The human genome is constantly under the attack by various damaging agents, leading to the breakage of one or both strands of DNA that might interfere with RNA processing. Importantly, our cells have evolved diverse mechanisms to rapidly repair various DNA lesions, highlighting the importance of genetic integrity. Defects in DNA repair and/or RNA metabolism can lead to a variety of human hereditary diseases, with pathologies including growth and developmental defects, immunodeficiency, predisposition to cancer, and neurodegeneration. Mutations in the BRAT1 (BRCA1-associated ATM activator-1) protein have been associated with neurological disorders characterized by heterogenous phenotypes with varying levels of clinical severity ranging from microcephaly, hypertonia, epilepsy, seizures, and early death in the first two years of life to mild cerebellar atrophy and ataxia. Previously, BRAT1 protein has been implicated in the cellular response to DNA double-strand breaks and ATM signalling. However, the exact mechanism/s by which mutations in BRAT1 gene trigger neurological disorders are largely unknown. Recently, we have identified a homozygous missense c.185T>A (p.Val62Glu) variant in BRAT1 that markedly reduced the level of BRAT1 protein in patient-derived cell lines. Surprisingly, our data show that...

Synthetic aperture sonar (SAS) is a wide-beam sonar technique commonly used for mapping the seafloor at high resolution. The Acoustics Research Group at the University of Canterbury operates a towed SAS system known as KiwiSAS-IV. This is currently being redesigned with the aim of reducing the weight, size and power requirements of the system. The long term goal is to make it capable of being mounted on an autonomous underwater vehicle (AUV) so that mapping of remote and/or dangerous waters can be accomplished without human interaction. This thesis presents the design of the front-end electronics used to drive the 36 transducers to produce the acoustic beam and receive the returning signals after they have reflected off a target. To achieve sufficient range, the transducers are driven with a 200 Vₚ₋ₚ signal with a maximum frequency of 110 kHz. This design uses class D switching amplifiers to generate these waveforms. The AD9271 integrated circuit, which can handle eight transducers simultaneously, is used to amplify the incoming signals and sample them at up to 50 MHz. This high sampling rate multiplied by all 36 transducers results in an amount of data which is too great for a conventional microprocessor-based system to handle. Instead, an FPGA is used to receive this data, decimate it using multiplier-free cascaded integrator-comb (CIC) filters, and then pass it to the back-end system for further processing and storage. A prototype circuit was created to test the theory developed in this thesis. This showed that the system is capable of generating the necessary waveforms and amplifying, capturing, and decimating the returning signals. However, further refinement is required before it is able to be used in the sonar system.

Dynamical maps for magnetic components are fundamental to studies of beam dynamics in accelerators. However, it is usually not possible to write down maps in closed form for anything other than simplified models of standard accelerator magnets. In the work presented here, the magnetic field is expressed in analytical form obtained from fitting Fourier series to a 3D numerical solution of Maxwell’s equations. Dynamical maps are computed for a particle moving through this field by applying a second order (with the paraxial approximation) explicit symplectic integrator. These techniques are used to study the beam dynamics in the first non-scaling FFAG ever built, EMMA, especially challenging regarding the validity of the paraxial approximation for the large excursion of particle trajectories. The EMMA lattice has four degrees of freedom (strength and transverse position of each of the two quadrupoles in each periodic cell). Dynamical maps, computed for a set of lattice configurations, may be efficiently used to predict the dynamics in any lattice configuration. We interpolate the coefficients of the generating function for the given configuration, ensuring the symplecticity of the solution. An optimisation routine uses this tool to look for a lattice defined by four constraints on the time of flight at different beam energies. This provides a way to determine the tuning of the lattice required to produce a desired variation of time of flight with energy, which is one of the key characteristics for beam acceleration in EMMA. These tools are then benchmarked against data from the recent EMMA commissioning.

