Rare diseases, when considered as a whole, affect up to 7% of the population, which would represent 3.5 million individuals in the United Kingdom alone. However, while 'personalised medicine' is now yielding remarkable results using recent sequencing technologies in terms of diagnosing genetic conditions, we have made much less headway in translating this patient information into therapies and effective treatments. Even with recent calls for greater research into personalised treatments for those affected by a rare disease, progress in this area is still severely lacking, in part due to the astronomical cost and time involved in bringing treatments to the clinic. Gene correction using the recently-described genome editing technology CRISPR/Cas9, which allows precise editing of DNA, offers an exciting new avenue of treatment, if not cure, for rare diseases; up to 80% of which have a genetic component. This system allows the researcher to target any locus in the genome for cleavage with a short guide-RNA, as long as it precedes a highly ubiquitous NGG sequence motif. If a repair sequence is then also provided, such as a wild-type copy of the mutated gene, it can be incorporated by homology-directed repair (HDR), leading to gene correction. As both guide-RNA and repair template are easily generated, whilst the machinery for editing and delivery remain the same, this system could usher in the era of 'personalised medicine' and offer hope to those with rare genetic diseases. However, currently it is difficult to test the efficacy of CRISPR/Cas9 for gene correction, especially in vivo. Therefore, in my PhD I have developed a novel fluorescent reporter system which provides a rapid, visual read-out of both non-homologous end joining (NHEJ) and homology-directed repair (HDR) driven by CRISPR/Cas9. This system is built upon a cassette which is stably and heterozygously integrated into a ubiquitously expressed locus in the mouse genome. This cassette contains a strong hybrid promoter driving expression of membrane-tagged tdTomato, followed by a strong stop sequence, and then membrane-tagged EGFP. Unedited, this system drives strong expression of membrane-tdTomato in all cell types in the embryo and adult mouse. However, following the addition of CRISPR/Cas9 components, and upon cleavage, the tdTomato is rapidly excised, resulting via NHEJ either in cells without fluorescence (due to imperfect deletions) or with membrane-EGFP. If a repair template containing nuclear tagged-EGFP is also supplied, the editing machinery may then use the precise HDR pathway, which results in a rapid transition from membrane-tdTomato to nuclear- EGFP. Thereby this system allows the kinetics of editing to be visualised in real time and allows simple scoring of the proportion of cells which have been edited by NHEJ or corrected by HDR. It therefore provides a simple, fast and scalable manner to optimise reagents and protocols for gene correction by CRISPR/Cas9, especially compared to sequencing approaches, and will prove broadly useful to many researchers in the field. Further to this, I have shown that methods which lead to gene correction in our reporter system are also able to partially repair mutations found in the disease-causing gene, Zmynd10; which is implicated in the respiratory disorder primary ciliary dyskinesia (PCD), for which there is no effective treatment. PCD is an autosomal-recessive rare disorder affecting motile cilia (MIM:244400), which results in impaired mucociliary clearance leading to neonatal respiratory distress and recurrent airway infections, often progressing to lung failure. Clinically, PCD is a chronic airway disease, similar to CF, with progressive deterioration of lung function and lower airway bacterial colonization. However, unlike CF which is monogenic, over 40 genes are known to cause PCD. The high genetic heterogeneity of this rare disease makes it well suited to such a genome editing strategy, which can be tailored for the correction of any mutated locus.

No description available.

Thesis (M.A.)--Hong Kong Baptist University, 2005. / Dissertation submitted to the School of Communication. Includes bibliographical references (leaves 49-53).

