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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
81

Confined magnetohydrodynamics applied to magnetic fusion plasmas / Magnétohydrodynamique confinée appliquée aux plasmas de fusion magnétiques

Morales Mena, Jorge 01 October 2013 (has links)
La description magnétohydrodynamique est utilisée pour étudier les plasmas de fusion par confinement magnétique dans deux configurations: tokamak et reversed field pinch. Une méthode de Fourier pseudo-spectrale et une technique de pénalisation en volume sont employées pour résoudre les équations. La méthode de pénalisation permet d’introduire des conditions aux limites de Dirichlet et donc de faire varier facilement la géométrie considérée. Les simulations dans des géométries toroïdales de type tokamak montrent l’apparition spontanée de vitesses. Une importante composante toroïdale se développe si le système est peu dissipatif. Il est aussi montré que la brisure de symétrie dans la forme de la section du tore fait apparaitre un moment angulaire toroïdal. Pour le Reversed Field Pinch on montre l’émergence de structures hélicoïdales. La forme de ces structures varie en fonction des coefficients de transport ainsi que du paramètre de pincement du champ magnétique imposé. Pour compléter l’étude on compare les résultats du tore aux calculs dans un cylindre périodique. Les différences dans la dynamique des deux cas sont mises en avant. Finalement les simulations sont confrontées à des expériences et un meilleur accord est observé entre simulation et expérience pour la géométrie toroïdale que pour la géométrie cylindrique. / A magnetohydrodynamic description is used to study magnetic fusion plasmas in two different configurations: tokamak and reversed field pinch. A Fourier pseudo-spectral method with a volume penalization technique are used to solve the system of equations. The penalization method is used to introduce Dirichlet boundary conditions and it al- lows to easily modify the consider geometry. The simulations of a tokamak configuration in a toroidal geometry show the spontaneous appearance of velocities. These velocities are dominated by their toroidal component if the system is little dissipative. It is also shown that the symmetry breaking of the cross section of the torus causes a toroidal angular momentum to develop. For the Reversed Field Pinch configuration we show the appearance of helical structures. The shape of these structures varies with the value of the transport coefficients and with the pinch ratio parameter of the imposed magnetic field. To complete the study, we compare the results of simulations obtained in toroidal and in periodic cylindrical geometries. The differences in the dynamics of these two cases are highlighted. Finally, simulations are compared to experimental data and a significant better agreement is observed between the simulation and the experiment for the toroidal geometry than for the cylindrical case.
82

Self powered wrist extension orthosis

Singer, Mathew Kyle January 2006 (has links)
One of the most devastating effects of tetraplegia is the inability to grasp and manipulate everyday objects necessary to living an independent life. Currently surgery is widely accepted as the solution to improve hand functionality. However, surgery becomes difficult when the user has paralysed wrists as is the case with C5 tetraplegia. The aim of this research was to develop a solution which provided controlled wrist flexion and extension which, when combined with surgery, achieves a 'key pinch' grip. This particular grip is critically important for people with C5 tetraplegia as it is used for countless grasping activities, necessary on a day-to-day basis. A systematic design process was used to evolve the solution to provide controlled wrist flexion and extension. Concept brainstorming identified four alternative solutions which were evaluated to find the preferred concept. The chosen solution was called the Self Powered Wrist Extension Orthosis, more commonly referred to as the 'orthosis'. This concept contained a shoulder harness which provided both energy and control to the wrist harness, which in turn changed the wrist position. The orthosis was developed with the use of a mathematical model which theoretically predicted the functional performance by comparing the required force needed to move the wrist harness to the achievable force supplied by the user's shoulders. Using these parameters, the orthosis was optimized using the matlab Nelder-Mead algorithm which adjusted the wrist harness geometries to maximize the functional performance. A prototype was constructed and tested with the help of two participants who when combined, achieved an average of 18.5° of wrist rotation. The theoretical model however predicted an average range of motion of 28.4°. The discrepancy found between the theoretical and experimental result can be contributed to incorrect assumptions in the theoretical model. This included unaccounted friction and inaccurate modeling of the orthosis dynamics. The feedback from potential users of the orthosis was enthusiastic and encouraging especially towards the simplicity, usability and practicality of the design.
83

