<p>Spermatogenesen är i många organismer en av de mest dramatiska förvandlingar som en cell kan genomgå – en vanlig, rund, diploid cell omvandlas till en nålformad, haploid cell med ett tätt packat cellmaskineri. I bananfluga, <i>Drosophila melanogaster</i>, innebär denna process flera karaktäristiska stadier. Ett av dessa är det primära spermatocyt-stadiet, som infaller innan cellen påbörjar meios-delning. Stadiet karaktäriseras av en uppluckrad kromatinstruktur i cellens kärna och ovanligt höga transkriptions- och translationshastigheter, för att producera allt det mRNA och de proteiner som behövs senare under spermatidomvandlingen. Två av de proteiner som uttrycks i höga nivåer i primära spermatocyter är ThioredoxinT (TrxT) och Painting of fourth (POF).</p><p>Thioredoxiner är små proteiner som har som funktion att reducera disulfidbryggor i andra proteiner, en mekanism som används i många olika fysiologiska sammanhang. I denna avhandling visar jag att <i>TrxT</i>-genen kodar för ett testikelspecifikt thioredoxin som binder specifikt till Y-kromosom-loopar i primära spermatocyter. <i>TrxT</i>-genen ligger precis bredvid <i>deadhead</i> (<i>dhd</i>), en gen som kodar för ett hon-specifikt thioredoxin som är lokaliserat till cellkärnorna i flugans äggstockar. Ett tredje thioredoxin i <i>Drosophila</i> är det allmänt uttryckta Thioredoxin-2 (Trx-2). Jag har upptäckt att flugor som saknar Trx-2 är livsdugliga, men att de lever kortare än vildtypsflugor, medan flugor med extra mycket Trx-2 har en ökad tålighet mot oxidativ stress. Slående nog är en total avsaknad av alla tre thioredoxiner inte förenat med letalitet, tvärtemot vad man skulle kunnat vänta sig. Alla tre thioredoxiner finns i de olika <i>Drosophilider</i> som undersökts och den ovanliga genorganisation som delas av <i>TrxT</i> och <i>dhd</i> är generellt konserverad.</p><p>Gen-namnet <i>Painting of fourth</i> härstammar från upptäckten att POF binder till (”målar”) <i>Drosophilas</i> kromosom 4. Jag visar i min avhandling att POFs bindning till den fjärde kromosomen är bevarad i olika <i>Drosophila</i>-arter och att POF kolokaliserar med både ett protein och en histon-modifiering, som är förknippade med doskompensation, i arter där POF också binder till hanens X-kromosom. POF uttrycks överallt i både honor och hanar, men i väldigt höga nivåer i hanens testiklar. Jag visar här att POF finns i cellkärnan hos primära spermatocyter, men också i kärnan på mognande spermatider, och att avsaknad av POF in hanens könsceller orsakar en global nedreglering av gener som ligger på kromosom 4. Kombinationen av mina POF- resultat tyder på att POF har en viktig funktion i det första kända fallet av genreglering av en hel autosomal kromosom.</p> / <p>The process of spermatogenesis is in many organisms one of the most dramatic cellular transformations - a normal round diploid cell is ultimately transformed into a needle shaped haploid cell with tightly packaged cell machinery. In <i>Drosophila melanogaster</i> this process involves several characteristic stages, one of these being the primary spermato-cyte stage, which is the stage prior to meiosis. This stage is characterized by a loose chromatin structure in the nucleus and exceptionally high rates of transcription and translation to produce essentially all the mRNAs and proteins that are needed later during spermatid formation. Two proteins that are expressed in high levels in primary spermatocytes are ThioredoxinT (TrxT) and Painting of fourth (POF).</p><p>Thioredoxins are small thiol proteins that reduce disulfides in other proteins, a mechanism that is utilized in many different contexts. In this thesis I show that the <i>TrxT</i> gene encodes a testis-specific thioredoxin that specifically associates to Y-chromosome loops in primary spermatocytes. <i>TrxT</i> is located right next to <i>deadhead</i> (<i>dhd</i>), a gene that encodes a female-specific thioredoxin that specifically locates to nuclei in the ovaries. A third thioredoxin in <i>Drosophila</i> is the ubiquitously expressed Thioredoxin-2 (Trx-2). I have found that flies lacking Trx-2 are viable but have shorter life spans than wild type flies, while over-expression of Trx-2 mediates an increased resistance to oxidative stress. Interestingly, a lack of all three thioredoxins does not result in lethality, contrary to what could be expected. All three thioredoxins are conserved among <i>Drosophilids</i> and the striking genomic organization of <i>TrxT</i> and <i>dhd</i> is generally conserved.