Thesis (MPhil)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: Since South Africa’s transition from a nationalistic state to a democracy in 1994, debates about the media’s role have intensified as the challenges and complexities of the South African society unfolded. In this debate, which mainly played out between the government and the media, the liberal theory and the developmental theory were used as the two main normative positions from which to contest the media’s role. As normative theories they describe the ideal role of the press within societal systems and thus fall within the functionalist paradigm. Historically, the liberal approach was seen as the accepted normative framework for the media within a democracy to protect that very democracy. The liberal consensus adopted by the post-apartheid media therefore came as no surprise. However, the optimism initially experienced regarding the independence of the new, liberal media, its professionalisation and economic restructuring, is gradually being challenged by the critical perspective. This perspective questions the extent of transformation in a public sphere where entrance is still restricted by class structures. The argument of this paper is that although the above changes to the media landscape are recognised as important, they do not account for issues of class and how the poor, the spaces they live in and the factors impacting on their lives, are framed by the media. This paper is presented as a normative undertaking and presents civic journalism as alternative normative framework. It moves from the premise that the representations afforded to the poor in die media are being hampered by the individualistic aims of the Western, liberal, journalistic tradition. The argument is further that the use of a community-driven approach should lead to broader representation of the poor in the media and the inclusion of this currently marginalised group in the public sphere. Reframing, one of the most important methods of civic journalism, is singled out to explore the possibility of applying civic journalism to the South African context. The motivation for this paper is the belief that the need exists for a greater plurality of voices and discourses. / AFRIKAANSE OPSOMMING: Sedert Suid-Afrika in 1994 beweeg het van ’n nasionalistiese staat na ’n demokrasie, het die debat oor die rol van die media algaande verdiep namate die uitdagings en kompleksiteite van die Suid-Afrikaanse situasie ontvou het. In die debat tussen die postapartheid media en die regering was die twee normatiewe posisies van waar die media se rol by uitstek betwis is, die libertynse en ontwikkelingsteorie. As normatiewe teorieë wat die ideale rol van die pers binne samelewingsisteme verwoord, val dit binne die funksionalistiese paradigma. Histories word die liberale benadering gesien as die vanselfsprekende roete wat ’n media binne ’n demokrasie moet volg om daardie demokrasie te beskerm. Die liberale konsensus van die post-apartheid media was in die lig hiervan geen verrassing nie. Maar die optimisme wat aanvanklik ervaar is oor die onafhanklike, liberale media, sy professionalisering en ekonomiese herstrukturering, word algaande uitgedaag deur ’n kritiese perspektief. Hierdie perspektief bevraagteken die waarde van ’n getransformeerde media waar toelating tot die openbare sfeer steeds deur klasstrukture gereguleer word. Alhoewel die bogenoemde erken word as belangrike veranderinge, is die argument dat die liberale normatiewe paradigma nie genoeg was om kwessies van klas te verreken en hoe armes, die kwessies wat hulle lewens beïnvloed en die ruimtes waarin hulle ’n bestaan maak, deur die media beraam word nie. Hierdie werkstuk is ’n normatiewe onderneming wat burgerlike joernalistiek as normatiewe raamwerk wil voorstel. Die uitgangspunt is dat representasie van armes in die media deur die individualistiese doelstellings van die Westerse, liberale joernalistieke tradisie beperk word. Die argument is verder dat die toepassing van ’n gemeenskapsgerigte benadering behoort te lei tot ’n breër representasie van armes en die insluiting van dié tans gemarginaliseerde gemeenskappe by die openbare sfeer. Herberaming, een van die belangrikste metodes van burgerlike joernalistiek, word uitgesonder om die toepassingsmoontlikheid van burgerlike joernalistiek as alternatief te ondersoek. Die motivering vir die werkstuk is die oortuiging dat daar in die Suid-Afrikaanse mediakonteks ’n behoefte bestaan aan ’n groter diversiteit van stemme en diskoerse.