Transcription of human protein-coding genes and most small nuclear RNA genes is mediated by RNA Polymerase II (Pol II). During a cycle of transcription, Pol II recruits a variety of factors that facilitate transcription elongation, RNA processing and termination, through its long, unstructured C-terminal domain (CTD). The CTD in humans comprises 52 tandem heptapeptide repeats with the consensus sequence Y₁S₂P₃T₄S₅P₆S₇. Each amino acid of the heptapeptide can be chemically modified, which influences the recruitment of other protein factors to the transcription machinery. Not all enzymes that modify the CTD have been discovered. Recent studies have identified a novel CTD phosphatase: RPAP2 in humans and its yeast homologue Rtr1, which dephosphorylate phospho-Ser5 of the heptapeptide repeats. RPAP2 has been shown to stimulate 3' end cleavage of nascent snRNAs through recruitment of the Integrator complex, and unpublished work suggests the involvement of RPAP2 in regulating vertebrate developmental programs. However, the exact mechanisms that regulate the function of human RPAP2, and thus impact on CTD modification, are not well-understood. This thesis presents a novel mechanism whereby RPAP2 recruits protein phosphatase 1 (PP1) to snRNA genes, where PP1 is postulated to activate P-TEFb to phosphorylate Ser2 of the CTD. At the same time, P-TEFb may have a role in activating the phosphatase activity of RPAP2. Furthermore, RPAP2 itself is shown to be recruited to a number of gene promoters by the RPRD1A protein, which also stimulates its phosphatase activity. RPAP2 was shown to have another role in regulating transcription termination: by recruiting the Integrator complex, which is shown here to mediate termination of snRNA genes, and by a so far unknown mechanism on a long protein-coding gene. An attempt was made to purify and crystallise the human RPAP2 to obtain a crystal structure, however the crystallisation trials were not successful. Finally, a correlation was found in human embryonic stem cells and induced pluripotent stem cells between low levels of RPAP2 and high levels of CTD Ser5P, suggesting a potential involvement of RPAP2 in regulating transcription at a key developmental stage. The results presented here contribute to the understanding of human transcriptional mechanisms and the numerous interactions within the transcription machinery. In particular, the mechanism of terminating the transcription of snRNA genes is identified. An interesting possibility is the regulation of development and stem cell differentiation by RPAP2; however the exact pathways by which this occurs are yet to be discovered.

Este estudo trata-se de uma revisão sistemática cujo objetivo foi levantar as evidências na literatura científica da eficácia dos integradores químicos no monitoramento dos ciclos de esterilização a vapor. As estratégias de busca foram realizadas nas bases de dados MEDLINE, LILACS, CINAHL, DEDALUS, OVID, Cochrane e Google Acadêmico, através de combinações dos termos esterilização (sterilization), integrador químico (chemical integrator), indicador químico (chemical indicator), indicador biológico (biological indicator), monitoramento (monitoring) e reagente (reagent). Foi realizado ainda busca em árvore das referências dos artigos selecionados. Os estudos foram selecionados sem restrições quanta a data de publicação e a língua, com critérios de inclusão de estudos básicos experimentais comparativos quanto ao desempenho dos indicadores químicos frente a cinética de morte microbiana ou resultados obtidos por meio de indicadores biológicos em ciclos de esterilização a vapor e exclusão de estudos realizados com métodos de esterilização que não a vapor e estudos que evidenciam utilização de indicadores químicos classes 1, 2, 3 e 4. No total foram selecionados 7 estudos, sendo que o mais antigo data 1975 e o mais recente 2006, 6 destes estudos compararam indicadores químicos à indicadores biológicos e 1 estudo comparou indicadores químicos frente a curva da cinética de morte microbiana dos Bacillus stearothermophilus. Em relação à origem dos estudos 1 é europeu e 6 americanos, sendo 1 destes brasileiro. Para análise e avaliação dos estudos utilizou-se a seguinte categorização: escopo, tipo de estudo, unidades amostrais, amostra, esterilizador utilizado, procedimentos, análise dos dados, limitações, resultados, conclusões e comentários. Observou-se uma tendência de utilização de temperaturas de 132º e 121ºC para a realização dos experimentos. O tamanho amostral variou de 1 a 47 indicadores por ciclo e o número de ciclos reproduzidos de 1 a 12. Não houve uma tendência em relação aos esterilizadores utilizados e tempos de exposição adotados. 