It is estimated that one in 59 children in the US are affected by autism spectrum disorder (ASD). ASD is distinguished by social and communication deficits that can be displayed throughout a wide range of severity. This resulting spectrum of behaviors observed in ASD suggests that a complex etiology is involved. Previous studies have shown a genetic susceptibility to autism including paternal age, twin and sibling concordance. Genetic sequencing of those affected as well as first order relatives have identified alterations in genes associated with neuronal synaptic communication. However, very little information is available regarding the pathophysiology of synapses in ASD. Neuronal communication between anterior cingulate cortical neurons via synapses with other brain regions is vital in the execution of social behaviors in individuals. The aim of this study was to evaluate the protein expression of the synaptic marker spinophilin and post-synaptic density protein-95 (PSD-95) in postmortem ASD gray matter brain tissue from the anterior cingulate and frontal cortex to compare to typically developing (TD) control brain tissue. Postmortem brain tissue of ASD and TD subjects was acquired from nationally funded brain repositories previously matched by brain area, age and gender. Immunoblotting for spinophilin and PSD-95 was performed using anterior cingulate and frontal cortical gray matter brain tissue from matched ASD and TD brain tissue. Spinophilin and PSD-95 protein amounts for all donors were normalized using GAPDH. Frontal cortical tissue demonstrated no significant differences in spinophilin protein expression between TD and ASD groups (N=6). Anterior cingulate tissue demonstrated no significant differences in spinophilin protein expression between TD and ASD groups (N=5). PSD-95 protein expression levels did not result in any significant differences between ASD donors and their control pairs for either brain tissue region. Although no changes were detected in the frontal cortex or anterior cingulate cortex, more brain areas and subjects must be evaluated to determine if spinophilin or PSD-95 can be reliable markers for synaptic alterations in ASD. These data are critical in determining synaptic pathology in ASD which may lead to future treatments.

Dans le système nerveux central, la synaptogenèse est un processus complexe multi-étapes qui se déroule aux contacts axones/dendrites. Les molécules d’adhérence neurexines/neuroligines jouent un rôle essentiel dans ce processus, en créant un lien physique entre les compartiments pré- et post-synaptiques et en participant au recrutement des complexes macromoléculaires essentiels à la fonction synaptique. Plus spécifiquement, le complexe neurexine-1β/neuroligine-1 induit la formation de post-synapses excitatrices, en recrutant des molécules d’échafaudage telles que PSD-95 et des récepteurs du glutamate.Mon travail de thèse a consisté à étudier les mécanismes moléculaires mis en jeu par les adhésions neurexines/neuroligines lors de la formation des post-synapses glutamatergiques. En utilisant des systèmes biomimétiques (neurexine purifiée fixée sur des billes, ou agrégée par des anticorps réticulés), nous avons induit des adhésions spécifiques neurexine-1β/neuroligine-1 sur des neurones d’hippocampe en culture. Nous avons ainsi étudié la distribution dynamique des composants post-synaptiques (récepteurs AMPA, PSD-95) endogènes ou étiquetés avec des protéines fluorescentes, par vidéo-microscopie. Dans un premier article, nous avons montré que la formation de ces contacts induisait un recrutement rapide de PSD-95 ainsi que des récepteurs NMDA et AMPA fonctionnels. En utilisant des récepteurs AMPA recombinants, j’ai montré que ce recrutement était dicté par la sous-unité GluA2. Dans une deuxième étude, en comparant le recrutement de PSD-95 induit par la neurexine avec des anticorps non–activants, nous avons mis en évidence un mécanisme d’activation spécifique de neuroligine-1 induit par la liaison de neurexine-1β. L’utilisation de mutants ponctuels de neuroligine-1 a permis de montrer que cette activation passe probablement par la déphosphorylation d’une tyrosine unique située dans le domaine C-terminal de la neuroligine-1.Enfin, en étudiant la diffusion latérale des rAMPA de surface par suivi de particules uniques fluorescentes (Quantum dots), ainsi qu’une batterie d’outils moléculaires pour moduler les adhésions neurexine/neuroligine (sur-expression, siRNA, souris KO), nous avons montré que les rAMPA sont recrutés aux adhésions neurexine-1β/neuroligine-1 via l’échafaudage PSD-95 et que ce recrutement nécessite la diffusion des récepteurs dans la membrane plasmique. Nous proposons ainsi que les récepteurs AMPA soient recrutés aux contacts naissants via un mécanisme original de diffusion/piégeage. / In the central nervous system, synaptogenesis is a multi step process occuring at axo-dendritic contacts. Neurexins/neuroligins adhesions are particularly involved in this process, making a bridge between the pre- and the post-synapse, and participating to the recruitment of macromolecular complexes essential for synaptic function. More precisely neurexin-1β/neuroligin-1 complex is specifically involved in the formation of excitatory synapses, inducing the recruitment of glutamatergic post-synapses components, such as PSD-95, and glutamate receptors.During my PhD, I focused on the molecular mechanisms involved in glutamatergic post-synapses formation triggered by neurexin-1β/neuroligin-1 adhesions. Using biomimetic models (beads coated with purified neurexin, or purified neurexin cross-linked with aggregated antibodies) we induced specific neurexin-1β/neuroligin-1 adhesions on cultured hippocampal neurons. We then studied the dynamic distribution of either endogenous or recombinant post-synaptic components (PSD-95, AMPARs) with live-imaging techniques. First, we showed that the formation of these contacts induced a rapid recruitment of PSD-95 and functional NMDA and AMPA receptors. Using recombinant AMPA receptors, I showed that this recruitment was mediated by GluA2 subunit.In a second study, using systematic comparison between the recruitment of PSD-95 induced either by neurexin-1β or by “non activating” antibody binding on neuroligin-1, we revealed a specific activation mechanism of neuroligin-1 induced by neurexin-1β binding. Using point mutations on neuroligin-1, we showed that this activation mechanism is mediated by a tyrosine dephosphorylation on neuroligin-1 intracellular tail.Finally, we studied AMPA receptor surface diffusion with single particle tracking experiments, using different molecular tools to perturb neurexin-1β/neuroligin-1 adhesions (overexpression, RNA interference, KO mice). We showed that AMPA receptors recruitment at new-formed neurexin-1β/neuroligin-1 adhesions occurs through PSD-95, and involves surface diffusion of AMPA receptors. We proposed an original diffusion/trap mechanism of AMPA receptors at nascent contacts.

