Le tabagisme actif par la mère expose le fœtus en développement à des agents qui peuvent traverser la barrière placentaire et interférer avec les fonctions placentaires. Un large éventail de fonctions immunologiques, pourrait être compromises. Dans cette étude, nous avons évalué l'effet de l'extrait de la fumée de cigarette (CSE) sur les macrophages isolés à partir de placentas humains (pMφs), qui sont les principaux partenaires de l'immunité de fœto-maternelle innée. J’ai pu montrer que le CSE inhibe la formation des cellules géantes multinucléées (MGC). Cette propriété du CSE est spécifique aux macrophages car la fusion des macrophages dérivés des monocytes est inhibée lors de la formation de granulomes in vitro. J’ai également étudié l'absorption de particules et la production de cytokines par pMφs exposés au CSE. Le CSE a inhibé l'absorption des particules de zymosan, mais pas celle du zymosan opsonisé, ce qui suggère qu’il interfère avec les récepteurs phagocytaires et non phagocytaires. Le CSE augmente la libération de TNF et d'IL-33, et une diminue celle de l'IL-10, ce qui montre que l'équilibre entre les cytokines est affecté par le CSE. En outre, l’expression des métalloprotéinases telles que les MMP-1, MMP-10 et MMP-12, connues pour être impliquées dans le remodelage des tissus et la fusion des macrophages est dérégulée. Enfin, j’ai montré que la nicotine, l'un des principaux composés de tabac, n'a pas affecté les propriétés fonctionnelles des pMφs. / Active smoking by the mother exposes the developing fetus to agents that can cross the placental barrier and interfere with placental functions. A wide range of immunological functions, including innate and adaptive immune responses, might be impaired. In this study, we assessed the effect of cigarette smoke extract (CSE) on macrophages isolated from human placentas (pMφs), which are major partners of innate feto-maternal immunity. I showed that CSE significantly inhibited the formation of multinucleated giant cells (MGCs). This property of CSE is specific to macrophages because the fusion of monocyte-derived macrophages is inhibited during the in vitro formation of granulomas. I also investigated particle uptake and cytokine production by pMφs exposed to CSE. CSE inhibited the uptake of zymosan, but not that of opsonized zymosan, suggesting that it interferes with phagocytic receptors, not with the phagocytic machinery of pMφs. CSE increased the release of Tumor Necrosis Factor and interleukin-33, and decreased that of interleukin-10, demonstrating that the balance between inflammatory and anti-inflammatory cytokines is affected by CSE. Furthermore, CSE enhanced the expression of metalloproteinase (MMPs) genes such as MMP-1, MMP-10 and MMP-12, known to be involved in tissue remodeling including macrophage fusion. Finally, I showed that nicotine, one of the major compounds of tobacco, did not affect the functional properties of pMφs.

Research on sex and gender in chronic obstructive pulmonary disease (COPD) has primarily focused on differences in pulmonary function. Detailed gender- and sex-based analyses of other aspects of COPD, including epidemiology, risk factors other than cigarette smoke, pathophysiology, and measurement tools are warranted. In Chapter Two we analyzed administrative health services data to compare the prevalence, mortality and use of drugs and spirometry in men and women with COPD. Contrary to recent predictions, we did not detect a dramatic increase in the prevalence or mortality of COPD over time in women compared to men. We discuss how different coding practices in medical billing can impact the results. In Chapter Three we examined sex differences in COPD phenotypes. We hypothesized that male smokers would have more emphysema whereas female smokers would have more airway wall remodeling using data from high resolution computed tomography (HRCT) scans. We did detect more emphysema in male smokers but there was no evidence of increased airway remodeling in women. We discuss the limits of HRCT to detect airway differences in women and men. In Chapter Four we examined the use of HRCT in assessing emphysema. We hypothesized that the computer-derived estimates of emphysema (the fractal value and the % low attenuation area (%LAA)) would differentiate COPD from non-COPD as accurately as the radiologist’s emphysema scores, and would provide similar predictions in both men and women. Instead, we found that the subjective rating of emphysema best differentiated COPD, and the fractal value (a measure of emphysematous lesion size) better differentiated COPD compared with an established objective measurement, the %LAA. These results were generally the same in men and women. In Chapter Five we examined characteristics of COPD in women exposed to biomass smoke. We hypothesized that biomass smoke would induce an airway disease-predominant phenotype. We found that women with biomass smoke-exposed COPD had greater airway remodeling and less emphysema than women with tobacco smoke-exposed COPD. In summary, these findings suggest that sex and gender differences are present in COPD epidemiology and pathophysiology. However, current research measurement tools may limit the ability to accurately measure these differences. / Graduate and Postdoctoral Studies / Graduate

