The global analysis fields of the Met Office stratospheric assimilated data set have been investigated. Systematic biases for select years were identified through val- idation with independent satellite observations. Particular attention was given to analyses from January 2005 to October 2009 produced from a 50 level (L50) configuration of the UM with model lid at ∼0.1 hPa, and the impact on analyses fields from November 2009 to September 2010 when the middle atmospheric configuration of the UM was extended to ∼0.01 hPa using 70 levels (L70). Validation results from both the L50 and L70 analyses show that largest tem- perature biases occur at polar latitudes approaching the model lid in the meso- sphere, exhibiting a clear seasonal cycle. Here cold biases in the winter season of the L50 analyses and warm biases in the summer season of the L70 analyses would strongly suggest that the mean meridional circulation in the mesosphere is underestimated, and that small scale gravity wave forcing supplied by the op- erational Ultra Simple Spectral Parameterisation (USSP) scheme is insufficient. Based on the above validation results numerous experiments were conducted to investigate the temperature response in the mesosphere to increased gravity wave forcing. Such experiments concentrated on tuning the energy scale factor (β) in the USSP scheme and the application of a momentum conserving ”opaque” lid. Furthermore, the impact of developing the USSP scheme to include direct heating from gravity wave induced turbulent dissipation was also investigated. Maximum temperature responses in the summer polar upper mesosphere of ∼22 K were found when increasing the standard value of β=0.1 to β=0.14 combined with the application of an opaque lid. Magnitudes of direct heating rates due to gravity wave turbulent dissipation diagnosed via the USSP scheme were found to be consistent with previous estimates. However applying such heating would most likely have a negative impact on the L70 analyses, which already display warm biases in the upper mesosphere, strongly suggesting that additional phys- ical processes such as eddy diffusion must also be accounted for when applying direct heating from gravity wave breaking.

Durant l’exécution de l’apoptose, plus de 2 000 protéines sont protéolysées par les caspases, une famille de protéases à cystéine. Le clivage de plusieurs d’entre elles a pour effet d’interrompre les processus régulant le trafic intracellulaire. Durant mes études, je me suis intéressée à deux substrats potentiels des caspases, soit les sorting nexins SNX1 et SNX2. Leur clivage en N-terminal avait auparavant été identifié par protéomie dans des extraits cellulaires apoptotiques, respectivement aux sites LFAD91[flèche vers le bas]A et VSLD84[flèche vers le bas]S. Conjointement avec le complexe rétromère, SNX1 et SNX2 jouent un rôle essentiel dans le transport rétrograde de cargos, tel le récepteur lysosomal CI-MPR, des endosomes vers le TGN, évitant ainsi leur dégradation aux lysosomes. Notamment, l’association entre SNX1 et SNX2 et le complexe rétromère, via la sous-unité Vps35, requerrait leur domaine N-terminal, or, celui-ci est clivé durant l’apoptose. Dans le but de déterminer l’impact de la protéolyse de SNX1 et SNX2 sur la fonction du complexe rétromère et le transport rétrograde, nous avons étudié leur clivage par les caspases. Nos résultats indiquent qu’in vitro, les caspases initiatrices 8, 9 et 10 protéolysent SNX1 et SNX2 tandis que seule la caspase-6 exécutrice clive SNX2. Plusieurs fragments de SNX1 sont générés par le clivage à 16 sites, dont le site LFAD91[flèche vers le bas]A en N-terminal ainsi que plusieurs suivant un résidu glutamate. Durant l’apoptose, SNX2 est entre autres clivée par la caspase-6, et ce au site VSLD84[flèche vers le bas]S en N-terminal. Nous avons par la suite étudié l’effet de la protéolyse de SNX1 et SNX2 sur la fonction du complexe rétromère. Nos résultats démontrent que SNX2 tronquée, imitant le clivage au site VSLD84[flèche vers le bas]S, n’interagit plus avec Vps35, la sous-unité centrale du complexe rétromère. De plus, la déplétion de SNX1 et SNX2, récapitulant potentiellement leur protéolyse, a pour effet de délocaliser Vps26, une autre sous-unité du complexe rétromère. Par ailleurs, nous avons évalué l’effet de la protéolyse de SNX2 sur la régulation du récepteur Met, lequel serait régulé entre autres par SNX1 et SNX2. La déplétion de SNX2 induit une augmentation de la phosphorylation du récepteur Met et de ERK1/2 suivant sa stimulation. De plus, l’ARNm de SNX1 et SNX2 sont tous deux réduits dans les tissus de tumeurs de patients atteints du cancer colorectal (CCR) et une diminution des niveaux de SNX2 corrèle avec une hausse de mortalité chez ces patients. Pour conclure, notre étude démontre un effet direct de la protéolyse de SNX2 sur le complexe rétromère durant l’apoptose et suggère un lien entre SNX2 et la pathogenèse du CCR. / Abstract: During the execution of apoptosis, more than 2,000 proteins are proteolysed by caspases, a family of cysteine proteases. The cleavage of several