Made available in DSpace on 2017-07-21T14:35:55Z (GMT). No. of bitstreams: 1 CAROLYN DE GEUS WENCESLAU.pdf: 1200941 bytes, checksum: 94de972e28ecf64328f568ac13958cef (MD5) Previous issue date: 2016-08-15 / In recent years, Patient Related Outcomes (PROs) have received more importance by providing meaningful informations answered by the patients about their symptoms, functional status, quality of life and satisfaction, and also for giving relevant information about treatment efficacy. The main objective of this study was to evaluate the satisfaction of fibromyalgia patients through PASS and determine the correlation of scores obtained with FIQR in relation to PASS. Other objectives were:to determine the value of best accuracy of FIQR in relation to PASS; to compare the FIQR scores between satisfied and dissatisfied patients and FIQR scores between patients with disability claims or on work disability, in relation to the rest of the sample; to compare the mean scores from HAQ, Beck and PSD questionnaires between satisfied and not satisfied patients and evaluate the correlation between the questionnaires. In the studied sample, 82 fibromyalgia patients were assessed, from public and private healthcare services, according to the modified ACR 2010 criteria. Sociodemographic and clinical data were collected and the impact of fibromyalgia was assessed by FIQR, the satisfaction by PASS and Likert scale, functional capacity by HAQ, depression by the Beck Depression Inventory and the polysymptomatic distress by PSD. In this sample depression (87%) and rheumatological diseases (64%) were the main comorbidities. Most patientes made use of antidepressants (96%) and analgesics (81%), but only 21% of patients performed at least 150 minutes of aerobic exercise per week. The results from the questionnaires showed severe impact of fibromyalgia, severe polysymptomatic distress, moderate to severe functional disability and moderate to severe depression symptoms. Patients with disability claims, or on work disability showed statistical difference in FIQR and Beck mean scores when compared to the rest of the sample. Patient satisfaction was considerably low in PASS (15% satisfied), as well as in Likert scale: 2.3 ± 2.8. There was no statistical difference between sociodemographic and clinical variables in relation to PASS satisfaction, except in older patients (p = 0.03) and patients with longer time since disease diagnosis (p = 0.003), who showed higher satisfaction. Correlation between FIQR and PASS was weak and negative (r = -0.26), showing that alterations in FIQR are little related to patient satisfaction. There was statistical difference (p = 0.001) in FIQR scores between the satisfied and the not satisfied group, and also in scores from other questionnaires comparing both groups, showing that dissatisfied patients have lower quality of life. Strong correlation was demonstrated between FIQR and HAQ questionnaires (r = 0.68) and FIQR and Beck (r = 0.61). The value of best accuracy of FIQR in relation to PASS was 65 (ROC curve), but with low sensitivity and specificity. The best specificity values, which reflect values where 100% of patients are satisfied, were very low for each questionnaire. This sample showed low satisfaction, severe physical and psychological symptoms in fibromyalgia patients, suggesting reinforcement of non pharmacological strategies for the treatment of the disease. And that in studies addressing therapeutic measures for fibromyalgia, satisfaction measures should be used. / Nos últimos anos os PROs: Patient