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Cardiovascular disease remains the leading cause of death in the developed world. In this thesis computational modelling techniques were used to study the mechanisms and genesis of atrial arrhythmias. It is separated into 2 parts: (1) The mechanistic links between mutations of the fast Na+ channel (INa) and the ability of the sinoatrial node to pace the surrounding atrial muscle were investigated. The mutations were separated into two groups, one for the mutations affecting the steady-state activation, and the other for those affecting steady-state inactivation. On the single cell level it was found that all mutations slowed the pacing rate of the sinoatrial node in a similar way, but at the 2D level the two mutation groups modulated the excitation of the tissue differently. One caused a conduction block between the sinoatrial node and atrium, where the other abolished pacemaking all together. (2) A new set of mathematical models were then developed for the sheep atria. This was incorporated into an anatomically detailed 3D geometry of the whole sheep atria to form a platform suitable for the study of clinical atrial fibrillation, and other atrial arrhythmias. Due to the lack of single cell electrophysiology data available, a method of cross-species modelling was utilised. A biophysically detailed model of the 3D sheep atria was created, and used in a preliminary study into the susceptibility of tissue to atrial fibrillation from the rapid pacing of the pulmonary vein area. It was found that both electrical heterogeneity and the complex fibre structure of the atria need to be considered for sustained atrial fibrillation to be seen.

The residential sector in England is often identified as having the largest potential for emissions reduction at some of the lowest costs when compared against other sectors. In spite of this, decarbonisation within the residential sector has not materialised. This thesis explores the complexities of decarbonising the residential sector in England using a whole systems approach. It is only when the interaction between social, psychological, regulatory, technical, material and economic factors are considered together that the behaviour of the system emerges and the relationships between different system components can be explained giving insight into the underlying issues of decarbonisation. Building regulations, assessments and certification standards are critical for motivating and driving innovation towards decarbonising the building stock. Many existing building performance and evaluation tools are shown to be ineffective and confound different policy objectives. Not only is the existing UK SAP standard shown to be a poor predictor of dwelling level energy demand but it perversely incentivises households to increase CO2 emissions. At the dwelling level, a structural equation model is developed to quantify direct, indirect and total effects on residential energy demand. Interestingly, building efficiency is shown to have reciprocal causality with a household’s propensity to consume energy. That is, dwellings with high-energy efficiency consume less energy, but homes with a propensity to consume more energy are also more likely to have higher energy efficiency. Internal dwelling temperature is one of the most important parameters for explaining residential energy demand over a heterogeneous building stock. Yet bottom up energy demand models inadequately incorporate internal temperature as a function of human behaviour. A panel model is developed to predict daily mean internal temperatures from individual dwellings. In this model, socio-demographic, behavioural, physical and environmental variables are combined to estimate the daily fluctuations of mean internal temperature demand. The internal temperature prediction model is then incorporated in a bottom-up engineering simulation model. The residential energy demand model is then used to project decarbonisation scenarios to 2050. Under the assumption of consistent energy demand fuel share allocation, modelling results suggest that emissions from the residential sector can be reduced from 125 MtCO2 to 44 MtCO2 after all major energy efficiency measures have been applied, the power sector is decarbonised and all newly constructed dwellings are zero carbon. Meeting future climate change targets will thus not only require extensive energy efficiency upgrades to all existing dwellings but also the complete decarbonisation of end use energy demand. Such a challenge can only be met through the transformation of existing building regulations, models that properly allow for the effects of human behaviour, and flexible policies capable of maximising impact from a heterogeneous residential building stock.

Dissertation submitted to the Faculty of Science, University of the Witwatersrand, for completion of the Degree of' Master of Science / The atmospheric response of the Colorado State University Regional Atmospheric Modelling System (RAMS) to sea-surface temperature anomaliesis investigated. A period of four days was chosen from 21 to 24 January 1981, where focus was placed on the development and dissipation of a tropical-temperate trough across Southern Africa. Previous experimenting this mesoscalenumerical model have detemined the kinematic, moisture, and thermodynamic nature of these synoptic features. The research in this dissertation focuses specifically on the sensitivity of the numerical model's simulated responses to positive sea-surface temperature anomalies. Three separate experiments were devised, in which positive anomalous temperatures were added to the ocean surface north of Madagascar (in the tropical Indian Ocean), at the region of the Agulhas Current retroflection, and along the tropical African west coast (in the Northern Benguela and Angola currents). The circulation aspects of each sensitivity test were investigated through the comparison of simulated variables such as vapour and cloud mixing ratios, temperature, streamlines and vertical velocity, with the same variables created by a control simulation. The results indicate that for the first sensitivity test, (the Madagascar anomaly), cyclogenesis was initiated over the area of modified sea temperatures which resulted in a marginal decrease in continental precipitation. The second sensitivity test (over the Agulhas retroflection) produced a much smaller simulated response to the addition of anomalously warm sea temperatures than the tropical Indian Ocean anomaly. Instability and precipitation values increased over the anomalously warm retroflection region, and were slowly transferred along the westerly wave perturbation and the South African east coast. The third sensitivity experiment showed a predominantly localised simulated increase in precipitation over Gabon and the Congo, with the slow southward progression of other simulated circulation differences taking place. The small perturbations in each of the simulated meteorological responses are consistent with the expected climate response to anomalously warm sea-surface temperatures in those areas. / AC 2018

