simulated by means of contact springs between the two materials. The model was validated using ten 45 × 145 × 3000 mm beams of Pinus sylvestris L. which presented knots and graindeviation. The fracture stress data obtained was compared with the results of numerical simulations, resulting in an adjustment error less of than 9.7%
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This paper investigates the propagation of airblast or pressure waves in air produced by bench blasting (i.e. detonation of the explosive in a row of blastholes, breaking the burden of rock towards the free vertical face of the block). Peak overpressure is calculated as a function of blasting parameters (explosive mass per delay and velocity at which the detonation sequence proceeds along the bench) and the polar coordinates of the position of interest (distance to the source and azimuth with respect to the free face). The model has been fitted to empirical data using linear least squares. The data set is composed of 122 airblast records monitored at distances less than 400 m in 41 production blasts carried out in two quarries. The model is statistically significant and has a determination coefficient of 0.87. The formula is validated from 12 airblast measurements gathered in five additional blasts.
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ZnO nanofibre networks (NFNs) were grown by vapour transport method on Si-based substrates. One type of substrate was SiO2 thermally grown on Si and another consisted of a Si wafer onto which Si nanowires (NWs) had been grown having Au nanoparticles catalysts. The ZnO-NFN morphology was observed by scanning electron microscopy on samples grown at 600 °C and 720 °C substrate temperature, while an focused ion beam was used to study the ZnO NFN/Si NWs/Si and ZnO NFN/SiO2 interfaces. Photoluminescence, electrical conductance and photoconductance of ZnO-NFN was studied for the sample grown on SiO2. The photoluminescence spectra show strong peaks due to exciton recombination and lattice defects. The ZnO-NFN presents quasi-persistent photoconductivity effects and ohmic I-V characteristics which become nonlinear and hysteretic as the applied voltage is increased. The electrical conductance as a function of temperature can be described by a modified three dimensional variable hopping model with nanometer-ranged typical hopping distances.
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RESUMEN Las enfermedades cardiovasculares constituyen en la actualidad la principal causa de mortalidad en el mundo y se prevé que sigan siéndolo en un futuro, generando además elevados costes para los sistemas de salud. Los dispositivos cardiacos implantables constituyen una de las opciones para el diagnóstico y el tratamiento de las alteraciones del ritmo cardiaco. La investigación clínica con estos dispositivos alcanza gran relevancia para combatir estas enfermedades que tanto afectan a nuestra sociedad. Tanto la industria farmacéutica y de tecnología médica, como los propios investigadores, cada día se ven involucrados en un mayor número de proyectos de investigación clínica. No sólo el incremento en su volumen, sino el aumento de la complejidad, están generando mayores gastos en las actividades asociadas a la investigación médica. Esto está conduciendo a las compañías del sector sanitario a estudiar nuevas soluciones que les permitan reducir los costes de los estudios clínicos. Las Tecnologías de la Información y las Comunicaciones han facilitado la investigación clínica, especialmente en la última década. Los sistemas y aplicaciones electrónicos han proporcionado nuevas posibilidades en la adquisición, procesamiento y análisis de los datos. Por otro lado, la tecnología web propició la aparición de los primeros sistemas electrónicos de adquisición de datos, que han ido evolucionando a lo largo de los últimos años. Sin embargo, la mejora y perfeccionamiento de estos sistemas sigue siendo crucial para el progreso de la investigación clínica. En otro orden de cosas, la forma tradicional de realizar los estudios clínicos con dispositivos cardiacos implantables precisaba mejorar el tratamiento de los datos almacenados por estos dispositivos, así como para su fusión con los datos clínicos recopilados por investigadores y pacientes. La justificación de este trabajo de investigación se basa en la necesidad de mejorar la eficiencia en la investigación clínica con dispositivos cardiacos implantables, mediante la reducción de costes y tiempos de desarrollo de los proyectos, y el incremento de la calidad de los datos recopilados y el diseño de soluciones que permitan obtener un mayor rendimiento de los datos mediante la fusión de datos de distintas fuentes o estudios. Con este fin se proponen como objetivos específicos de este proyecto de investigación dos nuevos modelos: - Un modelo de recuperación y procesamiento de datos para los estudios clínicos con dispositivos cardiacos implantables, que permita estructurar y estandarizar estos procedimientos, con el fin de reducir tiempos de desarrollo Modelos de Métrica para Sistemas Electrónicos de Adquisición de Datos y de Procesamiento para Investigación Clínica con Dispositivos Cardiacos Implantables de estas tareas, mejorar la calidad del resultado obtenido, disminuyendo en consecuencia los costes. - Un modelo de métrica integrado en un Sistema Electrónico de Adquisición de Datos (EDC) que permita analizar los resultados del proyecto de investigación y, particularmente del rendimiento obtenido del EDC, con el fin de perfeccionar estos sistemas y reducir tiempos y costes de desarrollo del