Orientador: Louis Bernard Klaczko / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T08:34:55Z (GMT). No. of bitstreams: 1 Brianti_MitsueTaukeuti_D.pdf: 10353784 bytes, checksum: 0344027abe18c39b3dd4826fe982299a (MD5) Previous issue date: 2009 / Resumo: Acredita-se que no gênero Drosophila, o subgênero Drosophila é procedente do subgênero Sophophora e deu origem a outros gêneros e subgêneros e, particularmente, a duas radiações: virilis-repleta e immigrans-Hirtodrosophila. Esta última teve uma origem paleotropical, onde inicialmente se diversificou e se expandiu, enviando a radiação tripunctata aos Neotrópicos. A radiação tripunctata sofreu uma diversificação neotropical importante e atualmente é composta por 9 grupos de espécies adaptadas a áreas florestais. Este projeto se insere num amplo contexto de compreender a evolução da radiação tripunctata de Drosophila. Para isso foram usadas duas abordagens: a) analisamos a posição do rDNA nos cromossomos mitóticos de 16 espécies da radiação tripunctata; b) e, com cromossomos politênicos, focalizamos nossa atenção no estudo detalhado de um agrupamento monofilético dentro do grupo tripuntata - o agrupamento de espécies relacionadas com D. mediopunctata (D. mediopunctata, D. unipunctata e D. roehrae) - usando métodos de citogenética clássica e molecular. Deste modo os objetivos deste trabalho foram: - Examinar a variação da posição dos genes codificantes do RNA ribossomal (rDNA) em espécies da radiação tripunctata. - Produzir fotomapas de cromossomos politênicos de D. roehrae e D. unipunctata. - Caracterizar as inversões cromossômicas (pontos de quebra) que ocorrem em populações de D. roehrae e D. unipunctata - Identificar os elementos cromossômicos de Muller pela localização, através de hibridação in situ, de genes de cópia única de D. melanogaster em cromossomos politênicos das espécies D. mediopunctata, D. roehrae e D. unipunctata. As conclusões gerais foram: - A presença de uma NOR em cada cromossomo sexual é uma condição ancestral no gênero Drosophila e este caráter é bem conservado neste gênero. - Os cromossomos politênicos das três espécies são bem similares, sendo possível determinar com relativa facilidade a homologia dos cromossomos menos polimórficos. - Existe um padrão de polimorfismo de inversões entres os elementos de Muller nestas espécies: o elemento E é o mais polimórfico, com muitas inversões em cada espécie; o elemento C é o segundo mais polimórfico, enquanto B e D são os menos polimórficos. - Drosophila unipunctata apresenta uma conformação cariotípica singular, a despeito das espécies D. mediopunctata e D. unipunctata serem consideradas filogeneticamente mais próximas que D. roehrae, o que sugere uma rápida evolução cromossômica / Abstract: In the genus Drosophila, the subgenus Drosophila arose from the subgenus Sophophora and subsequently gave rise to various subgenera and genera, and to two particularly important radiations: virilis-repleta and immigrans-Hirtodrosophila. The latter originated in the Paleotropics, where it initially diversified and expanded, taking the tripunctata radiation to the Neotropics. The tripunctata radiation suffered significant Neotropical diversification and, at present, is composed of nine species groups adapted to forest habitats. The ultimate aim underlying this project is to understand the evolution of the tripunctata radiation of Drosophila. To address this matter, two approaches were used: a) we investigated the rDNA position, on mitotic chromosomes, in 16 species of the tripunctata radiation; b) and, with polytene chromosomes, we focused our attention in the detailed study of three closely related species of the tripunctata group. (d. mediopunctata, D. unipunctata and D. roehrae) - using classical and molecular cytogenetic analysis. More specifically, we aimed to: - investigate the rDNA position in species of tripunctata radiation through in situ hybridization on mitotic chromosomes. - prepare photomaps of the polytene chromosome of D. roehrae and D. unipunctata, locating the breaking points of the inversions. - identify Muller's elements, in polytene chromosomes of D. mediopunctata, D. roehrae and D. unipunctata through in situ hybridization using genes of D. melanogaster as probes. Our conclusions were: - The presence of a single nucleolus organizer region (NOR) on each sex chromosome is an ancestral and conserved state in the genus Drosophila. - Drosophila mediopunctata, D. roehrae and D. unipunctata have similar polytene chromosomes, which allowed us to establish the homology of chromosomal elements through the comparison of banding patterns. - In these species, the distribution of breaking points through the Muller's elements is non-random: element E is the most polymorphic, with many inversions in each species; and element C is the second most polymorphic; while B and D are the least polymorphic. - With the help of molecular genetic markers it has been previously established that D. mediopunctata is more closely related to D. unipunctata than to D. roehrae. However, D. unipunctata shows a notably different karyotype configuration, which suggests rapid chromosomal evolution / Doutorado / Genetica Animal e Evolução / Doutor em Genetica e Biologia

