956 resultados para Type III secretion system


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Operationsziel Geschlossene, anatomische Reposition und sichere Fixation von problematischen suprakondylären Typ-III- und Typ-IV-Humerusfrakturen, die mit den herkömmlichen Operationsmethoden nur schwierig geschlossen zu behandeln sind. Indikationen Gemäß der AO-Kinderklassifikation der suprakondylären Humerusfrakturen vom Typ III und IV: Frakturen, welche nicht geschlossen mittels üblicher Repositionsmethoden reponierbar sind sowie Frakturen, die nicht mittels der üblichen, gekreuzten perkutanen Kirschner-Draht-Technik zu fixieren sind. Bei schweren Schwellungszuständen, offener Fraktur oder initial neurologischen und/oder vaskulären Problemen („pulseless pink hand“) sowie bei mehrfachverletzten Kindern, welche eine optimale Rehabilitation benötigen und die Extremität gipsfrei sein sollte. Bei Kindern mit Komorbiditäten (z. B. Anfälle, Spastizität), die eine bessere Stabilität benötigen. Kontraindikationen Prinzipiell keine Kontraindikationen Operationstechnik Im nichtreponierten Zustand unter Durchleuchtungskontrolle Einbringen einer einzelnen Schanz-Schraube in den lateralen (radialen) Aspekt des distalen Fragments, welches sich in der streng seitlichen Röntgenprojektion als „Sand-Uhr“- bzw. Kreisform des Capitulum humeri darstellt. Je nach Größe dieses distalen Fragments kann die Schanz-Schraube rein epiphysär oder metaphysär liegen. Danach in absolut streng seitlicher Projektion des distalen Humerus im Bereich des meta-diaphysären Übergangs Einbohren einer 2. Schanz-Schraube unabhängig von der Ersten, die möglichst rechtwinklig zur Längsachse des Humerus in der a.-p.-Ebene zu liegen kommen sollte, um spätere Manipulationen mittels „Joy-Stick“-Technik zu erleichtern. Sind die beiden Schanz-Schrauben mehr oder weniger in beiden Ebenen parallel, so ist die Fraktur praktisch anatomisch reponiert. Nach erreichter Reposition Feinjustierung aller Achskomponenten. Sicherung der Flexion/Extension mittels einem von radial, distal eingebrachten sog. Anti-Rotations-Kirschner-Drahts, der die Stabilität signifikant erhöht und eine Drehung des distalen Fragments um die einzelne Schanz-Schraube verhindert. Postoperative Behandlung Keine zusätzliche Gipsruhigstellung notwendig. Es sollte eine funktionelle Nachbehandlung erfolgen. Ergebnisse Gemäß unserer Langzeitstudien bewegen die meisten Kinder bereits zum Zeitpunkt der ambulanten Pin-Entfernung in der Frakturambulanz ihren Ellbogen weitgehend normal. Bei einer Follow-up-Zeit über 40 Monate hatten 30/31 Kindern eine seitengleiche Achse und Beweglichkeit.

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BACKGROUND Treatment of displaced tarsal navicular body fractures usually consists of open reduction and internal fixation. However, there is little literature reporting results of this treatment and correlation to fracture severity. METHODS We report the results of 24 patients treated in our institution over a 12-year period. Primary outcome measurements were Visual-Analogue-Scale Foot and Ankle score (VAS-FA), AOFAS midfoot score, and talonavicular osteoarthritis at final follow-up. According to a new classification system reflecting talonavicular joint damage, 2-part fractures were classified as type I, multifragmentary fractures as type II, and fractures with talonavicular joint dislocation and/or concomitant talar head fractures as type III. Spearman's coefficients tested this classification's correlation with the primary outcome measurements. Mean patient age was 33 (range 16-61) years and mean follow-up duration 73 (range 24-159) months. RESULTS Average VAS-FA score was 74.7 (standard deviation [SD] 16.9), and average AOFAS midfoot score was 83.8 (SD = 12.8). Final radiographs showed no talonavicular arthritis in 5 patients, grade 1 in 7, grade 2 in 3, grade 3 in 6, and grade 4 in 1 patient. Two patients had secondary or spontaneous talonavicular fusion. Spearman coefficients showed strong correlation of the classification system with VAS-FA score (r = -0.663, P < .005) and talonavicular arthritis (r = 0.600, P = .003), and moderate correlation with AOFAS score (r = -.509, P = .011). CONCLUSION At midterm follow-up, open reduction and internal fixation of navicular body fractures led to good clinical outcome but was closely related to fracture severity. A new classification based on the degree of talonavicular joint damage showed close correlation to clinical and radiologic outcome. LEVEL OF EVIDENCE Level IV, retrospective case series.

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A series of upper Pliocene to Pleistocene sediment samples from DSDP Sites 582 and 583 (Nankai Trough, active margin off Japan) were investigated by organic geochemical methods including organic carbon determination, Rock- Eval pyrolysis, gas chromatography of extractable hydrocarbons, and kerogen microscopy. The organic carbon content is fairly uniform and moderately low (0.35 to 0.77%) at both sites, although accompanied by high sedimentation rates. The low organic matter concentrations are the result of the combined effect of several factors: low bioproductivity, oxic depositional environment, and dilution with lithogenic material. Organic petrography revealed a mixture of three maceral types: (1) fresh, green fluorescent alginites of aquatic origin probably transported by turbidites from the shelf edge, (2) gelified huminites and paniculate liptinites derived from the erosion of unconsolidated peat, and (3) highly reflecting inertinites derived from continental erosion. By a combination of organic petrography and Rock-Eval pyrolysis results, the organic matter is characterized as mainly type III kerogen with a slight tendency to a mixed type II-III. During Rock-Eval pyrolysis, a mineral matrix effect on the generated hydrocarbons was observed. The organic matter in all sediments has a low level of maturity (below 0.45% Rm) and has not yet reached the onset of thermal hydrocarbon generation according to several geochemical maturation parameters. This low maturity is in contrast to anomalously high extract yields at both sites and large hydrocarbon proportions in the extracts at Site 583. This contrast may be due to early generation of polar compounds and perhaps redistribution of hydrocarbons caused by subduction tectonics. Carbon isotope data of the interstitial hydrocarbon gases indicate their origin from bacterial degradation of organic matter, although only very few bacterially degraded maceral components were detected.