4 estudos utilizaram integradores químicos nos experimentos, sendo que 2 destes utilizaram indicadores não classificados, concomitantemente. Analisando os resultados dos estudos conclui-se que nenhum integradores classe 5 nem indicadores biológicos apresenta respostas 100% sensíveis ou 100% específicas quanto ao desempenho esperado e que Integradores químicos classe 5 e indicadores biológicos apresentam variações de sensibilidade e resistência muito próximos uns dos outros, não cabendo neste momento classificá-los numa escala de efetivos a não efetivos. Os resultados obtidos dos integradores classe 6 mostram 100% de viragem dentro do tempo estimado, sugerindo que estes integradores são efetivos para o monitoramento dos ciclos a vapor / This study is a systematic review, with the objective of collecting evidences in the scientific literature, on the efficacy of the chemical integrators in the monitoring of the steam sterilization cycles. The search strategies were carried out in the MEDLINE, LILACS, CINAHL, DEDALUS, OVID, Cochrane and Academic Google data bases, through the combination of the terms sterilization (esterilização), chemical integrator (integrador químico), chemical indicator (indicador químico), biological indicator (indicador biológico), monitoring (monitoramento), and reagent (reagente). A search in the references tree of the selected articles was also carried out. The studies were selected without restrictions concerning publication date and language, with inclusion criteria of basic experimental comparative studies as for the performance of chemical indicators concerning the kinetics of the microbial death or the results obtained by means of biological indicators in steam sterilization cycles and, the exclusion of studies carried out with non–steam sterilization methods and studies that show the use of chemical indicators classes 1, 2, 3 and 4. A total of 7 studies were selected, the oldest from 1975 and the most recent from 2006; 6 of these studies compared chemical indicators to biological indicators and 1 study compared chemical indicators facing the microbial death kinetics curve of the stearothermophilus Bacillus. In relation to the origin of the studies, 1 is European and 6 are American, 1 of them being Brazilian. For the analyses and assessment of the studies, the following categorization was used: purpose, kind of study, sample units, sample, sterilizer used, procedures, data analyses, limitations, results, conclusions and comments. It was observed a trend of utilization of temperatures between 132º and 121º Celsius for the carrying out of the experiments was observed. The sample size varied from 1 to 47 indicators per cycle and the number of cycles reproduced from 1 to 12. There was no trend concerning the sterilizers used and the exposure time periods adopted. Four studies used chemical integrators in the experiments, and 2 of them used non-classified indicators, concurrently. By analyzing the results of the studies, we came to the conclusion that neither class 5 integrators nor biological indicators present 100% sensitive or 100% specific answers, as for the expected performance, and the class 5 chemical integrators and the biological indicators present variations of sensibility and resistance very close to each other, thus, at the moment they should not be classified in a effective to non-effective scale. The results obtained from integrators class 6 show a 100% turning inside the estimated time, suggesting that these integrators are effective for the monitoring of the steam cycles

Nos últimos anos, há uma crescente preocupação com o ensino de engenharia, no Brasil e no mundo. Um dos problemas dos cursos são as disciplinas do Ciclo Básico, que são muito teóricas e fora do contexto dos futuros engenheiros. O objetivo deste trabalho é estabelecer e caracterizar correlações entre disciplinas básicas do curso de Engenharia Elétrica, da Escola Politécnica da Universidade de São Paulo, tendo como referência a Estrutura Curricular vigente no período de 2000 a 2010. Para este estudo, foi realizada uma revisão da literatura, abordando-se fatos históricos no ensino de engenharia, na Europa e no Brasil, bem como um levantamento e estudo do programa de ensino, de gabaritos e provas das disciplinas escolhidas para essa pesquisa. Foram identificados conteúdos e/ou habilidades que caracterizam as correlações, verificando a importância deles para o desenvolvimento das disciplinas. Entre os resultados deste estudo, propõe-se um Projeto Integrador como alternativa para a melhoria do desempenho acadêmico dos estudantes considerados de alto risco, de forma a possibilitar a compreensão de correlações entre disciplinas, promovendo a interdisciplinaridade e a articulação de conhecimentos em cada semestre letivo trabalhado. Entre as conclusões, destaca-se a importância de os docentes do Ciclo Básico e do Ciclo Profissionalizante abrirem amplo debate, para que se estabeleça conexões importantes entre as disciplinas do curso, de forma a possibilitar a amenização dos problemas do Ciclo Básico de cursos de engenharia. / In recent years, there is growing concern with on the teaching of engineering in Brazil and world. One of the problems of the courses is the disciplines of the Basic Cycle, which are very theoretical and out of the context of the future engineers. The objective of this work is to establish and characterize correlations between basic disciplines of the Electrical Engineering course, at