Background: Clinical findings indicate that touch massage has the ability to induce positive emotions and influence stress responses. However, little is known about mechanisms that can explain observed responses. Aim: To understand mechanisms behind observed emotional and physiological responses during and after touch massage. Methods: This thesis is based upon healthy volunteers in Studies I, II, IV and patients undergone aortic surgery in Study III. Study I had a crossover design, participants served as their own controls. After randomization they received TM on one occasion and the other occasion served as control. Heart rate variability (HRV), heart rate (HR) saliva cortisol concentration, glucose, insulin in serum and extracellular (ECV) levels of glucose, lactate, glycerol and pyruvat were measured before, during and after TM/control. In study II, functional magnetic resonance imaging (fMRI) was used in order to measure brain activity during TM movement. The study design included four different touch stimulations, human touch with movement (TM movement) human stationary touch and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale). Study III had a randomized controlled design. The intervention group received TM and the control group rested. HRV, cortisol, glucose, insulin in serum, blood pressure, oxygen saturation, respiratory frequency and anxiety levels were measured before, during and after TM/control. In study IV participants were interviewed about experiences after TM and the text was analyzed in by qualitative content analyze. Results: Study I. TM reduced the stress response as indicated by decreased heart rate and decreased activity in the sympathetic nervous system, followed by a compensatory decrease in parasympathetic nervous activity in order to maintain balance. Cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control session. There were no significant differences in ECV concentrations of analyzed substances. Study II. Human moving touch (TM movement) was significantly rated as the most pleasant touch stimulation. The fMRI results revealed that human moving touch (TM movement) most strongly activated the pregenual anterior cingulate cortex (pgACC). Study III. Selfrated anxiety levels significantly decreased in the patient group that received TM compared with control group. There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls. Study IV. In this study participants talked about the experience of TM in terms of rewards. Expressions like need, desire, pleasure and conditioning could be linked with a theoretical model of reward. Four different categories were identified as wanting, liking, learning and responding. In conclusion: Results from these studies indicate that receiving TM is experienced as rewarding. Touch massage movement activates a brain area involved in coding of rewarding pleasant stimulations. TM decreases anxiety and dampens the stress response by a decreased activation of the sympathetic nervous activity. Our results indicate that TM is a caring intervention that can be used to induce pleasure, decrease anxiety and stress in the receiver.

The work detailed in this dissertation relates to thedevelopment of high performance manufacturing systems. Theperformance factor aimed for is especially flexibility, butthere is an intention of making the results adaptable to focuson performance factors of the readers or users choice. Thefocus of the presented research is not only to provide meansfor accomplishing manufacturing that can handle changes butalso to accomplish flexibility in another area. The resultsshould be applicable in many different situations. The researchhas been divided into three parts: the further development of amanufacturing strategy, the development of a base for amanufacturing system design method and the development of amanufacturing control system. The developed strategy is called Assembly-InitiatedProduction (AIP). An implementation of the strategy shouldprovide high manufacturing system flexibility but at the sametime contribute to the lowering of inventory levels andlead-times. Different solutions coupled to technicalrequirements found are also discussed. The design method research focuses on basic manufacturingsystem properties and the possibility of expressing theseproperties by using simple combinable abstract units calledconcepts. The principle is the same as in physics where realworld phenomena may be expressed by using standard concepts asfor example time and mass. The intended use of the results isin an early manufacturing system design phase. The method isnot directly linked to the AIP strategy, but could be used forimplementing it. Production Planning and Control (PPC) is an important partof a manufacturing system. After having reviewed current PPCpractices, a need for a factory floor PPC system workingregardless of factory floor layout, was identified. Based ontheoretical and industrial studies, the suggested solution is acomputerised, decentralised control system, physicallyseparated from the PPC/ERP system. In order to be able to makequick changes in the schedule, to obtain flexibility and toprovide the organisation with a tool for manufacturing controland decision-making, the system works in real time to provideaccurate and valid data.