</p><p>The gene name <i>Painting of fourth</i> originates from the finding that POF stains the 4th chromosome of <i>Drosophila</i> in a banded pattern on salivary gland chromosomes. I show in this thesis that POF binding to the equivalent of the 4th chromosome is conserved in genus <i>Drosophila</i> and that POF co-localizes with both a protein and a histone modification associated with dosage compensation in species where POF also binds the male X. POF is expressed ubiquitously in both males and females, but at very high levels in male testes. I show that POF is present in nuclei of primary spermatocytes, but also in nuclei of maturing spermatids and that a lack of POF in the male germline causes a global down-regulation of chromosome 4 genes. These results combined suggest a function of POF in the first known case of chromosome-wide gene regulation of an autosome.</p>

Kunststofflichtwellenleiter (POFs) stellen ein verhältnismäßig neues Medium zur optische Datenkommunikation über kurzen Strecken dar. Während ihrer Einsatzdauer unterliegen POFs unterschiedlichen Arten von Umweltbeanspruchungen, hauptsächlich durch hohe Temperatur, hohe Feuchtigkeit und mechanischen Belastungen. Zahlreiche experimentelle Forschungen beschäftigten sich mit der standardisierten Prüfung der Zuverlässigkeit von im Handel erhältlichen Fasern. Jedoch gab es bisher wenig Erfolg bei der Bemühung, zwei grundlegende optische Erscheinungen, Absorption und Streuung, die die Lichtausbreitung in Fasern stark beeinflussen, zu verstehen und praktisch zu modellieren: Diese beiden Effekte beschreiben nicht nur die Qualität neuer Fasern, sondern sie werden auch stark durch die Alterungsprozess beeinflusst.<br><br> Der Hauptzweck dieser Doktorarbeit war es, ein praktisch verwendbares und theoretisch gut fundiertes Modell der Lichtausbreitung in nicht gealterten und gealterten POFs zu entwickeln und es durch optische Experimente zu verifizieren. Dabei wurden anwendungsorientierte Aspekte mit theoretischer POF-Modellierung kombiniert. Die Arbeit enthält die erste bekannte Anwendung der Wellenanalyse zur Untersuchung der winkelabhängigen Eigenschaften der Streuung in Lichtwellenleitern.<br><br> Für die praktischen Experimente wurden mehrere POF-Proben unterschiedlicher Hersteller künstlich gealtert, indem sie bis 4500 Stunden bei 100 °C gelagert wurden (ohne Feuchtekontrolle). Die Parameter der jeweiligen Simulationen wurden mittels einer systematischen Optimierung an die gemessen optischen Eigenschaften der gealterten Proben angeglichen. Die Resultate deuten an, dass der Übertragungsverlust der gealterten Fasern in den ersten Tagen und Wochen der Alterung am stärksten durch eine wesentliche physikalische Verschlechterung der Kern-Mantel-Grenzfläche verursacht wird. Chemische Effekte des Alterungsprozesses scheinen im Faserkernmaterial zuerst nach einigen Monaten aufzutreten. / This thesis discusses theoretical and practical aspects of modelling of light propagation in non-aged and aged step-index polymer optical fibres (POFs). Special attention has been paid in describing optical characteristics of non-ideal fibres, scattering and attenuation, and in combining application-oriented and theoretical approaches. The precedence has been given to practical issues, but much effort has been also spent on the theoretical analysis of basic mechanisms governing light propagation in cylindrical waveguides.<br><br>As a result a practically usable general POF model based on the raytracing approach has been developed and implemented. A systematic numerical optimisation of its parameters has been performed to obtain the best fit between simulated and measured optical characteristics of numerous non-aged and aged fibre samples. The model was verified by providing good agreement, especially for the non-aged fibres. The relations found between aging time and optimal values of model parameters contribute to a better understanding of the aging mechanisms of POFs.

