Orientador: Paulo Inácio da Costa / Banca: Marcos da Fonseca / Banca: Fernanda de Freitas Anibal / Resumo: A infecção pelo vírus da imunodeficiência humana (HIV) ocorre com aumento dos níveis de anticorpos séricos e com grande quantidade de imunocomplexos circulantes. A associação entre as disfunções da fagocitose mediadas por receptores do tipo FcR, na infecção pelo HIV e, principalmente, na co-infecção com o Mycobacterium tuberculosis, têm sido amplamente descrita na literatura científica. A tuberculose (TB) é a infecção oportunista mais comum entre pacientes infectados pelo HIV e a causa de morte mais frequente entre os pacientes com a síndrome da imunodeficiência adquirida (AIDS). Sabe-se que a infecção pelo HIV torna o paciente susceptível às infecções oportunistas, como a tuberculose, e, essas co-infecções aumentam o potencial de replicação viral. A ineficiência do mecanismo de clearance de imunocomplexo (IC) e de fagocitose pode contribuir para o aumento da suscetibilidade às infecções oportunistas em indivíduos infectados pelo HIV. Sendo assim, a determinação dos genótipos para as variantes polimórficas funcionais dos receptores para a porção Fc da imunoglobulina de classe G (FcR), bem como das combinações dos diferentes genótipos, pode constituir um marcador importante para a patogênese da infecção pelo HIV, na co-infecção pelo M. tuberculosis e em infecções pelo M. tuberculosis isoladamente, ou seja, independente da infecção pelo vírus da AIDS. Desta forma, o objetivo deste estudo foi determinar os genótipos para os polimorfismos dos receptores FcRIIa (CD32; H/R131) e FcRIIIb (CD16; NA1/NA2) em portadores da infecção pelo HIV-1, co-infectados pelo M. tuberculosis e infectados apenas pelo M. tuberculosis, assim como a avaliação da função fagocítica através do burst oxidativo (formação de espécies reativas de oxigênio - EROs) induzido por polissacarídeos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Infection with human immunodeficiency virus (HIV) occurs along with increased levels of serum antibodies and a large amount of circulating immune complexes. The association between FcR-dependent phagocytosis dysfunction in HIV infection and, especially, when in co-infection with Mycobacterium tuberculosis, has been widely described in scientific literature. Tuberculosis (TB) is the most common opportunistic infection among HIV-infected patients and the most frequent cause of death among patients with acquired immunodeficiency syndrome (AIDS). It is known that HIV infection makes the patient susceptible to opportunistic infections such as tuberculosis, and these co-infections increase the potential for viral replication. The inefficiency of the immune complex (IC) clearance mechanism and phagocytosis may contribute to increased susceptibility to opportunistic infections in HIV-infected individuals. Thus, determination of the functional polymorphic variants‟ genotypes for class G immunoglobulin Fc receptors (FcR) as well as combinations of different genotypes may be an important marker for the pathogenesis of HIV infection, for co- infection with M. tuberculosis and for M. tuberculosis infection alone, i.e. independent of infection with AIDS virus. Thus, the aim of this study was to determine the genotypes for FcRIIa (CD32; H/R131) and FcRIIIb (CD16; NA1/NA2) polymorphisms in patients carrying HIV-1 infection, co-infected with M. tuberculosis and infected with M. tuberculosis alone, as well as evaluating the phagocytic function via oxidative burst (formation of reactive oxygen species - ROS) induced by cell wall polysaccharides from Saccharomyces cerevisiae, known as zymosan, in peripheral blood neutrophils from these patients. Our results demonstrated reduced capacity... (Complete abstract click electronic access below) / Mestre

With increasing amounts of data being collected in various fields of neuroscience, there is a growing need for robust techniques for the analysis of this information. This thesis focuses on the evaluation and development of quantitative frameworks for the analysis and classification of neuronal data from a variety of contexts. Firstly, I investigate methods for analysing spontaneous neuronal network activity recorded on microelectrode arrays (MEAs). I perform an unbiased evaluation of the existing techniques for detecting ‘bursts’ of neuronal activity in these types of recordings, and provide recommendations for the robust analysis of bursting activity in a range of contexts using both existing and adapted burst detection methods. These techniques are then used to analyse bursting activity in novel recordings of human induced pluripotent stem cell-derived neuronal networks. Results from this review of burst analysis methods are then used to inform the development of a framework for characterising the activity of neuronal networks recorded on MEAs, using properties of bursting as well as other common features of spontaneous activity. Using this framework, I examine the ontogeny of spontaneous network activity in in vitro neuronal networks from various brain regions, recorded on both single and multi-well MEAs. I also develop a framework for classifying these recordings according to their network type, based on quantitative features of their activity patterns. Next, I take a multi-view approach to classifying neuronal cell types using both the morphological and electrophysiological features of cells. I show that a number of multi-view clustering algorithms can more reliably differentiate between neuronal cell types in two existing data sets, compared to single-view clustering techniques applied to either the morphological or electrophysiological ‘view’ of the data, or a concatenation of the two views. To close, I examine the properties of the cell types identified by these methods.