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Esta tese aborda diversos temas em evolução molecular, usando extensivamente o formalismo de funções geratrizes para obter resultados analíticos sempre que possível. Em primeiro lugar, apresenta-se a solução exata para o comportamento dinâmico de uma população infinita de seqüências infinitamente longas (não há mutações reversas) evoluindo sob a ação de mutações deletérias em um relevo adaptativo multiplicativo ou truncado. Além disso, foi estudado o comportamento de uma população submetida a sucessivas diluições de intensidades arbitrárias, como ocorre em alguns protocolos de evolução experimental. Foram obtidas expressões matemáticas que, em princípio, podem ser úteis na caracterização de populações reais de microorganismos. Demonstrou-se também que um processo estocástico de ramificação multidimensional generalizado é uma excelente ferramenta para analisar numericamente os efeitos da degeneração mutacional (especificamente, de um fenômeno denominado catraca de Muller) em populações sob variadas condições de crescimento exponencial. Finalmente, simulações foram extensivamente utilizadas para analisar a história evolutiva de populações finitas e averiguar a possibilidade de certas grandezas, como certas medidas da topologia de árvores genealógicas, serem empregadas na elaboração de testes estatísticos capazes de detectar as marcas deixadas pela seleção natural. / This thesis discusses some topics of molecular evolution, extensively using generating function methods to find analytical results whenever possible. In first place, it gives the exact solution for the dynamics of an infinite population of infinitely long sequences (no back mutations) evolving under the action of deleterious mutations on either multiplicative or truncated fitness landscapes. In addition, the behavior of a population subject to successive dilutions of arbitrary intensity, just like some experimental evolution protocols, is found. The mathematical expressions, in principle, may prove useful in characterizing real populations of microor¬ganisms. It was also demonstrated that a generalized multidimensional branching process is a nice tool in numerically studying mutational degeneration effects (specifically a pheno¬menon called Muller\'s ratchet) in populations under a wide variety of exponential growth settings. Finally, the evolutionary history of finite populations was studied by simulations to probe the viability of certain statistic, like some topological measures in genealogical trees, being incorporated in statistical tests to detect the fingerprints of natural selection.

Estudos sobre evolução têm sido desenvolvidos desde a publicação dos trabalhos de Charles Darwin sobre a origem das espécies pela seleção natural em 1859. Durante o século XX grandes avanços foram obtidos com a utilização de modelagens matemáticas e computacionais, pois com exceção de algumas espécies que podem ter sua evolução analisada in vivo, o tempo necessário para aquisição de dados é enorme e por este motivo o enfoque computacional passou a representar uma ferramenta essencial. Nesta tese são apresentados os conceitos básicos para se entender o processo evolutivo de populações assexuadas como mutação, seleção e relevos adaptativos, bem como os resultados numéricos sobre sua evolução através do processo conhecido como catraca de Muller, que baseia-se na perda estocástica da classe de indivíduos mais adaptados da população através das mutações adquiridas ao longo de sua linhagem. Neste trabalho foram estudadas diversas dinâmicas, como a de populações que estão sujeitas à passagens seriais com gargalo, onde observamos que a velocidade da catraca na não pára devido aos altos valores de epistase, enquanto que para populações com tamanho variável (crescimento e decrescimento exponencial) a catraca pára durante o período de crescimento até a população atingir o limite permitido pelo meio-ambiente, sendo que a partir deste ponto ela se comporta como no modelo de infinitos sítios tradicional. Por último, são apresentados os resultados de populações que interagem entre si em uma dinâmica presa-predador, onde o comportamento da catraca pode ser entendido com base nas dinâmicas das populações descritas anteriormente. Um outro problema abordado nesta tese é o da utilização de medidas da topologia de árvores genealógicas para verificar a presença da seleção na evolução de uma população. Apesar dos comprimentos dos ramos das árvores apresentarem alterações quando comparados ao caso neutro, observamos que os testes estatísticos utilizados não são suficientes para inferir o efeito da seleção em populações reais. / Studies about evolution have been developed since Charles Darwin\'s publications about the Origin of species and Natural Selection in 1859. During the XX century major developments were achieved through mathematical and computational modeling, since only few number of species that their evolution can be studied in vivo, once that the time scale involed for data acquisition procedure is considerable, and for this reason the computational approach become an important tool in this study. In this thesis are presented the basic concepts to understand the process of evolution in a population as mutation, selection and adaptive landscapes, in addition some numerical results about the evolution of an asexual population using the process known as Muller\'s ratchet, that can be characterized by the stochastic loss of the most fitted class of individuals through mutations that are acquired in their lineages. During this work several dynamics were studied, likewise the populations under serial bottleneck passages, where we observed that the velocity of the ratchet never stops for high epistatic coefficients, while in population whose size can varies (increasing or decreasing exponentially) the ratchet halts during population\'s increasing until these individuals do not reach the maximum number permitted, and after this point this population behaves like the traditional infinite genome size model. At last, we show the results of populations that can interact between themselves in a predator-prey dynamics, where the behaviour of the ratchet can be understood in the previous dynamics. Another problem that was studied in this thesis is related with several topology measures of genealogical trees in order to verify the selection in a population evolution. Despite branch\'s length of the trees changed due to the selection, we could see that the statistical tests used do not be sufficient to infer the effect of selection under real populations.

