Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

Discriminant analysis of the specialty of elite cyclist

The different demands of competition coupled with the morphological and physiological characteristics of cyclists have led to the appearance of cycling specialities. The aims of this study were to determine the differences in the anthropometric and physiological features in road cyclists with different specialities, and to develop a multivariate model to classify these specialities and predict which speciality may be appropriate to a given cyclist. Twenty male, elite amateur cyclists were classified by their trainers as either flat terrain riders, hill climbers, or all-terrain riders. Anthropometric and cardiorespiratory studies were then undertaken. The results were analysed by MANOVA and two discriminant tests. Most differences between the speciality groups were of an anthropometric nature. The only cardiorespiratory variable that differed significantly (p < 0.05) was maximum oxygen consumption with respect to body weight (VO2max/kg). The first discriminant test classified 100% of the cyclists within their true speciality; the second, which took into account only anthropometric variables, correctly classified 75%. The first discriminant model allows the likely speciality of still non-elite cyclists to be predicted from a small number of variables, and may therefore help in their specific training.

Diseño de un equipo experimental para el estudio de emisiones producidas durante procesos de autocombustión de sólidos

El objetivo de este proyecto es desarrollar un equipo para la realización de un ensayo de emisión de gases. Con esto se pretende simplificar el ensayo de calentamiento de sólidos y emisión de gases y hacerlo más fiable. Para la realización de este proyecto se utilizo un método de ensayo más rudimentario pero también eficaz. Así mismo se analizara el fenómeno de la autocombustión y las propiedades de distintos tipos de biomasa, en concreto dos tipos: astillas de madera y pellets de madera. Las propiedades que son caso de estudio son: las emisiones de gases que se producen durante el proceso de autocombustión; y las temperaturas de inflamación en capa a diferentes tamaños de grano y grosores de capa. Para analizar las propiedades de las muestras de biomasa se realizaran dos tipos de ensayos: ensayos de extracción de gases, y ensayos de temperatura mínima de inflamación en capa. Abstract: The main object of this Project is to develop an equipment to simplify our gas emissions test. During this project a more elementary method was used, however this method is extremely efficient. Also the self-heating phenomenon will be analyzed and several kinds of biomass properties, specifically two: wood chops and wood pellets. The properties that will be analyzed are: gas emissions during the self-heating process; and layer inflammation temperatures at several grain size and layer thickness. The biomass properties will be analyzed with two different tests: gas extraction tests, and TIMc.

Modelo de análisis organizativo para la mejora del desempeño de empresas sociales