As influências etárias do sistema imune de bezerros são descritas na primeira fase de vida desses animais e a hipótese de também ocorrerem ariações nos principais mecanismos de resposta inata do pulmão pode identificar períodos de maior suscetibilidade às principais doenças respiratórias que acometem os bezerros nesse período. Com a finalidade de minimizar os prejuízos econômicos associados às doenças respiratórias em bezerros, este estudo objetivou avaliar a dinâmica imunológica inata do sistema respiratório de bezerros sadios nos três primeiros meses de vida, no qual nove bezerros sadios foram acompanhados por três meses e submetidos a oito avaliações imunológicas. O material recuperado do lavado broncoalveolar colhido por broncoscopia foi submetido à avaliação funcional dos macrófagos alveolares utilizando as provas de fagocitose (SaPI e E.coli), burst oxidativo, quantificação de imunoglobulinas e expressão de CD14. Os dados foram avaliados pelo teste ANOVA oneway (unstacked) (paramétricos) e pelo teste Mann-Whitney (não paramétricos). Verificaramse alterações funcionais de fagócitos CD14+, que apesar de se manterem constantes em seus valores relativos durante todo o período, apresentou intensidade de fagocitose elevada pontual na terceira semana de vida e um aumento da fagocitose por mononucleares CD14+ aos 45 dias de idade com diminuição da intensidade da fagocitose por essas mesmas células a partir dessa idade. Conclui-se que a partir de 45 dias de vida os animais começam a montar uma resposta imune própria, porém pontual e que até os 90 dias não atingem a estabilidade necessária para atestar a conclusão do processo de maturação da resposta inata local. / The influences of age in calves\' immune system are described in their first phase of life. The hypothesis that variations occur in the main mechanisms of lung innate response can help to identify periods of greater susceptibility to the respiratory diseases that affect calves in the first stage of their life. With the purpose of minimizing the economic losses associated with respiratory disease in calves, this study aimed to evaluate the innate immune dynamics of the respiratory system of healthy calves in the first three months of life. Nine healthy calves were monitored for three months and eight immunologic evaluations were performed. Bronchoalveolar lavage samples were recovered by bronchoscopy. Then, the alveolar macrophages in samples were identified by protein expression of CD14 and undergone functional evaluation of phagocytosis (SAPI and E.coli) and oxidative burst. Immunoglobulin were also quantified in samples. Data was assessed by one-way ANOVA (unstacked) (parametric) and the Mann-Whitney test nonparametric). Functional alterations in phagocytes CD14 + were observed, and although their relative values were kept throughout the period, higher intensity of phagocytosis in the third week and increased phagocytosis by macrophages CD14 + at 45 days of life was observed. Decreased intensity of phagocytosis was observed after this age. It is concluded that from 45 days of life on, calves began to maintain their immune response, but until 90 days of life they did not achieve the stability to conclude the maturation of local innate response.

Interruption to water services and low water pressure conditions are commonly observed problems in water distribution systems (WDSs). Of particular concern are the unplanned events, such as pipe bursts. The current regulation in the UK requires water utilities to provide reliable water service to consumers resulting in as little as possible interruptions and of as short possible duration. All this pushes water utilities toward developing and using smarter responses to these events, based on advanced tools and solutions. All with the aim to change network management style from reactive to a proactive, and reduce water losses, optimize energy use and provide better services for consumers. This thesis presents a novel methodology for efficient and effective operational, short time response to an unplanned failure event (such as pipe burst) in a WDS. The proposed automated, near real-time operational response methodology consists of isolating the failure event followed by the recovery of the affected system area by restoring the flows and pressures to normal conditions. The isolation is typically achieved by manipulating the relevant on/off valves that are located closely to the event location. The recovery involves selecting an optimal combination of suitable operational network interventions. These are selected from a number of possible options with the aim to reduce the negative impact of the failure over a pre-specified time horizon. The intervention options considered here include isolation valve manipulations, changing the pressure reducing valve’s (PRV) outlet pressure and installation and use of temporary overland bypasses from a nearby hydrant(s) in an adjacent, unaffected part of the network. The optimal mix of interventions is identified by using a multi-objective optimization approach driven by the minimization of the negative impact on the consumers and the minimization of the corresponding number of operational interventions (which acts as a surrogate for operational costs). The negative impact of a failure event was quantified here as a volume of water undelivered to consumers and was estimated by using a newly developed pressure-driven model (PDM) based hydraulic solver. The PDM based hydraulic solver was validated on a number of benchmark and real-life networks under different flow conditions. The results obtained clearly demonstrate its advantages when compared to a number of existing methods. The key advantages include the simplicity of its implementation and the ability to predict network pressures and flows in a consistently accurate, numerically stable and computationally efficient manner under both pressure-deficient and normal-flow conditions and in both steady-state and extended period simulations. The new real-time operational response methodology was applied to a real world water distribution network of D-Town. The results obtained demonstrate the effectiveness of the proposed methodology in identifying the Pareto optimal network type intervention strategies that could be ultimately presented to the control room operator for making a suitable decision in near real-time.

