Alumínio Pulverizado Termicamente (TSA) é amplamente utilizado em instalações offshore como revestimento de ânodo de sacrifício em tubulações de aço carbono. O transporte e a instalação desses componentes podem levar a pequenos danos no revestimento, o que pode expor a superfície do aço à água do mar. Sabe-se que o depósito calcário é formado na superfície do aço polarizado catodicamente. Assim, esta pesquisa avaliou o TSA aplicado por sistema de pulverização de arco duplo (TWAS) no aço ao carbono S355J2 + N quando ocorrem danos (holidays) para estudar a formação de depósitos calcários no aço e adquirir dados sobre o desempenho do TSA sob altas temperaturas. A aplicação de diferentes condições também foi considerada: presença de selantes; liga do revestimento (99,5% de Al e Al-5% de Mg) e condições enterradas/não enterradas. Dois tipos de experimentos foram realizados: i) testes em potencial livre sob temperaturas constantes (30, 60 e 90°C) e diferentes tamanhos de holidays (expondo 5, 10 e 20% da superfície do aço) e ii) testes sob gradient térmico onde óleo a ~125°C foi adicionado em uma torre polimérica e água externa a ~10°C ficou em contato com a superfície das amostras (tanto potencial livre como polarização de -950 mVAg/AgCl foram aplicados). Análises incluíram inspeção visual, microscópio eletrônico de varredura e difração de Raio-X. A partir dos testes em temperaturas constante, o TSA atingiu um bom potencial de proteção (-800 a -900 mVAg/AgCl) e pouca diferença nos resultados devido à diferença na composição doTSA e no tamanho do holiday foi observada. As taxas de corrosão foram mantidas entre 0,02 e 0,01 mm/ano. No ensaio sob gradiente térmico e potencial livre, a perda de revestimento e as taxas de corrosão foram de 0,4 a 0,002 mm/ano. Além disso, o potencial alcançado foi de uma faixa menor do que a obtida anteriormente (-745 a -835 mVAg/AgCl). No entanto, quando o TSA foi combinado com proteção catódica externa e gradiente térmico, a espessura do TSA foi satisfatório e as taxas de corrosão obtidas foram inferiores a 0,076 mm/ano. O depósito calcário formado no holiday protegeu o aço contra a corrosão e seu mecanismo de crescimento baseado nesta pesquisa foi construído. / Thermally Sprayed Aluminium (TSA) is widely used in offshore facilities as sacrificial anode coating for carbon-steel risers and pipelines. Transportation and installation of those components can lead to small damages in the coating, which can expose the steel surface to the seawater. It is known that calcareous deposit is formed on the cathodically polarised steel surface. Thus, this research evaluated the TSA applied by twin wire arc spray system (TWAS) on S355J2+N carbon-steel when damage (holidays) is present in order to study the calcareous deposit formation on steel and acquire data regarding the TSA performance at high temperatures. Application of different conditions was also considered: presence of sealing; coating alloy (99.5%Al and Al-5%Mg) and buried/unburied conditions. Generally, two types of experiment were conducted – i) tests at free potential at steady temperatures (30, 60 and 90°C) and different holiday sizes (exposing 5, 10 and 20% of the steel surface) and ii) tests under thermal gradient where oil at ~125°C was added in polymeric tower and external water at ~10°C was in contact with the samples surface (both free potential and polarisation of -950 mVAg/AgCl were applied). Methodology of analyses included visual inspection, scanning electron microscope and X-ray Diffraction. From the tests at steady temperatures, the TSA reached a very good protective potential (-800 to -900 mVAg/AgCl) and little difference in results due to difference in TSA composition and holiday size was observed. Corrosion rates were kept between 0.02 and 0.01 mm/year. From the thermal gradient test under free potential, the coating loss and corrosion rates were 0.4 to 0.002 mm/year. Also, the potential achieved was in a lower range than previously obtained (-745 to -835 mVAg/AgCl). However, when TSA was combined with external cathodic protection and thermal gradient, the thickness of the TSA was satisfactory and corrosion rates obtained were below 0.076 mm/year. The calcareous deposit formed within the holiday protected the steel substrate against corrosion and its growth mechanism based in this research was built.