Kunststofflichtwellenleiter (POFs) stellen ein verhältnismäßig neues Medium zur optische Datenkommunikation über kurzen Strecken dar. Während ihrer Einsatzdauer unterliegen POFs unterschiedlichen Arten von Umweltbeanspruchungen, hauptsächlich durch hohe Temperatur, hohe Feuchtigkeit und mechanischen Belastungen. Zahlreiche experimentelle Forschungen beschäftigten sich mit der standardisierten Prüfung der Zuverlässigkeit von im Handel erhältlichen Fasern. Jedoch gab es bisher wenig Erfolg bei der Bemühung, zwei grundlegende optische Erscheinungen, Absorption und Streuung, die die Lichtausbreitung in Fasern stark beeinflussen, zu verstehen und praktisch zu modellieren: Diese beiden Effekte beschreiben nicht nur die Qualität neuer Fasern, sondern sie werden auch stark durch die Alterungsprozess beeinflusst. <br><br> Der Hauptzweck dieser Doktorarbeit war es, ein praktisch verwendbares und theoretisch gut fundiertes Modell der Lichtausbreitung in nicht gealterten und gealterten POFs zu entwickeln und es durch optische Experimente zu verifizieren. Dabei wurden anwendungsorientierte Aspekte mit theoretischer POF-Modellierung kombiniert. Die Arbeit enthält die erste bekannte Anwendung der Wellenanalyse zur Untersuchung der winkelabhängigen Eigenschaften der Streuung in Lichtwellenleitern. <br><br> Für die praktischen Experimente wurden mehrere POF-Proben unterschiedlicher Hersteller künstlich gealtert, indem sie bis 4500 Stunden bei 100 °C gelagert wurden (ohne Feuchtekontrolle). Die Parameter der jeweiligen Simulationen wurden mittels einer systematischen Optimierung an die gemessen optischen Eigenschaften der gealterten Proben angeglichen. Die Resultate deuten an, dass der Übertragungsverlust der gealterten Fasern in den ersten Tagen und Wochen der Alterung am stärksten durch eine wesentliche physikalische Verschlechterung der Kern-Mantel-Grenzfläche verursacht wird. Chemische Effekte des Alterungsprozesses scheinen im Faserkernmaterial zuerst nach einigen Monaten aufzutreten. / This thesis discusses theoretical and practical aspects of modelling of light propagation in non-aged and aged step-index polymer optical fibres (POFs). Special attention has been paid in describing optical characteristics of non-ideal fibres, scattering and attenuation, and in combining application-oriented and theoretical approaches. The precedence has been given to practical issues, but much effort has been also spent on the theoretical analysis of basic mechanisms governing light propagation in cylindrical waveguides. <br><br> As a result a practically usable general POF model based on the raytracing approach has been developed and implemented. A systematic numerical optimisation of its parameters has been performed to obtain the best fit between simulated and measured optical characteristics of numerous non-aged and aged fibre samples. The model was verified by providing good agreement, especially for the non-aged fibres. The relations found between aging time and optimal values of model parameters contribute to a better understanding of the aging mechanisms of POFs.<br><br>

Spermatogenesen är i många organismer en av de mest dramatiska förvandlingar som en cell kan genomgå – en vanlig, rund, diploid cell omvandlas till en nålformad, haploid cell med ett tätt packat cellmaskineri. I bananfluga, Drosophila melanogaster, innebär denna process flera karaktäristiska stadier. Ett av dessa är det primära spermatocyt-stadiet, som infaller innan cellen påbörjar meios-delning. Stadiet karaktäriseras av en uppluckrad kromatinstruktur i cellens kärna och ovanligt höga transkriptions- och translationshastigheter, för att producera allt det mRNA och de proteiner som behövs senare under spermatidomvandlingen. Två av de proteiner som uttrycks i höga nivåer i primära spermatocyter är ThioredoxinT (TrxT) och Painting of fourth (POF). Thioredoxiner är små proteiner som har som funktion att reducera disulfidbryggor i andra proteiner, en mekanism som används i många olika fysiologiska sammanhang. I denna avhandling visar jag att TrxT-genen kodar för ett testikelspecifikt thioredoxin som binder specifikt till Y-kromosom-loopar i primära spermatocyter. TrxT-genen ligger precis bredvid deadhead (dhd), en gen som kodar för ett hon-specifikt thioredoxin som är lokaliserat till cellkärnorna i flugans äggstockar. Ett tredje thioredoxin i Drosophila är det allmänt uttryckta Thioredoxin-2 (Trx-2). Jag har upptäckt att flugor som saknar Trx-2 är livsdugliga, men att de lever kortare än vildtypsflugor, medan flugor med extra mycket Trx-2 har en ökad tålighet mot oxidativ stress. Slående nog är en total avsaknad av alla tre thioredoxiner inte förenat med letalitet, tvärtemot vad man skulle kunnat vänta sig. Alla tre thioredoxiner finns i de olika Drosophilider som undersökts och den ovanliga genorganisation som delas av TrxT och dhd är generellt konserverad. Gen-namnet Painting of fourth härstammar från upptäckten att POF binder till (”målar”) Drosophilas kromosom 4. Jag visar i min avhandling att POFs bindning till den fjärde kromosomen är bevarad i olika Drosophila-arter och att POF kolokaliserar med både ett protein och en histon-modifiering, som är förknippade med doskompensation, i arter där POF också binder till hanens X-kromosom. POF uttrycks överallt i både