L’intégration sensori motrice (ISM) est le processus par lequel les afférences sensitives sont intégrées par le système nerveux central et utilisées pour assister l’exécution des programmes moteurs. Plusieurs données suggèrent que celle-ci est anormale dans la maladie de Parkinson et serait impliquée dans la pathophysiologie de l’akinésie. En effet, la discrimination cutanée, l’acuité tactile spatiale, la kinesthésie ont été décrites déficientes dans cette maladie. Sa sensibilité aux traitements dopaminergiques est controversée. L’objectif de notre travail a été de tacher de mettre en évidence cette ISM anormale dans la maladie de Parkinson grâce à 2 techniques neurophysiologiques. Il s’agissait pour la 1e de la synchronisation liée à l’évènement des rythmes bêta (SLE bêta) qui permet d’étudier la désactivation corticale à la fin d’un mouvement actif mais aussi l’intégration corticale des afférences somesthésiques notamment lors des mouvements passifs et de la stimulation électrique des nerfs périphériques. La 2nde était l’étude de la modulation de l’excitabilité du cortex moteur primaire (évalué par la stimulation magnétique transcrânienne (TMS)) par des afférences somesthésiques générées par la stimulation électrique du nerf médian. Le but était de mettre en évidence des anomalies dans la modulation de l’excitabilité du cortex moteur primaire dans les intervalles inhibiteurs courts et longs (SAI et LAI) et/ou facilitateur (AIF). L’effet des traitements dopaminergiques a été évalué dans les deux cas par un enregistrement des patients après un sevrage thérapeutique. De nombreux protocoles de stimulation magnétique transcrânienne répétitive du cortex moteur que ce soit à basse ou haute fréquence, ont montré une efficacité sur l’akinésie. Il semblerait que les séances à fréquence plus rapides soient plus efficaces. Nous avons testé une nouvelle technique excitatrice à haute fréquence dite theta burst intermittente (ITBS) en regard du cortex moteur primaire chez des patients parkinsoniens et évalué l’effet sur l’akinésie. Nous avons par ailleurs étudié l’effet de cette stimulation sur l’ISM évaluée en conditionnant la TMS par une stimulation électrique du nerf médian. Notre 1e partie de l’étude a mis en évidence un effondrement de la SLE bêta dans la maladie de Parkinson après un mouvement actif, passif et une stimulation électrique du nerf médian. La levodopa a amélioré seulement la SLE bêta lors du mouvement actif. Nous avons pu ainsi confirmer l’atteinte de la SLE bêta active dans la maladie de Parkinson en lien avec un déficit de désactivation corticale en fin de mouvement mais aussi mettre en évidence une atteinte de la SLE bêta sensitive témoin d’un déficit du traitement cortical des afférences proprioceptives. La SLE bêta active a été améliorée par la levodopa alors que la SLE sensitive n’a pas été modifiée ce qui montre la dopa sensibilité de la désactivation corticale et le caractère non dopa sensible de l'ISM. Notre 2e partie n’a pas mis en évidence de différence significative dans la modulation de l’excitabilité du cortex moteur primaire par la stimulation électrique du nerf médian entre des patients parkinsoniens en début de maladie ni à un stade plus avancé par rapport à des témoins appariés par l’âge. En revanche la prise de levodopa a été associée à une aggravation de la LAI ce qui suggère aussi l’absence d’amélioration de l’ISM dans la maladie de Parkinson voire son aggravation par le traitement dopaminergique. Nous avons par contre montré que la modulation de l’excitabilité du cortex moteur primaire déclinait avec le vieillissement normal pour ce qui concerne les intervalles longs inhibiteurs (LAI) et facilitateurs (AIF) grâce à une comparaison d’une population de sujets contrôles jeunes et âgés sains. La session unique d’ITBS appliquée sur le cortex moteur primaire des patients parkinsoniens a permis d’améliorer transitoirement l’akinésie et la rigidité du membre supérieur controlatéral. [...] / Sensori motor integration (SMI) is the process whereby sensory inputs are integrated by the central nervous system and used for assisting motor program execution. Further data suggest that SMI is deficient in Parkinson's disease and might be implied in pathophysiology of akinesia. Indeed, two point skin discrimination, precision in tactile spatial acuity, kinaesthesia have been described deficient in Parkinson's disease. Dopaminergic treatment effects in sensory processing are controversial. The aim of our study was to investigate SMI in Parkinson's disease by using two neurophysiological techniques. The first one was the event related synchronization of beta rhythms (ERS beta) which reflects neural deactivation of the motor network at the end of active movement and also somesthesic afferences processing after passive movement or electric nerve stimulation. The second technique was the modulation of primary motor cortex excitability (investigated by trans cranial magnetic stimulation (TMS)) by somesthesic afferences generated by median nerve electric stimulation. This electric nerve stimulation consisted in inhibitory short or long interstimulation intervals (respectively SAI and LAI) and also facilitatory interval (AIF). Dopaminergic treatment effect was investigated in both techniques by recording patients after treatment withdrawal. Many protocols of repetitive transcranial stimulation over the primary motor cortex have been shown to be effective to reduce akinesia in Parkinson’s disease. High frequencies of stimulation seem to be more effective. We aimed at studying if a new excitatory protocol of high frequency called intermittent theta-burst (iTBS) over the primary motor cortex also affects akinesia and SMI investigated by conditioning TMS by median nerve stimulation. The first part of our study showed a decrease in ERS beta in Parkinson disease after an active movement, a passive movement and en electric median nerve stimulation. We have confirmed that the active ERS beta is deficient in Parkinson's disease and is associated to a deficient motor cortex deactivation at the end of the movement. Furthermore, we showed that sensory ERS beta is deficient, reflecting that cortical processing of sensory afferences is also deficient. Levodopa enhanced active but not sensory beta ERS. This suggests the dopa sensitivity of motor cortex deactivation and the absence of dopasensitivity of cortical processing of somesthesic afferences generated by movement.The second part failed to show a significant difference between parkinsonian patients and age matched controls in the modulation of primary motor cortex by median nerve stimulation. In patients with Parkinson's disease, levodopa worsened LAI. This suggests that SMI in Parkinson disease is not dopa sensitive and is even worsened by treatment. In control subjects, the modulation of primary motor cortex excitability by sensory afferences declined with normal aging because LAI and AIF decreased in old compared to young controls.The unique session of iTBS over primary motor cortex in parkinsonian patients improved akinesia and rigidity of contralateral upper limb. This improvement was higher in patients under their usual dopaminergic treatment than in de novo patients or after treatment withdrawal. AIF was clearly enhanced but only in patients under usual dopaminergic treatment suggesting that iTBS over primary motor cortex has improved akinesia in patients treated by levodopa via an improvement of SMI.