<p>The work detailed in this dissertation relates to thedevelopment of high performance manufacturing systems. Theperformance factor aimed for is especially flexibility, butthere is an intention of making the results adaptable to focuson performance factors of the readers or users choice. Thefocus of the presented research is not only to provide meansfor accomplishing manufacturing that can handle changes butalso to accomplish flexibility in another area. The resultsshould be applicable in many different situations. The researchhas been divided into three parts: the further development of amanufacturing strategy, the development of a base for amanufacturing system design method and the development of amanufacturing control system.</p><p>The developed strategy is called Assembly-InitiatedProduction (AIP). An implementation of the strategy shouldprovide high manufacturing system flexibility but at the sametime contribute to the lowering of inventory levels andlead-times. Different solutions coupled to technicalrequirements found are also discussed.</p><p>The design method research focuses on basic manufacturingsystem properties and the possibility of expressing theseproperties by using simple combinable abstract units calledconcepts. The principle is the same as in physics where realworld phenomena may be expressed by using standard concepts asfor example time and mass. The intended use of the results isin an early manufacturing system design phase. The method isnot directly linked to the AIP strategy, but could be used forimplementing it.</p><p>Production Planning and Control (PPC) is an important partof a manufacturing system. After having reviewed current PPCpractices, a need for a factory floor PPC system workingregardless of factory floor layout, was identified. Based ontheoretical and industrial studies, the suggested solution is acomputerised, decentralised control system, physicallyseparated from the PPC/ERP system. In order to be able to makequick changes in the schedule, to obtain flexibility and toprovide the organisation with a tool for manufacturing controland decision-making, the system works in real time to provideaccurate and valid data.</p>

Thesys is focused on wireless transfer of the sensor data. It describes different wireless standards for potential use and realization of interface between sensor's data and their transfer. Crux of the matter is in detailed description of whole system with created utility programs. In the end it is summarized acquiered features of the realization.

L'augmentation du nombre des sinistres à grande échelle d'origine climatique, technologique, sanitaire, et bien d'autres, nous interpelle sur le mode de gouvernance des systèmes concernés, sur les choix de couverture de ces risques et sur les mesures de prévention mises en place. La question qui a animé notre recherche est : dans quelle mesure la gouvernance d'un système favorise-t-elle la gestion des risques ? Notre analyse empirique s'appuie sur deux cas d'étude, qui se concentrent, sur la gouvernance d'un système face à des risques catastrophiques pour l'un, et des risques communs pour l'autre. D'une part, les risques majeurs sont connus comme étant très peu probables mais avec de possibles lourdes conséquences. La dynamique de la gouvernance adaptative, pour la gestion des risques majeurs d'un système, souligne la nécessité d'adopter une approche flexible (dynamique). Nous proposons ainsi un cadre d'évaluation de la capacité d'adaptation d'un système dans le domaine des risques majeurs. D'autre part, les risques communs affectent l'ensemble de la population. Face aux risques communs dont les conséquences s'étalent dans le futur, nous considérons que la gouvernance adaptative dans une démocratie délibérative se réfère au paradigme selon lequel la gouvernance permet aux décideurs de se projeter vers le long terme. Le dilemme consiste à prendre (à présent) des décisions (c.-à-d. des risques, au sens général du terme) dont les effets (ou les conséquences) ne se font sentir que dans le futur. La gouvernance d'un système doit favoriser la gestion des risques. Notre travail de recherche est structuré autour de trois parties (i.e. « Gouvernances et risques », « La gouvernance d'un système exposé à un risque catastrophique », et « La gouvernance d'un système exposé à un risque commun »), chacune composée de trois chapitres. L'objectif ultime de la gestion des risques, voire des incertitudes qui caractérisent nos sociétés contemporaines est une raison d'être légitime des modes dynamiques de gouvernance qui incitent les différents acteurs à travailler ensemble, de diverses manières, afin de relever les défis auxquels ils sont confrontés. / The increase in large-scale climate, technological, sanitary, and many other types of losses, challenges us on the governance of the concerned systems, the choices made to hedge these risks and implement prevention measures. The question which animated our research is : to what extent the governance of a system promotes a better risk management?Our empirical analysis is based on two case studies which focus on the governance of a system while facing catastrophic risks for first one, and on common risks for the other. On the one hand, catastrophic risks are known to be highly improbable but with possible serious consequences. The dynamic of the adaptive governance system facing catastrophic risks underlines the need for a (dynamic) flexible approach. We therefore suggest an assessment framework for the adaptive capacity of a system in the field of catastrophic risks. On the other hand, common risks affect the whole population. We consider that the adaptive governance in a deliberative democracy refers to the governance paradigm which addresses common risks whose consequences spread out into the future. Thus, it induces decision makers to look at the long run. The dilemma consists in taking (now) decisions (i.e. Risk, in the general sense of the word) whose effects (or consequences) are only felt in the future. The governance of a system shall promote risk management. Our research is structured into three parts (i.e. "Governance and risk", "Governance of a system exposed to a catastrophic risk" and "Governance of a system exposed to a common risk"), each composed of three chapters. The ultimate objective of the management of risks, or even uncertainties, which characterize our contemporary societies is a legitimate reason for having dynamic modes of governance that prompt different actors to work together in various ways, in order to meet challenges they face.

