El acelerado crecimiento de las comunicaciones a través de plataformas de transmisión en banda ancha por vía alámbrica e inalámbrica, sumado al uso cada vez más extenso de modulaciones de amplitud no constante que, debido a su alta eficiencia espectral y bajo coste de implementación, han sido adoptadas en el marco de desarrollo de diversos estándares de transmisión, son aspectos que han servido de soporte y motivación fundamental para el presente trabajo de investigación en el campo de la compensación de distorsiones no lineales en sistemas de comunicación. El estudio de los efectos de la distorsión no lineal y su compensación ha sido desde hace ya muchos años objeto de atención para investigadores de diversas áreas. Hoy, en particular, este estudio sigue siendo fundamental ya que se encuentra directamente implicado en el desarrollo de tecnologías de última generación en el área de las comunicaciones. Los nuevos sistemas de transmisión digital, en especial aquellos basados en OFDM (Orthogonal Frequency Division Multiplexing), son capaces de ofrecer altos niveles de eficiencia espectral utilizando modulaciones lineales multinivel sobre un numeroso conjunto de subportadoras que, al ser (idealmente) ortogonales en frecuencia, pueden ser ubicadas en un ancho de banda muy reducido permitiendo así transmitir elevadas tasas de información por segundo y por ancho de banda. Sin embargo, y a consecuencia de esto, problemas como las interferencias por canal adyacente o la presencia de una distorsión no lineal en la cadena de transmisión afectan de manera crítica las prestaciones de estos sistemas imponiendo severos límites a su viabilidad. De hecho, en el campo de las comunicaciones móviles y satelitales, existen actualmente diversas aplicaciones donde estos esquemas de modulación y multicanalización están ya operativos. En estos casos, la eficiencia de potencia en transmisión resulta primordial para, entre otras razones, lograr una máxima autonomía del equipamiento. En este contexto, el comportamiento no lineal de los amplificadores de alta potencia utilizados en transmisión de radiofrecuencia, constituye el principal obstáculo (desde el punto de vista de la distorsión no lineal) para el buen funcionamiento de los sistemas de comunicación digital basados en OFDM. Afortunadamente, este nocivo efecto puede ser compensado mediante diversas técnicas clásicas de linealización cuyas variantes -ad-hoc' han sido propuestas y ampliamente investigadas, existiendo al día de hoy una nutrida literatura parte de la cual referimos a lo largo de este trabajo. Entre dichas técnicas, la pre-distorsión digital ofrece óptimas condiciones para el diseño de linealizadores adaptativos ya que puede ser implementada a muy bajo coste sobre la información discreta de las señales de banda base. El objetivo que se persigue, en general, es el de proveer las condiciones de linealidad necesarias para explotar las capacidades propias de las modulaciones de alta eficiencia espectral, y al mismo tiempo alcanzar un máximo aprovechamiento de la potencia disponible. En este trabajo de investigación, efectuamos inicialmente una revisión sintetizada de algunas importantes técnicas de linealización para luego dar paso a una revisión más detallada de dos modelos relevantes utilizados para caracterizar el comportamiento no lineal de los amplificadores de alta potencia (modelo se Series de Volterra y modelo de Saleh para amplificadores nolineales sin memoria). Junto con ello se examinan algunas interesantes propiedades estadísticas asociadas al fenómeno de la distorsión no lineal que han dado pie a considerar durante la investigación posibles nuevas aplicaciones en estrategias de pre-distorsión. Se ha querido también incluir la descripción, a nivel de sistema y modelo de señal, de un esquema de transmisión OFDM genérico incluyendo caracterizaciones analíticas detalladas del efecto no lineal a objeto de formalizar en propiedad un modelo discreto exacto que otorgue una visión más profunda para la comprensión del fenómeno estudiado. Finalmente se presenta el diseño y evaluación de un esquema de pre-distorsión basado en un algoritmo iterativo que considera, como principal aporte, la optimización bidimensional de un reducido número de coeficientes de interpolación que identifican de manera adaptativa la característica inversa de ganancia compleja de un amplificador, tanto en función de la particular morfología no lineal de dicha curva, como también de la distribución de probabilidad de las señales de entrada en banda base. / The rapid growth of wired and wireless broad-band communications and the pervasive use of spectrally efficient non-constant amplitude modulations, adopted in the framework of several standardized transmission formats, motivates and supports the present research work in the field of non-linear distortion in communication systems. The compensation of nonlinearities has received a lot of attention in past and recent years, presenting direct implications on industrial development of last generation communication technologies. New digital transmission systems, particularly those based on Orthogonal Frequency Division Multiplexing (OFDM), feature high spectral efficiency as they exploit multilevel linear modulations to transmit at high