La empresa social es un modelo organizativo que presenta un interesante potencial para resolver problemáticas sociales. La empresa social ha despertado interés tanto en países industrializados como en economías en vías de desarrollo porque representa un modelo dentro del capitalismo que persigue objetivos sociales mediante la realización de actividades de mercado (compra y venta de productos y/o servicios principalmente). A pesar de sus raíces lejanas en el tiempo se trata de un campo de conocimiento relativamente joven, donde la literatura académica presenta escasez de estudios empíricos. El desarrollo teórico para buscar claridad conceptual ha sido el principal caballo de batalla de los últimos años, y por tanto, se ha prestado poca atención a generar evidencias sobre cómo funcionan las empresas sociales y sobre sus claves de su éxito. Se considera que la mejora en la comprensión de este modelo organizativo pasa por la construcción de herramientas para que académicos y practicantes mejoren su conocimiento sobre los mecanismos internos de las empresas sociales. En este contexto nace la presente tesis doctoral sobre empresa social, que tiene por objetivo la creación de un marco de análisis que permita el estudio de las empresas sociales desde una dimensión organizativa, es decir, que aborde los elementos clave que describen el funcionamiento de este tipo de organizaciones. Para ello, en este trabajo se aborda la construcción del modelo para el análisis organizativo de las empresas sociales a partir del análisis semántico de las 45 principales definiciones de empresa social. A partir de este análisis se identifican dos dimensiones de análisis de la empresa social: -Cuatro principios, comunes a todas las manifestaciones del fenómeno, que recogen la esencia del concepto. -Ocho elementos organizativos específicos de la empresa social que describen la forma en la que cada iniciativa se implementa en un contexto determinado. Es decir, elementos de diseño presentes en diferente medida que dan lugar a tipologías de empresa social diferentes. Estos elementos son: la proposición de valor social, la búsqueda de impacto a largo plazo, la cultura organizativa, la conexión con los beneficiarios, el liderazgo emprendedor y los mecanismos de gobernanza, el ecosistema colaborativo, la estrategia empresarial y la orientación a la autosuficiencia económica. A partir de este marco de análisis, se construyen dos herramientas de diagnóstico que permiten su aplicación al estudio de empresas sociales: una tabla de indicadores para el análisis externo (por parte de un investigador ajeno a la organización) y un cuestionario de diagnóstico para el análisis interno (a través del personal de la empresa social objeto de estudio). Las herramientas intentan dar respuesta a la necesidad de desarrollar constructos para el estudio empírico de las empresas sociales. Para analizar la utilidad del modelo y de las herramientas se llevaron a cabo tres estudios de caso: -La empresa social ACCIONA Microenergía Perú que proporciona energía eléctrica a comunidades rurales aisladas en la región peruana de Cajamarca. -La empresa social Integra-e que propone un mecanismo de inserción socio-laboral en Madrid para jóvenes en riesgo de exclusión a través de la formación en Tecnologías de la Información y la Comunicación (TIC). -Un conjunto de redes de telecentros pertenecientes a la red LAC de la fundación Telecentres.org que proporcionan acceso a servicios de información (Internet entre otros) en diferentes países de Latinoamérica. La aplicación de las herramientas mostró ser útil en los tres estudios de caso para obtener una relación de evidencias con las que analizar la proximidad de una organización al ideal de empresa social. El ejercicio de análisis también resultó interesante como ejercicio reflexivo para las entidades participantes. Los resultados del cuestionario fueron especialmente interesantes en los telecentros de la Fundación Telecentre.org ya que al ser un estudio multicaso se pudo realizar un rico análisis estadístico sobre el funcionamiento de los telecentros y su desempeño. El estudio permitió identificar relaciones interesantes entre los ocho elementos de diseño del modelo propuesto y el desempeño de la organización. En particular, se detectó que para todos los casos estudiados: -La dimensión económica es la componente del desempeño que mayor desafíos plantea. -La existencia de una alta correlación entre el desempeño y siete de los ocho elementos organizativos del modelo. -La importancia de la cultura organizativa como elemento que explica el desempeño global de la organización y la satisfacción de los empleados. El campo de la empresa social presenta importantes retos de futuro, como la claridad conceptual, el desarrollo de estudios empíricos y la medida de su impacto social. El conocimiento de las claves organizativas puede ayudar a diseñar empresas sociales más robustas o a que organizaciones con fines sociales que no se basan en mecanismos de mercado consideren la posibilidad de incorporar éstos en su estrategia. ABSTRACT Social enterprise is an organizational model with a strong potential to help solving social problems. Recently, interest for the model has risen in both industrialized and developing countries because it is organized to achieve altruistic or social goals through market activities (mainly sales of products and services). Despite its historic roots, it is a relatively young field of research, where academic literature has little empirical data to accompany the theoretical development of social enterprise. Conceptual clarification has been the main challenge during the recent years, and there has been little attention given to generate evidence on how social enterprises operate and their keys to success. Progress in empirical study involves the construction of tools for researchers, in order to increase understanding of the internal mechanisms of social enterprises. This thesis aims to create a conceptual framework to study social enterprises from an organizational point of view, by analyzing the key elements that explain the operation and organization of this organizational model. The framework for the organizational analysis of social enterprises was built supported by the semantic analysis of 45 main definitions of social enterprise. The framework is divided into two dimensions: -There are four principles which capture the essence of the social enterprise concept, and are present in the manifestations of cases. -There are eight design elements which help analyze the characteristics of each particular social enterprise initiative: the social value proposition, social impact orientation, organizational culture, links to beneficiaries, entrepreneurial leadership, collaborative ecosystem, entrepreneurial strategy and orientation to economic self-sufficiency. Two diagnostic tools were developed to apply the framework to case studies: a scoreboard of indicators (to be used by the researcher during external analysis of the organization) and a questionnaire (to be answered by the social enterprise staff). The dissertation undertakes the study of three case studies: -ACCIONA Microenergia Peru, a social enterprise that provides electricity to isolated rural communities in the Peruvian region of Cajamarca. -Integra-e, a social enterprise located in Madrid that promotes socioprofessional integration of young people through training in ICT. -A sample of telecenters of the LAC network that provide access to information services (such as Internet) in Latin America. Applying the tools proved to be useful in all three cases, because it helped to obtain evidence to compare the proximity of an organization to an ideal type of social enterprise. In all the cases studied, the economic sustainability proved to be the biggest challenge for the organizations. The application of the questionnaire to the telecenters was especially informative because it was a multicase study which provided a rich statistical analysis on the performance of call centers. The study identified unique relationships between the model elements and the organziation performance. A statistical analysis shows a high correlation between performance and seven organizational elements described in the model. The organizational culture seems to be an important factor in explaining the overall organizational performance and employee satisfaction. The field of social enterprise has significant future challenges -such as conceptual clarity, the development of empirical studies and social impact assessment. A deep understanding of key organizational aspects of social enterprises can help in the design of more robust organizations and to bring success to social-purpose organizations.