Introdução: A formação da memória envolve mudanças na expressão de genes neuronais. Remodelações epigenéticas da cromatina e modificações pós-traducionais reversíveis no DNA ou nas proteínas histonas representam mecanismos centrais na regulação da expressão gênica durante o desenvolvimento do cérebro e a aprendizagem inicial ou recuperação da memória. Desequilíbrios nos níveis de acetilação de histonas estão associados à uma ampla variedade de desordens cerebrais. Histonas deacetilases (HDACs) desempenham um papel fundamental na homeostase da acetilação de histonas e na regulação de atividades celulares fundamentais como a transcrição, tornando-as um foco de estudo. Evidências mostram que a administração de inibidores de histonas deacetilases (HDACis) restauram a memória associada à regulação da expressão gênica e melhora a memória em ratos. Estudos em modelos animais têm mostrado que a formação da memória envolve uma série de alterações bioquímicas em várias áreas do sistema nervoso central, entre as quais se destacam o hipocampo e a amígdala basolateral (BLA). Neste contexto, fármacos experimentais, como a tricostatina A (TSA), que atuam sobre mecanismos epigenéticos, têm sido recentemente propostos como potenciais terapias para o tratamento de disfunção cognitiva e memória associados a doenças neurológicas e psiquiátricas. Objetivo: Neste trabalho objetivamos compreender e elucidar o papel da acetilação de histonas em processos envolvidos na modulação da memória utilizando o fármaco TSA e se baseia na hipótese de que a atividade de HDACs é essencial para a modulação das respostas de aprendizado na tarefa de esquiva inibitória (IA). Métodos: Ratos Wistar foram canulados bilateralmente na amígdala. Os efeitos das micro-infusões intra-amigdalares de TSA foram observados na consolidação e na extinção da memória após o treino na tarefa de esquiva inibitória e nos níveis do fator neurotrófico derivado do cérebro (BDNF) na BLA e no hipocampo referentes à consolidação da memória. Resultados: Os resultados demonstraram que a infusão intra-amigdalar de TSA 1.5 h, 3 h e 6 h após o treino na tarefa de esquiva inibitória resulta na melhora da memória de longa duração (LTM). TSA acelerou a extinção da memória quando infundido imediatamente pós-teste. Além disso, aumentou os níveis de BDNF no hipocampo. Conclusão: Estes resultados indicam que eventos epigenéticos possuem um papel importante no aprendizado e na memória através da atividade de HDACs. / Introduction: Memory formation involves changes in the expression of neuronal genes. Epigenetic remodeling of chromatin and reversible post-translational modifications in the DNA or in the histone proteins represent central mechanisms in the regulation of gene expression during brain development and early learning or memory retrieval. Imbalances in the levels of histone acetylation are associated with a wide variety of brain disorders. Histone deacetylases (HDACs) play a key role in homeostasis of histone acetylation and regulation of fundamental cellular activities, such as transcription, making them a focus of study. Evidences shows that the administration of histone deacetylases inhibitors (HDACis) restore the memory associated with the regulation of gene expression and improves memory in rats. Studies in animal models have shown that memory formation involves a series of biochemical changes in several areas of the central nervous system, which the hippocampus and basolateral amygdala (BLA) are the most highlighted. In this context, experimental drugs, such as trichostatin A (TSA), that act on epigenetic mechanisms, have recently been proposed as potential therapies for the treatment of memory and cognitive dysfunction associated with psychiatric and neurological disorders. Objective: In this work we aimed to understand and elucidate the role of histone acetylation in processes involved in memory modulation using the drug TSA and is based on the hypothesis that HDACs activity is essential for the modulation of learning answers in the inhibitory avoidance (IA) task. Methods: Wistar rats were cannulated bilaterally in the amygdala. The effects of TSA micro-infusions into the BLA were observed in the consolidation and extinction of memory after training in the inhibitory avoidance task and the levels of brain-derived neurotrophic factor (BDNF) in the BLA and hippocampus related to memory consolidation. Results: The results demonstrated that the TSA infusion into BLA 1.5 h , 3 h and 6 h posttraining in the inhibitory avoidance task results in improved long-term memory (LTM). TSA accelerated the extinction of memory when infused immediately post-test. In addition, increased levels of BDNF in the hippocampus. Conclusion: These results indicate that epigenetic events play an important role in learning and memory by HDAC activity.