La bronchopneumopathie chronique obstructive (BPCO) est une maladie caractérisée par une réaction inflammatoire intense avec une destruction du parenchyme pulmonaire et une perte d’élasticité du poumon conduisant à une obstruction quasi-irréversible des voies aériennes. L’utilisation du tabac est le principal facteur de risque de cette maladie. La fumée de cigarette active les cellules épithéliales et les macrophages résidents en libérant des protéases et des chimiokines. Ces phénomènes sont responsables de l’infiltration de cellules inflammatoires dans le poumon, telles que les neutrophiles, les macrophages et les lymphocytes. Ces cellules libèrent des enzymes protéolytiques capables de dégrader les composants de la matrice extracellulaire. Parmi ces protéases, l’élastase du neutrophile (NE) semble stimuler la sécrétion de cytokines, participant ainsi à une inflammation chronique. De fortes évidences montrent que des infections bactériennes récurrentes contribuent à ce processus inflammatoire et par conséquent à l’aggravation de la BPCO. A partir de ces observations, nous nous sommes intéressés aux événements précoces du développement de la BPCO associés à une infection bactérienne récurrente. Dans un premier temps, nous avons montré que l’association d’un extrait de fumée de cigarette à de faibles doses de LPS est capable d’augmenter de façon synergique la libération des chimiokines par les cellules épithéliales alvéolaires. Ce phénomène implique l’activation des voies de signalisation MAP kinase ERK1/2 et JAK/STAT. Nous avons mis en évidence que l’inhibiteur de la phosphodiestérase 4, le roflumilast N-oxide, empêche la sécrétion de ces cytokines inactivant ainsi les voies JAK/STAT et ERK1/2. Dans un deuxième temps, nous avons démontré que la NE peut conduire à la libération de chimiokines par des cellules épithéliales alvéolaires en activant la voie de signalisation p38 et que le roflumilast N-oxide diminue le taux de ces chimiokines. Une approche in vitro sur un modèle de cellules épithéliales alvéolaires a permis de démontrer l’effet synergique du CSE associé au LPS sur la libération de cytokines et sur l’activation des voies de signalisation. Cet effet pourrait être responsable de la progression et de l’exacerbation de la BPCO. Notre étude montre aussi les effets du roflumilast sur la libération de cytokines induites par la NE ou par le CSE/LPS. Ces résultats mettent en lumière d’autres mécanismes par lesquels le roflumilast N-oxide exerce son effet anti-inflammatoire dans la BPCO. / Chronic obstructive pulmonary disease (COPD) is a pathology characterized by an abnormal inflammatory response and associated with a destruction of lung parenchyma and loss of lung elasticity, leading to an airway limitation not fully reversible. Tobacco smoking continues to be a major cause of COPD. Cigarette smoke activates epithelial cells and resident macrophages by releasing proteases and chemokines. This phenomenon is responsible of the migration of inflammatory cells in the lung tissue such as neutrophils, macrophages and lymphocytes. These cells are able to release proteolytic enzymes leading to the degradation of components of the extracellular matrix. Among these proteases, neutrophil elastase (NE) seems to stimulate the secretion of cytokines involved in chronic inflammation. Strong evidence shows that recurrent bacterial infections contribute to the inflammatory process and consequently to the worsening of COPD. Based on these observations, we studied the early events in the development of COPD associated with recurrent bacterial infection. Initially we showed that the combination of a cigarette smoke extract associated with low doses of LPS is able to synergistically increase the release of chemokines, by alveolar epithelial cells through the activation of MAP kinase signaling pathways ERK1/2 and JAK/STAT. We also demonstrated that the phosphodiesterase 4 inhibitor, roflumilast N-oxide (RNO) inhibits the secretion of these cytokines, thereby inactivating pathways JAK/STAT and ERK1/2. Moreover, we have demonstrated that neutrophil elastase (NE) can lead to the release of chemokines by alveolar epithelial cells by activating the p38 signaling pathway. Moreover the treatment of the cells with roflumilast N-oxide significantly reduces the production of these chemokines. This in vitro model demonstrates the synergistic effect of CSE associated with LPS on the release of cytokines and activation of signaling pathways. This effect could be responsible for the progression and exacerbation of COPD. Our study also shows the effect of RNO on the release of cytokines induced by NE or by the combination CSE/LPS. These results highlight other mechanisms by which Roflumilast N-oxide exerts its anti-inflammatory effect in COPD