Integração energética da etapa de extração de óleo de soja, utilizando a análise Pinch / Energetic integration of extraction step of soybean oil, using Pinch analysis

Fernandes Junior, Carlos Coutinho 13 October 2009 (has links)
Made available in DSpace on 2017-07-10T18:08:13Z (GMT). No. of bitstreams: 1 Carlos Coutinho Fernandes Junior.pdf: 1216021 bytes, checksum: 140e087a28751c7c2ea0079d79d89a2d (MD5) Previous issue date: 2009-10-13 / In the process of soy oil the consumption of energy is extremely high, which is always important to create new alternatives to energetic consumption reduction. This paper is carried on a case study of energetic integration in a soy oil factory operating with an average production of 15.000 tons/month. At first, the rate of flow, the input and output temperatures and the calorific capacity of all currents in the extraction phase were evaluated. After this assessment, based on the thermal potential change, four currents were selected, two denominated hot currents and two denominated cold currents. The first hot current (Q1) consists of a crude oil current from the post-separation phase of the solvent hexane with the input temperature of 110 ºC and output temperature of 80ºC. The second hot current (Q2) consists of a water current coming out of a boiler with an input temperature of 90 ºC and goes to the effluent treatment station having to be cooled to 55 ºC. These two currents have a thermal potential change of 262,8 kW/h. The third current denominated cold current F1, consists of a water current that comes from the decanter with a input temperature of 40 ºC and enters in the heater to reach an output temperature of 90 ºC, where the residual hexane is evaporated. The fourth current, denominated cold current F2, is a mixture of 70% of oil and 30% of hexane with an input temperature of 60 ºC and output temperature of 90 ºC. These two currents have a thermal necessity of 330 kW, for their heating. The synthesis methodology adopted for the heat exchangers network synthesis, due to the easiness in application and interaction with the user, was the Pinch Analysis. In the synthesis procedure, the Problem Table was developed and the Pinch Point was identified and the goals for the consumption of utilities were obtained for the maximum energy recovery. The problem was divided into two regions, below and above the Pinch Point. After the synthesis and optimization, the total cost for the network was calculated and all thermal exchange occurs above the Pinch Point . The proposed network consists of two heat exchangers and two boilers, so that a exchanger performs the thermal change between the Q1 (crude oil) and Q2 (miscela) currents. The second exchanger performs the change between Q2 (the water in the boiler exit) and F1 (water in the decanter exit) currents. The additional heating for the cold currents to reach final temperatures is provided by the boilers that are already being used in the factory. The economy generated by the reduction in the consumption of utilities was of R$ 91,000.00/year, meaning a reduction of steam consumption of 79,6% and a reduction of 5,3% in the global consumption of the plant steam. The investment needed for the two proposed heat exchangers in the network, is R$ 16.540,00. Evaluating the year total cost, that includes the annual capital cost of the exchangers, an annual reduction of R$ 114.445,00 for R$ 25.800,00 is verified corresponding to 77.5% reduction in the annual total cost after the network synthesis. The return rate for the investment proposed is only 3 months. Therefore, Pinch Analysis is confirmed to be efficient in the energetic integration of processes reaching meaningful economy results in thermal energy, contributing for the industrial processes that are more and more competitive. / No processo de fabricação de óleo de soja, o consumo de energia é extremamente alto, sendo sempre um tema de foco para criar alternativas de redução do consumo energético. Neste trabalho, realizou-se um estudo de caso de integração energética na etapa da extração de uma fábrica de óleo de soja operando com produção média de 15.000 toneladas/mês. Inicialmente avaliou-se as vazões, as temperaturas de entrada e saída e as capacidades caloríficas de todas as correntes da etapa de extração. Após esta avaliação, baseando-se no potencial de troca térmica, foram selecionadas quatro correntes, sendo duas delas denominadas de correntes quentes e outras duas denominadas de correntes frias. A primeira corrente quente (Q1), consiste em uma corrente de óleo bruto oriunda da etapa pós-separação do solvente hexano, com temperatura de entrada de 110 ºC e temperatura de saída de 80ºC. A segunda corrente quente (Q2), consiste em uma corrente de água que sai de um aquecedor com temperatura de entrada de 90ºC e vai para a estação de tratamento de efluentes, necessitando ser resfriada até 55 ºC. Essas duas correntes quentes têm um potencial de troca térmica de 262,8 kW/h. A terceira corrente, denominada de corrente fria F1, consiste em uma corrente de água que sai do decantador a 40 ºC, e entra no aquecedor para atingir a temperatura de saída de 90 ºC, onde hexano residual é evaporado. A quarta corrente, denominada de corrente fria F2, consiste em uma mistura de 70% óleo e 30% hexano com temperaturas de entrada de 60 ºC e de saída de 90 ºC. Essas duas correntes (F1 e F2) tem uma necessidade térmica para seu aquecimento de 330 kW. A metodologia de síntese adotada para a síntese da rede de trocadores de calor, devido à facilidade de aplicação e interação com o usuário, foi a Análise Pinch. No procedimento de síntese, inicialmente é construída a tabela do problema onde identificou-se o ponto de estrangulamento energético, ou ponto Pinch, obtendo-se assim as metas de consumo de utilidades para a máxima recuperação de energia. Após esta etapa, o problema foi dividido em duas regiões: abaixo e acima do Pinch, sendo realizada a síntese da rede. No caso estudado, toda a troca térmica ocorre na região acima do Pinch. Assim, após a síntese e otimização da rede, calculou-se o custo total anual. A rede proposta consiste em 2 trocadores de calor e dois aquecedores, sendo que um trocador realiza troca térmica entre a corrente Q1 (óleo bruto) e a corrente F2 (a miscela), e o segundo trocador realiza troca entre a corrente Q2 (água na saída do aquecedor) e a corrente F1 (água na saída do decantador). O aquecimento complementar para as correntes frias atingirem suas temperaturas finais, é provido pelos aquecedores já existentes na linha. A economia gerada pela redução de consumo de utilidades foi de R$ 91.000,00/ano, o que representa uma economia de consumo de vapor de 79,6%, acarretando uma redução de 5,3% do consumo global de vapor da planta. O investimento necessário para os dois trocadores de calor propostos na rede é de R$ 16.540,00, e avaliando-se o custo total anual, verifica-se uma redução de R$ 114.445,00 para R$ 25.800,00, correspondendo a uma redução de 77,5% no custo total anual, após a síntese da rede. A taxa de retorno para o investimento proposto é de apenas 3 meses. Desta forma, confirma-se a eficiência da Análise Pinch na integração energética de processos, atingindo resultados significativos de economia de energia térmica,contribuindo para processos industriais cada vez mais competitivos.
84