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The source rock potential of Cretaceous organic rich whole rock samples from deep sea drilling project (DSDP) wells offshore southwestern Africa was investigated using bulk and quantitative pyrolysis techniques. The sample material was taken from organic rich intervals of Aptian, Albian and Turonian aged core samples from DSDP site 364 offshore Angola, DSDP well 530A north of the Walvis Ridge offshore Namibia, and DSDP well 361 offshore South Africa. The analytical program included TOC, Rock-Eval, pyrolysis GC, bulk kinetics and micro-scale sealed vessel pyrolysis (MSSV) experiments. The results were used to determine differences in the source rock petroleum type organofacies, petroleum composition, gas/oil ratio (GOR) and pressure-volume-temperature (PVT) behavior of hydrocarbons generated from these black shales for petroleum system modeling purposes. The investigated Aptian and Albian organic rich shales proved to contain excellent quality marine kerogens. The highest source rock potential was identified in sapropelic shales in DSDP well 364, containing very homogeneous Type II and organic sulfur rich Type IIS kerogen. They generate P-N-A low wax oils and low GOR sulfur rich oils, whereas Type III kerogen rich silty sandstones of DSDP well 361 show a potential for gas/condensate generation. Bulk kinetic experiments on these samples indicate that the organic sulfur contents influence kerogen transformation rates, Type IIS kerogen being the least stable. South of the Walvis Ridge, the Turonian contains predominantly a Type III kerogen. North of the Walvis Ridge, the Turonian black shales contain Type II kerogen and have the potential to generate P-N-A low and high wax oils, the latter with a high GOR at high maturity. Our results provide the first compositional kinetic description of Cretaceous organic rich black shales, and demonstrate the excellent source rock potential, especially of the Aptian-aged source rock, that has been recognized in a number of the South Atlantic offshore basins.

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Anthropogenic ocean acidification is likely to have negative effects on marine calcifying organisms, such as shelled pteropods, by promoting dissolution of aragonite shells. Study of shell dissolution requires an accurate and sensitive method for assessing shell damage. Shell dissolution was induced through incubations in CO2 enriched seawater for between 4 and 14 days. We describe a procedure that allows the level of dissolution to be assessed and classified into three main types: Type I with partial dissolution of the prismatic layer; Type II with exposure of underlying crossed-lamellar layer, and Type III, where crossed-lamellar layer shows signs of dissolution. Levels of dissolution showed a good correspondence to the incubation conditions, with the most severe damage found in specimens held for 14 d in undersaturated condition (Ohm ~ 0.8). This methodology enables the response of small pelagic calcifiers to acidified conditions to be detected at an early stage, thus making pteropods a valuable bioindicator of future ocean acidification.

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I. GENERALIDADES 1.1. Introducción Entre los diversos tipos de perturbaciones eléctricas, los huecos de tensión son considerados el problema de calidad de suministro más frecuente en los sistemas eléctricos. Este fenómeno es originado por un aumento extremo de la corriente en el sistema, causado principalmente por cortocircuitos o maniobras inadecuadas en la red. Este tipo de perturbación eléctrica está caracterizado básicamente por dos parámetros: tensión residual y duración. Típicamente, se considera que el hueco se produce cuando la tensión residual alcanza en alguna de las fases un valor entre 0.01 a 0.9 pu y tiene una duración de hasta 60 segundos. Para un usuario final, el efecto más relevante de un hueco de tensión es la interrupción o alteración de la operación de sus equipos, siendo los dispositivos de naturaleza electrónica los principalmente afectados (p. ej. ordenador, variador de velocidad, autómata programable, relé, etc.). Debido al auge tecnológico de las últimas décadas y a la búsqueda constante de automatización de los procesos productivos, el uso de componentes electrónicos resulta indispensable en la actualidad. Este hecho, lleva a que los efectos de los huecos de tensión sean más evidentes para el usuario final, provocando que su nivel de exigencia de la calidad de energía suministrada sea cada vez mayor. De forma general, el estudio de los huecos de tensión suele ser abordado bajo dos enfoques: en la carga o en la red. Desde el punto de vista de la carga, se requiere conocer las características de sensibilidad de los equipos para modelar su respuesta ante variaciones súbitas de la tensión del suministro eléctrico. Desde la perspectiva de la red, se busca estimar u obtener información adecuada que permita caracterizar su comportamiento en términos de huecos de tensión. En esta tesis, el trabajo presentado se encuadra en el segundo aspecto, es decir, en el modelado y estimación de la respuesta de un sistema eléctrico de potencia ante los huecos de tensión. 1.2. Planteamiento del problema A pesar de que los huecos de tensión son el problema de calidad de suministro más frecuente en las redes, hasta la actualidad resulta complejo poder analizar de forma adecuada este tipo de perturbación para muchas compañías del sector eléctrico. Entre las razones más comunes se tienen: - El tiempo de monitorización puede llegar a ser de varios años para conseguir una muestra de registros de huecos estadísticamente válida. - La limitación de recursos económicos para la adquisición e instalación de equipos de monitorización de huecos. - El elevado coste operativo que implica el análisis de los datos de los medidores de huecos de tensión instalados. - La restricción que tienen los datos de calidad de energía de las compañías eléctricas. Es decir, ante la carencia de datos que permitan analizar con mayor detalle los huecos de tensión, es de interés de las compañías eléctricas y la academia poder crear métodos fiables que permitan profundizar en el estudio, estimación y supervisión de este fenómeno electromagnético. Los huecos de tensión, al ser principalmente originados por eventos fortuitos como los cortocircuitos, son el resultado de diversas variables exógenas como: (i) la ubicación de la falta, (ii) la impedancia del material de contacto, (iii) el tipo de fallo, (iv) la localización del fallo en la red, (v) la duración del evento, etc. Es decir, para plantear de forma adecuada cualquier modelo teórico sobre los huecos de tensión, se requeriría representar esta incertidumbre combinada de las variables para proveer métodos realistas y, por ende, fiables para los usuarios. 1.3. Objetivo La presente tesis ha tenido como objetivo el desarrollo diversos métodos estocásticos para el estudio, estimación y supervisión de los huecos de tensión en los sistemas eléctricos de potencia. De forma específica, se ha profundizado en los siguientes ámbitos: - En el modelado realista de las variables que influyen en la caracterización de los huecos. Esto es, en esta Tesis se ha propuesto un método que permite representar de forma verosímil su cuantificación y aleatoriedad en el tiempo empleando distribuciones de probabilidad paramétricas. A partir de ello, se ha creado una herramienta informática que permite estimar la severidad de los huecos de tensión en un sistema eléctrico genérico. - Se ha analizado la influencia la influencia de las variables de entrada en la estimación de los huecos de tensión. En este caso, el estudio se ha enfocado en las variables de mayor divergencia en su caracterización de las propuestas existentes. - Se ha desarrollado un método que permite estima el número de huecos de tensión de una zona sin monitorización a través de la información de un conjunto limitado de medidas de un sistema eléctrico. Para ello, se aplican los principios de la estadística Bayesiana, estimando el número de huecos de tensión