Related Outcomes tem apresentado maior importância por fornecerem informações importantes respondidas pelo próprio paciente em relação aos seus sintomas, estado funcional, qualidade de vida e satisfação, além de permitir avaliar a resposta do paciente ao tratamento instituído. O objetivo principal deste estudo foi avaliar a satisfação dos pacientes com fibromialgia através do PASS e determinar a correlação dos escores obtidos através do FIQR com o PASS. Objetivos específicos foram determinar o valor de melhor acurácia do FIQR em relação ao PASS, comparar as médias dos escores do FIQR,entre pacientes satisfeitos e não satisfeitos e os escores do FIQR entre pacientes afastados do trabalho ou em litígio trabalhista, comparados com o restante da amostra. Também comparar as médias dos escores dos questionários: HAQ, Beck e PSD entre pacientes satisfeitos e não satisfeitos e fazer a correlação entre os questionários. Na amostra estudada foram avaliados 82 pacientes com fibromialgia, provenientes de rede pública e privada, de acordo com os critérios do ACR 2010 modificados. Foram coletados dados sociodemográficos e clínicos, foi avaliado o impacto da fibromialgia através do FIQR, a satisfação pelo PASS e escala de Likert, a capacidade funcional pelo HAQ, a depressão através do Inventário de Depressão de Beck e o estresse polissintomático pelo PSD. Nesta amostra depressão (87%) e doenças reumatológicas (64%) eram as comorbidades mais frequentes. A maioria dos pacientes (96%) fazia uso de antidepressivos e 81% utilizavam analgésicos;mas somente 21% dos pacientes realizavam pelo menos 150 minutos de exercício aeróbico por semana O resultado dos questionários demonstrou um impacto importante da fibromialgia, estresse polissintomático severo, incapacidade funcional moderada a grave e sintomas depressivos de intensidade moderada a grave.Pacientes em litígio trabalhista e aqueles afastados do trabalho demonstraram diferença estatística entre as médias do FIQR e do Beck comparado com o restante da amostra. A satisfação dos pacientes foi bastante reduzida, tanto pelo PASS (15% satisfeitos), quanto pela escala de Likert: 2,3 ± 2,8. Não houve diferença estatística entre as variáveis sociodemográficas e clínicas em relação à satisfação avaliada pelo PASS, exceto em pacientes mais velhos (p = 0,03) e pacientes com maior tempo de diagnóstico da doença (p = 0,003), os quais apresentaram maior satisfação. A correlação entre o FIQR e o PASS foi fraca e negativa (r= -0,26), demonstrando que as alterações no FIQR estão pouco relacionadas com a satisfação do paciente. Houve diferença estatística (p = 0,001) nos escores do FIQR entre o grupo satisfeito e o não satisfeito, e também nos escores dos outros questionários comparando os dois grupos, demonstrando que pacientes insatisfeitos apresentaram menor qualidade de vida. Foi demonstrada correlação forte entre os questionários FIQR e HAQ (r = 0,68) e FIQR e Beck (r = 0,61). O valor de melhor acurácia do FIQR em relação ao PASS foi 65 (curva ROC) mas com sensibilidade e especificidade baixos. Os valores de melhor especificidade, valores onde 100% dos pacientes se encontram satisfeitos, foram bastante baixos para cada questionário analisado. Esta amostra demonstrou pouca satisfação nos pacientes com fibromialgia, impacto importante da doença, associado com severidade de sintomas físicos e psíquicos, sugerindo que no tratamento sejam enfatizadas medidas não farmacológicas e que também, nos estudos que abordam medidas terapêuticas para a fibromialgia, sejam utilizadas medidas de satisfação.