information rates in combination with a dense allocation of a large number of (ideally) orthogonal sub-carriers in a relatively reduced bandwidth. As a result, problems such as adjacent channel interference and non-linear distortion become critical for system performance and, therefore, must be reduced to a minimum. Moreover, numerous applications of such transmission schemes are already operative in the field of satellite and mobile communications, where power efficiency is of primary concern due to, among other reasons, operation autonomy of the equipment and effective transmitted power. In this context, the non-linear behaviour of high power amplifiers (HPAs) constitutes a major impairment for OFDM-based digital communications systems. The compensation of these harmful effects can be achieved using a variety of techniques that have been proposed and widely dealt with in the literature. Among these techniques, digital pre-distortion, which can be carried out at a very low cost over the discrete base-band information, provides optimal features for the efficient implementation of adaptive linearization. Thence, in order to provide good conditions for the reliable use of high spectral efficiency modulations while taking the maximum advantage from the transmitting power budget, it is necessary to incorporate a suitable linearization technique.In the present work, we begin by reviewing some background on linearization techniques. This leads us to continue analyzing two relevant theoretical models typically used in characterizing memory and memoryless nonlinear HPAs (Volterra Series model and Saleh model for memoryless nonlinear HPAs). In addition to this a generic OFDM system and signal structure is described in detail by including the non-linear effect in the analytical model of the transmission chain. This is done in order to formalize an exact discrete OFDM model that help us in achieving a deeper understanding of the phenomenon under consideration. Then, some useful statistical properties and parameters associated to the nonlinear distortion are examined as well as the application of a CDF-based estimation of nonlinearities which is proposed as a new pre-distortion strategy. Finally, a new discrete adaptive pre-distortion scheme is formulated and then tested via simulation. The analysis and design of the main algorithm proposed considers the adaptive identification of the inverse complex gain characteristic of a nonlinear HPA. For this purpose, an iterative 2-D optimization of a reduced number of interpolation functions is formulated under a special two-fold criterion which accounts for the particular morphology of the HPA's nonlinear gain characteristic, as well as the probability distribution of the input base-band information.

Le trouble du déficit de l’attention/hyperactivité (TDA/H) est un des troubles comportementaux le plus commun chez les enfants. TDAH a une étiologie complexe et des traitements efficaces. Le médicament le plus prescrit est le méthylphénidate, un psychostimulant qui bloque le transporteur de la dopamine et augmente la disponibilité de la dopamine dans la fente synaptique. Des études précliniques et cliniques suggèrent que le cortisol peut potentialiser les effets de la dopamine. Un dysfonctionnement du système hypothalamo-hypophyso-surrénalien (HHS) est associé avec plusieurs maladies psychiatriques comme la dépression, le trouble bipolaire, et l’anxiété. Nous avons fait l’hypothèse que le cortisol influence l’efficacité du traitement des symptômes du TDAH par le méthylphénidate. L’objectif de cette étude est de mesurer les niveaux de cortisol le matin au réveil et en réponse à une prise de sang dans un échantillon d’enfants diagnostiqué avec TDAH âgé de 8 ans. Le groupe était randomisé dans un protocole en chassé croisé et en double aveugle avec trois doses de méthylphénidate et un placebo pour une période de quatre semaines. Les enseignants et les parents ont répondu aux questionnaires SWAN et à une échelle d’évaluation des effets secondaires. Les résultats ont démontrés qu’un niveau de cortisol élevé au réveil prédit les sujets qui ne répondent pas au traitement du TDAH, si on se fie aux rapports des parents. En plus, la réactivité au stress élevé suggère un bénéfice additionnel d’une dose élevée de méthylphénidate selon les enseignants. Aussi, les parents rapportent une association entre la présence de troubles anxieux co-morbide avec le TDAH et une meilleure réponse à une dose élevée. Cette étude suggère qu’une forte réactivité de l’axe HHS améliore la réponse clinique à des doses élevées, mais qu’une élévation chronique du niveau de cortisol pourrait être un marqueur pour les non répondeurs. Les résultats de cette étude doivent être considérés comme préliminaires et nécessitent des tests plus approfondis des interactions possibles entre les médicaments utilisés pour traiter le TDAH et l’axe HHS. / ADHD is the most common behavioural disorder in children with complex aetiology and efficacious treatments. The most prescribed medication for ADHD is methylphenidate, a psychostimulant that blocks the dopamine transporter and increases dopamine availability in the synaptic cleft. Preclinical and clinical studies show that cortisol may enhance dopamine effects. Dysregulation