proyecto y mejorar la calidad de los datos clínicos recopilados. Como resultado de esta investigación, el modelo de procesamiento propuesto ha permitido reducir el tiempo medio de procesamiento de los datos en más de un 90%, los costes derivados del mismo en más de un 85% y todo ello, gracias a la automatización de la extracción y almacenamiento de los datos, consiguiendo una mejora de la calidad de los mismos. Por otro lado, el modelo de métrica posibilita el análisis descriptivo detallado de distintos indicadores que caracterizan el rendimiento del proyecto de investigación clínica, haciendo factible además la comparación entre distintos estudios. La conclusión de esta tesis doctoral es que los resultados obtenidos han demostrado que la utilización en estudios clínicos reales de los dos modelos desarrollados ha conducido a una mejora en la eficiencia de los proyectos, reduciendo los costes globales de los mismos, disminuyendo los tiempos de ejecución, e incrementando la calidad de los datos recopilados. Las principales aportaciones de este trabajo de investigación al conocimiento científico son la implementación de un sistema de procesamiento inteligente de los datos almacenados por los dispositivos cardiacos implantables, la integración en el mismo de una base de datos global y optimizada para todos los modelos de dispositivos, la generación automatizada de un repositorio unificado de datos clínicos y datos de dispositivos cardiacos implantables, y el diseño de una métrica aplicada e integrable en los sistemas electrónicos de adquisición de datos para el análisis de resultados de rendimiento de los proyectos de investigación clínica. ABSTRACT Cardiovascular diseases are the main cause of death worldwide and it is expected to continue in the future, generating high costs for health care systems. Implantable cardiac devices have become one of the options for diagnosis and treatment of cardiac rhythm disorders. Clinical research with these devices has acquired great importance to fight against these diseases that affect so many people in our society. Both pharmaceutical and medical technology companies, and also investigators, are involved in an increasingly number of clinical research projects. The growth in volume and the increase in medical research complexity are contributing to raise the expenditure level associated with clinical investigation. This situation is driving health care sector companies to explore new solutions to reduce clinical trial costs. Information and Communication Technologies have facilitated clinical research, mainly in the last decade. Electronic systems and software applications have provided new possibilities in the acquisition, processing and analysis of clinical studies data. On the other hand, web technology contributed to the appearance of the first electronic data capture systems that have evolved during the last years. Nevertheless, improvement of these systems is still a key aspect for the progress of clinical research. On a different matter, the traditional way to develop clinical studies with implantable cardiac devices needed an improvement in the processing of the data stored by these devices, and also in the merging of these data with the data collected by investigators and patients. The rationale of this research is based on the need to improve the efficiency in clinical investigation with implantable cardiac devices, by means of reduction in costs and time of projects development, as well as improvement in the quality of information obtained from the studies and to obtain better performance of data through the merging of data from different sources or trials. The objective of this research project is to develop the next two models: • A model for the retrieval and processing of data for clinical studies with implantable cardiac devices, enabling structure and standardization of these procedures, in order to reduce the time of development of these tasks, to improve the quality of the results, diminish therefore costs. • A model of metric integrated in an Electronic Data Capture system (EDC) that allow to analyze the results of the research project, and particularly the EDC performance, in order to improve those systems and to reduce time and costs of the project, and to get a better quality of the collected clinical data. As a result of this work, the proposed processing model has led to a reduction of the average time for data processing by more than 90 per cent, of related costs by more than 85 per cent, and all of this, through automatic data retrieval and storage, achieving an improvement of quality of data. On the other hand, the model of metrics makes possible a detailed descriptive analysis of a set of indicators that characterize the performance of each research project, allowing inter‐studies comparison. This doctoral thesis results have demonstrated that the application of the two developed models in real clinical trials has led to an improvement in projects efficiency, reducing global costs, diminishing time in execution, and increasing quality of data collected. The main contributions to scientific knowledge of this research work are the implementation of an intelligent processing system for data stored by implantable cardiac devices, the integration in this system of a global and optimized database for all models of devices, the automatic creation of an unified repository of clinical data and data stored by medical devices, and the design of a metric to be applied and integrated in electronic data capture systems to analyze the performance results of clinical research projects.