Aluminium alloys are widely used in the aerospace industry due to their lightweight and high specific strength. However, these alloys are particularly sensitive to localized corrosion in chloride environments and need to be protected by a robust system. One of the protection methodologies consists in anodizing. The produced layer increases the corrosion resistance and also serves as anchoring site for organic coatings application. Chromium-based anodizing has been usually employed, nevertheless, as chromate compounds are toxic for health and the environment, chromium-based surface treatments will be prohibited in the aerospace industry in a near future. Tartaric-sulphuric acid (TSA) anodizing is a promising environment compliant alternative, which is already being used at industrial level with appropriate corrosion protection and paint adhesion properties. This study aims at proposing a hybrid sol-gel treatment after TSA anodizing of AA2524 specimens in order to improve the corrosion resistance of the anodized layer while maintaining its compatibility with organic coatings. For this, anodic aluminium oxides (AAO) were produced at different anodizing voltages and protected by dip-coating with a hybrid sol-gel layer obtained from a tetraethoxysilane (TEOS) and 3-glycidoxypropyltrimethoxysilane (GPTMS) hydrolysis solution with high water content. Corrosion resistance evaluation was carried out by means of electrochemical impedance spectroscopy (EIS) in NaCl 0.1 mol L-1 and salt-spray chamber exposure (ASTM B117-11 standard). The morphology of the anodic porous layer was investigated by means of FE-SEM, whereas glow discharge optical emission spectroscopy (GDOES) was employed to evaluate the distribution of the sol-gel layer within the porous AAO. FE-SEM characterization confirmed that the layer properties (pore distribution, porosity and thickness) were strongly dependent on the anodizing conditions, whereas GDOES depth profile showed penetration of the hybrid coating within the pores of the anodized layer. The two characterization techniques showed inefficient surface sol-gel coverage for the samples anodized at higher voltage, likely due to insufficient sol-gel deposition. The results of the EIS characterization tests up to 1008 h (42 days) showed that, irrespectively to the anodizing voltage, the hybrid sol-gel protected AAO was stable with only slight evolution of the diagrams with immersion time. Moreover, the hybrid coating protected samples presented higher low frequency impedance modulus than hydrothermally sealed (HTSed) reference TSA anodized samples, which was confirmed by electrical equivalent circuit (EEC) fitting of the EIS data. EEC fitting also revealed that the resistance of the pores to electrolyte penetration was increased by the application of the sol-gel coating when compared to the resistance of the HTSed reference samples and indicated better anticorrosion performance for the sample anodized at 16 V. These results were confirmed by the salt-spray tests. Investigation on the ageing of the hybrid sol-gel hydrolysis solution showed that its viscosity hardly changed up to two weeks of test and that hybrid coatings applied from these solutions were stable and afforded good corrosion protection to the TSA anodized substrate, an improvement of the anticorrosion properties of the hybrid coating was verified for an ageing time of 168 h. Preliminary tests performed with a solvent-free organic coating (epoxy) indicated good compatibility with the hybrid TEOS-GPTMS coating characterized by very high impedance and good stability upon exposure to the salt-spray chamber. / Ligas de alumínio são muito utilizadas na indústria aeronáutica por serem materiais leves e altamente resistentes. Porém, essas ligas são particularmente sensíveis à corrosão localizada em meios que contêm cloretos, e precisam de sistemas robustos de proteção. Uma das metodologias de proteção consiste em anodização. A camada produzida aumenta a resistência à corrosão e também serve como sítio de ancoragem para aplicação de revestimentos orgânicos. A anodização crômica tem sido usualmente empregada na indústria aeronáutica. No entanto, como compostos contendo íons cromato são tóxicos para a saúde e para o meio-ambiente, tratamentos de superfície à base de cromo serão proibidos na indústria espacial em um futuro próximo. Anodização em banho de ácido sulfúrico-tartárico (TSA) é uma alternativa promissora e ambientalmente compatível, a qual já está sendo usada industrialmente com apropriada proteção à corrosão e adesão para pintura. Este estudo tem como objetivo propor um tratamento utilizando um revestimento híbrido sol-gel para melhorar a resistência à corrosão da liga AA2524 anodizada em TSA e que mantenha sua compatibilidade com revestimentos orgânicos. Para isso, camadas anodizadas de alumínio (CAA) foram produzidas em diferentes voltagens e protegidas por camada de híbrido sol-gel obtida pela hidrólise de tetraetilortosilano (TEOS) e glicidóxipropiltrimetóxisilano (GPTMS) em solução com alto teor de água e aplicada pela técnica de dip-coating. A avaliação da resistência à corrosão foi realizada através de espectroscopia de impedância eletroquímica (EIS) em NaCl 0,1 mol.L-1 e por exposição à câmara de névoa salina (norma ASTM B117-11). A morfologia da camada porosa foi investigada por MEV e a espectroscopia de emissão óptica por descarga luminescente (GDOES) foi empregada para avaliar a distribuição do híbrido sol-gel no interior dos poros da camada porosa. As caracterizações por MEV confirmaram que as propriedades da camada (distribuição dos poros, porosidade e espessura) são fortemente dependentes das condições de anodização, e a composição em profundidade obtida por GDOES mostrou que o revestimento híbrido penetrou nos poros da camada anodizada. As duas técnicas de caracterização mostraram uma cobertura ineficiente da