Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Ciência da Computação, 2015. / Submitted by Ana Cristina Barbosa da Silva (annabds@hotmail.com) on 2015-04-27T15:56:38Z No. of bitstreams: 1 2015_DaniloFilgueiraMendonça.pdf: 15442097 bytes, checksum: 3fd8f92515216f0962560e658342894f (MD5) / Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2015-05-14T19:16:39Z (GMT) No. of bitstreams: 1 2015_DaniloFilgueiraMendonça.pdf: 15442097 bytes, checksum: 3fd8f92515216f0962560e658342894f (MD5) / Made available in DSpace on 2015-05-14T19:16:39Z (GMT). No. of bitstreams: 1 2015_DaniloFilgueiraMendonça.pdf: 15442097 bytes, checksum: 3fd8f92515216f0962560e658342894f (MD5) / Um contexto de operação estático não é a realidade para muitos sistemas de software atualmente. Variações de contextos impõe novos desafios ao desenvolvimento de sistemas seguros, o que inclui a ativação de falhas apenas em contextos específicos de operação. A engenharia de requisitos orientada a objetivos (GORE) explicita o ‘por quê’ dos requisitos de um sistema, isto é, a intencionalidade por trás de objetivos do sistema e os meios de se atingi-los. Um Runtime goal model (RGM) adiciona especificação de comportamento ao modelo de objetivos convencional, enquanto um Contextual goal model (CGM) especifica efeitos de contextos sobre objetivos, meios e métricas de qualidade. Visando uma verificação formal da dependabilidade de um Contextual-Runtime goal model (CRGM), nesse trabalho é proposta uma nova abordagem para a análise de dependabilidade orientada a objetivos baseada na técnica de verificação probabilística de modelos. Em particular, são definidas regras para a transformação de um CRGM para um modelo cadeia de Makov de tempo discreto (DTMC) com o qual se possa verificar a confiabilidade de se satisfazer um ou mais objetivos do sistema. Adicionalmente, para diminuir o esforço de análise e aumentar a usabilidade de nossa proposta, um gerador automatizado de código CRGM para DTMC foi implementado e integrado com sucesso à ferramenta gráfica que dá suporte às fases de modelagem e análise de objetivos da metodologia TROPOS. A verificação contextual de dependabilidade resultante reflete os requisitos no CRGM, que podem representar: o projeto de um sistema, cuja verificação ocorreria em fase de projetos; ou um sistema em execução, cujo comportamento pode ser verificado em tempo de execução como parte de uma análise de auto-adaptação com foco em dependabilidade. / A static and stable operation environment is not a reality for many systems nowadays. Context variations impose many threats to systems safety, including the activation of context specific failures. Goal-oriented requirements engineering (GORE) brings forward the ‘why’ of system requirements, i.e., the intentionality behind system goals and the means to meet then. A runtime goal model adds a behaviour specification layer to a conventional design goal model, and a contextual goal model specifies the context effects over system goals, means and qualitative metrics. In order to formally verify the dependability of a CRGM, we propose a new goal-oriented dependability analysis based on the probabilistic model checking technique. In particular, we define rules for the transformation of a CRGM into a DTMC model that can be verified for the reliability of the fulfilment of one or more system goals. Also, to mitigate the analysis overhead and increase the usability of our proposal, we have successfully implemented and integrated a CRGM to DTMC code generator to the graphical tool that supports the goal modelling and analysis phases of the TROPOS development methodology. The resulting contextual dependability verification reflects the system requirements in a CRGM, which may represent: a system-to-be, whose verification would take place at design-time; or a running system, whose behaviour can be verified at runtime as part of a self-adaptation analysis targeting dependability.