Made available in DSpace on 2016-08-03T12:29:50Z (GMT). No. of bitstreams: 1 FABIO FERREIRA.pdf: 4801413 bytes, checksum: 2f2b2df32fe80e448724cbc4722d9b38 (MD5) Previous issue date: 2013-03-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work is an inventory about the existence of means of communication in Brazilian territory, on the period before its discovery by the European colonists (before 1500). The main goal of this survey is to trace how they used to produce their messages and how they established their folk communication channels between the Indians and the tribes that existed in pre-colonial Brazil. We also intend to study the elements of folk communication adopted by the Indians and to draw a parallel, coming from the starting point of the concepts of the pernambucano (a person who is born in the city of Pernambuco) researcher Luiz Beltrão and his disciples created. This will result in the application and updated review of the typology of folk communication that was used in that historical period. The study was made with empiric foundation due to observation, which shows the importance of Indian communication in the context of Brazil, where people lived in society groups and had their values reduced and destroyed by the colonists. The methodology used in the work was able to embrace a confluence of techniques, such as: bibliographic research (books, articles and journals), documental research (in specialized magazines, printed and virtual publications). All this material was gathered in public and private collections. / Trata-se de inventário da existência de meios de comunicação no território brasileiro no período anterior a descoberta pelos colonizadores europeus (pré-1500). O objetivo da pesquisa é mapear como se produziam as mensagens e como se estabeleciam os canais folkcomunicacionais entre os indígenas e as tribos existentes no Brasil pré-colonial. Pretendemos, ainda, estudar elementos de folkcomunicação adotados entre os índios e traçar um paralelo a partir dos conceitos do pesquisador pernambucano Luiz Beltrão e de seus discípulos, resultando na aplicação, revisão e atualização da Tipologia da Folkcomunicação em uso para aquele período histórico. O estudo tem como base empírica observáveis que demonstram a importância da comunicação indígena brasileira naquele contexto como pessoas que viviam agrupados em sociedade e tiveram valores subjugados e destruídos pelos colonizadores. A metodologia comportou uma confluência de técnicas quais sejam: pesquisa bibliográfica (livros, artigos e jornais) e pesquisa documental (em revistas especializadas, periódicos impressos e virtuais) localizadas em acervos públicos e privados.

The aim of this thesis is to describe and analyze the operational program Education for competitiveness due to its importance for high school. Show how a project application, what is the relevance and acceptability of a course project applications submitted. In conclusion, I focus on the success of university applicants and a brief assessment of whether there has been implementing projects in the area of ??support 2.2 Higher education to improve education at universities.