camada sol-gel para as amostras anodizadas nas voltagens mais elevadas, provavelmente devido à deposição insuficiente do híbrido. Os testes de EIS com duração de até 1008 h (42 dias) mostraram que, independentemente da voltagem de anodização empregada, a camada anódica coberta com sol-gel ficou estável ocorrendo apenas pequenas evoluções dos diagramas com o tempo de imersão. Além do mais, as amostras protegidas com o revestimento híbrido apresentaram maiores valores de módulo de impedância em baixa frequência do que as amostras anodizadas em TSA e hidrotermicamente seladas (HTsed) usadas como referências. Essa tendência foi confirmada pelo ajuste com circuitos elétricos equivalentes (EEC) dos resultados de EIS que também mostrou que a aplicação do sol-gel híbrido torna mais difícil a penetração do eletrólito agressivo nos poros da camada anodizada quando comparada com as amostras HTSed, e indicou melhor desempenho anticorrosivo para a amostra anodizada em 16 V. Esses resultados foram confirmados pelos testes de névoa salina. A investigação do envelhecimento da solução de sol-gel mostrou pouca mudança na viscosidade da solução de hidrólise em duas semanas de testes e que os revestimentos híbridos aplicados a partir dessas soluções foram estáveis e promoveram boa proteção à corrosão para as amostras anodizadas em TSA, com melhora das propriedades anticorrosivas após 168 h de envelhecimento. Testes preliminares realizados com revestimento orgânico livre de solvente (epóxi) indicaram boa compatibilidade deste com o revestimento híbrido TEOS-GPTMS. O revestimento epóxi propiciou valores de módulo de impedância elevados e estáveis e também boa estabilidade após exposição à câmara de névoa salina quando aplicado sobre o revestimento híbrido aplicado sobre a liga 2524.

De nombreuses études ont montré que les Troubles du Spectre de l’Autisme ont un impact significatif surla vie quotidienne de l’enfant et de son entourage, plus particulièrement de sa famille et ses parents. Lesrecherches dans ce domaine se sont donc de plus en plus centrées sur la famille, permettant l’apport deressources, de supports ou de services. En effet, leur rôle dans l’accompagnement de l’enfant est essentiel,et un soutien adapté aux parents c’est également un soutien indirect à l’enfant. Cependant, la disponibilitédes services à destination des parents reste insuffisante, et ces derniers sont très peu associés à la miseen place d’interventions correspondant à leurs besoins, alors qu’ils sont les premiers utilisateurs desdispositifs proposés.L’étude 1 propose la traduction et la validation du Family Needs Questionnaire (renommé Questionnairedes Besoins Familiaux – QBF). Les résultats montrent de bonnes qualités psychométriques, ce quiindique que cet instrument peut être utilisé pour évaluer les besoins des parents d’enfants avec TSA enpopulation française. L’objectif de l’étude 2 est d’explorer les besoins des mères d’enfants avec TSA, enutilisant deux méthodes d’évaluation : une évaluation quantitative grâce à des questionnairesd’évaluation des besoins, dont le QBF, et une évaluation qualitative par des entretiens et une questionouverte. Concernant l’étude 3, il s’agit de comparer les besoins des parents d’enfants avec TSA et desparents d’enfants dysphasiques. Les résultats de ces études montrent que les besoins principaux desparents d’enfants avec TSA sont des besoins centrés sur l’école, centrés sur la vie sociale de leur enfant, etdes besoins en temps de répit. Ces résultats sont retrouvés par l’utilisation des deux méthodesd’évaluation, et ne sont pas retrouvés chez les parents d’enfants dysphasiques, ce qui indique que ce sontdes besoins spécifiques aux parents d’enfants avec TSA. Enfin, l’étude 4 présente une étude longitudinalequi évalue l’impact d’un programme d’interventions à domicile permettant un temps de répit aux parentsd’enfants avec TSA. Aucun impact n’a été trouvé sur les variables évaluant la qualité de vie, bien que lasatisfaction des parents vis à vis de ce programme ait été élevée. / Many studies have highlighted that Autism Spectrum Disorders (ASD) have a significant impact on theindividual’s daily life, and his/her relatives (i.e. family and parents). Research in this area has thereforeincreasingly focused on the family, providing resources, support and services. Indeed, their role in thechild’s support is of prime importance, and appropriate support for carers is also indirect support for thechild. While parents are the primary users of the proposed devices, availability of such services stillremain inadequate, and do not play an important role in the implementation of interventionsStudy 1 aims to translate and validate a French version of the Family Needs Questionnaire (FNQ). Theresults have demonstrated good psychometric validity, suggesting that this instrument is adequate toevaluate family needs in a sample of French parents of children with ASD. Study 2, assesses the needs ofmothers of children with ASD, using the FNG-Fr and the Family Needs Survey. Qualitative measures suchas open questions and semi-structured interviews were also used. Study 3 focuses on evaluation of thefamily needs by comparing parents of children with ASD and parents of children with Specific LanguageImpairments (SLI). School-centered needs, needs for child’s social life and respite time needs were ratedas the most unmet needs by parents of children with ASD. Findings from semi-structured interviews andopen question have also highlight such needs that were significantly different compared to those ofparents of with SLI, suggesting specific needs for parents of children with ASD. And study 4 was based ona longitudinal design for evaluating the impact of an at-home intervention program, allowing a respitetime for the families. While parental satisfaction was high, no impact on variables assessing parents’quality of life was found.