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El viento, como factor medio-ambiental, ha sido objeto de numerosos estudios por los efectos que induce tanto en vehículos como en estructuras. Dentro del ámbito ferroviario, las cargas aerodinámicas debidas a la acción del viento transversal pueden poner en compromiso la seguridad de los vehículos en circulación, pudiendo llegar a ocasionar el vuelco del mismo. Incluso el sistema de cables encargado de realizar el suministro eléctrico necesario para la tracción del tren, conocido como catenaria, es sensible a la acción del viento. De hecho, al igual que ocurre en ciertas estructuras de cables, la interacción entre las fuerzas aerodinámicas no estacionarias y la catenaria puede ocasionar la aparición de oscilaciones de gran amplitud debido al fenómeno de galope. Una forma sencilla de reducir los efectos no deseados de la acción del viento, es la instalación de barreras cortavientos aguas arriba de la zona que se desea proteger. La instalación de estos dispositivos, reduce la velocidad en la estela generada, pero también modifica las propiedades del flujo dentro de la misma. Esta alteración de las condiciones del flujo puede contribuir a la aparición del fenómeno de galope en estructuras caracterizadas por su gran flexibilidad, como la catenaria ferroviaria. Estos dos efectos contrapuestos hacen evidente la importancia de mantener cierta visión global del efecto introducido por la instalación de barreras cortavientos en la plataforma ferroviaria. A lo largo de este documento, se evalúa desde un enfoque multidisciplinar el efecto inducido por las barreras cortavientos en varios subsistemas ferroviarios. Por un lado se analizan las mejoras en la estabilidad lateral del vehículo mediante una serie de ensayos en túnel de viento. La medición de la distribución de presiones en la superficie de un modelo bidimensional de vehículo ferroviario proporciona una buena estimación del nivel de protección que se consigue en función de la altura de una barrera cortavientos. Por otra parte, se analiza la influencia del mismo juego de barreras cortavientos en las características del flujo situado sobre la plataforma ferroviaria, mediante la utilización de anemometría de hilo caliente (HWA) y velocimetría de imágenes de párticulas (PIV). En particular se centra la atención en las características en la posición correspondiente a los hilos conductores de la catenaria. En la última parte del documento, se realiza un análisis simplificado de la aparición oscilaciones en la catenaria, por el efecto de la inestabilidad de galope. La información obtenida sobre las características del flujo se combinan con las propiedades aerodinámicas del hilo de contacto, obtenidas en mediante una serie de ensayos en túnel de viento. De esta manera se realiza una evaluación del riesgo a la aparición de este tipo de inestabilidad aeroeslástica aplicada a una catenaria ferroviaria situada sobre un viaducto tipo. ABSTRACT Wind as an environmental factor may induce undesirable effects on vehicles and structures. The analysis of those effects has caught the attention of several researchers. Concerning the railway system, cross-wind induces aerodynamic loads on rolling stock that may increase the overturning risk of the vehicle, threatening its safe operation. Even the cable system responsible to provide the electric current required for the train traction, known as the railway overhead or catenary, is sensitive to the wind action. In fact, the interaction between the unsteady aerodynamic forces and the railway overhead may trigger the development of undamped oscillations due to galloping phenomena. The inclusion of windbreaks upstream the area that needs wind protection is a simple mean to palliate the undesirable effects caused by the wind action. Although the presence of this wind protection devices reduces the wind speed downstream, they also modify the flow properties inside their wake. This modification on the flow characteristics may ease the apparition of the galloping phenomena on flexible structures, such as the railway overhead. This two opposite effects require to maintain a global perspective on the analysis of the influence of the windbreak presence. In the present document, a multidisciplinary analysis on the effect induced by windbreaks on