Application of PZT and FBG impedance sensors for structural health monitoring of reinforced concrete beams strengthened with FRP composite materials

Esta Tesis tiene como objetivo principal el desarrollo de métodos de identificación del daño que sean robustos y fiables, enfocados a sistemas estructurales experimentales, fundamentalmente a las estructuras de hormigón armado reforzadas externamente con bandas fibras de polímeros reforzados (FRP). El modo de fallo de este tipo de sistema estructural es crítico, pues generalmente es debido a un despegue repentino y frágil de la banda del refuerzo FRP originado en grietas intermedias causadas por la flexión. La detección de este despegue en su fase inicial es fundamental para prevenir fallos futuros, que pueden ser catastróficos. Inicialmente, se lleva a cabo una revisión del método de la Impedancia Electro-Mecánica (EMI), de cara a exponer sus capacidades para la detección de daño. Una vez la tecnología apropiada es seleccionada, lo que incluye un analizador de impedancias así como novedosos sensores PZT para monitorización inteligente, se ha diseñado un procedimiento automático basado en los registros de impedancias de distintas estructuras de laboratorio. Basándonos en el hecho de que las mediciones de impedancias son posibles gracias a una colocación adecuada de una red de sensores PZT, la estimación de la presencia de daño se realiza analizando los resultados de distintos indicadores de daño obtenidos de la literatura. Para que este proceso sea automático y que no sean necesarios conocimientos previos sobre el método EMI para realizar un experimento, se ha diseñado e implementado un Interfaz Gráfico de Usuario, transformando la medición de impedancias en un proceso fácil e intuitivo. Se evalúa entonces el daño a través de los correspondientes índices de daño, intentando estimar no sólo su severidad, sino también su localización aproximada. El desarrollo de estos experimentos en cualquier estructura genera grandes cantidades de datos que han de ser procesados, y algunas veces los índices de daño no son suficientes para una evaluación completa de la integridad de una estructura. En la mayoría de los casos se pueden encontrar patrones de daño en los datos, pero no se tiene información a priori del estado de la estructura. En este punto, se ha hecho una importante investigación en técnicas de reconocimiento de patrones particularmente en aprendizaje no supervisado, encontrando aplicaciones interesantes en el campo de la medicina. De ahí surge una idea creativa e innovadora: detectar y seguir la evolución del daño en distintas estructuras como si se tratase de un cáncer propagándose por el cuerpo humano. En ese sentido, las lecturas de impedancias se emplean como información intrínseca de la salud de la propia estructura, de forma que se pueden aplicar las mismas técnicas que las empleadas en la investigación del cáncer. En este caso, se ha aplicado un algoritmo de clasificación jerárquica dado que ilustra además la clasificación de los datos de forma gráfica, incluyendo información cualitativa y cuantitativa sobre el daño. Se ha investigado la efectividad de este procedimiento a través de tres estructuras de laboratorio, como son una viga de aluminio, una unión atornillada de aluminio y un bloque de hormigón reforzado con FRP. La primera ayuda a mostrar la efectividad del método en sencillos escenarios de daño simple y múltiple, de forma que las conclusiones extraídas se aplican sobre los otros dos, diseñados para simular condiciones de despegue en distintas estructuras. Demostrada la efectividad del método de clasificación jerárquica de lecturas de impedancias, se aplica el procedimiento sobre las estructuras de hormigón armado reforzadas con bandas de FRP objeto de esta tesis, detectando y clasificando cada estado de daño. Finalmente, y como alternativa al anterior procedimiento, se propone un método para la monitorización continua de la interfase FRP-Hormigón, a través de una red de sensores FBG permanentemente instalados en dicha interfase. De esta forma, se obtienen medidas de deformación de la interfase en condiciones de carga continua, para ser implementadas en un modelo de optimización multiobjetivo, cuya solución se haya por medio de una expansión multiobjetivo del método Particle Swarm Optimization (PSO). La fiabilidad de este último método de