Uma grande variedade de modelos é utilizada para estimar a pressão de ruptura de dutos contendo defeitos de corrosão. O presente trabalho tem como objetivo estudar a precisão dos modelos mais comuns e avaliar a pressão de ruptura de dutos submetidos à corrosão. Os modelos avaliados são: ASME B31G, ASME B31G modificado, DNV RP F101 e PCORRC. O estudo é baseado em mais de 400 resultados de ensaios de ruptura em dutos corroídos, todos coletados da literatura. A base de dados contem defeitos de corrosão reais e artificiais. Uma análise estatística foi realizada para a variável erro de modelo. Uma análise de regressão não-linear foi realizada para investigar os efeitos da variável erro de modelo, das variáveis mais relevantes, como profundidade e comprimento do defeito, e tensão de ruptura do aço. Uma análise de confiabilidade foi realizada a partir das estatísticas obtidas da variável erro de modelo, sendo estimado o índice de confiabilidade e a probabilidade de falha do duto com defeitos de corrosão, através do método iterativo de primeira ordem, denominado FORM (First Order Reliability Method). Nesta análise avaliou-se a evolução da probabilidade de falha com o aumento da profundidade do defeito, bem como foram identificadas as variáveis aleatórias mais importantes na falha do duto. O estudo pode ajudar aos operadores a eleger qual modelo utilizar em análises de risco, proporcionando mais segurança às operações dutoviárias. / A variety of models exist to estimate burst pressures of pipelines containing corrosion defects. The objective of this work is to study the accuracy of some of the most popular empirical burst pressure models. The study addresses the models: ASME B31G, ASME B31G Modified, DNV RP-F101 and PCORRC. The investigation is based on over 400 burst test results, all collected from the literature, containing both real and artificial corrosion defects. A statistical analysis is performed for assessing the accuracy of semi-empirical models by using a model error variable. A non-linear regression analysis is performed to identify the influence, on model errors, of the most relevant variables, such as defect depth and length and steels rupture tension. A reliability analysis was carried out, using model error statistics developed herein, in order to evaluate reliability index and probability of failure of pipelines containing corrosion defects, through the iterative first order reliability method, or FORM - First Order Reliability Method. The evolution of failure probabilities, with increasing defect depth, was investigated. The most relevant random variables were identified. The study can help operators choose a proper empirical model to use in their risk analysis, leading to greater safety in pipeline operations.