of them results in the interruption of intracellular trafficking processes. During my studies, I investigated two potential caspases substrates, namely the sorting nexin SNX1 and SNX2. Their cleavage at their N-terminus has previously been identified in apoptotic cell lysates by proteomics, respectively at LFAD91[down arrow]A and VSLD84[down arrow]S sites. Together with the retromer complex, SNX1 and SNX2 play an essential role in the retrograde transport of cargos, such as the lysosomal receptor CI-MPR, from endosomes to TGN, thus avoiding their degradation by lysosomes. In particular, the association between SNX1 and SNX2 and the retromer complex, via the Vps35 subunit, seems to require their N-terminal domain, which is thought to be cleaved during apoptosis. To determine the impact of SNX1 and SNX2 proteolysis on the function of the retromer complex and retrograde transport, we have first studied their cleavage by caspases. Our results indicate that in vitro, initiator caspases 8, 9, and 10 proteolyze SNX1 and SNX2 while only executioner caspase-6 cleaves SNX2. Several fragments of SNX1 are generated by the cleavage of up to 16 sites, including at the N-terminus LFAD91[down arrow]A site and following glutamate residues. During apoptosis, SNX2 is directly cleaved by caspase-6 at the site VSLD84[down arrow]S in its N-terminus. We next investigated the effect of SNX1 and SNX2 proteolysis on the function of retromer complex. Our results demonstrate that truncated SNX2, mimicking cleavage at the VSLD84[down arrow]S site, no longer interacts with Vps35, the central subunit of retromer complex. Furthermore, depletion of SNX1 and SNX2, potentially recapitulating their proteolysis, redistributes Vps26, another retromer subunit. In addition, we evaluated the effect of SNX2 proteolysis on the regulation of Met receptor, which has been shown to be regulated by SNX1 and SNX2. SNX2 depletion induces an increase in Met and ERK1/2 phosphorylation after stimulation. In addition, both SNX1 and SNX2 mRNAs are reduced in tumor tissues of colorectal cancer patients and decreased expression levels of SNX2 correlates with increased mortality. In conclusion, our study demonstrates a direct effect of SNX2 proteolysis on retromer complex association during apoptosis and suggests a link between SNX2 and the pathogenesis of colorectal cancer.

<p>Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors comprised of >70 subtypes. An important question is how the cell of origin and the pathways to tumor development shape the broad array of STS subtypes. By forcing identical tumor-promoting mutations to different cell types in Genetically Engineered Mouse Models (GEMMs) of STS, I have a unique model system to investigate this question. In the process of performing these experiments I observed that genetic mutations are necessary, but not sufficient for rapid sarcoma formation. However, tissue injury dramatically accelerates sarcoma formation in our GEMM of STS. For my thesis, I have worked to understand how cell of origin affects sarcoma subtype and how the microenvironment in our models promotes transformation. I have observed that cell of origin plays an important, but not the only, role in defining STS subtype. Additionally, I have concluded that the microenvironment, and specifically the HGF/c-MET signaling pathway play a crucial role in promoting sarcoma development after acute tissue injury.</p> / Dissertation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

This study focuses on the relation between the picareque genre and the way in which guilt is processed in literature. André Brink’s Inteendeel (On the contrary) was used in this examination and also, for a wider perspective than merely the South African situation, Arthur Japin’s De zwarte met het witte hart (The two hearts of Aquasi Boachi). The possibilities offerd by the picaresque in order to investigate the manifestation of guilt in literary texts were explored with the theories of, inter alia, Wicks, Ricoeur and Todorov. Tracing the origins of the picaresque reveals that this type of text exhibits specific characteristics, e.g. an unethical attitude that is usually imposed on the individual by a society in crisis – “guilt” and a confessional tone are therefore intrinsically part of the picaresque. Using Wicks’s modal-generic approach, the two novels are examined with the purpose of determining their degree of “picaresqueness” to test the validity of the hypothesis, i.e. that the more a text displays picaresque characteristics, the more the issue of guilt would be a central theme to that text. In the two novels relevant to this study, colonial guilt is the main form of guilt examined. / Prof. W. Burger