Made available in DSpace on 2015-05-08T14:59:34Z (GMT). No. of bitstreams: 1 parte1.pdf: 4101005 bytes, checksum: 33757d5f02284fb047ef8012260c0b4a (MD5) Previous issue date: 2011-12-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The design and development of an automated system for inspection of weld in pipelines main objective to ensure portability in areas of difficult access, improved detectability of errors, accurate reports, scan speed, easy handling and greater flexibility for different configurations in diameter and thickness. From the geometry of the duct, the system is capable of circumferential and longitudinal movements in order to scan the entire surface of the pipeline being inspected. The system consists of two DC motors, gears, a programmable logic controller and a graphical interface to show the maintence of inspection process. The project is based on an interchargeable external gear that rotates and supports the transducers, driven by other gear. Another engine generates the longitudinal movement of the system mensuring that the entire surface of the pipe to be inspected. Experimental tests have demonstrated the effectiveness and applicability of the developed system. / O projeto e desenvolvimento de um sistema automático de varredura para inspeção em juntas soldadas de dutos tem como objetivo principal garantir uma portabilidade do sistema em áreas de difícil acesso, melhor detectabilidade de falhas, precisão nos laudos, velocidade de análise, fácil manuseio e maior flexibilidade para diferentes configurações de diâmetro e espessura. A partir da geometria do duto, o sistema é capaz de realizar os movimentos circunferenciais e longitudinais com o objetivo de varrer toda a superfície do duto a ser inspecionada. O sistema é composto de dois motores de corrente contínua, engrenagens e um controlador lógico programável, além de uma interface gráfica para mostrar o andamento do processo de inspeção. O projeto é baseado em uma engrenagem externa intercambiável que gira e suporta os transdutores, movida por um pinhão. Outro motor gera o movimento longitudinal do sistema garantindo que toda a superfície do duto seja inspecionada. Testes experimentais demonstraram a eficácia e aplicabilidade do sistema desenvolvido.

