Amoebae are commonly studied to understand embryogenesis, and the best-characterized amoebozoan species is Dictyostelium discoideum (Dd). Dd has a very simple life cycle with a range of developmental stages, among which we are most interested in the stage of a migrating slug. It has been observed that different sizes of Dd slugs maintain a proportional distribution of prestalk cells and prespore cells: prestalk cells occupy the anterior 20% of the slug, while prespore cells occupy the posterior 80%. However, it remains unknown how the migrating slug forms and preserves this anterior-posterior proportional pattern under so many different dynamics including cell movement, signaling, and cell differentiation. Therefore, we constructed a mathematical model to simulate the cell movement and chemical distribution during slug migration, and we conducted numerical experiments to explore possible factors for this pattern. In particular, we divided the problem of interest into the following three parts to be investigated. (1) differential motion: the ability of prestalk cells to move through all the prespore cells and stay in the anterior region of the slug; (2) signaling: how cells of different types produce, receive, and respond to the signals in the environment; (3) cell differentiation: how prestalk and prespore cells differentiate into each other under the regulation of signaling. We finally combined and balanced these mechanisms appropriately to achieve the desired patterns observed in migrating slugs.

Atualmente, há inúmeras instalações offshore operando em regimes instáveis de escoamento. Tal regime é resultado de diâmetros superdimensionados das linhas de produção ou baixa vazão dos poços. Deve-se notar que, muitas vezes, o regime intermitente se instala no final da vida produtiva dos poços, devido ao declínio natural dos reservatórios, o que causa uma redução da produção do campo de petróleo. Tal instabilidade traz dificuldades na produção offshore, pois pode causar danos nos equipamentos da plataforma ou perdas de produção. Neste âmbito, é necessário estudar meios de atenuar ou suprimir este tipo de regime de escoamento. O objetivo deste trabalho é desenvolver métodos de forma a garantir a estabilidade do sistema através da modulação adequada da válvula choke, reduzindo ou mesmo eliminando o comportamento oscilatório da produção, mantendo a válvula choke na maior abertura possível, trazendo desta forma, ganhos econômicos através do aumento da produtividade do poço. Para a análise do sistema, utilizou-se um modelo dinâmico simplificado encontrado na literatura. Este modelo foi escolhido por reproduzir adequadamente o escoamento em golfadas severas, causado pela presença de trecho horizontal descendente na linha de produção. O sistema foi também modelado no OLGA®, sendo este, um software comercial com uso bastante disseminado na indústria de petróleo e com grande aplicação em simulações que exigem uma análise do comportamento transiente do problema. A avaliação da eficácia dos métodos de supressão das golfadas foi realizada através de duas abordagens distintas. Inicialmente, utilizou-se um controlador PI adaptativo com capacidade de operação em diferentes regiões de aberturas da válvula choke. Por fim, utilizou-se um Regulador Linear Quadrático associado a um observador de estados com filtro de Kalman Unscented com o objetivo de verificar como o sistema se comportaria em caso de necessidade de um observador para compensar uma possível falha do sensor submarino de pressão. Em ambos os casos, notou-se redução nas oscilações devido a golfadas do poço. As soluções foram implementadas através da integração entre o modelo do OLGA® e os algoritmos desenvolvidos no MATLAB utilizando servidor OPC. / Nowadays, there are numerous offshore installations operating in unstable flow regimes. Such unstable flow is the result of oversized diameters of production lines or low flow wells. It should be noticed that often the intermittent system occurs at the end of the productive life of wells due to the natural decline of the reservoir, which causes a reduction in oil field production. Such instability brings difficulties in offshore production, it can cause damage to the platform equipment or production losses. In this context, it is necessary to consider means to reduce or remove this type of flow regime. The objective of this work is to develop methods to ensure system stability by adequate modulation of choke valve, reducing or even eliminating the oscillatory behavior of the production, with the biggest choke valve opening possible, bringing economic gains by increasing well production The system analysis was carried out using a simplified dynamic model found in literature. This model was chosen by appropriately reproduction of severe slug flow, caused by the presence of downward horizontal section in the production line. The problem was also modeled on OLGA®, which is a commercial software with widespread use in the oil industry and large application in simulations that require a transient behavior analysis. The evaluation of the slugs suppression methods was carried out through two different approaches. First, an adaptive PI controller with capability to operate in different regions of choke valve openings was used. Finally, a Quadratic Linear Regulator associated to an Unscented Kalman Filter was used to verify how the system would behave in the event of a possible failure of subsea pressure sensor. In both cases, there was a reduction in oscillations due to slugs. The solutions were implemented through communication between the OLGA® model and the control algorithms developed in MATLAB using OPC server.