Problèmes autour de courbes élliptiques et modulaires / Topics in elliptic and modular curves

Sha, Min 27 September 2013 (has links)
Cette thèse se divise en deux parties. La première est consacrée aux points entiers sur les courbes modulaires, et l'autre se concentre sur les courbes elliptiques à couplages.Dans la première partie, nous donnons quelques majorations effectives de la hauteur des j-invariants des points entiers sur les courbes modulaires quelconques associées aux sous-groupes de congruence sur les corps de nombres quelconques en supposant que le nombre des pointes est au moins 3. De plus, dans le cas d'un groupe de Cartan non-déployé nous fournissons de meilleures bornes. Comme application, nous obtenons des résultats similaires pour certaines courbes modulaires avec moins de 3 pointes.Dans la deuxième partie, nous donnons une nouvelle majoration du nombre de classes d'isogénie de courbes elliptiques ordinaires à couplages. Nous analysons également la méthode de Cocks-Pinch pour confirmer certaines de ses propriétés communément conjecturées. Par ailleurs, nous présentons la première analyse heuristique connue qui suggère que toute construction efficace de courbes elliptiques à couplages peut engendrer efficacement de telles courbes sur tout corps à couplages. Enfin, quelques données numériques allant dans ce sens sont données. / This thesis is divided into two parts. One is devoted to integral points on modular curves, and the other concerns pairing-friendly elliptic curves. In the first part, we give some effective upper bounds for the $j$-invariant of integral points on arbitrary modular curves corresponding to congruence subgroups over arbitrary number fields assuming that the number of cusps is not less than 3. Especially, in the non-split Cartan case we provide much better bounds. As an application, we get similar results for certain modular curves with less than three cusps. In the second part, a new heuristic upper bound for the number of isogeny classes of ordinary pairing-friendly elliptic curves is given. We also heuristically analyze the Cocks-Pinch method to confirm some of its general consensuses. Especially, we present the first known heuristic which suggests that any efficient construction of pairing-friendly elliptic curves can efficiently generate such curves over pairing-friendly fields. Finally, some numerical evidence is given.
85