the Polytechnic School of University of São Paulo, with reference to the Curricular Structure from 2000 to 2010. For this study, a literature review was made, approaching historical facts in engineering education, in Europe and Brazil, as well as a survey and study of the teaching program, templates and tests of the disciplines chosen for this research. Content and/or skills that characterize the correlations were identified, verifying their importance for the development of the disciplines. Among the results of this study, we propose an Integrator Project as an alternative to improve the academic performance of students considered to be high-risk, as way of allow the understanding of correlations between disciplines, promoting the interdisciplinarity and the articulation of knowledge in each academic semester worked. Among the conclusions, stands out the importance of the teachers of Basic Cycle and Vocational Cycle opening a wide debate, to establishing important connections between the course materials, as way of make it possible to soften the problems of the Basic Cycle of engineering courses.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2016-12-23T11:50:44Z No. of bitstreams: 1 Vilma Justina da Silva.pdf: 6090269 bytes, checksum: c635aea974d86efc3d79709fb099a3b5 (MD5) / Made available in DSpace on 2016-12-23T11:50:44Z (GMT). No. of bitstreams: 1 Vilma Justina da Silva.pdf: 6090269 bytes, checksum: c635aea974d86efc3d79709fb099a3b5 (MD5) Previous issue date: 2016-12-09 / What are the contributions of Reggio Emilia educational approach to the curriculum of early childhood education? What is the curriculum proposed for the care of children of 4 (four) and (5) five years old, based on the mandatory admission to public schools in São Paulo? The overall objective of the research results from the context of its investigation: to analyze the proposal of the Integrator Curriculum for the children of São Paulo, based on the possible influences and inspirations of the curriculum for the Reggio Emilia children schools. The conceptual theoretical basis on the discussion of Curriculum, childhood education in São Paulo, and the educational approach to children of Reggio Emilia schools, was based on the studies of some experts authors in childhood education, which has contributed to the conception of a protagonist child, that owns its culture and the “hundred” languages. Publications of the Ministry of Education and the Municipal Secretary of São Paulo Education and the Statute for schools and early childhood care centers for the children of the commune of Reggio Emilia complement the theoretical foundation. The chosen methodological approach for this dissertation includes qualitative research, of bibliographical and documentary analysis. The date analyzed shows that it is possible to establish connections between both contexts, when it comes to principles, concepts and values. Therefore, it is possible to affirm that is a major challenge that the Public Early Childhood Education Policies become "Public Policies for Children" and the pedagogy of listening and of relations has much to contribute in building a curriculum that considers the child and its entirety / Quais contribuições da abordagem educativa de Reggio Emilia podem ser identificadas na construção de um currículo para Educação Infantil Paulistana? Qual o currículo proposto para o atendimento das crianças de 4 (quatro) e 5 (cinco) anos de idade, a partir da obrigatoriedade de ingresso nas escolas públicas do município de São Paulo? O objetivo geral da pesquisa decorre da contextualização da sua problemática: analisar a proposta de formulação do Currículo Integrador da Infância Paulistana, substantivada pelas possíveis influências e inspirações do currículo para infância das escolas de Reggio Emilia. Para discussão de temas como Currículo, Educação Infantil Paulistana e a abordagem educativa das escolas para infância de Reggio Emilia, foram utilizados como base teórico conceitual os estudos de alguns autores especialistas em educação infantil, que tem contribuído para uma concepção de criança protagonista, que possui sua cultura e “cem” linguagens. As publicações do Ministério da Educação, da Secretaria Municipal de Educação de São Paulo e o Regimento Escolas e Creches para a Infância da Comuna de Reggio Emilia, complementaram a fundamentação teórica. O caminho metodológico escolhido contempla a abordagem da pesquisa qualitativa, de natureza bibliográfica e análise documental. Os dados analisados demonstraram as pontes entre os dois contextos distintos no que se refere aos princípios, concepções e valores. Portanto, é possível afirmar que é um grande desafio que as Políticas Públicas de Educação Infantil tornem-se “Políticas Públicas da Infância”, e que a Pedagogia da Escuta e das Relações tem muito a contribuir na construção de um currículo que considera a criança em sua integralidade