of the hypothalamic-pituitaryadrenal axis is also associated with many psychiatric disorders such as depression, bipolar disease, and anxiety. We hypothesized that cortisol has an influence on the efficacy of the treatment of ADHD symptoms with methylphenidate. The objective of this study was to measure the salivary level of cortisol in a sample of 8-year-old children with ADHD upon waking and in response to a venipuncture. The children were then randomized to three doses of methylphenidate and a placebo in a double-blind cross-over design. Teachers and parents rated the behaviour of the children using the SWAN and a side effect rating scale. The results showed that high morning cortisol is a good predictor of a nonresponder under active medication, as reported by parents. Also, the high stress reactivity group, but not the low stress reactivity group, demonstrated a greater benefit going to a higher dose of methylphenidate, according to teachers. In addition, parents demonstrated an association between anxiety comorbid disorders and a better response to a high dose of methylphenidate. This study suggests that a strong reactivity of the HPA axis improves the clinical response at high dose, but that chronically elevated cortisol might be a marker for non responders. The results of this study should be seen as preliminary and require further testing of the possible interactions between ADHD medication and HPA activity.

Fatigue is common in the general population, and is the hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Although the occurrence of sleep difficulties is known to be common in subjects with fatigue, research on insomnia in such subjects is absent. The current study sought to examine the impact comorbid insomnia has on level of fatigue in subjects with chronic fatigue. The aim of this study is to assess the relationship between insomnia and chronic fatigue, and examine if the relationship is affected by the endocrine activity in the HPA axis. The following hypotheses were tested: 1) Do patients with chronic fatigue and comorbid insomnia experience more fatigue than patients with chronic fatigue without comorbid insomnia? 2) Do patients with chronic fatigue and with initially comorbid insomnia experience more fatigue after treatment than chronic fatigue patients without comorbid insomnia? 3) Do patients with chronic fatigue who experience improvement in insomnia after treatment also experience less fatigue by the end of treatment compared with patients who do not experience improvement in insomnia? 4) Is the potential relationship between insomnia and chronic fatigue influenced by the activity of the HPA axis as expressed by variation in cortisol output measured by Trier Social Stress Test for Groups (TSST-G)? The study sample consisted of 75 patients with chronic fatigue. Thirty-three met criteria for insomnia, while 42 did not. While staying at Hysnes Rehabilitation Center in Trondheim, Norway, they received a work-related Acceptance and Commitment Therapy (ACT) treatment intervention lasting 3.5 weeks. In addition, they participated in a standardized stress test (Trier Social Stress Test) pre- and post-treatment. Saliva cortisol samples were collected during the test in order to measure variation in cortisol output. The current finding is the first description of how insomnia in patients with chronic fatigue is associated with higher levels of fatigue (p < .05). Further, this study gives preliminary support indicating that remission of insomnia in patients with chronic fatigue can significantly reduce levels of fatigue (p < .05), and furthermore improve the physiological stress-response (p < .05). These results might encourage clinicians to assess and provide specific treatment for insomnia in patients with chronic fatigue as this might improve their treatment results. An aim for further research should be to investigate the effect of specified treatment for insomnia in patients with chronic fatigue.

Playing violent video games may provoke aggression. Psycho-physiological methods may provide knowledge about the underlying psychological processes. Most previous studies have been performed in laboratory settings at daytime with adults. Thus the aim of this thesis was to investigate psycho-physiological (autonomic and HPA related reactions), sleep-related and emotional responses in teenage boys to playing a violent and a non-violent video game at home before going to sleep. In Study I the autonomic responses differed between the violent and the non-violent game during playing and more distinctly during sleep. In Study II the HPA axis was not affected by video gaming at all. In Study III, the effect of habits of playing violent games was assessed (≤ 1h/day and ≥ 3h/day). High versus low experience of violent gaming were related to different autonomic, sleep-related and emotional processes at exposure to a violent and a non-violent game, during playing and during sleep. The present thesis demonstrated that violent and non-violent games induce different autonomic responses during playing and – more distinctly – during sleep. Frequent gaming seems to influence physiological, sleep-related and emotional reactions, possibly as an expression of desensitization processes.

