Estima-se que 3% da população mundial esteja infectada pelo vírus da hepatite C (HCV). O HCV tem como alvo o tecido hepático e a maioria dos pacientes infectados desenvolvem infecção crônica. Nos últimos anos, estudos in vitro têm demonstrado interações entre o miRNA-122 (miR-122) da célula hospedeira e dois sítios localizados na região 5\' UTR do genoma do vírus da hepatite C (HCV), os quais são essenciais ao processo de replicação viral. O miR-122 é altamente expresso no fígado, onde atua na regulação do metabolismo de lipídios juntamente com outro miRNA, o miRNA-33a (miR-33a), porém, o mecanismo envolvido nesta regulação ainda é pouco conhecido. Sabe-se que a infecção pelo HCV altera a expressão de genes envolvidos na biossíntese e transporte de lipídios, resultando na estimulação do metabolismo de lipídios e criando um ambiente favorável para sua replicação. Neste contexto os objetivos deste trabalho foram avaliar a expressão de miR-33a e miR-122 em indivíduos cronicamente infectados pelo HCV-1 e HCV-3 em amostras obtidas antes do início da terapia. Os miRNAs foram isolados a partir de amostras de sangue periférico e de tecido hepático. A quantificação da expressão relativa de ambos miRNAs foi pela técnica de PCR em tempo real. Os níveis de miR-33a no sangue periférico foram mais elevados do que no tecido hepático em indivíduos infectados pelo HCV-1(p < 0,0001) e HCV-3 (p=0,0025). Observou-se uma correlação inversa entre os níveis de miR-33a no sangue periférico e tecido hepático dos indivíduos infectados pelo HCV-1 (r=-0,281, p=0,039) e correlação positiva para os indivíduos infectados pelo HCV-3 (r=0,9286, p < 0,0001). Correlação inversa entre os níveis hepáticos de miR-33a com o nível sérico de insulina (r=-0,371, p =0,005) nos indivíduos infectados pelo HCV-1 e correlação positiva entre os níveis no sangue periférico com os níveis séricos de GGT (r=0,553, p=0,049) foram observadas. Em relação ao miR-122, de maneira geral o nível hepático foi mais elevado do que o sérico (p < 0,0001). Entretanto, o nível hepático de miR-122 em indivíduos infectados pelo HCV-3 foi maior quando comparado aos infectados pelo HCV-1 (6,22 vezes, p < 0,001). Uma correlação inversa entre os níveis séricos de ApoA-II e os níveis de expressão de miR-122 no sangue (r=-0,330; p=0,014) e tecido hepático (r=-0,311; p=0,020) foi observada nos pacientes infectados pelo HCV-1. Os pacientes infectados pelo HCV- 3 mostraram correlação positiva entre os níveis hepáticos de miR-122 e os níveis de HDL (r=0,412, p=0,036) e insulina (r=0,478, p=0,044). O miR-33a e o miR-122 atuam regulando genes que controlam o metabolismo dos lipídios no fígado. Até o presente momento, não existem relatos que associem a expressão do miR-33a e do miR-122 com o perfil lipídico na infecção pelo HCV. Além disso, o acúmulo de lipídio (esteatose) intensamente descrito na infecção pelo HCV-3 pode sugerir interação diferenciada desse genótipo com os mecanismos envolvidos na regulação do metabolismo lipídico, envolvendo o miR-33a e miR-122 / The prevalence of infection by hepatitis C virus (HCV) is about 3% of the world population. HCV targets the liver tissue and the majority of infected patients develop chronic infection. In recent years, in vitro studies have demonstrated interactions between miRNA-122 (miR-122) the host cell to two places located in the 5\' untranslated region of the HCV genome which are essential for virus replication process. miR-122 is highly expressed in the liver, which has been implicated as a fatty acid metabolism regulator. Another mine has also been described as a key regulator of lipid metabolism, miRNA-33a (miR-33a), however, the mechanisms involved in this regulation are still little known. It is known that HCV infection changes the expression of genes involved in the biosynthesis and transport of lipids, resulting in stimulation of the lipid metabolism and creating a favorable environment for replication of the virus. To our knowledge, there are no reports linking the expression of miR-33a with lipid profile in HCV infection. In this context the objectives of this study were to evaluate the expression of miR-33a and miR-122 in chronically infected individuals with HCV-1 and HCV-3 in samples obtained prior to initiation of therapy. MiRNAs were isolated from peripheral blood samples and liver tissue. The quantification of relative expression of both miRNAs was by PCR in real time. MiR-33a levels in peripheral blood were higher than in liver tissue in patients infected with HCV-1 (p < 0.0001) and HCV-3 (p=0.0025). Levels in the peripheral blood of miR-33a were lower in patients infected with HCV-3 (p=0.0169). There was an inverse correlation between hepatic levels of miR-33a with serum insulin levels (p=0.005) in individuals infected with HCV-1 and a positive correlation between the levels in the peripheral blood serum levels of GGT (p=0.049). Hepatic levels of miR-122 were higher than the levels in the peripheral blood of individuals infected by HCV-1 and HCV-3 (p < 0.0001). Hepatic miR-122 levels were higher in patients infected with HCV-3 than those infected with HCV-1 (6.22 times, p < 0.001). There was a positive correlation between miR-122 levels in the blood and liver tissue of patients infected with HCV-1 (r=0.302, p=0.026). An inverse correlation between serum ApoA-II was observed in these patients the levels of expression of miR-122 in blood (r=-0.330; p =0.014) and liver tissue (r=-0.311; p=0.020). Patients infected with HCV-3 showed a positive correlation between hepatic miR-122 levels to HDL levels (r=0.412, p=0.036) and insulin levels (r=0.478, p=0.044). The miR-33a and miR-122 act by regulating genes that control lipid metabolism in the liver. The different interactions with lipid metabolism exerted by HCV-3 may explain why his relationship with the miR-33a and miR-122 was different when compared with HCV-1