Chemotaxis, the ability of a cell to change its motility as a response to environmental stimuli, belongs to the most important signal transduction mechanisms in life. Evolution has created a plethora of different molecular mechanisms to enable cells to react appropriately to extracellular changes. In this thesis, chemotactic signal transduction pathways in bacteria, in particular two component signalling in R. sphaeroides, and eukaryotes, in particular human axon guidance, are studied by means of X-ray crystallography complemented with biophysical, biochemical and cellular studies. Two-component signal transduction in bacteria is one of the most abundant signalling pathways in biology. Here the determinants for specificity for a crucial sensor kinase-response regulator interaction are presented and used to design novel, synthetic two-component pairs. The activation mechanism of response regulators has been extensively studied and a model for activation that crucially involves a Thr and a Tyr residue has been widely accepted in the field. In this thesis, two structures of a response regulator from R. sphaeroides are presented and together with biophysical and cellular assays suggest a novel paradigm for response regulator activation. Axon guidance is an essential process in human development and relies crucially on chemotaxis. Two signalling pathways, the plexin-semaphorin and the Rgm-Neogenin pathway are studied extensively in this work. Structures of the intracellular region of Plexin-B1 provide an elegant mechanism explaining how ligand binding events on the extracellular and intracellular side can be integrated into a single signalling output. The study of RgmB in complex with its receptor Neogenin provides the first structural insight into the important family of repulsive guidance molecules and explains their role in the disease juvenile hemachromatosis. In summary, this work provides insights into a plethora of chemotactic pathways and extends our current knowledge of these important mechanisms significantly.

De nombreux noyaux atomiques et hypernoyaux se modélisent comme des structures à trois corps. C'est le cas, par exemple, de noyaux à halo, comme 6He, ou de noyaux stables, comme 12C et 9Be. En effet, 6He se caractérise comme un système à trois corps, formé d'un coeur (une particule alpha) et de deux neutrons de valence faiblement liés. Le noyau de 12C peut s'étudier comme un système lié formé de trois particules alphas, tandis que 9Be peut être décrit comme la liaison de deux particules alphas et d'un neutron. Dans les exemples précédents, les particules alphas sont des amas de nucléons. Elles possèdent donc une structure interne dont il faut tenir compte en raison du principe de Pauli. Les modèles les plus réalistes pour décrire les structures à trois corps sont les modèles "microscopiques". Ces modèles prennent en compte explicitement tous les nucléons et respectent exactement le principe d'antisymétrisation de Pauli. Cependant, l'application de ces modèles est fortement limitée en pratique, car ils exigent de trop nombreux et trop longs calculs. Par conséquent, pour simplifier considérablement les calculs et permettre l'étude des structures à trois corps, des modèles moins détaillés, de type "semi-microscopiques", sont également développés. Dans ces modèles, on représente les amas de nucléons comme de simples particules ponctuelles. Dans ce cas, la modélisation consiste à construire les potentiels effectifs entre les amas, puis à les employer dans les modèles à trois corps. Dans ce travail, nous avons développé les modèles "semi-microscopiques à trois corps". Les potentiels effectifs entre amas sont directement déduits des forces entre nucléons (selon la RGM à 2 corps). Ces potentiels sont "non-locaux", et dépendent des énergies des amas qui interagissent. Ils permettent de simuler le principe de Pauli et les échanges de nucléons entre les amas. La dépendance en l'énergie se révèle être un inconvénient dans les modèles à trois corps. Les potentiels effectifs sont par conséquent transformés en de nouveaux potentiels (non-locaux) indépendants de l'énergie, bien adaptés aux modèles à trois corps. Les modèles "semi-microscopiques" sont beaucoup plus simples et plus rapides que les modèles "microscopiques". Ils fournissent les fonctions d'onde des états liés à trois corps des noyaux légers et hypernoyaux. Cela permet d'une part de comprendre les propriétés spectroscopiques nucléaires, et d'autre part, cela ouvre la voie pour de futurs modèles de réactions nucléaires impliquant les structures à trois corps. / Several atomic nuclei and hypernuclei can be modelled as three-body structures: e.g., two-neutron halo nuclei, such as 6He, and other nuclei, such as 12C