Bipolar disorders and recurrent depressions are two common psychiatric disorders with a life time prevalence of approximately 1% and 8%, respectively. Despite treatment these patients suffer from affective symptoms up to 50% of the time, resulting in lower well-being. The average life length is also reduced with 10-15 years, mainly attributable to suicide and cardiovascular disease. Increased stress is one of many factors that have been shown to be linked to an increased risk for developing affective disorders and some comorbid somatic conditions such as metabolic disturbances and cardiovascular disease. An increased stress level is known to cause hyperactivity of the hypothalamic-pituitary-adrenal-axis (HPA-axis) with increased cortisol secretion. Hyperactivity of the HPA-axis (or hypercortisolism) is one of the most replicated neurobiological finding in depression. In other stress related disorders it has however been shown that prolonged stress over long periods of time can lead to a state of low HPA-axis activity, hypocortisolism. Since persons with recurrent affective disorders such as bipolar disorder and recurrent depression are exposed to a high degree of recurrent and chronic stress it could be expected that in addition to hypercortisolism, a state of hypocortisolism could also develop in these disorders, potentially exerting an influence upon the psychological and somatic wellbeing among these patients. The major aim of this thesis was to evaluate whether hypocortisolism is related to relevant psychiatric and somatic phenotypes in recurrent affective disorders. In bipolar disorder, individuals with hypocortisolism exhibited a higher degree of depression and low quality of life compared to patients with normal HPA-axis activity. In recurrent depression, individuals with hypocortisolism exhibited shorter leukocyte telomere length than patients with normal or high HPA-axis activity, which is an indication of an accelerated aging process. In a sample of both bipolar and recurrent depression patients, hypocortisolism was associated with an increased proportion of obesity, dyslipidemia and metabolic syndrome compared with patients with normal or high HPA-axis activity. Patients with recurrent depression showed a higher occurrence of hypocortisolism than the control sample representative of the general population. Patients with bipolar disorder showed a similar occurrence of hypocortisolism as the control sample. Among bipolar disorder patients with a low degree of lifetime with lithium prophylaxis, there was an inverse correlation between age and HPA-axis activity. In contrast, among patients with a higher degree of lifetime with lithium prophylaxis as well as among the controls, there was no correlation between age and HPA-axis activity. Accordingly, hypocortisolism was most common among older patients with a low degree of lifetime with lithium prophylaxis. In conclusion, hypocortisolism in both recurrent depression and bipolar disorder was associated with multiple clinically-relevant phenotypes. Additionally it was shown for bipolar disorder patients that increasing age was a risk factor for hypocortisolism and that prophylactic lithium treatment was a protective factor. It is argued that the protective effect of lithium towards the HPA-axis is attributable to its mood-stabilizing effect, which in turn reduces the chronic stress level. These results provide new insight into the role of hypocortisolism and chronic stress in recurrent affective disorders warranting further studies and hopefully providing clues to improved treatment strategies.

During adolescence, animals leave the natal home and interact with potentially threatening stimuli (i.e. stressors), e.g. unfamiliar environments and conspecifics. Adolescent stressors can result in fewer interactions with unfamiliar stimuli in adulthood, plausibly due to sustained effects of glucocorticoid exposure on stress physiology (e.g. glucocorticoid secretion and receptor expression). The current thesis tested the hypothesis that adolescent glucocorticoid exposure and social experiences act as stressors by quantifying the effects of the adolescent experiences on behavioural responses to unfamiliar stimuli and the underlying neuroendocrine mechanisms when in adulthood using two captive species, zebra finches and rats. In study one, adolescent zebra finches were dosed with the glucocorticoid corticosterone. In adulthood, birds dosed with corticosterone in early adolescence took longer to enter an unfamiliar environment when tested individually and had lower expression of the glucocorticoid receptor GR in the hippocampus and hypothalamus, brain regions that regulate stress responses. Glucocorticoids therefore appear to be an endocrine mechanism behind the long-term effects of adolescent stress. Subsequent studies explored whether higher social density and more unfamiliar social interactions during adolescence act as stressors. In study two, early adolescent zebra finches were housed in groups varying in conspecific number and density. In adulthood, females raised in larger groups secreted a higher stressor-induced corticosterone concentration and, if raised at lower density, spent more time in an unfamiliar environment when group housed. In study three, adolescent female rats were housed in familiar pairs or exposed to unfamiliar conspecifics. Unfamiliar adolescent interactions had no effects on responses to unfamiliar environments or stress physiology in adulthood, but heightened ultrasonic call rates. In this thesis, adolescent social experiences do not act like stressors, but modulate (especially female) social behaviour. Adolescent stressors and social experiences therefore have distinct effects on responses to unfamiliar stimuli and stress physiology that are maintained into adulthood.