O objetivo desta tese é adaptar um modelo de integração industrial baseado no protocolo de comunicação XML Interface for Robots and Peripherals (XIRP), de modo que este pudesse ser aplicado à realidade de pequenas e médias empresas brasileiras (PMEs). Para que isto fosse possível, é necessário estudar os ambientes industriais existentes e a complexidade envolvida na tarefa de integração de dispositivos para os mesmos. Observa-se que estes ambientes são orientados a fabricante com relação às soluções criadas em termos de equipamentos e softwares. Este é o exemplo de grandes empresas como ABB, KUKA, Reis Robotics etc. O fabricante detém a solução de integração e os dispositivos, e estes só podem ser integrados em plataformas deste fabricante. O protocolo de comunicação industrial, no caso o protocolo XIRP, possibilita a comunicação entre dispositivos e sistemas controladores de maneira padronizada, permitindo que dispositivos de um fabricante se comuniquem com sistemas de outros fabricantes. Este protocolo é baseado na linguagem eXtensible Markup Language (XML) e fornece a especificação dos arquivos de esquema XML (XML schema), os quais permitem a criação de uma descrição de dispositivos e a composição de mensagens a serem trocadas entre eles. Para tanto, foi necessário criar a partir do padrão, toda a infra-estrutura de comunicação e sistema de integração de dispositivos. Vale observar que o padrão XIRP foi criado levando em consideração dispositivos microprocessados. Como este padrão ainda está em desenvolvimento, e em caso de uma eventual adaptação a ele, seria impraticável modificar inteiramente um ambiente de produção por meio de substituição de equipamentos. Desta forma, este projeto de pesquisa apresenta uma infra-estrutura que consista em um sistema integrador para a adaptação gradativa a este protocolo de comunicação. O sistema integrador proposto permite a incorporação de dispositivos XIRP ou não-XIRP. Considerando que um dispositivo já troque mensagens compatíveis com o XIRP, a sua integração e operação em um ambiente de produção seria mais simples. Todavia, mesmo neste caso, o dispositivo ainda precisaria de suporte para trabalhar em uníssono com as demais entidades pertencentes ao ambiente. Esta sinergia é incluída na especificação do ambiente integrador, porém, não faz parte dos resultados pretendidos para a presente pesquisa. Desta forma, a hipótese prevista trata os mecanismos necessários para a incorporação de dispositivos não-XIRP em um ambiente de produção compatível com o padrão XIRP, desde o processo de indexação/identificação do dispositivo à geração automática da aplicação de controle e integração em baixo nível, de modo a permitir a operação do mesmo. / The goal of this research is to adapt an industrial integration model based on the XML Interface for Robots and Peripherals (XIRP) communication protocol, such that it could be applied to the reality of Brazilian small and medium enterprises (SMEs). In order to enable this, it is necessary to study the existing industrial environments and the complexity involved in the device integration task. We observed these environments are manufacture centered considering the solutions created in terms of equipments and softwares. This is the example set by manufacturers like ABB, KUKA, Reis Robotics etc. The manufacturer detains the integration solution and the devices, and these can only be integrated in platforms of the same manufacturer. The industrial communication protocol, in this case XIRP, enables the communication among devices and controller systems in a standardized way, allowing devices from one manufacturer to communicate with systems from another. This protocol is based on the eXtensible Markup Language (XML) and supplies the specification of the XML schema files, which allows the crea- tion of a device description and the composition of messages to be exchanged among devices. Therefore a communication infrastructure and device integra- tion system was built from the standard. Note that the XIRP standard was created considering processor based devices. As this standard is still in development, and in case of an eventual adaptation to it, it would be impracticable to change an entire production environment by means of equipment exchange. Therefore, this research project presents an infrastructure that consists in an integrator system to gradually adapt to this communication protocol. The proposed integrator system allows the incorporation of XIRP or non-XIRP devices. Considering a device already exchanges messages by means of XIRP compliant messages, its integration and operation would be simpler in a production environment. However, even in this case, the device would still need support to operate in unison with other entities pertaining to the environment. This synergy is included in the specification of the integrator environment, although, it is not part of the intended results for this research. Therefore, the foreseen hypothesis deals with the necessary mechanisms to incorporate non-XIRP devices in a production environment compliant with the XIRP standard, from the device indexing/identification to the automatic generation of the control application and its low level integration, in order to allow its operation.

