Atualmente, as pesquisas sobre a as células epiteliais biliares expressam uma grande quantidade de conexina 43. O presente estudo avaliou influência do genótipo de camundongos Cx 43 +/- ou Cx 43 +/+, sobre a hiperplasia de ductos biliares, após a ligação do ducto biliar comum (colédoco). Neste estudo, foram utilizados seis grupos de camundongos BALB/c fêmeas de ambos os genótipos, que foram submetidos à ligação do ducto biliar com fio de seda por meio de procedimento cirúrgico, sendo eutanasiados nos tempos de 48 horas, 7 e 14 dias. Aproveitando-se o campo microscópico, cinco estruturas hepáticas: hepatócitos, arteríolas, vênulas, ductos biliares e veia centrolobular foram quantificados para verificar a existência de possível diferença entre os genótipos. Observou-se na análise quantitativa, diferença significante somente quanto ao número de vasos sanguíneos entre os dois grupos, sendo que as outras estruturas hepáticas quantificadas não apresentaram diferenças significativas. A proliferação celular foi avaliada pela técnica western blot para a proteína PCNA (Proliferation Cell Nuclear Antigen), somente dos grupos de 48 horas pós-cirúrgico, quando ocorre o pico de proliferação. Quanto à análise quantitativa do western blot, não houve diferenças significativas quanto ao genótipo. Já na das bandas protéicas, observou-se maior concentração nos camundongos controle, indicando maior número de células em divisão. / The goal in this study was evidence, after duct biliar common ligation (coledoco), using mice geneticly modified with connection in one of the alels to connexin 43 (Cx 43+/-) and comparing them to the group control (Cx 43+/+), in order to find out the participation of this protein, even though the epithelials biliary cells express a big quantity of cx 43. The experimental outline were made up of three mice groups BALB/c females of different genotypes which were subdued to surgery procedure using a wire of silk 3.0 and euthanased in each 48 hours during 7 to 14 days. Also using the microscopic view the fives hepatics structures such as, hepatocites, arterioles, veins, bile ductules and centrelobular vein were quantified, trying to obtain possible differences among the genetypes and to do the qualification of protein concentration was used the western blot to PCNA in order to compare the cells divided in 48 hours. It has observed in the quantitative analysis, strong difference only in the blood vein number among the two groups, however the orders quantitative hepatics structures did not present strong differences. About the quantitative analysis related to western blot did not have strong differences in the genotype, and finally in the proteic staff it has observed bigger concentration in the mice control showing bigger number of cells in division.

A maior parte do ruído de aeronaves é advinda dos motores. Como houve grande avanço no controle do ruído tonal, atualmente grande parte do esforço se dá para redução do ruído de banda larga, que é menos compreendido. O ruído de banda larga é gerado pela interação entre um escoamento turbulento e uma superfície, como por exemplo, a turbulência ingerida interagindo com o rotor, o escoamento na ponta das pás, entre outros. Apesar das diversas fontes citadas, sabe-se que a principal fonte de ruído de banda larga em tal tipo de motor é a interação da esteira turbulenta do rotor com as aletas da estatora. Assim, o presente estudo manterá seu enfoque apenas em tal causa. O objetivo deste então é o desenvolvimento de um modelo capaz de previsão do ruído de banda larga pela interação da esteira turbulenta causada pelo rotor, interagindo com as aletas da estatora, bem como o entendimento da propagação do ruído em duto. A primeira abordagem em relação a tal tipo de ruído é através da previsão do ruído gerado. Para previsão de ruído podem ser utilizados métodos analíticos, numéricos, ou empíricos, cada qual com suas vantagens e penalizações. Para tal, foi utilizado um método semi-analítico, em tais métodos utiliza-se simulação numérica para previsão da característica da turbulência e uma teoria analítica para a geração e propagação do ruído no duto. A principal motivação para o método semi-analítico é sua vantagem em relação aos métodos numéricos que demandam custo computacional extremamente alto e vantagem em relação a métodos analíticos que necessitariam