and 9Be. Indeed 6He can be represented as a three-body system, made up of a core (an alpha particle) and two weakly bound valence neutrons. The 12C nucleus can be studied as a bound system formed by three alpha particles, while the 9Be nucleus can be described as the binding of two alpha particles and one neutron. In these typical examples, the alpha particles are clusters of nucleons. They have an internal structure that must be taken into account because of the Pauli principle. The most realistic models are the "microscopic models". In these models, all the nucleons are taken into account, and the Pauli antisymmetrisation principle is fully respected. However, the application of the "microscopic models" is limited in practice, because they require too many laborious calculations. Therefore, in order to greatly simplify the calculations, "semi-microscopic models" are developed. In those models, the clusters of nucleons are treated as ("structureless") pointlike particles. The models then consist in determining the effective potentials between the clusters, and in using them in three-body models. In the present work, we have developed "semi-microscopic models". The effective potentials between the clusters are directly obtained from the interactions between nucleons (according to the two-cluster RGM). These potentials are "nonlocal", and depend on the energy of the interacting clusters. The non-locality is a direct consequence of the Pauli principle and the exchanges of nucleons between the clusters. The energy-dependence of the potentials turns out to be a drawback in three-body models. Therefore, the effective potentials are transformed into energy-independent potentials, which can be used in three-body models. The "semi-microscopic models" are much simpler and faster than the "microscopic models". They provide the three-body bound-state wave functions (i.e., the spectroscopic properties and the structure) of light nuclei and hypernuclei. Such wave functions are also the basic ingredient that will be used in future reactions models.

Ronnie Gardiner Method (RGM) is a multi-sensory training method aimed for peoplewith brain damage. The method is based on music, rhythm and movement. Previousstudies show that the method provides improved balance, gait, grip strength andworking memory and has positive effects regarding motor skills, cognition and on anemotional level. Few studies have studied RGM's impact on language. However, RGMhas been seen to have a positive effect on word flow. The purpose of the present thesisis to deepen knowledge about how RGM affects the flow of words in people withacquired brain damage with and without aphasia, and to investigate relatives' experienceof communication ability before and after RGM training. Eight participants withacquired brain injury, with and without aphasia participated. Tests that was used werethe language battery Western Aphasia Battery - Revised (WAB-R), "Tell a picture"from WAB-R and FAS, animals and verbs and the related form CommunicativeEffectiveness Index (CETI). An improvement in phonological word flow in bothpersons with and without aphasia was noted. However, no difference was seen in termsof semantic word flow and relative estimation of communication ability. Unexpectedly,lower number of words / minute and decreased lexical density after treatment werenoted, while a tendency for increased lexical variation was measured. / Ronnie Gardiner Method (RGM) är en multisensorisk träningsmetod som riktar sig tillpersoner med hjärnskada. Metoden bygger på musik, rytm och rörelse. Tidigare studiervisar att metoden ger förbättrad balans, gång, greppstyrka samt arbetsminne och harpositiva effekter avseende motorik, kognition samt på ett känslomässigt plan. Få studierhar studerat RGM:s påverkan på språket. Man har dock sett att RGM förefaller påverkaordflödet positivt. Syftet med föreliggande uppsats är att fördjupa kunskapen om hurRGM påverkar ordflödet hos personer med förvärvad hjärnskada med respektive utanafasi samt att undersöka anhörigas upplevelse av kommunikationsförmågan före ochefter RGM-träning. Åtta deltagare med förvärvad hjärnskada, med respektive utan afasideltog. Tester som användes var: språkbatteriet Western Aphasia Battery – Revised(WAB-R), ”Berätta till en bild” ur WAB-R och FAS, djur och verb samtanhörigformuläret Communicative Effectiveness Index (CETI). En förbättring påfonologiskt ordflöde hos både personer med respektive utan afasi kunde konstateras.Däremot sågs ingen skillnad vad gäller semantiskt ordflöde respektive anhörigskattningav kommunikationsförmåga. Oväntat konstaterades lägre antal ord/minut och minskadlexikal densitet efter behandling, medan en tendens till ökad lexikal variationuppmättes.