Breast cancer is the most prevalent cancer in women in the UK with over 50,000 new cases diagnosed each year. Almost all breast cancer deaths are due to metastatic disease. The RUNX1-CBFbeta transcription factor complex has been implicated in the development of human breast cancer and recent evidence from our laboratory indicated that it might have a role in metastasis. The aim of this project was therefore to determine the role of the RUNX1 transcription factor in breast cancer metastasis. Initial experiments to knockdown RUNX1 by shRNA also decreased the expression of RUNX2. Therefore, due to the off-target effect of shRUNX1, CRISPR-Cas9n was used to establish a RUNX1-negative cell line by targeting the first exon of the RUNX1 gene. Migration and invasion capacity of the cells decreased in the absence of RUNX1 and it was comparable to the absence of RUNX2 and CBFbeta respectively, which are known to play roles in migration and invasion of MDA-MB-231 cells. The cells also formed spherical clusters in 3D culture which was associated with the changes in cell morphology from stellate to round shape in the absence of RUNX1. The expression of the metastasis-related genes MMP13, MMP9, OPN and SLUG also decreased in parallel with the loss of the mesenchymal-like phenotype whilst the expression of the epithelial markers cytokeratin, desmoplakin and E-cadherin increased concomitantly. Importantly, re-expression of RUNX1 in the RUNX1-negative cell lines using an inducible expression system rescued migration and invasion. Therefore, RUNX1 is required to maintain the mesenchymal-like phenotype of MDA-MB-231 cells and hence is important for the epithelial to mesenchyme transition (EMT), a key characteristic of metastatic cells. The transcription factor SLUG is a known regulator of EMT. Data obtained shows that RUNX1 down-regulates the expression of SLUG. ChIP analysis demonstrated that RUNX1 was bound to the SLUG promoter and RUNX1 was subsequently shown to activate the promoter activity. Finally, experiments to inhibit the activity of the RUNX transcription factors pharmacologically showed changes in cell differentiation and also affected cell viability, possibly by off-target effects. Taken together, data presented in this work demonstrates that RUNX1 is required for EMT in the metastatic breast cancer cells and it is therefore a potential therapeutic target to prevent breast cancer metastasis.

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of FN into insoluble fibrils is crucial for Epithelial-Mesenchymal Transition (EMT) [3]. The transition from epithelial to mesenchymal cell type has been implicated as an early event in tumor formation and breast cancer. We were previously able to find that upregulation of FN fibrils drive EMT through contractility due to the increase of the GF latent TGF-β complex concentration at the cell membrane [3]. The challenge in the current work is to exploit the role of Heparin-II binding domain and to concentrate growth factors of interest, such as those that are pro-EMT or anti-EMT at the signaling sites of the cell membrane. Initially, we investigated the localization of the fragments FNIII 12-14 delivered to cell membrane using FITC conjugated protein. We then investigated the effects of exogenous FNIII 12-14 on EMT using breast epithelial cells (MCF10A) in the presence or absence of TGF-β1 to determine whether FNIII 12-14 alters EMT signaling. Quantification of mRNA expression, for EMT markers such as Slug, Snail, Twist, and ZEB1 were analyzed. Results showed that dosage increase of FNIII 12-14 appears to inhibit EMT transcription factors. This study will develop a new understanding of disease and gene control using ECM proteins. The exploitation of ECM natural protein interactions could become a new method in turning on/off genes of interest. While we are currently investigating this as a mechanism of blocking EMT, it could also have implications in wound healing, fibrosis, and tissue engineering, where EMT is an important aspect of the physiologic progression.