Avaliação de um ciclo de liquefação usando a tecnologia de refrigerante misto para plantas de pequena escala de GNL. / Analysis of a liquefaction cycle using mixed refrigerant technology for LNG small scale plants.

Tacuse Begazo, Christian Daniel 14 November 2008 (has links)
Este trabalho tem como objetivo analisar a tecnologia do ciclo refrigerante misto para obtenção de gás natural liquefeito (GNL). Nessa tecnologia, o GNL é obtido por meio do seu resfriamento através de um ciclo de refrigeração, cujo fluido refrigerante é formado por uma mistura de diversos componentes. O ciclo de refrigeração é usado para resfriar a corrente de gás natural até as condições criogênicas por meio de um trocador de calor. A determinação da composição ótima dessa mistura de refrigerantes é de suma importância para a correta e eficiente operação da planta. O modelo termodinâmico para o cálculo de equilíbrio de fases dos componentes da mistura refrigerante é o baseado na Lei de Raoult, válido para misturas e soluções ideais. Inicialmente, revisam-se os conceitos de refrigerantes mistos, curvas compostas e o ponto de pinça (pinch point), utilizados na implementação da solução computacional. A aplicação dos modelos de gás e solução ideal influencia nos resultados, mas, não obstante, produz bons resultados como os obtidos no presente trabalho. A operação eficiente do ciclo depende, sobretudo, de três parâmetros principais, quais sejam: vazão da mistura refrigerante, razão de pressões alta e baixa do ciclo de refrigeração e composição da mistura refrigerante. Da análise dos resultados obtidos conclui-se que a alteração nas proporções da composição do refrigerante muda significativamente a forma das curvas composta quente e composta fria, quando comparados à alteração dos níveis de pressão e da vazão do ciclo refrigerante. Entretanto, a operacionalização do ciclo somente ocorre se um dado conjunto de valores daqueles parâmetros satisfaça uma determinada diferença mínima de temperatura, ou ponto de pinça, entre as curvas composta quente e composta fria dentro do trocador de calor. Assim, a operação eficiente do ciclo de refrigeração requer a otimização daqueles três parâmetros operacionais. / This work has the objective of analyzing the technology of mixed refrigerant cycle for obtaining liquefied natural gas (LNG). In that technology, the liquefied natural gas is obtained by means of cooling through a refrigeration cycle, whose fluid refrigerant is formed by a mixture of various components. The refrigeration cycle is used to cool the natural gas stream to cryogenic condition with the use of a heat exchanger. The determination of the optimal composition of this refrigerant mixture is very important for the correct and efficient operation of the plant. The thermodynamic model for the equilibrium phase calculation of the refrigerant mixture is based on the Law of Raoult, which is valid for ideal mixtures and solutions. Initially, the concepts of refrigerant mixture, composite curves and pinch point used in the implementation of the numerical solution were reviewed. The application of ideal-gas and ideal-solution models has influence on the results. Nevertheless, it produces good results as those obtained in the present work. The efficient operation of the cycle depends essentially of three key parameters, which are: refrigerant flow rate, the ratio of high to low pressures of the refrigerant cycle and the mixed refrigerant composition. The results indicated that the composition variation of the refrigerant changes significantly the shape of hot and cold composite curves in comparison to the modification in the pressure levels and the refrigerant flow rate of the refrigerant cycle. However, the process will operate only if a given set of values of those parameters satisfies a minimum temperature difference, or pinch point, between the hot and cold composite curves within the heat exchanger. Thus, the efficient operation of the refrigerant cycle requires the optimization of those three operational parameters.
86