Made available in DSpace on 2015-05-14T12:39:43Z (GMT). No. of bitstreams: 1 ArquivoTotal.pdf: 1020314 bytes, checksum: 537a5807209898a911ce64ccd9765244 (MD5) Previous issue date: 2013-03-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This research aims to investigate and develop a semiotic study about the dialogical interactions between the theatre and the song systems in the play Gota D Água (1975) written by Chico Buarque and Paulo Pontes. To achieve this purpose will be required a combination of theories from the Semiotics of Culture, the dramatic language and the song, emphasizing the studies on Brazilian Popular Music (MPB). Thus, we intend to create an inter-semiotic dialogue between the theatre and the song, considering them as two structural semiotic languages to the understanding of the play Gota D Água. In this study, both dramatic language and the song (MPB) language will be considered as a second-degree modelling system, once they convey their own meaning and have singular codifications in relation to the natural language, the first-degree modelling system. Through the establishment of this semiotic network, we hope contribute to the increasing of the systemic communication network of culture itself. / Esta pesquisa visa investigar e desenvolver um estudo semiótico entre os sistemas de linguagens dialogantes da canção e do texto dramático na obra Gota D Água (1975), de Chico Buarque e Paulo Pontes. Para a concretização deste exercício de modelização, utilizar-se-á como lastro teórico os conceitos da Semiótica da Cultura somados aos estudos acerca da linguagem dramática e da canção, com enfoque na Música Popular Brasileira (MPB). Através deste respaldo conceitual, pretende-se tecer um diálogo intersemiótico entre o teatro e a canção, duas linguagens que consideramos estruturais do ponto de vista do significado da peça. Nesta pesquisa, tanto a canção popular, quanto o texto dramático serão considerados sistemas modelizantes de segundo grau uma vez que transmitem significados próprios e também por possuírem codificações singulares em relação à língua natural que é o sistema modelizante de primeiro grau. Por fim, espera-se, através das construções de sentido geradas a partir desta interação semiótica, estarmos contribuindo para a ampliação da rede de comunicação sistêmica da cultura.

Human immunodeficiency virus (HIV-1) is the pathogenic agent of HIV infection thatprecedes the total breakdown of cellular immunity, a condition known as acquiredimmunodeficiency syndrome (AIDS). The pandemic nature of the disease has promptedintense research into its biology. Already, much is known about HIV-1 infection, lifecycle,and progression to aids. Systems biology enables the combination of complex data fromthese studies into a framework where their effect on the various levels of cellularorganization (i.e. Pathways, cells, tissues, organs and the whole body) could be studied insilico. In this thesis, first, we reviewed our knowledge of the HIV-1 Human InteractionDatabase. We examined its contents and identified processes that HIV-1 was not previouslyknown to interact with. Then, we attempted an in silico dynamic model of HIV-1 interaction. We built a model of HIV-1 interaction with the CD4 T cell activation pathway comprised of137 nodes (16 HIV-1, 121 human) and 336 interactions. The model reproduced expectedpatterns of T cell activation. Using interaction graph properties, we identified 26 host cellfactors, including MAPK1&3, Ikkb-Ikky-Ikka and PKA, which contribute to the net activationor inhibition of viral proteins. By following a logical Boolean formalism, we identified 9 hostcell factors essential to the functions of viral proteins in the activation pathway. This wasthe first attempt to model dynamic viral-host interaction relationships. Then, we organize HIV-1 interacting host genes into modules to represent cellular processesneeded by the virus. We combined HIV-1 interactions with host gene GO annotations toclassify host genes according to these needed cellular processes. We obtained 201 modulesand found the same set of viral proteins do not interact with host genes having similarmodules suggesting intelligence in its co-ordination of host processes. This work is one of agrowing list that explores coordination of HIV-1 interactions. But more importantly, it would bebeneficial to functionally downsize the large dynamic HIV-1 interaction network. Finally, in our discussion, we discuss our results and suggest possible ways in which our workon dynamic models could be improved. This work is opening up a new field of systems virologythat studies the effect of viruses on the host in terms of its temporal and spatial aspects.