No description available.

Este é o primeiro estudo detalhado do acidente do OLAPA (vazamento de óleo diesel de mistura) ocorrido em 2001. Objetivou avaliar a qualidade ambiental da área afetada, incluindo os pontos de contingência 2, 3 e 4; caracterizar o comportamento do óleo nos 4 diferentes compartimentos geológico-geomorfológicos existentes e identificar se ocorreram outros vazamentos na área. O setor mais contaminado é o Ponto Zero, onde o solo ainda apresenta concentração de TPH acima do Valor de Intervenção (VI) em 8 locais, de fenantreno em 2 locais e de benzo(a)antraceno, benzo(a)pireno e indeno(123-cd)pireno em um local, e a água de 1 poço apresentou TPH acima do VI. Devido aos caminhos preferenciais (raízes de arbustos e árvores), o terreno natural, foi bem mais afetado em profundidade a partir do fluxo superficial de óleo do que a área de domínio do duto; nesta, ocorreu alguma migração de óleo em subsuperfície, pela trincheira. No rio do Meio (Serra do Mar), em somente um local, o solo apresentou TPH acima do VI. Ocorrências de baixas concentrações de hidrocarbonetos, assim como evidências organolépticas, ainda são muito frequentes. Nas partes com maior declividade e vale bem encaixado, elas ocorrem no material argiloso (rocha alterada) que forma barrancos verticais na margem. Nos trechos de menor declividade, com depósitos aluviais mais significativos, o óleo se infiltrou lateralmente, através do freático, por distâncias de até 4 m do canal. Nestes casos, enquadram-se os Pontos de Contingência 2, 3 e 4. No Ponto 3, TPH ultrapassou o VI em 3 amostras de solo e em uma de água subterrânea. Nos Pontos 2 e 4 não ocorrem concentrações de hidrocarbonetos acima de VI. Este último é o local mais a jusante com evidências de contaminação; aparentemente foi bastante contaminado, mas, por ser constituído por aluvião extremamente grosseiro, fortemente aerado, o contaminante foi facilmente degradado. Não existem evidências de contaminação nos compartimentos zona de transição (médio rio Sagrado), planície aluvial (baixo rio Sagrado) e Complexo Estuarino de Paranaguá (rios do Neves e Nhundiaquara). O óleo que eventualmente atingiu o complexo, a partir de um fluxo muito bem canalizado no rio Sagrado, encontrou um ambiente dinâmico, com um tempo de renovação da água de apenas 3,5 dias em média, que tendeu a direcioná-lo para o mar e não a mantê-lo neste sistema. Estudos de quantificação e distribuição de HPA foram efetuados no solo dos dois locais mais contaminados (Ponto Zero e rio do Meio). As amostras apresentaram predomínio de compostos HPA de 2 e 3 anéis aromáticos, assim como o observado no óleo derramado, destacando-se principalmente, as séries de homólogos alquilados de naftalenos > fenantrenos > fluorenos > pirenos e crisenos, caracterizando aporte petrogênico. Entretanto, em apenas 2 casos (um em cada local) constatou-se a presença de contaminante não proveniente do óleo vazado, pois destacam-se os HPA de 4 a 6 anéis aromáticos, o que configura aporte pirolítico. / This is the first detailed study of the accident OLAPA (leakage diesel fuel mixture) occurred in 2001. Aimed to evaluate the environmental quality of the affected area, including points of contingency 2, 3 and 4; characterize the behavior of oil in four different geological and geomorphological compartments existing and identify whether there were other leaks in the area. The sector most contaminated is the Point Zero, where the soil still presents TPH concentration above the value of Intervention (VI) in 8 locations of phenanthrene in two places and benzo (a) anthracene, benzo (a) pyrene and indeno (123-cd) pyrene in one place, and water from a well presented TPH above the VI. Due to preferential ways (roots of shrubs and trees), the natural terrain was much more affected in depth from the surface flow of oil than the domain area of the duct; in this, there was some migration of oil in the subsurface, the trench . In the rio do Meio (Serra do Mar), in only one location, the soil showed TPH above the VI. Occurrences of low concentrations of hydrocarbons, as well as organoleptic evidence, are still very frequent. In parts with greater slope embedded well valley, they occur in the clayey material (weathered rock) that form vertical slope on the margin. In the section with lower slope, with the most significant alluvial deposits, the oil infiltrade laterally through the groundwater, for distances of up to 4 m of the channel. In these cases, fits Contingency Points 2, 3 and 4. In Point 3, TPH exceeded the VI in three soil samples and one of