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Although there is a considerable body of research into various aspects of the teaching and learning of English as a foreign language, there appear to be few studies into the teaching of modern foreign languages (ML) to adolescents in the context of a secondary school setting. This thesis reports the findings of research aimed at identifying the strategies that ML teachers, considered examples of good practice, used to engage secondary school learners in interaction in the target language (TL) with the objective of developing their communicative competence. Four teachers’ lessons with their pupils aged 14-15, in their third year of learning a foreign language at secondary school, were observed and audio-recorded. Three of each of the teachers’ observed lessons were subjected to fine grained analysis with the aim of delineating their TL moves which appeared to influence pupils so that they used the TL themselves readily to communicate meaning ‘naturally’ as well as to practise structures in more controlled exercises. The teachers and a sample of their pupils were subsequently interviewed to provide confirmation or disconfirmation of initial patterns arising from examination of the observational data set. Although the data were analysed predominantly qualitatively, quantitative methods were also employed to provide a clear picture of the teachers’ TL use and the way it was deployed to assist learners in developing effective communicative skills. Goffman’s (1981) production and Wadensjö’s (1998) reception formats, not normally associated with the classroom, were considered appropriate to describe the participation frameworks within which the development of the learners’ communicative proficiency was supported. The findings display ways in which the TL used by the teachers helped to create a secure collaborative atmosphere where pupils were disposed to respond in the TL. The teachers’ use of different ‘types’ of TL, depending on the focus in the lesson, was viewed as supporting learners in preparation for communicating their own meaning in exchanges in ‘real world’ interaction outside the classroom. A particularly successful scaffolding strategy employed by the teachers was the provision of TL cues offered to the learners before they responded to initiations which enabled them to express their meaning in the TL. Revoicing of learners’ incomplete TL utterances also appeared successful in supporting learners to use their limited language resource effectively. Through its close analysis of classroom talk, this thesis offers an important contribution to the understanding of the complex nature of interaction in the ML classroom and the role that teachers’ use of TL plays in assisting adolescent learners to develop TL communication skills in interaction. Beginning teachers, as well as those more experienced practitioners, should benefit from the strategies identified, which appear to highlight the importance of establishing a collaborative classroom ethos which supports the learners, allowing them to contribute in the TL successfully.

This report concerns a detection module used for a pellet tracking system. Spheres of frozen hydrogen known as pellets can be used as internal targets in hadron physics experiments. Pellets are created some distance above the accelerator beam and directed in a pellet beam pipe to intersect the accelerator beam. To determine the position of a pellet in the interaction region in the case of an interaction, the pellets need to be tracked. This is done using tracking sections along the pellet beam pipe with measurement levels containing lasers illuminating the pellets and cameras, detecting the light. The pellet position in the interaction region can be reconstructed with an accuracy of 0.1 mm. To reach this accuracy there are high demands on the alignment of the cameras and lasers. Alignment by a pellet beam pipe is generally difficult so a solution enabling alignment elsewhere is desired. Therefore a detection module consisting of a plate with cameras and lasers mounted to it has been constructed. These cameras and lasers can be aligned in an alignment bench setup before being transported to a pellet beam pipe. The alignment of the cameras and lasers on the detection module must be maintained under certain conditions e.g. transportation, temperature changes, exposure to vibrations. This report covers investigations regarding the mechanical stability of the detection module under these conditions. Different alignment bench targets are investigated. The effects of the optics of the cameras and lasers and the functionality of the detection module are investigated.

There has been an increase in number of human infections by mycobacteria and opportunistic pathogens of the closely related nocardioform bacteria. Frequent multiple drug resistance in these organisms makes it desirable to identify novel targets for antimicrobial agents. Bacteriophages offer one way to do this as analysis of their DNA reveals great diversity in their genetic makeup, suggesting variety in the way they interfere with host cells. Four novel nocardiophages were therefore isolated from soil and characterized. Libraries of their nucleic acid were constructed and screened for clones inhibitory to a nocardioform of the genus Rhodococcus. Nine clones were characterized, and minimum necessary DNA for inhibitory activity sequenced. Of 18 ORFs predicted on these DNAs, 13 could not be assigned a function. Genes similar to ones in databases apparently interfered with DNA metabolism, protein synthesis, or integrity of plasma membrane. This genetic approach may be an efficient and effective way to discover novel targets for antibiotics.