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Den svenska Försvarsmakten (FM) har förändrats och gått ifrån invasionsförsvar till insatsförsvar, detta har lett till att FM fokuserar på insatser utomlands och hotet skiljer sig insatser emellan. De konflikter som är aktuella idag och där de svenska styrkorna bidrar med resurser utspelar sig i länder där urban miljö med lågteknologisk motståndare förekommer. Motståndaren har med tiden lärt sig att hantera strider i urban miljö och uppträder i alla dimensioner. Man anser att strid i denna typ av miljö kommer att öka i framtiden. Stora nationer har stridit i urban miljö med framgång. Med tanke på var vi befinner oss idag när det gäller insatser av varierande grad har hotet ökat mot våra trupper vilket i sin tur har lett till ett större behov av skydd. Syftet med arbetet är att genom en kvalitativ textanalys (som är studiens tyngdpunkt) och en modellstudie påvisa hur man kan möta det nya hotet i urban terräng med hjälp av tekniska anpassningar på tyngre fordon som stridsvagnar. Under den beskrivande delen beskrivs hotbilden idag, erfarenheter från olika krig där stridsvagnar har nyttjats och stridsvagnens sårbarhet i urban miljö. Därefter behandlar modellstudien en tänkbar miljö och hot i syfte att ta fram den mest fördelaktiga anpassningen för att möta det nya hotet som utspelar sig i alla dimensioner. Resultatet visar att det största hotet som våra trupper utsätts för är den typ av hot där motståndare strävar efter att strida i urban miljö. Undersökningen visar att vi idag behöver mer skydd i form av pansar och de svenska stridsvagnarna behöver anpassas med olika system för att kunna möta dessa nya hot. / The Swedish Armed Forces (SAF) is currently in a phase of evolution transferring from being an old strategic defense to an expeditionary force. The SAF has forces deployed in several locations all over the world and the threat they meet is different from place to place, the conflicts often conducted by low-tech insurgents in urban terrain.The insurgents have learned how to fight in urban terrain and can operate in every dimension of the battlefield. It is believed that the battle in this type of environment will increase in future. Being where we are today in terms of operations the threat against our troops has increased which has led us to a greater need for protection.The purpose of this paper is that using a qualitative textual analysis and a model study to show how the new threat can be met in urban terrain with the help of technical adjustments on heavy vehicles such as tanks. At first the writer will describe the threat that is common in urban terrain today. Then the lessons learned from wars where tanks have been used and later on the tank’s vulnerability in urban terrain will be described. Thereafter, the model study will elaborate a potential environment and threat in order to highlight the most advantageous adjustment for tanks to meet the new threat.The result shows that the greatest threat that our troops are exposed to today is; battles that takes place in urban terrain. The study shows that we need more protection in form of armour. The Swedish tanks should be adapted with different systems to meet today’s threat in the urban terrain.