Für die Untersuchung von Luft/Wasser-Strömungen wurde ein horizontaler Acrylglas-Kanal mit rechteckigem Querschnitt gebaut. Der Kanal ermöglicht Gleich- und Gegenstrom-Versuche bei Atmosphärendruck, insbesondere die Untersuchung der Schwallströmung. Es wurden optische Messungen mit einer Hochgeschwindigkeits-Kamera durchgeführt, die durch synchronisierte dynamische Druckmessungen ergänzt wurden. Für die Analyse der Bilder wurde eine Methode zur Erfassung der Phasengrenze entwickelt und diese anhand möglicher Anwendungen getestet. Die Druckmessungen zeigten, dass der Druck bei Schwallströmungen um einige Kilopascal ansteigt und wieder abfällt, sobald der Schwall aus dem Kanal austritt. Zudem wurden Geschwindigkeiten in der flüssigen Phase mittels nicht invasiver Verfahren gemessen. Das durchschnittliche Geschwindigkeits-Profil am Kanaleintritt wurde mit Ultraschall-Köpfen bestimmt. Die Ermittlung des Geschwindigkeitsfeldes in einem Schwall erfolgte mit PIV (Particle Image Velocimetry).

This experimental study explores the heat transfer from heated bare and finned tubular surfaces to particulates in packed bed cross flow. The results from this experiment will be used to help select the type of particulates that will be used. Additionally, these results will assist in estimating heat transfer in prototype and commercial particle to fluid heat exchangers (PFHX). This research is part of larger effort in the use of particulates in concentrating solar power technology. These solid particles are heated by concentrated sunlight to very high temperatures at which they are a suitable heat source for various thermal power and thermochemical cycles. Furthermore, one of the advantages of this concept is the ability to store thermal energy in the solid particles at relatively low cost. However, an important feature of any Particle Heat Receiver (PHR) system is the PFHX, which is the interface between the solar energy system and the thermal power or chemical system. In order to create this system material data is needed for the design and optimization of this PFHX. The paper focuses on the heat transfer properties of particulates to solid surfaces under plug flow conditions. The particulates will be evaluated for three grain sizes of sand and two grain sizes of proppants. These two materials will be tested at one, five and ten millimeters per second in order to see how the various flow rates, which will be required for different loads, will affect the heat transfer coefficient. Finally the heat transfer coefficient will also be evaluated for both finned and non-finned heat exchangers to see the effect that changes in the surface geometry and surface area have on the heat transfer coefficient. The heat transfer coefficient will help determine the appropriate material that will be used in the PHR system.