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The agile principles applied to software engineering include iterative and incremental development, frequent releases of software, direct stakeholder involvement, minimal documentation and welcome changing requirements even late in the development cycle. The Agile Requirements Engineering applies the above mentioned principles to the Requirements Engineering process. Agile Requirements Engineering welcomes changing requirements even late in the development cycle. This is achieved by using the agile practice of evolutionary requirements which suggests that requirements should evolve over the course of many iterations rather than being gathered and specified upfront. Hence, changes to requirements even late in the development cycle can be accommodated easily. There is however, no real process to the agile approach to Requirements Engineering. In order to overcome this disadvantage, we propose to adapt the Requirements Generation Model (a plan-driven Requirements Engineering model) to an agile environment in order to structure the Agile Requirements Engineering process. The hybrid model named the Agile Requirements Generation Model is a soft-structured process that supports the intents of the agile approach. This model combines the best features of the Requirements Generation Model and Agile Software Development. / Master of Science

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Em diversos estados do Brasil, foram relatadas epidemias de infecções causadas por micobactérias de crescimento rápido (MCR) desde o ano 2000. A maioria dos casos foi principalmente associada ao clone BRA100 de Mycobacterium massiliense, recentemente renomeada para Mycobacterium abscessus subsp. bolletii, isolado de pacientes submetidos a procedimentos invasivos nos quais os instrumentos médicos não foram adequadamente esterilizados e/ou desinfetados. Sendo as quinolonas uma opção no tratamento de infecções por MCR e sugerida para esquemas terapêuticos para esses surtos, foram avaliadas nesse trabalho as atividades in vitro de quatro gerações de quinolonas para cepas clinicas e de referência de MCR através da microdiluição em caldo. Também foram analisadas as sequências peptídicas das regiões determinantes da resistência a quinolonas (RDRQ) das subunidades A e B da DNA gyrase (GyrA e GyrB) após o seqüenciamento de DNA seguido pela tradução da sequência de aminoácidos. Cinquenta e quatro cepas de M. abscessus subsp bolletii, incluindo o clone BRA100, isoladas em diferentes estados do Brasil, e 19 cepas de referência de MCR foram caracterizadas. Todas as 54 cepas clínicas de M. abscessus subsp. bolletii foram resistentes a todas as gerações de quinolonas e mostraram o mesmo resíduo nas RDRQ, incluindo Ala-83 em GyrA, Arg-447 e Asp-464 em GyrB, descritos como sendo responsáveis por gerar um baixo nível de resistência a quinolonas em micobactérias. Porém, outras espécies de MCR apresentaram diferentes susceptibilidade e padrões de mutações contrários aos classicamente já definidos, sugerindo que outros mecanismos de resistência, diferentes de mutações em gyrA e gyrB também possam estar envolvidos na alta resistência a quinolonas. / Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) have been reported in many Brazilian states since 2000. Most of the cases were mainly associated to Mycobacterium massiliense, recently renamed as Mycobacterium abscessus subsp. bolletii, BRA100 clone recovered from patients who had undergone invasive procedures, in which medical instruments have not been properly sterilized and / or disinfected. Since quinolones have represented an option for the treatment of general RGM infections and suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro activities of four generations of quinolones for clinical and reference RGM by broth microdilution, and analysis of peptide sequences of the quinolone resistance determining regions (QRDR) of GyrA and GyrB after DNA sequencing followed by amino acid translation. Fifty four isolates of M. abscessus subsp bolletii, including clone BRA100, recovered in different states of Brazil, and 19 reference strains of RGM species were characterized. All 54 M. abscessus subsp. bolletii isolates were resistant to all generations of quinolones and showed the same amino acids in the QRDR including the Ala-83 in GyrA, Arg-447 and Asp-464 in GyrB, described as responsible for an intrinsic low level of resistance to quinolones in mycobacteria. But other RGM species presented distinct susceptibilities to this class of antimicrobials and patterns of mutations contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones.