honor och hanar, men i väldigt höga nivåer i hanens testiklar. Jag visar här att POF finns i cellkärnan hos primära spermatocyter, men också i kärnan på mognande spermatider, och att avsaknad av POF in hanens könsceller orsakar en global nedreglering av gener som ligger på kromosom 4. Kombinationen av mina POF- resultat tyder på att POF har en viktig funktion i det första kända fallet av genreglering av en hel autosomal kromosom. / The process of spermatogenesis is in many organisms one of the most dramatic cellular transformations - a normal round diploid cell is ultimately transformed into a needle shaped haploid cell with tightly packaged cell machinery. In Drosophila melanogaster this process involves several characteristic stages, one of these being the primary spermato-cyte stage, which is the stage prior to meiosis. This stage is characterized by a loose chromatin structure in the nucleus and exceptionally high rates of transcription and translation to produce essentially all the mRNAs and proteins that are needed later during spermatid formation. Two proteins that are expressed in high levels in primary spermatocytes are ThioredoxinT (TrxT) and Painting of fourth (POF). Thioredoxins are small thiol proteins that reduce disulfides in other proteins, a mechanism that is utilized in many different contexts. In this thesis I show that the TrxT gene encodes a testis-specific thioredoxin that specifically associates to Y-chromosome loops in primary spermatocytes. TrxT is located right next to deadhead (dhd), a gene that encodes a female-specific thioredoxin that specifically locates to nuclei in the ovaries. A third thioredoxin in Drosophila is the ubiquitously expressed Thioredoxin-2 (Trx-2). I have found that flies lacking Trx-2 are viable but have shorter life spans than wild type flies, while over-expression of Trx-2 mediates an increased resistance to oxidative stress. Interestingly, a lack of all three thioredoxins does not result in lethality, contrary to what could be expected. All three thioredoxins are conserved among Drosophilids and the striking genomic organization of TrxT and dhd is generally conserved. The gene name Painting of fourth originates from the finding that POF stains the 4th chromosome of Drosophila in a banded pattern on salivary gland chromosomes. I show in this thesis that POF binding to the equivalent of the 4th chromosome is conserved in genus Drosophila and that POF co-localizes with both a protein and a histone modification associated with dosage compensation in species where POF also binds the male X. POF is expressed ubiquitously in both males and females, but at very high levels in male testes. I show that POF is present in nuclei of primary spermatocytes, but also in nuclei of maturing spermatids and that a lack of POF in the male germline causes a global down-regulation of chromosome 4 genes. These results combined suggest a function of POF in the first known case of chromosome-wide gene regulation of an autosome.

[pt] Apesar do recente aumento do número de pesquisas sobre orçamento familiar e marketing no Brasil, pouco se estudou, ainda, acerca da categoria Educação. Visando contribuir para reduzir essa lacuna de pesquisa, a presente dissertação teve como objetivo determinar se existem diferentes padrões de alocação do orçamento familiar na categoria educação nas diversas faixas de renda da população metropolitana do Rio de Janeiro, e se há diferenças no padrão de alocação das despesas em educação dessas famílias entre os anos de 2002/2003 e 2008/2009. Com base nos dados fornecidos pela Pesquisa de Orçamentos Familiares (POF/IBGE), e utilizando técnicas estatísticas, verificou-se que, tanto na pesquisa de 2002/2003 quanto na de 2008/2009, não há diferença significativa na média de gastos com educação entre as diferentes classes sociais. Do ponto de vista diacrônico, percebeu-se uma diminuição dos gastos com educação entre os anos de 2002/2003 e 2008/2009. Tal resultado contrasta com indicadores socioeconômicos do Brasil no período, como o aumento da renda total familiar que provocou uma melhora do padrão geral de consumo das famílias e de sua qualidade de vida. / [en] Despite the recent increase in the research on the family budget and marketing in Brazil, little has also been studied on the Education category. To contribute to reduce this research gap, this thesis aimed to determine whether there are different patterns of household budget allocation in education category in different income brackets of the population of metropolitan Rio de Janeiro, and if there are differences in the pattern of allocation of expenditure on education these families between the years 2002/2003 and 2008/2009. Based on data provided by the Household Budget Survey (POF / IBGE), and using statistical techniques, it was found that both in search of 2002/2003 as in 2008/2009, there is no significant difference in education spending between different social classes. By diachronic point of view, we noticed a decrease in education spending between the years 2002/2003 and 2008/2009. This result contrasts with socio-economic indicators in Brazil in the period, as the increase in total household income which caused an improvement in the overall pattern of household consumption and quality of life.