A saliva humana possui diversas enzimas que apresentam atividades específicas e algumas delas podem estar envolvidas no processo inflamatório que acometem os implantes dentários. A arginase é uma enzima hidrolítica que utiliza a L-arginina como substrato para formação da L-ornitina e uréia. Acredita-se que um aumento na produção de arginase possa levar à uma redução na produção de óxido nítrico, consequentemente aumentando a suscetibilidade à infecção bacteriana. Considerando a hipótese de que o número de implantes nos indivíduos e o fumo possam alterar a produção de arginase e que o mesmo é considerado um fator de risco para o sucesso da terapia com implantes, o presente estudo objetivou avaliar o efeito de ambas as variáveis sobre a atividade da arginase salivar (AS) em pacientes portadores de implantes dentários. Amostras de saliva de 102 indivíduos foram coletadas: 26 não-fumantes e sem implantes dentais (A), 28 pacientes com até 4 implantes dentais e não-fumantes (B), 29 pacientes com cinco ou mais implantes dentais e não-fumantes (C), dez fumantes com implantes (D) e nove fumantes sem implantes (E). Os níveis de AS foram expressos em U/mg proteína e determinados por espectrofotometria através da mensuração da L-ornitina e da proteína salivar. Houve um aumento significativo dos níveis de AS no grupo D (64.26) em relação aos grupos A (10.72, p=0), B (10.66, p=0), C (11.21, p=0) e E (13.66, p=0). Não houve diferença estatisticamente significante entre os grupos A, B, C e E (p>0,05). Dentro dos limites do presente estudo, pode-se concluir que a atividade da arginase salivar encontra-se elevada em indivíduos fumantes portadores de implante dentário, sugerindo um possível mecanismo pelo qual o fumo pode levar ao insucesso desta terapia reabilitadora. / Human saliva possesses many enzymes with activity and some of them might be involved in the inflammatory process of dental implants. Arginase is a hydrolytic enzyme that catalyses L- arginine into ornithine and urea. Its known that a high production of arginase can decreased the production of nitric oxide, consequently leading to bacterial infection susceptibility. To regard the hypothesis of number of implants and smoking might change the production of arginase and considering that smoking is a risk factor of implant therapy, the aim of this study was to evaluate the effect of both on the activity of arginase in saliva of subjects with dental implants. Saliva of 102 subjects were collected: 26 non-smoking and without dental implants (A), 28 with 4 dental implants or less and non-smoking (B), 29 with five dental implants or more and non-smoking (C), ten smokers with implants (D) and nine smokers and without dental implants (E). The arginase levels were expressed in U/mg and analyzed by spectophotometry and it was determined by measuring the Lornitine formation from L-arginine. The result showed that the mean values of arginase in group D (64.26) were statistically different among groups A (10.72, p=0), B (10.66, p=0), C (11.21, p=0) e D (13.66, p=0). There was no statistically difference among groups A, B, C and E (p>0,05). By the limits of the present study, it can be concluded that arginase activity shown higher in subjects smokers with dental implants, suggesting a possible mechanism that smoke may lead to unsuccess of this rehabilitation therapy.