uma demasiada simplificação geométrica. Dessa maneira, utilizou-se a geometria do ANCF, uma plataforma de ensaios desenvolvida pela NASA, onde havia geometria e resultados divulgados, tornando possível a verificação dos resultados obtidos. Os resultados mostram que as tendências capturadas são condizentes com o esperado, e então com um tempo relativamente baixo, de maneira prática, é possível a previsão do ruído de interação e sua propagação em dutos nos motores turbofans. / The major noise source in aircraft is the engine. Since tonal noise control is well developed, the current effort concentrates on broadband noise reduction, which is less understood. The broadband noise is generated when a turbulent flow interacts with a surface as, for example, rotor blade tip flow, boundary layer and the rotor interaction. Although there are different sources of broadband noise it is known that the major broadband source in turbofan engine is the rotor turbulent wake interacting with the stator vanes. This study is focused in that source of noise and the goal is to develop a model capable of predicting the rotor/stator interaction noise as well as in duct noise propagation. Noise prediction can be carried out by analytical, numerical or empirical methods, each one with advantages and disadvantages. In the present work the semi-analytical method was used. Turbulence characteristics were estimated by a numerical method and the noise generation and duct propagation was estimated by an analytical method. The biggest advantage comparing with the numerical methods is that this method is less time consuming. A purely analytical method would require excessive geometric simplification. The ANCF, a rig developed by NASA was used as basis for the simulations, since its geometry and noise data are available. The results show that the correct trends are consistently captured. So it is concluded that it is possible to predict the broadband noise and its propagation in turbofans engines with a practical and low cost method.

Base teórica: A Síndrome Hepatopulmonar (SHP) caracteriza-se por uma tríade clínica que inclui doença hepática, anormalidades em trocas gasosas e presença de dilatações vasculares pulmonares, sendo a obstrução prolongada do ducto biliar utilizada em modelos experimentais de cirrose biliar secundária que leva a reações inflamatórias agudas, podendo, ainda, ocasionar alterações sistêmicas. Animais com cirrose induzida experimentalmente por ligadura de ducto biliar (LDB) apresentam aumento do estresse oxidativo no tecido hepático, mas a inter-relação com o tecido pulmonar ainda não está bem esclarecida. O estresse oxidativo desempenha papel central na patogênese e na progressão de doenças crônicas, e o uso de antioxidantes tem sido proposto como agente terapêutico para compensar danos sistêmicos e hepáticos. Em estudos em que a utilização da melatonina foi comparada com a utilização de outros antioxidantes conhecidos como as vitaminas C e E, tal componente mostrou-se mais eficiente na redução do estresse oxidativo/nitrosativo, demonstrando que a melatonina atua como potente antioxidante. Objetivo: A presente tese teve como objetivo investigar o efeito do antioxidante Melatonina sobre o tecido pulmonar no modelo experimental de Síndrome Hepatopulmonar por ligadura de ducto biliar. Métodos: O trabalho está dividido em três partes: Parte I- Artigo de revisão intitulado “Hepatopulmonary Syndrome: Oxidative Stress and Physical Exercise,” enviado para publicação no periódico European Medical Journal; Parte II- Artigo original intitulado “Efeitos da melatonina sobre o tecido pulmonar no modelo experimental de síndrome hepatopulmonar”, enviado para o periódico Jornal de Pneumologia; Parte III- Artigo original intitulado “Efeitos da melatonina sobre o tecido hepático e pulmonar em animais com síndrome hepatopulmonar por ligadura do ducto biliar”, a ser enviado para o periódico Digestive Diseases and Sciences. Foi utilizado o modelo de cirrose biliar secundária, induzida pelo modelo de ligadura de ducto biliar (LDB), com ratos machos Wistar, pesando ± 300 gramas, divididos em quatro grupos: CO (controle), CO+MLT, SHP e SHP+MLT. Os animais foram tratados com MLT a partir do 15° dia e com LDB até o 28° dia. No 29° dia, mediante administração de fármacos anestésicos, foram coletados sangue, fígado, pulmão e