A busca por alimentos provenientes de sistemas de produção sustentáveis, como por exemplo, os métodos orgânicos de produção é uma tendência que vem se fortalecendo mundialmente. Mudanças nos hábitos alimentares têm sido observadas, revelando a complexidade dos modelos de consumo e de seus fatores determinantes. Sendo assim, este estudo teve por objetivo descrever a disponibilidade domiciliar de alimentos orgânicos no Brasil. Utilizou-se como base de dados informações contidas na Pesquisa de Orçamentos Familiares (POF 2008- 2009), realizada pelo Instituto Brasileiro de Geografia e Estatística (IBGE) sobre aquisições de alimentos e bebidas orgânicos. Os resultados revelam comportamentos distintos na aquisição de alimentos orgânicos entre os brasileiros, quando são discriminados de acordo com as regiões e situação do domicílio (urbano ou rural). Os valores de disponibilidade (média) domiciliar foram superiores entre as famílias residentes nas áreas rurais, notadamente entre as regiões Sul e Centro- Oeste. Nota-se a relação existente entre as condições socioculturais que privilegia a perspectiva ligada à renda, havendo tendência de aumento sistemático de alimentos orgânicos, conforme ocorre crescimento dos rendimentos. Os resultados revelam ainda que quanto menor o número de moradores por domicílio, independente da região, maior a disponibilidade alimentar de orgânicos. Em relação aos grupos alimentares, merece destaque a maior participação do grupo dos laticínios, principalmente entre as famílias residentes nas áreas rurais. Os dados relativos à disponibilidade per capita de energia e participação dos macronutrientes e micronutrientes oriunda dos alimentos orgânicos no Valor Energético Total - VET revelou reduzida contribuição para a totalidade das regiões brasileiras. Quanto às características sociodemográficas das famílias, verifica-se que com o aumento da renda registra-se crescimento na disponibilidade de orgânicos nos domicílios com chefe/responsável do sexo feminino. A maior propensão ao consumo é verificada entre pessoas mais velhas (60 anos ou mais) e com nível de escolaridade superior incompleto. Paralelamente, verificou-se a reduzida quantidade média disponível para a totalidade das famílias brasileiras. / The search for food from sustainable production systems, for example, the organic methods of production, is a trend which rises worldwide. Changes in dietary habits had been observed, showing the complexity of consumption patterns and their corresponding determinant factors. Thus, the aim of this study was to report the household availability of organic food in Brazil. This work was based on information available on Family Budget Research (POF 2008-2009), carried out by the Brazilian Institute of Geography and Statistics (IBGE) about food acquisition for household consumption. The results showed distinct behavior regarding organic food acquisition between Brazilians, which are discriminated accordingly with different regions and household situation (rural or urban). The household availability values (mean) was higher between families located in rural regions, remarkably between South and Middle-West regions. It can be observed a relationship between socio-cultural conditions which allows the perspectives related to income, with systematic rising trend of organic food, when income growth occurs. Also, the results suggested that as lower the numbers of dwellers, independent of region, the household availability of organic foods are increased. Regarding the dietary groups, more emphasis was given about the major contribution of dairy group, mainly within family household in rural areas. Data related to per capita availability of energy and contribution of macronutrients and micronutrients derived from organic food on Total Energy Value showed reduced contribution for totality of the Brazilian regions. About the family socio-demographic features, it was observed an increasing income promoted by a rising availability in households which are headed by women. The major consumption propensity was verified between elderly individuals (60 years old or more) and with incomplete higher education. In addition, it was found the reduced average amount available for totality of Brazilian families.