detección se investiga a través de sendos ejemplos tanto numéricos como experimentales. ABSTRACT This thesis aims to develop robust and reliable damage identification methods focused on experimental structural systems, in particular Reinforced Concrete (RC) structures externally strengthened with Fiber Reinforced Polymers (FRP) strips. The failure mode of this type of structural system is critical, since it is usually due to sudden and brittle debonding of the FRP reinforcement originating from intermediate flexural cracks. Detection of the debonding in its initial stage is essential thus to prevent future failure, which might be catastrophic. Initially, a revision of the Electro-Mechanical Impedance (EMI) method is carried out, in order to expose its capabilities for local damage detection. Once the appropriate technology is selected, which includes impedance analyzer as well as novel PZT sensors for smart monitoring, an automated procedure has been design based on the impedance signatures of several lab-scale structures. On the basis that capturing impedance measurements is possible thanks to an adequately deployed PZT sensor network, the estimation of damage presence is done by analyzing the results of different damage indices obtained from the literature. In order to make this process automatic so that it is not necessary a priori knowledge of the EMI method to carry out an experimental test, a Graphical User Interface has been designed, turning the impedance measurements into an easy and intuitive procedure. Damage is then assessed through the analysis of the corresponding damage indices, trying to estimate not only the damage severity, but also its approximate location. The development of these tests on any kind of structure generates large amounts of data to be processed, and sometimes the information provided by damage indices is not enough to achieve a complete analysis of the structural health condition. In most of the cases, some damage patterns can be found in the data, but none a priori knowledge of the health condition is given for any structure. At this point, an important research on pattern recognition techniques has been carried out, particularly on unsupervised learning techniques, finding interesting applications in the medicine field. From this investigation, a creative and innovative idea arose: to detect and track the evolution of damage in different structures, as if it were a cancer propagating through a human body. In that sense, the impedance signatures are used to give intrinsic information of the health condition of the structure, so that the same clustering algorithms applied in the cancer research can be applied to the problem addressed in this dissertation. Hierarchical clustering is then applied since it also provides a graphical display of the clustered data, including quantitative and qualitative information about damage. The performance of this approach is firstly investigated using three lab-scale structures, such as a simple aluminium beam, a bolt-jointed aluminium beam and an FRP-strengthened concrete specimen. The first one shows the performance of the method on simple single and multiple damage scenarios, so that the first conclusions can be extracted and applied to the other two experimental tests, which are designed to simulate a debonding condition on different structures. Once the performance of the impedance-based hierarchical clustering method is proven to be successful, it is then applied to the structural system studied in this dissertation, the RC structures externally strengthened with FRP strips, where the debonding failure in the interface between the FRP and the concrete is successfully detected and classified, proving thus the feasibility of this method. Finally, as an alternative to the previous approach, a continuous monitoring procedure of the FRP-Concrete interface is proposed, based on an FBGsensors Network permanently deployed within that interface. In this way, strain measurements can be obtained under controlled loading conditions, and then they are used in order to implement a multi-objective model updating method solved by a multi-objective expansion of the Particle Swarm Optimization (PSO) method. The feasibility of this last proposal is investigated and successfully proven on both numerical and experimental RC beams strengthened with FRP.

The Conserved Core of a Human SIR2 Homologue Functions in Yeast Silencing

Silencing is a universal form of transcriptional regulation in which regions of the genome are reversibly inactivated by changes in chromatin structure. Sir2 (Silent Information Regulator) protein is unique among the silencing factors in Saccharomyces cerevisiae because it silences the rDNA as well as the silent mating-type loci and telomeres. Discovery of a gene family of Homologues of Sir Two (HSTs) in organisms from bacteria to humans suggests that SIR2’s silencing mechanism might be conserved. The Sir2 and Hst proteins share a core domain, which includes two diagnostic sequence motifs of unknown function as well as four cysteines of a putative zinc finger. We demonstrate by mutational analyses that the conserved core and each of its motifs are essential for Sir2p silencing. Chimeras between Sir2p and a human Sir2 homologue (hSir2Ap) indicate that this human protein’s core can substitute for that of Sir2p, implicating the core as a silencing domain. Immunofluorescence studies reveal partially disrupted localization, accounting for the yeast–human chimeras’ ability to function at only a subset of Sir2p’s target loci. Together, these results support a model for the involvement of distinct Sir2p-containing complexes in HM/telomeric and rDNA silencing and that HST family members, including the widely expressed hSir2A, may perform evolutionarily conserved functions.

Effectiveness of the postcoital test: randomised controlled trial

Objectives: To investigate the impact of the postcoital test on the pregnancy rate among subfertile couples and on the number of other diagnostic tests and treatments.

The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the protein huntingtin (htt). Pathogenesis in HD appears to involve the formation of ubiquitinated neuronal intranuclear inclusions containing N-terminal mutated htt, abnormal protein interactions, and the aggregate sequestration of a variety of proteins (noticeably, transcription factors). To identify novel htt-interacting proteins in a simple model system, we used a yeast two-hybrid screen with a Caenorhabditis elegans activation domain library. We found a predicted WW domain protein (ZK1127.9) that interacts with N-terminal fragments of htt in two-hybrid tests. A human homologue of ZK1127.9 is CA150, a transcriptional coactivator with a N-terminal insertion that contains an imperfect (Gln-Ala)38 tract encoded by a polymorphic repeat DNA. CA150 interacted in vitro with full-length htt from lymphoblastoid cells. The expression of CA150, measured immunohistochemically, was markedly increased in human HD brain tissue compared with normal age-matched human brain tissue, and CA150 showed aggregate formation with partial colocalization to ubiquitin-positive aggregates. In 432 HD patients, the CA150 repeat length explains a small, but statistically significant, amount of the variability in the onset age. Our data suggest that abnormal expression of CA150, mediated by interaction with polyglutamine-expanded htt, may alter transcription and have a role in HD pathogenesis.

Distribution of Sulfur within Oilseed Rape Leaves in Response to Sulfur Deficiency during Vegetative Growth1

The distribution of S to sulfate, glucosinolates, glutathione, and the insoluble fraction within oilseed rape (Brassica napus L.) leaves of different ages was investigated during vegetative growth. The concentrations of glutathione and glucosinolates increased from the oldest to the youngest leaves, whereas the opposite was observed for SO42−. The concentration of insoluble S was similar among all of the leaves. At sufficient S supply and in the youngest leaves, 2% of total S was allocated to glutathione, 6% to glucosinolates, 50% to the insoluble fraction, and the remainder accumulated as SO42−. In the middle and oldest leaves, 70% to 90% of total S accumulated as SO42−, whereas glutathione and glucosinolates together accounted for less than 1% of S. When the S supply was withdrawn (minus S), the concentrations of all S-containing compounds, particularly SO42−, decreased in the youngest and middle leaves. Neither glucosinolates nor glutathione were major sources of S during S deficiency. Plants grown on nutrient solution containing minus S and low N were less deficient than plants grown on solution containing minus S and high N. The effect of N was explained by differences in growth rate. The different responses of leaves of different ages to S deficiency have to be taken into account for the development of field diagnostic tests to determine whether plants are S deficient.

Transposon tools for recombinant DNA manipulation: characterization of transcriptional regulators from yeast, Xenopus, and mouse.