Introduction : Le système nerveux autonome (SNA) est le marqueur le plus puissant du vieillissement global de l'organisme, en particulier du vieillissement vasculaire cérébral et cardiaque. Bien que la peau soit richement innervée par les nerfs autonomes et le SNA contrôle de nombreuses fonctions cutanées, la relation entre le SNA et le vieillissement cutané n'a pas été étudiée. Méthodes : Nous avons évalué le vieillissement cutané chez 209 sujets âgés (105 femmes et 104 hommes, âge moyen 77,5 ans) appartenant à la cohorte stéphanoise PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) qui explore la fonctionnalité du SNA. Le vieillissement cutané a été mesuré par le score clinique SCINEXA (SCore for INtrinsic and EXtrinsic skin Aging), par VISIA, vidéodermatoscopie et cutométrie. L’activité du SNA a été mesurée par la variabilité de la fréquence cardiaque sur enregistrement de l’électrocardiogramme de 24 heures. Résultats : Une relation entre SNA et SCINEXA n’a pas pu être démontrée. Cependant, une relation entre l'activité du SNA et certains items du SCINEXA et certains paramètres du VISIA, de la vidéodermatoscopie et de la cutométrie a été trouvée. En particulier, l'analyse des paramètres VISIA a mis en évidence une relation entre porphyrines élevées et baisse de l’activité sympathique du SNA. Discussion et Conclusion : Quoique nous n’ayons pas trouvé de relation entre le vieillissement cutané global et la fonction du SNA, il est possible que le SNA joue un rôle sur le vieillissement intrinsèque de la peau, mais d’une manière négligeable en comparaison des facteurs externes tels que l’exposition solaire, et que cette partie du vieillissement soit difficile à mettre en évidence. De plus ayant trouvé une relation entre certains paramètres du vieillissement cutané et le SNA, notre étude encourage les futures recherches sur l’influence du SNA sur les différents composants du vieillissement cutané / Background : The autonomic nervous system (ANS) is the most powerful marker of the overall body aging, especially for what concerns the vascular aging of the heart and the brain. Although the skin is richly innervated by ANS nerves and the ANS controls many skin functions, the relation between the ANS and skin aging has not been studied. Methods : We evalusated skin aging of 209 elderly subjects (105 women and 104 men, mean age 77.5 years) belonging to the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) cohort of Saint-Etienne which explores the functionality of the ANS. Skin aging was measured by the clinical score SCINEXA (SCore for INtrinsic and EXtrinsic skin Aging), by VISIA, videodermoscopy and cutometry. The ANS status was measuredby the heart rate variability on a 24 hours recording of the electrocardiogram. Results : A relation between ANS and SCINEXA could not be demonstrated. However, a relation between the activity of the ANS and some items of SCINEXA and certain parameters of VISIA, videodermoscopy and cutometry was found. In particular, the analysis of VISIA parameters showed a relation between elevated porphyrins and a decreased sympathetic activity of the ANS. Discussion and conclusion : Although we did not find a relationship between overall skin aging and ANS activity, ANS might play a role in intrinsic skin aging, albeit marginally if compared to external factors such a sun exposure. Moreover, the intrinsic part of the skin aging and the ANS, our study encourages further research on the influence of the ANS on the various components of skin aging.

Medium-Voltage Direct-Current (MVDC) power system has been considered as the trending technology for future All-Electric Ships (AES) to produce, convert and distribute electrical power. With the wide employment of highrequency power electronics converters and motor drives in DC system, accurate and fast assessment of system dynamic behaviors , as well as the optimization of system transient performance have become serious concerns for system-level studies, high-level control designs and power management algorithm development. The proposed technique presents a coordinated and automated approach to determine the system adjustment strategy for naval power systems to improve the transient performance and prevent potential instability following a system contingency. In contrast with the conventional design schemes that heavily rely on the human operators and pre-specified rules/set points, we focus on the development of the capability to automatically and efficiently detect and react to system state changes following disturbances and or damages by incooperating different system components to formulate an overall system-level solution. To achieve this objective, we propose a generic model-based predictive management framework that can be applied to a variety of Shipboard Power System (SPS) applications to meet the stringent performance requirements under different operating conditions. The proposed technique is proven to effectively prevent the system from instability caused by known and unknown disturbances with little or none human intervention under a variety of operation conditions. The management framework proposed in this dissertation is designed based on the concept of Model Predictive Control (MPC) techniques. A numerical approximation of the actual system is used to predict future system behaviors based on the current states and the candidate control input sequences. Based on the predictions the optimal control solution is chosen and applied as the current control input. The effectiveness and efficiency of the proposed framework can be evaluated conveniently based on a series of performance criteria such as fitness, robustness and computational overhead. An automatic system modeling, analysis and synthesis software environment is also introduced in this dissertation to facilitate the rapid implementation of the proposed performance management framework according to various testing scenarios.