Introdução: Os gastos em saúde são crescentes ao redor do mundo, sendo os medicamentos parte importante destes. Os medicamentos contribuem, em muitos casos, de forma decisiva para o controle das doenças e o aumento da expectativa e da qualidade de vida da população, sendo que sua ausência ou uso irracional coloca em risco os investimentos nas ações de saúde. No Brasil, a constituição garante acesso gratuito e integral a todo tratamento de saúde, incluindo acesso gratuito aos medicamentos. Apesar disso e dos avanços nas políticas públicas do setor, ainda existe uma parcela da população excluída desses recursos. Objetivos: Analisar o consumo de medicamentos pela população brasileira, seus custos e principais fontes de obtenção. Metodologia: A Pesquisa de Orçamentos Familiares de 2009 (POF) e a Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), realizada em 2013, são as fontes de dados utilizadas nesse trabalho para análise sobre o consumo de medicamentos. A POF é uma pesquisa domiciliar, feita por amostragem, com abrangência geográfica nacional, é desenhada para o enfoque familiar, entretanto, algumas abordagens individuais são possíveis. A PNAUM consiste em inquérito populacional nacional, realizado por amostragem, cobrindo apenas as áreas urbanas. Resultados: de acordo com os dados da POF 2008-2009, as despesas totais com medicamentos equivaleram a cerca de 4,5 bilhões de reais, sendo as despesas monetárias sozinhas responsáveis por aproximadamente 80% desse valor. A maioria das aquisições monetárias de medicamentos foi realizada em farmácias ou drogarias, enquanto que a maior parte das aquisições não monetárias foi realizada em hospitais, postos de saúde e farmácias vinculadas ao SUS. A PNAUM demonstra que a maioria dos medicamentos de elevado custo e para o tratamento de doenças crônicas são adquiridos exclusivamente pelo SUS ou farmácia popular (FP). Os medicamentos de uso contínuo têm 3,66 vezes a chance de serem adquiridos em pelo SUS ou pela FP. Já os medicamentos de uso eventual têm 73% menos chances de serem adquiridos no SUS ou FP. Pertencer às classes socioeconômicas D e E aumentam em 78% as chances de se adquirir medicamentos pelo SUS ou FP quando comparados a pessoas das classes A e B. Conclusões: Há uma tendência de a população obter seus medicamentos de forma gratuita especialmente quando seu custo é mais elevado e o tratamento prolongado. Porém, os indivíduos podem esbarrar na falta de abastecimento das farmácias relacionadas ao SUS e acabam sendo obrigados a comprarem na rede privada seu tratamento. Ainda existem lacunas a serem aprimoradas, a fim de se estabelecer uma assistência farmacêutica capaz de prover o tratamento integral ao usuário do sistema de saúde, mas salientamos a importância da mesma no fornecimento de medicamentos para o tratamento do diabetes e doenças cardiovasculares. / Introduction: Health care expenses are rising around the world and medicines play an important role in this scenario. Medicines have a decisive role in the control of diseases, increasing of the population life expectancy and quality of life. Its absence or irrational use may put the investments in health care at risk. In Brazil, the Constitution provides free and full access to all health care, including free access to medicines. Despite this and the advances on public policies, there are portions of the population who are still denied these resources. Objectives: To analyze the consumption of medicines by the Brazilian population, their costs and the major sources of acquisition. Methodology: The Household Budget Survey 2009 (POF) and the National Survey on Access, Use and Promotion of Rational Drug Use (PNAUM) held in 2013 are the sources of data used in this study for analysis of medicine consumption. The POF is a household survey conducted with national geographic coverage and is designed with household focus; however, some individual approaches are possible. The PNAUM consists of national population survey conducted by sampling and covers only the urban areas of Brazil. Results: According to the data from the POF 2008-2009 total spending on drugs amounted to about 4.5 billion of reais, and the monetary costs alone accounted for approximately 80% of this amount. Most of the monetary purchases of medicines were performed in pharmacies or drugstores, while most of the non-cash purchases were made in hospitals, health centers and pharmacies linked to SUS. The PNAUM shows that most of the high cost medicines and medicines for treating chronic diseases are acquired exclusively by the SUS or popular pharmacy (PF). The medications of continuous use have 3.66 times the chance of being acquired in the SUS or by FP. However the medicines of eventual use have almost 73% less likely to be acquired in the SUS or FP. Belong to social- economic classes D and E increase by 78% the chances of acquiring drugs by SUS or FP when compared to people from classes A and B. Conclusions: The population have a tendency to acquire their medications free of charge medications especially when their cost are higher or the treatment is long. However they can stumble on the lack of supply of pharmacies related to SUS and end up being forced to buy on the private network their treatment. There are still gaps to be improved in order to establish pharmaceutical care capable of providing integral treatment to the health system user, but we emphasize its importance on providing medications for the treatment of diabetes and cardiovascular disease.