The central nervous system is a complex, yet well-organised, often laminated, tissue. This robust organisation is evident in the architecture of the retina: consisting of 5 different neuronal types organised into distinct layers: Retinal Ganglion Cell (RGC), Amacrine Cell (AC), Bipolar Cell (BP), Horizontal Cell (HC) and Photoreceptor cell (PR) layers. This remarkable organisation is evolutionarily conserved in vertebrates, yet little is known about the mechanisms by which these cells form the correct layers. Live imaging has revealed overlapping periods of birth and extensive inter-digitation followed by cells sorting out into their appropriate positions, suggesting cell-cell interactions are important. To investigate possible cellular and molecular mechanisms responsible for the establishment of the tissue architecture I developed an organoid culture system for zebrafish retinal cells. To identify the cells in culture I used a Spectrum of Fates fish line which is a multiply transgenic line in which each retinal cell type can be identified based on expression of a combination of fluorescently tagged cell fate markers. The development of the protocol by which I cultured the cells and observed their cell-cell interactions involved establishing the best methods to dissociate and culture zebrafish retinal cells in a non-adhesive environment, then imaging the resulting reaggregates to examine the position of the different retinal cell types. By doing this I observed their inherent self-organising properties, in the absence of extrinsic cues or scaffolds. These cells appeared to be arranged in an inside-out layering, although all cell types are layered in the same relative order as they are in vivo. To analyse the organization in these aggregates I developed a Matlab script in collaboration with Leila Muresan which analyses the relative positioning of cells in concentric rings from the periphery to the centre of the aggregates according to the cell fate-tagged fluorescent markers. The script then fits this data as an empirical cumulative distribution function for different groups of cells to determine how spatially distinct populations of cells are. This gave me my measure of organisation. I then investigated the cell-cell interactions involved in this self-organisation by genetically or pharmacologically removing individual cell types and assaying the resulting organisation of the reaggregated, cell-type deficient, retinal organoids. I revealed that Müller Glia are important for retinal cell self-organisation. I also investigated the role of Retinal Pigment Epithelial (RPE) cells and Retinal Ganglion Cells and found they had no impact on the ability of the remaining cell types to organize. I began to investigate the role of Amacrine Cells but found that retinas void of ACs were susceptible to disaggregating in our dissection setup, preventing me from collecting the material needed for culture. I also investigated the role of candidate molecules in this system and revealed that R-Cognin is critical for retinal cells to reaggregate. Not only can I remove cells or molecules from the system, but I show how it can also be manipulated to replace molecules of interest such as laminin, by coating beads with the substance of choice and placing it amongst the cells to see if their organisational behaviour is affected. In summary, I have developed a system which provides a simple and easy platform to manipulate in various ways to help us potentially reveal some of the important players in neuronal patterning.

Geometrical optical illusions such as the Muller Lyer illusion and the Ponzo illusion have been widely researched over the past 100+ years, yet researchers have not reached a consensus on why human perception is deceived by these illusions or which illusions are the results of the same effects. In this paper, I study these illusions through the lens of a convolutional neural network. First, I successfully train the network to correctly classify how a human would perceive a particular class of illusion (such as the Muller Lyer illusion), then I test the network’s ability to generalize to illusions that it was not trained on (like the Ponzo illusion). I do not find that these networks generalize effectively. Tests to better understand how the network learns to classify these illusions suggest the networks are checking for image data in specific ‘activation regions’ in order to make classifications rather than analyzing the entire illusions.