Background: The Platinum mining operations in South Africa mining platinum containing ore from areas where variable amounts of uranium are found, leading to the possibility of occupational exposure to the radioactive disintegration products of Uranium-238 and in particular the gas Radon-222. No scientific data is available for occupational exposure to Radon-222 in South African platinum mining operations. Objective: To determine the risk of occupational exposure to the radioactive disintegration products of naturally occurring Radon-222 gas in a South African platinum mine. Design: Quantitative sampling (personal and static) to establish baseline data on exposure to radioactive disintegration products of naturally occurring Radon-222 gas in a underground South African platinum mine. Setting: The Bafokeng Rasimone platinum mine located 30 km North West of Rustenburg in the Bushveld complex in the North West Province of South Africa. Study subjects: One hundred and seventy four potentially highest exposed underground employees and one hundred and twelve static underground samples were sampled. Method: Personal and area samples were taken on selected employees and in locations using RGM samplers using CR-39 plastic as a detection medium. Employees were selected to sample the highest exposed occupations and static samples were located to sample returning air from levels underneath the sampling point before it is exhausted to the above ground atmosphere. After analysis by an accredited laboratory, the results were converted to exposure following the National Council on Radiation Protection-78 methodology. Main outcome measures: Quantify the relative risks of potentially highest exposed employee`s exposure to the radioactive disintegration products of naturally occurring Radon-222 gas in underground working areas in milliSievert per year. Results: The mean reference background exposure averaged 0.6168 mSv/a with underground personal exposure averaging 0.6808 mSv/a, and underground static exposure averaging 0.8726 mSv/a. These values are substantially below the 50 mSv/a Occupational Exposure Limit, and only pose a slightly elevated risk for the development of lung cancer above the normal back-ground exposure. Mining Team leaders and rock drill operators were identified as the potentially highest exposed employees due to the close proximity to the working face, large amounts of time spent close to the working face and the lower ventilation volumes at the working face, with Team leaders having the highest exposure of the sampled occupations with a average of 1.16 mSv/a. Conclusions: Occupational exposure to radioactive disintegration products of naturally occurring Radon-222 gas in the underground air of a South African platinum mine does not pose a significant risk to the health of employees working in the platinum mine. / Thesis (MSc (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2013.

Background: The Platinum mining operations in South Africa mining platinum containing ore from areas where variable amounts of uranium are found, leading to the possibility of occupational exposure to the radioactive disintegration products of Uranium-238 and in particular the gas Radon-222. No scientific data is available for occupational exposure to Radon-222 in South African platinum mining operations. Objective: To determine the risk of occupational exposure to the radioactive disintegration products of naturally occurring Radon-222 gas in a South African platinum mine. Design: Quantitative sampling (personal and static) to establish baseline data on exposure to radioactive disintegration products of naturally occurring Radon-222 gas in a underground South African platinum mine. Setting: The Bafokeng Rasimone platinum mine located 30 km North West of Rustenburg in the Bushveld complex in the North West Province of South Africa. Study subjects: One hundred and seventy four potentially highest exposed underground employees and one hundred and twelve static underground samples were sampled. Method: Personal and area samples were taken on selected employees and in locations using RGM samplers using CR-39 plastic as a detection medium. Employees were selected to sample the highest exposed occupations and static samples were located to sample returning air from levels underneath the sampling point before it is exhausted to the above ground atmosphere. After analysis by an accredited laboratory, the results were converted to exposure following the National Council on Radiation Protection-78 methodology. Main