De par la richesse et la nature des informations qu’il véhicule, le visage joue un rôle essentiel dans les interactions sociales. Les difficultés que manifestent dès le plus jeune âge les personnes présentant un Trouble du Spectre de l’Autisme (TSA) sur le plan de l’interaction sociale ont conduit à s’intéresser aux modalités de traitement du visage dans cette population. Les travaux de cette thèse ont pour but d’explorer le traitement du visage chez les jeunes enfants avec un TSA, âgés de 24 à 60 mois, au moyen de la technique de suivi du regard. Dans la première étude, nous montrons que les jeunes enfants avec un TSA, comme les enfants typiques, sont sensibles à la visagéité d’un objet, ce qui suggère un traitement de la configuration de premier ordre. Ce résultat suggère que la nature des représentations faciales dans les TSA n’est pas qualitativement différente de celle des personnes typiques. Dans la seconde étude, nous testons la présence d’un biais du regard vers l’hémichamp visuel gauche en réponse à un visage présenté en vision centrale. Les résultats de cette étude indiquent que les jeunes enfants avec un TSA ne présentent pas ce biais du regard, ce qui pourrait refléter une altération de la dominance hémisphérique droite pour le traitement du visage dans les TSA. Enfin, dans la troisième étude, l’analyse du parcours visuel des jeunes enfants avec un TSA sur les visages révèle une exploration atypique concentrée au niveau de la région des yeux. Dans l’ensemble, ces études suggèrent que même si les enfants avec un TSA traitent les visages à partir de leur configuration, la manière d’y parvenir pourrait être différente. Des études futures devront spécifier les mécanismes du traitement configural du visage dans les TSA. / Faces are important for social interactions as they convey important information about social environment. Impairment in social interactions is one of the core symptoms of Autism Spectrum Disorders (ASD) and has been related to atypical face processing. Here, we investigated face processing in preschool children with ASD using eye-tracking methodology. In the first study, we showed that young children with ASD, just like typically developing children are sensitive to face-like objects suggesting that processing first order configuration is intact in ASD. According to these results, the nature of facial representation might be qualitatively similar between groups. In the second study, we tested the presence of a left gaze bias in response to faces presented at central vision. A lack of left gaze bias was found in young children with ASD, reflecting atypical right hemispheric lateralization for face processing. Finally, the third study analyzed the visual scanning of static faces and showed an abnormal exploration pattern limited to the eyes. Overall, these studies argue for the presence of configural face processing in preschoolers with ASD despite differences in strategy from typically developing children. Futures studies will have to specify the mechanisms underlying atypical configural face processing in ASD.

Tato diplomová práce se především zabývá vztahem národního hospodářství a cestovního ruchu, jejich vzájemného vymezení a působení. Velký prostor je také věnován satelitnímu účtu cestovního ruchu, který slouží jako nástroj ke statistickému zachycení těchto vlivů. Toto téma je dále pak z praktického hlediska znázorněno na dvou ukázkových zemích, na České republice a Chorvatsku. Po uvedení do problematiky, která je obsahem první kapitoly, je v druhé kapitole nastíněn vývoj cestovního ruchu ve světě a jeho pohled do budoucnosti. Třetí kapitola rozebírá satelitní účet cestovního ruchu, jeho metodologii, tvorbu, aplikaci a výsledky v obou srovnávaných zemích, a to jak z pohledu národních tak mezinárodních statistik. Ve čtvrté kapitole jsou samostatně analyzovány jednotlivé vlivy cestovního ruchu na národní hospodářství s konkrétní ukázkou v obou výše zmíněných zemích. Poslední kapitola obsahuje srovnání České republiky a Chorvatska dle mezinárodní statistik.