Stimulation or repression of gene expression by genome-wide regulatory mechanisms is an important epigenetic regulatory function which can act to efficiently regulate larger regions or specific groups of genes, for example by compensating for loss or gain of chromosome copy numbers. In Drosophila melanogaster there are two known chromosome-wide regulatory systems; the MSL complex, which mediates dosage compensation of the single male X-chromosome and POF, which stimulates expression from the heterochromatic 4th chromosome. POF also interacts with the heterochromatin inducing protein HP1a, which represses expression from the 4th chromosome but which also has been assigned stimulatory functions. In addition to these two, there is another more elusive and less well-characterized genome-wide mechanism called buffering, which can act to balance transcriptional output of aneuploidy regions of the genome (i.e. copy number variation). In my thesis, I describe the presence of a novel physical link between dosage compensation and heterochromatin; mediate by two female-specific POF binding sites, proximal to roX1 and roX2 on the X chromosome (the two non-coding RNAs in the MSL complex). These sites can also provide clues to the mechanisms behind targeting of chromosome-specific proteins. Furthermore, to clarify the conflicting reports about the function of HP1a, I have suggested a mechanism in which HP1a has adopted its function to different genomic locations and gene types. Different binding mechanisms to the promoter vs. the exon of genes allows HP1a to adopt opposite functions; at the promoter, HP1a binding opens up the chromatin structure and stimulates gene expression, whereas the binding to exons condense the chromatin and thus, represses expression. This also causes long genes to be more bound and repressed by HP1a. Moreover, I show that buffering of monosomic regions is a weak but significant response to loss of chromosomal copy numbers, and that this is mediated via a general mechanism which mainly acts on differentially expressed genes, where the effect becomes stronger for long genes. I also show that POF is the factor which compensates for copy number loss of chromosome 4.

In Drosophila there are two different chromosome-wide targeting systems, the dosage compensation system that equalizes the transcriptional output from X-linked genes between males and females, and the regulation of the 4th chromosome mediated by the POF protein.   The best studied of these two mechanisms is the dosage compensation system. To attain dosage compensation in Drosophila at least five different proteins, encoded by the male-specific lethal genes msl1, msl2, msl3, mle and mof, are required. These proteins together with two non-coding RNAs (roX1 and roX2) form a dosage compensation complex (MSL complex), which binds exclusively to the X chromosome in Drosophila males and up-regulates the transcription approximately two times.   In this thesis I show that roX1 and roX2 are most likely the only non-coding RNAs within the MSL complex. As expected, the roX transcripts were enriched within the MSL complex. Interestingly, one additional transcript was identified within the MSL complex. This transcript did not associate with the X chromosome and is therefore not believed to be involved in up-regulation of the X-linked genes. This transcript encodes for the rate limiting component in the MSL complex, the MSL2 protein. A model is proposed in which free, partial or complete, MSL complex feed-back regulates the amount of msl2 transcript, and thereby limits the MSL complex production.   The second chromosome-wide regulatory system in flies acts on an autosome, the heterochromatic 4th chromosome. This regulation is a balancing mechanism between at least two different proteins, the chromosome 4 specific protein painting of fourth (POF) and heterochromatin protein 1 (HP1). POF binds to nascent RNAs transcribed from the 4th chromosome and HP1 target the same set of genes at the chromatin level. POF stimulates the transcribed genes, while HP1 represses them; together they create the most optimal condition for these genes. This type of balancing mechanism may be a more general way to fine-tune transcription at a chromosome-wide level and raises the question about autosomal gene regulation as a general mechanism.