Doctor of Philosophy (Medicine) / Background: Diabetic vascular complications affect both the macro- and microvasculature. Microvascular pathology in diabetes may be mediated by biochemical factors that precipitate cellular changes at both the gene and protein levels. In the diabetic retina, vascular pathology is found mainly in microvessels, including the retinal precapillary arterioles, capillaries and venules. Macular oedema secondary to breakdown of the inner blood-retinal barrier is the most common cause of vision impairment in diabetic retinopathy. Müller cells play a critical role in the trophic support of retinal neurons and blood vessels. In chronic diabetes, Müller cells are increasingly unable to maintain their supportive functions and may themselves undergo changes that exacerbate the retinal pathology. The consequences of early diabetic changes in retinal cells are primarily considered in this thesis. Aims: This thesis aims to investigate the effect of perivascular cells (Müller cells, RPE, pericytes) on retinal endothelial cell permeability using an established in vitro model. Methods: Immunohistochemistry, cell morphology and cell growth patterns were used to characterise primary bovine retinal cells (Müller cells, RPE, pericytes and endothelial cells). An in vitro model of the blood-retinal barrier was refined by coculturing retinal endothelial cells with perivascular cells (Müller cells or pericytes) on opposite sides of a permeable Transwell filter. The integrity of the barrier formed by endothelial cells was assessed by transendothelial electrical resistance (TEER) measurements. Functional characteristics of endothelial cells were compared with ultrastructural morphology to determine if different cell types have barrier-enhancing effects on endothelial cell cultures. Once the co-culture model was established, retinal endothelial cells and Müller cells were exposed to different environmental conditions (20% oxygen, normoxia; 1% oxygen, hypoxia) to examine the effect of perivascular cells on endothelial cell permeability under reduced oxygen conditions. Barrier integrity was assessed by TEER measurements and permeability was measured by passive diffusion of radiolabelled tracers from the luminal to the abluminal side of the endothelial cell barrier. A further study investigated the mechanism of laser therapy on re-establishment of retinal endothelial cell barrier integrity. Müller cells and RPE, that comprise the scar formed after laser photocoagulation, and control cells (Müller cells and pericytes, RPE cells and ECV304, an epithelial cell line) were grown in long-term culture and treated with blue-green argon laser. Lasered cells were placed underneath confluent retinal endothelial cells growing on a permeable filter, providing conditioned medium to the basal surface of endothelial cells. The effect of conditioned medium on endothelial cell permeability was determined, as above. Results: Co-cultures of retinal endothelial cells and Müller cells on opposite sides of a permeable filter showed that Müller cells can enhance the integrity of the endothelial cell barrier, most likely through soluble factors. Low basal resistances generated by endothelial cells from different retinal isolations may be the result of erratic growth characteristics (determined by ultrastructural studies) or the selection of vessel fragments without true ‘barrier characteristics’ in the isolation step. When Müller cells were co-cultured in close apposition to endothelial cells under normoxic conditions, the barrier integrity was enhanced and permeability was reduced. Under hypoxic conditions, Müller cells had a detrimental effect on the integrity of the endothelial cell barrier and permeability was increased in closely apposed cells. Conditioned medium from long-term cultured Müller cells and RPE that typically comprise the scar formed after lasering, enhanced TEER and reduced permeability of cultured endothelial cells. Conclusions: These studies confirm that bovine tissues can be used as a suitable model to investigate the role of perivascular cells on the permeability of retinal endothelial cells. The dual effect of Müller cells on the retinal endothelial cell barrier under different environmental conditions, underscores the critical role of Müller cells in regulating the blood-retinal barrier in health and disease. These studies also raise the possibility that soluble factor(s) secreted by Müller cells and RPE subsequent to laser treatment reduce the permeability of retinal vascular endothelium. Future studies to identify these factor(s) may have implications for the clinical treatment of macular oedema secondary to diseases including diabetic retinopathy.