AerotechTelub bedriver, på uppdrag av den svenska försvarsmakten, en så kallad tech-transfer process eller tekniköverföringsprocess för den från Tyskland inköpta stridsvagnen Leopard 2 (svensk beteckning; strv 122). Syftet med processen är bland annat att säkerställa att den kunskap som behövs för att hålla stridsvagnen i drift. Uppgiften är att studera erhållna dokument och ritningar för stridsvagnens siktessystem. Med hjälp av dessa har en modell av systemet som stabiliserar siktet byggts upp i Matlab och Simulink. / Aerotechtelub is conducting a so called tech-transfer process of the German purchased main battle tank Leopard 2 (Swedish designation Strv 122). The main purpose of the process is to guarantee that the knowledge that is required to keep the tank in operation. The task is to study the obtained documents and schematics concerning the bore sight system of the tank.

<p>AerotechTelub bedriver, på uppdrag av den svenska försvarsmakten, en så kallad tech-transfer process eller tekniköverföringsprocess för den från Tyskland inköpta stridsvagnen Leopard 2 (svensk beteckning; strv 122). Syftet med processen är bland annat att säkerställa att den kunskap som behövs för att hålla stridsvagnen i drift. Uppgiften är att studera erhållna dokument och ritningar för stridsvagnens siktessystem. Med hjälp av dessa har en modell av systemet som stabiliserar siktet byggts upp i Matlab och Simulink. </p> / <p>Aerotechtelub is conducting a so called tech-transfer process of the German purchased main battle tank Leopard 2 (Swedish designation Strv 122). The main purpose of the process is to guarantee that the knowledge that is required to keep the tank in operation. The task is to study the obtained documents and schematics concerning the bore sight system of the tank.</p>

The aim of this thesis is to examine the quality of the disclosure IAS 1 Presentation of Financial Statements, paragraphs 122 and 125 in the annual reports of Swedish publicly listed firms. These paragraphs state that firms are required to disclose judgments made by management in preparing financial statements that may have significant impact on the recognized carrying amount. These paragraphs should also include information about major sources of estimation uncertainty. A quantitative research approach is used and the sample consists of 1,519 annual reports over a 7-year period. We construct a disclosure index to assess the quality of the disclosures in Critical judgements and key sources of estimation uncertainty (IAS 1:122 and 1:125) note and categorize the annual reports into four index groups. Additionally, the number of headlines in the note are counted and sorted into three other groups, creating a headline index. Lastly, we multiply the disclosure index with the headline index to get a score, which then enable us to distinguish and rank the quality of disclosure between firms. Further, we count the number of words in each individual disclosure in each annual report. This additional quantitative data enable regression analyses, further ensuring objectivity in assessing the disclosure quality. Agency theory and political cost theory are used as base for determining which firm characteristics may affect disclosure quality. We examine the firm characteristics firm visibility, ownership concentration and leverage to investigate any relationship with disclosure quality. We use the ordinary least squares (OLS) regression method to analyse this data. The analysis shows that firm visibility and leverage have positive relationships with disclosure quality. This supports the political cost theory and suggests that firms that are more visible have stronger incentives to attain a high disclosure quality. Our findings also support debt-associated agency problems and are also in line with prior studies that found a positive relationship between disclosure quality and the degree of leverage, which indicates that disclosures reduces the information gap.