several railways subsystems is conducted. On the one hand, a set of wind tunnel tests is conducted to assess the improvement on the rolling stock lateral stability. The qualitative estimation of the shelter effect, as function of the windbreak height, is established through the pressure distribution measured on the surface of a two-dimensional train model. On the other hand, the flow properties above the railway platform are assessed using the same set of windbreaks. Two experimental techniques are used to measure the flow properties, hot-wire anemometry (HWA) and particle image velocimetry (PIV). In particular, the attention is focused on the flow characteristics on the contact wire location. A simplified analysis on the catenary oscillations due to galloping phenomena is conducted in the last part of the document. Both, the flow characterization performed via PIV and the aerodynamic properties of the contact wire cross-section are combined. In this manner, the risk of the aeroelastic instabilities on a railway overhead placed on a railway bridge is assessed through a practical application.
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Las poblaciones de salmónidos en la Península Ibérica (trucha común, Salmo trutta; y salmón atlántico, Salmo salar) se encuentran cerca del límite meridional de sus distribuciones naturales, y por tanto tienen una gran importancia para la conservación de estas especies. En la presente Tesis se han investigado algunos aspectos de la reproducción y de la gestión del hábitat, con el objeto de mejorar el conocimiento acerca de estas poblaciones meridionales de salmónidos. Se ha estudiado la reproducción de la trucha común en el río Castril (Andalucía, sur de España), donde se ha observado que la freza ocurre desde diciembre hasta abril con el máximo de actividad en febrero. Este hecho representa uno de los periodos reproductivos más tardíos y con mayor duración de toda la distribución natural de la especie. Además, actualmente se sabe que el resto de poblaciones andaluzas tienen periodos de reproducción similares (retrasados y extendidos). Análisis en la escala de la distribución natural de la trucha común, han mostrado que la latitud explica parcialmente tanto la fecha media de reproducción (R2 = 62.8%) como la duración del periodo de freza (R2 = 24.4%) mediante relaciones negativas: a menor latitud, la freza ocurre más tarde y durante más tiempo. Es verosímil que un periodo de freza largo suponga una ventaja para la supervivencia de las poblaciones de trucha en hábitats impredecibles, y por tanto se ha propuesto la siguiente hipótesis, que deberá ser comprobada en el futuro: la duración de la freza es mayor en hábitats impredecibles que en aquellos más predecibles. La elevada tasa de solapamiento de frezaderos observada en el río Castril no se explica únicamente por una excesiva densidad de reproductores. Las hembras de trucha eligieron lugares específicos para construir sus frezaderos en vez de dispersarse aleatoriamente dentro del hábitat adecuado para la freza que tenían disponible. Estas observaciones sugieren que las hembras tienen algún tipo de preferencia por solapar sus frezaderos. Además, en ríos calizos como el Castril, las gravas pueden ser muy cohesivas y difíciles de excavar, por lo que el solapamiento de frezaderos puede suponer una ventaja para la hembra, porque la excavación en sustratos que han sido previamente removidos por frezas anteriores requerirá menos gasto de energía que en sustratos con gravas cohesivas que no han sido alteradas. Por tanto, se ha propuesto la siguiente hipótesis, que deberá ser comprobada en el futuro: las hembras tienen una mayor preferencia por solapar sus frezaderos en ríos con sustratos cohesivos que en ríos con sustratos de gravas sueltas. En el marco de la gestión del hábitat, se han empleado dos enfoques diferentes para la evaluación del hábitat físico, con el objeto de cuantificar los cambios potenciales en la disponibilidad de hábitat, antes de la implementación real de determinadas medidas sobre el hábitat. En primer lugar, se ha evaluado el hábitat físico del salmón atlántico en el río Pas (Cantabria, norte de España), en la escala del microhábitat, empleando la metodología IFIM junto con un modelo hidráulico bidimensional (River2D). Se han simulado una serie de acciones