Os sistemas de sinalização de dois componentes são sistemas prevalentes em bactérias, permitindo a adaptação a diferentes condições ambientais. O sistema de dois componentes classicamente possui uma proteína histidina quinase, o primeiro componente, capaz de reconhecer o estímulo ambiental e fosforilar o regulador de resposta, o segundo componente. Pseudomonas aeruginosa é uma proteobactéria ubíqua, capaz de infectar hospedeiros filogeneticamente distintos. Esse patógeno oportunista apresenta um dos maiores conjuntos de sistemas de dois componentes em bactérias, que permite que ela sobreviva numa grande gama de ambientes, incluindo humanos. P. aeruginosa UCBPP-PA14 apresenta pelo menos 64 histidina quinases e 76 reguladores de resposta codificados em seu genoma. Diversos sistemas de dois componentes já foram correlacionados com a virulência, sendo o sistema GacSA o exemplo melhor caracterizado. Há poucos estudos sistemáticos sobre o envolvimendo dos reguladores de resposta na virulência de P. aeruginosa e os sinais que induzem a ativação dos reguladores de resposta precisam ser encontrados. Para identificar novos reguladores de resposta envolvidos na patogenicidade, infecções in vitro em macrófagos e in vivo em Drosophila melanogaster foram realizadas neste trabalho. Os macrófagos foram infectados com cada mutante dos reguladores de resposta ou com a linhagem selvagem, e a produção da citocina pró-inflamatória TNF-&#945; e o clearance bacteriano foram determinados. Alternativamente, as moscas foram infectadas utilizando-se a estratégia de feeding e a sobrevivência foi verificada. Utilizando-se essas abordagens, a identificação de diversos reguladores de resposta com papel na virulência foi alcançada, além de se corfirmar o papel de reguladores de resposta já estudados. Um dos novos genes envolvidos em virulência, PA14_26570 (nomeado neste trabalho de atvR), codifica um regulador de resposta atípico com substituição no aspartato fosforilável para glutamato, o que usualmente induz um estado sempre ativo. Um mutante não polar em atvR foi construído e macrófagos infectados com a linhagem &#916;atvR confirmaram um maior clearance bacteriano e maior produção de TNF-&#945; em comparação aos macrófagos infectados com a linhagem selvagem. Para comprovar a participação de AtvR durante a patogênese, um modelo de pneumonia aguda em camundongos foi utilizado. Camundongos infectados com a linhagem &#916;atvR apresentaram uma maior sobrevivência em comparação aos camundongos infectados com a linhagem selvagem. Além disso, os camundongos infectados com &#916;atvR apresentaram menor carga bacteriana, aumento no recrutamento de neutrófilos ativados e aumento na produção de citocinas pró-inflamatórias (TNF-&#945; e IFN-&#947;). Utilizando-se uma abordagem transcritômica (RNA-Seq), foi determindo diversos genes são regulados positivamente na linhagem superexpressando AtvR em relação à linhagem controle. Dentre esses, os clusters de respiração anaeróbia nar, nir, nor e nos estão incluídos. Esse resultado foi confirmado por qRT-PCR e análises fenotípicas, em que a linhagem &#916;atvR apresentou menor crescimento e expressão da nitrato redutase durante condições de hipóxia em comparação à linhagem selvagem. Em suma, neste trabalho foi demonstrado que diversos reguladores de resposta são importantes para a virulência de P. aeruginosa em macrófagos in vitro e in vivo em Drosophila, além de caracterizar o regulador de resposta atípico AtvR, que regula a respiração anaeróbica por desnitrificação, permitindo que P. aeruginosa possa infectar e colonizar o hospedeiro com maior eficiência. / Two-component systems are widespread in bacteria, allowing the adaptation to environmental changes. A two-component system is classically composed by a sensor kinase that phosphorylates a cognate response regulator. Pseudomonas aeruginosa is a ubiquitous proteobacterium able to cause disease in several hosts. This opportunistic pathogen presents one of the largest sets of two-component systems known in bacteria, which certainly contributes to its ability to thrive in a wide range of environmental settings, including humans. P. aeruginosa UCBPP-PA14 genome codes for at least 64 sensor kinases and 76 response regulators. Some response regulators are already known to be related to virulence, with the GacSA system as the best characterized. There are no systematic studies about the involvement of