groundwater. In Points 2 and 4 did not occur hydrocarbon concentrations above VI. The latter is the place most the downstream with evidence of contamination; apparently was very polluted, but because it consists of very coarse alluvial, strongly aerated, the contaminant was easily degraded. There are not evidences of contamination in the transition zone compartments (medium Rio Sagrado) alluvial plain (low Rio Sagrado) and Paranagua Estuarine Complex (rio do Neves and Nhundiaquara). The oil which eventually reached the complex, from a well channeled in flow rio Sagrado, found a dynamic environment with a water renewal time of only 3.5 days on average, which tended to direct you to the sea and not keep it in this system. Studies of quantification and distribution of PAHs were made in the soil of two contaminated places most (Point Zero and rio do Meio). The samples showed a predominance of PAH compounds 2 and 3 aromatic rings, as well as observed in the oil spill, highlighting mainly the homologous series of alkylated naphthalenes> phenanthrenes> Fluorenes> pyrene and Chrysenes, featuring petrogenico input. However, in only 2 cases (one in each location) revealed the presence of contaminant not derived from the oil leak out, because highlights are the PAHs from 4 to 6 aromatic rings, which sets pyrolytic input.

Introdução: A neurobiologia dos transtornos de ansiedade (TA) é complexa e envolve interações ambientais e genéticas ainda não conhecidas. Esses transtornos, comumente, iniciam durante a infância e adolescência, persistindo ao longo da vida. O comprometimento da resposta biológica frente ao estímulo estressor, encontrado em muitos pacientes com TA, sugere a influência do eixo hipotálamo-hipófise-adrenal (HHA) nestes transtornos e, portanto, os polimorfismos associados ao eixo HHA poderiam ser estudados em genes candidatos. Os estudos que almejam entender a etiologia dos TA devem, também, explorar as alterações epigenéticas (incluindo a metilação do DNA) decorrentes das influências ambientais. Objetivos: Estudar, em adolescentes, polimorfismos genéticos funcionais do eixo HHA, interações Gene x Ambiente (G x A) e metiloma do DNA, considerando as diferentes trajetórias dos TA. Métodos: Foi realizada a extração de DNA das células do epitélio bucal de 228 adolescentes (131 casos e 97 controles para os TA) e foram genotipados, por PCR em tempo real, polimorfismos funcionais envolvidos com o eixo HHA (FKBP5: rs3800373, rs9296158, 3800373, rs9296158, 3800373, rs9296158, rs1360780, rs9470080 rs1360780, rs9470080 e rs4713916; NR3C1NR3C1 : rs6198;: rs6198;: rs6198; NR3C2NR3C2 : rs2070951;: rs2070951;: rs2070951; CRHR1CRHR1 CRHR1 : rs878886 : rs878886 e SERPINA6 SERPINA6 : rs746530) : rs746530) . Os participantes responderam à escala auto-aplicativa SCARED (Screen for Children Anxiety Related Emotional Disorder – Children rated) e realizaram entrevistas semiestruturadas para avaliação diagnóstica utilizando o K-SADS-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime). O questionário CTQ (Childhood Trauma Questionnaire) foi aplicado em 90 adolescentes (54 casos e 36 controles para os TA) para avaliar a interação entre o trauma emocional e o polimorfismo do gene NR3C2 nos níveis séricos de BDNF. Uma subamostra de adolescentes (n=47) foi reavaliada, cinco anos após a primeira coleta, através das mesmas entrevistas psiquiátricas e nova extração de DNA salivar. Alguns participantes, na última avaliação, responderam ao MINI (Mini International Neuropsychiatric Interview) apropriado para a idade atual. A amostra foi organizada em 4 grupos, conforme o diagnóstico dos TA e o ano da coleta de saliva (anos de 2008 e 2013): (1) Desenvolvimento típico da adolescência (Controle; n=14); (2) Incidentes para os TA (ITA; n=11); (3) Persistentes para os TA (Caso; n=14) e (4) Remitentes para os TA (RTA; n=08). O metiloma do DNA foi analisado com o Infinium HumanMethylation 450 BeadChip da Illumina. Resultados: Não foi encontrada associação entre os polimorfismos estudados e os TA. Em relação à interação G x A, sugere-se que o polimorfismo rs2070951 do gene NR3C2 modera a associação entre negligência física e os níveis séricos de BDNF. Do ponto de vista epigenético, foi observada, nos grupos ITA e RTA, vias biológicas com padrão homogêneo e relacionadas ao sistema nervoso. Já nos grupos casos e controles para os TA, foram evidenciadas vias biológicas com padrão mais heterogêneo. Um perfil de hipometilação do DNA foi predominante nas vias encontradas. Na análise transversal, nós encontramos padrões opostos de metilação