Low Temperature Waste Heat Solutions : with proposals for energy technological actions based on Scania’s building 64 / Lågtemperaturlösningar : samt energitekniska åtgärdsförslag utifrån Scanias byggnad 64

Svensson, Klas, Wallenskog, Jonas January 2009 (has links)
<p>The report comprises two separate parts:</p><ul><li>part 1:  Temperature needs for district heating in the paint shop for axles in building 210</li><li>part 2:  Energy and low temperature waste heat solutions in heating and cooling systems for   building 64 with surroundings</li></ul><p>The paint shop for axles in part 1 has air quality requirements in places for coating of axles. Toachieve desired air properties there are different process ventilation systems, which consist ofventilation coils for heating and cooling, plus air humidifier. The ventilations coils for heating usedistrict heating. Today the ventilation coils use water of 100°C to achieve necessary air demands inthe coating boxes. This part of the report investigates whether the existing system would achievethe air requirements with a water temperature of 75°C instead of 100°C in the ventilation coilsduring the coldest parts of the year. The conclusion is that it is not possible; the existing system isadjusted for a water temperature of 100°C to achieve the air requirements. To use a watertemperature of 75°C, more or major ventilation coils are needed.</p><p>The focus of the report is at part 2. In this part, possibilities for low temperature waste heatsolutions are investigated. Those partly aim at specific local solutions for building 64 withsurroundings and on the other part of general waste heat solutions for new buildings andreconstructions in the future. To make these parts possible, the systems for heating and cooling inbuilding 64 have been identified. During this identification, potential savings that are not of wasteheat character have also been observed.</p><p>The most profitable saving concerns the control of temperature for the inner hardening vat. It isthe hardening vat for gas carburizing oven SV16838 that has been studied in this report. Today thetemperature of the hardening vat is controlled very ineffective. The conclusion is that a betteradjustment of the controller would save 180 000 SEK/year with a pay off time around two months.Worth mentioning (SV16838 included), is that there are at least five similar gas carburizing ovens atthe Scania area in Södertälje.</p><p>A pinch analysis has also been done for building 64, with it’s primarily conclusion that the groundheating is violating the pinch rules during long periods of the year. To remedy the ground heatingwill only need a different control and will lead to a saving between 20 000 – 75 000 SEK/year. Tomore accurate determine the saving, an investigation of the ground heating during winter time isneeded. Another conclusion concerning the pinch analysis is that the method for a real scenariorather shows the potential of the system than gives you an optimal solution possible to implement.More actions are to use the exhaustions of the endo gas generators and that the washing andrinsing systems if possible not should be heated with electricity. The exhaustions from the endo gasgenerators have a very high temperature, more then 300°C. If these, instead of hot water boilers,could warm the closely located water for the LPG (liquefied petroleum gas) evaporation, 125 000SEK/year can be saved. Today the hot water boilers are heated with electricity. If the washing andrinsing systems existing electricity heating instead can be heated with secondary heat (˜ districtheating), a save of 500 000 SEK/year is possible.</p><p>For waste heat solutions there are a few different approaches. Close to building 64, the largestpotential to use waste heat is in building 62 and 75, where air heaters are assessed with the largestpotential. In difference to other investigated buildings, building 210 has the possibility to use wasteheat even during the summer. This building is located 1 km from building 64. To use waste water inbuilding 210, a complex net of waste heating will be required where several buildings with asurplus of waste heat can be connected. A net like this has calculated pipe costs of 5, 2 million SEK.The saving for the use of waste heat only in building 210 will be around 1,4 million SEK/year. Thissave corresponds to the air handling systems that occur in part 1.</p>
87