P. aeruginosa response regulators in virulence. Moreover, the input signal that triggers the response regulator activation is yet to be uncovered for most systems. To find new response regulators involved in virulence, in vitro infections werecarried out using macrophages. Briefly, the macrophages were infected with each response regulator mutant or the wild-type strain, the pro-inflammatory cytokine production (TNF-&#945;) and the bacterial clearance were evaluated. Using this approach, we identified several response regulators involved in virulence, and we also confirmed the involvement of known response regulators in this process. One of the novel virulence-related response regulators, PA14_26570 (named here as AtvR), is an atypical response regulator with a substitution in the phosphorylable aspartate to glutamate, that usually leads to an always-on state. A non-polar mutant was constructed, and macrophage infection with &#916;atvR confirmed an increased bacterial clearance as well as a higher TNF-&#945; production as compared to the wild-type strain. To ascertain the role of AtvR during the pathogenic process, an acute pneumonia model was used. Mice infected with &#916;atvR showed an increased survival as compared to mice infected with the wildtype strain. In addition, &#916;atvR infected mice showed reduced bacterial burden, increased neutrophil recruitment and activation, as well as increased pro-inflammatory cytokine production (TNF-&#945; and IFN-&#947;). Also, using a transcriptomic approach (RNASeq), we showed that several genes were upregulated in the strain overexpressing AtvR. These genes include the anaerobic respiration clusters nar, nir, nor and nos. This result was confirmed by qRT-PCR and phenotypic analysis, in which &#916;atvR showed reduced growth and nitrate reductase expression during hypoxic conditions as compared to the wild-type strain. In conclusion, we have demonstrated that several response regulators are important for P. aeruginosa virulence in vitro. In addition, we further characterized the atypical response regulator AtvR, which regulates anaerobic respiration via denitrification, allowing this bacterium to infect and colonize the host more efficiently.

Os sistemas de sinalização de dois componentes são sistemas prevalentes em bactérias, permitindo a adaptação a diferentes condições ambientais. O sistema de dois componentes classicamente possui uma proteína histidina quinase, o primeiro componente, capaz de reconhecer o estímulo ambiental e fosforilar o regulador de resposta, o segundo componente. Pseudomonas aeruginosa é uma proteobactéria ubíqua, capaz de infectar hospedeiros filogeneticamente distintos. Esse patógeno oportunista apresenta um dos maiores conjuntos de sistemas de dois componentes em bactérias, que permite que ela sobreviva numa grande gama de ambientes, incluindo humanos. P. aeruginosa UCBPP-PA14 apresenta pelo menos 64 histidina quinases e 76 reguladores de resposta codificados em seu genoma. Diversos sistemas de dois componentes já foram correlacionados com a virulência, sendo o sistema GacSA o exemplo melhor caracterizado. Há poucos estudos sistemáticos sobre o envolvimendo dos reguladores de resposta na virulência de P. aeruginosa e os sinais que induzem a ativação dos reguladores de resposta precisam ser encontrados. Para identificar novos reguladores de resposta envolvidos na patogenicidade, infecções in vitro em macrófagos e in vivo em Drosophila melanogaster foram realizadas neste trabalho. Os macrófagos foram infectados com cada mutante dos reguladores de resposta ou com a linhagem selvagem, e a produção da citocina pró-inflamatória TNF-&#945; e o clearance bacteriano foram determinados. Alternativamente, as moscas foram infectadas utilizando-se a estratégia de feeding e a sobrevivência foi verificada. Utilizando-se essas abordagens, a identificação de diversos reguladores de resposta com papel na virulência foi alcançada, além de se corfirmar o papel de reguladores de resposta já estudados. Um dos novos genes envolvidos em virulência, PA14_26570 (nomeado neste trabalho de atvR), codifica um regulador de resposta atípico com substituição no aspartato fosforilável para glutamato, o que usualmente induz um estado sempre ativo. Um mutante não polar em atvR foi construído e macrófagos infectados com a linhagem &#916;atvR confirmaram um maior clearance bacteriano e maior produção de TNF-&#945; em comparação