Dans cette thèse, nous étudions les codes de Reed-Muller qui constituent une des familles de codes correcteurs les plus étudiées, et les plus utilisées dans la transmission des communications numériques. Grâce à leur rapidité d'encodage et de décodage, ils furent notamment utilisés pour les transmissions satellitaires. Ils ont également un lien très fort avec les notions de fonctions booléennes. L'étude de ces dernières constitue le coeur de la réalisation et de la sécurité des systèmes de chiffrement à clé secrète, tant par blocs que par flot. Depuis l'introduction de ces codes, de très nombreux algorithmes de décodage virent le jour, et aujourd'hui encore étudier leur structure afin de construire des algorithmes de décodage constitue un fructueux domaine de recherche. Ces algorithmes de décodage peuvent être utilisés dans l'étude de la structure de systèmes de chiffrement à clé secrète. Nous exposons un point de vue unificateur à l'ensemble des algorithmes de décodage des codes de Reed-Muller, ce point de vue étant celui de la dérivée discrète. Nous exposons un algorithme performant pour le décodage des codes d'ordre deux, que nous analysons ensuite. Nous discutons les résultats de simulations des algorithmes étudiés pour les petites et moyennes longueurs de code. Ces résultats montrent que l'algorithme proposé décode beaucoup plus loin en pratique que les autres algorithmes.

Gegenstand dieser Arbeit war die Untersuchung von Raubtiernetzhäuten hinsichtlich ihrer zellulären Zusammensetzung in der Peripherie. Anhand der Neuron:Glia-Verhältnisse sollte festgestellt werden, ob alle Raubtiere ähnliche Zellverhältnisse in der Netzhaut aufweisen und welche funktionellen Besonderheiten daraus resultieren können. Es wurde nach Rückschlüssen gesucht auf allgemeine Regeln, nach welchen sich die Säugetiernetzhaut auch in der Peripherie abseits des zentralen scharfen Sehens in ihrer Funktion und Leistungsfähigkeit den Lebensbedingungen anpasst. Im Focus der Betrachtung stand dabei die Müller-Radialgliazelle mit den sie umgebenden Neuronen, welche gemeinsam als funktionelle Einheit in Form einer Zellsäule den Grundbaustein der Netzhaut darstellt. Bereits zuvor wurde bei diesen radiären Säulen eine nicht-stochastische Verteilung der Zellverhältnisse festgestellt, was bedeutet, dass die Anzahl der Neurone je Müllerzelle im Wesentlichen durch die Anzahl der Zellteilungen der späten Vorläuferzellen bestimmt wird und daher mit einer spezifischen Zunahme der Stäbchenanzahl verbunden ist. So wurde eine Korrelation der retinalen Zellverhältnisse mit der Art des vorherrschenden Photorezeptors bzw. der Lebensweise der betreffenden Spezies angenommen. Tagaktive Spezies waren in früheren Arbeiten durch oligozelluläre Netzhautsäulen aufgefallen, während sich nachtaktive Säugetiere durch zellreiche radiäre Säulen auszeichneten. Diese Ansätze sollten weiter verfolgt werden. Raubtiere sind für eine erfolgreiche Jagd auf eine rasche und präzise Wahrnehmung ihrer Umwelt angewiesen. Dabei kommt dem Sehsinn besondere Bedeutung zu. Dieser muss den Lebens- und Jagdgewohnheiten optimal angepasst sein. Räumliches Sehen und Entfernungseinschätzung sind dabei ebenso wichtig wie eine besonders gute Sehschärfe, ein großes Gesichtsfeld und das Erkennen von Formen und Bewegungen bei unterschiedlichsten Lichtverhältnissen. Bei dem Zusammenspiel verschiedener Komponenten, welche den Raubtieren zu einem optimalen Sehen bei Tag und Nacht verhelfen, nimmt die Netzhaut eine zentrale Rolle ein. Im Rahmen dieser Arbeit wurden 17 Vertreter von neun verschiedenen Raubtierspezies betrachtet. Dazu wurden Präparate ihrer Netzhäute verwendet, in welchen die Müller-Radialgliazellen immunhistochemisch durch ein Immunperoxidaseverfahren dargestellt worden waren, jeweils mit dem Primärantikörper α–GFAP, α–Glutaminsynthetase oder α–Vimentin V3B4. Die Gegenfärbung der Zellkerne erfolgte mit Haemalaun. Von diesen Präparaten wurden am Lichtmikroskop mit einer digitalen Kamera Bilder erstellt und im Computer gespeichert. Die morphometrische Auswertung der Aufnahmen erfolgte mit der Software analySIS pro 5.0. Auf diese Weise konnten die Zelldichten in der Netzhaut bestimmt und die zelluläre Zusammensetzung der retinalen Säulen als Zahlenverhältnis von Neuronen je Gliazelle dargestellt werden. Anhand der ermittelten Ergebnisse lassen sich zur vorliegenden Arbeit folgende wesentliche Aussagen treffen: 1. Unter Berücksichtigung der präparationsbedingten Gewebeschrumpfung liegt die Dichte der Müllerzellen etwa zwischen 8.000 – 14.000 Zellen/mm², die der Photorezeptoren im Wesentlichen bei 200.000 – 500.000 Zellen/mm². 2. Die Dichte der Müllerzellen ist zwischen den Arten relativ konstant und unabhängig von der Dichte der Neuronen in der Netzhaut. 