A técnica de análises PIXE (Particle Induced X-ray Emission) de alvos finos é rotineiramente usado no Instituto de Física da Universidade de São Paulo (USP) pelo Lamfi (Laboratório de Materiais e Feixes Iônicos) em análises quantitativas elementares. A calibração do arranjo experimental do Lamfi é realizada através da irradiação de filmes finos padrões evaporados, sendo o rendimento de produção de raios X ajustado a partir deprimeiros princípios. Em análises PIXE de alvos espessos (TTPIXE), a composição daparticular amostra introduz efeitos de perda de energia das partículas incidentes e autoabsorção dos raios X produzidos. Estes efeitos são inexistentes na análise PIXE de alvosfinos. Paradoxalmente há a necessidade de se conhecer a composição da amostra, paracomputar estes efeitos, numa análise elementar quantitativa de alvos espessos. Este trabalhopropõe a diluição de amostras sólidas numa matriz conhecida onde as características de perda de energia das partículas incidentes e auto absorção da radiação produzida estejam caracterizadas (exemplo: ácido bórico, grafite) e supostamente não sofram alterações devido à introdução da amostra (diluição). Para o cálculo do rendimento de produção de raios X em análises TTPIXE é proposto um fator de correção para alvos espessos, dependente exclusivamente da matriz diluidora, aplicado ao rendimento de produção de raios X de alvos finos. Este procedimento viabiliza a utilização da curva de resposta para análises de alvos finos, já calibrada, do arranjo. Utilizando os modelos mais aceitos para o poder de freamento para prótons incidentes, seções de choque de produção de raios X e coeficientes de absorção de radiação pela matéria, o software (Clara) foi desenvolvido para o cálculo do rendimento de produção de raios X em alvos espessos, bem como os fatores de correção para dado raio X e determinada matriz. Alvos espessos foram confeccionados a partir de amostra padrão de referência (SRM-IAEA356 Marine sediment) para verificar os valores calculados pelo Clara e da metodologia de análise proposta. Os valores experimentais encontram-se em concordância com os valores certificados para um coeficiente de intervalo de confiança de 95% considerando o novo limite de detecção imposto pela diluição. Um roteiro para preparação de alvos espessos a partir de amostras sólidas, bem como a descrição do arranjo experimental, estão inclusos. / Thin film PIXE (Particle Induced X-ray Emission) analysis is been routinely used in the Institute of Physics of the University of Sao Paulo (USP) for quantitative analysis of materials. The X-ray production yield of the PIXE-SP setup is calibrated with monoelementary evaporated thin film standards, and fitted with a first principles yield function. However, in thick target PIXE (TTPIXE) analysis, the particular sample composition needs to be known in advance to calculate the stopping power and the X-ray absorption coefficients. In this work, a matrix standardization is proposed, in which a powdered solid sample is diluted in a known light element matrix (like graphite, boric acid, etc.) whose energy loss and selfabsorption are known and supposed almost unchanged. Furthermore, a scheme is proposed where elementary TTPIXE yields are calculated applying a pre-determined thick target correction factor to the thin target PIXE yields. This procedure enables the use of the already calibrated thin film X-ray yields also for thick target analysis. Using the most accepted stopping power model, ionization cross-sections and X-ray attenuation coefficients, a software (Clara) was developed to calculate the elementary TTPIXE X-ray yields and the corresponding thick target correction factors, for a given and pre-determined matrix. The program also allows testing the addition of any contaminant to the primary matrix and to compute the corresponding change in the thick target PIXE X-ray yields. This option was used to calculate the effect of increasing sample mass in the light element matrix, on the calculated yields, the effect of small changes in target composition, and the quantitative limitations of the proposed scheme. Thick test targets were prepared with a standard reference material (SRM-IAEA356 Marine sediment) and used to verify the accuracy of Clara and of the proposed scheme. The experimental values of the sample composition agreed with the certified values for 95% confidence interval coefficient to the new detection limit imposed by dilution. A protocol for target preparation of solid samples using this technique as well as the description of the experimental setup, are included.