do DNA, conforme o período desenvolvimental avaliado: hipometilação no início da adolescência e hipermetilação em jovens adultos. Conclusão: Esse estudo abordou, em uma amostra de adolescentes, aspectos genéticos (genes candidatos envolvidos com o eixo HHA), ambientais (trauma emocional) e epigenéticos (metiloma do DNA) dos TA. Os achados sugerem que, embora sem associações entre os TA e genes envolvidos no eixo HHA, existe uma interação entre a presença de trauma emocional, polimorfismo genético do eixo HHA e marcadores biológicos. Os achados do metiloma do DNA sugerem, também, influências epigenéticas no curso dos TA. Novos estudos devem ser delineados para corroborar as influências genéticas e ambientais neste transtorno. / Background: The neurobiology of Anxiety Disorders (AD) is complex and involves environmental and genetic interactions understood. These disorders may have their onset during childhood and adolescence, persisting throughout life. The impairment of biological response against the stressor stimulus, described in many patients with AD, suggests a possible role of genetic polymorphisms of the hypothalamic-pituitary-adrenal (HPA) axis in these individuals. Studies that aim to understand the etiology of AD should also explore the epigenetic changes (including DNA methylation) arising from environmental influences. Objective: To study, in adolescents, functional genetic polymorphisms of HPA axis, Gene x Environment (G x E) interactions and DNA methylome, considering different AD outcomes. Methods: Saliva DNA was extracted from 228 adolescents (131 cases and 97 controls to AD) and we genotyped, by real time PCR, the functional polymorphisms involved with HPA axis (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; 3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1NR3C1 : rs6198; : rs6198; : rs6198; NR3C2NR3C2 : rs2070951; : rs2070951; CRHR1CRHR1CRHR1 CRHR1: rs878886 and : rs878886 and : rs878886 and : rs878886 and SERPINA6 SERPINA6 SERPINA6SERPINA6 : rs746530) : rs746530) . Participants responded to the scale self-applied Screen for Children Anxiety Related Emotional Disorder – Children rated (SCARED) and were diagnosed according to the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (K-SADS-PL). The Childhood Trauma Questionnaire (CTQ) was applied in 90 adolescents (54 cases e 36 controls to AD) to evaluate the interaction between emotional trauma and the NR3C2 polymorphism in the serum levels of BDNF. A sub-sample of adolescents (n = 47) was reassessed five years after the first evaluation by the same psychiatric semi-structured interviews and new extraction salivary DNA was performed. Some participants in the last evaluation responded to Mini International Neuropsychiatric Interview (MINI), which is a semi structure interview appropriate for the present age. The sample was organized in four groups according to the diagnosis of AD and the year of saliva collection (2008 and 2013): (1) Typically Developing Controls (TDC; n = 14); (2) Incident Anxiety Disorder (IAD; n = 11); (3) Persistent Anxiety Disorder (PAD; n = 14); (4) Remittent Anxiety Disorder (RAD; n = 8). DNA methylome was evaluated with Infinium HumanMethylation450 BeadChip. Results: We did not find any association between the genetic polymorphisms and AD. Considering the G x E interaction we suggest that rs2070951 polymorphism of NR3C2 gene moderates the association between physical neglect and serum BDNF levels. When we evaluated the DNA methylome, we observed more homogeneous biological pathways and mostly related with nervous system in individuals from IAD and RAD groups. On the other hand, in the TDC and PAD groups, we found biological pathways with a more heterogeneous pattern. A DNA hypomethylation profile was found predominant in the pathways. In a cross-sectional analysis, we found opposite patterns of DNA methylation, as the developmental period assessed: hypomethylation at the beginning of adolescence and hypermethylation in young adults. Conclusion: This study addressed, in an adolescent sample, genetics (candidate genes linked to HPA axis), environmental (emotional trauma) and epigenetic (DNA methylome) aspects of AD. The findings suggest that although there are no associations between AD and genes involved in HPA axis, there is an interaction between the presence of trauma, genetic polymorphism involved in this axis and biomarkers. The DNA methylome findings also suggest epigenetic influences on the course of TA. Further studies should be designed to corroborate the genetic influences in this disorder.