3. Je Müllerzelle ist weniger als eine Ganglienzelle zu finden, in der inneren Körnerschicht sind einer Müllerzelle etwa drei bis sechs Neuronen zuzuordnen. In der äußeren Körnerschicht liegen annähernd 22 bis 42 Photorezeptoren pro Müllerzelle vor. Insgesamt findet sich ein Zellverhältnis von ca. 30 – 50 Netzhautneuronen je Müllerzelle. 4. Es wird ersichtlich, dass die radiären Säulen in der mittleren Netzhautperipherie eine vergleichsweise hohe Zellzahl aufweisen. Dabei ist in erster Linie die große Anzahl an Photorezeptorzellen maßgeblich. 5. Innerhalb der Ordnung der Raubtiere ist anhand der vorliegenden Ergebnisse keine Unterscheidung zwischen den einzelnen Spezies oder zwischen der Familie der Felidae und der Canidae anhand der Neuron:Glia-Verhältnisse in der Netzhautperipherie möglich. 6. Die gefundenen Zellzahlenverhältnisse zeigen eine starke Konvergenz bei der Signalverarbeitung in der mittperipheren Netzhaut an. Dies lässt auf eine hohe Lichtempfindlichkeit im peripheren Gesichtsfeld auf Kosten der Sehschärfe in diesem Bereich schließen. 7. Alle untersuchten Raubtiere teilen die Eigenschaft der Nachtaktivität bzw. teilweise der Dämmerungsaktivität und alle weisen multizelluläre radiäre Säulen in der peripheren Netzhaut auf. Dies unterstützt die Hypothese, dass die Zusammensetzung der Netzhautsäulen neben der Verwandtschaft ganz wesentlich aus der Lebensweise der Säugetiere resultiert. 8. Für die Nutzung von Boden oder Bäumen als Jagd-/ Lebensraum ließ sich bei den untersuchten Raubtieren hingegen kein Zusammenhang mit einer entsprechenden Spezialisierung der peripheren Netzhaut finden. Die ermittelten Ergebnisse ergänzen die vorhandene Datenlage in der Literatur hinsichtlich der zellulären Verhältnisse in der mittleren Netzhautperipherie von Raubtieren. Dies mag als Basis für künftige Untersuchungen sowie Vergleiche zwischen den Ordnungen dienen. Abschließend werden in dieser Arbeit Überlegungen angestellt zu medizinischen Gesichtspunkten und Forschungsbestrebungen bei der Erkrankung von Auge und Netzhaut, und in wie weit dem wachsenden Wissen um die Müller-Radialgliazelle dabei eine tragende Rolle zufallen kann.

Solutions to the problem of large peak to average power ratio (PAPR) in orthogonal frequency division multiplexing (OFDM) systems are proposed. Although the design of PAPR reduction codewords has been extensively studied and the existence of asymptotically good codes with low PAPR has been proved, still no reduced PAPR capacity achieving code has been constructed. This is the topic of the current thesis.This goal is achieved by implementing a time-frequency turbo block coded OFDM. In this scheme, we design the frequency domain component code to have a PAPR bounded by a small number. The time domain component code is designed to obtain good performance while the decoding algorithm has reasonable complexity. Through comparative numerical evaluation we show that our method achieves considerable improvement in terms of PAPR with slight performance degradation compared to capacity achieving codes with similar block lengths. For the frequency domain component code, we used the realization of Golay sequences as cosets of the fi rst order Reed-Muller code and the modi cation of dual BCH code. A simple MAP decoding algorithm for the modi ed dual BCH code is also provided. Finally, we provide a flexible and practical scheme based on probabilistic approach to a PAPR problem. This approach decreases the PAPR without any signi cant performance loss and without any adverse impact or required change to the system. / Engineering and Applied Sciences