Submitted by Morgana Andrade (morgana.andrade@ufes.br) on 2016-03-17T15:48:28Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) tese_9059_Dissertação Raquelli Natale PDF.pdf: 1958630 bytes, checksum: 2fb61d6473e43c617fafa8a12e9ad5c9 (MD5) / Approved for entry into archive by Patricia Barros (patricia.barros@ufes.br) on 2016-03-17T16:59:27Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) tese_9059_Dissertação Raquelli Natale PDF.pdf: 1958630 bytes, checksum: 2fb61d6473e43c617fafa8a12e9ad5c9 (MD5) / Made available in DSpace on 2016-03-17T16:59:27Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) tese_9059_Dissertação Raquelli Natale PDF.pdf: 1958630 bytes, checksum: 2fb61d6473e43c617fafa8a12e9ad5c9 (MD5) / CAPES e Fapes / O objetivo principal deste trabalho é analisar como os meios de comunicação ajudam a construir a representação social da violência de gênero contra a mulher no Espírito Santo, que lidera o ranking nacional de feminicídios, com taxa de 9,8 homicídios para cada 100 mil mulheres. Elegemos como corpus de pesquisa notícias sobre violência de gênero no ES, veiculadas no ano de 2013, nos jornais A Gazeta e A Tribuna. Em hipótese, acreditamos que essas notícias ajudam a construir representações sociais acerca da violência de gênero a partir da apresentação de estereótipos de vítima e agressor na sociedade, da individualização do problema da violência, da associação desse problema às classes sociais menos privilegiadas e da apresentação do crime de violência de gênero como crime passional. O estudo dessas notícias apresenta-se como algo complexo, do qual não participam apenas informações de ordem linguística, mas também de carácter social, histórico, cultural e cognitivo, uma vez que a análise discursiva não pode ser dissociada do contexto, dos atores sociais e das instituições envolvidas na produção da notícia, bem como das ideologias presentes nesse processo. Por esse motivo, assumimos como base teórica de nossa investigação uma proposta multidisciplinar: a Teoria Sociocognitiva de Teun A. van Dijk (1999a; 2011a; 2012; 2014b). Ademais, contamos com as contribuições dos estudos sobre gênero e discurso de Cameron (1985, 1997), Wodak (1997), West, Lazar e Kramarae (2000), Fernández Díaz (2003), Lazar (1993, 2005, 2007), Magalhães (2005; 2009), Heberle, Ostermann e Figueiredo (2006). Além das análises discursivo-analíticas, também utilizamos o programa de linguística de corpus WordSmith Tools para realizar análises quantitativas. Os resultados das análises nos levaram à confirmação das hipóteses iniciais: o discurso das notícias reforça estereótipos de vítima e agressor, típicos de uma estrutura social patriarcal, na qual é atribuída à vítima ou aos vícios (álcool e drogas) a responsabilidade da violência sofrida; além disso, a violência de gênero é apresentada como um problema individual e associada às classes sociais menos favorecidas; e, por último, o discurso das notícias apresenta grande parte dos crimes de violência de gênero como crimes passionais. / The main objective of this study is to analyze how the media help to build the social representation of gender violence the Espírito Santo, the state that leads the national ranking of femicide, with 9.8 homicide rate for every hundred thousand women. Elected as corpus research news on gender violence in ES, aired in 2013, in the newspapers A Gazeta and A Tribuna. Under no circumstances, we believe that this news helps to build social representations of gender violence from the presentation of victim and perpetrator stereotypes in society, the individualization of the problem of violence, this problem Association to less privileged social classes and presentation of crime of gender violence as a crime of passion. The study of this news comes as something complex, which not only participate in information, language problems, but also social, historical, cultural and cognitive, since the discursive analysis cannot be dissociated from the context of social actors and institutions involved in the production of news, and of these ideologies in the process. For this reason, we assume as theoretical basis of our research a multidisciplinary proposal: a Sociocognitive Theory from Teun A. van Dijk (1999a; 2011a; 2012; 2014b). In addition, we rely on the contributions of studies on gender and discourse from Cameron (1985, 1997), Wodak (1997), West, Lazar and Kramarae (2000), Fernández Díaz (2003), Lazar (1993, 2005, 2007), Magellan (2005; 2009), Heberle, Ostermann and Figueiredo (2006). Also we used the corpus linguistics program WordSmith Tools to perform quantitative analysis. The results of the analysis led us to the confirmation of the initial hypothesis: the discourse of news reinforces stereotypes victim and aggressor, typical of a patriarchal social structure, which is attributed to the victim or vices (alcohol and drugs) the responsibility of the violence suffered; moreover, gender violence is presented as an individual problem and associated to lower social classes; and, finally, the discourse of the news has much of crimes of gender violence as crimes of passion.