de mejora del hábitat y se han cuantificado los cambios en el hábitat bajo estas acciones. Los resultados mostraron un aumento muy pequeño en la disponibilidad de hábitat, por lo que no sería efectivo implementar estas acciones en este tramo fluvial. En segundo lugar, se ha evaluado el hábitat físico de la trucha común en el río Tajuña (Guadalajara, centro de España), en la escala del mesohábitat, empleando la metodología MesoHABSIM. Actualmente, el río Tajuña está alterado por los usos agrícolas de sus riberas, y por tanto se ha diseñado una restauración para mitigar estos impactos y para llevar al río a un estado más natural. Se ha cuantificado la disponibilidad de hábitat tras la restauración planteada, y los resultados han permitido identificar los tramos en los que la restauración resultaría más eficaz. ABSTRACT Salmonid populations in the Iberian Peninsula (brown trout, Salmo trutta; and Atlantic salmon, Salmo salar) are close to the southern limit of their natural ranges, and therefore they are of great importance for the conservation of the species. In the present dissertation, some aspects of spawning and habitat management have been investigated, in order to improve the knowledge on these southern salmonid populations. Brown trout spawning have been studied in the river Castril (Andalusia, southern Spain), and it has been observed that spawning occurs from December until April with the maximum activity in February. This finding represents one of the most belated and protracted spawning periods within the natural range of the species. Furthermore, it is now known that the rest of Andalusian populations show similar (belated and extended) spawning periods. Broad-scale analyses throughout the brown trout natural range showed that latitude partly explained both spawning mean time (R2 = 62.8%) and spawning duration (R2 = 24.4%) by negative relationships: the lower the latitude, the later the spawning time and the longer the spawning period. It is plausible that a long spawning period would be an advantage for survival of trout populations in unpredictable habitats, and thus the following hypothesis has been proposed, which is yet to be tested: spawning duration is longer in unpredictable than in predictable habitats. High rate of redd superimposition observed in the river Castril was not only caused by high density of spawners. Trout females chose specific sites for redd construction instead of randomly dispersing over the suitable spawning habitat. These observations suggest that female spawners have some kind of preference for superimposing redds. Moreover, in limestone streams such as Castril, unused gravels can be very cohesive and hard to dig, and thus redd superimposition may be an advantage for female, because digging may require less energy expenditure in already used redd sites than in cohesive and embedded unused sites. Hence, the following hypothesis has been proposed, which is yet to be tested: females have a higher preference for superimposing redds in streambeds with cohesive and embedded substrates than in rivers with loose gravels. Within the topic of habitat management, two different approaches have been used for physical habitat assessment, in order to quantify the potential change in habitat availability, prior to the actual implementation of proposed habitat measures. Firstly, physical habitat for Atlantic salmon in the river Pas (Cantabria, northern Spain) has been assessed at the microhabitat scale, using the IFIM approach along with a two dimensional hydraulic model (River2D). Proposed habitat enhancement actions have been simulated and potential habitat change has been quantified. Results showed a very small increasing in habitat availability and therefore it is not worth to implement these measures in this stream reach. Secondly, physical habitat for brown trout in the river Tajuña (Guadalajara, central Spain) has been assessed at the mesohabitat scale, using the MesoHABSIM approach. The river Tajuña is currently impacted by surrounding agricultural uses, and thus restoration was designed to mitigate these impacts and to drive the river to a more natural state. Habitat availability after the planned restoration has been quantified, and the results have permitted to identify in which sites the restoration will be more effective.