fêmur. Resultados: Nos artigos II e III, ao se avaliar as transaminases, observou-se aumento significativo nas enzimas ALT, AST e FA no grupo SHP quando comparadas aos grupos controles, o que determina a presença de doença hepática. Posteriormente à administração da 7 melatonina, houve diminuição significativa do grupo SHP+MLT quando comparado ao grupo SHP na avaliação da lipoperoxidação, atividade das enzimas Catalase (CAT), superóxido dismutase (SOD) e glutationa Peroxidade (GPx), bem como na de Nitritos/Nitratos (NO2/NO3) e no sistema inflamatório, quando da avaliação da expressão da Óxido Nítrico Sintase Induzível (iNOS) e da região p65 do fator de transcrição nuclear-kB (NF-kB). Também houve diferença na gasometria arterial e na histologia do tecido pulmonar pelas técnicas de Hematoxilina e Eosina e Picrosírius, especialmente no diâmetro dos vasos pulmonares. Ao avaliar o dano ao DNA pelo Ensaio Cometa, foi observado aumento do índice e da frequência de dano no grupo SHP, com redução após o uso da MLT. Conclusão: Os resultados sugerem efeito protetor da melatonina no tecido hepático e pulmonar, no modelo de Síndrome Hepatopulmonar por ligadura de ducto biliar. / Background: Hepatopulmonary syndrome (HPS) is clinically characterized by a combination of liver disease, gas exchange abnormalities, and pulmonary vascular dilation. Prolonged biliary duct obstruction was used in experimental models of secondary biliary cirrhosis leading to acute inflammatory reactions and possibly to systemic changes. Animals with cirrhosis experimentally induced by biliary duct ligation (BDL) showed increased oxidative stress in liver tissue, but the lung tissue has not been investigated yet. Oxidative stress has a key role in the pathogenesis and progression of chronic diseases, and antioxidants have been proposed as therapeutic agents to compensate for systemic and liver damages. In studies comparing melatonin with other known antioxidants such as vitamins C and E, melatonin was found to be more efficient in reducing oxidative/nitrosative stress, showing that it is a potent antioxidant. Objective: The present doctoral dissertation aimed to investigate the effect of the antioxidant melatonin on lung and liver tissues in an experimental model of BDL-induced HPS. Methods: This dissertation is divided into three parts: Part I consists of the review article entitled “Hepatopulmonary Syndrome: Oxidative Stress and Physical Exercise,” which was submitted to the European Medical Journal; Part II consists of the original article entitled “Efeitos da melatonina sobre o tecido pulmonar no modelo experimental de síndrome hepatopulmonar”, which was submitted to Jornal de Pneumologia; and Part III consists of the original article entitled “Effects of melatonin on liver and lung tissues of animals with bile duct ligation-induced hepatopulmonary syndrome”, which will be submitted to Digestive Diseases and Sciences. A model of secondary BDL-induced biliary cirrhosis was used in male Wistar rats weighing ± 300 g and divided into four groups: control group (CG), CG+MLT, HPS, and HPS+MLT. Animals were treated with MLT or vehicle from day 15 to day 28 after BDL. On day 29, blood, liver, lung, and femur samples were collected after the administration of anesthetic drugs. Results: As for transminases, papers II e III found that there was a significant increase in enzymes ALT, AST e FA in the HPS group compared with the control groups, which indicates the presence of liver disease. The administration of melatonin led to a significant decrease in the HPS group compared with the control groups with regard to the following variables: lipid peroxidation; catalase, superoxide dismutase, and glutathione peroxidase activity; nitrite/nitrate ratio; and inducible nitric oxide synthase and p65 region of nuclear factor kappa B. There were also differences in blood gas analysis and histology of lung tissues as assessed by hematoxylin and eosin (HE) and picrosirius red staining, especially in the diameter of pulmonary vessels. The comet assay revealed an increase the index and frequency of DNA damage in the HPS group compared with the control groups, but these parameters were reduced with the use of melatonin in the HPS+MLT group. Conclusion: Results suggest that melatonin has a protective effect in liver and lung tissues using a BLD-induce HPS model.