The performance of the ATLAS missing transverse momentum (ETmiss) high-level trigger during 2015 operation is presented. In 2015, the Large Hadron Collider operated at a higher centre-of-mass energy and shorter bunch spacing (sqrt(s) = 13 TeV and 25 ns, respectively) than in previous operation. In future operation, the Large Hadron Collider will operate at even higher instantaneous luminosity (O(10^34 cm^−2 s^−1)) and produce a higher average number of interactions per bunch crossing, <mu>. These operating conditions will pose significant challenges to the ETmiss trigger efficiency and rate. An overview of the new algorithms implemented to address these challenges, and of the existing algorithms is given. An integrated luminosity of 1.4 fb^−1 with <mu> = 14 was collected from pp collisions of the Large Hadron Collider by the ATLAS detector during October and November 2015 and was used to study the efficiency, correlation with offline reconstruction, and rates of the trigger algorithms. The performance was found to be satisfactory. From these studies, recommendations for future operating specifications of the trigger were made. / Graduate / 0798, / jchiu@uvic.ca

Many interesting physical processes produce non-interacting particles that could only be measured using the missing transverse momentum. The increase of the proton beam intensity in the Large Hadron Collider (LHC) provides sensitivity to rare physics processes while inevitably increasing the number of simultaneous proton collisions in each event. The missing transverse momentum (MET) is a variable of great interest, defined as the negative sum of the transverse momentum of all visible particles. The precision of the MET determination deteriorates as the complexity of the recorded data escalates. Given the current complexity of data analysis, a new algorithm is developed to effectively determine the MET. Several well-understood physics processes were used to test the effectiveness of the newly designed algorithm. The performance of the new algorithm is also compared to that of the standard algorithm used in the ATLAS experiment. / Graduate

[pt] Nesse trabalho foi realizada uma avaliação microestrutural da influência do ciclo térmico em três aços da classe API5LX80: Nb-Cr, Nb-Cr-Mo e Nb-Cr-Mo-V fabricados no Brasil. Estes aços foram fabricados através de processo termo-mecânico controlado sem passarem por uma etapa subseqüente de resfriamento acelerado. Foi realizada uma caracterização microestrutural em duas condições, pós- laminação e austenitização a 900oC seguida de três (3) ciclos térmicos: resfriamento ao ar (1,5oC/s), ao óleo (30oC/s) e a água (115oC/s). Na condição de pós-laminado, os aços Nb-Cr, Nb-Cr-Mo, e Nb-Cr-Mo-V não apresentaram diferenças significativas quanto ao TG, distribuição de fases (ferrita, bainita e AM), dureza e microdureza mas foram verificadas diferenças em suas subestruturas (subgrãos, células e precipitação fina) observada em MET. Concluise que a inclusão de Mo e V nos aços Nb-Cr-Mo e Nb- Cr-Mo-V não ocasionou influência a nível microestrutural, mas ocasionou mudanças a nível subestrutural verificadas em MET que talvez possam justificar a diferença entre propriedades mecânicas.Verificamos a diminuição do tamanho de grão com o aumento da taxa de resfriamento nos aços Nb- Cr, Nb-Cr-Mo, e Nb-Cr-Mo-V. Os valores de dureza e microdureza são os mesmos para os aços Nb-Cr e Nb-Cr-Mo na condição de após aplicação dos ciclos térmicos, e uma associação pode ser feita com a quantidade de fases de cada um, pois a distribuição quantitativa das fases para ambos os aços é muito similar. O aço Nb-Cr-Mo-V apresenta uma distribuição diferente, com a formação da fase martensítica já no resfriamento ao óleo (30oC/s) e o aumento da quantidade desta fase a medida que a taxa de resfriamento diminui. / [en] The present work presents a microstructural evaluation of three different chemical compositions of API5LX80 classified as Nb-Cr, Nb-Cr-Mo e Nb-Cr- Mo-V steel in two conditions, as received and after three applied cooling rates: air-cooled (1,5oC/s), oil-cooled (30oC/s) e water- cooled (115oC/s). This material under study is a microalloyed HSLA steel used for pipeline purposes produced in Brazil. Usually this steel is processed by thermo- mechanical controlled hot rolling followed by accelerated cooling. However, the material under study was not accelerated cooled after thermo-mechanical controlled hot rolling. Instead, chemical composition was changed to obtain similar mechanical properties of this class of steel. The Nb-Cr, Nb-Cr-Mo, e Nb-Cr-Mo-V as-received steels studied in this work presented the same quantitative distribution of grain size and volumetric fraction of the phases (ferrite, bainite and MA), as well as, the same hardness Rockwell (HRB) and Vickers (HV100). However, the substructures (subgrains, cells and fine precipitation) of the three steels were different when examed in Transmission Electron Microscopy - TEM. The Nb-Cr, Nb-Cr- Mo, e Nb-Cr-Mo- V steels, after submitted to the three cooling rates, presented a decrease in grain size with the increasing of the cooling rate. The same hardness Rockwell (HRB) and Vickers (HV100) values were found for Nb-Cr e Nb- Cr-Mo steels and this fact can be associated to the volumetric fraction of both steels, because both have very similar phase distribution. The Nb-Cr-Mo-V steel presented a different phase distribution with increased of martensite as the cooling rate decreases.