Introdução: Os gastos em saúde são crescentes ao redor do mundo, sendo os medicamentos parte importante destes. Os medicamentos contribuem, em muitos casos, de forma decisiva para o controle das doenças e o aumento da expectativa e da qualidade de vida da população, sendo que sua ausência ou uso irracional coloca em risco os investimentos nas ações de saúde. No Brasil, a constituição garante acesso gratuito e integral a todo tratamento de saúde, incluindo acesso gratuito aos medicamentos. Apesar disso e dos avanços nas políticas públicas do setor, ainda existe uma parcela da população excluída desses recursos. Objetivos: Analisar o consumo de medicamentos pela população brasileira, seus custos e principais fontes de obtenção. Metodologia: A Pesquisa de Orçamentos Familiares de 2009 (POF) e a Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), realizada em 2013, são as fontes de dados utilizadas nesse trabalho para análise sobre o consumo de medicamentos. A POF é uma pesquisa domiciliar, feita por amostragem, com abrangência geográfica nacional, é desenhada para o enfoque familiar, entretanto, algumas abordagens individuais são possíveis. A PNAUM consiste em inquérito populacional nacional, realizado por amostragem, cobrindo apenas as áreas urbanas. Resultados: de acordo com os dados da POF 2008-2009, as despesas totais com medicamentos equivaleram a cerca de 4,5 bilhões de reais, sendo as despesas monetárias sozinhas responsáveis por aproximadamente 80% desse valor. A maioria das aquisições monetárias de medicamentos foi realizada em farmácias ou drogarias, enquanto que a maior parte das aquisições não monetárias foi realizada em hospitais, postos de saúde e farmácias vinculadas ao SUS. A PNAUM demonstra que a maioria dos medicamentos de elevado custo e para o tratamento de doenças crônicas são adquiridos exclusivamente pelo SUS ou farmácia popular (FP). Os medicamentos de uso contínuo têm 3,66 vezes a chance de serem adquiridos em pelo SUS ou pela FP. Já os medicamentos de uso eventual têm 73% menos chances de serem adquiridos no SUS ou FP. Pertencer às classes socioeconômicas D e E aumentam em 78% as chances de se adquirir medicamentos pelo SUS ou FP quando comparados a pessoas das classes A e B. Conclusões: Há uma tendência de a população obter seus medicamentos de forma gratuita especialmente quando seu custo é mais elevado e o tratamento prolongado. Porém, os indivíduos podem esbarrar na falta de abastecimento das farmácias relacionadas ao SUS e acabam sendo obrigados a comprarem na rede privada seu tratamento. Ainda existem lacunas a serem aprimoradas, a fim de se estabelecer uma assistência farmacêutica capaz de prover o tratamento integral ao usuário do sistema de saúde, mas salientamos a importância da mesma no fornecimento de medicamentos para o tratamento do diabetes e doenças cardiovasculares. / Introduction: Health care expenses are rising around the world and medicines play an important role in this scenario. Medicines have a decisive role in the control of diseases, increasing of the population life expectancy and quality of life. Its absence or irrational use may put the investments in health care at risk. In Brazil, the Constitution provides free and full access to all health care, including free access to medicines. Despite this and the advances on public policies, there are portions of the population who are still denied these resources. Objectives: To analyze the consumption of medicines by the Brazilian population, their costs and the major sources of acquisition. Methodology: The Household Budget Survey 2009 (POF) and the National Survey on Access, Use and Promotion of Rational Drug Use (PNAUM) held in 2013 are the sources of data used in this study for analysis of medicine consumption. The POF is a household survey conducted with national geographic coverage and is designed with household focus; however, some individual approaches are possible. The PNAUM consists of national population survey conducted by sampling and covers only the urban areas of Brazil. Results: According to the data from the POF 2008-2009 total spending on drugs amounted to about 4.5 billion of reais, and the monetary costs alone accounted for approximately 80% of this amount. Most of the monetary purchases of medicines were performed in pharmacies or drugstores, while most of the non-cash purchases were made in hospitals, health centers and pharmacies linked to SUS. The PNAUM shows that most of the high cost medicines and medicines for treating chronic diseases are acquired exclusively by the SUS or popular pharmacy (PF). The medications of continuous use have 3.66 times the chance of being acquired in the SUS or by FP. However the medicines of eventual use have almost 73% less likely to be acquired in the SUS or FP. Belong to social- economic classes D and E increase by 78% the chances of acquiring drugs by SUS or FP when compared to people from classes A and B. Conclusions: The population have a tendency to acquire their medications free of charge medications especially when their cost are higher or the treatment is long. However they can stumble on the lack of supply of pharmacies related to SUS and end up being forced to buy on the private network their treatment. There are still gaps to be improved in order to establish pharmaceutical care capable of providing integral treatment to the health system user, but we emphasize its importance on providing medications for the treatment of diabetes and cardiovascular disease.