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This study presents the nonlinear design of a state space controller to control hydraulic actuators under displacement control, specifically for real-time pseudo-dynamic testing applications. The proposed control design process uses the nonlinear state space model of the dynamics of the system to be controlled; and utilizes state feedback linearization through a transformation of the state variables. Comparisons of numerical simulation results for linear state-space and nonlinear state-space controllers are given. Also robustness of the control design with respect to identified parameters is investigated. It is shown that a controller with improved performance can be designed using nonlinear state space control design techniques, provided that a representative model of the system is available. / Structural Engineering

Made available in DSpace on 2016-12-23T13:49:05Z (GMT). No. of bitstreams: 1 Marcelo Hubner Moreira.pdf: 3712393 bytes, checksum: 15fd9ae9b7dca34b84a7222592799e3d (MD5) Previous issue date: 2013-01-20 / This work aims to characterize the fatigue from myoelectric signals and use them as an aid to the diagnosis of rheumatic diseases such as Fibromyalgia. The condition for this is the analysis of muscle fatigue. Through the evaluation of myoelectric signals, the behavior of muscle in some work situations was measured, such as isotonic and isometric muscle contraction, which describes the static and dynamic motor behavior. With the myoelectric signals, digital filtering techniques were applied to mitigate the noise corrupting the myoelectric signal. Then some algorithms were implemented to detect fatigue. With that, a protocol for assessing motor response based on the condition of muscle fatigue was established. In this situation, with the working muscle, the myoelectric signal acquisition was made from surface electrodes, using a commercial acquisition system. The data were processed in MATLAB R platform; algorithms were implemented for the identification of fatigue, such as RMS, MNF, ARV, MDF and AIF. In the final result, it was found that for both isometric tasks and isotonic tasks, it is recommended the use of constant weight with 60% of MCV, using MNF and RMS indicators, which were the most consistent indicators among them / Este trabalho tem a finalidade de caracterizar a fadiga a partir da coleta de sinais mioelétricos e usá-lo como ajuda no diagnóstico de doenças reumáticas, como a fibromialgia. A condição para tal é a análise da fadiga muscular. Através da avaliação dos sinais mioelétricos, foi verificado o comportamento do músculo em algumas situações de trabalho, como a contração muscular isotônica e isométrica, que descreve o comportamento motor dinâmico e estático. Com os sinais obtidos, foram aplicadas técnicas de filtragem digital a fim de atenuar os ruídos que corrompem o sinal mioelétrico. Em seguida, foi estabelecida a implementação dealgoritmos para detectar a fadiga. Com isso, pôde-se estabelecer um protocolo de avaliação motora baseada na resposta do músculo à condição de fadiga. Nessa situação de trabalho muscular, a aquisição de sinais mioelétricos foi feita a partir de eletrodos de superfície e aparelho comercial (EMG System do Brasil). Os dados foram processados em plataforma MATLAB R, onde foram implementados algoritmos para a identificação de fadiga, tais como RMS, MNF, ARV, MDF e AIF. No resultado final, foi constatado que, tanto para tarefas isométricas quanto para tarefas isotônicas, é recomendado a utilização de peso constante com 60% da MCV, segundo indicadores MNF e RMS, que foram os mais coerentes dos indicadores pesquisados.

Simple low-cost temperature feedback control loop was created, using personal computer as control and data acquisition element. It controlled the temperature inside mircowave pressure reactor. Medium in reactor tank (volume about 600 ml) was calorified by 1,8 kW magnetron, which power was driven by PSD controller. The PC- process interface was made by USB data acquisition modul UD128A8D. The utility program was written. It implemented PSD controller and data acquisition function. Furhtermore it implemented interface which enabled user to set the technological curve (time-temperature relation). The protocol of experiment was automatically stored to Micosoft Excel file before the program’s termination.

The aim of the project is a design of the temperature controler based on microprocessor. There are described the most widely used sensors for the temperature measuring and their involvement in the electric circuit. The temperature controler is based on the Peltier’s thermoelectric battery. Project desribes power control of this thermoelectric battery and also a design of the entire system and a description of the blocks takes a part.

This masters's thesis deals with choice and implementation of two free real-time operating systems into powerful 32-bit microcontroller with ARM Cortex-M4F core. First, there is shortly described the ARM architecture in general, its programmer's model, instruction set and Cortex-M4F core in brief. Next is description of the architecture of used microcontroller STM32F407VGT6 from ST Microelectronics, description of its integrated memories and their organization and functions of its integrated A/D and D/A converters. Next part of this thesis deals with searching real-time operating systems with ARM Cortex-M4F core support and then choose two of these systems for the implementation. The chosen operating systems are more closely described in two following chapters. Next chapter analyses possible implementations of the digital PSD controller and more complex system of such controllers using real-time operating system. Following chapter describes implementation of chosen operating systems and designed controllers. Last chapter deals with evaluation of features and qualities of the chosen real-time operating systems for implementation of embedded control system.

Abstract Cognitive Radio (CR) improves the efficiency of spectrum utilization by allowing non- licensed users to utilize bands when not occupied by licensed users. In this thesis, we address several challenges currently limiting the wide use of cognitive radios. These challenges include identification of unoccupied bands, energy consumption and other technical challenges. Improved accuracy edge detection techniques are developed for CR to mitigate both noise and estimation error variance effects. Next, a reduced complexity Simplified DFT (SDFT) is proposed for use in CR. Then, a sub-Nyquist rate A to D converter is introduced to reduce energy consumption. Finally, a novel multi-resolution PSD estimation based on expectation-maximization algorithm is introduced that can obtain a more accurate PSD within a specified sensing time.