Malignancy within the pancreatic head can arise from pancreatic duct, distal bile duct, ampulla or duodenum. Since September 2000, surgery for all pancreatic head malignancy (PHM) has been centralised into regional pancreatic centres where assessment of preoperative imaging and subsequent surgery is undertaken. As part of this guidance, surgery must be performed within 62-days of referral. This project will assess four aspects of the pre-operative pathway in PHM: 1) Potential variation in outcome of patients referred from different sites within a Cancer Network 2) Potential variation in outcome associated with different intervals to surgery within the 62 day guideline 3) The ability of interpretation of heterogeneous pre-operative CT scans from different hospitals to determine the resectability of PHM 4) The ability of CT scan to distinguish the different tumour types of PHM Images of a consecutive series of patients were re-reported and compared with final pathology reports. Good agreement was noted in determining the tumour origin of PHM (observed agreement = 0.758, Kappa= 0.6 (0.51-0.68)). In the assessment surgical outcomes, geographical isolation from the regional centre was not associated with delay to surgery. Variation in outcome between referral centres was however noted but this was not associated with travel distance. Although little association was noted between delay to surgery and outcome overall, a paradoxical improvement in survival was noted however for the small group of patients with ampullary tumours who waited longer than the median interval to surgery.

Atualmente, as pesquisas sobre a as células epiteliais biliares expressam uma grande quantidade de conexina 43. O presente estudo avaliou influência do genótipo de camundongos Cx 43 +/- ou Cx 43 +/+, sobre a hiperplasia de ductos biliares, após a ligação do ducto biliar comum (colédoco). Neste estudo, foram utilizados seis grupos de camundongos BALB/c fêmeas de ambos os genótipos, que foram submetidos à ligação do ducto biliar com fio de seda por meio de procedimento cirúrgico, sendo eutanasiados nos tempos de 48 horas, 7 e 14 dias. Aproveitando-se o campo microscópico, cinco estruturas hepáticas: hepatócitos, arteríolas, vênulas, ductos biliares e veia centrolobular foram quantificados para verificar a existência de possível diferença entre os genótipos. Observou-se na análise quantitativa, diferença significante somente quanto ao número de vasos sanguíneos entre os dois grupos, sendo que as outras estruturas hepáticas quantificadas não apresentaram diferenças significativas. A proliferação celular foi avaliada pela técnica western blot para a proteína PCNA (Proliferation Cell Nuclear Antigen), somente dos grupos de 48 horas pós-cirúrgico, quando ocorre o pico de proliferação. Quanto à análise quantitativa do western blot, não houve diferenças significativas quanto ao genótipo. Já na das bandas protéicas, observou-se maior concentração nos camundongos controle, indicando maior número de células em divisão. / The goal in this study was evidence, after duct biliar common ligation (coledoco), using mice geneticly modified with connection in one of the alels to connexin 43 (Cx 43+/-) and comparing them to the group control (Cx 43+/+), in order to find out the participation of this protein, even though the epithelials biliary cells express a big quantity of cx 43. The experimental outline were made up of three mice groups BALB/c females of different genotypes which were subdued to surgery procedure using a wire of silk 3.0 and euthanased in each 48 hours during 7 to 14 days. Also using the microscopic view the fives hepatics structures such as, hepatocites, arterioles, veins, bile ductules and centrelobular vein were quantified, trying to obtain possible differences among the genetypes and to do the qualification of protein concentration was used the western blot to PCNA in order to compare the cells divided in 48 hours. It has observed in the quantitative analysis, strong difference only in the blood vein number among the two groups, however the orders quantitative hepatics structures did not present strong differences. About the quantitative analysis related to western blot did not have strong differences in the genotype, and finally in the proteic staff it has observed bigger concentration in the mice control showing bigger number of cells in division.