This master’s thesis applies dielectric relaxation spectroscopy to analyse impact of climatic changes on dielectric properties of composite material samples (TSA 220S varnish combined with 60.030 mica). Experiments aim to analyse effect of mica composite mass ratio (0, 4, 8 and 16 % of mica), relative humidity (0, 33, 55, 65, 75 and 95 %) and temperature (23, 30, 40 and 50 C) on complex permitivity as a function of frequency.

[ES] Esta tesis explora en profundidad la viabilidad técnica y las prestaciones de un sistema de transmisión para comunicaciones ópticas, de bajo coste y alta velocidad, basado en la multiplexación por división de frecuencia ortogonal (OFDM) mediante la implementación de los algoritmos de procesamiento digital de la señal en tiempo real sobre dispositivos de lógica programable (FPGA). Los sistemas de transmisión de modulación de intensidad y detección directa (IM/DD) parecen ser la solución más interesante para las redes ópticas pasivas (PONs) de bajo coste que serán necesarias para responder a la gran demanda de tráfico de los próximos años, producto del aumento significativo de dispositivos conectados a internet, servicios y programas en la nube, vídeo de alta definición, entre otros. Por tanto, esta tesis tiene como objetivo principal obtener la máxima tasa binaria y eficiencia espectral posible de un sistema IM/DD OFDM en PON (de una sola banda y una sola longitud de onda). Con esta finalidad se ha desarrollado la arquitectura hardware de un receptor OFDM de alta velocidad que opera en tiempo real en un dispositivo FPGA Virtex-7 a una frecuencia de reloj de 312,5 MHz utilizando un conversor analógico digital con una tasa de muestreo de 5 GS/s. Para lograr las mejores prestaciones posibles, se ha intentado aprovechar al máximo el ancho de banda del sistema (acercándose al límite de Nyquist) y se ha realizado una carga variable de las subportadoras del símbolo OFDM atendiendo a las características del canal electro-óptico. Además, se han diseñado e implementado los algoritmos de procesamiento necesarios para la detección y demodulación de los símbolos OFDM, y se ha desarrollado una plataforma experimental que ha permitido validarlos en tiempo real a través de un enlace de fibra monomodo estándar (SSMF). El principal resultado de esta tesis es el haber demostrado experimentalmente que con el sistema propuesto se puede alcanzar una tasa binaria de 19,63 Gb/s y una eficiencia espectral de 8,07 bit/s/Hz sobre 20 km de SSMF, lo cual implica casi duplicar las mejores prestaciones publicadas hasta la fecha. Para completar el diseño del receptor, se ha desarrollado un algoritmo de sincronización de tiempo basado en la correlación cruzada entre un preámbulo conocido y la señal OFDM recibida, el cual presenta una tasa de error extremadamente baja, aun en condiciones de muy baja SNR, y su diseño optimizado requiere menos recursos que otros sincronizadores publicados hasta la fecha. También se ha desarrollado un procesador de FFT de longitud variable mediante una arquitectura paralela segmentada que permite alcanzar hasta una tasa de 10 GS/s en dispositivos Virtex-7 con una eficiencia (área/velocidad) superior a la de otros trabajos publicados, y un ecualizador de canal basado en una técnica de estimación y compensación en frecuencia, que utiliza un preámbulo característico para poder disminuir la complejidad hardware y aumentar la precisión de la estimación. Todos los algoritmos implementados en esta tesis doctoral han sido diseñados para procesar 16 muestras en paralelo, y así poder reducir la frecuencia de reloj (5 GHz/16) hasta valores aceptables para los dispositivos FPGA. / [CA] Aquesta tesi explora en profunditat la viabilitat tècnica i les prestacions d'un sistema de transmissió per a comunicacions òptiques, de baix cost i alta velocitat, basat en la multiplexació per divisió en freqüència ortogonal (OFDM) mitjançant la implementació d'algorismes de processat digital del senyal en temps real sobre dispositius de lògica programable (FPGA). Els sistemes de transmissió de modulació d'intensitat i detecció directa (IM/DD) semblen ser la solució més interesant per a les xarxes òptiques passives (PON) de baix cost que seran necessàries per respondre a la gran demanda de tràfic dels propers anys, producte de l'augment significatiu de dispositius connectats a Internet, serveis i programari al núvol, vídeo d'alta definició, entre d'altres. Per tant, aquesta tesi té com objectiu principal obtenir la màxima taxa binaria i eficiència espectral possible d'un sistema IM/DD OFDM en PON (amb una sola banda i una sola longitud