[pt] Um dos maiores desafios da produção de petróleo offshore é garantir um escoamento regular do reservatório até a unidade de processamento da produção. Entre os fenômenos que podem dificultar esta tarefa está o estabelecimento de um escoamento em golfadas no riser de produção, caracterizado por oscilações periódicas e de grande amplitude nas vazões do sistema, que diminuem a eficiência da planta de separação, sujeitam equipamentos a esforços cíclicos e causam graves descontroles de processo. Por esta razão, foram desenvolvidas nas últimas décadas diversas soluções que visam a evitar a formação das golfadas, ou ao menos, atenuar suas consequências. Entre as soluções mais promissoras estão os controladores que evitam a formação das golfadas através da manipulação ativa da válvula choke e os controladores que amortecem as golfadas nos vasos separadores da planta de processo. Neste trabalho, estas estratégias de controle são revisitadas sob a óptica do controle inteligente, possibilitando a obtenção de resultados fora do alcance dos controladores lineares. Além de um modelo computacional que descreve um sistema de produção do poço ao vaso separador, também foram desenvolvidos neste trabalho dois controladores inteligentes. O primeiro deles é um controlador anti-golfada de arquitetura híbrida Fuzzy-PID, que é capaz de suprimir as golfadas mesmo em sistemas desprovidos de medições submarinas e com válvula choke lenta. O segundo é um controlador amortecedor de golfadas fuzzy, otimizado por um algoritmo genético, com alta capacidade de atenuação das golfadas e capaz de manter o nível dentro de uma faixa considerada segura. Ambos os controladores são testados em diversos cenários e têm seus resultados comparados aos obtidos por controladores lineares. / [en] One of the major challenges of offshore oil production is to ensure a regular flow from the reservoir to the production processing unit. Among the phenomena that may hamper this task is the establishment of slug flow in the production riser, characterized by periodic oscillations of large amplitude in the system flow rates, which reduce the efficiency of the separation plant, subject equipment to cyclical fatigue and cause serious process instabilities. For this reason, several solutions that aim at avoiding the formation of slugs or, at least, mitigating their consequences have been developed in the last decades. Among the most promising solutions are controllers that prevent the formation of slugs by actively manipulating the choke valve and controllers that dampen the slugs in the vessels of the separation plant. In this work, these control strategies are revisited from perspective of intelligent control, allowing the obtainment of results beyond the reach of linear controllers. In addition to a computational model that comprises a production system from the well to the separation vessel, two intelligent controllers were developed in this work. One of them is a hybrid Fuzzy-PID anti-slug controller that is capable of suppressing slugs even in systems without submarine measurements available and with slow choke valve. The other one is a fuzzy slug damping controller, optimized by a genetic algorithm, with high slug attenuation capacity and able to maintain the level within a specified range. Both controllers are tested in several scenarios and have their results compared to those obtained by linear controllers.

Made available in DSpace on 2014-06-11T19:23:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-27Bitstream added on 2014-06-13T18:50:59Z : No. of bitstreams: 1 mendes_faa_me_ilha.pdf: 2673818 bytes, checksum: 120558e9283b734ad04dda5b07ec06d0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O princípio de funcionamento de um sistema gas-lift é bastante simples, baseando-se na injeção de um gás inerte próximo à extremidade submersa de um tubo utilizado para ascensão do líquido (riser). Esse sistema tem sido utilizado em diversos setores da indústria, dentre os quais se destaca o setor petroquímico. Apesar de ter sido concebido há mais de um século, e a despeito do considerável número de artigos publicados sobre o assunto, vários aspectos relativos às características do escoamento bifásico dentro do riser e ao funcionamento do sistema são, ainda, pouco conhecidos. No presente trabalho, um sistema air-lift de pequeno porte foi inteiramente desenvolvido e testado, permitindo observar o comportamento do sistema quando submetido a variações na vazão de ar, na razão de submersão e na geometria do injetor – contendo três (3F) ou quinze furos (15F). Ensaios de visualização foram conduzidos, possibilitando a caracterização do escoamento bifásico no interior do riser. Medições experimentais foram, também, realizadas para a obtenção da eficiência e das curvas características do sistema. Os resultados quantitativos foram interpretados em associação com imagens estáticas do escoamento, capturadas com uma câmera fotográfica digital, e com imagens dinâmicas, tomadas com o auxílio de uma filmadora de alta velocidade. A partir destas imagens, foi possível, ainda, a estimativa de alguns importantes parâmetros