The collecting duct of the distal nephron marks the final location where adjustments to Na+ excretion can be made, therefore determining the final concentration of Na+ conserved in the extracellular fluid which plays a role in governing overall blood volume and pressure. This transport of Na+ is subject to hormonal regulation but the signalling pathways underpinning this regulation however, are not fully understood. In this thesis the signalling pathways allowing both basal and insulin-stimulated Na+ absorption were explored in the murine collecting duct cell line, mpkCCDcl4. The effects of two insulin-sensitizing drugs, TZDs, on ENaC-mediated Na+ transport were investigated and the signalling pathways underlying two other hormonal regulators of ENaC, dexamethasone and vasopressin, were also examined. Unstimulated monolayers of mpkCCDcl4 cells generated spontaneous Na+ absorption which was quantified by measuring equivalent short circuit current (Ieq). Selective inhibition of PI3-kinase, mTORC2 and SGK1 left ~80 % of the current intact, indicating these signalling molecules are not required for basal Na+ transport. Acute addition of insulin stimulated Ieq and this occurred with a concomitant increase in mTORC2, SGK1 and Akt activity. Inhibition of PI3-kinase abolished the insulin-stimulated response as well as phosphorylation of downstream substrates, indicating a crucial role of PI3-kinase. Inhibition of mTORC1 with rapamycin did not alter basal or insulin-stimulated Na+ transport. The mTOR inhibitors TORIN1 and PP242 could therefore be used to evaluate the role of mTORC2. These inhibitors greatly reduced insulin-stimulated ENaC-mediated Na+ transport and also abolished SGK1 and mTORC2 activity, indicating a novel role of mTORC2. An inhibitor of SGK1, GSK650394A abolished insulin-stimulated Na+ transport and specifically inhibited SGK1 acitivty demonstrating the importance of SGK1 in insulin signalling. The inhibitor Akti-1/2 also abolished insulin-mediated Na+ transport but this compound inhibited both Akt and SGK1 activity. The TZDs pioglitazone and rosiglitazone did not alter basal or insulin-stimulated Na+ transport and had no effect on SGK1 activity indicating these drugs do not alter Na+ absorption in this cell line. Dexamethasone stimulated ENaC-mediated Na+ transport in a similar manner to insulin and this could be blocked with rapamycin. This drug did not alter phosphorylation of NDRG1 indicating that dexamethasone stimulates Na+ transport in an mTORC1-dependent manner but without altering SGK1 activity. Arginine vasopressin also stimulated Ieq but did so by reducing Rt with an associated depolarisation of Vt. Ieq could be blocked with amiloride and vasopressin-stimulated Ieq was insensitive to TORIN1 and PP242. Vasopressin suppressed SGK1 phosphorylation of NDRG1 but did stimulate protein kinase A (PKA) activity. Therefore vasopressin stimulates Ieq via a PKA-dependent but mTOR- and SGK1-independent pathway.

This research deals with determining the acoustic attenuation of heating, ventilation, and air conditioning (HVAC) ductwork. A finite element approach was developed for calculating insertion loss and breakout transmission loss. Procedures for simulating the source and receiving rooms were developed and the effect of structureborne flanking was included. Simulation results have been compared with measurements from the literature and the agreement is very good. With a good model in place, the work was extended in three ways. 1) Since measurements on full-scale equipment are difficult, scale modeling rules were developed and validated. 2) Two different numerical approaches were developed for evaluating the transmission loss of silencers taking into account the effect of higher order modes. 3) A power transfer matrix approach was developed to assess the acoustic performance of several duct components connected in series.

Increased national and international travel over the lastdecades has caused an increase in the global number ofpassengers using different means of transportation. Greateffort is being directed to improving the noisy environment inthe residential community. This is to face the growing strictnoise requirements which are implemented by international noiseregulatory authorities, governments, and local airports. Thereis also a strong competition between different manufacturers tomake their products quieter. The propulsion system in anaircraft is the major source of noise during relevant flightconditions. The engine noise in a vehicle dominates the totalradiated noise at low speeds especially inside cities. Manyrecent studies on noise reduction involve the use of perforatedplates in the air and gas flow ducting connected to the engine.This thesis deals with the modelling of perforates as anabsorbent. There are many difficulties in using liners in theseapplications. The most important is that there is no largesurface area to which the linings may be applied. Equally, theenvironment in which linings have to survive is hostile.Therefore, liners have to be carefully tailored in order toachieve the most efficient attenuation. The full-scalesimulation testing, which is usually necessary to define thenoise attenuation produced by a liner installation, is bothtime-consuming and expensive. Therefore, a need for accuratemodels is a must. This thesis fills some gaps in the impedancemodelling of perforated liners. It also concentrates on thosecomplicated situations of sound propagation in ducts that weresolved earlier using Finite Element Methods. Alternateanalytical solutions to these problems are developed here,which gives more physical insight into the results. The key design parameter of perforates is the acousticimpedance. The impedance is what determines their efficiency toabsorb sound waves. A semi empirical impedance model wasdeveloped to be capable of accurately predicting the linerimpedance as a function of its physical properties and thesurrounding conditions. It was compared to all previous modelsin the literature. Nothing in the literature has been reportedon the effect of temperature on the perforate impedance,therefore a complete study was performed. A new inverseanalytical impedance measurement technique was proposed. It isbased on educing the impedance value based on the measurementof the attenuation across a lined duct section. Twoapplications were further considered: The effect of hard stripsin lined ducts on there attenuation properties; and themodelling of perforations in a complicated automotive mufflersystem. Keywords:Perforates–Liners–Acousticimpedance–Hot stream liners–Hard splices–Mufflers–Lined ducts–Collocation–Flowduct.