Resistive Wall Mode Stability and Control in the Reversed Field Pinch

Yadikin, Dmitriy January 2006 (has links)
Control of MHD instabilities using a conducting wall together with external magnetic fields is an important route to improved performance and reliability in fusion devices. Active control of MHD modes is of interest for both the Advanced Tokamak and the Reversed Field Pinch (RFP) configurations. A wide range of unstable, current driven MHD modes is present in the RFP. An ideally conducting wall facing the plasma can in principle provide stabilization to these modes. However, a real, resistive wall characterized by a wall field diffusion time, cannot stabilize the ideal MHD modes unless they rotate with Alfvénic velocity, which is usually not the case. With a resistive wall, the ideal modes are converted into resistive wall modes (RWM) with growth rates comparable to the inverse wall time. Resistive wall modes have been studied in the EXTRAP T2R thin shell RFP device. Growth rates have been measured and found in agreement with linear MHD stability calculations. An advanced system for active control has been developed and installed on the EXTRAP T2R device. The system includes an array of 128 active saddle coils, fully covering the torus surface. Experiments on EXTRAP T2R have for the first time demonstrated simultaneous active suppression of multiple independent RWMs. In experiments with a partial array, coupling of different modes due to the limited number of feedback coils has been observed, in agreement with theory. Different feedback strategies, such as the intelligent shell, the rotating shell, and mode control have been studied. Further, feedback operation with different types of magnetic field sensors, measuring either the radial or the toroidal field components have been compared / QC 20100929
88

Shock Attenuation in Two-Phase (Gas-Liquid) Jets for Inertial Fusion Applications

Lascar, Celine Claire 24 August 2007 (has links)
Z-Pinch IFE (Inertial Fusion Energy) reactor designs will likely utilize high yield targets (~ 3 GJ) at low repetition rates (~ 0.1 Hz). Appropriately arranged thick liquid jets can protect the cavity walls from the target x-rays, ions, and neutrons. However, the shock waves and mechanical loadings produced by rapid heating and evaporation of incompressible liquid jets may be challenging to accommodate within a small reactor cavity. This investigation examines the possibility of using two-phase compressible (liquid/gas) jets to protect the cavity walls in high yield IFE systems, thereby mitigating the mechanical consequences of rapid energy deposition within the jets. Two-phase, free, vertical jets with different cross sections (planar, circular, and annular) were examined over wide ranges of liquid velocities and void fractions. The void fraction and bubble size distributions within the jets were measured; correlations to predict variations of the slip ratio and the Sauter mean diameter were developed. An exploding wire system was used to generate a shock wave at the center of the annular jets. Attenuation of the shock by the surrounding single- or two-phase medium was measured. The results show that stable coherent jets can be established and steadily maintained over a wide range of inlet void fractions and liquid velocities, and that significant attenuation in shock strength can be attained with relatively modest void fractions (~ 1%); the compressible two-phase jets effectively convert and dissipate mechanical energy into thermal energy within the gas bubbles. The experimental characteristics of single- and two-phase jets were compared against predictions of a state-of-art CFD code (FLUENT®). The data obtained in this investigation will allow reactor system designers to predict the behavior of single- and two-phase jets and quantify their effectiveness in mitigating the consequences of shock waves on the cavity walls in high yield IFE systems.
89

Molecular and Biological Characteristics of Stroma and Tumor Cells in Colorectal Cancer