Generally Hepatitis C Virus tropism is limited to hepatocytes. This limited tropism is a result of the receptors HCV requires for cellular entry and other host cellular factors including, uniquely, a liver specific miRNA, miR-122. The relationship between HCV and miR-122 is interesting, as commonly, miRNA are associated with suppression of function, but in the case of HCV, miR-122 actively promotes HCV proliferation. In-depth studies have demonstrated that miR-122 along with the RNA induced silencing complex (RISC) protein Argonaute 2 (Ago2) binds directly to two seed sequences separated by 8-9 nucleotides on HCV 5’UTR. Binding to the 5’UTR results in an increase in viral replication and translation. The method by which miR-122 promotes HCV translation and replication is not fully understood but evidence suggests that part of the function of miR-122 is to stabilize the HCV genome and protect it from exonuclease degradation by Xrn1, but other mechanisms remain to be identified. The reliance of HCV on miR-122 is best exemplified by the fact that removal of miR-122 by a miR-122 antagonist drastically impedes HCV viral titers in Chimpanzees and humans with no indication of escape mutants. The observation that HCV augmentation of the HCV life cycle by miR-122 requires Ago2 suggests that other components downstream in the miRNA suppression pathway may also be part of the mechanism of action. Our studies focused specifically on the processing body (p-body) associated DEAD-box helicase DDX6. DDX6 is essential for p-body assembly, required for robust miRNA suppression activity and elevated in HCV associated hepatocellular carcinomas. As such we hypothesized that DDX6 and p-bodies were directly or in-directly associated with the mechanism of action of miR-122. Knocking down DDX6 with siRNA indicated that DDX6 augments both HCV replication and translation. To examine whether DDX6 augmentation of HCV replication was related to the effects of miR-122 on the HCV life cycle, HCV replication and translation were assessed in the presence or absence of miR-122 when DDX6 was knocked down. Our data indicated that HCV replication and translation were augmented equally by miR-122 whether DDX6 was present or not. Our data also demonstrated that HCV replication and translation that was occurring independent of miR-122 was also still affected by DDX6 knockdown. Taken together our observations strongly suggest that the role DDX6 has on HCV is independent of HCV and miR-122’s relationship. In order to better understand miR-122’s relationship with HCV, we hypothesized that targeting the miR-122 binding region with siRNA would inhibit HCV replication initially, but that over the course of several rounds of treatment with the same siRNA, HCV would mutate to escape the siRNA, producing escape mutants that replicate without a dependency on miR-122. These escape mutants could be evaluated on how they replicate without using miR-122, shedding light on miR-122 and HCV’s relationship. Conversely if no escape mutants arose the siRNA could be further studied as a potential therapeutic for HCV. siRNA designed to target the miR-122 binding region inhibited HCV replication, confirming that the designed siRNAs could access the miR-122 binding region and function as an siRNA. Interestingly, when the siRNAs were used against a replication competent HCV RNA having a single nucleotide mutation in the first miR-122 binding site, instead of abolishing siRNA knockdown, two of the siRNA showed enhanced inhibition activity. The target sequences of these siRNAs spanned both miR-122 binding sites and we speculate that their inhibitory activity was due to competition for miR-122 binding to site 2. This observation indicates that siRNA targeting the miR-122 binding region have dual activity, by siRNA induced cleavage, and as a competitive inhibitor of miR-122 binding. Selection for viral escape mutants of the miR-122-binding site targeting siRNAs revealed viral RNAs having mutations within the miR-122 binding sites, in the surrounding region, and to other areas within the HCV IRES. The mutant viruses will be used to assess the influence of miR-122 binding site mutations on HCV replicative fitness, and to determine if the virus can evolve to replicate independent from augmentation by miR-122.

No description available.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Direito, Programa de Pós-Graduação em Direito, 2016. / Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2017-02-15T17:05:50Z No. of bitstreams: 1 2016_LeonardodaSilvaSantana.pdf: 2464622 bytes, checksum: ece96464acf82175301a3629714afdbe (MD5) / Approved for entry into archive by Ruthléa Nascimento(ruthleanascimento@bce.unb.br) on 2017-03-03T18:42:02Z (GMT) No. of bitstreams: 1 2016_LeonardodaSilvaSantana.pdf: 2464622 bytes, checksum: ece96464acf82175301a3629714afdbe (MD5) / Made available in DSpace on 2017-03-03T18:42:02Z (GMT). No. of bitstreams: 1 2016_LeonardodaSilvaSantana.pdf: 2464622 bytes, checksum: ece96464acf82175301a3629714afdbe (MD5) / O presente trabalho intenta investigar a atuação de grupos religiosos no Congresso Nacional e a limitação da cidadania das pessoas LGBT. Para tanto, realizamos uma caracterização do movimento LGBT e da bancada evangélica e, em seguida, analisamos discursos de senadores e senadoras durante a tramitação do PLC 122/2006 no Senado Federal, utilizando a Teoria Fundamentada nos Dados. Os dados obtidos permitiram conhecer a visão de parlamentares sobre o tema e identificar o atual estágio da laicidade no Brasil. / This study intends to investigate the role of religious groups in Congress and the limitation of citizenship of LGBT people. Thus, we performed a characterization of the LGBT movement and the evangelical bench and then analyze speeches of senators in the course of PLC 122/2006 in the Senate, using Grounded Theory. It was possible to know the view of parliamentarians on the subject and identify the current status of secularism in Brazil.

No description available.