d'ona). Amb aquesta finalitat s'ha desenvolupat l'arquitectura hardware d'un receptor OFDM d'alta velocitat que treballa en temps real a un dispositiu FPGA Virtex-7 amb una freqüència de rellotge de 312,5 MHz utilitzant un convertidor analògic a digital amb una taxa de mostreig de 5 GS/s. Per aconseguir les millors prestacions possibles, s'ha intentat aprofitar al màxim l'ample de banda del sistema (aproximant-se al límit de Nyquist) i s'ha realitzat una càrrega variable de les subportadores del símbol OFDM atenent a les característiques del canal electró-òptic. A més, s'han dissenyat e implementat els algorismes de processament necessaris per la detecció i desmodulació dels símbols OFDM, i s'ha desenvolupat una plataforma experimental que ha permès validar-los en temps real a través d'un enllaç de fibra monomode estàndard (SSMF). El principal resultat d'aquesta tesi és haver demostrat experimentalment que amb el sistema proposat es pot arribar a una taxa binaria de 19,63 Gb/s amb una eficiència espectral de 8,07 bits/s/Hz sobre 20 km de SSMF, la qual cosa implica quasi duplicar les millors prestacions publicades fins aquest moment. Per completar el disseny del receptor, s'ha desenvolupat un algorisme de sincronització de temps basat en la correlació creuada entre un preàmbul conegut i el senyal OFDM rebut, el qual presenta una taxa d'error extremadament baixa, inclòs en condicions de molt baixa SNR, i el seu disseny optimitzat requereix menys recursos que altres sincronitzadors publicats fins el moment. També s'ha desenvolupat un processador de FFT de longitud variable mitjançant una arquitectura paral·lela segmentada que permet arribar fins una taxa de 10 GS/s en dispositius Virtex-7 amb una eficiència (àrea/velocitat) superior a la d'altres treballs publicats, i un equalitzador de canal basat en una tècnica d'estimació i compensació en freqüència, que utilitza un preàmbul característic per poder disminuir la complexitat hardware i augmentar la precisió de l'estimació. Tots els algorismes implementats a aquesta tesi doctoral han sigut dissenyats per processar 16 mostres en paral·lel, i així poder reduir la freqüència de rellotge (5 GHz/16) fins valors acceptables pels dispositius FPGA. / [EN] This thesis presents an in-depth exploration of the technical feasibility and achievable performance of a low-cost and high-speed optical communication system based on orthogonal frequency division multiplexing (OFDM) through the implementation of real-time digital signal processing algorithms over programmable logic devices (FPGA). Optical transmission systems based on intensity modulation and direct detection (IM/DD) is considered as one of the most interesting solutions for the deployment of the low-cost passive optical networks (PONs) that will be needed to cover the high traffic demand in the coming years. This demand is fueled, among others, by the significant increase of connected devices to the Internet, services and programs in the cloud, high definition video, etc. The main objective of this thesis is to achieve the maximum bitrate and spectral efficiency of an IM/DD PON OFDM system (using a single band and a single wavelength). To this end, the hardware architecture of a high-speed real-time OFDM receiver, including all the necessary algorithms to perform the detection and demodulation of the OFDM symbols, has been implemented in a Virtex-7 FPGA device at a clock frequency of 312.5 MHz using a digital analog converter with a sampling rate of 5 GS/s. To reach the best possible performance, all the system bandwidth has been employed and the OFDM subcarriers have been loaded according to the characteristics of the electro-optical channel. An experimental platform for optical transmission through standard single-mode fiber (SSMF) has been developed to evaluate in real-time the performance of the implemented receiver. The main result of this thesis is the experimental validation of the proposed system that has achieved a bit rate of 19.63 GS/s and a spectral efficiency of 8.07 bit/s/Hz over 20 km SSMF. These results almost double the best performance published to date. The receiver implementation included the design and development of several algorithms. First, it was designed a time synchronization algorithm (TSA) based on the cross-correlation between a known preamble and the received OFDM signal. This TSA has a good performance in low-SNR scenarios and its optimized design requires fewer resources than other synchronizers published in the literature. Second, a variable length parallel pipelined FFT processor has been implemented in