Gao, Jingfang January 2008 (has links)
Carcinogenesis is a progressive process involving multiple genetic alterations in tumor cells and complex interactions in the tumor-host microenvironment. To better understand the contribution of molecular alterations in tumor cells and stromal variables to the development of colorectal cancer (CRC) and identify prognostic factors, in this study we examined the clinicopathological and biological significance of stromal variables, including particularly interesting new cysteine-histidine rich protein (PINCH), inflammatory infiltration, angiogenesis and lymphangiogenesis, as well as hRAD50/hMRE11/hNBS1 proteins and hRAD50 mutation in tumor cell in CRC. PINCH protein expression in the stroma was increased from normal mucosa to primary tumors and further to lymph node metastases. In particular, PINCH expression was most intense at the tumor invasive margin, which was related to low inflammatory infiltration and independently related to an unfavorable prognosis. Low inflammatory infiltration at the tumor invasive margin was related to advanced tumor stage, worse differentiation and microsatellite instability (MSI). Further, it was independently related to an unfavorable prognosis. Increased blood and lymphatic vessel density was observed in the primary tumors compared with the corresponding normal mucosa. However, neither angiogenesis nor lymphangiogenesis was associated with tumor stage and patients’ survival. Moreover, PINCH was present in a proportion of endothelial cells of the tumor vasculature, and PINCH expression in tumor-associated stroma was positively related to blood vessel density. In primary tumor cells of CRC, strong expression of hRAD50, hMRE11 or hNBS1 was related to microsatellite stability (MSS). A high percentage of hMRE11 expression was associated with less local recurrence and high apoptotic activity. Further, we observed that the expression of hRAD50, hMRE11 or hNBS1 among normal mucosa, primary tumors and metastases in MSS CRC differed from that in MSI CRC. In MSS CRC, the expression intensity of hRAD50, hMRE11 and hNBS1 was consistently increased with respect to normal mucosa, but there was no difference between the primary tumors and metastases. In the primary MSS tumors, the expression of individual or combination of hRAD50/hMRE11/hNBS1 was associated with a favorable prognosis in the same series of the CRCs. Moreover, strong/high hRAD50 in MSS primary tumors was related to earlier tumor stage, better differentiation and high inflammatory infiltration, whereas strong hNBS1 expression tended to be independently related to a favorable prognosis in MSS CRC with earlier tumor stage. However, in MSI CRC, there were neither differences in the expression of hRAD50/hMRE11/hNBS1 among normal mucosa, primary tumors and metastases, nor any association of the protein expressions with clinicopathological variables. On the other hand, frameshift mutations of (A)9 at coding region of hRAD50 were only found in MSI CRC. Our study indicates that 1) PINCH is likely a regulator of angiogenesis, and PINCH expression at the tumor invasive margin is an independent prognostic indicator in CRC. 2) Inflammatory infiltration at the tumor invasive margin is also an independent prognostic indicator in CRC. The lack of association between high inflammatory infiltration and MSI may help to explain the non-association of MSI with survival in CRC patients. 3) Angiogenesis and lymphangiogenesis occur in the early stage of CRC development, but do not associate with CRC progression and patients’ prognosis. 4) hRAD50/hMRE11/hNBS1 may act dependently and independently, playing different roles in MSS and MSI CRC development. In MSS CRC, the strong expression of the three proteins, associated with a favorable prognosis, may present the cellular response against tumor progression. Expression of hNBS1 may be a prognostic indicator for MSS CRC patients in the earlier tumor stage. In MSI CRC, the frameshift mutations at the coding region of hRAD50 may contribute to tumor development.
90

Μελέτη της έκφρασης του πρωτεϊνικού συμπλέγματος ΙLK-PINCH-Parvin (IPP) και της πρωτεΐνης RSU1 στο μη-μικροκυτταρικό καρκίνωμα του πνεύμονα στον άνθρωπο