The convective mass transfer coefficient is determined for evaporation in a horizontal rectangular duct, which forms the test section of the transient moisture transfer (TMT) facility. In the test facility, a short pan is situated in the lower panel of the duct where a hydrodynamically fully developed laminar or turbulent airflow passes over the surface of the water. The measured convective mass transfer coefficients have uncertainties that are typically less than ±10% and are presented for Reynolds numbers (ReD) between 560 and 8,100, Rayleigh numbers (RaD) between 6,100 and 82,500, inverse Graetz numbers (Gz) between 0.003 and 0.037, and operating conditions factors (H*) between -3.6 and -1.4. The measured convective mass transfer coefficients are found to increase as ReD, RaD, Gz and H* increase and these effects are included in the Sherwood number (ShD) correlations presented in this thesis, which summarize the experimental data.<p> An analogy between heat and mass transfer is developed to determine the convective heat transfer coefficients from the experimentally determined ShD correlations. The convective heat transfer coefficient is found to be a function of ShD and the ratio between heat and moisture transfer potentials (S*) between the surface of the water and the airflow in the experiment. The analogy is used in the development of a new method that converts a pure heat transfer NuD (i.e., heat transfer with no mass transfer) and a pure mass transfer ShD (i.e., mass transfer with no heat transfer) into NuD and ShD that are for simultaneous heat and mass transfer. The method is used to convert a pure heat transfer NuD from the literature into the NuD and ShD numbers measured in this thesis. The results of the new method agree within experimental uncertainty bounds, while the results of the traditional method do not, indicating that the new method is more applicable than the traditional analogy between heat and mass transfer during simultaneous heat and mass transfer.<p>A numerical model is developed that simulates convective heat and mass transfer for a vapor permeable Tyvek® membrane placed between an airflow and liquid water. The boundary conditions imposed on the surfaces of the membrane within the model are typical of the conditions that are present within the TMT facility. The convective heat and mass transfer coefficients measured in this thesis are applied in the model to determine the heat and moisture transfer through the membrane. The numerical results show that the membrane responds very quickly to a step change in temperature and relative humidity of the air stream. Since the transients occur over a short period of time (less than 1 minute), it is feasible to use a steady-state model to determine the heat and mass transfer rates through the material for HVAC applications.<p>The TMT facility is also used to measure the heat and moisture transfer through a vapor permeable Tyvek® membrane. The membrane is in contact with a water surface on its underside and air is passed over its top surface with convective boundary conditions. The experimental data are used to verify the numerically determined moisture transfer rate through the Tyvek® membrane. The numerical model is able to determine the mass transfer rates for a range of testing conditions within ±26% of the experimental data. The differences between the experiment and the model could be due to a slightly different mass transfer coefficient for flow over Tyvek® than for flow over a free water surface.

Salivary duct carcinoma (SDC) is an uncommon neoplasm showing extensive local invasion and metastasis. Histologically it exhibits ductal differentiation without myoepithelial participation and resembles intraductal and invasive ductal carcinoma of the breast. This study investigates the incidence of intraductal disease within invasive SDC and characterizes the expression of CK19, COX-2, MMP-2, 9 and 11 in intraductal and invasive SDC. 21 conventional SDC, 8 SDC arising as carcinoma ex-pleomorphic adenoma (CaExPA), 2 pure low-grade intraductal SDC, 1 pure high-grade intraductal SDC and 1 intraductal SDC with de-differentiation were studied. The presence of intraductal tumor in SDC is relatively common (52.4%) but is not a prominent component. SDC tumor cells were strongly positive for CK19 and COX-2. MMP-2 and 9 expression showed no significant pattern. MMP-11 was expressed by fibroblasts surrounding invasive tumor and was significantly associated with lymph node positivity (p=0.02).