O presente trabalho tem por objetivo a análise da evolução da semiótica da cultura na obra de estudioso da cultura e literatura, crítico e filósofo russo Iúri Lótman por meio de traduções e dos comentários concernentes aos seus ensaios, escritos em diferentes épocas e dedicados aos principais conceitos da semiótica da cultura, tais como o fenômeno da cultura e os seus processos dinâmicos, o fenômeno da arte, o problema do texto, a memória cultural e a semiosfera. A obra de Lótman enquanto semioticista é inseparável do contexto histórico dos estudos da literatura, linguística, semiótica, cultura tanto na Rússia, quanto no Ocidente. Entre os seus precursores russos estão os escritores e os filósofos do século XIX e, no século XX, os simbolistas, os futuristas e os formalistas. A essência da semiótica da cultura lotmaniana começou a se formar no âmbito da Escola Semiótica de Tártu- Moscou e com a base na tradição dos estudos linguísticos, já nos trabalhos posteriores ela adquiriu um caráter mais filosófico, ao lidar com a imprevisibilidade dos processos culturais universais. Definimos ainda os pontos de coerência entre as ideias de Lótman e a obra dos estruturalistas e pós-estruturalistas franceses, além de Mikhail Bakhtin e Umberto Eco. / The present work aims at analyzing the development of semiotics of culture in the work of Russian culture and literature scholar, critic and philosopher Yuri Lotman through translation and commentary of his essays, written at different periods and dedicated to the core concepts of semiotics of culture, such as culture phenomenon and its dynamic processes, the phenomenon of art, the problem of the text, the cultural memory and semiosphere. Lotman`s work as a semiotician is inseparable from the historical context of the literature, linguistics, semiotics and culture studies both in Russia and the West. Among his precursors are Russian writers and philosophers of the nineteenth and twentiethcentury, the symbolists, futurists and formalists. The essence of Lotman`s semiotics of culture began to form in the Tartu-Moscow Semiotic School on the basis of language studies tradition, though in later works he developed a more philosophical approach, dealing with the unpredictability of universal cultural processes. Further, we point out the connection between Lotman\'s ideas and work of French structuralists and poststructuralists, Mikhail Bakhtin and Umberto Eco.

O presente trabalho tem por objetivo a análise da evolução da semiótica da cultura na obra de estudioso da cultura e literatura, crítico e filósofo russo Iúri Lótman por meio de traduções e dos comentários concernentes aos seus ensaios, escritos em diferentes épocas e dedicados aos principais conceitos da semiótica da cultura, tais como o fenômeno da cultura e os seus processos dinâmicos, o fenômeno da arte, o problema do texto, a memória cultural e a semiosfera. A obra de Lótman enquanto semioticista é inseparável do contexto histórico dos estudos da literatura, linguística, semiótica, cultura tanto na Rússia, quanto no Ocidente. Entre os seus precursores russos estão os escritores e os filósofos do século XIX e, no século XX, os simbolistas, os futuristas e os formalistas. A essência da semiótica da cultura lotmaniana começou a se formar no âmbito da Escola Semiótica de Tártu- Moscou e com a base na tradição dos estudos linguísticos, já nos trabalhos posteriores ela adquiriu um caráter mais filosófico, ao lidar com a imprevisibilidade dos processos culturais universais. Definimos ainda os pontos de coerência entre as ideias de Lótman e a obra dos estruturalistas e pós-estruturalistas franceses, além de Mikhail Bakhtin e Umberto Eco. / The present work aims at analyzing the development of semiotics of culture in the work of Russian culture and literature scholar, critic and philosopher Yuri Lotman through translation and commentary of his essays, written at different periods and dedicated to the core concepts of semiotics of culture, such as culture phenomenon and its dynamic processes, the phenomenon of art, the problem of the text, the cultural memory and semiosphere. Lotman`s work as a semiotician is inseparable from the historical context of the literature, linguistics, semiotics and culture studies both in Russia and the West. Among his precursors are Russian writers and philosophers of the nineteenth and twentiethcentury, the symbolists, futurists and formalists. The essence of Lotman`s semiotics of culture began to form in the Tartu-Moscow Semiotic School on the basis of language studies tradition, though in later works he developed a more philosophical approach, dealing with the unpredictability of universal cultural processes. Further, we point out the connection between Lotman\'s ideas and work of French structuralists and poststructuralists, Mikhail Bakhtin and Umberto Eco.