a Virtex-7 device, it reaches a throughput of 10 GS/s with an efficiency (area/speed) higher than that of other published works. And finally, a channel equalizer working in the frequency domain to estimate and compensate channel distortions, which uses a known preamble to decrease the hardware complexity and increase the accuracy of the estimation, has been implemented. All the algorithms in this thesis have been developed to process 16 samples in parallel, thus reducing the required clock frequency (5 GHz/16) to acceptable values for the FPGA devices. / Deseo expresar mi gratitud a las autoridades de la Facultad Regional Buenos Aires de la Universidad Tecnológica Nacional por el apoyo económico y personal recibido durante la realización de esta tesis. / Bruno, JS. (2019). Algoritmos y arquitecturas hardware para la implementación de OFDM en sistemas de comunicaciones ópticos [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/119988 / TESIS

DNA methylation and histone modifications have emerged as key mechanisms in transcriptional regulation. The target of methylation-induced silencing 1 (TMS1) is a bipartite protein. Recent studies have indicated that methylation-associated silencing of TMS1 occurs in many cancers. However, whether and how TMS1 is regulated by epigenetic mechanisms in cancers remains unknown. In this study we showed that methylation of the TMS1 promoter occurred in five of six hepatocellular carcinoma (HCC) cell lines. TMS1 expression was reduced in four HCC cell lines and correlated with methylation status. Furthermore, the TMS1 promoter was completely methylated and mRNA expression was undetectable. TMS1 expression could be restored by 5-aza-2′-deoxycitidine (5-Aza-dC) (a DNA methyltransferase inhibitor) or trichostatin A (TSA) (a histone deacetylase inhibitor) alone and the promoter methylation. was partially reversible. TSA was more efficient than 5-Aza-dC in inducing TMS1 expression, and the combination of 5-Aza-dC and TSA resulted in markedly synergistic reactivation of the gene and completely reversed promoter methylation. Interestingly, TMS1 promoter methylation-associated gene silencing was accompanied by histone H3 Lysine 9 (H3K9) hypoacetylation and trimethylation. 5-Aza-dC and/or TSA also had some effect on conversion of methylated to acetylated H3K9 in restoring TMS1. This conversion was dynamic at the TMS1 promoter and a decrease in H3K9 trimethylation preceded an increase in H3K9 acetylation after 5-Aza-dC and/or TSA treatment. Our results thus suggest that epigenetic inactivation of TMS1 expression is regulated by promoter hypermethylation and H3K9 modifications in a coordinated way.

Vitamin D plays an important role in preserving healthy bones, and has additional roles in the body, including modulation of cell growth, differentiation, neuromuscular and immune function, and anti-inflammatory function. The vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily and regulates transcription of vitamin D-dependent target genes, such as those for key proteins involved in calcium and phosphorus absorption and bone development. Histone acetylation weakens the association of histones with DNA, and increases the accessibility of transcriptional regulatory proteins to chromatin templates, thereby increasing transcriptional activity of gene expression. Histone deacetylases remove the acetyl groups and condense chromatin structure, thereby preventing transcription. TSA is a potent histone deacetylase inhibitor and can significantly enhance gene expression. Bioactive food component, sulforaphane (SFN) is found in cruciferous vegetables and is known to be a histone deacetylase inhibitor, leading to transcriptional activation of gene expression. The objective of this study is to demonstrate that the bioactive food components modulate vitamin D action in adipocytes. To investigate the effects of TSA and SFN on vitamin D response, 3T3L1 mouse preadipocytes were treated with the combination of various concentrations of 1,25(OH)2 vitamin D, TSA, and SFN. Upon harvesting cells, the amounts of 24-hydroxylase mRNA, marker of vitamin D response, were measured by semiquantitative reverse transcriptase-PCR analysis. The results showed that the cells treated with 1μM TSA increased 1,25(OH)2 vitamin D-induced CYP24 mRNA level nearly 3.5-fold (p < 0.05) at 1nM 1,25(OH)2 vitamin D and nearly 2.5-fold (p < 0.05) in 10 nM 1,25(OH)2 vitamin D, and the cells treated with 5μM SFN increased 1,25(OH)2 vitamin D-induced CYP24 mRNA level nearly 1.4-fold at 1nM 1,25(OH)2 vitamin D and nearly 1.2-fold at 10 nM 1,25(OH)2 vitamin D.