Os produtos cárneos prontos para consumo estão entre os principais alimentos associados a surtos de listeriose, uma doença causada por Listeria monocytogenes. Este estudo objetivou avaliar a ação antimicrobiana do lactato de sódio e de duas formulações comerciais à base de nisina (produtos A e B) em mortadela, e do lactato de sódio e fumaça líquida em salsicha, experimentalmente contaminadas com um pool de seis cepas de L. monocytogenes, durante o armazenamento à vácuo à 8 ºC. Os aditivos com melhor atividade anti-listeria também foram avaliados quanto ao controle de bactérias láticas (BAL) e bolores e leveduras em produto cárneo, durante o armazenamento à 8 ºC. O produto A é uma mistura de nisina encapsulada, nisina livre e extrato de alecrim, enquanto o produto B é uma mistura de nisina livre e extrato de alecrim. L. monocytogenes foi capaz de se multiplicar em todas as formulações de mortadela ao longo do período de armazenamento. Entretanto, o produto A exerceu efeito antimicrobiano contra este patógeno. Após 10 dias de armazenamento, as contagens de L. monocytogenes nas mortadelas formuladas com o produto A foram 3 log UFC/g inferiores às contagens observadas nas demais formulações avaliadas (produto B, lactato de sódio e controle), além disso, o produto A foi capaz de reduzir a velocidade de multiplicação deste microrganismo. Em relação às salsichas tratadas com fumaça líquida, as contagens de L. monocytogenes, no oitavo dia de armazenamento foram 3 log UFC/g inferiores às contagens de L. monocytogenes nas salsichas formuladas com lactato de sódio e controle. Ao final do período de armazenamento (28 dias) observou-se diferença de 2 log UFC/g nas contagens de L. monocytogenes entre as salsichas formuladas com lactato de sódio + fumaça líquida e as demais formulações. A fumaça líquida foi capaz de inibir a multiplicação de bolores e leveduras por 21 dias de armazenamento, observando-se diferença de 2 log UFC/g entre as contagens observadas nas salsichas imersas em fumaça líquida e não imersas. As contagens de BAL permaneceram baixas ao longo do período de armazenamento (< 2 log UFC/g). Também não foi observada alteração nos valores de pH e atividade de água dos produtos cárneos, o que permite concluir que as diferenças observadas nas contagens de L. monocytogenes e bolores e leveduras são devidas à ação dos antimicrobianos adicionados aos produtos cárneos. A partir destes resultados é possível concluir que o produto A e a fumaça líquida são uma barreira adicional para o controle de L. monocytogenes em mortadela e salsichas, respectivamente, durante armazenamento a 8ºC. / Ready-to-eat meat products are among the foods most frequently associated to outbreaks of listeriosis, a disease caused by Listeria monocytogenes. The objective of the present study was to evaluate the antimicrobial activity of sodium lactate and two nisin-based commercial products (A and B) in bologna, and sodium lactate and liquid smoke in frankfurters, experimentally contaminated with a pool of six strains of L. monocytogenes, during storage at 8 ºC under vacuum. The antimicrobial with better activity against L. monocytogenes was also evaluated against yeasts and molds and lactic acid bacteria. Product A is a mixture of encapsulated nisin, free nisin and rosemary extract, and product B is a mixture of free nisin and rosemary extract. L. monocytogenes was able to grow in all bologna formulations during storage. However, product A was capable of reducing the growth rate of the microorganism. Besides, L. monocytogenes populations in bologna formulated with product A were 3 log CFU/g lower than the population observed for control samples, after 10 days of storage at 8 ºC. Regarding frankfurter samples, the use of liquid smoke alone or in combination with sodium lactate resulted in a 3 log CFU/g difference between L. monocytogenes counts found in control and treated samples, after 8 days of storage at 8 ºC. However, after 28 days only the samples treated with liquid smoke combined with sodium lactate presented lower counts than controls (2 log CFU/g). Liquid smoke was also able to inhibit the growth of yeasts and molds in frankfurters, for 21 days of storage at 8 ºC. Low counts of lactic acid bacteria (< 2 log CFU/g) were detected in frankfurters during the storage. There was no variation on pH and water activity values in the meat products during storage period; therefore, the differences found in counts of L. monocytogenes in the meat products can be attributed to the presence of the antimicrobials added in the formulations. Hence, product A and liquid smoke appear to be an additional barrier to control L. monocytogenes in bologna and frankfurters, respectively, during storage at 8 ºC.

Forest fires has become an increasing threat all over the world. Pollution and rising greenhouse gases has led to an ever increase in global temperatures. Sweden has previously been spared from larger fires, but in the past few year it has been been made clear that these climate changes will affect the number and intensity of forest fires.  In this project I have investigated how forest fires work and how the process of  extinguishing them looks today. With a focus on the personal equipment I have looked into how to improve the working environment and the safety for fire-fighters. Using the design process this problem is tackled from a holistic point of view, looking at both the users and context. The solutions presented in this project is a professional safety product called “Phoenix. PPe Wildfire respirator”. A lightweight portable oxygen harness with an attached emergency mask.

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The main goal of this Master's thesis was to design heat recovery steam boiler for cogenera-tion unit of a biogas plant while flue gas was flowing from an engine exhaust. Its temperature and required pressure of a steam were assigned. The thesis contains thermal, aerodynamic, hyd-raulic calculations and verification of wall thicknesses for pressure parts of the boiler. Follow-up results of these calculations served for making of projection drawings as well as equipment needed for reliable boiler operation.

This diploma thesis deals with the detection of fire and smoke from the image signal. The approach of this work uses a combination of convolutional and recurrent neural network. Machine learning models created in this work contain inception modules and blocks of long short-term memory. The research part describes selected models of machine learning used in solving the problem of fire detection in static and dynamic image data. As part of the solution, a data set containing videos and still images used to train the designed neural networks was created. The results of this approach are evaluated in conclusion.

The thesis deals with the implementation of a suction system for laser welding. The specific product is grate used for outdoor drainage. The original GMAW production technology is to be replaced by a laser. During the welding of S235JR steel, a significant development of exhaust gases was observed, which subsequently made the actual process impossible. Practical experiments were performed and evaluated using tensile testing and metallographic cut. Based on the results, the optimal position of the suction nozzle and welding parameters were recommended. The obtained values were re-verified by experiment. Furthermore, a suitable extraction device was proposed and an economic evaluation was performed.