Este trabalho procura debater a liberdade constitucional de informação sob um viés não usual ao direito constitucional brasileiro. Seu ponto de partida é a proteção ao sigilo de fonte para jornalistas profissionais, consagrada pelo texto constitucional. Essa regra parece pressupor uma distinção possível e clara entre jornalistas e demais cidadãos. Mas como compreendê-la em um cenário atual no qual: a) as condições tecnológicas permitem que qualquer cidadão, a um custo baixo ou quase inexistente, publique informações para um número indistinto de pessoas, e; b) o Supremo Tribunal Federal tenha reconhecido que o Estado não pode exigir a obtenção de um diploma de ensino superior para diferenciar a categoria de jornalistas? Logo, o pano de fundo deste trabalho é a possibilidade de o Estado diferenciar jornalistas de demais cidadãos com relação à concessão de prerrogativas para o exercício da liberdade de informação. Nos Estados Unidos, esse é um debate relevante ao menos desde a década de 1970. São apresentados seus principais aspectos: por um lado, a jurisprudência de sua Suprema Corte, que se negou sistematicamente a diferenciar direitos próprios à liberdade de imprensa (Press Clause) em comparação com a liberdade de expressão (Speech Clause); por outro, as abordagens funcional e institucional à liberdade de imprensa, composta respectivamente por autores favoráveis e críticos àquela linha jurisprudencial. Ao final, a partir de uma perspectiva crítica e da adoção de fundamentos jurídicos, busca-se analisar a regra constitucional do sigilo de fonte e propor parâmetros interpretativos para sua aplicação. / This paper seeks to debate the constitutional freedom of information under an aspect not common to Brazilian constitutional law. The departure point is the reporters privilege, constitutionally protected for professionals by law. That rule seems assume a possible and clear distinction between journalists and other citizens. But how to understand it under a scenario where: a) the technological conditions allow any citizen, with very cheap or barely existing costs, to publish information for an indistinct number of people, and; b) the Supreme Federal Court has recognized that the State may not license journalists by a college degree diploma? Thus, the background subject of this paper is the possibility that the State differentiates journalists from other citizens in regard to the concession of prerogatives for the exercise of the freedom of information. In the United States, this has been a relevant debate at least since de 1970s. The main aspects are presented: on one hand, the Supreme Courts case law that has systematically denied to differentiate exclusive rights deriving from the Press Clause in comparison to the Speech Clause; on the other hand, the functional and institutional approaches to freedom of the press, respectively representing the authors favorable and critics to that judicial construction. Finally, taking on from a critic perspective and adopting legal fundaments, it seeks to analyze the constitutional rule of the reporters privilege and to propose interpretative standards for it.

M.A. / Het doel van deze studie is te komen tot een inventarisatie van de problemen -zowel op praktisch als theoretisch vlak- aan welke de nieuw gekozen plaatselijke overheden het hoofd moeten bieden, zoals deze zijn overgeleverd vanuit het verleden. Daarnaast wordt middels het empirische gedeelte bekeken, hoe de dagbladen in de provincie Gauteng - vaak het 'hart' van Zuid-Afrika genoemd - met deze problematiek en geschiedenis omgingen om de lezer annex kiezer adequaat te informeren. 3 Gekozen is voor een media-onderzoek over enkele maanden rond de twee laatste verkiezingen voor plaatselijke overheden: oktober 1988 en november 1995. Daarnaast wordt gekeken naar enkele van de vele begripsverwarringen binnen de Zuid-Afrikaanse politieke en media-context, zoals deze bijvoorbeeld onder meer bestaan rond zaken als 'democratie', 'macht', 'detribalisatie' en 'non-racialisme; allen termen die er in het discours omtrent regeren en geregeerd worden, nieuws produceren en nieuws ontvangen voortdurend met de haren bijgesleept worden maar voor de verschillende deelnemers aan het debat soms geheel uiteenlopende betekenissen hebben. De scriptie hoopt met deze onderwerpskeuze een bijdrage te leveren aan het voortdurende debat in Zuid-Afrika over het heden, verleden en wellicht ook toekomst van de gedrukte media, de politieke en sociaal-economische geschiedschrijving en de functionering en definiring van plaatselijk bestuur. Hoewel deze studie weliswaar nauwelijks alternatieve voorstellen voor de toekomstige behandeling van deze kwesties aandraagt, kan een kritisch en samenvattend overzicht hiervan zoals gepresenteerd in de hierna volgende hoofdstukken hemieuwde stof tot nadenken bieden, zowel gedragen als beperkt door de buitenlandse kijk van de auteur.

No description available.