A filogenia dos diferentes grupos de Cnidaria permanece de certa forma pouco resolvida, uma vez que não há um consenso de quais são as relações entre as diferentes classes e ordens que compõem o filo. A espermiotaxonomia vem sendo utilizada como critério filogenético em diversos grupos de Metazoa. Para Cnidaria são poucos os trabalhos descrevendo a morfologia do sistema reprodutor masculino e do espermatozoide em nível de microscopia de luz e de microscopia eletrônica de transmissão. Exemplares das espécies Tamoya haplonema e Chiropsalmus quadrumanus (Cubozoa), Lychnorhiza lucerna e Chrysaora lactea (Scyphozoa), foram coletados próximos ao Centro de Biologia Marinha da Universidade de São Paulo e junto às bases do Instituto Oceanográfico da USP (Base de Cananéia e Base de Ubatuba) nos meses de agosto a outubro de 2014 e de abril a junho de 2015. Amostras das espécies Carukia barnesi, Chironex fleckeri e Chiropsella bronzie (Cubozoa) e Cassiopea sp. (Scyphozoa) foram coletadas ao longo da costa leste australiana de março a maio de 2016. Para a descrição histológica e histoquímica da gônada masculina, amostras do tecido gonadal foram fixadas em paraformaldeído 4% preparado com água do local da coleta e tampão fosfato de sódio 0,2M por 24 horas e as amostras foram processadas de acordo com o protocolo para historesina. Fragmentos da gônada masculina foram fixados em solução Karnovsky modificado (glutaraldeído 2,5% e 0,08% de paraformaldeído em tampão cacodilato de sódio 0,1 M, pH 7,4) e solução de Glutaraldeído (2.5% glutaraldeido em tampão cacodilato de sódio 0.1M em água do mar filtrada a vácuo, pH 7.2-7.4). Em seguida as amostras foram processadas de acordo com protocolo de microscopia eletrônica transmissão. Na presente dissertação é descrito de forma comparada o processo de espermatogênese dos cubozoários T. haplonema e C. quadrumanus através da histologia e histoquímica evidenciando o ciclo gonadal de ambos (capítulo 1). Descreve-se a espermatogênese e morfologia do espermatozoide, através da microscopia de luz e ultraestrutura para as espécies de Cubozoa T. haplonema, C. quadrumanus, Carukia barnesi, Chironex fleckeri e Chiropsella bronzie (Capítulo 2). Para as espécies de Scyphozoa Lychnorhiza lucerna, Chrysaora lactea e Cassiopea sp. descreve-se o processo de espermatogênese através da microscopia de luz e da microscopia eletrônica de transmissão, além do aspecto macroscópico da gônada masculina (Capítulo 3). Adicionalmente, nas considerações finais, é ressaltada a morfologia comparada dos espermatozoides de todas as espécies aqui estudadas evidenciando possíveis características únicas de cada classe, enumerando eventuais caracteres diagnósticos dos espermatozoides das espécies estudadas (Capítulo 4) / The phylogeny of the different groups of cnidarians remains elusive, since there is no consensus of what are the relationships between the different classes and orders that comprise the phylum. The spermiotaxonomy has been used as phylogenetic criteria in different groups of Metazoa. For Cnidaria there are few studies describing the morphology of the male reproductive system and sperm at the level of light microscopy and transmission electron microscopy. Specimens of the species Tamoya haplonema and Chiropsalmus quadrumanus (Cubozoa), Lychnorhiza lucerna and Chrysaora lactea (Scyphozoa), were collected near the Marine Biology Center of the University of São Paulo and near the bases of the Oceanographic Institute of USP (Cananéia and Ubatuba Bases) from August to October 2014 and from April to June 2015. Samples of the species Carukia barnesi, Chironex fleckeri