más probable de un emplazamiento basándose en los registros de huecos de otros nudos de la red. - Plantear una estrategia para optimizar la monitorización de los huecos de tensión en un sistema eléctrico. Es decir, garantizar una supervisión del sistema a través de un número de medidores menor que el número de nudos de la red. II. ESTRUCTURA DE LA TESIS Para plantear las propuestas anteriormente indicadas, la presente Tesis se ha estructurado en seis capítulos. A continuación, se describen brevemente los mismos. A manera de capítulo introductorio, en el capítulo 1, se realiza una descripción del planteamiento y estructura de la presente tesis. Esto es, se da una visión amplia de la problemática a tratar, además de describir el alcance de cada capítulo de la misma. En el capítulo 2, se presenta una breve descripción de los fundamentos y conceptos generales de los huecos de tensión. Los mismos, buscan brindar al lector de una mejor comprensión de los términos e indicadores más empleados en el análisis de severidad de los huecos de tensión en las redes eléctricas. Asimismo, a manera de antecedente, se presenta un resumen de las principales características de las técnicas o métodos existentes aplicados en la predicción y monitorización óptima de los huecos de tensión. En el capítulo 3, se busca fundamentalmente conocer la importancia de las variables que determinen la frecuencia o severidad de los huecos de tensión. Para ello, se ha implementado una herramienta de estimación de huecos de tensión que, a través de un conjunto predeterminado de experimentos mediante la técnica denominada Diseño de experimentos, analiza la importancia de la parametrización de las variables de entrada del modelo. Su análisis, es realizado mediante la técnica de análisis de la varianza (ANOVA), la cual permite establecer con rigor matemático si la caracterización de una determinada variable afecta o no la respuesta del sistema en términos de los huecos de tensión. En el capítulo 4, se propone una metodología que permite predecir la severidad de los huecos de tensión de todo el sistema a partir de los registros de huecos de un conjunto reducido de nudos de dicha red. Para ello, se emplea el teorema de probabilidad condicional de Bayes, el cual calcula las medidas más probables de todo el sistema a partir de la información proporcionada por los medidores de huecos instalados. Asimismo, en este capítulo se revela una importante propiedad de los huecos de tensión, como es la correlación del número de eventos de huecos de tensión en diversas zonas de las redes eléctricas. En el capítulo 5, se desarrollan dos métodos de localización óptima de medidores de huecos de tensión. El primero, que es una evolución metodológica del criterio de observabilidad; aportando en el realismo de la pseudo-monitorización de los huecos de tensión con la que se calcula el conjunto óptimo de medidores y, por ende, en la fiabilidad del método. Como una propuesta alternativa, se emplea la propiedad de correlación de los eventos de huecos de tensión de una red para plantear un método que permita establecer la severidad de los huecos de todo el sistema a partir de una monitorización parcial de dicha red. Finalmente, en el capítulo 6, se realiza una breve descripción de las principales aportaciones de los estudios realizados en esta tesis. Adicionalmente, se describen diversos temas a desarrollar en futuros trabajos. III. RESULTADOS En base a las pruebas realizadas en las tres redes planteadas; dos redes de prueba IEEE de 24 y 118 nudos (IEEE-24 e IEEE-118), además del sistema eléctrico de la República del Ecuador de 357 nudos (EC-357), se describen los siguientes puntos como las observaciones más relevantes: A. Estimación de huecos de tensión en ausencia de medidas: Se implementa un método estocástico de estimación de huecos de tensión denominado PEHT, el cual representa con mayor realismo la simulación de los eventos de huecos de un sistema a largo plazo. Esta primera propuesta de la tesis, es considerada como un paso clave para el desarrollo de futuros métodos del presente trabajo, ya que permite emular de forma fiable los registros de huecos de tensión a largo plazo en una red genérica. Entre las novedades más relevantes del mencionado Programa de Estimación de Huecos de Tensión (PEHT) se tienen: - Considerar el efecto combinado de cinco variables aleatorias de entrada para simular los eventos de huecos de tensión en una pseudo-monitorización a largo plazo. Las variables de entrada modeladas en la caracterización de los huecos de tensión en el PEHT son: (i) coeficiente de fallo, (ii) impedancia de fallo, (iii) tipo de fallo, (iv) localización del fallo y (v) duración. - El modelado estocástico de las variables de entrada impedancia de fallo y duración en la caracterización de los eventos de huecos de tensión. Para la parametrización de las variables mencionadas, se realizó un estudio detallado del comportamiento real de las mismas en los sistemas eléctricos. Asimismo, se define la función estadística que mejor representa la naturaleza aleatoria de cada variable. - Considerar como variables de salida del PEHT a indicadores de severidad de huecos de uso común en las normativas, como es el caso de los índices: SARFI-X, SARFI-Curve, etc. B. Análisis de sensibilidad de los huecos de tensión: Se presenta un estudio causa-efecto (análisis de sensibilidad) de las variables de entrada de mayor divergencia en su parametrización entre las referencias relacionadas a la estimación de los huecos de tensión en redes eléctricas. De forma específica, se profundiza en el estudio de la influencia de la parametrización de las variables coeficiente de fallo e impedancia de fallo en la predicción de los huecos de tensión. A continuación un resumen de las conclusiones más destacables: - La precisión de la variable de entrada coeficiente de fallo se muestra como un parámetro no influyente en la estimación del número de huecos de tensión (SARFI-90 y SARFI-70) a largo plazo. Es decir, no se requiere de una alta precisión del dato tasa de fallo de los elementos del sistema para obtener una adecuada estimación de los huecos de tensión. - La parametrización de la variable impedancia de fallo se muestra como un factor muy sensible en la estimación de la severidad de los huecos de tensión. Por ejemplo, al aumentar el valor medio de esta variable aleatoria, se disminuye considerablemente la severidad reportada de los huecos en la red. Por otra parte, al evaluar el parámetro desviación típica de la impedancia de fallo, se observa una relación directamente proporcional de este parámetro con la severidad de los huecos de tensión de la red. Esto es, al aumentar la desviación típica de la impedancia de fallo, se evidencia un aumento de la media y de la variación interanual de los eventos SARFI-90 y SARFI-70. - En base al análisis de sensibilidad desarrollado en la variable impedancia de fallo, se considera muy cuestionable la fiabilidad de los métodos de estimación de huecos de tensión que omiten su efecto en el modelo planteado. C. Estimación de huecos de tensión en base a la información de una monitorización parcial de la red: Se desarrolla un método que emplea los registros de una red parcialmente monitorizada para determinar la severidad de los huecos de todo el sistema eléctrico. A partir de los casos de estudio realizados, se observa que el método implementado (PEHT+MP) posee las siguientes características: - La metodología propuesta en el PEHT+MP combina la teoría clásica de cortocircuitos con diversas técnicas estadísticas para estimar, a partir de los datos de los medidores de huecos instalados, las medidas de huecos de los nudos sin monitorización de una red genérica. - El proceso de estimación de los huecos de tensión de la zona no monitorizada de la red se fundamenta en la aplicación del teorema de probabilidad condicional de Bayes. Es decir, en base a los datos observados (los registros de los nudos monitorizados), el PEHT+MP calcula de forma probabilística la severidad de los huecos de los nudos sin monitorización del sistema. Entre las partes claves del procedimiento propuesto se tienen los siguientes puntos: (i) la creación de una base de datos realista de huecos de tensión a través del Programa de Estimación de Huecos de Tensión (PEHT) propuesto en el capítulo anterior; y, (ii) el criterio de máxima verosimilitud empleado para estimar las medidas de huecos de los nudos sin monitorización de la red evaluada. - Las predicciones de medidas de huecos de tensión del PEHT+MP se ven potenciadas por la propiedad de correlación de los huecos de tensión en diversas zonas de un sistema eléctrico. Esta característica intrínseca de las redes eléctricas limita de forma significativa la respuesta de las zonas fuertemente correlacionadas del sistema ante un eventual hueco de tensión. Como el PEHT+MP está basado en principios probabilísticos, la reducción del rango de las posibles medidas de huecos se ve reflejado en una mejor predicción de las medidas de huecos de la zona no monitorizada. - Con los datos de un conjunto de medidores relativamente pequeño del sistema, es posible obtener estimaciones precisas (error nulo) de la severidad de los huecos de la zona sin monitorizar en las tres redes estudiadas. - El PEHT+MP se puede aplicar a diversos tipos de indicadores de severidad de los huecos de tensión, como es el caso de los índices: SARFI-X, SARFI-Curve, SEI, etc. D. Localización óptima de medidores de huecos de tensión: Se plantean dos métodos para ubicar de forma estratégica al sistema de monitorización de huecos en una red genérica. La primera propuesta, que es una evolución metodológica de la localización óptima de medidores de huecos basada en el criterio de observabilidad (LOM+OBS); y, como segunda propuesta, un método que determina la localización de los medidores de huecos según el criterio del área de correlación (LOM+COR). Cada método de localización óptima de medidores propuesto tiene un objetivo concreto. En el caso del LOM+OBS, la finalidad del método es determinar el conjunto óptimo de medidores que permita registrar todos los fallos que originen huecos de tensión en la red. Por otro lado, en el método LOM+COR se persigue definir un sistema óptimo de medidores que, mediante la aplicación del PEHT+MP (implementado en el capítulo anterior), sea posible estimar de forma precisa las medidas de huecos de tensión de todo el sistema evaluado. A partir del desarrollo de los casos de estudio de los citados métodos de localización óptima de medidores en las tres redes planteadas, se describen a continuación las observaciones más relevantes: - Como la generación de pseudo-medidas de huecos de tensión de los métodos de localización óptima de medidores (LOM+OBS y LOM+COR) se obtienen mediante la aplicación del algoritmo PEHT, la formulación del criterio de optimización se realiza en base a una pseudo-monitorización realista, la cual considera la naturaleza aleatoria de los huecos de tensión a través de las cinco variables estocásticas modeladas en el PEHT. Esta característica de la base de datos de pseudo-medidas de huecos de los métodos LOM+OBS y LOM+COR brinda una mayor fiabilidad del conjunto óptimo de medidores calculado respecto a otros métodos similares en la bibliografía. - El conjunto óptimo de medidores se determina según la necesidad del operador de la red. Esto es, si el objetivo es registrar todos los fallos que originen huecos de tensión en el sistema, se emplea el criterio de observabilidad en la localización óptima de medidores de huecos. Por otra parte, si se plantea definir un sistema de monitorización que permita establecer la severidad de los huecos de tensión de todo el sistema en base a los datos de un conjunto reducido de medidores de huecos, el criterio de correlación resultaría el adecuado. De forma específica, en el caso del método LOM+OBS, basado en el criterio de observabilidad, se evidenciaron las siguientes propiedades en los casos de estudio realizados: - Al aumentar el tamaño de la red, se observa la tendencia de disminuir el porcentaje de nudos monitorizados de dicho sistema. Por ejemplo, para monitorizar los fallos que originan huecos en la red IEEE-24, se requiere monitorizar el 100\% de los nudos del sistema. En el caso de las redes IEEE-118 y EC-357, el método LOM+OBS determina que con la monitorización de un 89.5% y 65.3% del sistema, respectivamente, se cumpliría con el criterio de observabilidad del método. - El método LOM+OBS permite calcular la probabilidad de utilización del conjunto óptimo de medidores a largo plazo, estableciendo así un criterio de la relevancia que tiene cada medidor considerado como óptimo en la red. Con ello, se puede determinar el nivel de precisión u observabilidad (100%, 95%, etc.) con el cual se detectarían los fallos que generan huecos en la red estudiada. Esto es, al aumentar el nivel de precisión de detección de los fallos que originan huecos, se espera que aumente el número de medidores requeridos en el conjunto óptimo de medidores calculado. - El método LOM+OBS se evidencia como una técnica aplicable a todo tipo de sistema eléctrico (radial o mallado), el cual garantiza la detección de los fallos que originan huecos de tensión en un sistema según el nivel de observabilidad planteado. En el caso del método de localización óptima de medidores basado en el criterio del área de correlación (LOM+COR), las diversas pruebas realizadas evidenciaron las siguientes conclusiones: - El procedimiento del método LOM+COR combina los métodos de estimación de huecos de tensión de capítulos anteriores (PEHT y PEHT+MP) con técnicas de optimización lineal para definir la localización óptima de los medidores de huecos de tensión de una red. Esto es, se emplea el PEHT para generar los pseudo-registros de huecos de tensión, y, en base al criterio planteado de optimización (área de correlación), el LOM+COR formula y calcula analíticamente el conjunto óptimo de medidores de la red a largo plazo. A partir de la información registrada por este conjunto óptimo de medidores de huecos, se garantizaría una predicción precisa de la severidad de los huecos de tensión de todos los nudos del sistema con el PEHT+MP. - El método LOM+COR requiere un porcentaje relativamente reducido de nudos del sistema para cumplir con las condiciones de optimización establecidas en el criterio del área de correlación. Por ejemplo, en el caso del número total de huecos (SARFI-90) de las redes IEEE-24, IEEE-118 y EC-357, se calculó un conjunto óptimo de 9, 12 y 17 medidores de huecos, respectivamente. Es decir, solamente se requeriría monitorizar el 38\%, 10\% y 5\% de los sistemas indicados para supervisar los eventos SARFI-90 en toda la red. - El método LOM+COR se muestra como un procedimiento de optimización versátil, el cual permite reducir la dimensión del sistema de monitorización de huecos de redes eléctricas tanto radiales como malladas. Por sus características, este método de localización óptima permite emular una monitorización integral del sistema a través de los registros de un conjunto pequeño de monitores. Por ello, este nuevo método de optimización de medidores sería aplicable a operadores de redes que busquen disminuir los costes de instalación y operación del sistema de monitorización de los huecos de tensión. ABSTRACT I. GENERALITIES 1.1. Introduction Among the various types of electrical disturbances, voltage sags are considered the most common quality problem in power systems. This phenomenon is caused by an extreme increase of the current in the network, primarily caused by short-circuits or inadequate maneuvers in the system. This type of electrical disturbance is basically characterized by two parameters: residual voltage and duration. Typically, voltage sags occur when the residual voltage, in some phases, reaches a value between 0.01 to 0.9 pu and lasts up to 60 seconds. To an end user, the most important effect of a voltage sags is the interruption or alteration of their equipment operation, with electronic devices the most affected (e.g. computer, drive controller, PLC, relay, etc.). Due to the technology boom of recent decades and the constant search for automating production processes, the use of electronic components is essential today. This fact makes the effects of voltage sags more noticeable to the end user, causing the level of demand for a quality energy supply to be increased. In general, the study of voltage sags is usually approached from one of two aspects: the load or the network. From the point of view of the load, it is necessary to know the sensitivity characteristics of the equipment to model their response to sudden changes in power supply voltage. From the perspective of the network, the goal is to estimate or obtain adequate information to characterize the network behavior in terms of voltage sags. In this thesis, the work presented fits into the second aspect; that is, in the modeling and estimation of the response of a power system to voltage sag events. 1.2. Problem Statement Although voltage sags are the most frequent quality supply problem in electrical networks, thistype of disturbance remains complex and challenging to analyze properly. Among the most common reasons for this difficulty are: - The sag monitoring time, because it can take up to several years to get a statistically valid sample. - The limitation of funds for the acquisition and installation of sag monitoring equipment. - The high operating costs involved in the analysis of the voltage sag data from the installed monitors. - The restrictions that electrical companies have with the registered power quality data. That is, given the lack of data to further voltage sag analysis, it is of interest to electrical utilities and researchers to create reliable methods to deepen the study, estimation and monitoring of this electromagnetic phenomenon. Voltage sags, being mainly caused by random events such as short-circuits, are the result of various exogenous variables such as: (i) the number of faults of a system element, (ii) the impedance of the contact material, (iii) the fault type, (iv) the fault location, (v) the duration of the event, etc. That is, to properly raise any theoretical model of voltage sags, it is necessary to represent the combined uncertainty of variables to provide realistic methods that are reliable for users. 1.3. Objective This Thesis has been aimed at developing various stochastic methods for the study, estimation and monitoring of voltage sags in electrical power systems. Specifically, it has deepened the research in the following areas: - This research furthers knowledge in the realistic modeling of the variables that influence sag characterization. This thesis proposes a method to credibly represent the quantification and randomness of the sags in time by using parametric probability distributions. From this, a software tool was created to estimate the severity of voltage sags in a generic power system. - This research also analyzes the influence of the input variables in the estimation of voltage sags. In this case, the study has focused on the variables of greatest divergence in their characterization of the existing proposals. - A method was developed to estimate the number of voltage sags of an area without monitoring through the information of a limited set of sag monitors in an electrical system. To this end, the principles of Bayesian statistics are applied, estimating the number of sags most likely to happen in a system busbar based in records of other sag network busbars. - A strategy was developed to optimize the monitorization of voltage sags on a power system. Its purpose is to ensure the monitoring of the system through a number of monitors lower than the number of busbars of the network assessed. II. THESIS STRUCTURE To describe in detail the aforementioned proposals, this Thesis has been structured into six chapters. Below is are brief descriptions of them: As an introductory chapter, Chapter 1, provides a description of the approach and structure of this thesis. It presents a wide view of the problem to be treated, in addition to the description of the scope of each chapter. In Chapter 2, a brief description of the fundamental and general concepts of voltage sags is presented to provide to the reader a better understanding of the terms and indicators used in the severity analysis of voltage sags in power networks. Also, by way of background, a summary of the main features of existing techniques or methods used in the prediction and optimal monitoring of voltage sags is also presented. Chapter 3 essentially seeks to know the importance of the variables that determine the frequency or severity of voltage sags. To do this, a tool to estimate voltage sags is implemented that, through a predetermined set of experiments using the technique called Design of Experiments, discusses the importance of the parameters of the input variables of the model. Its analysis is interpreted by using the technique of analysis of variance (ANOVA), which provides mathematical rigor to establish whether the characterization of a particular variable affects the system response in terms of voltage sags or not. In Chapter 4, a methodology to predict the severity of voltage sags of an entire system through the sag logs of a reduced set of monitored busbars is proposed. For this, the Bayes conditional probability theorem is used, which calculates the most likely sag severity of the entire system from the information provided by the installed monitors. Also, in this chapter an important property of voltage sags is revealed, as is the correlation of the voltage sags events in several zones of a power system. In Chapter 5, two methods of optimal location of voltage sag monitors are developed. The first one is a methodological development of the observability criteria; it contributes to the realism of the sag pseudo-monitoring with which the optimal set of sag monitors is calculated and, therefore, to the reliability of the proposed method. As an alternative proposal, the correlation property of the sag events of a network is used to raise a method that establishes the sag severity of the entire system from a partial monitoring of the network. Finally, in Chapter 6, a brief description of the main contributions of the studies in this Thesis is detailed. Additionally, various themes to be developed in future works are described. III. RESULTS. Based on tests on the three networks presented, two IEEE test networks of 24 and 118 busbars (IEEE-24 and IEEE-118) and the electrical system of the Republic of Ecuador (EC-357), the following points present the most important observations: A. Estimation of voltage sags in the absence of measures: A stochastic estimation method of voltage sags, called PEHT, is implemented to represent with greater realism the long-term simulation of voltage sags events in a system. This first proposal of this thesis is considered a key step for the development of future methods of this work, as it emulates in a reliable manner the voltage sag long-term records in a generic network. Among the main innovations of this voltage sag estimation method are the following: - Consideration of the combined effect of five random input variables to simulate the events of voltage sags in long-term monitoring is included. The input variables modeled in the characterization of voltage sags on the PEHT are as follows: (i) fault coefficient, (ii) fault impedance, (iii) type of fault, (iv) location of the fault, and (v) fault duration. - Also included is the stochastic modeling of the input variables of fault impedance and duration in the characterization of the events of voltage sags. For the parameterization of these variables, a detailed study of the real behavior in power systems is developed. Also, the statistical function best suited to the random nature of each variable is defined. - Consideration of sag severity indicators used in standards as PEHT output variables, including such as indices as SARFI-X, SARFI-Curve, etc. B. Sensitivity analysis of voltage sags: A cause-effect study (sensitivity analysis) of the input variables of greatest divergence between reference parameterization related to the estimation of voltage sags in electrical networks is presented. Specifically, it delves into the study of the influence of the parameterization of the variables fault coefficient and fault impedance in the voltage sag estimation. Below is a summary of the most notable observations: - The accuracy of the input variable fault coefficient is shown as a non-influential parameter in the long-term estimation of the number of voltage sags (SARFI-90 and SARFI-70). That is, it does not require a high accuracy of the fault rate data of system elements for a proper voltage sag estimation. - The parameterization of the variable fault impedance is shown to be a very sensitive factor in the estimation of the voltage sag severity. For example, by increasing the average value of this random variable, the reported sag severity in the network significantly decreases. Moreover, in assessing the standard deviation of the fault impedance parameter, a direct relationship of this parameter with the voltage sag severity of the network is observed. That is, by increasing the fault impedance standard deviation, an increase of the average and the interannual variation of the SARFI-90 and SARFI-70 events is evidenced. - Based on the sensitivity analysis developed in the variable fault impedance, the omission of this variable in the voltage sag estimation would significantly call into question the reliability of the responses obtained. C. Voltage sag estimation from the information of a network partially monitored: A method that uses the voltage sag records of a partially monitored network for the sag estimation of all the power system is developed. From the case studies performed, it is observed that the method implemented (PEHT+MP) has the following characteristics: - The methodology proposed in the PEHT+MP combines the classical short-circuit theory with several statistical techniques to estimate, from data the of the installed sag meters, the sag measurements of unmonitored busbars of a generic power network. - The estimation process of voltage sags of the unmonitored zone of the network is based on the application of the conditional probability theorem of Bayes. That is, based on the observed data (monitored busbars records), the PEHT+MP calculates probabilistically the sag severity at unmonitored system busbars. Among the key parts of the proposed procedure are the following: (i) the creation of a realistic data base of voltage sags through of the sag estimation program (PEHT); and, (ii) the maximum likelihood criterion used to estimate the sag indices of system busbars without monitoring. - The voltage sag measurement estimations of PEHT+MP are potentiated by the correlation property of the sag events in power systems. This inherent characteristic of networks significantly limits the response of strongly correlated system zones to a possible voltage sag. As the PEHT+MP is based on probabilistic principles, a reduction of the range of possible sag measurements is reflected in a better sag estimation of the unmonitored area of the power system. - From the data of a set of monitors representing a relatively small portion of the system, to obtain accurate estimations (null error) of the sag severity zones without monitoring is feasible in the three networks studied. - The PEHT+MP can be applied to several types of sag indices, such as: SARFI-X, SARFI-Curve, SEI, etc. D. Optimal location of voltage sag monitors in power systems: Two methods for strategically locating the sag monitoring system are implemented for a generic network. The first proposal is a methodological development of the optimal location of sag monitors based on the observability criterion (LOM + OBS); the second proposal is a method that determines the sag monitor location according to the correlation area criterion (LOM+COR). Each proposed method of optimal location of sag monitors has a specific goal. In the case of LOM+OBS, the purpose of the method is to determine the optimal set of sag monitors to record all faults that originate voltage sags in the network. On the other hand, the LOM+COR method attempts to define the optimal location of sag monitors to estimate the sag indices in all the assessed network with the PEHT+MP application. From the development of the case studies of these methods of optimal location of sag monitors in the three networks raised, the most relevant observations are described below: - As the generation of voltage sag pseudo-measurements of the optimal location methods (LOM+OBS and LOM+COR) are obtained by applying the algorithm PEHT, the formulation of the optimization criterion is performed based on a realistic sag pseudo-monitoring, which considers the random nature of voltage sags through the five stochastic variables modeled in PEHT. This feature of the database of sag pseudo-measurements of the LOM+OBS and LOM+COR methods provides a greater reliability of the optimal set of monitors calculated when compared to similar methods in the bibliography. - The optimal set of sag monitors is determined by the network operator need. That is, if the goal is to record all faults that originate from voltage sags in the system, the observability criterion is used to determine the optimal location of sag monitors (LOM+OBS). Moreover, if the objective is to define a monitoring system that allows establishing the sag severity of the system from taken from information based on a limited set of sag monitors, the correlation area criterion would be appropriate (LOM+COR). Specifically, in the case of the LOM+OBS method (based on the observability criterion), the following properties were observed in the case studies: - By increasing the size of the network, there was observed a reduction in the percentage of monitored system busbars required. For example, to monitor all the faults which cause sags in the IEEE-24 network, then 100% of the system busbars are required for monitoring. In the case of the IEEE-118 and EC-357 networks, the method LOM+OBS determines that with monitoring 89.5 % and 65.3 % of the system, respectively, the observability criterion of the method would be fulfilled. - The LOM+OBS method calculates the probability of using the optimal set of sag monitors in the long term, establishing a relevance criterion of each sag monitor considered as optimal in the network. With this, the level of accuracy or observability (100%, 95%, etc.) can be determined, with which the faults that caused sags in the studied network are detected. That is, when the accuracy level for detecting faults that cause sags in the system is increased, a larger number of sag monitors is expected when calculating the optimal set of monitors. - The LOM + OBS method is demonstrated to be a technique applicable to any type of electrical system (radial or mesh), ensuring the detection of faults that cause voltage sags in a system according to the observability level raised. In the case of the optimal localization of sag monitors based on the criterion of correlation area (LOM+COR), several tests showed the following conclusions: - The procedure of LOM+COR method combines the implemented algorithms of voltage sag estimation (PEHT and PEHT+MP) with linear optimization techniques to define the optimal location of the sag monitors in a network. That is, the PEHT is used to generate the voltage sag pseudo-records, and, from the proposed optimization criterion (correlation area), the LOM+COR formulates and analytically calculates the optimal set of sag monitors of the network in the long term. From the information recorded by the optimal set of sag monitors, an accurate prediction of the voltage sag severity at all the busbars of the system is guaranteed with the PEHT+MP. - The LOM + COR method is shown to be a versatile optimization procedure, which reduces the size of the sag monitoring system both at radial as meshed grids. Due to its characteristics, this optimal location method allows emulation of complete system sag monitoring through the records of a small optimal set of sag monitors. Therefore, this new optimization method would be applicable to network operators that looks to reduce the installation and operation costs of the voltage sag monitoring system.

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The neurosteroid 3α-hydroxysteroid-5α-pregnan-20-one (allopregnanolone) acts as a positive allosteric modulator of γ-aminobutyric acid at γ-aminobutyric acid type A receptors and hence is a powerful anxiolytic, anticonvulsant, and anesthetic agent. Allopregnanolone is synthesized from progesterone by reduction to 5α-dihydroprogesterone, mediated by 5α-reductase, and by reduction to allopregnanolone, mediated by 3α-hydroxysteroid dehydrogenase (3α-HSD). Previous reports suggested that some selective serotonin reuptake inhibitors (SSRIs) could alter concentrations of allopregnanolone in human cerebral spinal fluid and in rat brain sections. We determined whether SSRIs directly altered the activities of either 5α-reductase or 3α-HSD, using an in vitro system containing purified recombinant proteins. Although rats appear to express a single 3α-HSD isoform, the human brain contains several isoforms of this enzyme, including a new isoform we cloned from human fetal brains. Our results indicate that the SSRIs fluoxetine, sertraline, and paroxetine decrease the Km of the conversion of 5α-dihydroprogesterone to allopregnanolone by human 3α-HSD type III 10- to 30-fold. Only sertraline inhibited the reverse oxidative reaction. SSRIs also affected conversions of androgens to 3α- and 3α, 17β-reduced or -oxidized androgens mediated by 3α-HSD type IIBrain. Another antidepressant, imipramine, was without any effect on allopregnanolone or androstanediol production. The region-specific expression of 3α-HSD type IIBrain and 3α-HSD type III mRNAs suggest that SSRIs will affect neurosteroid production in a region-specific manner. Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs.

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The same heterozygous T -> C transition at nt 8567 of the von Willebrand factor (vWF) transcript was found in two unrelated patients with type III) von Willebrand disease, with no other apparent abnormality. In one family, both alleles were normal in the parents and one sister; thus, the mutation originated de novo in the proposita. The second patient also had asymptomatic parents who, however, were not available for study. The structural consequences of the identified mutation, resulting in the CyS2010 -> Arg substitution, were evaluated by expression of the vWF carboxyl-terminal domain containing residues 1366-2050. Insect cells infected with recombinant baculovirus expressing normal vWF sequence secreted a disulfide linked dimeric molecule with an apparent molecular mass of 150 kDa before reduction, yielding a single band of 80 kDa after disulfide bond reduction. In contrast, cells expressing the mutant fragment secreted a monomeric molecule of apparent molecular mass of 80 kDa, which remained unchanged after reduction. We conclude that CyS2010 is essential for normal dimerization of vWF subunits through disulfide bonding of carboxyl-terminal domains and that a heterozygous mutation in the corresponding codon is responsible for defective multimer formation in type III) von Willebrand disease.

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To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1-/- mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/- mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-1 and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/- mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/- mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1 -/- mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/- mice, there was no signaling in response to IFN-alpha or -beta as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-alpha and -beta.

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Os ratos Wistar são amplamente empregados como modelo animal na pesquisa biomédica e o controle sanitário dos biotérios é essencial para garantir a qualidade dos experimentos. O objetivo do estudo foi a caracterização do estado sanitário da colônia de ratos Wistar em sistema de criação convencional e para tanto determinar as bactérias, fungos, virus e parasitos, bem como caracterizar as lesões anatomopatológicas do sistema respiratório. Foram utilizados 273 ratos (N), machos (M) e fêmeas (F), das faixas etárias 4, 8, 12, 16 a 20 semanas e entre 12 a 18 meses, para as determinações de peso e condição corpórea (N=273, 140M, 133F); avaliação bacteriológica de orofaringe, mucosa intestinal e lavado traqueobrônquico (N=40, 20M, 20F); determinação de anticorpos para vírus e bactérias (N=20, 10M, 10F); exame parasitológico (N=60, 30M, 30F); identificação molecular de Mycoplasma pulmonis em amostras de pulmão (N=25, 15M, 10F), e caracterização anatomopatológica da cavidade nasal, orofaringe, laringe, traqueia e pulmão (N=106, 53M, 53F). Foram realizadas ainda avaliações microbiológicas das salas dos ratos em três períodos com isolamento de Micrococcus spp., Staphylococcus spp., Bacillus spp., Aspergillus spp. e Penicillium spp. O peso se mostrou homogêneo dentro da faixa etária e gênero, com apenas sete animais magros (2,56%) e nove em sobrepeso (3,30%). Não foram isoladas bactérias patogênicas na orofaringe, mucosa intestinal e lavado traqueobrônquico por cultivo. Mycoplasma pulmonis foi determinado em 72% das amostras pulmonares e em 100% dos soros testados. Em 35% foram detectados anticorpos para Reovirus tipo III e em 100% para bacilos associados ao epitélio respiratório ciliado. Syphacia muris foi diagnosticada em 91,67%, Eimeria spp. em 3,33% e Entamoeba muris em 1,67%. Lesões relacionadas a infecção por agentes exógenos foram observadas em cavidade nasal e na orofaringe, laringe e traqueia a partir da 4 semanas de idade e, em pulmão desde as 12 semanas, com aumento de frequência de ocorrência e do grau de progressão, com o avançar da idade, nos vários segmentos estudados. Concluímos que a caracterização do estado sanitário dos ratos permite conhecer as particularidades do modelo biológico utilizado e compor base de dados para auxiliar no desenho e na interpretação experimental dos pesquisadores, além de garantir uma base para o programa de monitorização sanitária de biotérios em condições similares

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O nicho endosteal da medula óssea abriga as células-tronco hemopoéticas (CTH) em quiescência/autorrenovação. As CTH podem ser classificadas em dois grupos: células que reconstituem a hemopoese em longo prazo (LT-CTH) e curto prazo (CT-CTH). Investigamos, neste trabalho, os efeitos da desnutrição proteica (DP) no tecido ósseo e a participação do nicho endosteal na sinalização osteoblasto-CTH. Para tanto, utilizamos camundongos submetidos à DP induzida pelo consumo de ração hipoproteica. Os animais desnutridos apresentaram pancitopenia e diminuição nas concentrações de proteínas séricas e albumina. Quantificamos as CTH por citometria de fluxo e verificamos que os desnutridos apresentaram menor porcentagem de LT-CTH, CT-CTH e de progenitores multipotentes (PMP). Avaliamos a expressão das proteínas CD44, CXCR4, Tie-2 e Notch-1 nas LT-CTH. Observamos diminuição da expressão da proteína CD44 nos desnutridos. Isolamos as células LT-CTH por cell sorting e avaliamos a expressão gênica de CD44, CXCR4 e NOTCH-1. Verificamos que os desnutridos apresentaram menor expressão de CD44. Em relação ao ciclo celular, verificamos maior quantidade de LT-CTH nas fases G0/G1. Caracterizamos as alterações do tecido ósseo femoral, in vivo. Observamos diminuição da densidade mineral óssea e da densidade medular nos desnutridos. A desnutrição acarretou diminuição da área média das seções transversais, do perímetro do periósteo e do endósteo na cortical do fêmur dos animais. E na região trabecular, verificou-se diminuição da razão entre volume ósseo e volume da amostra e do número de trabéculas, aumento da distância entre as trabéculas e prevalência de trabéculas ósseas em formato cilíndrico. Avaliamos a expressão de colágeno, osteonectina (ON) e osteocalcina (OC) por imuno-histoquímica, e de osteopontina (OPN) por imunofluorescência no fêmur e verificamos diminuição da marcação para OPN, colágeno tipo I, OC e ON nos desnutridos. Evidenciamos, pela técnica do Picrosírius, desorganização na distribuição das fibras colágenas e presença de fibras tipo III nos fêmures dos desnutridos, além de maior número de osteoclastos evidenciados pela reação da fosfatase ácida tartarato resistente. Os osteoblastos da região femoral foram isolados por depleção imunomagnética, imunofenotipados por citometria de fluxo e cultivados em meio de indução osteogênica. Observamos menor positividade para fosfatase alcalina e vermelho de alizarina nas culturas dos osteoblastos dos desnutridos. Avaliamos, por Western Blotting, a expressão de colágeno tipo I, OPN, osterix, Runx2, RANKL e osteoprotegerina (OPG), e, por PCR em tempo real, a expressão de COL1A2, SP7, CXCL12, ANGPT1, SPP1, JAG2 e CDH2 nos osteoblastos isolados. Verificamos que a desnutrição acarretou diminuição da expressão proteica de osterix e OPG e menor expressão gênica de ANGPT1. Avaliamos a proliferação das células LSK (Lin-Sca1+c-Kit+) utilizando ensaio de CFSE (carboxifluoresceína succinimidil ester). Foi realizada cocultura de células LSK e osteoblastos (MC3T3-E1) na presença e ausência de anti-CD44. Após uma semana, verificamos menor proliferação das LSK dos desnutridos. O bloqueio de CD44 das LSK do grupo controle diminuiu a proliferação destas em três gerações. Entretanto, nos desnutridos, esse bloqueio não afetou a proliferação. Concluímos que a DP promoveu alterações no tecido ósseo e nas CTH. Entretanto, não podemos afirmar que as alterações observadas no sistema hemopoético foram decorrentes de alterações exclusivas do nicho endosteal.

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Introduction: The vasoconstricting peptide Endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, AAA, hypertension and hypercholesterolemia. It is known to stimulate quiescent vascular smooth muscle cells (VSMC) into the growth cycle and has been linked to intimal thickening following endothelial injury and is associated with vessel wall remodelling in salt-sensitive hypertension models. Enhanced ET-1 expression has been reported in the internal mammary artery (IMA) and was markedly higher in patients undergoing cardiac bypass surgery who were diabetic and /or hypercholesterolemic. Aims: To firstly review the histopathology of the IMA and secondly, determine the relationship between ET-1 expression in this vessel and mitogenic activity in the medial VSMC. Methods: Vessel tissue collected at the time of CABG surgery was formalin-fixed and paraffin-embedded for histological investigation. Cross sections of the left distal IMAwere stained with Alcian Blue/Verhoeff’s van Gieson to assess medial degeneration and identify the elastic lamellae and picrosirius red to determine the collagen content (specifically type I and type III). Immunohistochemistry staining was used to assess VSMC growth (PCNA label), tissue ET-1 expression, VSMC (SMCa-actin) area and macrophage/monocyte (anti-CD68) infiltration. Quantitative analysis was performed to measure the VSMC area in relation to ET-1 staining. Results: Fifty-five IMA specimens from the CABG patients (10F; 45M; mean age 65 years) were collected for this study. Fourteen donor IMAspecimens were used as controls (7F; 7M; mean age 45 years). Significant medial hypertrophy, VSMC disorganisation and elastic lamellae destruction was detected in the CABG IMA. The amount of Alcian blue staining in the CABG IMA was almost double that of the control (31.85+/14.52% Vs 17.10+/9.96%, P= .0006). Total collagen and type I collagen content was significantly increased compared with controls (65.8+/18.3% Vs 33.7 + / 13.7%, P= .07), (14.2 + /10.0% Vs 4.8 + /2.8%, P= .01), respectively. Tissue ET-1 and PCNA labelling were also significantly elevated the CABG IMA specimens relative to the controls (69.99 + /18.74%Vs 23.33 + /20.53%, P= .0001, and 37.29 + /12.88% Vs 11.06 + /8.18, P= .0001), respectively. There was mild presence of macrophages and monocytes in both CABG and control tissue. Conclusions: The IMA from CABG patients has elevated levels of type I collagen in the extracellular matrix indicative of fibrosis and was coupled with deleterious structural remodelling. Abnormally high levels of ET-1 were measured in the medial SMC layer and was associated with VSMC growth but not related to any chronic inflammatory response within the vessel wall.

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The primary purpose of this research is to study the linkage between perceived job design characteristics and information system environment characteristics before and after the replacement of a legacy information system with a new type of information system (referred to as an Enterprise Resource Planning or ERP system). A public state University implementing an academic version of an ERP system was selected for the study. Three survey instruments were used to examine the perception of the information system, the job characteristics, and the organizational culture before and after the system implementation. The research participants included two large departments resulting in a sample of 130 workers. Research questions were analyzed using multivariate procedures including factor analysis, path analysis, step-wise regression, and matched pair analysis. ^ Results indicated that the ERP system has introduced new elements into the working environment that has changed the perception of how the job design characteristics and organization culture dimensions are viewed by the workers. The understanding of how the perceived system characteristics align with an individual's perceived job design characteristics is supported by each of the system characteristics significantly correlated in the proposed direction. The stronger support of this relationship becomes visible in the causal flow of the effects seen in the path diagram and in the step-wise regression. The perceived job design characteristics aligning with dimensions of organizational culture are not as strong as the literature suggests. Although there are significant correlations between the job and culture variables, only one relationship can be seen in the causal flow. ^ This research has demonstrated that system characteristics of ERP do contribute to the perception of change in an organization and do support organizational culture behaviors and job characteristics. ^

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Nerve development, which includes axon outgrowth and guidance, is regulated by many protein families, including receptor protein tyrosine phosphatases (RPTP's).Protein tyrosine phosphatase receptor type 0 (PTPRO) is a type III RPTP that is important for axon growth and guidance, as observed in chicks and flies. In order to examine the effects ofPTPRO on mammalian development, standard behavioral tests were used to compare mice lacking the gene for PTPRO (ROKO mice) to wild-type (WT) mice. The ROKO mice showed a significant delay in reacting to a thermal noxious stimulus, hotplate analgesia, when compared to the WT mice suggesting deficient nociceptive function. In a rotarod test for proprioceptive function the ROKO mice exhibited a significant decrease in the amount of time spent on the rotating rod than did the WT mice. Additional proprioception tests were performed including the climb, step reflex, beam, and mesh walk tests. In the climb and step (place) test, the ROKO group had a significantly lower accuracy in performing the tests than did the WT mice. Thus, mice lacking the PTPRO gene showed behavioral deficiencies that reflect impairment in sensory function, specifically for nociception and proprioception.