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In this work the thermal analysis of a small satellite orbiting around the Earth has been approached by direct integration of the heat balance equations of a two-node reduced model, obtaining a linearized second order ODE problem, similar in form to the classical case of the forced vibration of a damped system. As the thermal loads (solar radiation, albedo, etc.) are harmonic, the problem is solved by means of Fourier analysis methods. Research on that field can be directly applied to the analysis of thermal problems and the results obtained are satisfactory. Working on the frequency domain streamlines the analysis, simplifies the study and facilitates the experimental testing. The transfer functions are obtained for the two-node case but the study can be extended to an n-node model.
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The genetic basis of spontaneous melanoma formation in spotted dorsal (Sd) Xiphophorus platyfish–swordtail hybrids has been studied for decades, and is adequately explained by a two-gene inheritance model involving a sex-linked oncogene, Xmrk, and an autosomal tumor suppressor, DIFF. The Xmrk oncogene encodes a receptor tyrosine kinase related to EGFR; the nature of the DIFF tumor suppressor gene is unknown. We analyzed the genetic basis of UV-B-induced melanoma formation in closely related, spotted side platyfish–swordtail hybrids, which carry a different sex-linked pigment pattern locus, Sp. We UV-irradiated spotted side Xiphophorus platyfish–swordtail backcross hybrids to induce melanomas at frequencies 6-fold higher than occur spontaneously in unirradiated control animals. To identify genetic determinants of melanoma susceptibility in this UV-inducible Xiphophorus model, we genotyped individual animals from control and UV-irradiated experimental regimes using allozyme and DNA restriction fragment length polymorphisms and tested for joint segregation of genetic markers with pigmentation phenotype and UV-induced melanoma formation. Joint segregation results show linkage of a CDKN2-like DNA polymorphism with UV-B-induced melanoma formation in these hybrids. The CDKN2-like polymorphism maps to Xiphophorus linkage group V and exhibits recombination fractions with ES1 and MDH2 allozyme markers consistent with previous localization of the DIFF tumor suppressor locus. Our results indicate that the CDKN2-like sequence we have cloned and mapped is a candidate for the DIFF tumor suppressor gene.
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The world contains boundaries (e.g., continental edge for terrestrial taxa) that impose geometric constraints on the distribution of species ranges. Thus, contrary to traditional thinking, the expected species richness pattern in absence of ecological or physiographical factors is unlikely to be uniform. Species richness has been shown to peak in the middle of a bounded one-dimensional domain, even in the absence of ecological or physiographical factors. Because species ranges are not linear, an extension of the approach to two dimensions is necessary. Here we present a two-dimensional null model accounting for effects of geometric constraints. We use the model to examine the effects of continental edge on the distribution of terrestrial animals in Africa and compare the predictions with the observed pattern of species richness in birds endemic to the continent. Latitudinal, longitudinal, and two-dimensional patterns of species richness are predicted well from the modeled null effects alone. As expected, null effects are of high significance for wide ranging species only. Our results highlight the conceptual significance of an until recently neglected constraint from continental shape alone and support a more cautious analysis of species richness patterns at this scale.
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In the last 15 years, many class number formulas and main conjectures have been proven. Here, we discuss such formulas on the Selmer groups of the three-dimensional adjoint representation ad(φ) of a two-dimensional modular Galois representation φ. We start with the p-adic Galois representation φ0 of a modular elliptic curve E and present a formula expressing in terms of L(1, ad(φ0)) the intersection number of the elliptic curve E and the complementary abelian variety inside the Jacobian of the modular curve. Then we explain how one can deduce a formula for the order of the Selmer group Sel(ad(φ0)) from the proof of Wiles of the Shimura–Taniyama conjecture. After that, we generalize the formula in an Iwasawa theoretic setting of one and two variables. Here the first variable, T, is the weight variable of the universal p-ordinary Hecke algebra, and the second variable is the cyclotomic variable S. In the one-variable case, we let φ denote the p-ordinary Galois representation with values in GL2(Zp[[T]]) lifting φ0, and the characteristic power series of the Selmer group Sel(ad(φ)) is given by a p-adic L-function interpolating L(1, ad(φk)) for weight k + 2 specialization φk of φ. In the two-variable case, we state a main conjecture on the characteristic power series in Zp[[T, S]] of Sel(ad(φ) ⊗ ν−1), where ν is the universal cyclotomic character with values in Zp[[S]]. Finally, we describe our recent results toward the proof of the conjecture and a possible strategy of proving the main conjecture using p-adic Siegel modular forms.