and Chiropsella bronzie (Cubozoa) and Cassiopea sp. (Scyphozoa), were collected along the Australian east coast from March to May 2016. For histological and histochemistry description of the male gonads, samples were fixed in 4% paraformaldehyde prepared with water from the collection site and sodium phosphate buffer 0.2M for 24 hours. After that, the samples were processed following the protocol for historesin. Fragments of male gonads were fixed in modified Karnovsky solution (2.5% glutaraldehyde and 0.08% paraformaldehyde in 0.1 M sodium cacodylate buffer, pH 7.4) and glutaraldehyde (2.5% glutaraldehyde in cacodylate buffer 0.1M sodium in seawater vacuum Millipore filtered, pH 7.2-7.4). Then the samples were processed according to transmission electronic microscopy protocol. In this dissertation it is described the comparative spermatogenesis of the cubozoans T. haplonema and C. quadrumanus, under histology and histochemistry, showing the gonadal cycle (Chapter 1). We also describe the spermatogenesis and sperm morphology, under light microscopy and ultrastructure, for the Cubozoa species T. haplonema, C. quadrumanus, Carukia barnesi, Chironex fleckeri and Chiropsella bronzie (Chapter 2). For the Scyphozoa species, Lychnorhiza lucerna, Chrysaora lactea and Cassiopea sp., we describe the spermatogenesis process, under light transmission electronic microscopy, describing the macroscopic structure of the male gonad (Chapter 3). Additionally, in the final chapter, it is highlighted the comparative morphology of sperm of all species studied, evidencing possible unique features of each class, enumerating possible sperm characters (Chapter 4)

Made available in DSpace on 2015-04-14T13:58:25Z (GMT). No. of bitstreams: 1 400368.pdf: 4977900 bytes, checksum: 08b0f646dbce22d8e73ab4450850b4f0 (MD5) Previous issue date: 2008-03-25 / Nesse presente trabalho foi desenvolvido uma metodologia de fus?o e solidifica??o unidirecional ascendente para a obten??o de lingotes, de metais puros, com macroestrutura colunar grosseira e que possa ser aplicada na produ??o de lingotes de sil?cio multicristalinos para a ind?stria fotovoltaica. Visando gerar as condi??es necess?rias para a obten??o da macroestrutura desejada, a metodologia baseia-se no monitoramento e controle de par?metros t?rmicos tais como: velocidade de solidifica??o, gradiente t?rmico e taxa de resfriamento, e na correla??o desses par?metros com a macroestrutura. Para o desenvolvimento do trabalho foi projetado um forno de fus?o e solidifica??o unidirecional ascendente com sistema de aquecimento resistivo capas de atingir temperatura de 1650 ?C. Tamb?m foi constru?da uma lingoteira, para trabalhar com os metais zinco e alum?nio, de a?o inoxid?vel com 180 mm de comprimento por 51 mm de di?metro com duas configura??es de sistema de resfriamento capaz de gerar varia??es nos par?metros t?rmicos. Para trabalhar com sil?cio foi utilizado cadinho de quartzo e um sistema para atmosfera de prote??o tamb?m constru?do em quartzo. Com os resultados obtidos foi poss?vel observar que a taxa de resfriamento tem uma importante correla??o com a macroestrutura bruta obtida no processo de solidifica??o unidirecional ascendente. Os lingotes de zinco e alum?nio apresentam TCE bastante evidente e as taxas de resfriamentos que ocasionaram essa transi??o foram da ordem de 0,0035 ? 0,0049 ?C/s para o Zn e 0,013 ? 0,028 ?C/s para o Al. Das an?lises dos par?metros de solidifica??o e correla??o com a macroestrutura, foram determinadas as express?es do tipo: expoentT = cons tan te. TG e o. No forno foi poss?vel fundir e solidificar sil?cio in-situ.