No description available.

Low-density parity-check (LDPC) codes provide excellent error correction performance and can approach the channel capacity, but their performance degrades significantly in the presence of burst noise. Bursts of errors occur in many common channels, including the magnetic recording and the wireless communications channels. Strategies such as interleaving have been developed to help compensate for bursts errors. These techniques do not exploit the correlations that can exist between the noise variance on observations in and out of the bursts. These differences can be exploited in calculations of prior probabilities to improve accuracy of soft information that is sent to the LDPC decoder. Effects of using different noise variances in the calculation of prior probabilities are investigated. Using the true variance of each observation improves performance. A novel burst detector utilizing the forward/backward algorithm is developed to determine the state of each observation, allowing the correct variance to be selected for each. Comparisons between this approach and existing techniques demonstrate improved performance. The approach is generalized and potential future research is discussed.

Objective: The air conduction click is currently the most widespread stimulus used to estimate the pure tone audiogram as part of auditory brainstem response (ABR) testing. The click is characterized by its broad spectral content and rapid onset, which may not make it the best choice for frequency specificity. An alternative stimulus is a short duration tone burst stimuli with notched noise masking. When obtaining an ABR using standard unmasked tone bursts, the brief stimulus onset may cause spectral splatter producing response contributions from unwanted regions of the cochlea; thus reducing the frequency specificity of the ABR. Notched noise masking used in conjunction with the tone burst ABR, limits the evoked response to those frequencies within the notch, thereby reducing the likelihood of spectral splatter and increasing frequency specificity. The presence of a sloping sensory hearing impairment creates additional difficulties for achieving frequency specificity because of the likelihood that lower frequency cochlea regions, with less sensory damage, will contribute to the evoked response. It is theorized that notched noise masking will reduce the neural contributions from regions of the cochlear outside those within the notch, resulting in more frequency specific results than those achieved with a standard unmasked tone burst stimulus. The present study was designed to investigate the differences in Wave V latency between the notched noise ABR and the standard unmasked tone burst ABR as a measure of frequency specificity. Design: Twenty-five participants with normal hearing in at least one ear and 16 participants with bilateral SNHL participated in this investigation. Each participant was given an audiological evaluation, a click ABR screening to determine neural synchrony, a standard tone burst ABR and a notched noise tone burst ABR. Results: An Analysis of Variance (ANOVA) failed to reveal any significant Wave V latency differences between the ABRs obtained with unmasked tone bursts versus ABRs obtained with a notched noise tone burst. Conclusion: The results of this study do not support the use of notched noise tone bursts for improved ABR frequency specificity. This finding is contrary to previously reported results (Stapells & Picton, 1981), which indicated improved frequency specificity when obtaining a tone burst ABR in notched noise versus a standard unmasked tone burst ABR.

<p>The X-ray Multi-mirror Mission, XMM-Newton was launched by the European Space Agency, ESA, in 1999. XMM-Newton carries six cameras, including a silicon pn-junction Charge Coupled Device, or pn-CCD camera. This camera has six operating modes, spatially as well as time resolved. The main objective of this project is to refine the Burst mode energy correction in order to align the measured energy spectra observed in the Burst mode with the spectra taken in the Full Frame mode. An observation of the line-rich supernova remnant called Cassiopeia A is used to evaluate the line positions in each mode such that the energy correction function used for the alignment can be modified accordingly. The analysis further treats the application of the correction on a source with a continuous spectrum, the Crab nebula. Discussion shows how to reduce eventual residuals in the Crab spectrum by modifying the correction function while keeping the alignment of the Cas-A spectra. The final product is an update of the corresponding published calibration file.</p>