A exaustão de um veículo de motor a diesel é uma importante fonte de poluentes atmosféricos, pois forma uma matriz complexa composta de poluentes regulados e não regulados pelos órgãos governamentais. Dentre os poluentes regulados podemos citar óxidos de nitrogênio (NOx) e material particulado. Os poluentes não regulados são pouco estudados até hoje e dentre estes encontra-se a classe dos hidrocarbonetos policíclicos aromáticos e seus derivados nitrados (nitro-HPA). Estes são encontrados na exaustão do diesel na forma gasosa ou agregados ao material particulado. Hoje, o interesse em estudos destes compostos vem aumentando, devido às suas atividades carcinogênicas e mutagênicas às quais estão sujeitas as populações dos centros urbanos. O impacto causado pelos nitro-HPA emitidos por motores a ciclo diesel ao ambiente não está ainda completamente estabelecido. Este estudo consiste na modelagem e simulação do processo de combustão de hidrocarbonetos na faixa de C1 a C4 com o objetivo de descrever a formação de compostos aromáticos, principalmente HPA, e óxidos de nitrogênio a partir de modelos cinéticos de combustão propostos na literatura como referência e fazendo uso do software de simulação Kintecus. Este projeto tem como objetivo em longo prazo propor um modelo cinético para combustão do óleo Diesel. Foi iniciada a construção de um modelo cinético de combustão a partir de modelos de hidrocarbonetos simples de C1 a C4, com formação de aromáticos, HPA e óxidos de nitrogênio. Os modelos originais foram avaliados e modificados a fim de estudar como parâmetros do modelo afetam a concentração das espécies de interesse. Foi observado a tendência de formação de benzeno e fulveno em baixas temperaturas e a tendência de formação de antraceno, pireno, fenantreno a temperaturas mais altas. Foi avaliado que a conversão NO-NO2 ocorre em maiores proporções em reações iniciadas a baixas temperaturas, 600 K. Os resultados indicam que propano é o maior responsável por esta conversão. O modelo final obtido resultou da união dos modelos de combustão Hori e Marinov mais inclusão do GRI-Mech 3.0 e reações adicionais de NOx retiradas da base de dados NIST / The diesel engine exhaust is an important source of air pollutants, which comprises a complex matrix of regulated and unregulated pollutants. The nitrogen oxides (NOx) and the particulate material are examples of regulated pollutants found in the engine exhaust. The unregulated pollutants are poorly studied until today, being the polycyclic aromatic hydrocarbons and its nitrated derivatives (nitro-PAH) a class of unregulated pollutant observed in diesel exhaust. The nitro-PAHs are observed in gas phase or aggregated to the particulate material. At the present, the interest in those compounds raised due to their carcinogenic and mutagenic properties, which the population of urban centers are subject. The environmental impact caused by nitro-PAH is not fully established. This study consists in the modeling and simulation of the hydrocarbons combustion process comprising the C1 to C4 hydrocarbons using kinetic models proposed in the literature as reference models and the Kintecus software. The purpose of the present study is to describe the formation of aromatic compounds, mainly PAH, and nitrogen oxides. The long term goal is to build a combustion model to Diesel oil. The kinetic model was constructed based on known combustion models of C1 to C4 hydrocarbons, which includes the formation of aromatics, PAH and nitrogen oxides. The original models were evaluated and modified to analyze how the model parameters affects the species concentration. There is a trend to the formation of benzene and fulvene at low temperatures, and a tendency to formation of antracene, pyrene and antracene at high temperatures. The NO-NO2 conversion was evaluated and the high rates of conversion was obtained in simulations started at temperature. The results indicates that propene is the major hydrocarbon that promotes the NO-NO2 conversion. The final model proposed is based in the combination of Marinov and Hori models with the inclusion of GRI-Mech 3.0 plus additional reactions extracted from NIST database