Nos últimos anos, há uma crescente preocupação com o ensino de engenharia, no Brasil e no mundo. Um dos problemas dos cursos são as disciplinas do Ciclo Básico, que são muito teóricas e fora do contexto dos futuros engenheiros. O objetivo deste trabalho é estabelecer e caracterizar correlações entre disciplinas básicas do curso de Engenharia Elétrica, da Escola Politécnica da Universidade de São Paulo, tendo como referência a Estrutura Curricular vigente no período de 2000 a 2010. Para este estudo, foi realizada uma revisão da literatura, abordando-se fatos históricos no ensino de engenharia, na Europa e no Brasil, bem como um levantamento e estudo do programa de ensino, de gabaritos e provas das disciplinas escolhidas para essa pesquisa. Foram identificados conteúdos e/ou habilidades que caracterizam as correlações, verificando a importância deles para o desenvolvimento das disciplinas. Entre os resultados deste estudo, propõe-se um Projeto Integrador como alternativa para a melhoria do desempenho acadêmico dos estudantes considerados de alto risco, de forma a possibilitar a compreensão de correlações entre disciplinas, promovendo a interdisciplinaridade e a articulação de conhecimentos em cada semestre letivo trabalhado. Entre as conclusões, destaca-se a importância de os docentes do Ciclo Básico e do Ciclo Profissionalizante abrirem amplo debate, para que se estabeleça conexões importantes entre as disciplinas do curso, de forma a possibilitar a amenização dos problemas do Ciclo Básico de cursos de engenharia. / In recent years, there is growing concern with on the teaching of engineering in Brazil and world. One of the problems of the courses is the disciplines of the Basic Cycle, which are very theoretical and out of the context of the future engineers. The objective of this work is to establish and characterize correlations between basic disciplines of the Electrical Engineering course, at the Polytechnic School of University of São Paulo, with reference to the Curricular Structure from 2000 to 2010. For this study, a literature review was made, approaching historical facts in engineering education, in Europe and Brazil, as well as a survey and study of the teaching program, templates and tests of the disciplines chosen for this research. Content and/or skills that characterize the correlations were identified, verifying their importance for the development of the disciplines. Among the results of this study, we propose an Integrator Project as an alternative to improve the academic performance of students considered to be high-risk, as way of allow the understanding of correlations between disciplines, promoting the interdisciplinarity and the articulation of knowledge in each academic semester worked. Among the conclusions, stands out the importance of the teachers of Basic Cycle and Vocational Cycle opening a wide debate, to establishing important connections between the course materials, as way of make it possible to soften the problems of the Basic Cycle of engineering courses.

<p>Normally the operational amplifier is used as a component in active filter design. The goal for future components in filter design is large bandwith and the use of low supply voltages. The use of current-mode instead of voltage-mode circuits gets a step closer to the required performance. A component that use current as the signal conveying part is the current conveyor. In this report a comparative study between two current conveyor structures of second generation (CCII) is performed. The most suited is later implemented and simulated using the CMOS process AMS.C035. The component is also tested in a continuous-time elliptic low-pass filter of leapfrog type. The filter does not behave as it should. However, better performance can be obtained by redesigning the current conveyor.</p>