Transposon Tn1000 has been adapted to deliver novel DNA sequences for manipulating recombinant DNA. The transposition procedure for these "tagged" Tn1000s is simple and applicable to most plasmids in current use. For yeast molecular biology, tagged Tn1000s introduce a variety of yeast selective markers and replication origins into plasmids and cosmids. In addition, the beta-globin minimal promoter and lacZ gene of Tn(beta)lac serve as a mobile reporter of eukaryotic enhancer activity. In this paper, Tn(beta)lac was used to localize a mouse HoxB-complex enhancer in transgenic mice. Other tagged transposons create Gal4 DNA-binding-domain fusions, in either Escherichia coli or yeast plasmids, for use in one- and two-hybrid tests of transcriptional activation and protein-protein interaction, respectively. With such fusions, the Saccharomyces cerevisiae Swi6 G1/S-phase transcription factor and the Xenopus laevis Pintallavis developmental regulator are shown to activate transcription. Furthermore, the same transposon insertions also facilitated mapping of the Swi6 and Pintallavis domains responsible for transcriptional activation. Thus, as well as introducing novel sequences, tagged transposons share the numerous other applications of transposition such as producing insertional mutations, creating deletion series, or serving as mobile primer sites for DNA sequencing.

Detecção e caracterização moleculares dos paramixovírus aviários tipo 1 em materiais provenientes de aves silvestres utilizando testes para a detecção dos vírus da família viral Paramyxoviridae

As aves silvestres são importantes reservatórios de vírus que podem acometer as aves domésticas. O monitoramento da circulação viral em aves silvestres é de extrema importância para garantir a sanidade dos plantéis avícolas. O presente estudo teve como objetivo 1) comparar dois testes moleculares de RT-PCR para a detecção dos vírus da família Paramyxoviridae em aves silvestres e sinantrópicas; 2) caracterizar os vírus detectados nestas amostras. Dois testes de RT-PCR e testes específicos de RT-PCR em tempo real (RRT-PCR) para o vírus da doença de Newcastle (NDV) e o metapneumovírus aviário (aMPV) foram utilizados para comparar o limite de detecção entre as amostras. As amostras de aves silvestres foram testadas por dois testes de RT-PCR. Um pequeno fragmento da região do sítio de clivagem do gene F das amostras positivas foi sequenciado. Os testes de RT-PCR foram validados com sucesso, mas apresentaram diferenças entre os limites de detecção quando comparados aos testes específicos de RRT-PCR utilizando diferentes vírus. No total, 100 amostras de aves (suabes) foram testados pelo teste RT-PCR que apresentou um limite de detecção similar entre os diferentes agentes virais. O teste selecionado foi capaz de detectar duas amostras de aves silvestres que foram também detectadas pelo testes específico para NDV e relacionadas às amostras de NDV vacinais do genótipo II da classe II referentes aos vírus de NDV lentogênico (113RQGR ↓ L117). Nosso estudo demonstra a deficiência na biosseguridade adotada pelos sistemas avícolas por permitir a saída dos vírus vacinais para as aves silvestres

PCDD/F Emissions from Light-Duty Diesel Vehicles Operated under Highway Conditions and a Diesel-Engine Based Power Generator

PCDD/F emissions from three light-duty diesel vehicles–two vans and a passenger car–have been measured in on-road conditions. We propose a new methodology for small vehicles: a sample of exhaust gas is collected by means of equipment based on United States Environmental Protection Agency (U.S. EPA) method 23A for stationary stack emissions. The concentrations of O2, CO, CO2, NO, NO2 and SO2 have also been measured. Six tests were carried out at 90-100 km/h on a route 100 km long. Two additional tests were done during the first 10 minutes and the following 60 minutes of the run to assess the effect of the engine temperature on PCDD/F emissions. The emission factors obtained for the vans varied from 1800 to 8400 pg I-TEQ/Nm3 for a 2004 model year van and 490-580 pg I-TEQ/Nm3 for a 2006 model year van. Regarding the passenger car, one run was done in the presence of a catalyst and another without, obtaining emission factors (330-880 pg I-TEQ/Nm3) comparable to those of the modern van. Two other tests were carried out on a power generator leading to emission factors ranging from 31 to 78 pg I-TEQ/Nm3. All the results are discussed and compared with literature.

Polissensibilização alimentar : um caso clínico

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

Alergia a beta-lactâmicos : uma revisão sistemática

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

O desenvolvimento da compreensão audiovisual na aula de E/LE (nível A1)

Relatório da Prática de Ensino Supervisionada, Mestrado em Ensino de Inglês e Espanhol, Universidade de Lisboa, 2016