Νίκου, Σοφία 22 May 2015 (has links)
Το ετεροτριμερές πρωτεϊνικό σύμπλεγμα IPP (ILK-PINCH-Parvin) εντοπίζεται στις εστιακές συνδέσεις και ρυθμίζει την σηματοδότηση από την εξωκυττάρια ουσία μέσω ιντεγκρινών και αυξητικών παραγόντων, αλληλεπιδρώντας με τον κυτταροσκελετό ακτίνης και με ποικίλες σηματοδοτικές οδούς. Οι πρωτεΐνες του συμπλεγματος IPP ελέγχουν σημαντικές κυτταρικές λειτουργίες όπως ο πολλαπλασιασμός, η επιβίωση, η κυτταρική κίνηση-μετανάστευση και ενέχονται σημαντικά στην καρκινογένεση (Legate et al., 2006). Συγκεκριμένα η πρωτεΐνη ILK (integrin-linked kinase) έχει συσχετιστεί με την εξέλιξη-προαγωγή του όγκου και δυσμενή πρόγνωση στο μη μικροκυτταρικό καρκίνωμα του πνεύμονα (Ζhao et al., 2013). Η πρωτεΐνη Ras supressor protein 1 (Rsu-1), γνωστή για την ογκοκατασταλτική της δράση και την συμμετοχή της στη σηματοδοτική οδό του ογκογονιδίου Ras, πρόσφατα βρέθηκε οτι αλληλεπιδρά με την πρωτεΐνη PINCH του ΙPP συμπλέγματος και μέσω αυτής της αλληλεπίδρασης ρυθμίζει διεργασίες όπως η κυτταρική μετανάστευση και διήθηση(Gonzalez-Nieves et al., 2013). Σκοπός της παρούσας μελέτης είναι η διερεύνηση του ρόλου του IPP συμπλέγματος και της πρωτεΐνης Rsu-1 στο μη μικροκυτταρικό καρκίνωμα του πνεύμονα στον άνθρωπο καθώς και της συμμετοχής του ΙPP συμπλόκου στην σηματοδότηση από το ογκογονιδίο Ras. Για το σκοπό αυτό μελετάται η πρωτεϊνική έκφραση των ILK, PINCH, α-Parvin, β- Parvin και Rsu-1 1) σε ιστικά δείγματα μη-μικροκυτταρικού καρκινώματος του πνεύμονα σε σχέση με κλινικοπαθολογοανατομικές παραμέτρους της νόσου και 2) σε καρκινικές κυτταρικές σειρές με διαφορετικά επίπεδα ενεργοποίησης της Ras σηματοδότησης. Για τα στοιχεία του ΙΡΡ συμπλέγματος παρατηρήθηκε αυξημένη ανοσοϊστοχημική έκφραση ενώ για την πρωτεΐνη Rsu1 βρέθηκε μειωμένη στα μη μικροκυτταρικά καρκινώματα του πνεύμονα σε σχέση με το μη νεοπλασματικό παρέγχυμα του πνεύμονα. Η έκφραση των ILK και PARVA ήταν σημαντικά υψηλότερη στα χαμηλής διαφοροποίησης νεοπλάσματα και σε όγκους προχωρημένου pT αντίστοιχα. Η έκφραση της πρωτεΐνης PINCH σχετίστηκε στατιστικώς σημαντικά με την παρουσία λεμφαδενικών μεταστάσεων. Δεν παρατηρήθηκε εξάρτηση της πρωτεϊνικής έκφρασης των Rsu-1 και PINCH από τη σηματοδοτική οδό Ras. Τα αποτελέσματα υποστηρίζουν ότι η υπερέκφραση των στοιχείων του ΙΡΡ συμπλέγματος και η μειωμένη έκφραση του Rsu1 ενέχονται στην παθογένεια του καρκίνου του πνεύμονα. / The integrin-linked kinase (ILK)-PINCH-parvin (IPP) complex at integrin adhesion sites is a critical regulator of cell migration, invasion and metastasis. Deregulation of the IPP complex has been implicated in human carcinogenesis (Legate et al, 2006). Recent observations suggest that RSU-1, a protein first identified as a suppressor of v-Ras mediated cell transformation is a PINCH-binding partner that regulates PINCH mediated adhesion and migration (Gonzalez-Nieves et al., 2013). This study aims to evaluate the expression of the IPP complex and RSU-1 in human non-small cell lung carcinomas (NSCLC). Protein expression of ILK, PINCH, alpha-parvin, beta-parvin and RSU-1 in relation to clinicopathological parameters was evaluated by immunohistochemistry in 82 FFPE tissue samples of non-small cell lung cancer (NSCLC). All components of the IPP complex were overexpressed while RSU-1 was downregulated in lung cancer cells compared to non-neoplastic lung parenchyma. ILK and alpha-parvin expression was significantly higher in high grade (p=0.002) and high pT (p=0.047) tumors respectively. Expression of PINCH associated significantly with lymph node metastasis (p=0.045). Our results suggest that overexpression of the IPP complex and downregulation of RSU-1 may be implicated in lung carcinogenesis.

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