característicos do escoamento pistonado, associados ao deslocamento da chamada bolha de Taylor. Os dados assim obtidos foram comparados com valores oriundos de correlações empíricas propostas por outros autores, apresentando boa concordância. Com relação aos resultados quantitativos, observou-se que, sob determinadas condições de operação, o injetor 3F é capaz de atribuir ao sistema um rendimento significativamente maior... / The operation principle of a gas-lift system is very simple: it is based on the injection of an inert gas close to the immersed edge of a tube, which is used for the rising of the liquid (riser). This system has been used in several industrial areas and more often in the petrochemical industry. Despite the fact that it was conceived over a century ago and that there have been a considerable amount of articles published on the subject, several aspects concerning the two-phase flow characteristics inside the riser as well as its operational system are still not very well known. In the present work, a small size air-lift system was thoroughly developed and tested, which facilitated the visualization of the system behavior when submitted to variations in the air flow, the immersion ratio and the injector geometry – containing three (3H) or fifteen holes (15H). Observation experiments were carried out making it possible to characterize the two-phase flow inside the riser. Experimental measurements were also taken in order to obtain the system characteristic efficiency and slopes. The quantitative results were analyzed together with the statistic images of the flow - taken by a digital photo camera, and with the dynamic images – taken by a high-speed filming camera. Through these images, it was also possible to estimate some important characteristic parameters of the slug flow associated to the displacement of the so-called Taylor bubble. The data obtained this way were compared to the figures originated from experimental correlations proposed by other authors, and they showed a fine agreement. Regarding the quantitative results, it was observed that under certain operation conditions the 3F injector is able to give the system a significantly greater efficiency than when the 15F injector is used

Resumo: O princípio de funcionamento de um sistema gas-lift é bastante simples, baseando-se na injeção de um gás inerte próximo à extremidade submersa de um tubo utilizado para ascensão do líquido (riser). Esse sistema tem sido utilizado em diversos setores da indústria, dentre os quais se destaca o setor petroquímico. Apesar de ter sido concebido há mais de um século, e a despeito do considerável número de artigos publicados sobre o assunto, vários aspectos relativos às características do escoamento bifásico dentro do riser e ao funcionamento do sistema são, ainda, pouco conhecidos. No presente trabalho, um sistema air-lift de pequeno porte foi inteiramente desenvolvido e testado, permitindo observar o comportamento do sistema quando submetido a variações na vazão de ar, na razão de submersão e na geometria do injetor - contendo três (3F) ou quinze furos (15F). Ensaios de visualização foram conduzidos, possibilitando a caracterização do escoamento bifásico no interior do riser. Medições experimentais foram, também, realizadas para a obtenção da eficiência e das curvas características do sistema. Os resultados quantitativos foram interpretados em associação com imagens estáticas do escoamento, capturadas com uma câmera fotográfica digital, e com imagens dinâmicas, tomadas com o auxílio de uma filmadora de alta velocidade. A partir destas imagens, foi possível, ainda, a estimativa de alguns importantes parâmetros característicos do escoamento pistonado, associados ao deslocamento da chamada bolha de Taylor. Os dados assim obtidos foram comparados com valores oriundos de correlações empíricas propostas por outros autores, apresentando boa concordância. Com relação aos resultados quantitativos, observou-se que, sob determinadas condições de operação, o injetor 3F é capaz de atribuir ao sistema um rendimento significativamente maior... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The operation principle of a gas-lift system is very simple: it is based on the injection of an inert gas close to the immersed edge of a tube, which is used for the rising of the liquid (riser). This system has been used in several industrial areas and more often in the petrochemical industry. Despite the fact that it was conceived over a century ago and that there have been a considerable amount of articles published on the subject, several aspects concerning the two-phase flow characteristics inside the riser as well as its operational system are still not very well known. In the present work, a small size air-lift system was thoroughly developed and tested, which facilitated the visualization of the system behavior when submitted to variations in the air flow, the immersion ratio and the injector geometry - containing three (3H) or fifteen holes (15H). Observation experiments were carried out making it possible to characterize the two-phase flow inside the