aos macrófagos infectados com a linhagem selvagem. Para comprovar a participação de AtvR durante a patogênese, um modelo de pneumonia aguda em camundongos foi utilizado. Camundongos infectados com a linhagem &#916;atvR apresentaram uma maior sobrevivência em comparação aos camundongos infectados com a linhagem selvagem. Além disso, os camundongos infectados com &#916;atvR apresentaram menor carga bacteriana, aumento no recrutamento de neutrófilos ativados e aumento na produção de citocinas pró-inflamatórias (TNF-&#945; e IFN-&#947;). Utilizando-se uma abordagem transcritômica (RNA-Seq), foi determindo diversos genes são regulados positivamente na linhagem superexpressando AtvR em relação à linhagem controle. Dentre esses, os clusters de respiração anaeróbia nar, nir, nor e nos estão incluídos. Esse resultado foi confirmado por qRT-PCR e análises fenotípicas, em que a linhagem &#916;atvR apresentou menor crescimento e expressão da nitrato redutase durante condições de hipóxia em comparação à linhagem selvagem. Em suma, neste trabalho foi demonstrado que diversos reguladores de resposta são importantes para a virulência de P. aeruginosa em macrófagos in vitro e in vivo em Drosophila, além de caracterizar o regulador de resposta atípico AtvR, que regula a respiração anaeróbica por desnitrificação, permitindo que P. aeruginosa possa infectar e colonizar o hospedeiro com maior eficiência. / Two-component systems are widespread in bacteria, allowing the adaptation to environmental changes. A two-component system is classically composed by a sensor kinase that phosphorylates a cognate response regulator. Pseudomonas aeruginosa is a ubiquitous proteobacterium able to cause disease in several hosts. This opportunistic pathogen presents one of the largest sets of two-component systems known in bacteria, which certainly contributes to its ability to thrive in a wide range of environmental settings, including humans. P. aeruginosa UCBPP-PA14 genome codes for at least 64 sensor kinases and 76 response regulators. Some response regulators are already known to be related to virulence, with the GacSA system as the best characterized. There are no systematic studies about the involvement of P. aeruginosa response regulators in virulence. Moreover, the input signal that triggers the response regulator activation is yet to be uncovered for most systems. To find new response regulators involved in virulence, in vitro infections werecarried out using macrophages. Briefly, the macrophages were infected with each response regulator mutant or the wild-type strain, the pro-inflammatory cytokine production (TNF-&#945;) and the bacterial clearance were evaluated. Using this approach, we identified several response regulators involved in virulence, and we also confirmed the involvement of known response regulators in this process. One of the novel virulence-related response regulators, PA14_26570 (named here as AtvR), is an atypical response regulator with a substitution in the phosphorylable aspartate to glutamate, that usually leads to an always-on state. A non-polar mutant was constructed, and macrophage infection with &#916;atvR confirmed an increased bacterial clearance as well as a higher TNF-&#945; production as compared to the wild-type strain. To ascertain the role of AtvR during the pathogenic process, an acute pneumonia model was used. Mice infected with &#916;atvR showed an increased survival as compared to mice infected with the wildtype strain. In addition, &#916;atvR infected mice showed reduced bacterial burden, increased neutrophil recruitment and activation, as well as increased pro-inflammatory cytokine production (TNF-&#945; and IFN-&#947;). Also, using a transcriptomic approach (RNASeq), we showed that several genes were upregulated in the strain overexpressing AtvR. These genes include the anaerobic respiration clusters nar, nir, nor and nos. This result was confirmed by qRT-PCR and phenotypic analysis, in which &#916;atvR showed reduced growth and nitrate reductase expression during hypoxic conditions as compared to the wild-type strain. In conclusion, we have demonstrated that several response regulators are important for P. aeruginosa virulence in vitro. In addition, we further characterized the atypical response regulator AtvR, which regulates anaerobic respiration via denitrification, allowing this bacterium to infect and colonize the host more efficiently.