Multi-target tracking is the process that allows the extraction of object motion patterns of interest from a scene. Motion patterns are often described through metadata representing object locations and shape information. In the first part of this thesis we discuss the state-of-the-art methods aimed at accomplishing this task on monocular views and also analyse the methods for evaluating their performance. The second part of the thesis describes our research contribution to these topics. We begin presenting a method for multi-target tracking based on track-before-detect (MTTBD) formulated as a particle filter. The novelty involves the inclusion of the target identity (ID) into the particle state, which enables the algorithm to deal with an unknown and unlimited number of targets. We propose a probabilistic model of particle birth and death based on Markov Random Fields. This model allows us to overcome the problem of the mixing of IDs of close targets. We then propose three evaluation measures that take into account target-size variations, combine accuracy and cardinality errors, quantify long-term tracking accuracy at different accuracy levels, and evaluate ID changes relative to the duration of the track in which they occur. This set of measures does not require pre-setting of parameters and allows one to holistically evaluate tracking performance in an application-independent manner. Lastly, we present a framework for multi-target localisation applied on scenes with a high density of compact objects. Candidate target locations are initially generated by extracting object features from intensity maps using an iterative method based on a gradient-climbing technique and an isocontour slicing approach. A graph-based data association method for multi-target tracking is then applied to link valid candidate target locations over time and to discard those which are spurious. This method can deal with point targets having indistinguishable appearance and unpredictable motion. MT-TBD is evaluated and compared with state-of-the-art methods on real-world surveillance.

Part I: Target identification studies are one of the most difficult but rewarding challenges in chemical biology. Part I of this thesis describes target identification studies for 5-nitrofuran containing hits. The 5-nitrofurans used in this study were identified in a phenotypic screen for compounds that induced melanocyte cells death in zebrafish. Chapter 1 provides brief overviews on three related areas of the project: 1) the use of zebrafish as a model organism in drug discovery; 2) phenotypic screening using zebrafish and 3) the strategies used in target identification studies. Chapter 2 describes the synthesis of and SAR studies on two series of 5-nitrofuran containing analogues. The design and preparation of biotinylated chemical probes based on the SAR data is also described. These chemical tools are then used in affinity chromatography studies and genetic validation of a potential target (zebrafish Aldh2) of the 5-nitrofuran compounds is reported. Chapter 3 provides a review of the biological and chemical processes that human ALDHs are known to mediate. In addition, small molecules that modulate ALDH2 activity are reviewed. A detailed study of the interaction between 5-nitrofurans and human ALDH2 including in vitro enzymatic assays is described leading to the conclusion that the 5- nitrofurans under study are substrates of human ALDH2. Further mechanism of action investigations using model reactions are also presented. Chapter 4 introduces the use of 5-nitrofuran containing drugs in the clinic and highlights the reported side-effects. Further investigation of the interaction between ALDH2 and 5- nitrofurans in zebrafish and yeast using ALDH2 inhibitors is described. Based on these results, a combination therapy strategy is proposed. Finally, the trypanocidal activity of the newly synthesised 5-nitrofurans is discussed. Experimental details and future work for Part I are presented in Chapters 5 and 6 respectively. Part II: Human sirtuins are associated with various biological functions and diseases, including cancer and neurodegeneration. Previous work from the Westwood Lab has led to the discovery of the tenovins that act as inhibitors of SIRT1 and SIRT2. Part II of the thesis reports the development of potent fixed ring tenovin analogues with high SIRT2 selectivity. Chapter 7 provides a brief review of the biology of human SIRT2 and the reported SIRT2 inhibitors available to date. This is followed by a short summary of the previous work on the tenovins in the Westwood Lab and the design of the fixed ring tenovin analogues. Chapter 8 describes the synthesis of three series of fixed ring tenovin analogues. SAR data is generated based on in vitro enzymatic assays against both SIRT1 and SIRT2 and the prepared analogues showed relatively high potency and selectivity against SIRT2. Further cell-based deacetylation assay are also discussed. All the experimental details are reported in Chapter 9 and Chapter 10 provides with conclusions and proposed future work.