riser. Experimental measurements were also taken in order to obtain the system characteristic efficiency and slopes. The quantitative results were analyzed together with the statistic images of the flow - taken by a digital photo camera, and with the dynamic images - taken by a high-speed filming camera. Through these images, it was also possible to estimate some important characteristic parameters of the slug flow associated to the displacement of the so-called Taylor bubble. The data obtained this way were compared to the figures originated from experimental correlations proposed by other authors, and they showed a fine agreement. Regarding the quantitative results, it was observed that under certain operation conditions the 3F injector is able to give the system a significantly greater efficiency than when the 15F injector is used / Orientador: Sérgio Said Mansur / Coorientador: Edson Del Rio Vieira / Banca: André Luiz Seixlack / Banca: Ricardo Augusto Mazza / Mestre

Atualmente, há inúmeras instalações offshore operando em regimes instáveis de escoamento. Tal regime é resultado de diâmetros superdimensionados das linhas de produção ou baixa vazão dos poços. Deve-se notar que, muitas vezes, o regime intermitente se instala no final da vida produtiva dos poços, devido ao declínio natural dos reservatórios, o que causa uma redução da produção do campo de petróleo. Tal instabilidade traz dificuldades na produção offshore, pois pode causar danos nos equipamentos da plataforma ou perdas de produção. Neste âmbito, é necessário estudar meios de atenuar ou suprimir este tipo de regime de escoamento. O objetivo deste trabalho é desenvolver métodos de forma a garantir a estabilidade do sistema através da modulação adequada da válvula choke, reduzindo ou mesmo eliminando o comportamento oscilatório da produção, mantendo a válvula choke na maior abertura possível, trazendo desta forma, ganhos econômicos através do aumento da produtividade do poço. Para a análise do sistema, utilizou-se um modelo dinâmico simplificado encontrado na literatura. Este modelo foi escolhido por reproduzir adequadamente o escoamento em golfadas severas, causado pela presença de trecho horizontal descendente na linha de produção. O sistema foi também modelado no OLGA®, sendo este, um software comercial com uso bastante disseminado na indústria de petróleo e com grande aplicação em simulações que exigem uma análise do comportamento transiente do problema. A avaliação da eficácia dos métodos de supressão das golfadas foi realizada através de duas abordagens distintas. Inicialmente, utilizou-se um controlador PI adaptativo com capacidade de operação em diferentes regiões de aberturas da válvula choke. Por fim, utilizou-se um Regulador Linear Quadrático associado a um observador de estados com filtro de Kalman Unscented com o objetivo de verificar como o sistema se comportaria em caso de necessidade de um observador para compensar uma possível falha do sensor submarino de pressão. Em ambos os casos, notou-se redução nas oscilações devido a golfadas do poço. As soluções foram implementadas através da integração entre o modelo do OLGA® e os algoritmos desenvolvidos no MATLAB utilizando servidor OPC. / Nowadays, there are numerous offshore installations operating in unstable flow regimes. Such unstable flow is the result of oversized diameters of production lines or low flow wells. It should be noticed that often the intermittent system occurs at the end of the productive life of wells due to the natural decline of the reservoir, which causes a reduction in oil field production. Such instability brings difficulties in offshore production, it can cause damage to the platform equipment or production losses. In this context, it is necessary to consider means to reduce or remove this type of flow regime. The objective of this work is to develop methods to ensure system stability by adequate modulation of choke valve, reducing or even eliminating the oscillatory behavior of the production, with the biggest choke valve opening possible, bringing economic gains by increasing well production The system analysis was carried out using a simplified dynamic model found in literature. This model was chosen by appropriately reproduction of severe slug flow, caused by the presence of downward horizontal section in the production line. The problem was also modeled on OLGA®, which is a commercial software with widespread use in the oil industry and large application in simulations that require a transient behavior analysis. The evaluation of the slugs suppression methods was carried out through two different approaches. First, an adaptive PI controller with capability to operate in different regions of choke valve openings was used. Finally, a Quadratic Linear Regulator associated to an Unscented Kalman Filter was used to verify how the system would behave in the event of a possible failure of subsea pressure sensor. In both cases, there was a reduction in oscillations due to slugs. The solutions were implemented through communication between the OLGA® model and the control algorithms developed in MATLAB using OPC server.