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The structure of a multisubunit protein (immunoglobulin light chain) was solved in three crystal forms, differing only in the solvent of crystallization. The three structures were obtained at high ionic strength and low pH, high ionic strength and high pH, and low ionic strength and neutral pH. The three resulting "snapshots" of possible structures show that their variable-domain interactions differ, reflecting their stabilities under specific solvent conditions. In the three crystal forms, the variable domains had different rotational and translational relationships, whereas no alteration of the constant domains was found. The critical residues involved in the observed effect of the solvent are tryptophans and histidines located between the two variable domains in the dimeric structure. Tryptophan residues are commonly found in interfaces between proteins and their subunits, and histidines have been implicated in pH-dependent conformation changes. The quaternary structure observed for a multisubunit protein or protein complex in a crystal may be influenced by the interactions of the constituents within the molecule or complex and/or by crystal packing interactions. The comparison of buried surface areas and hydrogen bonds between the domains forming the molecule and between the molecules forming the crystals suggest that, for this system, the interactions within the molecule are most likely the determining factors.
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Mice carrying an ovine beta-lactoglobulin (BLG) transgene secrete BLG protein into their milk. To explore transgene expression stability, we studied expression levels in three BLG transgenic mouse lines. Unexpectedly, two lines exhibited variable levels of transgene expression. Copy number within lines appeared to be stable and there was no evidence of transgene rearrangement. In the most variable line, BLG production levels were stable within individual mice in two successive lactations. Backcrossing demonstrated that genetic background did not contribute significantly to variable expression. Tissue in situ hybridization revealed mosaicism of transgene expression within individual mammary glands from the two variable lines; in low expressors, discrete patches of cells expressing the transgene were observed. Transgene protein concentrations in milk reflected the proportion of epithelial cells expressing BLG mRNA. Furthermore, chromosomal in situ hybridization revealed that transgene arrays in both lines are situated close to the centromere. We propose that mosaicism of transgene expression is a consequence of the chromosomal location and/or the nature of the primary transgene integration event.
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As additivity is a very useful property for a distance measure, a general additive distance is proposed under the stationary time-reversible (SR) model of nucleotide substitution or, more generally, under the stationary, time-reversible, and rate variable (SRV) model, which allows rate variation among nucleotide sites. A method for estimating the mean distance and the sampling variance is developed. In addition, a method is developed for estimating the variance-covariance matrix of distances, which is useful for the statistical test of phylogenies and molecular clocks. Computer simulation shows (i) if the sequences are longer than, say, 1000 bp, the SR method is preferable to simpler methods; (ii) the SR method is robust against deviations from time-reversibility; (iii) when the rate varies among sites, the SRV method is much better than the SR method because the distance is seriously underestimated by the SR method; and (iv) our method for estimating the sampling variance is accurate for sequences longer than 500 bp. Finally, a test is constructed for testing whether DNA evolution follows a general Markovian model.
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We summarize recent evidence that models of earthquake faults with dynamically unstable friction laws but no externally imposed heterogeneities can exhibit slip complexity. Two models are described here. The first is a one-dimensional model with velocity-weakening stick-slip friction; the second is a two-dimensional elastodynamic model with slip-weakening friction. Both exhibit small-event complexity and chaotic sequences of large characteristic events. The large events in both models are composed of Heaton pulses. We argue that the key ingredients of these models are reasonably accurate representations of the properties of real faults.
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Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.