outcome measures: Quantify the relative risks of potentially highest exposed employee`s exposure to the radioactive disintegration products of naturally occurring Radon-222 gas in underground working areas in milliSievert per year. Results: The mean reference background exposure averaged 0.6168 mSv/a with underground personal exposure averaging 0.6808 mSv/a, and underground static exposure averaging 0.8726 mSv/a. These values are substantially below the 50 mSv/a Occupational Exposure Limit, and only pose a slightly elevated risk for the development of lung cancer above the normal back-ground exposure. Mining Team leaders and rock drill operators were identified as the potentially highest exposed employees due to the close proximity to the working face, large amounts of time spent close to the working face and the lower ventilation volumes at the working face, with Team leaders having the highest exposure of the sampled occupations with a average of 1.16 mSv/a. Conclusions: Occupational exposure to radioactive disintegration products of naturally occurring Radon-222 gas in the underground air of a South African platinum mine does not pose a significant risk to the health of employees working in the platinum mine. / Thesis (MSc (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2013.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Em diversos estados do Brasil, foram relatadas epidemias de infecções causadas por micobactérias de crescimento rápido (MCR) desde o ano 2000. A maioria dos casos foi principalmente associada ao clone BRA100 de Mycobacterium massiliense, recentemente renomeada para Mycobacterium abscessus subsp. bolletii, isolado de pacientes submetidos a procedimentos invasivos nos quais os instrumentos médicos não foram adequadamente esterilizados e/ou desinfetados. Sendo as quinolonas uma opção no tratamento de infecções por MCR e sugerida para esquemas terapêuticos para esses surtos, foram avaliadas nesse trabalho as atividades in vitro de quatro gerações de quinolonas para cepas clinicas e de referência de MCR através da microdiluição em caldo. Também foram analisadas as sequências peptídicas das regiões determinantes da resistência a quinolonas (RDRQ) das subunidades A e B da DNA gyrase (GyrA e GyrB) após o seqüenciamento de DNA seguido pela tradução da sequência de aminoácidos. Cinquenta e quatro cepas de M. abscessus subsp bolletii, incluindo o clone BRA100, isoladas em diferentes estados do Brasil, e 19 cepas de referência de MCR foram caracterizadas. Todas as 54 cepas clínicas de M. abscessus subsp. bolletii foram resistentes a todas as gerações de quinolonas e mostraram o mesmo resíduo nas RDRQ, incluindo Ala-83 em GyrA, Arg-447 e Asp-464 em GyrB, descritos como sendo responsáveis por gerar um baixo nível de resistência a quinolonas em micobactérias. Porém, outras espécies de MCR apresentaram diferentes susceptibilidade e padrões de mutações contrários aos classicamente já definidos, sugerindo que outros mecanismos de resistência, diferentes de mutações em gyrA e gyrB também possam estar envolvidos na alta resistência a quinolonas. / Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) have been reported in many Brazilian states since 2000. Most of the cases were mainly associated to Mycobacterium massiliense, recently renamed as Mycobacterium abscessus subsp. bolletii, BRA100 clone recovered from patients who had undergone invasive procedures, in which medical instruments have not been properly sterilized and / or disinfected. Since quinolones have represented an option for the treatment of general RGM infections and suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro activities of four generations of quinolones for clinical and reference RGM by broth microdilution, and analysis of peptide sequences of the quinolone resistance determining regions (QRDR) of GyrA and GyrB after DNA sequencing followed by amino acid translation. Fifty four isolates of M. abscessus subsp bolletii, including clone BRA100, recovered in different states of Brazil, and 19 reference strains of RGM species were characterized. All 54 M. abscessus subsp. bolletii isolates were resistant to all generations of quinolones and showed the same amino acids in the QRDR including the Ala-83 in GyrA, Arg-447 and Asp-464 in GyrB, described as responsible for an intrinsic low level of resistance to quinolones in mycobacteria. But other RGM species presented distinct susceptibilities to this class of antimicrobials and patterns of mutations contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones.