This thesis participates to the effort launched after the Fukushima-Daiichi disaster to improve the robustness of national institutions involved in nuclear safety because of the role that the failing nuclear regulator had in the accident. The driving idea is to investigate how engineering techniques used in high-risk industries can be applied to institutions involved in nuclear safety to improve their robustness. The thesis focuses specifically on the Office for Nuclear Regulation (ONR), the British nuclear regulator, and its process for structured inspections. The first part of the thesis demonstrates that the hazard and operability (HAZOP) technique, used in the nuclear industry to identify hazards associated with an activity, can be adapted to qualitatively assess the robustness of organisational processes. The HAZOP method was applied to the ONR inspection process and led to the identification of five significant failures or errors. These are: failure to focus on an area/topic deserving regulatory attention; failure to evaluate an area/topic of interest; failure to identify a non-compliance; failure to identify the underlying issue, its full extent and/or safety significance and failure to adequately share inspection findings. In addition, the study identified the main causal chains leading to each failure. The safeguards of the process, i.e. the mechanisms in place to prevent, detect, resolve and mitigate possible failures, were then analysed to assess the robustness of the inspection process. The principal safeguard found is the superintending inspector who performs reviews of inspection reports and debriefs inspectors after inspections. It was concluded that the inspection process is robust provided recruitment and training excellence. However, given the predominant role of the superintending inspector, the robustness of the process could be improved by increasing the diversity of safeguards. Finally, suggestions for improvement were made such as establishing a formal handover procedure between former and new site inspectors, formalising and generalising the shadowing scheme between inspectors and setting minimum standards for inspection debriefs. These results were shared with ONR, which had reached the same conclusions independently, thus validating the new application for the HAZOP method. The second part of the thesis demonstrates that computational modelling techniques can be used to build digital twins of institutions involved in safety which can then be used to assess their effectiveness. The knowledge learned thanks to the HAZOP study was used in association with computational modelling techniques to build a digital twin of the ONR and its structural inspection process along with a simple model of a nuclear plant. The model was validated using the face-validity and predictive validation processes. They respectively involved an experienced ONR inspector checking the validity of the model’s procedures and decision-making processes and comparing the model’s output for oversight work done to data provided by the ONR. The effectiveness of the ONR was then evaluated using a scenario where a hypothetical, newly discovered phenomenon threatens the integrity of the plant, with ONR inspectors gradually learning and sharing new information about it. Monte-Carlo simulation was used to estimate the cost of regulatory oversight and the probability that the ONR model detects and resolves the issue introduced before it causes an accident. Different arrangements were tested and in particular with a superintending inspector reviewing inspection reports and a formal information sharing process. For this scenario, these two improvements were found to have a similar impact on the success probability. However, the former achieves it for only half the cost.

Submitted by Joana Azevedo (joanad@id.uff.br) on 2017-08-19T18:52:14Z No. of bitstreams: 1 Dissert RICARDO NICOLL JUNIOR.pdf: 3627999 bytes, checksum: 62639dcab37e133915213367543cc1ec (MD5) / Approved for entry into archive by Biblioteca da Escola de Engenharia (bee@ndc.uff.br) on 2017-08-22T16:19:02Z (GMT) No. of bitstreams: 1 Dissert RICARDO NICOLL JUNIOR.pdf: 3627999 bytes, checksum: 62639dcab37e133915213367543cc1ec (MD5) / Made available in DSpace on 2017-08-22T16:19:02Z (GMT). No. of bitstreams: 1 Dissert RICARDO NICOLL JUNIOR.pdf: 3627999 bytes, checksum: 62639dcab37e133915213367543cc1ec (MD5) Previous issue date: 2016-11-25 / Os órgãos reguladores são responsáveis pela regulação em diversos setores da sociedade. No Brasil, atuam em várias áreas para o desenvolvimento do país e têm como objetivo principal o equilíbrio social, econômico e o desenvolvimento nacional. O progresso de novas tecnologias no campo nuclear e sua comercialização acendem a necessidade de uma regulamentação de acordo com padrões de segurança internacionais. A presente pesquisa busca por meio de extensa revisão da literatura, identificar as orientações internacionais para órgãos de regulação e fazer uma análise comparativa entre o Brasil e cinco países que tem organismos regulatórios independentes no setor nuclear. O propósito do trabalho é de contribuir com os setores públicos brasileiros, com uma avaliação da regulação no país na percepção de especialistas e propor diretrizes para a estruturação de um órgão de regulação independente, respeitando acordos internacionais e a legislação vigente no país. / Regulatory bodies are responsible for regulation in various sectors of society. In Brazil, they work in various areas for the development of the country and have as main objective the social, economic and national development. The progress of new technologies in the nuclear field and their commercialization underscores the need for regulation according to international safety standards. The present research searches through an extensive review of the literature identify the international guidelines for regulatory bodies and make a comparative analysis between Brazil and five countries that have independent regulatory bodies in the nuclear sector. The purpose of the work is to contribute to the Brazilian public sectors, with an evaluation of the country's regulation in the perception of specialists and propose guidelines for the structuring of an independent regulatory body, respecting international agreements and the legislation in force in the country.

Les miARN sont de petits ARN non codant dont la taille varie entre 21-24 nucléotides. Ils jouent un rôle de régulateurs post-transcriptionnels en utilisant leur complémentarité de séquence avec l’ARN messager (ARNm) cible afin d’induire sa répression. Grâce à la protéine Argonaute 2 (Ago2) dans laquelle les miARN sont incorporés formant ainsi le complexe miRISC, des cofacteurs sont recrutés afin d’induire la dégradation ou le blocage de la traduction de l’ARNm cible. Initialement connus pour réguler leurs cibles dans le cytoplasme, les miARN sont de plus en plus décrits comme étant des régulateurs de l’expression génique au niveau nucléaire. Dans ce travail, nous avons démontré la présence, au sein du noyau, d’un nouveau mécanisme de régulation post-transcriptionel par les miARN dont les facteurs majeurs sont Sfpq et Pspc1 / Micro-RNA, nuclear regulation, gene silencing, SfpqThere is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here we show by quantitative proteomic analysis that Ago2 interacts with the complex formed by Sfpq, Pspc1 and NonO in a RNA-dependent fashion. Sfpq mediates the interaction between miRISC with Pspc1 and NonO in the nucleoplasm. By HITS-CLIP coupled with transcriptomic analysis, we demonstrated that Sfpq specifically controls the downregulation of a subset of crucial let-7a-target mRNAs in stem cells, including Lin28a, Prtg, and Igf2bp1. Sfpq directly binds to specific sequence in the 3'UTR to promote the recruitment of selected nucleoplasmic miRNAs and triggers the decay, as we show for Lin28a mRNA. These results extend the miRNA-mediated post-transcriptional gene silencing into the nucleus and indicate that a dual strategy